FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Van Gool, F Galli, M Gueydan, C Kruys, V Prevot, PP Bedalov, A Mostoslavsky, R Alt, FW De Smedt, T Leo, O AF Van Gool, Frederic Galli, Mara Gueydan, Cyril Kruys, Veronique Prevot, Pierre-Paul Bedalov, Antonio Mostoslavsky, Raul Alt, Frederick W. De Smedt, Thibaut Leo, Oberdan TI Intracellular NAD levels regulate tumor necrosis factor protein synthesis in a sirtuin-dependent manner SO NATURE MEDICINE LA English DT Article ID COLONY-ENHANCING FACTOR; NF-KAPPA-B; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE; DEFICIENT MICE; INFLAMMATION; MOLECULE; INHIBITOR; APOPTOSIS; POLY(ADP-RIBOSE); LETHALITY AB Tumor necrosis factor (TNF) synthesis is known to play a major part in numerous inflammatory disorders, and multiple transcriptional and post-transcriptional regulatory mechanisms have therefore evolved to dampen the production of this key proinflammatory cytokine(1,2). The high expression of nicotinamide phosphoribosyltransferase (Nampt), an enzyme involved in the nicotinamide-dependent NAD biosynthetic pathway, in cells of the immune system(3) has led us to examine the potential relationship between NAD metabolism and inflammation. We show here that intracellular NAD concentration promotes TNF synthesis by activated immune cells. Using a positive screen, we have identified Sirt6, a member of the sirtuin family(4), as the NAD-dependent enzyme able to regulate TNF production by acting at a post-transcriptional step. These studies reveal a previously undescribed relationship between metabolism and the inflammatory response and identify Sirt6 and the nicotinamide-dependent NAD biosynthetic pathway as novel candidates for immunointervention in an inflammatory setting. C1 [Van Gool, Frederic; Galli, Mara; Leo, Oberdan] Univ Libre Bruxelles, Inst Biol & Med Mol, Physiol Anim Lab, B-6041 Gosselies, Belgium. [Gueydan, Cyril; Kruys, Veronique] Univ Libre Bruxelles, Inst Biol & Med Mol, Chim Biol Lab, B-6041 Gosselies, Belgium. [Prevot, Pierre-Paul] Univ Libre Bruxelles, Inst Biol & Med Mol, Lab Mol Biol Ectoparasites, B-6041 Gosselies, Belgium. [Bedalov, Antonio] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Mostoslavsky, Raul; Alt, Frederick W.] Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. [Mostoslavsky, Raul; Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [De Smedt, Thibaut] TopoTarget Switzerland SA, CH-1004 Lausanne, Switzerland. RP Leo, O (reprint author), Univ Libre Bruxelles, Inst Biol & Med Mol, Physiol Anim Lab, 12 Rue Prof Jeneer & Brachet, B-6041 Gosselies, Belgium. EM oleo@ulb.ac.be OI Gueydan, Cyril/0000-0003-3097-7667 FU The Belgian Program in Interuniversity Poles of Attraction initiated by the Belgian state, the Prime Minister's office; Research Concerted Action of the Communaute francaise de Belgique; Direction Generale des Technologies de la Recherche et de l'Energie, Region Wallonne ( Belgium); Fonds Jean Brachet and by TopoTarget Switzerland; Fonds national de la recherche scientifique (FRS-FNRS); French community of Belgium FX APO866 was synthesized and kindly provided by Astellas Pharma. We wish to thank G. de Murcia ( formerly at the Ecole Superieure de Biotechnologie de Strasbourg, Illkirch Cedex) for providing the Parp1-knockout mouse strain and V. Sartorelli ( US National Institutes of Health) for providing the pHan-SIRT1 vector ( wild-type and mutant forms). This work was supported by The Belgian Program in Interuniversity Poles of Attraction initiated by the Belgian state, the Prime Minister's office, Science Policy Programming, by a Research Concerted Action of the Communaute francaise de Belgique, by grants from the Direction Generale des Technologies de la Recherche et de l'Energie, Region Wallonne ( Belgium), by a grant from the Fonds Jean Brachet and by TopoTarget Switzerland SA. F. V. G. and M. G. have been supported by research grants from the Fonds national de la recherche scientifique (FRS-FNRS), French community of Belgium. The scientific responsibility is assumed by the authors. NR 26 TC 120 Z9 122 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2009 VL 15 IS 2 BP 206 EP 210 DI 10.1038/nm.1906 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 403ZB UT WOS:000263119400024 PM 19151729 ER PT J AU Wu, D Vu, Q Nguyen, A Stone, JR Stubbs, H Kuhlmann, G Sholl, LM Iafrate, AJ AF Wu, David Vu, Quynh Nguyen, Anhthu Stone, James R. Stubbs, Hannah Kuhlmann, Georgiana Sholl, Lynette M. Iafrate, A. John TI In situ genetic analysis of cellular chimerism SO NATURE MEDICINE LA English DT Article ID POLYMERASE-CHAIN-REACTION; HUMAN GENOME; STEM-CELLS; EPITHELIAL-CELLS; POLYMORPHISMS; TRANSPLANTATION; ENGRAFTMENT; HEART AB Copy number variants are a recently discovered source of large-scale genomic diversity present in all individuals. We capitalize on these inherent genomic differences, focusing on deletion polymorphisms, to develop informative fluorescence in situ hybridization probes with the ability to unequivocally distinguish between donor and recipient cells in situ. These probes are accurate, specific, highly polymorphic and, notably, can be used to assign genetic identity in situ in a completely gender-independent fashion. We anticipate that these polymorphic deletion probes will be useful in further understanding the dynamics of cellular chimerism after transplantation, including the details of chronic organ rejection, post-transplant lymphoproliferative disorder and graft-versus-host disease, and in optimizing future tissue engineering and pluripotent stem cell therapies. C1 [Wu, David; Vu, Quynh; Nguyen, Anhthu; Stone, James R.; Stubbs, Hannah; Kuhlmann, Georgiana; Sholl, Lynette M.; Iafrate, A. John] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Wu, David; Sholl, Lynette M.] Harvard Univ, Sch Mol Genet Pathol Fellowship, Boston, MA 02115 USA. [Wu, David; Stone, James R.; Sholl, Lynette M.; Iafrate, A. John] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM aiafrate@partners.org FU Department of Pathology, Massachusetts General Hospital FX We thank M. Han, J. Miller-Batten and J. Reid for excellent technical assistance. We thank C. Lee (Brigham and Women's Hospital) and S. Kantarci (Beth Israel Deaconess Medical Center) for helpful discussions and reagents. We thank S. Ogino for helpful discussions. This work was supported in part by intramural funding from the Department of Pathology, Massachusetts General Hospital to A.J.I. NR 24 TC 8 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD FEB PY 2009 VL 15 IS 2 BP 215 EP 219 DI 10.1038/nm.1862 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 403ZB UT WOS:000263119400026 PM 19151730 ER PT J AU Perentes, JY Mckee, TD Ley, CD Mathiew, H Dawson, M Padera, TP Munn, LL Jain, RK Boucher, Y AF Perentes, Jean Y. McKee, Trevor D. Ley, Carsten D. Mathiew, Hannah Dawson, Michelle Padera, Timothy P. Munn, Lance L. Jain, Rakesh K. Boucher, Yves TI In vivo imaging of extracellular matrix remodeling by tumor-associated fibroblasts SO NATURE METHODS LA English DT Article ID COLLAGEN; RELAXIN AB Here we integrated multiphoton laser scanning microscopy and the registration of second harmonic generation images of collagen fibers to overcome difficulties in tracking stromal cell-matrix interactions for several days in live mice. We show that the matrix-modifying hormone relaxin increased tumor-associated fibroblast (TAF) interaction with collagen fibers by stimulating beta(1)-integrin activity, which is necessary for fiber remodeling by matrix metalloproteinases. C1 [Perentes, Jean Y.; McKee, Trevor D.; Ley, Carsten D.; Mathiew, Hannah; Dawson, Michelle; Padera, Timothy P.; Munn, Lance L.; Jain, Rakesh K.; Boucher, Yves] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Perentes, Jean Y.; McKee, Trevor D.; Ley, Carsten D.; Mathiew, Hannah; Dawson, Michelle; Padera, Timothy P.; Munn, Lance L.; Jain, Rakesh K.; Boucher, Yves] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Boucher, Y (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM yves@steele.mgh.harvard.edu RI Munn, Lance/L-3950-2016; OI Munn, Lance/0000-0003-0698-7232; Padera, Timothy/0000-0002-3453-9384; McKee, Trevor/0000-0002-2195-6146 FU US National Cancer Institute [R01-CA98706, R01-CA85140, P01-CA80124]; Swiss National Funding [107362]; Fond Decker and Fond de Perfectionement du Centre Hospitalier Universitaire Vaudois FX This work was supported by US National Cancer Institute grants R01-CA98706 (Y.B.), R01-CA85140 and P01-CA80124 ( R. K. J.), and fellowship Swiss National Funding for young scientists 107362, Fond Decker and Fond de Perfectionement du Centre Hospitalier Universitaire Vaudois (J.Y.P.). We thank J. Kahn for technical assistance. NR 12 TC 67 Z9 67 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD FEB PY 2009 VL 6 IS 2 BP 143 EP 145 DI 10.1038/NMETH.1295 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 405CA UT WOS:000263198500014 PM 19151720 ER PT J AU Ho, IC Tai, TS Pai, SY AF Ho, I-Cheng Tai, Tzong-Shyuan Pai, Sung-Yun TI GATA3 and the T-cell lineage: essential functions before and after T-helper-2-cell differentiation SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID TRANSCRIPTION FACTOR GATA-3; DOMINANT-NEGATIVE MUTANT; HEMATOPOIETIC STEM-CELLS; TH2 CYTOKINE EXPRESSION; POSITIVE SELECTION; GENE-EXPRESSION; NKT CELLS; THYMOCYTE DEVELOPMENT; ENFORCED EXPRESSION; DNA-BINDING AB Many advances in our understanding of the molecules that regulate the development, differentiation and function of T cells have been made over the past few years. One important regulator of T-cell differentiation is the transcription factor GATA-binding protein 3 (GATA3). Although the main function of GATA3 is to act as a master transcription factor for the differentiation of T helper 2 (T(H)2) cells, new research has helped to uncover crucial functions of GATA3 in T cells that go beyond T(H)2-cell differentiation and that are important at earlier stages of haematopoietic and lymphoid-cell development. This Review focuses on the functions of GATA3 from early thymocyte development to effector T-cell differentiation. In addition, we discuss the interactions between GATA3 and other transcription factors and signalling pathways, and highlight the functional significance of the GATA3 protein structure. C1 [Ho, I-Cheng; Tai, Tzong-Shyuan] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Pai, Sung-Yun] Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. [Pai, Sung-Yun] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ho, IC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. EM iho@partners.org FU National Institutes of Health, USA [AI054451, AI050601]; Charles H. Hood Foundation Child Health Research Grant; National Science Council, Taiwan FX Owing to space constraints, we could not include every relevant reference and apologize to our colleagues whose work we did not mention. This work is supported by a R01 grant AI054451 ( to I.-C. H.) and a K08 award (AI050601 ( to S.-Y.P.) from the National Institutes of Health, USA, a Charles H. Hood Foundation Child Health Research Grant ( to S.-Y.P.), and a Merit Scholarship ( to T.- S. T.) from National Science Council, Taiwan. NR 117 TC 160 Z9 166 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD FEB PY 2009 VL 9 IS 2 BP 125 EP 135 DI 10.1038/nri2476 PG 11 WC Immunology SC Immunology GA 397BX UT WOS:000262638000015 PM 19151747 ER PT J AU Cantor, H Shinohara, ML AF Cantor, Harvey Shinohara, Mari L. TI Regulation of T-helper-cell lineage development by osteopontin: the inside story SO NATURE REVIEWS IMMUNOLOGY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; COLLAGEN-INDUCED ARTHRITIS; CENTRAL-NERVOUS-SYSTEM; BOVIS-BCG INFECTION; DENDRITIC CELLS; INTRACELLULAR OSTEOPONTIN; AUTOIMMUNE ENCEPHALOMYELITIS; RHEUMATOID-ARTHRITIS; BORRELIA-BURGDORFERI; MULTIPLE-SCLEROSIS AB Studies of osteopontin (OPN)-dependent regulation of immune responses have focused on the cytokine activities of the secreted form of this protein. Recent evidence has revealed that an intracellular form of OPN expressed by dendritic cells regulates the expression of pro-inflammatory cytokines and the differentiation of T helper (T(H))-cell lineages. In this Opinion article, we discuss the properties of both OPN isoforms and their respective contributions to the immune response. We propose that cell-type-specific expression of secreted and intracellular OPN regulates the development of distinct effector T(H) cells, including that of T(H)1 and T(H)17 cells. C1 [Cantor, Harvey] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Cantor, Harvey] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Shinohara, Mari L.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. RP Cantor, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Harvey_Cantor@dfci.harvard.edu FU NCI NIH HHS [T32 CA070083-07, T32 CA070083, T32 CA070083-06, T32 CA070083-08]; NIAID NIH HHS [R01 AI048125, R01 AI048125-01, R01 AI048125-02, R01 AI048125-03, R01 AI048125-04, R01 AI048125-05, R01 AI048125-06A2, R37 AI012184, R37 AI012184-24, R37 AI012184-24S1, R37 AI012184-25, R37 AI012184-26, R37 AI012184-27, R37 AI012184-28, R37 AI012184-29, R37 AI012184-30, R37 AI012184-31] NR 61 TC 73 Z9 79 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD FEB PY 2009 VL 9 IS 2 BP 137 EP 141 DI 10.1038/nri2460 PG 5 WC Immunology SC Immunology GA 397BX UT WOS:000262638000016 PM 19096390 ER PT J AU Norden, AD Drappatz, J Ciampa, AS Doherty, L LaFrankie, DC Kesari, S Wen, PY AF Norden, Andrew D. Drappatz, Jan Ciampa, Abigail Slate Doherty, Lisa LaFrankie, Debra Conrad Kesari, Santosh Wen, Patrick Y. TI Colon perforation during antiangiogenic therapy for malignant glioma SO NEURO-ONCOLOGY LA English DT Article DE antiangiogenic drugs; bevacizumab; gastrointestinal perforation; malignant glioma ID PHASE-II TRIAL; COLORECTAL-CANCER; BOWEL PERFORATION; BEVACIZUMAB; IRINOTECAN; CORTICOSTEROIDS; STEROIDS AB Antiangiogenic drugs have emerged as effective treatment options for patients with recurrent malignant gliomas (MGs). Though this class of drugs is generally well tolerated, rare life-threatening complications, including thromboembolism, hemorrhage, and gastrointestinal (GI) perforation, are reported. We describe six cases of GI perforation among 244 glioma patients (2.5%) during treatment with antiangiogenic agents in combination with chemotherapy and corticosteroids. Two patients succumbed to this complication, and the others recovered. Because GI perforation is a life-threatening yet treatable complication, neurooncologists must have a low threshold to consider it in patients on antiangiogenic drug therapy who present with abdominal pain and other GI complaints. Neuro-Oncology 11, 92-95, 2009 (Posted to Neuro-Oncology [serial online], Doc. D08-00073, August 29, 2008. URL http://neuro-oncology.dukejournals.org; DOI: 10.1215/15228517-2008-071) C1 [Norden, Andrew D.; Drappatz, Jan; Ciampa, Abigail Slate; Doherty, Lisa; LaFrankie, Debra Conrad; Kesari, Santosh; Wen, Patrick Y.] Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, Boston, MA 02115 USA. [Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. [Norden, Andrew D.; Drappatz, Jan; Kesari, Santosh; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. RP Norden, AD (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM anorden@partners.org RI Kesari, Santosh/E-8461-2013 NR 17 TC 13 Z9 13 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1522-8517 EI 1523-5866 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD FEB PY 2009 VL 11 IS 1 BP 92 EP 95 DI 10.1215/15228517-2008-071 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 406LK UT WOS:000263296800011 PM 18757774 ER PT J AU Webster, CM Kelly, S Koike, MA Chock, VY Giffard, RG Yenari, MA AF Webster, Carla M. Kelly, Stephen Koike, Maya A. Chock, Valerie Y. Giffard, Rona G. Yenari, Midori A. TI Inflammation and NF kappa B activation is decreased by hypothermia following global cerebral ischemia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Global cerebral ischemia; Hypothermia; Inflammation; Nuclear factor-kappa B; Microglia ID LEUKOCYTE-ENDOTHELIUM INTERACTION; TRANSIENT FOCAL ISCHEMIA; CENTRAL-NERVOUS-SYSTEM; NITRIC-OXIDE SYNTHASE; MILD HYPOTHERMIA; EXPERIMENTAL STROKE; THERAPEUTIC HYPOTHERMIA; POSTISCHEMIC HYPOTHERMIA; ARTERY OCCLUSION; MICROGLIAL ACTIVATION AB We previously showed that hypothermia attenuates inflammation in focal cerebral ischemia (FCI) by suppressing activating kinases of nuclear factor-kappa B (NF kappa B). Here we characterize the inflammatory response in global cerebral ischemia (GCI), and the influence of mild hypothermia. Rodents were subjected to GCI by bilateral carotid artery occlusion. The inflammatory response was accompanied by microglial activation, but not neutrophil infiltration, or blood brain barrier disruption. Mild hypothermia reduced CA1 damage, decreased microglial activation and decreased nuclear NF kappa B translocation and activation. Similar anti-inflammatory effects of hypothermia were observed in a model of pure brain inflammation that does not cause brain cell death. Primary microglial cultures subjected to oxygen glucose deprivation (OGD) or stimulated with LPS under hypothermic conditions also experienced less activation and less NF kappa B translocation. However, NF kappa B regulatory proteins were not affected by hypothermia. The inflammatory response following GCI and hypothermia's anti-inflammatory mechanism is different from that observed in FCI. Published by Elsevier Inc. C1 [Webster, Carla M.; Koike, Maya A.; Yenari, Midori A.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. [Webster, Carla M.; Koike, Maya A.; Yenari, Midori A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Webster, Carla M.; Koike, Maya A.; Chock, Valerie Y.; Giffard, Rona G.] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. [Kelly, Stephen] Univ Bristol, Bristol BS1 3NY, Avon, England. RP Yenari, MA (reprint author), Univ Calif San Francisco, Dept Neurol, 4150 Clement St, San Francisco, CA 94121 USA. EM yenari@alum.mit.edu RI Kelly, Stephen/A-8307-2010 FU NIH [RO1 NS40516, P50 NS14543, P01 NS37520, R01 NS53898]; AHA [EIA0540066N] FX This work was made possible by the following institutions and grants: NIH RO1 NS40516 (MAY), AHA EIA0540066N (MAY), NIH P50 NS14543 and P01 NS37520 (RGG, MAY), NIH R01 NS53898 (RGG). NR 61 TC 57 Z9 67 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD FEB PY 2009 VL 33 IS 2 BP 301 EP 312 DI 10.1016/j.nbd.2008.11.001 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 403ZM UT WOS:000263120500018 PM 19063968 ER PT J AU Goldstein, JN Fazen, LE Wendell, L Chang, YC Rost, NS Snider, R Schwab, K Chanderraj, R Kabrhel, C Kinnecom, C FitzMaurice, E Smith, EE Greenberg, SM Rosand, J AF Goldstein, Joshua N. Fazen, Louis E. Wendell, Lauren Chang, Yuchiao Rost, Natalia S. Snider, Ryan Schwab, Kristin Chanderraj, Rishi Kabrhel, Christopher Kinnecom, Catherine FitzMaurice, Emilie Smith, Eric E. Greenberg, Steven M. Rosand, Jonathan TI Risk of Thromboembolism Following Acute Intracerebral Hemorrhage SO NEUROCRITICAL CARE LA English DT Article DE Cerebral hemorrhage; Warfarin; Venous thrombosis; Pulmonary embolism; Brain ischemia; Myocardial ischemia ID RECOMBINANT FACTOR VIIA; ACUTE ISCHEMIC-STROKE; DEEP-VEIN THROMBOSIS; DOSE ANTICOAGULATION RATHER; ACTIVATED FACTOR-VII; QUALITY-OF-CARE; VENOUS THROMBOEMBOLISM; EFFECTIVE PROPHYLAXIS; CONTROLLED-TRIALS; HEPARIN-THERAPY AB Intracerebral hemorrhage (ICH) is the most feared complication of oral anticoagulant therapy (OAT). While anticoagulated patients have increased severity of bleeding following ICH, they may also be at increased risk for thromboembolic events (TEs) given that they had been prescribed OAT prior to their ICH. We hypothesized that TEs are relatively common following ICH, and that anticoagulated patients are at higher risk for these complications. Consecutive patients with primary ICH presenting to a tertiary care hospital from 1994 to 2006 were prospectively characterized and followed. Hospital records were retrospectively reviewed for clinically relevant in-hospital TEs and patients were prospectively followed for 90 day mortality. For 988 patients of whom 218 (22%) were on OAT at presentation, median hospital length of stay was 7 (IQR 4-13) days and 90-day mortality was 36%. TEs were diagnosed in 71 patients (7.2%) including pulmonary embolism (1.8%), deep venous thrombosis (1.1%), myocardial ischemia (1.6%), and cerebrovascular ischemia (3.0%). Mean time to event was 8.4 +/- A 7.0 days. Rates of TE were 5% among those with OAT-related ICH and 8% among those with non-OAT ICH (P = 0.2). After multivariable Cox regression, the only independent risk factor for developing a TE was external ventricular drain placement (HR 2.1, 95% CI 1.1-4.1, P = 0.03). TEs had no effect on 90-day mortality (HR 0.7, 95% CI 0.5-1.1, P = 0.1). The incidence of TEs in an unselected ICH population was 7.2%. Patients with OAT-related ICH were not at increased risk of TEs. C1 [Goldstein, Joshua N.; Kabrhel, Christopher] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Fazen, Louis E.; Wendell, Lauren; Rost, Natalia S.; Snider, Ryan; Schwab, Kristin; Chanderraj, Rishi; Kinnecom, Catherine; FitzMaurice, Emilie; Smith, Eric E.; Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Fazen, Louis E.; Rost, Natalia S.; Snider, Ryan; Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Chang, Yuchiao] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Goldstein, JN (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgoldstein@partners.org RI Smith, Eric/C-5443-2012; Goldstein, Joshua/H-8953-2016; OI Smith, Eric/0000-0003-3956-1668; Kabrhel, Christopher/0000-0002-8699-7176 FU Novo Nordisk A/S; Miles and Eleanor Shore 50th Anniversary Fellowship Award; National Institute of Neurological Disorders and Stroke [NIH 1 K23 NS42695, R01 NS04217]; Jerome Lyle Rappaport Charitable Foundation FX This work was supported by an unrestricted research grant from Novo Nordisk A/S, the Miles and Eleanor Shore 50th Anniversary Fellowship Award, the National Institute of Neurological Disorders and Stroke (NIH 1 K23 NS42695, R01 NS04217), and the Jerome Lyle Rappaport Charitable Foundation. NR 37 TC 27 Z9 31 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2009 VL 10 IS 1 BP 28 EP 34 DI 10.1007/s12028-008-9134-3 PG 7 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 397GZ UT WOS:000262652200004 PM 18810667 ER PT J AU Salomone, S Soydan, G Moskowitz, MA Sims, JR AF Salomone, Salvatore Soydan, Guray Moskowitz, Michael A. Sims, John Randall TI Inhibition of Cerebral Vasoconstriction by Dantrolene and Nimodipine SO NEUROCRITICAL CARE LA English DT Article DE Dantrolene; Nimodipine; Vasospasm; Ryanodine receptor; Calcium; Serotonin; Endothelin-1; Phenylephrine; Basilar artery; Sarco-endoplasmic reticulum ID SMOOTH-MUSCLE-CELLS; EXPERIMENTAL SUBARACHNOID HEMORRHAGE; ISOLATED BASILAR ARTERY; BLOOD-FLOW REDUCTION; ADP-RIBOSYL CYCLASE; RYANODINE RECEPTOR; 5-HYDROXYTRYPTAMINE RECEPTORS; 5-HT1-LIKE RECEPTORS; CONTRACTILE RESPONSE; HYPERTENSIVE-RATS AB Cerebral vasoconstriction is associated with increased cytosolic Ca(2+) concentration in vascular smooth muscle, presumably due to Ca(2+) influx and Ca(2+) release from intracellular stores. We tested the hypothesis that dantrolene (a blocker of Ca(2+)-induced Ca(2+) release from the ryanodine receptor channel on the sarco-endoplasmic reticulum) would potentiate the action of nimodipine (a voltage-dependent L-type Ca(2+) channel blocker, considered standard therapy for SAH) in inhibiting the vasoconstriction of isolated cerebral arteries. Sprague-Dawley rat basilar and femoral arteries were analyzed for ryanodine receptor expression by immunofluorescence and PCR. Vasoconstriction of basilar artery ex vivo was measured in a wire myograph while exposed to serotonin (5-HT) or endothelin-1 (ET-1) in the presence or absence of dantrolene (10-100 mu M) and/or nimodipine (30 nM). Femoral artery was examined for comparison. Basilar and femoral arteries express only the ryanodine receptor 3 (RyR3) isoform. In both basilar and femoral arteries, dantrolene significantly inhibited the constriction to 5-HT, whereas it poorly affected the constriction to ET-1. The inhibitory effect of dantrolene on 5-HT was substantially increased by nimodipine, inducing a 10-fold increase in the 50% effective concentration of 5-HT and a 46% reduction in maximum basilar constriction. In femoral artery, dantrolene modestly affected constriction to phenylephrine and there was no interaction with nimodipine. Dantrolene has synergistic effects with nimodipine against 5-HT-induced vasoconstriction in isolated cerebral arteries. Dantrolene-nimodipine interaction will require testing in a pathophysiological model but might provide treatment for reducing SAH-related vasospasm or other 5-HT-related vasospastic syndromes, such as Call-Fleming syndrome. C1 [Salomone, Salvatore; Soydan, Guray; Moskowitz, Michael A.; Sims, John Randall] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Sims, John Randall] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Div Neurocrit Care & Acute Stroke, Charlestown, MA 02129 USA. RP Sims, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, CNY149 Rm64212A,13th St, Charlestown, MA 02129 USA. EM jsims@partners.org OI Salomone, Salvatore/0000-0001-5307-6103 FU NIH [1 K08 NS049241-01A2] FX Dr. John Sims is supported by NIH 1 K08 NS049241-01A2. NR 57 TC 23 Z9 25 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2009 VL 10 IS 1 BP 93 EP 102 DI 10.1007/s12028-008-9153-0 PG 10 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 397GZ UT WOS:000262652200016 PM 18923817 ER PT J AU Muehlschlegel, S Sims, JR AF Muehlschlegel, Susanne Sims, John R. TI Dantrolene: Mechanisms of Neuroprotection and Possible Clinical Applications in the Neurointensive Care Unit SO NEUROCRITICAL CARE LA English DT Review DE Dantrolene; Vasospasm; Ryanodine receptor; Calcium; Serotonin; Sarco-endoplasmic reticulum; Neuroprotection, ischemia, seizure; Trauma ID METHYL-D-ASPARTATE; OXYGEN-GLUCOSE-DEPRIVATION; CEREBRAL CORTICAL-NEURONS; CEREBELLAR GRANULE CELLS; RAT HIPPOCAMPAL-NEURONS; RETICULUM CA2+ RELEASE; ENDOPLASMIC-RETICULUM; SARCOPLASMIC-RETICULUM; INDUCED NEUROTOXICITY; CALCIUM HOMEOSTASIS AB Calcium plays a central role in neuronal function and injury. Dantrolene, an inhibitor of the ryanodine receptor, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We review the available data of dantrolene as a potential neuroprotective agent and briefly summarize its other pharmacologic effects that may have potential applications for patients in the neurointensive care unit (NICU). Areas with the need for continued research are identified. C1 [Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Neurocrit Care & Acute Stroke, Boston, MA 02129 USA. [Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Sch Med, Charlestown, MA 02129 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, UMASS Mem Med Ctr, Dept Neurol, Worcester, MA 01605 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, UMASS Mem Med Ctr, Dept Anesthesiol Crit Care, Worcester, MA 01605 USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, UMASS Mem Med Ctr, Dept Surg, Worcester, MA 01605 USA. RP Sims, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Div Neurocrit Care & Acute Stroke, Boston, MA 02129 USA. EM jsims@partners.org FU NIH [1 K08 NS049241-01A2] FX Dr. John R. Sims is supported by NIH 1 K08 NS049241-01A2. We would like to thank Susanne L. Loomis for help in preparing Fig. 1. NR 117 TC 32 Z9 36 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 EI 1556-0961 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2009 VL 10 IS 1 BP 103 EP 115 DI 10.1007/s12028-008-9133-4 PG 13 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 397GZ UT WOS:000262652200017 PM 18696266 ER PT J AU Muehlschlegel, S Rordorf, G Bodock, M Sims, JR AF Muehlschlegel, Susanne Rordorf, Guy Bodock, Michael Sims, John R. TI Dantrolene Mediates Vasorelaxation in Cerebral Vasoconstriction: A Case Series SO NEUROCRITICAL CARE LA English DT Article DE Subarachnoid hemorrhage; Vasospasm; Cerebral vasoconstriction; Dantrolene; Transcranial Doppler; Delayed ischemic neurologic deficit ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; VASOSPASM DIAGNOSIS; ANGIOGRAPHY; ARTERIES; RECEPTOR; NEURONS; KINASE; DEATH; CA2+; RAT AB Cerebral vasoconstriction syndromes such as vasospasm after subarachnoid hemorrhage (SAH) and trauma, or Call-Fleming syndrome are difficult to treat, and can lead to substantial disability and death. Dantrolene, a ryanodine receptor antagonist, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We examined the effect of dantrolene on middle cerebral artery (MCA) blood flow velocities as measured by transcranial Doppler (TCD). Three consecutive patients with elevated MCA TCD velocities receiving dantrolene (2.5 mg/kg i.v. q6h) were retrospectively reviewed. Average MCA peak systolic, mean flow velocities, and the pulsatility index (PI) before and after the dantrolene infusion were compared within patients. Systemic physiological parameters (blood pressure, heart rate, central venous pressure, intracranial pressure, body temperature, and cooling water temperature) were retrospectively collected 6 h before and after the dantrolene infusion. MCA peak systolic velocities (mean +/- A SE) for the three patients were 297 +/- A 3, 248 +/- A 8, and 268 +/- A 19 cm/s before dantrolene and 159 +/- A 9, 169 +/- A 8, and 216 +/- A 12 cm/s after dantrolene. Average mean flow velocities showed the same trend. Interestingly, the PI increased slightly from 0.6, 0.52, and 0.67 before dantrolene, to 1.17, 0.71, and 0.77 after dantrolene. Systemic physiological parameters remained stable in all three patients. Dantrolene attenuated cerebral vasoconstriction as measured by TCD without altering systemic physiological parameters. This suggests that intracellular calcium release from ryanodine channels in smooth muscle might play a role in vasospasm. A prospective study is underway to test this hypothesis. C1 [Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Rordorf, Guy; Sims, John R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol Neurocrit Care & Acute Stroke, Boston, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Neurol, UMASS Mem Med Ctr, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Anesthesiol Crit Care, UMASS Mem Med Ctr, Worcester, MA USA. [Muehlschlegel, Susanne] Univ Massachusetts, Sch Med, Dept Surg, UMASS Mem Med Ctr, Worcester, MA USA. [Bodock, Michael] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pharm, Boston, MA USA. RP Sims, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, CNY149 Rm 6212A, Charlestown, MA 02129 USA. EM jsims@partners.org FU NINDS NIH HHS [1 K08 NS049241-01A2, K08 NS049241, K08 NS049241-01A2] NR 24 TC 11 Z9 13 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1541-6933 J9 NEUROCRIT CARE JI Neurocrit. Care PD FEB PY 2009 VL 10 IS 1 BP 116 EP 121 DI 10.1007/s12028-008-9132-5 PG 6 WC Critical Care Medicine; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA 397GZ UT WOS:000262652200018 PM 18696267 ER PT J AU Goldstein, AM Mwizerwa, O Nagy, N AF Goldstein, A. M. Mwizerwa, O. Nagy, N. TI Endothelial cells promote migration and proliferation of enteric neural crest cells via beta 1 integrin signaling SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Goldstein, A. M.; Mwizerwa, O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Nagy, N.] Semmelweis Univ, H-1085 Budapest, Hungary. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD FEB PY 2009 VL 21 IS 2 BP XV EP XV PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 397UT UT WOS:000262688300063 ER PT J AU Nagy, N Csikos, G Molnar, D Goldstein, AM Olah, I AF Nagy, N. Csikos, G. Molnar, D. Goldstein, A. M. Olah, I. TI Characterization and origin of a novel cell type in the avian enteric nervous system SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Meeting Abstract C1 [Nagy, N.; Csikos, G.; Molnar, D.; Olah, I.] Semmelweis Univ, Fac Med, Dept Human Morphol & Dev Biol, H-1085 Budapest, Hungary. [Goldstein, A. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD FEB PY 2009 VL 21 IS 2 BP XX EP XX PG 1 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 397UT UT WOS:000262688300082 ER PT J AU Schjeide, BM McQueen, MB Mullin, K DiVito, J Hogan, MF Parkinson, M Hooli, B Lange, C Blacker, D Tanzi, RE Bertram, L AF Schjeide, Brit-Maren M. McQueen, Matthew B. Mullin, Kristina DiVito, Jason Hogan, Meghan F. Parkinson, Michele Hooli, Basavaraj Lange, Christoph Blacker, Deborah Tanzi, Rudolph E. Bertram, Lars TI Assessment of Alzheimer's disease case-control associations using family-based methods SO NEUROGENETICS LA English DT Article DE Alzheimer's disease; Risk factors; Genetic association; Meta-analysis; Family-based association testing ID ANGIOTENSIN-CONVERTING ENZYME; NICOTINIC ACETYLCHOLINE-RECEPTORS; CANDIDATE GENES; IRON; AGE; TRANSFERRIN; BETA; ACE; POLYMORPHISMS; METAANALYSIS AB The genetics of Alzheimer's disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32.13, and GWA_7p15.2), all showing significant association with AD risk in the AlzGene meta-analyses, in a large collection of family-based samples comprised of 4,180 subjects from over 1,300 pedigrees. Overall, we observe significant association with risk for AD and polymorphisms in ACE, CHRNB2, TF, and an as yet uncharacterized locus on chromosome 7p15.2 [rs1859849]. For all four loci, the association was observed with the same alleles as in the AlzGene meta-analyses. The convergence of case-control and family-based findings suggests that these loci currently represent the most promising AD gene candidates. Further fine-mapping and functional analyses are warranted to elucidate the potential biochemical mechanisms and epidemiological relevance of these genes. C1 [Schjeide, Brit-Maren M.; Mullin, Kristina; DiVito, Jason; Hogan, Meghan F.; Parkinson, Michele; Hooli, Basavaraj; Tanzi, Rudolph E.; Bertram, Lars] Massachusetts Gen Hosp, Dept Neurol, MassGeneral Inst Neurodegenerat Dis MIND, Genet & Aging Res Unit,MGH E MIND, Charlestown, MA 02129 USA. [McQueen, Matthew B.; Blacker, Deborah] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [McQueen, Matthew B.] Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA. [Lange, Christoph] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Blacker, Deborah] Massachusetts Gen Hosp, Dept Psychiat, Gerontol Res Unit, Charlestown, MA 02129 USA. RP Bertram, L (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGeneral Inst Neurodegenerat Dis MIND, Genet & Aging Res Unit,MGH E MIND, 114 16th St, Charlestown, MA 02129 USA. EM bertram.lars@gmail.com RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NIA; NIMH; Extendicare Foundation; Cure Alzheimer's Fund FX The authors wish to thank all families for participating in this study. This work was sponsored by grants from the NIA (to L. B.), NIMH (to R. T.), and the Extendicare Foundation (to L. B.). The AlzGene database project is funded by the Cure Alzheimer's Fund (to L. B.). NR 31 TC 43 Z9 46 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1364-6745 J9 NEUROGENETICS JI Neurogenetics PD FEB PY 2009 VL 10 IS 1 BP 19 EP 25 DI 10.1007/s10048-008-0151-3 PG 7 WC Genetics & Heredity; Clinical Neurology SC Genetics & Heredity; Neurosciences & Neurology GA 397HA UT WOS:000262652300004 PM 18830724 ER PT J AU Ou, WM Hamalainen, MS Golland, P AF Ou, Wanmei Haemaelaeinen, Matti S. Golland, Polina TI A distributed spatio-temporal EEG/MEG inverse solver SO NEUROIMAGE LA English DT Article DE EEG; MEG; Inverse solver; l(1)-norm; Temporal basis functions; Second-order cone programming ID SPARSE SIGNAL RECONSTRUCTION; SURFACE-BASED ANALYSIS; HUMAN-BRAIN; SOURCE LOCALIZATION; CORTICAL ACTIVITY; SIMPLEX-METHOD; MEDIAN NERVE; MEG DATA; MODEL; MAGNETOENCEPHALOGRAPHY AB We propose a novel l(1)l(2)-norm inverse solver for estimating the sources of EEG/MEG signals. Based on the standard l(1)-norm inverse solvers, this sparse distributed inverse solver integrates the l(1)-norm spatial model with a temporal model of the source signals in order to avoid unstable activation patterns and "spiky" reconstructed signals often produced by the currently used sparse solvers. The joint spatio-temporal model leads to a cost function with an l(1)l(2)-norm regularizer whose minimization can be reduced to a convex second-order cone programming (SOCP) problem and efficiently solved using the interior-point method. The efficient computation of the SOCP problem allows us to implement permutation tests for estimating statistical significance of the inverse solution. Validation with simulated and human MEG data shows that the proposed solver yields source time course estimates qualitatively similar to those obtained through dipole fitting, but without the need to specify the number of dipole sources in advance. Furthermore, the l(1)l(2)-norm solver achieves fewer false positives and a better representation of the source locations than the conventional l(2) minimum-norm estimates. (C) 2008 Elsevier Inc. All rights reserved. C1 [Ou, Wanmei; Golland, Polina] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA. [Haemaelaeinen, Matti S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Martinos Ctr Biomed Imaging, Boston, MA USA. RP Ou, WM (reprint author), MIT, Comp Sci & Artificial Intelligence Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM wanmei@mit.edu; msh@nmr.mgh.harvard.edu; polina@csail.mit.edu RI Hamalainen, Matti/C-8507-2013 FU NIH NAMIC [U54-EB005149]; NIH NCRR mBIRN [U24-RR021382]; NIH NINDS [R01-NS051826]; NIH BRP [R01-E006385]; NIH NCRR NAC [P41RR13218]; NIH NCRR CFNT [P41-RR14075]; NSF CAREER Award [0642971]; U.S. DOE Award [DE-FG02-99ER62764]; NSF graduate fellowship FX We thank Dr. Dmitry Malioutov and Dr. Xin Huang for the interesting discussion on SOCP. We also thank Biswajit Bose, Hesheng Liu, and Thomas Yeo for helpful comments on this work, and Dr. Van Leemput for proof reading this draft. This work was supported in part by NIH NAMIC U54-EB005149, NIH NCRR mBIRN U24-RR021382, NIH NINDS R01-NS051826, NIH BRP R01-E006385, NIH NCRR NAC P41RR13218 and NIH NCRR CFNT P41-RR14075 grants, by the NSF CAREER Award 0642971, and by U.S. DOE Award Number DE-FG02-99ER62764 to the MIND Institute. Wanmei Ou is partially supported by an NSF graduate fellowship. NR 59 TC 82 Z9 82 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2009 VL 44 IS 3 BP 932 EP 946 DI 10.1016/j.neuroimage.2008.05.063 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KL UT WOS:000262301500033 PM 18603008 ER PT J AU Humbert, IA Fitzgerald, ME McLaren, DG Johnson, S Porcaro, E Kosmatka, K Hind, J Robbins, J AF Humbert, Ianessa A. Fitzgerald, Michelle E. McLaren, Donald G. Johnson, Sterling Porcaro, Eva Kosmatka, Kris Hind, Jacqueline Robbins, JoAnne TI Neurophysiology of swallowing: Effects of age and bolus type SO NEUROIMAGE LA English DT Article ID CEREBRAL CORTICAL REPRESENTATION; PENETRATION-ASPIRATION SCALE; HEMISPHERIC ASYMMETRIES; SUSTAINED ATTENTION; NORMAL ADULTS; CORTEX; MOTOR; FMRI; INDIVIDUALS; DEGLUTITION AB This study examined age-related changes in swallowing from an integrated biomechanical and functional imaging perspective in order to more comprehensively characterize changes in swallowing associated with age. We examined swallowing-related fMRI brain activity and videoflouroscopic biomechanics of three bolus types (saliva, water and barium) in 12 young and 11 older adults. We found that age-related neurophysiological changes in swallowing are evident. The group of older adults recruited more cortical regions than young adults, including the pericentral gyri and inferior frontal gyrus pars opercularis and pars triangularis (primarily right-sided). Saliva swallows elicited significantly higher BOLD responses in regions important for swallowing compared to water and barium. In separate videofluoroscopy sessions, we obtained durational measures of supine swallowing. The older cohort had significantly longer delays before the onset of the pharyngeal swallow response and increased residue of ingested material in the pharynx. These findings suggest that older adults without neurological insult elicit more cortical involvement to complete the same swallowing tasks as younger adults. (C) 2008 Elsevier Inc. All rights reserved. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. Univ Wisconsin, Madison, WI 53706 USA. RP Humbert, IA (reprint author), 98 N Broadway,Suite 413, Baltimore, MD 21231 USA. EM ihumber1@jhmi.edu RI McLaren, Donald/G-9906-2011; OI Johnson, Sterling/0000-0002-8501-545X FU National Institutes of Health (NIH); NCRR; The Training and Education to Advance MultidisciplinaryClinical- Research (TEAM) Program [8K12RR023268-02]; National Institutes of Health and National Institute [T32 AG20013]; William S. Middleton Memorial VA Hospital Geriatric Research Education and Clinical Center (GRECC) [2008-16] FX This is GRECC manuscript # 2008-16. NR 55 TC 44 Z9 49 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD FEB 1 PY 2009 VL 44 IS 3 BP 982 EP 991 DI 10.1016/j.neuroimage.2008.10.012 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KL UT WOS:000262301500037 PM 19010424 ER PT J AU Wilcox, T Bortfeld, H Woods, R Wruck, E Armstrong, J Boas, D AF Wilcox, Teresa Bortfeld, Heather Woods, Rebecca Wruck, Eric Armstrong, Jennifer Boas, David TI Hemodynamic changes in the infant cortex during the processing of featural and spatiotemporal information SO NEUROPSYCHOLOGIA LA English DT Article DE Infants; Near-infrared spectroscopy; Object processing; Featural information; Spatiotemporal information ID NEAR-INFRARED SPECTROSCOPY; LATERAL OCCIPITAL COMPLEX; POSITRON EMISSION TOMOGRAPHY; MONKEY INFEROTEMPORAL CORTEX; INFERIOR TEMPORAL CORTEX; OBJECT RECOGNITION; BRAIN ACTIVITY; OXYGENATION CHANGES; OPTICAL TOPOGRAPHY; OCCLUSION EVENTS AB Over the last 20 years neuroscientists have learned a great deal about the ventral and dorsal object processing pathways in the adult brain, yet little is known about the functional development of these pathways. The present research assessed the extent to which different patterns of neural activation, as measured by changes in blood volume and oxygenation, are observed in infant visual and temporal cortex in response to events that involve processing of featural differences or spatiotemporal discontinuities. Infants aged 6.5 months were tested. Increased neural activation was observed in visual cortex in response to a featural-difference and a spatiotemporal-discontinuity event. In addition, increased neural activation was observed in temporal cortex in response to the featural-difference but not the spatiotemporal-discontinuity event. The outcome of this experiment reveals early functional specialization of temporal cortex and lays the foundation for future investigation of the maturation of object processing pathways in humans. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Wilcox, Teresa] Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. [Boas, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Anthinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. RP Wilcox, T (reprint author), Texas A&M Univ, Dept Psychol, 4235 TAMU, College Stn, TX 77843 USA. EM tgw@psyc.tamu.edu OI Bortfeld, Heather/0000-0002-3545-5449 FU National Institutes of Health [HD48943, HD46533, P41-RR14075] FX This research was supported by grants from the National Institutes of Health (HD48943 to T.W., HD46533 to H.B., and P41-RR14075 to D.B.). We would like to thank Tracy Smith and the undergraduate assistants in the Infant Cognition Laboratory at Texas A&M University for their help with data collection and the parents who so graciously agreed to have their infants participate in the research. NR 58 TC 26 Z9 26 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3932 J9 NEUROPSYCHOLOGIA JI Neuropsychologia PD FEB PY 2009 VL 47 IS 3 BP 657 EP 662 DI 10.1016/j.neuropsychologia.2008.11.014 PG 6 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 419RP UT WOS:000264237300007 PM 19071143 ER PT J AU Benmansour, S Piotrowski, JP Altamirano, AV Frazer, A AF Benmansour, Saloua Piotrowski, Jonathan P. Altamirano, Alfonso V. Frazer, Alan TI Impact of Ovarian Hormones on the Modulation of the Serotonin Transporter by Fluvoxamine SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE serotonin transporter; estradiol; progesterone; fluvoxamine; chronoamperometry; hippocampus ID APPLIED UPTAKE INHIBITORS; ESTROGEN-RECEPTOR BETA; CLEARANCE IN-VIVO; ASTERISK-D REPORT; MESSENGER-RNA; RAT-BRAIN; GENDER-DIFFERENCES; PROTEIN-KINASE; FEMALE RATS; PROGESTERONE-RECEPTOR AB Most preclinical studies examining the mechanism(s) of action of antidepressants are carried out using male animals. Blockade of serotonin transporter (SERT) function by selective serotonin reuptake inhibitors (SSRIs) is the initial event that triggers a not completely understood process that results in clinical improvement in depression. To investigate whether there are differences in the ability of SSRIs to inhibit the SERT between male and female rats at different phases of the estrous cycle, clearance of locally applied serotonin (5-HT) was measured by in vivo chronoamperometry. Local application of the SSRI, fluvoxamine, directly into the CA3 area of hippocampus increased significantly 5-HT clearance time parameters in male rats and female rats in estrus or diestrus, but not in proestrus. The contribution of ovarian steroids to this result was investigated in ovariectomized (OVX) rats treated with estradiol benzoate (EB) and/or progesterone (P). In OVX-control rats, fluvoxamine increased clearance time parameters, whereas EB and/or P treatment blocked this effect, consistent with what was seen in female rats in proestrus. This effect was gender-specific, since treatment of castrated rats with EB/P had no effect on the ability of fluvoxamine to slow 5-HT clearance. The time course of hormonal effects showed that 1-60 min after local application of 17-beta-estradiol (E-2) into the CA3 region of OVX rats, fluvoxamine had no effect on clearance time of 5-HT. E-2-BSA mimicked E-2's effects at 10 min but not at 60 min. Pretreatment with estrogen receptor antagonists blocked the effects of E-2. The finding that acutely both estradiol and progesterone can inhibit the ability of an SSRI to slow the clearance of 5-HT, may have important implications for the use of SSRIs in women. C1 [Benmansour, Saloua; Piotrowski, Jonathan P.; Altamirano, Alfonso V.; Frazer, Alan] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Frazer, Alan] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Benmansour, S (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol MC 7764, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM benmansour@uthscsa.edu FU NARSAD; Department of Veterans Affairs; Forest Research Institute; Eli Lilly and Company; Wyeth Pharmaceuticals FX This work was supported by funds from NARSAD and the Department of Veterans Affairs. We thank Dr Andrea Gore for help with analysis of hormones levels and Kelly Sharp and Dr Georgianna Gould for technical assistance.; Dr Benmansour, Mr Piotrowski, and Mr Altamirano report no biomedical financial interests or potential conflicts of interest. Dr Frazer reports that he has been on advisory boards for Cyberonics Inc. and H Lundbeck A/S and that he has consulted and/or received research support for preclinical studies from Forest Research Institute, Eli Lilly and Company, and Wyeth Pharmaceuticals, but no support for this study was received by any pharmaceutical company. NR 66 TC 26 Z9 26 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X EI 1740-634X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2009 VL 34 IS 3 BP 555 EP 564 DI 10.1038/npp.2008.23 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 393MA UT WOS:000262376200004 PM 18322468 ER PT J AU Franklin, TR Lohoff, FW Wang, Z Sciortino, N Harper, D Li, Y Jens, W Cruz, J Kampman, K Ehrman, R Berrettini, W Detre, JA O'Brien, CP Childress, AR AF Franklin, Teresa R. Lohoff, Falk W. Wang, Ze Sciortino, Nathan Harper, Derek Li, Yin Jens, Will Cruz, Jeffrey Kampman, Kyle Ehrman, Ron Berrettini, Wade Detre, John A. O'Brien, Charles P. Childress, Anna Rose TI DAT Genotype Modulates Brain and Behavioral Responses Elicited by Cigarette Cues SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE fMRI; dopamine transporter; gene; smoking; reward; cue ID DOPAMINE TRANSPORTER GENE; DRD4 VNTR POLYMORPHISM; NUCLEUS-ACCUMBENS; SMOKING CUES; LIMBIC ACTIVATION; RECEPTOR GENE; CONDITIONED INCREASES; NICOTINE DEPENDENCE; INTRAVENOUS COCAINE; STRESS-DISORDER AB We previously demonstrated differential activation of the mesocorticolimbic reward circuitry in response to cigarette cues independent of withdrawal. Despite robust effects, we noted considerable individual variability in brain and subjective responses. As dopamine (DA) is critical for reward and its predictive signals, genetically driven variation in DA transmission may account for the observed differences. Evidence suggests that a variable number of tandem repeats (VNTRs) polymorphism in the DA transporter (DAT) SLC6A3 gene may influence DA transport. Brain and behavioral responses may be enhanced in probands carrying the 9-repeat allele. To test this hypothesis, perfusion fMR images were acquired during cue exposure in 19 smokers genotyped for the 40 bp VNTR polymorphism in the SLC6A3 gene. Contrasts between groups revealed that 9-repeat (9-repeats) had a greater response to smoking (vs nonsmoking) cues than smokers homozygous for the 10-repeat allele (10/10-repeats) bilaterally in the interconnected ventral striatal/pallidal/orbitofrontal cortex regions (VS/VP/OFC). Activity was increased in 9-repeats and decreased in 10/10-repeats in the VS/VP/OFC (p<0.001 for all analyses). Brain activity and craving was strongly correlated in 10/10-repeats in these regions and others (anterior cingulate, parahippocampal gyrus, and insula; r(2) = 0.79-0.86, p<0.001 in all regions). Alternatively, there were no significant correlations between brain and behavior in 9-repeats. There were no differences in cigarette dependence, demographics, or resting baseline neural activity between groups. These results provide evidence that genetic variation in the DAT gene contributes to the neural and behavioral responses elicited by smoking cues. C1 [Franklin, Teresa R.; Lohoff, Falk W.; Wang, Ze; Sciortino, Nathan; Harper, Derek; Li, Yin; Jens, Will; Cruz, Jeffrey; Kampman, Kyle; Ehrman, Ron; Berrettini, Wade; O'Brien, Charles P.; Childress, Anna Rose] Univ Penn, Dept Psychiat, Addict Treatment Res Ctr, Philadelphia, PA 19104 USA. [Kampman, Kyle; Ehrman, Ron; O'Brien, Charles P.; Childress, Anna Rose] Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. [Kampman, Kyle; Ehrman, Ron; O'Brien, Charles P.; Childress, Anna Rose] VA VISN 4 MIRECC, Philadelphia, PA USA. [Detre, John A.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Detre, John A.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Addict Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007; Lohoff, Falk/M-7951-2016; OI Jens, William/0000-0001-5201-1412 FU NIH [DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, NS045839, BCS-0224007, RR02305, 1K08MH080372-01A1 VA VISN 4 MIRECC]; GCRC of the University of Pennsylvania FX This work was supported by NIH grants DA015149, K01 DA 015426-011A1, 5-P60-DA-005186-18, and NS045839, BCS-0224007, RR02305, 1K08MH080372-01A1 VA VISN 4 MIRECC, and the GCRC of the University of Pennsylvania. We acknowledge the nursing staff at the University of Pennsylvania Addiction Treatment Research for conducting physical evaluations. We also thank our clinicians Anita Hole PhD, Jesse Suh, PsyD, and Marta MacDougal, PsyD for conducting the psychological evaluations. And third, we take this opportunity to thank the MRI technicians at the Hospital of the University of Pennsylvania for conducting the scanning sessions. NR 80 TC 64 Z9 67 U1 5 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD FEB PY 2009 VL 34 IS 3 BP 717 EP 728 DI 10.1038/npp.2008.124 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 393MA UT WOS:000262376200019 PM 18704100 ER PT J AU Sanchez-Mejia, RO McDermott, MW Tan, J Kim, H Young, WL Lawton, MT AF Sanchez-Mejia, Rene O. McDermott, Michael W. Tan, Jeffery Kim, Helen Young, William L. Lawton, Michael T. TI RADIOSURGERY FACILITATES RESECTION OF BRAIN ARTERIOVENOUS MALFORMATIONS AND REDUCES SURGICAL MORBIDITY SO NEUROSURGERY LA English DT Article DE Arteriovenous malformation; Endovascular embolization; Microsurgical resection; Multimodality treatment; Stereotactic radiosurgery ID GAMMA-KNIFE RADIOSURGERY; STEREOTACTIC RADIOSURGERY; MICROSURGICAL RESECTION; BIAS REDUCTION; HEMORRHAGE; OUTCOMES AB OBJECTIVE: Stereotactic radiosurgery makes brain arteriovenous malformations (AVM) more manageable during their microsurgical resection. To better characterize these effects, we compared results of microsurgical resection of radiated (RS(+)) and nonradiated (RS(-)) AVMs to demonstrate that previous radiosurgery facilitates surgery and decreases operative morbidity. METHODS: From our series of 344 patients who underwent AVM resections at the University of California, San Francisco (1997-2007), 21 RS(+) patients were matched with 21 RS- patients based on pretreatment clinical and AVM characteristics. Matching was blinded to outcomes, which were assessed with the modified Rankin Scale. RESULTS: Mean AVM volume was reduced by 78% (P < 0.01), and Spetzler-Martin grades were reduced in 52% of RS(+) patients (P < 0.001). Preoperative embolization was used less in RS+ than in RS- patients (P < 0.001). Mean operative time (P < 0.01), blood loss (P < 0.05), and length of hospital stay (P < 0.05) were lower in the RS(+) group. Surgical morbidity was 14% higher in RS- patients, and they demonstrated Significant worsening in modified Rankin Scale scores after surgery, whereas RS+ patients did not (P < 0.01). RS(+) patients deteriorated between AVM diagnosis and surgery owing to hemorrhages during the latency period (P < 0.05). CONCLUSION: Previous radiosurgery facilitates AVM microsurgery and decreases operative morbidity. Radiosurgery is recommended for unruptured AVMs that are not favorable for microsurgical resection. Microsurgical resection is recommended for radiated AVMs that are not completely obliterated after the 3-year latency period but are altered favorably for surgery, even in asymptomatic patients. Prompt resection of persistent AVMs should be considered to avoid the risk of postlatency hemorrhage and to optimize patient outcomes. C1 [Sanchez-Mejia, Rene O.; McDermott, Michael W.; Young, William L.; Lawton, Michael T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Tan, Jeffery] Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. [Kim, Helen] Univ Calif San Francisco, Cerebrovasc Res Ctr, San Francisco, CA 94143 USA. [Young, William L.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Young, William L.] Univ Calif San Francisco, Dept Perioperat Care, San Francisco, CA 94143 USA. RP Sanchez-Mejia, RO (reprint author), Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, 55 Fruit St,GRB-241, Boston, MA 02114 USA. EM rene_sanchez@post.harvard.edu OI Tan, Jeffrey/0000-0001-9939-9506 FU NINDS NIH HHS [P01 NS044155, R01 NS034949, R01 NS034949-12, P01 NS044155-05] NR 19 TC 27 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD FEB PY 2009 VL 64 IS 2 BP 231 EP 238 DI 10.1227/01.NEU.0000338068.44060.EA PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 399JY UT WOS:000262797400014 PM 19057424 ER PT J AU Fagan, P Rigotti, NA AF Fagan, Pebbles Rigotti, Nancy A. TI Light and intermittent smoking: The road less traveled SO NICOTINE & TOBACCO RESEARCH LA English DT Editorial Material C1 [Fagan, Pebbles] NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Rigotti, Nancy A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA. RP Fagan, P (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4042,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM faganp@mail.nih.gov NR 14 TC 32 Z9 32 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2009 VL 11 IS 2 BP 107 EP 110 DI 10.1093/ntr/ntn015 PG 4 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 421ZA UT WOS:000264395600001 PM 19264864 ER PT J AU Levy, DE Biener, L Rigotti, NA AF Levy, Douglas E. Biener, Lois Rigotti, Nancy A. TI The natural history of light smokers: A population-based cohort study SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CORONARY-HEART-DISEASE; NONDAILY SMOKERS; INTERMITTENT SMOKERS; DESCRIPTIVE ANALYSIS; NICOTINE DEPENDENCE; COLLEGE-STUDENTS; SMOKING; WOMEN; TIME; TRANSITIONS AB Among cigarette smokers, lower levels of consumption, defined as smoking fewer cigarettes per day (CPD) or not smoking daily, are becoming more common. The relationship between cigarette consumption and smoking frequency (daily or nondaily) is not well characterized, and the natural history of light smoking (defined here as smoking <= 10 CPD) is poorly understood. We assessed changes in CPD and smoking frequency over time among light smokers (<= 10 CPD) and very light smokers (<= 5 CPD), using a population-based longitudinal survey of 3,083 adult smokers in Massachusetts who were interviewed three times over a 4-year follow-up period (in 2000-2001, 2002-2003, and 2005-2006). We used logistic regression to identify factors associated with light smokers' progression to heavier smoking or smoking reduction/quitting. Seventy percent of very light smokers were nondaily smokers. Very light nondaily smokers differed from very light daily smokers by younger age, higher socioeconomic status, a social smoking pattern, later smoking initiation, less evidence of nicotine addiction, and more recent and planned cessation efforts. Very light nondaily smokers and smokers consuming 6-10 CPD were more likely to remain in the same smoking category and were less likely to increase consumption than were very light daily smokers. Factors independently associated with increasing consumption among very light smokers were smoking daily, nicotine dependence, White ethnicity, social smoking, and having more friends who smoked; among smokers consuming 6-10 CPD, male gender and lack of quitting self-efficacy were associated with increasing consumption. Our findings indicate that most light smoking is not a gateway to heavier smoking. C1 [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Inst Hlth Policy, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Levy, Douglas E.; Rigotti, Nancy A.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Biener, Lois] Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. RP Levy, DE (reprint author), MGH Inst Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM douglas_levy2@hms.harvard.edu OI Biener, Lois/0000-0002-4130-8138 FU National Heart, Lung, and Blood Institute [HL04440]; National Cancer Institute's Tobacco Research Initiative for State and Community Interventions [CA86257] FX National Heart, Lung, and Blood Institute (HL04440); National Cancer Institute's Tobacco Research Initiative for State and Community Interventions (CA86257). NR 37 TC 48 Z9 48 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD FEB PY 2009 VL 11 IS 2 BP 156 EP 163 DI 10.1093/ntr/ntp011 PG 8 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 421ZA UT WOS:000264395600008 PM 19264862 ER PT J AU Sander, JD Zaback, P Joung, JK Voytas, DF Dobbs, D AF Sander, Jeffry D. Zaback, Peter Joung, J. Keith Voytas, Daniel F. Dobbs, Drena TI An affinity-based scoring scheme for predicting DNA-binding activities of modularly assembled zinc-finger proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARTIFICIAL TRANSCRIPTION FACTORS; CONTROLLING GENE-EXPRESSION; RECOGNITION CODE; BUILDING-BLOCKS; NUCLEASES; CONSTRUCTION; SPECIFICITY; DESIGN; SEQUENCES; SELECTION AB Zinc-finger proteins (ZFPs) have long been recognized for their potential to manipulate genetic information because they can be engineered to bind novel DNA targets. Individual zinc-finger domains (ZFDs) bind specific DNA triplet sequences; their apparent modularity has led some groups to propose methods that allow virtually any desired DNA motif to be targeted in vitro. In practice, however, ZFPs engineered using this modular assembly approach do not always function well in vivo. Here we report a modular assembly scoring strategy that both identifies combinations of modules least likely to function efficiently in vivo and provides accurate estimates of their relative binding affinities in vitro. Predicted binding affinities for 53 three-finger ZFPs, computed based on energy contributions of the constituent modules, were highly correlated (r 0.80) with activity levels measured in bacterial two-hybrid assays. Moreover, K(d) values for seven modularly assembled ZFPs and their intended targets, measured using fluorescence anisotropy, were also highly correlated with predictions (r 0.91). We propose that success rates for ZFP modular assembly can be significantly improved by exploiting the score-based strategy described here. C1 [Sander, Jeffry D.; Zaback, Peter; Dobbs, Drena] Iowa State Univ, Dept Genet Dev & Cell Biol, Bioinformat & Computat Biol Program, Ames, IA 50011 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Canc Res, Mol Pathol Unit, Boston, MA 02129 USA. [Joung, J. Keith] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02129 USA. [Joung, J. Keith] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Voytas, Daniel F.] Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. [Voytas, Daniel F.] Univ Minnesota, Ctr Genome Engn, Minneapolis, MN 55455 USA. RP Sander, JD (reprint author), Iowa State Univ, Dept Genet Dev & Cell Biol, Bioinformat & Computat Biol Program, Ames, IA 50011 USA. EM jdsander@iastate.edu; ddobbs@iastate.edu FU National Institutes of Health [GM066387, GM069906, GM078369]; National Science Foundation [DBI0501678]; United States Department of Agriculture [MGET 2001-52100-11506, NSF IGERT0504304]; ISU's Center for Integrated Animal Genomics (CIAG) FX National Institutes of Health (GM066387 to D. D.); National Science Foundation (DBI0501678 to D. F. V.); National Institutes of Health (GM069906 and GM078369 to J.K.J.); and graduate research assistantships provided by United States Department of Agriculture (MGET 2001-52100-11506, NSF IGERT0504304 and ISU's Center for Integrated Animal Genomics (CIAG). Funding for open access charge: National Science Foundation (DBI0501678). NR 48 TC 29 Z9 32 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB PY 2009 VL 37 IS 2 BP 506 EP 515 DI 10.1093/nar/gkn962 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 401SW UT WOS:000262963400027 PM 19056825 ER PT J AU Samaha, FF Chou, CM AF Samaha, Frederick F. Chou, Carol M. TI Blockade of the Endocannabinoid System for the Reduction of Cardiometabolic Risk Factors SO OBESITY LA English DT Review ID CANNABINOID-1 RECEPTOR BLOCKER; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; DIET-INDUCED OBESITY; ADIPOSE-TISSUE; ENERGY-BALANCE; CARDIOVASCULAR-DISEASE; CB1 RECEPTORS; SCIENTIFIC STATEMENT; ANTAGONIST SR141716 C1 [Chou, Carol M.] Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Samaha, Frederick F.] Philadelphia Vet Affairs Med Ctr, Cardiovasc Sect, Philadelphia, PA USA. [Samaha, Frederick F.] Univ Penn, Dept Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA. RP Chou, CM (reprint author), Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. EM cchou@mail.med.upenn.edu NR 41 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD FEB PY 2009 VL 17 IS 2 BP 220 EP 225 DI 10.1038/oby.2008.476 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 400VJ UT WOS:000262897200004 PM 19039319 ER PT J AU Pulliam, SJ Berkowitz, LR AF Pulliam, Samantha J. Berkowitz, Lori R. TI Smaller Pieces of the Hysterectomy Pie Current Challenges in Resident Surgical Education SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID UNITED-STATES; CHOLECYSTECTOMY; PROGRAM AB Residents in obstetrics and gynecology are increasingly confronted with a wider range of techniques that must be mastered to perform hysterectomy, including abdominal, vaginal, laparoscopic, and robotic approaches. This is accompanied by a decrease in the number of hysterectomies performed annually. Possible solutions to the dilemma created for surgical teaching includes a comprehensive program evaluating surgical competency by establishing numbers needed to achieve competency for specific major procedures. C1 [Pulliam, Samantha J.] Massachusetts Gen Hosp, Brigham & Womens Hosp, Integrated Residency Training Program Obstet & Gy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Urogynecol & Pelv Reconstruct Surg, Boston, MA 02114 USA. RP Pulliam, SJ (reprint author), Massachusetts Gen Hosp, Brigham & Womens Hosp, Integrated Residency Training Program Obstet & Gy, 55 Fruit St,Founders 520A, Boston, MA 02114 USA. EM spulliam@partners.org NR 10 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2009 VL 113 IS 2 BP 395 EP 398 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 399YK UT WOS:000262835000021 PM 19155911 ER PT J AU Barth, WH AF Barth, William H., Jr. TI Fetoscopic Tracheal Occlusion for Previable Rupture of the Membranes Recklessness or Heroic Medical Innovation? SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID CONGENITAL DIAPHRAGMATIC-HERNIA; PRETERM PREMATURE RUPTURE; LUNGS C1 [Barth, William H., Jr.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. [Barth, William H., Jr.] Harvard Univ, Sch Med, Boston, MA USA. RP Barth, WH (reprint author), Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. EM wbarthjr@partners.org NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD FEB PY 2009 VL 113 IS 2 BP 473 EP 475 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 399YO UT WOS:000262835400001 PM 19155924 ER PT J AU Sobus, JR Waidyanatha, S McClean, MD Herrick, RF Smith, TJ Garshick, E Laden, F Hart, JE Zheng, Y Rappaport, SM AF Sobus, J. R. Waidyanatha, S. McClean, M. D. Herrick, R. F. Smith, T. J. Garshick, E. Laden, F. Hart, J. E. Zheng, Y. Rappaport, S. M. TI Urinary naphthalene and phenanthrene as biomarkers of occupational exposure to polycyclic aromatic hydrocarbons SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CHROMATOGRAPHY-MASS SPECTROMETRY; ASPHALT PAVING WORKERS; COKE-OVEN WORKERS; DIESEL EXHAUST; PLANT WORKERS; LUNG-CANCER; 1-HYDROXYPYRENE; ATMOSPHERE AB Objectives: The study investigated the utility of unmetabolised naphthalene (Nap) and phenanthrene (Phe) in urine as surrogates for exposures to mixtures of polycyclic aromatic hydrocarbons (PAHs). Methods: The report included workers exposed to diesel exhausts (low PAH exposure level, n=39) as well as those exposed to emissions from asphalt (medium PAH exposure level, n=26) and coke ovens (high PAH exposure level, n=28). Levels of Nap and Phe were measured in urine from each subject using head space-solid phase microextraction and gas chromatography-mass spectrometry. Published levels of airborne Nap, Phe and other PAHs in the coke-producing and aluminium industries were also investigated. Results: In post-shift urine, the highest estimated geometric mean concentrations of Nap and Phe were observed in coke-oven workers (Nap: 2490 ng/l; Phe: 975 ng/l), followed by asphalt workers (Nap: 71.5 ng/l; Phe: 54.3 ng/l), and by diesel-exposed workers (Nap: 17.7 ng/l; Phe: 3.60 ng/l). After subtracting logged background levels of Nap and Phe from the logged post-shift levels of these PAHs in urine, the resulting values (referred to as ln(adjNap) and ln(adjPhe), respectively) were significantly correlated in each group of workers (0.71 <= Pearson r <= 0.89), suggesting a common exposure source in each case. Surprisingly, multiple linear regression analysis of ln(adjNap) on ln(adjPhe) showed no significant effect of the source of exposure (coke ovens, asphalt and diesel exhaust) and further suggested that the ratio of urinary Nap/Phe (in natural scale) decreased with increasing exposure levels. These results were corroborated with published data for airborne Nap and Phe in the coke-producing and aluminium industries. The published air measurements also indicated that Nap and Phe levels were proportional to the levels of all combined PAHs in those industries. Conclusion: Levels of Nap and Phe in urine reflect airborne exposures to these compounds and are promising surrogates for occupational exposures to PAH mixtures. C1 [Rappaport, S. M.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Sobus, J. R.; Waidyanatha, S.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. [McClean, M. D.; Herrick, R. F.; Smith, T. J.; Laden, F.; Hart, J. E.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. [Garshick, E.] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. [Garshick, E.; Laden, F.; Hart, J. E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. [Zheng, Y.] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Beijing, Peoples R China. RP Rappaport, SM (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. EM srappaport@berkeley.edu RI Smith, Thomas/A-9640-2010; OI McClean, Michael/0000-0002-3902-8823 FU National Institutes of Health; National Institute for Environmental Health Sciences [T32ES07018, P42ES05948, P30ES10126, P30ES0002]; National Cancer Institute [R01CA90792] FX Financial support for this work was provided by the following grants from the National Institutes of Health: the National Institute for Environmental Health Sciences through training grant T32ES07018, research grant P42ES05948 (SMR), and centre grants P30ES10126 (SMR) and P30ES0002 (TJS) and the National Cancer Institute through research grant R01CA90792 (EG, TJS, FL, JEH). NR 25 TC 25 Z9 27 U1 1 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD FEB PY 2009 VL 66 IS 2 BP 99 EP 104 DI 10.1136/oem.2008.041418 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 396HG UT WOS:000262582200005 PM 19017700 ER PT J AU White-Gilbertson, S Mullen, T Senkal, C Lu, P Ogretmen, B Obeid, L Voelkel-Johnson, C AF White-Gilbertson, S. Mullen, T. Senkal, C. Lu, P. Ogretmen, B. Obeid, L. Voelkel-Johnson, C. TI Ceramide synthase 6 modulates TRAIL sensitivity and nuclear translocation of active caspase-3 in colon cancer cells SO ONCOGENE LA English DT Article DE TRAIL; ceramide; apoptosis; ceramide synthase; longevity assurance homologue ID LONGEVITY ASSURANCE GENE-1; INDUCED APOPTOSIS; FAMILY-MEMBERS; HUMAN HEAD; RESISTANCE; DEATH; METASTASIS; ACTIVATION; GROWTH; IDENTIFICATION AB We have previously shown that the death receptor ligand TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) induces an increase of intracellular C(16)-ceramide in sensitive SW480 but not in resistant SW620 cells. Resistance in SW620 cells was overcome by exogenous ceramide, leading us to propose that defective ceramide signaling contributes to TRAIL resistance. In this study we found that the increase in C16-ceramide in SW480 cells was inhibited by fumonisin B1, an inhibitor of ceramide synthases (CerS). Protein analysis revealed that TRAIL-resistant SW620 cells expressed lower levels of ceramide synthase 6 (CerS6, also known as longevity assurance homologue 6), which prompted us to investigate the effect of CerS6 modulation on TRAIL phenotype. RNAi against CerS6 resulted in a specific and significant decrease of the C(16)-ceramide species, which was sufficient to inhibit TRAIL-induced apoptosis. In cells with decreased levels of CerS6, caspase-3 was activated but failed to translocate into the nucleus. CerS6 localized primarily to the perinuclear region, suggesting this enzyme may be important in regulation of nuclear permeability. Moderate elevation in CerS6 expression was sufficient to reverse TRAIL resistance in SW620 cells. These results suggest that modulation of CerS6 expression may constitute a new therapeutic strategy to alter apoptotic susceptibility. C1 [White-Gilbertson, S.; Lu, P.; Voelkel-Johnson, C.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29403 USA. [Mullen, T.; Obeid, L.] Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. [Senkal, C.; Ogretmen, B.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29403 USA. [Obeid, L.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Voelkel-Johnson, C (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, POB 250504,173 Ashley Ave, Charleston, SC 29403 USA. EM johnsocv@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01CA097132, CA-088932, CA-097132, P01 CA097132, R01 CA088932, R01 CA088932-07, P01 CA097132-060004]; NCRR NIH HHS [1P20-RR17698, C06 RR018823, P20 RR017698, P20 RR017698-01, P20 RR017698-03, P20 RR017698-02]; NIA NIH HHS [R01 AG016583, AG016583]; NIDCR NIH HHS [DE016572, R01 DE016572-04, R01 DE016572]; NIEHS NIH HHS [1T32ES012878, T32 ES012878] NR 50 TC 65 Z9 68 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD FEB PY 2009 VL 28 IS 8 BP 1132 EP 1141 DI 10.1038/onc.2008.468 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 412KE UT WOS:000263722900008 PM 19137010 ER PT J AU Vinegoni, C Razansky, D Figueiredo, JL Nahrendorf, M Ntziachristos, V Weissleder, R AF Vinegoni, Claudio Razansky, Daniel Figueiredo, Jose-Luiz Nahrendorf, Matthias Ntziachristos, Vasilis Weissleder, Ralph TI Normalized Born ratio for fluorescence optical projection tomography SO OPTICS LETTERS LA English DT Article ID GENE-EXPRESSION AB We present a normalized Born approach for fluorescence optical projection tomography that takes into account tissue absorption properties. This approach can be particularly useful to study fluorochrome distribution within tissue. We use the algorithm to three-dimensionally reconstruct and characterize a fluorescein isothiocyanate containing absorptive phantom and an infarcted mouse heart previously injected with a fluorescent molecular probe. (C) 2009 Optical Society of America C1 [Vinegoni, Claudio; Figueiredo, Jose-Luiz; Nahrendorf, Matthias; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. [Razansky, Daniel; Ntziachristos, Vasilis] Tech Univ Munich, IBMI, D-85764 Neuherberg, Germany. [Razansky, Daniel; Ntziachristos, Vasilis] Helmholtz Ctr Munich, D-85764 Neuherberg, Germany. RP Vinegoni, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, 185 Cambridge St, Boston, MA 02114 USA. EM cvinegoni@mgh.harvard.edu OI Razansky, Daniel/0000-0001-8676-0964 FU National Institutes of Health (NIH) [1-RO1-EB006432] FX C. Vinegoni acknowledges support from National Institutes of Health (NIH) grant 1-RO1-EB006432. NR 4 TC 25 Z9 26 U1 0 U2 5 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD FEB 1 PY 2009 VL 34 IS 3 BP 319 EP 321 PG 3 WC Optics SC Optics GA 412WV UT WOS:000263755800032 PM 19183644 ER PT J AU Sonis, ST Watkins, BA Lyng, GD Lerman, MA Anderson, KC AF Sonis, Stephen T. Watkins, Brynmor A. Lyng, Gregory D. Lerman, Mark A. Anderson, Kenneth C. TI Bony changes in the jaws of rats treated with zoledronic acid and dexamethasone before dental extractions mimic bisphosphonate-related osteonecrosis in cancer patients SO ORAL ONCOLOGY LA English DT Article DE Bisphosphonates; Osteonecrosis; Jaw; Dental extractions; Animal model ID RISK-FACTORS; THERAPY; PREVENTION; DISEASE; TISSUE; SERIES AB Osteonecrosis of the jaw is associated with aminobisphosphonate use in patients treated with intravenous doses for the prevention of bony metastases. A more complete understanding of the natural history of bisphosphonate-related osteonecrosis of the jaws (BRONJ), factors associated with risk, and its pathobiology has been limited by the availability of human material and the absence of clinical predictabitity. We now describe an animal model, developed in female Sprague-Dawley rats, in which we replicate many of the clinical, radiographic, and histologic features described in humans. Animals treated with a sequence of zoledronic acid (ZA) and dexamethosone (DX) over a one to three week period developed BRONJ-like changes following extraction of mandibular or maxillary molars. Whereas the extraction sites of control animals underwent predictable heating with rapid epithelialization, animals treated with ZA/DX demonstrated clinical and histological evidence of ulceration overlying areas of necrotic bone. In contrast to images from control animals, radiographs from animals treated with ZA/DX demonstrated poor definition of the alveolar ridge with mixed radiodensity. Modest increases in the extent of the inflammatory infiltrate were seen fourteen days after extraction in ZA-only treated animals compared to control or ZA/DX-treated rats. However, by post-extraction day 28, no differences were observed. Tissue vascularity was most pronounced in ZA-only treated animals compared to ZA/DX or control specimens. Apoptosis of epithelial cells was not observed in any experimental groups, and no evidence of Actinomyces was observed as determined by Periodic Acid Schiff (PAS) staining. The administration of ZA/DX preceding dental extractions in rats therefore results in the development of bony and soft tissue changes that are similar to those noted humans who develop BRONJ, and may provide a useful model for study of its pathogenesis, as well as strategies for its prevention and treatment. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Sonis, Stephen T.; Lerman, Mark A.] Dana Farber Harvard Canc Ctr, Div Oral Med, Boston, MA USA. [Anderson, Kenneth C.] Dana Farber Harvard Canc Ctr, Dept Med, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Sonis, Stephen T.; Lerman, Mark A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Watkins, Brynmor A.; Lyng, Gregory D.] Biomodels LLC, Boston, MA USA. RP Sonis, ST (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM ssonis@partners.org FU Novartis FX This study was funded by a grant from Novartis. NR 22 TC 102 Z9 104 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD FEB PY 2009 VL 45 IS 2 BP 164 EP 172 DI 10.1016/j.oraloncology.2008.04.013 PG 9 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 412AU UT WOS:000263696400012 PM 18715819 ER PT J AU Yang, C Goodman, SB AF Yang, Cao Goodman, Stuart B. TI Outcome and Complications of Constrained Acetabular Components SO ORTHOPEDICS LA English DT Review ID TOTAL HIP-ARTHROPLASTY; FOLLOW-UP; RECURRENT DISLOCATION; CLOSED REDUCTION; FEMORAL-HEAD; OVERUSE SYNDROME; REVISION; LINER; INSTABILITY; FAILURE C1 [Goodman, Stuart B.] Stanford Univ, Dept Orthoped Surg, Stanford, CA 94305 USA. [Yang, Cao] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goodman, SB (reprint author), Stanford Univ, Dept Orthoped Surg, R144,300 Pasteur Dr, Stanford, CA 94305 USA. NR 68 TC 9 Z9 11 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0147-7447 J9 ORTHOPEDICS JI Orthopedics PD FEB PY 2009 VL 32 IS 2 BP 115 EP 123 PG 9 WC Orthopedics SC Orthopedics GA 413CK UT WOS:000263770300006 PM 19301794 ER PT J AU Nichols, AC Faquin, WC Westra, WH Mroz, EA Begum, S Clark, JR Rocco, JW AF Nichols, Anthony C. Faquin, William C. Westra, William H. Mroz, Edmund A. Begum, Shanaz Clark, John R. Rocco, James W. TI HPV-16 infection predicts treatment outcome in oropharyngeal squamous cell carcinoma SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID METASTATIC COLORECTAL-CANCER; HUMAN-PAPILLOMAVIRUS; NECK CANCERS; HEAD; SURVIVAL; P16; P16(INK4A); EXPRESSION; CETUXIMAB; STRATEGY AB OBJECTIVE: To determine if patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) treated with chemoradiation have improved outcomes. STUDY DESIGN: A retrospective search was used to identify patients with OPSCC treated with concurrent chemoradiation. Pretreatment biopsy specimens were tested for HPV-16 infection and p16 expression. METHODS: Forty-four patients with OPSCC treated with concurrent chemotherapy and intensity-modulated radiation therapy were identified. Eligibility criteria included a minimum two years of follow-up, or biopsy-proven recurrence. In situ hybridization was applied to archival tumor specimens, with HPV-16-positive status defined as positive staining of tumor cell nuclei. p16 expression was assessed by immunohistochemistry. RESULTS: Twenty-seven tumors (61%) were positive for HPV-16 and 29 tumors (66%) expressed p16. HPV-16 infection was highly correlated with p 16 expression (P < 10(-7)). Three-year disease-free and overall survival for all patients was 66 percent and 79 percent respectively. Patients with tumors infected with HPV-16 had improved overall (OS) and disease-free survival (DFS) after chemoradiation (OS: hazard ratio [HR] = 0.21, P = 0.01; DFS: HR = 0.30, P = 0.02). CONCLUSION: Patients with OPSCC tumors that are infected with HPV-16 have improved survival after treatment with concurrent chemoradiation. C1 [Faquin, William C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Clark, John R.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Nichols, Anthony C.; Rocco, James W.] Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. [Westra, William H.; Begum, Shanaz] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Mroz, Edmund A.; Rocco, James W.] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Rocco, JW (reprint author), Massachusetts Gen Hosp, Dept Surg, Jackson 904G,55 Fruit St, Boston, MA 02114 USA. EM jrocco@partners.org FU Murphy Fund for Head and Neck Cancer; Norman Knight Fund for Head and Neck Cancer FX Funding was provided by the Murphy Fund for Head and Neck Cancer and the Norman Knight Fund for Head and Neck Cancer. NR 25 TC 70 Z9 73 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 2009 VL 140 IS 2 BP 228 EP 234 DI 10.1016/j.otohns.2008.11.025 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 404LL UT WOS:000263153500017 PM 19201294 ER PT J AU Kulbersh, JS Day, TA Gillespie, MB Young, MRI AF Kulbersh, Jonathan S. Day, Terry A. Gillespie, M. Boyd Young, M. Rita I. TI 1 alpha,25-Dihydroxyvitamin D-3 to skew intratumoral levels of immune inhibitory CD34(+) progenitor cells into dendritic cells SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID NECK-CANCER PATIENTS; PERIPHERAL-BLOOD; HEAD; TUMOR; DIFFERENTIATION; SUPPRESSION; CARCINOMAS; MELANOMA AB OBJECTIVES: Prior studies showed that immune inhibitory CD34(+) progenitor cells, whose numbers are increased in head and neck squamous cell carcinoma (HNSCC) patients, can be differentiated into immune stimulatory dendritic cells by culture with 1 alpha,25-dihydroxyvitamin D-3 (1,25[OH](2)D-3'). This was extended to a pilot study to diminish intratumoral levels of CD34(+) progenitor cells by inducing their maturation into dendritic cells with 1,25(OH)(2)D-3. STUDY DESIGN: Newly diagnosed HNSCC patients were untreated for 3 weeks or received 3 weeks of 1,25(OH)(2)D-3 treatment befoer surgical treatment. SUBJECTS AND METHODS: HNSCC tissue was collected by biopsy from six patients who had no prior 1,25(OH)(2)D-3 treatment and at the time of surgical treatment from six untreated patients and 11 patients who completed 1,25(OH)(2)D-3 treatment. Tissues were analyzed by immunohistochemistry for levels of CD34(+) cells and dendritic cells. RESULTS: After 1,25(OH)(2)D-3 treatment, intratumoral levels of CD34(+) cells and levels of immature dendritic cells declined. However, levels of intratumoral mature dendritic cells increased. Clinical effects of 1,25(OH)(2)D-3 treatment are premature to analyze. CONCLUSIONS: Treatment of HNSCC patients with 1,25(OH)(2)D-3 reduced levels of immune inhibitory CD34(+) cells while increasing maturation of dendritic cells. This supports added studies to determine the effect of 1,25(OH)(2)D-3 on intratumoral immune competence. C1 [Young, M. Rita I.] Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC USA. [Kulbersh, Jonathan S.; Day, Terry A.; Gillespie, M. Boyd; Young, M. Rita I.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson VA Med Ctr, Res Serv 151, Charleston, SC 29401 USA. EM rita.young@va.gov FU Research Service of the Department of Veterans Affairs; National Institutes of Health [R01CA85266, R01CA97813] FX Supported by the Research Service of the Department of Veterans Affairs and by grants R01CA85266 and R01CA97813 from the National Institutes of Health to MRIY. NR 18 TC 15 Z9 16 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD FEB PY 2009 VL 140 IS 2 BP 235 EP 240 DI 10.1016/j.otohns.2008.11.011 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 404LL UT WOS:000263153500018 PM 19201295 ER PT J AU Kieran, MW Supko, JG Wallace, D Fruscio, R Poussaint, TY Phillips, P Pollack, I Packer, R Boyett, JM Blaney, S Banerjee, A Geyer, R Friedman, H Goldman, S Kun, LE MacDonald, T AF Kieran, Mark W. Supko, Jeffrey G. Wallace, Dana Fruscio, Robert Poussaint, Tina Young Phillips, Peter Pollack, Ian Packer, Roger Boyett, James M. Blaney, Susan Banerjee, Anu Geyer, Russ Friedman, Henry Goldman, Stewart Kun, Larry E. MacDonald, Tobey CA Pediat Brain Tumor Consortium TI Phase I Study of SU5416, a Small Molecule Inhibitor of the Vascular Endothelial Growth Factor Receptor (VEGFR) in Refractory Pediatric Central Nervous System Tumors SO PEDIATRIC BLOOD & CANCER LA English DT Article DE anti-angiogenesis; brain tumor; SU5416; VEGF ID ACUTE MYELOID-LEUKEMIA; HIPPEL-LINDAU-SYNDROME; RENAL-CELL CARCINOMA; ANTIANGIOGENIC AGENT; SOLID TUMORS; ANGIOGENESIS; CANCER; EXPRESSION; THERAPY; PATIENT AB SU5416 is a novel small molecule tyrosine kinase inhibitor of the VEGF receptors 1 and 2. A phase I dose escalation Study stratified by concurrent use (stratum II) or absence (stratum I) of enzyme-inducing anticonvulsant drugs was undertaken to estimate the maximum-tolerated close (MTD) and to describe the toxicity profile of SU5416 in pediatric patients with refractory brain tumors. Dose escalations were conducted independently for stratum I starting at 110 mg/m(2) while stratum II started at 48 mg/m(2). Thirty-three eligible patients were treated on stratum I (n=23) and stratum II (n=10). Tumor types included 23 glial tumors, 4 neural tumors, 4 ependymomas, and 2 choroid plexus carcinomas. The MTD in stratum I was initially estimated to be 110 mg/m(2). The protocol was amended to determine the MTD after excluding transient AST elevation. Re-estimation of the MTD began at the 145 mg/m(2) close level but clue to development of SU5416 being stopped by the sponsor, the trial was closed before completion. The most Serious drug-related toxicities were grade 3 liver enzyme abnormalities, arthralgia, and hallucinations. The plasma pharmacokinetics of SU5416 was not significantly affected by the concurrent administration of enzyme-inducing anticonvulsant drugs. Mean Value,.; of the total body clearance, apparent volume of distribution, and terminal phase half-life of SUS416 for the 19 patients in stratum I were 26.1 +/- 12.5 l/hr/m(2), 41.9 +/- 21.4 l/m(2), and 1.11 +/- 0.41 hr, respectively. The plasma pharmacokinetics of SU5416 in children was similar to previously reported findings in adult cancer patients. Prolonged disease stabilization was observed in 4 of 16 stratum I patients. Pediatr Blood Cancer 2009;52:169-176. (C) 2008 Wiley-Liss, Inc. C1 [Kieran, Mark W.] Dana Farber Canc Inst, Pediat Neurooncol Program, Boston, MA 02115 USA. [Supko, Jeffrey G.; Fruscio, Robert] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Wallace, Dana; Boyett, James M.] St Jude Childrens Hosp, Operat & Biostat Ctr, Memphis, TN 38105 USA. [Poussaint, Tina Young] Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. [Phillips, Peter] Childrens Hosp Philadelphia, Div Pediat Oncol, Philadelphia, PA 19104 USA. [Pollack, Ian] Childrens Hosp Pittsburgh, Dept Neurosurg, Pittsburgh, PA 15213 USA. [Packer, Roger] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Blaney, Susan] Baylor Coll Med, Texas Childrens Hosp, Houston, TX 77030 USA. [Banerjee, Anu] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. [Geyer, Russ] Childrens Hosp, Dept Pediat, Seattle, WA USA. [Geyer, Russ] Reg Med Ctr, Seattle, WA USA. [Friedman, Henry] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC USA. [Goldman, Stewart] Childrens Mem Hosp, Div Hematol Oncol, Memphis, TN USA. [Kun, Larry E.] St Jude Childrens Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. [MacDonald, Tobey] Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Pediat Neurooncol Program, 44 Binney St,Room SW331, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu RI Fruscio, Robert/F-8542-2011; MacDonald, Tobey/D-4554-2013; OI Fruscio, Robert/0000-0001-5688-2194; Kieran, Mark/0000-0003-2184-7692 FU NIH [U01 CA81457]; American Lebanese Syrian Associated Charities FX This work was supported in part by NIH grant U01 CA81457 for the Pediatric Brain Tumor Consortium (PBTC) and American Lebanese Syrian Associated Charities. NR 41 TC 26 Z9 27 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2009 VL 52 IS 2 BP 169 EP 176 DI 10.1002/pbc.21873 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 385EK UT WOS:000261796000008 PM 19065567 ER PT J AU Griffin, TC Weitzman, S Weinstein, H Chang, M Cairo, M Hutchison, R Shiramizu, B Wiley, J Woods, D Barnich, M Gross, TG AF Griffin, Timothy C. Weitzman, Sheila Weinstein, Howard Chang, Myron Cairo, Mitchell Hutchison, Robert Shiramizu, Bruce Wiley, Joseph Woods, Deborah Barnich, Margaret Gross, Thomas G. TI A Study of Rituximab and Ifosfamide, Carboplatin, and Etoposide Chemotherapy in Children with Recurrent/Refractory B-Cell (CD20+) Non-Hodgkin Lymphoma and Mature B-Cell Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group SO PEDIATRIC BLOOD & CANCER LA English DT Article DE Burkitt's lymphoma; chemotherapy; large cell lymphoma; non-Hodgkin's lymphoma ID MONOCLONAL-ANTIBODY RITUXIMAB; CANCER-GROUP EXPERIENCE; PLUS RITUXIMAB; PHASE-II; PEDIATRIC-ONCOLOGY; ADOLESCENTS; CHILDHOOD; RECURRENT; THERAPY; TRIAL AB Background. To estimate the response rate and therapy related toxicities of the anti-CD20 monoclonal antibody rituximab when combined with chemotherapy including ifosfamide, carboplatin, and etoposide (ICE) in patients with relapsed and refractory B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia (B-ALL). Methods. Patients received rituximab and ICE for 1-3 cycles, depending upon response. Rituximab (375 mg/m(2)) was given oil clay 1 and 3 of each cycle (day I only for cycle 3), with ifosfamide (3,000 mg/m(2)) and etoposide (100 mg/m(2)) given on days 3, 4, and 5 and carboplatin (635 mg/m(2)) given oil clay 3 only. Results. Twenty-one patients were enrolled, of whom 20 were eligible and evaluable. Although hematologic toxicities were common, only one patient was removed from study due to prolonged myelosuppression. Toxicities related to infusions of rituximab were frequent hot manageable. Of the six eligible patients With diffuse large B-cell lymphoma, three achieved complete remission (CR), one had stable disease (SD), and two had progressive disease (PD). Of the 14 eligible patients with Burkitt lymphoma and B-ALL, there were four complete responses (CR), five partial responses (PR), one SD, and four with PD. Thus, the CR/PR rate for the entire group was 12/20 (60%). Following completion of protocol therapy six patient. Were able to proceed to consolidation with high-close therapy and stern cell rescue. Conclusions. The combination of rituximab and ICE chemotherapy was associated with all encouraging objective response (OR) rate and in acceptable toxicity profile. Pediatr Blood Cancer 2009;52:177-181. (C) 2008 Wiley-Liss, Inc. C1 [Griffin, Timothy C.] Mem Hosp S Bend, South Bend, IN 46601 USA. [Weitzman, Sheila] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Weinstein, Howard] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, Myron] Childrens Oncol Grp, Gaines, FL USA. [Cairo, Mitchell] Columbia Presbyterian Coll Phys & Surg, New York, NY USA. [Hutchison, Robert] SUNY Syracuse, Syracuse, NY USA. [Shiramizu, Bruce] Canc Res Ctr Hawaii, Honolulu, HI 96813 USA. [Wiley, Joseph] Sinai Hosp, Baltimore, MD 21215 USA. [Woods, Deborah] Sutter Med Ctr, Sacramento, CA USA. [Barnich, Margaret] Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. [Gross, Thomas G.] Nationwide Childrens Hosp, Columbus, OH USA. RP Griffin, TC (reprint author), Mem Hosp S Bend, 615 N Michigan St, South Bend, IN 46601 USA. EM tgriffin@memorialsb.org FU COG [CA 98543] FX A complete listing of grain support for research conducted by CCO and POG before initiation of the COG grant in 2003 (CA 98543) is available online at: lit tp://www.childremsoneologygroup.org/admin/grantinfo.htm NR 21 TC 66 Z9 71 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2009 VL 52 IS 2 BP 177 EP 181 DI 10.1002/pbc.21753 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 385EK UT WOS:000261796000009 PM 18816698 ER PT J AU Mueller, BU Bennett, CM Feldman, HA Bussel, JB Abshire, TC Moore, TB Sawaf, H Loh, ML Rogers, ZR Glader, BE McCarthy, MC Mahoney, DH Olson, TA Feig, SA Lorenzana, AN Mentzer, WC Buchanan, GR Neufeld, EJ AF Mueller, Brigitta U. Bennett, Carolyn M. Feldman, Henry A. Bussel, James B. Abshire, Thomas C. Moore, Theodore B. Sawaf, Hadi Loh, Mignon L. Rogers, Zora R. Glader, Bertil E. McCarthy, Maggie C. Mahoney, Donald H. Olson, Thomas A. Feig, Stephen A. Lorenzana, Adonis N. Mentzer, William C. Buchanan, George R. Neufeld, Ellis J. CA Glaser Pediat Res Network TI One Year Follow-Up of Children and Adolescents With Chronic Immune Thrombocytopenic Purpura (ITP) Treated With Rituximab SO PEDIATRIC BLOOD & CANCER LA English DT Article DE clinical trial; immune thrombocytopenia; rituximab ID ANTI-CD20 MONOCLONAL-ANTIBODY; INTRAVENOUS GAMMA-GLOBULIN; CHILDHOOD; EFFICACY; ADULTS AB Background. We previously showed in a prospective Study that rituximab appears to be effective in some children and adolescents with severe chronic immune thrombocytopenia. Eleven of 36 patients achieved and maintained platelet counts Over 50,000/mm(3) within the first 12 weeks. These patients were followed for the next year. Methods. Platelet Count,; were monitored monthly and all subsequent bleeding manifestations and need for further treatment was noted. Results. Eight of the 11 initial responders maintained a platelet count over 150,000/mm(3) Without further treatment intervention. Three patients had a late relapse. One initial non-responder achieved a remission after 16 weeks, and two additional patients maintained platelet counts around 50,000/mm(3) without the need for further intervention. Conclusions. Rituximab resulted in sustained efficacy with platelet Counts of 50,000/mm(3) or higher in 11 of 36 patients (31%). Pediatr Blood Cancer 2009;52:259-262. (C) 2008 Wiley-Liss, Inc. C1 [Bennett, Carolyn M.; Neufeld, Ellis J.] Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Mueller, Brigitta U.; Mahoney, Donald H.] Baylor Coll Med, Hematol Serv, Houston, TX 77030 USA. [Mueller, Brigitta U.; Mahoney, Donald H.] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. [Bennett, Carolyn M.; Feldman, Henry A.; McCarthy, Maggie C.; Glaser Pediat Res Network] Harvard Univ, Sch Med, Boston, MA USA. [Feldman, Henry A.; McCarthy, Maggie C.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Bussel, James B.] Cornell Univ, Dept Pediat, Weill Med Coll, New York, NY 10021 USA. [Abshire, Thomas C.; Olson, Thomas A.] Emory Univ, Sch Med, Atlanta, GA USA. [Moore, Theodore B.; Feig, Stephen A.] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Sawaf, Hadi; Lorenzana, Adonis N.] St Johns Hosp, Van Eslander Canc Ctr, Detroit, MI USA. [Loh, Mignon L.; Mentzer, William C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rogers, Zora R.; Buchanan, George R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Glader, Bertil E.] Stanford Univ, Stanford, CA 94305 USA. RP Neufeld, EJ (reprint author), Childrens Hosp, Div Hematol Oncol, Dana Farber Canc Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM ellis.neufeld@childrens.harvard.edu RI Neufeld, Ellis/F-9331-2011 FU NCRR NIH HHS [M01RR-001271, M01-RR0000047, M01RR000188, M01RR000865, M01RR002172] NR 18 TC 30 Z9 36 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD FEB PY 2009 VL 52 IS 2 BP 259 EP 262 DI 10.1002/pbc.21757 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 385EK UT WOS:000261796000025 PM 18937333 ER PT J AU Assmann, A Hinault, C Kulkarni, RN AF Assmann, Anke Hinault, Charlotte Kulkarni, Rohit N. TI Growth factor control of pancreatic islet regeneration and function SO PEDIATRIC DIABETES LA English DT Review DE aging; cell cycle; islets; obesity; regeneration; T1D and T2D ID BETA-CELL MASS; INSULIN-RECEPTOR SUBSTRATE-2; GLUCAGON-LIKE PEPTIDE-1; EMBRYONIC STEM-CELLS; DEPENDENT DIABETES-MELLITUS; MICE LACKING INSULIN; K-ATP CHANNEL; GENE-EXPRESSION; FACTOR-I; TRANSCRIPTION FACTOR AB Assmann A, Hinault C, Kulkarni RN. Growth factor control of pancreatic islet regeneration and function.Pediatric Diabetes 2009: 10: 14-32. C1 [Kulkarni, Rohit N.] Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kulkarni, RN (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM rohit.kulkarni@joslin.harvard.edu OI hinault, charlotte/0000-0002-3588-039X FU National Institutes of Health (NIH) [RO1 DK 67536, RO1 DK 68721]; American Diabetes Association [7-04-RA-55]; Harvard Stem Cell Institute; NIH [1RL9EB008539-01)] FX We thank Lindsay Huse for excellent assistance with the preparation of the manuscript; R. N. K. acknowledges support from National Institutes of Health (NIH) RO1 DK 67536, RO1 DK 68721, American Diabetes Association Research grant 7-04-RA-55, and a grant from the Harvard Stem Cell Institute; C. H. is supported by a NIH training grant (1RL9EB008539-01) (SysCODE). NR 232 TC 41 Z9 41 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1399-543X J9 PEDIATR DIABETES JI Pediatr. Diabetes PD FEB PY 2009 VL 10 IS 1 BP 14 EP 32 DI 10.1111/j.1399-5448.2008.00468.x PG 19 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 397EL UT WOS:000262645100003 PM 18828795 ER PT J AU Prodhan, P Westra, SJ Lin, J Karni-Sharoor, S Regan, S Noviski, N AF Prodhan, Parthak Westra, Sjirk J. Lin, James Karni-Sharoor, Sarit Regan, Susan Noviski, Natan TI Chest radiological patterns predict the duration of mechanical ventilation in children with RSV infection SO PEDIATRIC RADIOLOGY LA English DT Article DE RSV infection; Pediatric ICU; Mechanical ventilation; Chest radiograph; Outcome ID RESPIRATORY SYNCYTIAL VIRUS; INTENSIVE-CARE-UNIT; RISK-FACTORS; VIRAL PNEUMONIA; US CHILDREN; TIME-COURSE; BRONCHIOLITIS; INFANTS; DIFFERENTIATION; BACTERIAL AB RSV-infected children demonstrate various radiographic features, some of which are associated with worse clinical outcomes. To investigate whether specific chest radiological patterns in RSV-infected children with acute respiratory failure (ARF) in the peri-intubation period are associated with prolonged duration of mechanical ventilation. We included RSV-infected children < 1 year of age admitted with ARF from 1996 through 2002 to the pediatric intensive care unit at Massachusetts General Hospital. Their chest radiographs were evaluated at three time-points: preintubation (day -1) and days 1 and 2 after intubation. Univariate and multiple logistic regressions models were utilized to investigate our objective. The study included 46 children. Using day 1 chest radiograph findings to predict duration of mechanical ventilation of > 8 days, a backward stepwise regression arrived at a model that included age and right and left lung atelectasis. Using day 2 chest radiograph results, the best model included age and left lung atelectasis. A model combining the two days' findings yielded an area under the ROC curve of 0.92 with a satisfactory fit (P = 0.95). Chest radiological patterns around the time of intubation can identify children with RSV-associated ARF who would require prolonged mechanical ventilation. C1 [Westra, Sjirk J.; Noviski, Natan] Massachusetts Gen Hosp, Div Pediat Radiol, Boston, MA 02114 USA. [Prodhan, Parthak] Univ Arkansas Med Sci, Coll Med, Div Pediat Crit Care & Cardiol, Little Rock, AR 72205 USA. [Lin, James] Univ Calif Los Angeles, Mattel Childrens Hosp, Div Pediat Crit Care, Los Angeles, CA USA. [Karni-Sharoor, Sarit] Shaarei Tzedek Med Ctr, Pediat Crit Care Unit, Jerusalem, Israel. [Regan, Susan] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Noviski, N (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, 175 Cambridge St 524, Boston, MA 02114 USA. EM NNOVISKI@PARTNERS.ORG RI Lin, James/E-4796-2010; OI Regan, Susan/0000-0003-0940-2017 NR 37 TC 11 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD FEB PY 2009 VL 39 IS 2 BP 117 EP 123 DI 10.1007/s00247-008-1042-3 PG 7 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 387NK UT WOS:000261958700004 PM 19005648 ER PT J AU Chen, CC Chiu, CH Lin, TY Shi, HN Walker, WA AF Chen, Chien-Chang Chiu, Cheng-Hsun Lin, Tzou-Yien Shi, Hai Ning Walker, W. Allan TI Effect of Probiotics Lactobacillus acidophilus on Citrobacter rodentium Colitis: The Role of Dendritic Cells SO PEDIATRIC RESEARCH LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; CYTOKINE RESPONSE; IN-VITRO; INFECTION; BACTERIA; MICE; MODULATION; VIRULENCE; IMMUNITY; DISEASE AB Modulation of the intestinal immune response early in life by administration of probiotic bacteria may be an effective strategy for preventing or attenuating infectious diarrhea. We preinoculated the mice early in life with the probiotic bacteria Lactobacillus acidophilus NCFM (La) at age 2 wk. Dendritic cells (DCs) were collected and purified front mesenteric lymph nodes (MLN) and spleens of the BalbC/ByJ mice. DC isolation and adoptive transfer was used to examine the function of probiotics. We demonstrated that when mice were adoptively transferred with La-primed DCs (t-LaDC) instead of oral consumption with La, there was a similar effect off fecal bacteria counts. IgA levels. and colonic histopathology, as well as cytokine levels in MLN when there was intestinal bacterial infection. The above findings suggest that DCs play a key role in probiotics attenuating Citrobacter rodentitum (Cr) colitis. Moreover, the location of La-primed DC hints that there is interaction of DCs and T cells in the digestive system of the host. Up-regulated expression Of a surface marker on DCs indicated that inoculation with probiotics will stimulate the function of DCs. thereby further increasing immune response triggered by DC. (Pediatr Res 65: 169-175, 2009) C1 [Chen, Chien-Chang; Chiu, Cheng-Hsun; Lin, Tzou-Yien] Chang Gung Univ, Coll Med, Dept Pediat, Chang Gung Mem Hosp,Chang Gung Childrens Hosp, Tao Yuan 333, Taiwan. [Shi, Hai Ning; Walker, W. Allan] Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. [Shi, Hai Ning; Walker, W. Allan] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Lin, TY (reprint author), Chang Gung Univ, Coll Med, Dept Pediat, Chang Gung Mem Hosp, 121 5 Fu-Hsing St, Tao Yuan 333, Taiwan. EM pidlin@adm.cgmh.org.tw FU Chang Gung Memorial Hospital Research [34010]; National science Council of Taiwan Grant [NSC 95-2314-B-182A-108] FX Supported in part by Chang Gung Memorial Hospital Research Project Grant 34010 and National science Council of Taiwan Grant NSC 95-2314-B-182A-108. NR 23 TC 18 Z9 19 U1 1 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD FEB PY 2009 VL 65 IS 2 BP 169 EP 175 PG 7 WC Pediatrics SC Pediatrics GA 398XX UT WOS:000262766100008 PM 19262293 ER PT J AU Cho, JI Ryoo, N Eom, JS Lee, DW Kim, HB Jeong, SW Lee, YH Kwon, YK Cho, MH Bhoo, SH Hahn, TR Park, YI Hwang, I Sheen, J Jeon, JS AF Cho, Jung-Il Ryoo, Nayeon Eom, Joon-Seob Lee, Dae-Woo Kim, Hyun-Bi Jeong, Seok-Won Lee, Youn-Hyung Kwon, Yong-Kook Cho, Man-Ho Bhoo, Seong Hee Hahn, Tae-Ryong Park, Youn-Il Hwang, Ildoo Sheen, Jen Jeon, Jong-Seong TI Role of the Rice Hexokinases OsHXK5 and OsHXK6 as Glucose Sensors SO PLANT PHYSIOLOGY LA English DT Article ID ORYZA-SATIVA L.; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; SIGNAL-TRANSDUCTION; NUCLEAR-LOCALIZATION; HIGHER-PLANTS; PLASMA-MEMBRANE; SUGAR SENSOR; KEY ROLE; ARABIDOPSIS AB The Arabidopsis (Arabidopsis thaliana) hexokinase 1 (AtHXK1) is recognized as an important glucose (Glc) sensor. However, the function of hexokinases as Glc sensors has not been clearly demonstrated in other plant species, including rice (Oryza sativa). To investigate the functions of rice hexokinase isoforms, we characterized OsHXK5 and OsHXK6, which are evolutionarily related to AtHXK1. Transient expression analyses using GFP fusion constructs revealed that OsHXK5 and OsHXK6 are associated with mitochondria. Interestingly, the OsHXK5 Delta mTP-GFP and OsHXK6 Delta mTP-GFP fusion proteins, which lack N-terminal mitochondrial targeting peptides, were present mainly in the nucleus with a small amount of the proteins seen in the cytosol. In addition, the OsHXK5NLS-GFP and OsHXK6NLS-GFP fusion proteins harboring nuclear localization signals were targeted predominantly in the nucleus, suggesting that these OsHXKs retain a dual-targeting ability to mitochondria and nuclei. In transient expression assays using promoter::luciferase fusion constructs, these two OsHXKs and their catalytically inactive alleles dramatically enhanced the Glc-dependent repression of the maize (Zea mays) Rubisco small subunit (RbcS) and rice alpha-amylase genes in mesophyll protoplasts of maize and rice. Notably, the expression of OsHXK5, OsHXK6, or their mutant alleles complemented the Arabidopsis glucose insensitive2-1 mutant, thereby resulting in wild-type characteristics in seedling development, Glc-dependent gene expression, and plant growth. Furthermore, transgenic rice plants overexpressing OsHXK5 or OsHXK6 exhibited hypersensitive plant growth retardation and enhanced repression of the photosynthetic gene RbcS in response to Glc treatment. These results provide evidence that rice OsHXK5 and OsHXK6 can function as Glc sensors. C1 [Cho, Jung-Il; Ryoo, Nayeon; Eom, Joon-Seob; Lee, Dae-Woo; Kim, Hyun-Bi; Kwon, Yong-Kook; Cho, Man-Ho; Bhoo, Seong Hee; Hahn, Tae-Ryong; Jeon, Jong-Seong] Kyung Hee Univ, Plant Metab Res Ctr, Yongin 446701, South Korea. [Cho, Jung-Il; Ryoo, Nayeon; Eom, Joon-Seob; Lee, Dae-Woo; Kim, Hyun-Bi; Kwon, Yong-Kook; Cho, Man-Ho; Bhoo, Seong Hee; Hahn, Tae-Ryong; Jeon, Jong-Seong] Kyung Hee Univ, Grad Sch Biotechnol, Yongin 446701, South Korea. [Jeong, Seok-Won; Park, Youn-Il] Chungnam Natl Univ, Dept Biol, Taejon 305764, South Korea. [Lee, Youn-Hyung] Kyung Hee Univ, Dept Hort Biotechnol, Yongin 446701, South Korea. [Hwang, Ildoo] Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. [Sheen, Jen] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Jeon, JS (reprint author), Kyung Hee Univ, Plant Metab Res Ctr, Yongin 446701, South Korea. EM jjeon@khu.ac.kr FU Ministry of Education, Science and Technology/Korea Science; Engineering Foundation [R11-2000-081]; Biogreen 21 Program; Rural Development Administration; Crop Functional Genomics Center of the 21st Century Frontier Research Program [CG2111-2]; Basic Research Program [R01-2007-000-20149-0]; Korea Science and Engineering Foundation FX This work was supported by the Science Research Center program of the Ministry of Education, Science and Technology/Korea Science and Engineering Foundation (grant no. R11-2000-081) through the Plant Metabolism Research Center, by the Biogreen 21 Program, Rural Development Administration, by the Crop Functional Genomics Center of the 21st Century Frontier Research Program (grant no. CG2111-2), and by the Basic Research Program (grant no. R01-2007-000-20149 -0) of the Korea Science and Engineering Foundation. NR 68 TC 59 Z9 61 U1 1 U2 27 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD FEB PY 2009 VL 149 IS 2 BP 745 EP 759 DI 10.1104/pp.108.131227 PG 15 WC Plant Sciences SC Plant Sciences GA 404CX UT WOS:000263129400013 PM 19010999 ER PT J AU Eberlin, KR McCormack, MC Nguyen, JT Tatlidede, HS Randolph, MA Austen, WG AF Eberlin, Kyle R. McCormack, Michael C. Nguyen, John T. Tatlidede, H. Soner Randolph, Mark A. Austen, William G., Jr. TI Sequential Limb Ischemia Demonstrates Remote Postconditioning Protection of Murine Skeletal Muscle SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Plastic-Surgery-Research-Council CY JUN 20-23, 2007 CL Stanford, CA SP Plast Surg Res Council ID REPERFUSION INJURY; ADENOSINE RECEPTORS; RENAL ISCHEMIA; FLAP SURVIVAL; INFARCT SIZE; MYOCARDIUM; ACTIVATION; MODEL; COMPLEMENT; MECHANISMS AB Background: Ischemic postconditioning, the process of exposing tissues to brief cycles of ischemia-reperfusion after critical ischemia, can mitigate local ischemia-reperfusion injury. Remote protection of skeletal muscle has never been demonstrated in postconditioning models of ischemia-reperfusion injury. Methods: Mice were subjected to 2 hours of ipsilateral hind limb ischemia followed by reperfusion. Contralateral limb ischemia was subsequently induced for 2 hours after either 0 (n = 6), 20 (n = 6), or 120 (n = 5) minutes of ipsilateral limb reperfusion. These groups were compared with animals subjected to bilateral simultaneous injury (n = 8) and sham animals that did not undergo ischemia (n = 6). The gastrocnemius muscles were harvested for histologic evaluation, and injury was recorded as the percentage of injured fibers. Results: The first limbs undergoing injury in the 20-minute interval group had a 59 percent injury reduction compared with contralateral limbs (16.0 +/- 2.4 percent versus 39.5 +/- 6.5 percent) after 24 hours of reperfusion and 62 percent reduction after 48 hours (24.4 +/- 3.0 percent versus 63.6 +/- 5.5 percent). In animals with no interval or a 120-minute interval between the onset of limb ischemia, there was no significant difference in injury between hind limbs. The injury in these groups was similar to that in hind limbs subjected to simultaneous bilateral ischemia. Conclusions: A 20-minute reperfusion interval between hind limb ischemia significantly protects against injury in the initially ischemic limb, while similar injury is observed with simultaneous ischemia or an interval of 120 minutes. This study demonstrates remote postconditioning of skeletal muscle and may lead to the development of post hoc therapies. (Plast. Reconstr. Surg. 123 (Suppl.): 8S, 2009.) C1 [Eberlin, Kyle R.; McCormack, Michael C.; Nguyen, John T.; Tatlidede, H. Soner; Randolph, Mark A.; Austen, William G., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Boston, MA 02114 USA. RP Austen, WG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Plast Surg Res Lab,Div Plast Surg, Wang Bldg 435,55 Fruit St, Boston, MA 02114 USA. NR 44 TC 17 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2009 VL 123 IS 2 BP 8S EP 16S DI 10.1097/PRS.0b013e318191bcd6 PG 9 WC Surgery SC Surgery GA 412JR UT WOS:000263721600003 PM 19182659 ER PT J AU Kubo, T Randolph, MA Groger, A Winograd, JM AF Kubo, Tateki Randolph, Mark A. Groeger, Andreas Winograd, Jonathan M. TI Embryonic Stem Cell-Derived Motor Neurons Form Neuromuscular Junctions In Vitro and Enhance Motor Functional Recovery In Vivo SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Plastic-Surgery-Research-Council CY JUN 20-23, 2007 CL Stanford, CA SP Plast Surg Res Council ID BABY-SITTER PROCEDURE; MOUSE EMBRYOS; MOTONEURONS; DENERVATION; MUSCLE AB Background: Transplantation of embryonic stem cell-derived motor neurons may support the biological integrity of denervated muscle by forming new neuromuscular junctions and up-regulating specific growth factors. The authors examined the functional properties of embryonic stem cell-derived motor neurons in vitro and the effect of these cells transplanted in vivo. Methods: Murine GFP/HB9 embryonic stem cells were differentiated into motor neurons. Co-cultures of motor neurons and myotubes were prepared to confirm the formation of neuromuscular junctions with synaptic markers. Athymic mice (n = 59) were assigned randomly to one of three experimental groups. A tibial nerve transection was performed without nerve repair, and motor neurons were transplanted into the gastrocnemius muscles immediately after transection (n = 24) or 3 weeks after denervation (n = 24). Quantitative and histologic assessments of gastrocnemius muscle were performed at days 7 and 21 after cell transplantation. Additional experimental groups (n = 11), where the tibial nerve underwent repair after transplantation, were formed. The effect of the transplants on motor recovery following nerve repair was investigated. Results: Co-culture experiments showed the formation of neuromuscular junctions. In the experiment with nerve transection without nerve repair, the muscles transplanted with motor neurons were less atrophied than control phosphate-buffered saline-injected muscles at days 7 and 21. Those muscles receiving cells transplanted 3 weeks after denervation were not preserved. The motor recovery after nerve repair with cell transplantation was significantly enhanced compared with the control group. Conclusions: Transplantation of motor neurons prevented denervation atrophy but was not capable of rescuing already atrophied muscle. After nerve repair, motor neuron transplantation improved functional recovery. (Plast. Reconstr. Surg. 123 (Suppl.): 139S, 2009.) C1 [Kubo, Tateki; Randolph, Mark A.; Groeger, Andreas; Winograd, Jonathan M.] Harvard Univ, Sch Med, Div Plast Surg, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Winograd, JM (reprint author), Harvard Univ, Sch Med, Div Plast Surg, Massachusetts Gen Hosp, Suite 435,15 Parkman St, Boston, MA 02114 USA. EM jwinograd@partners.org NR 18 TC 10 Z9 11 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD FEB PY 2009 VL 123 IS 2 BP 139S EP 148S DI 10.1097/PRS.0b013e3181923d07 PG 10 WC Surgery SC Surgery GA 412JR UT WOS:000263721600017 PM 19182673 ER PT J AU Kuraguchi, M Ohene-Baah, NY Sonkin, D Bronson, RT Kucherlapati, R AF Kuraguchi, Mari Ohene-Baah, Nana Yaw Sonkin, Dmitriy Bronson, Roderick Terry Kucherlapati, Raju TI Genetic Mechanisms in Apc-Mediated Mammary Tumorigenesis SO PLOS GENETICS LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; PRIMARY BREAST CANCERS; BETA-CATENIN; SOMATIC MUTATIONS; EXPRESSION PROFILES; MOUSE MODEL; WNT PATHWAY; STEM-CELLS; ACTIVATION; MICE AB Many components of Wnt/beta-catenin signaling pathway also play critical roles in mammary tumor development, yet the role of the tumor suppressor gene APC (adenomatous polyposis coli) in breast oncongenesis is unclear. To better understand the role of Apc in mammary tumorigenesis, we introduced conditional Apc mutations specifically into two different mammary epithelial populations using K14-cre and WAP-cre transgenic mice that express Cre-recombinase in mammary progenitor cells and lactating luminal cells, respectively. Only the K14-cre-mediated Apc heterozygosity developed mammary adenocarcinomas demonstrating histological heterogeneity, suggesting the multilineage progenitor cell origin of these tumors. These tumors harbored truncation mutation in a defined region in the remaining wild-type allele of Apc that would retain some down-regulating activity of beta-catenin signaling. Activating mutations at codons 12 and 61 of either H-Ras or K-Ras were also found in a subset of these tumors. Expression profiles of acinar-type mammary tumors from K14-cre; Apc(CKO/+) mice showed luminal epithelial gene expression pattern, and clustering analysis demonstrated more correlation to MMTV-neu model than to MMTV-Wnt1. In contrast, neither WAP-cre-induced Apc heterozygous nor homozygous mutations resulted in predisposition to mammary tumorigenesis, although WAP-cre-mediated Apc deficiency resulted in severe squamous metaplasia of mammary glands. Collectively, our results suggest that not only the epithelial origin but also a certain Apc mutations are selected to achieve a specific level of beta-catenin signaling optimal for mammary tumor development and explain partially the colon-but not mammary-specific tumor development in patients that carry germline mutations in APC. C1 [Kuraguchi, Mari; Ohene-Baah, Nana Yaw; Sonkin, Dmitriy; Kucherlapati, Raju] Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. [Kuraguchi, Mari; Kucherlapati, Raju] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Genet,Dept Med, Boston, MA 02115 USA. [Bronson, Roderick Terry] Dana Farber Harvard Canc Ctr, Boston, MA USA. RP Kuraguchi, M (reprint author), Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. EM rkucherlapati@partners.org OI Sonkin, Dmitriy/0000-0002-1649-0652 FU National Cancer Institute [CA-084301] FX This work was supported by the grant from the National Cancer Institute (CA-084301). NR 50 TC 32 Z9 32 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD FEB PY 2009 VL 5 IS 2 AR e1000367 DI 10.1371/journal.pgen.1000367 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 449GY UT WOS:000266320000008 PM 19197353 ER PT J AU Lowe, JK Maller, JB Pe'er, I Neale, BM Salit, J Kenny, EE Shea, JL Burkhardt, R Smith, JG Ji, WZ Noel, M Foo, JN Blundell, ML Skilling, V Garcia, L Sullivan, ML Lee, HE Labek, A Ferdowsian, H Auerbach, SB Lifton, RP Newton-Cheh, C Breslow, JL Stoffel, M Daly, MJ Altshuler, DM Friedman, JM AF Lowe, Jennifer K. Maller, Julian B. Pe'er, Itsik Neale, Benjamin M. Salit, Jacqueline Kenny, Eimear E. Shea, Jessica L. Burkhardt, Ralph Smith, J. Gustav Ji, Weizhen Noel, Martha Foo, Jia Nee Blundell, Maude L. Skilling, Vita Garcia, Laura Sullivan, Marcia L. Lee, Heather E. Labek, Anna Ferdowsian, Hope Auerbach, Steven B. Lifton, Richard P. Newton-Cheh, Christopher Breslow, Jan L. Stoffel, Markus Daly, Mark J. Altshuler, David M. Friedman, Jeffrey M. TI Genome-Wide Association Studies in an Isolated Founder Population from the Pacific Island of Kosrae SO PLOS GENETICS LA English DT Article ID C-REACTIVE PROTEIN; CONGENITAL HYPOTHYROIDISM; THYROID AGENESIS; LDL-CHOLESTEROL; CLEFT-PALATE; WHOLE-GENOME; LOCI; VARIANTS; MUTATION; LINKAGE AB It has been argued that the limited genetic diversity and reduced allelic heterogeneity observed in isolated founder populations facilitates discovery of loci contributing to both Mendelian and complex disease. A strong founder effect, severe isolation, and substantial inbreeding have dramatically reduced genetic diversity in natives from the island of Kosrae, Federated States of Micronesia, who exhibit a high prevalence of obesity and other metabolic disorders. We hypothesized that genetic drift and possibly natural selection on Kosrae might have increased the frequency of previously rare genetic variants with relatively large effects, making these alleles readily detectable in genome-wide association analysis. However, mapping in large, inbred cohorts introduces analytic challenges, as extensive relatedness between subjects violates the assumptions of independence upon which traditional association test statistics are based. We performed genome-wide association analysis for 15 quantitative traits in 2,906 members of the Kosrae population, using novel approaches to manage the extreme relatedness in the sample. As positive controls, we observe association to known loci for plasma cholesterol, triglycerides, and C-reactive protein and to a compelling candidate loci for thyroid stimulating hormone and fasting plasma glucose. We show that our study is well powered to detect common alleles explaining >= 5% phenotypic variance. However, no such large effects were observed with genome-wide significance, arguing that even in such a severely inbred population, common alleles typically have modest effects. Finally, we show that a majority of common variants discovered in Caucasians have indistinguishable effect sizes on Kosrae, despite the major differences in population genetics and environment. C1 [Lowe, Jennifer K.; Salit, Jacqueline; Kenny, Eimear E.; Burkhardt, Ralph; Noel, Martha; Blundell, Maude L.; Garcia, Laura; Sullivan, Marcia L.; Lee, Heather E.; Labek, Anna; Ferdowsian, Hope; Breslow, Jan L.; Stoffel, Markus; Friedman, Jeffrey M.] Rockefeller Univ, New York, NY 10021 USA. [Lowe, Jennifer K.; Shea, Jessica L.; Altshuler, David M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lowe, Jennifer K.; Maller, Julian B.; Pe'er, Itsik; Neale, Benjamin M.; Shea, Jessica L.; Smith, J. Gustav; Newton-Cheh, Christopher; Daly, Mark J.; Altshuler, David M.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Maller, Julian B.; Pe'er, Itsik; Neale, Benjamin M.; Newton-Cheh, Christopher; Daly, Mark J.; Altshuler, David M.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.] Kings Coll London, Social Genet & Dev Psychiat Ctr, Inst Psychiat, London, England. [Ji, Weizhen; Foo, Jia Nee; Lifton, Richard P.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. [Skilling, Vita] Kosrae Dept Hlth Serv, Kosrae, Micronesia. [Auerbach, Steven B.] Heath Resources & Serv Adm, Dept Hlth & Human Serv, New York, NY USA. [Lifton, Richard P.; Friedman, Jeffrey M.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Newton-Cheh, Christopher; Daly, Mark J.; Altshuler, David M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Lowe, JK (reprint author), Rockefeller Univ, 1230 York Ave, New York, NY 10021 USA. EM altshuler@molbio.mgh.harvard.edu; friedj@rockefeller.edu RI Altshuler, David/A-4476-2009; Breslow, Jan/B-7544-2008; Burkhardt, Ralph/F-5221-2013; Foo, Jia Nee/D-6069-2014; OI Altshuler, David/0000-0002-7250-4107; Foo, Jia Nee/0000-0001-9899-2308; Kenny, Eimear/0000-0001-9198-759X; Maller, Julian/0000-0002-1565-9559; Burkhardt, Ralph/0000-0003-1924-1202 FU NIH/NIDDK [5R01DK60089]; Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship; NIH [1F32DK070527, 5 U54 CA121852]; Deutsche Forschungsgemeinschaft [Bu2263/1-1] FX This work was supported by grants from the Starr Foundation and Howard Hughes Medical Institute. JKL was supported in part by an NIH/NIDDK grant (5R01DK60089) and by a Massachusetts Biomedical Research Corporation Tosteson Postdoctoral Fellowship. IP was partially supported by NIH grants 1F32DK070527 and 5 U54 CA121852. RB was supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft (DFG Bu2263/1-1). NR 43 TC 47 Z9 49 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD FEB PY 2009 VL 5 IS 2 AR e1000365 DI 10.1371/journal.pgen.1000365 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 449GY UT WOS:000266320000006 PM 19197348 ER PT J AU Sandgren, A Strong, M Muthukrishnan, P Weiner, BK Church, GM Murray, MB AF Sandgren, Andreas Strong, Michael Muthukrishnan, Preetika Weiner, Brian K. Church, George M. Murray, Megan B. TI Tuberculosis Drug Resistance Mutation Database SO PLOS MEDICINE LA English DT Editorial Material ID MYCOBACTERIUM-TUBERCULOSIS; PROTEIN INTERACTIONS; EXPRESSION PROFILES; CELLULAR NETWORKS; RPOB MUTATIONS; METAANALYSIS; TOOLS C1 [Sandgren, Andreas; Muthukrishnan, Preetika; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Muthukrishnan, Preetika] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. [Strong, Michael; Church, George M.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Weiner, Brian K.] Broad Inst MIT & Harvard, Cambridge, MA USA. RP Sandgren, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM asandgre@hsph.harvard.edu NR 26 TC 208 Z9 212 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD FEB PY 2009 VL 6 IS 2 BP 132 EP 136 AR e1000002 DI 10.1371/journal.pmed.1000002 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 410TA UT WOS:000263600000006 PM 19209951 ER PT J AU Little, J Higgins, JPT Ioannidis, JPA Moher, D Gagnon, F von Elm, E Khoury, MJ Cohen, B Davey-Smith, G Grimshaw, J Scheet, P Gwinn, M Williamson, RE Zou, GY Hutchings, K Johnson, CY Tait, V Wiens, M Golding, J van Duijn, C McLaughlin, J Paterson, A Wells, G Fortier, I Freedman, M Zecevic, M King, R Infante-Rivard, C Stewart, AFR Birkett, N AF Little, Julian Higgins, Julian P. T. Ioannidis, John P. A. Moher, David Gagnon, France von Elm, Erik Khoury, Muin J. Cohen, Barbara Davey-Smith, George Grimshaw, Jeremy Scheet, Paul Gwinn, Marta Williamson, Robin E. Zou, Guang Yong Hutchings, Kim Johnson, Candice Y. Tait, Valerie Wiens, Miriam Golding, Jean van Duijn, Cornelia McLaughlin, John Paterson, Andrew Wells, George Fortier, Isabel Freedman, Matthew Zecevic, Maja King, Richard Infante-Rivard, Claire Stewart, Alex F. R. Birkett, Nick TI STrengthening the REporting of Genetic Association Studies (STREGA) - An Extension of the STROBE Statement SO PLOS MEDICINE LA English DT Review DE gene-disease associations; genetics; gene-environment interaction; systematic review; meta analysis; reporting recommendations; epidemiology; genome-wide association ID GENOME-WIDE ASSOCIATION; HARDY-WEINBERG EQUILIBRIUM; SINGLE-NUCLEOTIDE POLYMORPHISMS; POPULATION STRATIFICATION; RANDOMIZED-TRIALS; DISEASE ASSOCIATIONS; GENOTYPING ERRORS; COMPLEX DISEASES; PROSTATE-CANCER; LINKAGE-DISEQUILIBRIUM AB Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy-Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data, and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct, or analysis. C1 [Little, Julian] Univ Ottawa, Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. [Little, Julian; Moher, David; Hutchings, Kim; Johnson, Candice Y.; Tait, Valerie; Wiens, Miriam; Birkett, Nick] Univ Ottawa, Dept Epidemiol & Community Med, Ottawa, ON, Canada. [Higgins, Julian P. T.] MRC, Biostat Unit, Cambridge CB2 2BW, England. [Ioannidis, John P. A.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece. [Ioannidis, John P. A.] Tufts Univ, Sch Med, Ctr Genet Epidemiol & Modeling, Boston, MA 02111 USA. [Gagnon, France] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada. [von Elm, Erik] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland. [von Elm, Erik] Univ Med Ctr, Dept Med Biometry & Med Informat, German Cochrane Ctr, Freiburg, Germany. [Khoury, Muin J.; Gwinn, Marta] Ctr Dis Control & Prevent, Natl Off Publ Hlth Genom, Atlanta, GA USA. [Cohen, Barbara] Publ Lib Sci, San Francisco, CA USA. [Davey-Smith, George] Univ Bristol, Dept Social Med, MRC, Ctr Causal Analyses Translat Epidemiol, Bristol, Avon, England. [Grimshaw, Jeremy] Univ Ottawa, Dept Med, Ottawa Hlth Res Inst, Clin Epidemiol Program, Ottawa, ON, Canada. [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Williamson, Robin E.] Amer Journal Human Genet, Boston, MA USA. [Zou, Guang Yong] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. [Zou, Guang Yong] Robarts Res Inst, London, ON N6A 5C1, Canada. [van Duijn, Cornelia] European Journal Epidemiol, Rotterdam, Netherlands. [McLaughlin, John] Canc Care Ontario, Toronto, ON, Canada. [McLaughlin, John] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada. [Paterson, Andrew] Hosp Sick Children SickKids, Canada Res Chair Genet Complex Dis, Toronto, ON, Canada. [Wells, George] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr, Ottawa, ON, Canada. [Fortier, Isabel] McGill Univ, Genome Quebec & P3G Observ, Montreal, PQ, Canada. [Fortier, Isabel] Genome Quebec Innovat Ctr, Montreal, PQ, Canada. [Freedman, Matthew] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zecevic, Maja] The Lancet, New York, NY USA. [King, Richard] Genet Med, Minneapolis, MN USA. [Golding, Jean] Paediat & Perinatal Epidemiol, Bristol, Avon, England. [King, Richard; Infante-Rivard, Claire] McGill Univ, Fac Med, Dept Epidemiol Biostatist & Occupat Hlth, Montreal, PQ, Canada. RP Little, J (reprint author), Univ Ottawa, Canada Res Chair Human Genome Epidemiol, Ottawa, ON, Canada. EM jlittle@uottawa.ca RI Ioannidis, John/G-9836-2011; Higgins, Julian/H-4008-2011; Stewart, Alexandre/A-5677-2011; Grimshaw, Jeremy/D-8726-2013; McLaughlin, John/E-4577-2013; Paterson, Andrew/A-4088-2011; Davey Smith, George/A-7407-2013; OI von Elm, Erik/0000-0002-7412-0406; Stewart, Alexandre/0000-0003-2673-9164; Grimshaw, Jeremy/0000-0001-8015-8243; Higgins, Julian/0000-0002-8323-2514; Paterson, Andrew/0000-0002-9169-118X; Davey Smith, George/0000-0002-1407-8314; Golding, Jean/0000-0003-2826-3307; Moher , David /0000-0003-2434-4206 FU Genome Canada; Genome Quebec FX The authors thank Kyle Vogan and Allen Wilcox for their participation in the workshop and for their comments; Michele Cargill (Affymetrix Inc) and Aaron del Duca (DNA Genotek) for their participation in the workshop as observers; and the Public Population Project in Genomics (P3G), hosted by the University of Montreal and supported by Genome Canada and Genome Quebec. This article was made possible thanks to input and discussion by the P3G International Working Group on Epidemiology and Biostatistics, discussion held in Montreal, May 2007. The authors also thank the reviewers for their very thoughtful feedback, and Silvia Visentin, Rob Moriarity, Morgan Macneill and Valery L'Heureux for administrative support. We were unable to contact Barbara Cohen to confirm her involvement in the latest version of this article. NR 154 TC 138 Z9 145 U1 5 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD FEB PY 2009 VL 6 IS 2 BP 151 EP 163 AR e1000022 DI 10.1371/journal.pmed.1000022 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 410TA UT WOS:000263600000009 PM 19192942 ER PT J AU Nakamoto, N Cho, H Shaked, A Olthoff, K Valiga, ME Kaminski, M Gostick, E Price, DA Freeman, GJ Wherry, EJ Chang, KM AF Nakamoto, Nobuhiro Cho, Hyosun Shaked, Abraham Olthoff, Kim Valiga, Mary E. Kaminski, Mary Gostick, Emma Price, David A. Freeman, Gordon J. Wherry, E. John Chang, Kyong-Mi TI Synergistic Reversal of Intrahepatic HCV-Specific CD8 T Cell Exhaustion by Combined PD-1/CTLA-4 Blockade SO PLOS PATHOGENS LA English DT Article ID HEPATITIS-C-VIRUS; IN-VITRO PROLIFERATION; ANTIGEN 4 CTLA-4; PD-1 EXPRESSION; COMBINATION IMMUNOTHERAPY; FUNCTIONAL RESTORATION; PROTECTIVE IMMUNITY; DISEASE PROGRESSION; VIRAL-INFECTION; UP-REGULATION AB Viral persistence is associated with hierarchical antiviral CD8 T cell exhaustion with increased programmed death-1 (PD-1) expression. In HCV persistence, HCV-specific CD8 T cells from the liver (the site of viral replication) display increased PD-1 expression and a profound functional impairment that is not reversed by PD-1 blockade alone. Here, we report that the inhibitory receptor cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is preferentially upregulated in PD-1(+) T cells from the liver but not blood of chronically HCV-infected patients. PD-1/CTLA-4 co-expression in intrahepatic T cells was associated with a profound HCV-specific effector dysfunction that was synergistically reversed by combined PD-1/CTLA-4 blockade in vitro, but not by blocking PD-1 or CTLA-4 alone. A similar effect was observed in circulating HCV-specific CD8 T cells with increased PD-1/CTLA-4 co-expression during acute hepatitis C. The functional response to combined blockade was directly associated with CTLA-4 expression, lost with CD28-depletion and CD4-independent (including CD4(+)FoxP3(+) Tregs). We conclude that PD-1 and CTLA-4 pathways both contribute to virus-specific T cell exhaustion at the site of viral replication by a redundant mechanism that requires combined PD-1/CTLA-4 blockade to reverse. These findings provide new insights into the mechanisms of virus-specific T cell dysfunction, and suggest that the synergistic effect by combined inhibitory receptor blockade might have a therapeutic application against chronic viral infection in vivo, provided that it does not induce autoimmunity. C1 [Nakamoto, Nobuhiro; Cho, Hyosun; Valiga, Mary E.; Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Nakamoto, Nobuhiro; Cho, Hyosun; Valiga, Mary E.; Chang, Kyong-Mi] Univ Penn, Sch Med, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Shaked, Abraham; Olthoff, Kim; Kaminski, Mary] Hosp Univ Penn, Dept Surg, Penn Liver Transplant Ctr, Philadelphia, PA 19104 USA. [Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff, S Glam, Wales. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wherry, E. John] Wistar Inst Anat & Biol, Program Immunol, Philadelphia, PA 19104 USA. RP Nakamoto, N (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. EM kmchang@mail.med.upenn.edu RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU National Institutes of Health (NIH) [AI47519]; American Gastroenterological Association Elsevier Research Initiative Award; NIH/National Institute of Diabetes and Digestive and Kidney Diseases Center of Molecular Studies in Digestive and Liver Diseases [P30DK50306]; Molecular Biology and Cell Culture Core Facilities, NIH Public Health Service Research [M01-RR00040]; NIH [AI56299, P30 CA016520]; Medical Research Council (UK) FX This study is supported by National Institutes of Health (NIH) grants AI47519, the American Gastroenterological Association Elsevier Research Initiative Award (K. M. C.); Philadelphia VA Medical Research, the NIH/National Institute of Diabetes and Digestive and Kidney Diseases Center of Molecular Studies in Digestive and Liver Diseases grant P30DK50306 and its Molecular Biology and Cell Culture Core Facilities, NIH Public Health Service Research grant M01-RR00040; a grant from the Foundation for the NIH through the Grand Challenges in Global Health Initiative, and NIH grant AI56299 (to G. J. F.); D. A. P. is a Medical Research Council (UK) Senior Clinical Fellow. Support for the Abramson Cancer Center Flow Cytometry and Cell Sorting Shared Resource of the University of Pennsylvania was funded through NIH grant P30 CA016520 from the National Cancer Institute. NR 54 TC 168 Z9 182 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7366 J9 PLOS PATHOG JI PLoS Pathog. PD FEB PY 2009 VL 5 IS 2 AR e1000313 DI 10.1371/journal.ppat.1000313 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 415IR UT WOS:000263928000004 PM 19247441 ER PT J AU Green, KE Iverson, KM AF Green, Kelly E. Iverson, Katherine M. TI Computerized Cognitive-Behavioral Therapy in a Stepped Care Model of Treatment SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article DE cognitive-behavioral therapies; computerized applications; treatment effectiveness evaluation; stepped care ID OBSESSIVE-COMPULSIVE DISORDER; RANDOMIZED CONTROLLED-TRIAL; AIDED SELF-HELP; WEIGHT-LOSS; ANXIETY; DEPRESSION; PROGRAM; FEASIBILITY; CLINICIAN; EFFICACY AB A growing body of literature suggests that computerized cognitive-behavioral therapies (CCBT) are effective in community settings in terms of symptom reduction, favorable client satisfaction, attrition comparable to standard cognitive-behavioral therapy, reduced clinician time, high cost-effectiveness, and ease of integration into community clinics. Clinicians report lack of knowledge about computerized programs as the main reason that they have not used CCBT in their practice. To mitigate this disconnect between empirical evidence and dissemination, this article first reviews empirical studies focusing on the efficacy of CCBT for specific psychological disorders, followed by a review of research on the effectiveness of CCBT in community settings. Next, issues related to dissemination and barriers to CCBT adoption by clinicians are discussed. Finally, the implications of CCBT for research and practice and the possible role of CCBT in a stepped care model of treatment is discussed in terms of cost-effectiveness, standards of care, and implications for public policy. C1 [Green, Kelly E.] VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. [Green, Kelly E.] Rutgers State Univ, Piscataway, NJ 08855 USA. [Iverson, Katherine M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Green, KE (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM Kelly.green3@va.gov NR 40 TC 18 Z9 19 U1 2 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD FEB PY 2009 VL 40 IS 1 BP 96 EP 103 DI 10.1037/a0012847 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 409OB UT WOS:000263514000017 ER PT J AU Duan, XB Berthiaume, F Yarmush, DM Yarmush, ML AF Duan, Xunbao Berthiaume, Francois Yarmush, David M. Yarmush, Martin L. TI Dissimilar hepatic protein expression profiles during the acute and flow phases following experimental thermal injury SO PROTEOMICS LA English DT Article DE Acute phase proteins; Antioxidants; Burn injury; Hepatic proteome; Metabolic enzymes ID CARBONIC-ANHYDRASE-III; BURN INJURY; 2-DIMENSIONAL ELECTROPHORESIS; ALPHA-1-ACID GLYCOPROTEIN; NEUTROPHIL SEQUESTRATION; HYPERMETABOLIC STATE; ANTIOXIDANT THERAPY; LIPID-PEROXIDATION; PROTEOMIC ANALYSIS; SKELETAL-MUSCLE AB The liver plays a major role in the early hypometabolic and later hypermetabolic phases after severe burn injury. Proteomic analysis was used to identify altered proteins in liver during these two phases. Sprague-Dawley rats were subjected to a full-thickness dorsal burn injury covering 40% of the total body surface area. Controls consisted of sham-treated animals. Liver tissues were collected on postburn days 1 and 7. The proteomic data show greater production of positive acute phase proteins on day 1 than on day 7. Many antioxidant enzymes were coordinately downregulated on day 1, including the potent biliverdin reductase. These antioxidants were restored and in some cases upregulated on day 7. This opposite trend in the change of antioxidant proteins corroborated our finding of more pronounced oxidative stress on day 1 than on day 7 as measured via protein carbonyl content. The changes of metabolic enzymes on days 1 and 7 were consistent with hypo- and hyper-metabolic states, respectively. Furthermore, a previously unreported decrease in ornithine aminotransferase on day 7 may be a key contributor to the observed increased urinary urea excretion during the hypermetabolic phase. Overall, the many differences in protein expression observed on postburn days 1 and 7 reflect the dissimilar hepatic metabolic patterns during the acute and flow phases following burn injury. C1 [Duan, Xunbao] Temple Univ, Dept Biochem, Sch Med, Philadelphia, PA 19122 USA. [Berthiaume, Francois; Yarmush, David M.; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Berthiaume, Francois; Yarmush, David M.; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv,Ctr Engn Med, Boston, MA USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org FU Shriners Hospitals for Children FX This work was supported by the Shriners Hospitals for Children. This work was partly carried out in the Boston Shriners Burns Hospital Special Shared Facility for Genomics and Proteomics. NR 38 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD FEB PY 2009 VL 9 IS 3 BP 636 EP 647 DI 10.1002/pmic.200700427 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410LL UT WOS:000263578600013 PM 19137545 ER PT J AU Lu, QY Yang, YN Jin, YS Zhang, ZF Heber, D Li, FP Dubinett, SM Sondej, MA Loo, JA Rao, JY AF Lu, Qing-Yi Yang, Yanan Jin, Yu Sheng Zhang, Zuo-Feng Heber, David Li, Frederick P. Dubinett, Steven M. Sondej, Melissa A. Loo, Joseph A. Rao, Jian Yu TI Effects of green tea extract on lung cancer A549 cells: Proteomic identification of proteins associated with cell migration SO PROTEOMICS LA English DT Article DE Green tea; Human lung adenocarcinoma cells; Lamins A/C; Proteomics ID ANNEXIN-I EXPRESSION; PROSTATIC INTRAEPITHELIAL NEOPLASIA; ATOMIC-FORCE MICROSCOPY; A-TYPE LAMINS; EPIGALLOCATECHIN GALLATE; VISCOELASTIC PROPERTIES; HEALTHY-INDIVIDUALS; NUCLEAR MECHANICS; HUMAN TISSUES; POLYPHENON-E AB Green tea polyphenols exhibit multiple antitumor activities, and the mechanisms of action are not completely understood. Previously, we reported that green tea extract (GTE)-induced actin remolding is associated with increased cell adhesion and decreased motility in A549 lung cancer cells. To identify the cellular targets responsible for green tea-induced actin remodeling, we performed 2-DE LC-MS/MS of A549 cells before and after GTE exposure. We have identified 14 protein spots that changed in expression (>= 2-fold) after GTE treatment. These proteins are involved in calcium-binding, cytoskeleton and motility, metabolism, detoxification, or gene regulation. In particular we found upregulation of several genes that modulate actin remodeling and cell migration, including lamin A/C. Our data indicated that GTE-induced lamin A/C upregulation appears to be at the transcriptional level and the increased expression results in the decrease in cell motility, as confirmed by siRNA. The result of the study demonstrates that GTE alters the levels of many proteins involved in growth, motility and apoptosis of A549 cells and their identification may explain the multiple antitumor activities of GTE. C1 [Yang, Yanan; Sondej, Melissa A.; Loo, Joseph A.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Lu, Qing-Yi; Heber, David] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Ctr Human Nutr, Los Angeles, CA 90095 USA. [Jin, Yu Sheng; Rao, Jian Yu] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. [Zhang, Zuo-Feng; Rao, Jian Yu] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. [Li, Frederick P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dubinett, Steven M.] Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Loo, Joseph A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. RP Loo, JA (reprint author), Univ Calif Los Angeles, Dept Chem & Biochem, 402 Paul D Boyer Hall, Los Angeles, CA 90095 USA. EM jloo@chem.ucla.edu FU NCI NIH HHS [P30 CA042710-21, CA42710, CA90833, P01 CA042710, P30 CA042710, P50 CA090388, P50 CA090388-020001, P50 CA090388-020004, P50 CA090388-04, R01 CA090833] NR 51 TC 22 Z9 24 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD FEB PY 2009 VL 9 IS 3 BP 757 EP 767 DI 10.1002/pmic.200800019 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 410LL UT WOS:000263578600023 PM 19137550 ER PT J AU Parker, LE Kirchner, JE Bonner, YM Fickel, JJ Ritchie, MJ Simons, CE Yano, EM AF Parker, Louise E. Kirchner, JoAnn E. Bonner, Laura M. Fickel, Jacqueline J. Ritchie, Mona J. Simons, Carol E. Yano, Elizabeth M. TI Creating a Quality-Improvement Dialogue: Utilizing Knowledge From Frontline Staff, Managers, and Experts to Foster Health Care Quality Improvement SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE health care decision making; health care professionals; health care workplace; quality improvement; research dissemination and utilization; research implementation ID DEPRESSION; PRACTITIONERS; PARTICIPATION; DECISIONS; ACADEMICS; BEHAVIOR AB There is a growing consensus that a hybrid of two common approaches to quality improvement (QI), local participatory QI and expert QI, might be the best method for achieving quality care. Achieving such a hybrid requires that content experts establish an ongoing dialogue with both frontline staff members and managers. In this study we examined frontline staff members' and managers' preferences regarding how to conduct such a dialogue, and we provide practical suggestions for implementation. The two groups shared a number of preferences (e.g., verbal face-to-face exchanges, discussions focused on quality of care). There were also some differences. For example, although managers were interested in discussions of business aspects (e.g., costs), frontline staff members were concerned with workload issues. Finally, although informants acknowledged that engaging in a QI dialogue was time consuming, they also believed it was essential if health care organizations are to improve the quality of care they provide. C1 [Parker, Louise E.; Kirchner, JoAnn E.] VA Ctr Mental Hlth Care & Outcomes Res, HSR&D Res Enhancement Award Program, N Little Rock, AR USA. [Parker, Louise E.; Ritchie, Mona J.] VA Mental Hlth Qual Enhancement Res Initiat Coord, N Little Rock, AR USA. [Kirchner, JoAnn E.] VA S Cent Mental Illness Res, Educ & Clin Ctr, N Little Rock, AR USA. [Bonner, Laura M.] VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence, Seattle, WA USA. [Fickel, Jacqueline J.; Yano, Elizabeth M.] VA HSR&D Ctr Excellence Study Hlth Care Provider, Sepulveda, CA USA. [Simons, Carol E.] VA Puget Sound Hlth Care Syst, HSR&D NW Ctr Excellence Outcomes Res Older Adults, Seattle, WA USA. RP Parker, LE (reprint author), VA Ctr Mental Hlth Care & Outcomes Res, HSR&D Res Enhancement Award Program, N Little Rock, AR USA. NR 39 TC 36 Z9 36 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD FEB PY 2009 VL 19 IS 2 BP 229 EP 242 DI 10.1177/1049732308329481 PG 14 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 396SX UT WOS:000262612500007 PM 19092141 ER PT J AU Boockvar, KS Liu, S Goldstein, N Nebeker, J Siu, A Fried, T AF Boockvar, K. S. Liu, S. Goldstein, N. Nebeker, J. Siu, A. Fried, T. TI Prescribing discrepancies likely to cause adverse drug events after patient transfer SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID MEDICATION RECONCILIATION; HOSPITALIZATION; SYSTEM; SAFETY; ERRORS; CARE AB Background: Medication-prescribing discrepancies are used as a quality measure for patients transferred between sites of care. The objective of this study was to quantify the rate of adverse drug events (ADEs) caused by prescribing discrepancies and the discrimination of an index of high-risk transition drug prescribing. Methods: We examined medical records of patients transferred between seven nursing homes and three hospitals between 1999 and 2005 in New York and Connecticut for transfer- associated prescribing discrepancies. ADEs caused by discrepancies were determined by two clinician raters. We calculated the fraction of medication discrepancies that caused ADEs in each of 22 drug classes by calculating positive predictive values (PPVs). We calculated the discrimination of a count of high-risk drug discrepancies, selected from published lists of high-risk medications and using observed PPVs. Results: 208 patients were hospitalised 304 times. Overall, 65 of 1350 prescribing discrepancies caused ADEs, for a PPV of 0.048 (95% CI 0.037 to 0.061). PPVs by drug class ranged from 0 to 0.28. Drug classes with the highest PPVs were opioid analgesics, metronidazole, and non-opioid analgesics. Patients with 0, 1-2 and >= 3 high-risk discrepancies had a 13%, 23% and 47% chance of experiencing a discrepancy-related ADE, respectively. Conclusions: Discrepancies in certain drug classes more often caused ADEs than other types of discrepancies in hospitalised nursing-home patients. Information about ADEs caused by medication discrepancies can be used to enhance measurement of care quality, identify high-risk patients and inform the development of decision-support tools at the time of patient transfer. C1 [Boockvar, K. S.; Goldstein, N.; Siu, A.] James J Peters Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Boockvar, K. S.; Goldstein, N.; Siu, A.] Mt Sinai Sch Med, Dept Geriatr, New York, NY USA. [Boockvar, K. S.; Goldstein, N.; Siu, A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Boockvar, K. S.] Jewish Home & Hosp, New York, NY USA. [Liu, S.; Fried, T.] Yale Univ, Sch Med, New Haven, CT USA. [Nebeker, J.] VA Geriatr Res Educ & Clin Ctr, Salt Lake City, UT USA. [Fried, T.] VA Connecticut Healthcare Syst, Clin Epidemiol Res Ctr, West Haven, CT USA. RP Boockvar, KS (reprint author), VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 FU VA Health Services Research and Development Service; New York State Department of Health; Doris Duke Clinical Research Fellowship FX Financial support was provided by the VA Health Services Research and Development Service and the New York State Department of Health. SL is the recipient of a Doris Duke Clinical Research Fellowship. NR 29 TC 47 Z9 47 U1 1 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD FEB PY 2009 VL 18 IS 1 BP 32 EP 36 DI 10.1136/qshc.2007.025957 PG 5 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 404UJ UT WOS:000263178200007 PM 19204129 ER PT J AU Friedman, D Hombeck, GN DeLucia, C Jandasek, B Zebracki, K AF Friedman, Deborah Hombeck, Grayson N. DeLucia, Christian Jandasek, Barbara Zebracki, Kathy TI Trajectories of Autonomy Development Across the Adolescent Transition in Children With Spina Bifida SO REHABILITATION PSYCHOLOGY LA English DT Article DE spina bifida; autonomy; growth curve; adolescence ID PSYCHOSOCIAL ADJUSTMENT; PHYSICAL DISORDERS; MULTILEVEL MODELS; AGE-DIFFERENCES; PUBERTAL STATUS; YOUNG-PEOPLE; SELF-CONCEPT; FAMILY; PARENT; PREADOLESCENTS AB Objective: The current study investigated individual growth in autonomy development across the adolescent transition, comparing the trajectories of children with and without spina bifida. Method: Individual growth curve modeling procedures were utilized to describe the developmental course of autonomy across four waves of data collection, from ages 9 to 15, and to test whether illness status [spina bifida vs. matched comparison group (N = 68 for both groups at Time 1)] would significantly predict individual variability in autonomy development. Potential moderators [child gender, SES, and Peabody Picture Vocabulary Test (PPVT) score] of the association between illness status and autonomy development were also examined. Results: Children with spina bifida demonstrated distinct developmental trajectories, though the nature of the group differences varied by type of autonomy development (emotional vs. behavioral), context (i.e. school vs. family), and reporter. Significant interactions with PPVT score and child gender were found. Conclusion: Overall, children with spina bifida show considerable developmental resiliency, but may lag behind their peers in specific areas of autonomy. Boys with spina bifida, and children with spina bifida who have lower than average levels of verbal intelligence, appear to be at greater risk for exhibiting delays in autonomy development. C1 [Friedman, Deborah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hombeck, Grayson N.] Loyola Univ Chicago, Chicago, IL 60626 USA. [DeLucia, Christian] Nova SE Univ, Ft Lauderdale, FL 33314 USA. [Jandasek, Barbara] Brown Univ, Warren Alpert Med Sch, Bradley Hasbro Childrens Res Ctr, Providence, RI 02912 USA. [Zebracki, Kathy] Shriners Hosp Children, Chicago, IL USA. RP Friedman, D (reprint author), Yawkey Ctr Outpatient Care, Yawkey 6A,55 Fruit St, Boston, MA 02114 USA. EM dfriedman@partners.org FU NICHD NIH HHS [R01 HD048629] NR 62 TC 30 Z9 30 U1 2 U2 10 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2009 VL 54 IS 1 BP 16 EP 27 DI 10.1037/a0014279 PG 12 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 410WJ UT WOS:000263608700002 PM 19618699 ER PT J AU Turner, AP Williams, RM Sloan, AP Haselkorn, JK AF Turner, Aaron P. Williams, Rhonda M. Sloan, Alicia P. Haselkorn, Jodie K. TI Injection Anxiety Remains a Long-term Barrier to Medication Adherence in Multiple Sclerosis SO REHABILITATION PSYCHOLOGY LA English DT Article DE multiple sclerosis; medication adherence; anxiety; health behavior ID DISEASE-MODIFYING THERAPIES; QUALITY-OF-LIFE; SELF-INJECT; PATIENT COMPLIANCE; CLINICAL-PRACTICE; IMPAIRMENT; DISABILITY; MS; DYSFUNCTION; VETERANS AB Objective: To evaluate the contribution injection anxiety to disease modifying therapy (DMT) adherence among individuals with multiple sclerosis (MS). Injection anxiety has been associated with medication discontinuation early in the course of treatment, but little is known about the relationship between injection anxiety and sustained DMT adherence over time. Method. Eighty-nine outpatients receiving care at a Veterans Administration MS clinic completed a telephone survey at baseline and monthly telephone follow-up for 6 months. Results: Participants were established DMT users (M = 3.43 years, SD = 3.29), with relatively high adherence overall (over 80% achieved 80% adherence or greater). Using logistic regression and controlling for demographics, MS disability, type of DMT, and time on DMT, the authors found that baseline injection anxiety predicted lower levels of adherence at 4 months and 6 months, with a similar trend at 2 months. Conclusion: Sustained adherence to DMT remains a challenge for a subset of individuals with MS well beyond the initial period of acclimation. Injection anxiety is an important and promising target of psychological intervention during all periods of medication use. C1 [Turner, Aaron P.] VA Puget Sound Hlth Care Syst, Rehabil Care Serv, VA Multiple Sclerosis Ctr Excellence W, VA Ctr Excellence Substance Abuse Treatment & Edu, Seattle, WA 98108 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Rehabil Med, VA Puget Sound Hlth Care Syst, VA Multiple Sclerosis Ctr Excellence W, Seattle, WA 98195 USA. [Haselkorn, Jodie K.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, VA Multiple Sclerosis Ctr Excellence W, VA Ctr Excellence Substance Abuse Treatment & Edu, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI sloan, alicia/0000-0003-4891-3266; Turner, Aaron/0000-0001-6897-8003 NR 39 TC 41 Z9 41 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD FEB PY 2009 VL 54 IS 1 BP 116 EP 121 DI 10.1037/a0014460 PG 6 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 410WJ UT WOS:000263608700014 PM 19618711 ER PT J AU Radwin, LE Cabral, HJ Wilkes, G AF Radwin, Laurel E. Cabral, Howard J. Wilkes, Gail TI Relationships Between Patient-Centered Cancer Nursing Interventions and Desired Health Outcomes in the Context of the Health Care System SO RESEARCH IN NURSING & HEALTH LA English DT Article DE Patient centered care; quality of care; desired health outcomes; health services research; cancer ID POWER ANALYSIS; PERCEPTIONS; QUALITY; SATISFACTION; MORTALITY; COLLABORATION; PERFORMANCE; PREDICTORS; MODELS; IMPACT AB A non-experimental longitudinal prospective study was conducted to examine the relationships between patient-centered nursing interventions (PCNIs), system characteristics, patient characteristics, and desired health outcomes (DHOs) for 173 hematology-oncology patients. Forty-nine nurse Participants Provided system characteristics data. Confirmatory factor analyses yielded Parsimonious scales to operationalize the variables. In the Path model, one PCNI-individualization-was positively related to three subsequent DHOs: authentic self-representation, optimism, and sense of well-being. Two additional PCNIs-responsiveness and proficiency-were positively related to subsequent trust in nurses. PCNIs did not vary with patient race, ethnicity, age, gender, or educational level. Patient-centeredness of care for cancer patients may be enhanced by quality improvement activities that measure and monitor these PCN Is and resultant outcomes. (c) 2008 Wiley Periodicals, Inc. Res Nurs Health 32:4-17, 2009 C1 [Radwin, Laurel E.] Massachusetts Gen Hosp, Inst Patient Care, Boston, MA 02114 USA. [Cabral, Howard J.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Wilkes, Gail] Boston Med Ctr, Boston, MA USA. RP Radwin, LE (reprint author), Massachusetts Gen Hosp, Inst Patient Care, 275 Cambridge St,POB 430, Boston, MA 02114 USA. OI Cabral, Howard/0000-0002-1185-8331 FU Agency for Health Care Research and Quality Mentored Clinical Scientist [HS K08 11625]; AHRQ FX This study was funded by an Agency for Health Care Research and Quality Mentored Clinical Scientist award to Dr. Radwin (HS K08 11625). The authors would like to extend appreciation to the Patients and nurses who Participated in the study, the research assistants who helped with the study's conduct, and to the panel of advisors on Dr. Radwin's AHRQ award. NR 63 TC 33 Z9 33 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD FEB PY 2009 VL 32 IS 1 BP 4 EP 17 DI 10.1002/nur.20302 PG 14 WC Nursing SC Nursing GA 395JX UT WOS:000262521500002 PM 18814304 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI Should Noninvasive Ventilation Be Used With the Do-Not-Intubate Patient? SO RESPIRATORY CARE LA English DT Article CT 42nd Respiratory Care Journal Conference on Noninvasive Ventilation in Acute Care - Controversies and Emerging Concepts CY MAR 07-09, 2008 CL Cancun, MEXICO DE respiratory failure; mechanical ventilation; noninvasive ventilation; do not intubate; do not resuscitate; comfort measures only; acute respiratory failure; end of life; death ID ACUTE RESPIRATORY-FAILURE; POSITIVE-PRESSURE VENTILATION; OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; REFUSED ENDOTRACHEAL INTUBATION; MECHANICAL VENTILATION; ACUTE EXACERBATIONS; ADVANCE DIRECTIVES; PALLIATIVE CARE; AIRWAY PRESSURE AB Most of the large quantity of data on noninvasive ventilation (NIV) in acute respiratory failure is from patients who want all possible treatments and life-support. Few data are available on NIV in patients who have elected specific limits on life support and treatments (eg, patients with do-not-intubate [DNI] orders) and patients who are near the end of life and will receive comfort measures only (CMO). The most critical issue regarding NIV in DNI and CMO patients is informed consent. The patient must be informed of the risks and potential benefits of NIV, and must consent to NIV. We have few data on patients' attitudes about NIV at end of life. Data from cancer patients at end of life suggest that they want to maintain control over care decisions and may want treatment that delays death long enough that they can put their affairs in order. If informed consent and control of care decisions are assured, then NIV can be appropriate in DNI and CMO patients to reverse an acute respiratory failure that is not necessarily life-terminating, or to improve patient comfort, or to delay death. C1 [Kacmarek, Robert M.] Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. [Kacmarek, Robert M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 45 TC 10 Z9 10 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD FEB PY 2009 VL 54 IS 2 BP 223 EP 229 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 404KK UT WOS:000263150200008 PM 19173754 ER PT J AU Hess, DR AF Hess, Dean R. TI How to Initiate a Noninvasive Ventilation Program: Bringing the Evidence to the Bedside SO RESPIRATORY CARE LA English DT Article CT 42nd Respiratory Care Journal Conference on Noninvasive Ventilation in Acute Care - Controversies and Emerging Concepts CY MAR 07-09, 2008 CL Cancun, MEXICO DE guidelines; noninvasive ventilation; NIV; mechanical ventilation; respiratory failure ID POSITIVE-PRESSURE VENTILATION; ACUTE RESPIRATORY-FAILURE; CARDIOGENIC PULMONARY-EDEMA; CLINICAL-PRACTICE GUIDELINES; MECHANICAL VENTILATION; KNOWLEDGE TRANSLATION; ACUTE EXACERBATIONS; HEALTH-CARE; METAANALYSIS; DISEASE AB Noninvasive ventilation (NIV) is under-utilized, despite robust evidence supporting its use in appropriately selected patients with acute respiratory failure. Diffusion of NIV into practice requires that clinicians view it as better than invasive ventilation, that it is perceived as compatible with existing approaches to mechanical ventilation, that it is not too difficult to apply, that it is trialable, and that its results are visible. Barriers to NIV use include lack of awareness of the evidence, lack of agreement with the evidence, lack of self-efficacy, unrealistic outcome expectations, and the inertia of previous practice. A flexible, tireless, enthusiastic, and knowledgeable clinical champion is important when initiating an NIV program. Knowledge and training are also important; ideally the training should be one-on-one and hands-on to the extent possible. Adequate personnel and equipment resources are necessary when implementing the program. Guidelines and protocols may be useful as educational resources, to avoid clinical conflict and consolidate authority. When initiating an NIV program it is important to recognize that NIV does not avoid intubation in all cases. Success often improves with experience. The available evidence suggests that NIV is cost-effective. For optimum success the multidisciplinary nature of NIV application must be recognized. The NIV program should be a quality-improvement initiative. Following these principles, a successful program can be initiated in any acute-care setting. C1 [Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. [Hess, Dean R.] Harvard Univ, Sch Med, Boston, MA USA. RP Hess, DR (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. EM dhess@partners.org NR 51 TC 10 Z9 11 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD FEB PY 2009 VL 54 IS 2 BP 232 EP 243 PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 404KK UT WOS:000263150200010 PM 19173755 ER PT J AU Batki, SL Meszaros, ZS Strutynski, K Dimmock, JA Leontieva, L Ploutz-Snyder, R Canfield, K Drayer, RA AF Batki, Steven L. Meszaros, Zsuzsa S. Strutynski, Katherine Dimmock, Jacqueline A. Leontieva, Luba Ploutz-Snyder, Robert Canfield, Kelly Drayer, Rebecca A. TI Medical comorbidity in patients with schizophrenia and alcohol dependence SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Alcohol; Medical illness; Substance abuse; Comorbidity ID ILLNESS RATING-SCALE; SUBSTANCE-ABUSE; MENTAL-ILLNESS; CO-MORBIDITY; SEVERITY; HEALTH; VALIDATION; DISORDERS; MORTALITY; PEOPLE AB Background: Schizophrenia and alcohol dependence are major risk factors for a variety of medical problems, yet there has been little research on the medical status of patients in whom both conditions coexist. Methods: We assessed the prevalence and severity of medical illness in 80 patients with schizophrenia or schizoaffective disorder and comorbid alcohol use disorders who entered a controlled trial of monitored naltrexone treatment, and analyzed the relationship between medical illness burden and demographic variables, alcohol and other substance use, and psychosis. Participants underwent physical examination, laboratory tests, medical record review and standardized assessments of medical illness burden, alcohol and other substance use, and psychosis. Nested block multiple regression analyses were used to assess the contribution to illness burden made by demographic variables, alcohol and substance use, and psychosis severity. Results: 83% of participants had at least one chronic medical illness, hypertension being the most common (43%). Medical comorbidity in this cohort was more severe than for schizophrenia patients in the CATIE trial (Chwastiak, L. Rosenheck, R., McEvoy, J.P., Keefe, R.S., Swartz, M.S., Lieberman,J.A., 2006. Interrelationships of Psychiatric Symptom Severity, Medical Comorbidity, and Functioning in Schizophrenia. Psychiatr. Serv., 57(8), 1102-1109.); the prevalence of hypertension, chronic obstructive pulmonary disease, and coronary artery disease, was more than twice greater. Medical illness burden correlated with alcohol use severity, but appeared to be independent of other substance use or psychosis severity. Conclusions: Patients with co-occurring alcohol use disorder may have significantly more medical illness burden than patients with schizophrenia or schizoaffective disorder alone. Interventions to reduce alcohol use may be necessary to lessen medical morbidity. Published by Elsevier B.V. C1 [Batki, Steven L.] Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr 116P, Addict Psychiat Res Program, San Francisco, CA 94121 USA. [Batki, Steven L.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Batki, Steven L.; Meszaros, Zsuzsa S.; Strutynski, Katherine; Dimmock, Jacqueline A.; Leontieva, Luba; Canfield, Kelly] SUNY Upstate Med Univ, Dept Psychiat, New York, NY USA. [Batki, Steven L.; Drayer, Rebecca A.] VA Ctr Integrated Healthcare Syracuse, New York, NY USA. [Ploutz-Snyder, Robert] NASA, Houston, TX USA. [Drayer, Rebecca A.] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA. RP Batki, SL (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco VA Med Ctr 116P, Addict Psychiat Res Program, 4150 Clement St, San Francisco, CA 94121 USA. EM steven.batki@ucsf.edu FU National Institutes of Health/the National Institute on Alcoholism and Alcohol Abuse (NIH/NIAAA) [RO1 AA013655] FX The sponsor, the National Institutes of Health/the National Institute on Alcoholism and Alcohol Abuse (NIH/NIAAA) had no role in the study design, in the collection, analysis and interpretation of data, in the writing of the report, or in the decision to Submit the paper for publication.; This research was supported by NIH/NIAAA grant "Naltrexone Treatment of Alcohol Abuse in Schizophrenia" number: RO1 AA013655 to Dr. Batki. The assistance of Michelle Cavallerano, Sara DeRycke, and Lisa Gallinger is gratefully acknowledged. NR 30 TC 24 Z9 27 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2009 VL 107 IS 2-3 BP 139 EP 146 DI 10.1016/j.schres.2008.10.016 PG 8 WC Psychiatry SC Psychiatry GA 407XM UT WOS:000263397600005 PM 19022627 ER PT J AU Kleinman, L Lieberman, J Dube, S Mohs, R Zhao, Y Kinon, B Carpenter, W Harvey, PD Green, MF Keefe, RSE Frank, L Bowman, L Revicki, DA AF Kleinman, Leah Lieberman, Jeffrey Dube, Sanjay Mohs, Richard Zhao, Yang Kinon, Bruce Carpenter, William Harvey, Philip D. Green, Michael F. Keefe, Richard S. E. Frank, Lori Bowman, Lee Revicki, Dennis A. TI Development and psychometric performance of the schizophrenia objective functioning instrument: An interviewer administered measure of function SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Functioning; Outcomes assessment; Schizophrenia; Cognitive impairment; Reliability; Validity ID QUALITY-OF-LIFE; NEUROCOGNITIVE DEFICITS; COGNITIVE IMPAIRMENT; SOCIAL-ADJUSTMENT; OLDER OUTPATIENTS; WORK PERFORMANCE; SCALE; VALIDITY; REHABILITATION; CONSEQUENCES AB Existing measures for functional assessment do not adequately address the relationship between cognitive impairment and function. The Schizophrenia Outcomes Functioning Interview (SOFI) was developed to measure community functioning related to cognitive impairment and psychopathology. Following review of existing measures and discussion with experts, caregivers, and patients, content was generated for four domains: 1) living situation; 2) IADLs; 3) productive activities; and 4) social functioning. The final SOFI was constructed with items informing domain scores, and an interviewer-completed global rating for each domain. Psychometric characteristics of the SOFI were evaluated in a sample of 104 community residing patients with schizophrenia and their informants. Test-retest reliability was evaluated in a subsample of patient-informant dyads using ICC; all values were >0.70 for both patient-interviews (SOFI-P) and informant-interviews (SOFI-I). Inter-rater reliability ICCs ranged from 0.50 to 0.79 on a different sub-sample. The SOFI demonstrated adequate construct validity based on correlations with the PSP (range 0.58 to 0.76; p < 0.0001) and the QLS (p < 0.001). Some correlations between SOFI and PETiT scores were low to moderate (p < 0.05). Discriminant validity was supported based on SOFI score comparisons for patient groups based on PANSS and BACS scores (p < 0.05); SOFI scores differed between borderline and moderately ill patients as measured by the CGI-S (p < 0.05). The SOFI expands on existing measures and more comprehensively captures functioning of patients in the real world than other performance-based (proxy) measures. The SOFI has good evidence supporting reliability and construct validity, and may be a useful measure of functional outcomes in schizophrenia. (C) 2008 Elsevier B.V. All rights reserved. C1 [Kleinman, Leah] United BioSource Corp, Seattle, WA USA. [Lieberman, Jeffrey] Columbia Univ, New York, NY USA. [Dube, Sanjay; Mohs, Richard; Zhao, Yang; Kinon, Bruce; Bowman, Lee] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Carpenter, William] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. [Carpenter, William] VISN 5 MIRECC, Baltimore, MD USA. [Harvey, Philip D.] Mt Sinai Sch Med, New York, NY USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. [Green, Michael F.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Keefe, Richard S. E.] Duke Univ, Med Ctr, Durham, NC USA. [Frank, Lori; Revicki, Dennis A.] United BioSource Corp, Bethesda, MD USA. RP Kleinman, L (reprint author), United BioSource Corp, Seattle, WA USA. EM leah.kleinman@unitedbiosource.com NR 45 TC 21 Z9 21 U1 7 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2009 VL 107 IS 2-3 BP 275 EP 285 DI 10.1016/j.schres.2008.10.002 PG 11 WC Psychiatry SC Psychiatry GA 407XM UT WOS:000263397600026 PM 19013769 ER PT J AU de Jong, JJ Hodiamont, PPG Van den Stock, J de Geldera, B AF de Jong, J. J. Hodiamont, P. P. G. Van den Stock, J. de Geldera, B. TI Audiovisual emotion recognition in schizophrenia: Reduced integration of facial and vocal affect SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Emotion recognition; Multisensory integration; Schizophrenia ID STARTLE GATING DEFICITS; MULTISENSORY INTEGRATION; SPEECH-PERCEPTION; NEUROCOGNITIVE DEFICITS; FUNCTIONAL-SIGNIFICANCE; CROSSMODAL BINDING; HUMAN BRAIN; VOICE; EXPRESSIONS; FACE AB Since Kraepelin called dementia praecox what we nowadays call schizophrenia, cognitive dysfunction has been regarded as central to its psychopathological profile. Disturbed experience and integration of emotions are, both intuitively and experimentally, likely to be intermediates between basic, non-social cognitive disturbances and functional outcome in schizophrenia. While a number of studies have consistently proven that, as part of social cognition, recognition of emotional faces and voices is disturbed in schizophrenics, studies on multisensory integration of facial and vocal affect are rare. We investigated audiovisual integration of emotional faces and voices in three groups: schizophrenic patients, non-schizophrenic psychosis patients and mentally healthy controls, all diagnosed by means of the Schedules of Clinical Assessment in Neuropsychiatry (SCAN 2.1). We found diminished crossmodal influence of emotional faces on emotional voice categorization in schizophrenics, but not in non-schizophrenia psychosis patients. Results are discussed in the perspective of recent theories on multisensory integration. (C) 2008 Elsevier B.V. All rights reserved. C1 [de Geldera, B.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [de Geldera, B.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [de Jong, J. J.; Van den Stock, J.; de Geldera, B.] Tilburg Univ, Cognit Neurosci Lab, NL-5000 LE Tilburg, Netherlands. [Hodiamont, P. P. G.] Tilburg Univ, Dept Dev Clin & Cross Cultural Psychol, NL-5000 LE Tilburg, Netherlands. [Van den Stock, J.] Univ Hosp Leuven, Old Age Psychiat Dept, B-3000 Louvain, Belgium. RP de Geldera, B (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Room 417,Bldg 36,1st St, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu RI Van den Stock, Jan/F-1906-2014 OI Van den Stock, Jan/0000-0001-5756-3195 NR 54 TC 59 Z9 59 U1 2 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD FEB PY 2009 VL 107 IS 2-3 BP 286 EP 293 DI 10.1016/j.schres.2008.10.001 PG 8 WC Psychiatry SC Psychiatry GA 407XM UT WOS:000263397600027 PM 18986799 ER PT J AU Szostak, J AF Szostak, Jack TI Ray Wu, as remembered by a former student In Memoriam SO SCIENCE IN CHINA SERIES C-LIFE SCIENCES LA English DT Biographical-Item C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Szostak, J (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Ctr Computat & Integrat Biol, 185 Cambridge St, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute NR 0 TC 4 Z9 5 U1 0 U2 0 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1006-9305 J9 SCI CHINA SER C JI Sci. China Ser. C-Life Sci. PD FEB PY 2009 VL 52 IS 2 BP 108 EP 110 DI 10.1007/s11427-009-0023-6 PG 3 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 417VG UT WOS:000264106000004 PM 19277516 ER PT J AU Robinson, KC Fisher, DE AF Robinson, Kathleen C. Fisher, David E. TI Specification and loss of melanocyte stem cells SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE Melanocytes; Stem cells; Bcl2; Graying ID TRANSCRIPTION FACTOR MITF; HAIR PIGMENTATION; MELANOCORTIN-1 RECEPTOR; WAARDENBURG-SYNDROME; MALIGNANT-MELANOMA; LINEAGE SURVIVAL; NEURAL CREST; BETA-CATENIN; COAT-COLOR; MICROPHTHALMIA AB The melanocyte stem cells of the hair follicle provide an attractive system for the study of stem cells. The stem cells exist in an anatomically defined niche clearly separated from their differentiated progeny, differentiated progeny can be selected against by treatment with an inhibitor of Stem Cell Factor signaling, perturbations which affect survival and differentiation have clearly visible pigmentation phenotypes, and genetic mutations can impair or completely abolish this lineage without lethality. In mice several coat color mutants have been shown to have impaired specification or survival of melanocyte stem cells. Furthermore understanding of the normal regulation and behaviors of melanocytes and melanocyte stem cells will allow development of better strategies for cancer treatment. This article will review the discovery and behaviors of melanoctye stem cells as well as some aspects of melanocyte biology. Published by Elsevier Ltd. C1 [Robinson, Kathleen C.; Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Boston, MA 02114 USA. EM dfisher3@partners.org NR 54 TC 13 Z9 13 U1 0 U2 6 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD FEB PY 2009 VL 20 IS 1 BP 111 EP 116 DI 10.1016/j.semcdb.2008.11.016 PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 456EK UT WOS:000266823400015 PM 19124082 ER PT J AU Mora, JR von Andrian, UH AF Mora, J. Rodrigo von Andrian, Ulrich H. TI Role of retinoic acid in the imprinting of gut-homing IgA-secreting cells SO SEMINARS IN IMMUNOLOGY LA English DT Review DE B cells; Retinoic acid; IgA; Antibody-secreting cells; Homing ID A-DEFICIENT RATS; VASOACTIVE-INTESTINAL-PEPTIDE; HUMAN B-CELLS; PATCH DENDRITIC CELLS; ORAL CHOLERA VACCINE; MURINE SPLEEN-CELLS; VITAMIN-A; IN-VIVO; T-CELLS; PEYERS PATCH AB Antibody-secreting cells (ASCs) lodging in the mucosa of the small intestine are derived from activated B cells that are thought to arise in gut-associated lymphoid tissues (GALT). Upon leaving the GALT, B cells return to the blood where they must express the gut-homing receptors alpha 4 beta 7 and CCR9 in order to emigrate into the small bowel. Recent evidence indicates that gut-associated dendritic cells (DCs) in GALT induce gut-homing receptors on B cells via a mechanism that depends on the vitamin A metabolite retinoic acid (RA). In addition, although ASC associated with other mucosal tissues secrete IgA in an RA-independent fashion, the presence of high levels of RA in intestine and GALT can promote B cell class switching to IgA and thus, boost the production of IgA in the intestinal mucosa. Here, we discuss the role of RA in the imprinting of gut-homing ASC and the evidence linking RA with the generation of intestinal IgA-ASCs. (C) 2008 Elsevier Ltd. All rights reserved. C1 [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Mora, J. Rodrigo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 77 Ave Louis Pasteur,Room 836, Boston, MA 02115 USA. EM j_rodrigo_mora@hms.harvard.edu; uva@hms.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU Crohn's & Colitis Foundation of America (CCFA); Cancer Research Institute (CRI); Center for the Study of IBD (CSIBD) [DK 43351]; Massachusetts Life Sciences Center (MLSC); Howard M. Goodman Fellowship (MGH); NIH [AI061663, AI069259, AI072252, HL56949, AR42689] FX We thank Susan Davis foreditorial assistance. JRM is indebted to Ingrid Ramos for constant support. JRM is supported by grants from Crohn's & Colitis Foundation of America (CCFA), Cancer Research Institute (CRI), Center for the Study of IBD (CSIBD, DK 43351), Massachusetts Life Sciences Center (MLSC) and the Howard M. Goodman Fellowship (MGH). UHvA is supported by NIH grants AI061663, AI069259, AI072252, HL56949 and AR42689. NR 151 TC 81 Z9 85 U1 0 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD FEB PY 2009 VL 21 IS 1 BP 28 EP 35 DI 10.1016/j.smim.2008.08.002 PG 8 WC Immunology SC Immunology GA 387ZG UT WOS:000261989500006 PM 18804386 ER PT J AU Restrepo, MI Anzueto, A AF Restrepo, Marcos I. Anzueto, Antonio TI The Role of Gram-Negative Bacteria in Healthcare-Associated Pneumonia SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Pneumonia; healthcare-associated; outcomes ID HOME-ACQUIRED PNEUMONIA; STAPHYLOCOCCUS-AUREUS INFECTION; LONG-TERM-CARE; RISK-FACTORS; MANAGEMENT; EPIDEMIOLOGY; OUTCOMES; DEFINITION; PREVENTION; GUIDELINES AB Healthcare-associated pneumonia (HCAP) is a unique entity that differs from community-acquired pneumonia in both bacteriology and outcomes and has similarities to hospital-acquired pneumonia and ventilator-associated pneumonia. HCAP patients are at higher risk of potential multidrug-resistant pathogens, including resistant grain-negative organisms, especially Pseudomonas aeruginosa and Acinetobacter spp., but also extended-spectrum beta-lactamases (ESBLs). This manuscript reviews the epidemiology, etiology, and clinical outcomes of hospitalized HCAP patients due to gram-negative bacteria. We win focus our attention on the potential multidrug-resistant pathogens to suggest a new treatment approach for these patients. C1 [Restrepo, Marcos I.] Audie L Murphy Div San Antonio, S Texas Vet Hlth Care Syst, VERDICT 11C6, Div Pulm & Crit Care Med, San Antonio, TX 78284 USA. [Restrepo, Marcos I.; Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Restrepo, MI (reprint author), Audie L Murphy Div San Antonio, S Texas Vet Hlth Care Syst, VERDICT 11C6, Div Pulm & Crit Care Med, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. EM restrepom@uthscsa.edu RI Restrepo, Marcos/H-4442-2014 NR 30 TC 18 Z9 20 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1069-3424 J9 SEMIN RESP CRIT CARE JI Semin. Respir. Crit. Care Med. PD FEB PY 2009 VL 30 IS 1 BP 61 EP 66 DI 10.1055/s-0028-1119810 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 427SF UT WOS:000264798700009 PM 19199188 ER PT J AU Ghebremichael, M Paintsil, E Larsen, U AF Ghebremichael, Musie Paintsil, Elijah Larsen, Ulla TI Alcohol Abuse, Sexual Risk Behaviors, and Sexually Transmitted Infections in Women in Moshi Urban District, Northern Tanzania SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; HIV-INFECTION; SOUTH-AFRICA; REPRODUCTIVE HEALTH; UGANDA; DRINKING; ACQUISITION; VIOLENCE; RAKAI; TRANSMISSION AB Background: To assess the covariates of alcohol abuse and the association between alcohol abuse, high-risk sexual behaviors and sexually transmitted infections (STIs). Methods: Two thousand and nineteen women aged 20 to 44 were randomly selected in a 2-stage sampling from the Moshi urban district of northern Tanzania. Participant's demographic and socio-economic characteristics, alcohol use, sexual behaviors, and STIs were assessed. Blood and urine samples were drawn for testing of human immunodeficiency virus, herpes simplex virus, syphilis, chlamydia, gonorrhea, trichomonas, and mycoplasma genitalium infections. Results: Adjusted analyses showed that a history of physical (OR 2.05; 95% CI: 1.06-3.98) and sexual violence (OR = 1.63; 95% CI: 1.05-2.51) was associated with alcohol abuse. Moreover, alcohol abuse was associated with number of sexual partners (OR = 1.66; 95% CI: 1.01-2.73). Women who abused alcohol were more likely to report STIs symptoms (OR = 1.61; 95%, CI: 1.08-2.40). Women who had multiple sexual partners were more likely to have an STI (OR = 2.41; 95% CI: 1.46-4.00.) compared to women with I sexual partner. There was no direct association between alcohol abuse and prevalence of STIs (OR = 0.86; 95% CI: 0.55-134). However, alcohol abuse was indirectly associated with STIs through its association with multiple sexual partners. Conclusions: The findings of alcohol abuse among physically and sexually violated women as well as the association between alcohol abuse and a history of symptoms of STIs and testing positive for STIs have significant public health implications. In sub-Saharan Africa, where women are disproportionately affected by the HIV epidemic screening for alcohol use should he part or comprehensive STIs and HIV prevention programs. C1 [Ghebremichael, Musie] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Ghebremichael, Musie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Paintsil, Elijah] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. [Paintsil, Elijah] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA. [Larsen, Ulla] Univ Maryland, Dept Sociol, College Pk, MD 20742 USA. RP Ghebremichael, M (reprint author), Harvard Univ, Sch Publ Hlth, 3 Blackfan Circle, Boston, MA 02115 USA. EM musie@jimmy.harvard.edu FU NIH/NICHD [R01 HD41202]; Harvard University Center for AIDS Research NIH/NAIDS [P30-A1 060354]; NIH/NIDA [5 U01-DA017387-03S] FX This Study was supported by grants NIH/NICHD R01 HD41202, and Harvard University Center for AIDS Research NIH/NAIDS P30-A1 060354. EP was Supported by NIH/NIDA 5 U01-DA017387-03S]. NR 37 TC 23 Z9 23 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD FEB PY 2009 VL 36 IS 2 BP 102 EP 107 DI 10.1097/OLQ.0b013e31818b20e6 PG 6 WC Infectious Diseases SC Infectious Diseases GA 400TC UT WOS:000262890500010 PM 19060779 ER PT J AU O'Hearn, DJ Gold, AR Gold, MS Diggs, P Scharf, SM AF O'Hearn, Daniel J. Gold, Avram R. Gold, Morris S. Diggs, Paul Scharf, Steven M. TI Lower extremity edema and pulmonary hypertension in morbidly obese patients with obstructive sleep apnea SO SLEEP AND BREATHING LA English DT Article DE Edema; Pulmonary hypertension; Morbid obesity; Obstructive sleep apnea ID LEFT-VENTRICULAR HYPERTROPHY; POSITIVE AIRWAY PRESSURE; CARDIAC-OUTPUT; COR-PULMONALE; HEART-FAILURE; LUNG-DISEASE; CLINICAL FEATURES; CYSTIC-FIBROSIS; HEMODYNAMICS; DYSFUNCTION AB In 70 consecutive male patients with obstructive sleep apnea (OSA) diagnosed at the Northport VA Medical Center Sleep Disorders Center, we have characterized the association between obesity, OSA, and pulmonary hypertension (PH). By including anthropometric, pulmonary function, and sleep study parameters in a multivariate logistic regression model, we found that a BMI of > 40 kg/m(2) and the minimum oxygen saturation in non-rapid eye movement (NREM) sleep predicted the presence of pretibial edema in this sleep apnea population. We then characterized the hemodynamics of those OSA patients that had lower extremity edema. Twenty-nine of the 70 consecutive patients with sleep apnea (41%) had pretibial edema, and right heart catheterization data was obtained for 28 (97%) of these patients. Ninety-three percent (26/28) of the patients had right heart failure (mean RAP > 5 mm Hg; RAP range = 0-32 mmHg) and PH (PA mean a parts per thousand yenaEuro parts per thousand 20 mm Hg) was present in 86% (24/28.) The OSA patients with lower extremity edema had an increased cardiac output (7.0 + 1.4 l/min) with a normal cardiac index (2.9 + 0.5 l/min/m(2)) in the setting of an elevated pulmonary capillary wedge pressure (PCWP 17 +/- 7 mmHg) and a normal pulmonary vascular resistance (122 + 70 dynes s cm(-5)). While PCWP, FEV(1)% predicted, and the minimum oxygen saturation in NREM sleep all independently predicted PH, PCWP was the most important predictor of PH. We conclude that pulmonary hypertension is commonly seen in patients with OSA with pretibial edema and that pretibial edema is a highly specific sign of PH in OSA patients. Pulmonary hypertension appears to result from an elevated back pressure and diastolic dysfunction with contributions from lung function and nocturnal oxygen saturation. C1 Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, Portland, OR 97239 USA. [Gold, Avram R.; Diggs, Paul] Northport VA Med Ctr NY, Dept Med, Northport, NY USA. [Gold, Avram R.; Diggs, Paul] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. [Gold, Morris S.] Novartis Consumer Hlth, Summit, NJ USA. [Scharf, Steven M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP O'Hearn, DJ (reprint author), Oregon Hlth & Sci Univ, Dept Med, Portland VA Med Ctr, P3-PULM,POB 1034, Portland, OR 97239 USA. EM ohearnd@ohsu.edu FU Novartis Consumer Health FX The authors wish to acknowledge Dr. John P. Dervan and the many attending physicians and fellows of the Cardiology Division of SUNY-Stony Brook School of Medicine who diligently obtained the catheterization data that made this study possible. The authors have no conflicts of interest to report. The work performed by Morris Gold was not connected to his position at Novartis Consumer Health. NR 69 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1520-9512 J9 SLEEP BREATH JI Sleep Breath. PD FEB PY 2009 VL 13 IS 1 BP 25 EP 34 DI 10.1007/s11325-008-0200-z PG 10 WC Clinical Neurology; Respiratory System SC Neurosciences & Neurology; Respiratory System GA 387NU UT WOS:000261959700005 PM 18615260 ER PT J AU Zebrowitz, LA Luevano, VX Bronstad, PM Aharon, I AF Zebrowitz, Leslie A. Luevano, Victor X. Bronstad, Philip M. Aharon, Itzhak TI Neural activation to babyfaced men matches activation to babies SO SOCIAL NEUROSCIENCE LA English DT Article ID FUSIFORM FACE AREA; DISTRIBUTED CORTICAL NETWORK; TEMPORAL CORTEX; FACIAL EXPRESSION; HUMAN AMYGDALA; PERCEPTION; FMRI; ATTRACTIVENESS; RECOGNITION; RESPONSES AB Behavioral data supports the commonsense view that babies elicit different responses than adults do. Behavioral research also has supported the babyface overgeneralization hypothesis that the adaptive value of responding appropriately to babies produces a tendency for these responses to be over-generalized to adults whose facial structure resembles babies. Here we show a neural substrate for responses to babies and babyface overgeneralization in the amygdala and the fusiform face area (FFA). Both regions showed greater percentage BOLD signal change compared with fixation when viewing faces of babies or babyfaced men than maturefaced men. Viewing the first two categories also yielded greater effective connectivity between the two regions. Facial qualities previously shown to elicit strong neural activation could not account for the effects. Babyfaced men were distinguished only by their resemblance to babies. The preparedness to respond to infantile facial qualities generalizes to babyfaced men in perceivers' neural responses just as it does in their behavioral reactions. C1 [Zebrowitz, Leslie A.] Brandeis Univ, Dept Psychol MS 062, Waltham, MA 02454 USA. [Aharon, Itzhak] Massachusetts Gen Hosp, Martinos Ctr, Cambridge, MA USA. RP Zebrowitz, LA (reprint author), Brandeis Univ, Dept Psychol MS 062, Waltham, MA 02454 USA. EM zebrowitz@brandeis.edu FU NIH [ME066836]; NSF [0315307, K02MH72603] FX This work was supported by NIH Grant ME066836 and NSF Grant 0315307 to the first and last authors and K02MH72603 to the first author. The Authors declare that they have no competing financial interests. NR 58 TC 8 Z9 9 U1 4 U2 14 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1747-0919 J9 SOC NEUROSCI JI Soc. Neurosci. PD FEB PY 2009 VL 4 IS 1 BP 1 EP 10 DI 10.1080/17470910701676236 PG 10 WC Neurosciences; Psychology SC Neurosciences & Neurology; Psychology GA 412EO UT WOS:000263706800001 PM 19101842 ER PT J AU Nogueira, RG Smith, WS AF Nogueira, Raul G. Smith, Wade S. CA MERCI & Multi MERCI Writing Comm TI Safety and Efficacy of Endovascular Thrombectomy in Patients With Abnormal Hemostasis Pooled Analysis of the MERCI and Multi MERCI Trials SO STROKE LA English DT Article DE acute stroke; anticoagulation; endovascular treatment; interventional neuroradiology; intracerebral hemorrhage; intracranial hemorrhage; thrombolysis; thrombectomy; thrombocytopenia ID ACUTE ISCHEMIC-STROKE; INTERVENTIONAL MANAGEMENT; PLASMINOGEN-ACTIVATOR; THROMBOLYSIS; TISSUE; PROUROKINASE; PROACT AB Background and Purpose-Patients with abnormal hemostasis are not considered candidates for thrombolysis. We analyzed the MERCI/Multi MERCI cohort as an attempt to establish the risks and benefits of thrombectomy in this patient population. Methods-Two patient groups were identified: Group 1 (n=35): patients with INR >1.7 or PTT >45 seconds or platelet count <100 000/mu L; Group 2 (n=270): patients with INR <= 1.7, PTT <= 45 seconds, and platelet count >= 100 000/mu L. Clinical, radiographic, and revascularization outcomes were subsequently compared. Results-In Group 1, 20 patients had INR >1.7 (mean: 2.4; range: 1.8 to 4.9), 11 had PTT >45 seconds (mean: 95; range: 46 to 190), and 6 had platelets <100 000/mu L (mean: 63 400; range: 16 000 to 94 000). Two patients had both INR >1.7 and PTT >45 seconds. The two groups did not significantly differ in terms of age, gender, baseline NIHSS scores, intraarterial thrombolytic use/dosage, or occlusion site. Time-to-treatment was slightly earlier in Group 1. There was no significant difference in the rates of revascularization (TIMI 2 to 3: 60% versus 65%), mortality (40% versus 38%), or major symptomatic intracranial hemorrhage (SICH; 8.6% versus 8.5%). Group 2 had higher rates of good clinical outcomes (9% versus 35%; P=0.002). This was likely related to a lower prestroke health status in Group 1 patients. In Group 1, successful revascularization was associated with improved outcomes (P=0.015) and lower mortality (24% versus 64%; P=0.033). Conclusion-Patients with abnormal hemostasis who undergo thrombectomy do not appear to be at a higher risk for SICH but have lower rates of good outcomes. In this patient group, successful revascularization appears to be associated with improved clinical outcomes and lower mortality. (Stroke. 2009;40:516-522.) C1 [Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, Boston, MA 02114 USA. [Nogueira, Raul G.] Massachusetts Gen Hosp, Dept Vasc & Crit Care Neurol, Boston, MA 02114 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB-2-241, Boston, MA 02114 USA. EM rnogueira@partners.org NR 13 TC 40 Z9 41 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2009 VL 40 IS 2 BP 516 EP 522 DI 10.1161/STROKEAHA.108.525089 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 399FD UT WOS:000262784900029 PM 19095994 ER PT J AU Reeves, MJ Smith, E Fonarow, G Hernandez, A Pan, WQ Schwamm, LH AF Reeves, Mathew J. Smith, Eric Fonarow, Gregg Hernandez, Adrian Pan, Wenqin Schwamm, Lee H. CA GWTG-Stroke Steering Comm & Invest TI Off-Hour Admission and In-Hospital Stroke Case Fatality in the Get With The Guidelines-Stroke Program SO STROKE LA English DT Article DE acute stroke; outcomes; quality improvement; quality of health care ID PRIVATE FOR-PROFIT; MORTALITY-RATES; ISCHEMIC-STROKE; MYOCARDIAL-INFARCTION; WEEKEND ADMISSION; METAANALYSIS; TIME; CARE; ONSET AB Background and Purpose-Previous reports have shown higher in-hospital mortality for patients with acute stroke who arrived on weekends compared with regular workdays. We analyzed the effect of presenting during off-hours, defined as weekends and weeknights (versus weekdays), on in-hospital mortality and on quality of care in the Get With The Guidelines (GWTG)-Stroke program. Methods-We analyzed data from 187 669 acute ischemic stroke and 34 845 acute hemorrhagic stroke admissions who presented to the emergency departments of 857 hospitals that participated in the GWTG-Stroke program during the 4-year period 2003 to 2007. Off-hour presentation was defined as presentation anytime outside of 7: 00 AM to 6: 00 PM on weekdays. Quality of care was measured using standard GWTG quality indicators covering acute, subacute, and discharge measures. The relationship between off-hour presentation and in-hospital case fatality was examined using generalized estimating equation logistic regression adjusting for demographics, risk factors, arrival mode, and hospital characteristics. Results-Half of ischemic stroke admissions and 57% of hemorrhagic stroke admissions presented during off-hours. Among ischemic stroke admissions, the in-hospital case fatality rate was 5.8% for off-hour presentation compared with 5.2% for on-hour presentation (P<0.001). For hemorrhagic stroke admissions, in-hospital case fatality was 27.2% for off-hour presentation compared with 24.1% for on-hour presentation (P<0.001). After adjusting for patient-level and hospital-level factors, presentation during off-hours was significantly associated with higher in-hospital mortality for both ischemic stroke (adjusted OR, 1.09; 95% CI, 1.03 to 1.14) and hemorrhagic stroke admissions (adjusted OR, 1.19; 95% CI, 1.12 to 1.27). No differences were observed between off-hour presentation and any of the quality of care measures. Conclusions-Off-hour presentation was associated with an increased risk of dying in-hospital, although the absolute effect was small for ischemic stroke admissions (0.6% difference; number needed to harm=166) and moderate for hemorrhagic stroke (3.1% difference; number needed to harm=32). Reducing the disparity in hospital-based outcomes for admissions that present during off-hours represents a potential target for quality improvement efforts, although evidence of differences in the quality of care by time of presentation was lacking. (Stroke. 2009;40:569-576.) C1 [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Smith, Eric; Schwamm, Lee H.] Massachusetts Gen Hosp, Div Neurol, Boston, MA 02114 USA. [Hernandez, Adrian; Pan, Wenqin] Duke Clin Res Ctr, Durham, NC USA. [Fonarow, Gregg] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. RP Reeves, MJ (reprint author), Michigan State Univ, Dept Epidemiol, B601 W Fee Hall, E Lansing, MI 48824 USA. EM reevesm@msu.edu RI Hernandez, Adrian F./A-7818-2016 OI Smith, Eric/0000-0003-3956-1668; Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616 FU Glaxo Smith Kline and Merck-Schering Plough FX Sponsorship for the GWTG program is provided by Glaxo Smith Kline and Merck-Schering Plough. NR 27 TC 67 Z9 68 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2009 VL 40 IS 2 BP 569 EP 576 DI 10.1161/STROKEAHA.108.519355 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 399FD UT WOS:000262784900037 PM 18988914 ER PT J AU Guo, SZ Arai, K Stins, MF Chuang, DM Lo, EH AF Guo, Shuzhen Arai, Ken Stins, Monique F. Chuang, De-Maw Lo, Eng H. TI Lithium Upregulates Vascular Endothelial Growth Factor in Brain Endothelial Cells and Astrocytes SO STROKE LA English DT Article DE growth factor; neuroprotection; neurovascular unit; stroke recovery ID GLYCOGEN-SYNTHASE KINASE-3; NEUROPROTECTION; VEGF; INHIBITION; INDUCTION; SURVIVAL; NEURONS; MODEL AB Background and Purpose-We recently reported that delayed lithium therapy can improve stroke recovery in rats by augmenting neurovascular remodeling. We tested the hypothesis that lithium can promote the expression of growth factors in brain endothelial cells and astrocytes. Methods-Human brain microvascular endothelial cells and primary rat cortical astrocytes were exposed to lithium chloride in serum-free medium. We examined 2 representative growth factors: brain-derived neurotrophic factor and vascular endothelial growth factor (VEGF). Cell lysates were collected for Western blot analysis. Conditioned media was analyzed with enzyme-linked immunosorbent assay. SB-216763 and LY294002 were used to assess the roles of the glycogen synthase kinase-3 beta (GSK-3 beta) and PI3-K signaling in the lithium-induced responses. Results-No consistent responses were observed for brain-derived neurotrophic factor. However, lithium (0.2 to 20 mmol/L) increased the phosphorylation of GSK-3 beta and promoted VEGF secretion in a concentration-dependent manner in both endothelial and astrocyte cells. For endothelial cells, the potent GSK-3 beta inhibitor SB-216763 upregulated VEGF, whereas inhibition of PI3-K with LY294002 suppressed lithium-induced responses in both phospho-GSK-3 beta and VEGF. In contrast, neither inhibition of GSK-3 beta nor inhibition of PI3-K had any detectable effects on VEGF levels in astrocytes. Conclusions-Lithium promotes VEGF expression through PI3-K/GSK-3 beta-dependent and-independent pathways in brain endothelium and astrocytes, respectively. This growth factor signaling mechanism may contribute to lithium's reported ability to promote neurovascular remodeling after stroke. (Stroke. 2009;40:652-655.) C1 [Chuang, De-Maw] NIMH, Mol Neurobiol Sect, Bethesda, MD 20892 USA. [Stins, Monique F.] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02114 USA. RP Lo, EH (reprint author), MGH East 149-2401, Charlestown, MA 02129 USA. EM Lo@helix.mgh.harvard.edu FU American Heart Association Bugher; National Institutes of Health [R01-NS48422, R01-NS53560, P50-NS10828, P01-NS55104] FX Supported in part by an American Heart Association Bugher award and National Institutes of Health grants R01-NS48422, R01-NS53560, P50-NS10828, and P01-NS55104. NR 18 TC 36 Z9 39 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2009 VL 40 IS 2 BP 652 EP 655 DI 10.1161/STROKEAHA.108.524504 PG 4 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 399FD UT WOS:000262784900050 PM 18974377 ER PT J AU Brausch, AM Gutierrez, PM AF Brausch, Amy M. Gutierrez, Peter M. TI The Role of Body Image and Disordered Eating as Risk Factors for Depression and Suicidal Ideation in Adolescents SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Article ID ATTITUDES TEST; FEMALE ADOLESCENTS; GENDER DIFFERENCES; BULIMIA-NERVOSA; SOCIAL SUPPORT; SELF-ESTEEM; WEIGHT; DISSATISFACTION; HOPELESSNESS; BEHAVIORS AB There is much empirical literature on factors for adolescent suicide risk, but body image and disordered eating are rarely included in these models. In the current study, disordered eating and body image were examined as risk factors for suicide ideation since these factors are prevalent in adolescence, particularly for females. It was hypothesized that disordered eating and body image, in addition to depressive symptoms, would contribute to suicide ideation. It was also hypothesized that these relationships would be stronger for females than for males. Structural equation modeling was used to test a model of risk for suicide ideation incorporating the above factors in a sample of 392 high school students. Results indicated that disordered eating contributed to both suicide ideation and depressive symptoms, while body image only contributed to depressive symptoms. Depressive symptoms contributed to suicide ideation. The model was found to be cross-validated with males and females, and no gender differences emerged. Implications of these findings and their importance in constructing future models of adolescent suicide risk are discussed. C1 [Brausch, Amy M.] Eastern Illinois Univ, Dept Psychol, Charleston, IL 61920 USA. [Gutierrez, Peter M.] Mental Illness Res Educ & Clin Ctr, Denver VA Med Ctr, Denver, CO USA. RP Brausch, AM (reprint author), Eastern Illinois Univ, Dept Psychol, 600 Lincoln Ave, Charleston, IL 61920 USA. EM abrausch@eiu.edu NR 37 TC 37 Z9 39 U1 3 U2 15 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD FEB PY 2009 VL 39 IS 1 BP 58 EP 71 PG 14 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 417PR UT WOS:000264089100007 PM 19298151 ER PT J AU Wong, DR Ali, IS Torchiana, DF Agnihotri, AK Bohmer, RMJ Salm, TJV AF Wong, Daniel R. Ali, Imtiaz S. Torchiana, David F. Agnihotri, Arvind K. Bohmer, Richard M. J. Salm, Thomas J. Vander TI Learning in a new cardiac surgical center: An analysis of precursor events SO SURGERY LA English DT Article ID SURGERY AB Background. Few studies of learning in the health care sector have analyzed measures of process, as opposed to outcomes. We assessed the learning carve for a new cardiac surgical center using precursor events (incidents or circumstances required for the occurrence of adverse outcomes). Methods. Intraoperative precursor events were recorded prospectively during major adult cardiac operations, categorized by blinded adjudicators, and counted for each case (overall and according to these categories). Trendy in the number of precursor events were analyzed by hospital and by defining 10 equal-sized groups across lime, as were trends ill outcomes obtained from institutional databases. Results from the first 101 cases performed (it a new cardiac surgical site (hospital A) Were compared with 2 established centers. Results. A steel) reduction in the total number of precursor events over time Was observed in the early experience of hospital A (9.2 +/- 4.9 to 2.0 +/- 1.2 events per case, from first to last decile of time, P(trend) < .0001) compared with qnalitatively stable levels in the other hospitals; this reduction was driven largely by decreases ill the minor Severity (P(trend) < .0001), compensated (P(trend) < .0001), and environment (P(trend) < .0001) categories of Precursor events. No delectable changes over time Were observed in postoperative mortality and complications. No significant improvement was observed in patient comorbid conditions or medical stains over time to explain the trend in hospital. Conclusion. Analyzing and targeting specific kinds of process-related failures (precursor events) may provide a novel and sensitive means of tracking, deconstructing, and optimizing organizational learning in medicine. (Surgery 2009;145:131-7) C1 [Salm, Thomas J. Vander] N Shore Med Ctr, Div Cardiac Surg, Salem, MA 01970 USA. [Wong, Daniel R.; Ali, Imtiaz S.] Maritime Heart Ctr, Halifax, NS, Canada. [Torchiana, David F.; Agnihotri, Arvind K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bohmer, Richard M. J.] Harvard Sch Business, Boston, MA USA. RP Salm, TJV (reprint author), N Shore Med Ctr, Div Cardiac Surg, 81 Highland Ave, Salem, MA 01970 USA. EM tvandersalm@partners.org FU Massachussetts General Hospital Rosetti Research Fellowship; Dalhousie University Killam scholarship FX Supported by a Massachussetts General Hospital Rosetti Research Fellowship and a Dalhousie University Killam scholarship (to D.R.W.). NR 19 TC 2 Z9 2 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD FEB PY 2009 VL 145 IS 2 BP 131 EP 137 DI 10.1016/j.surg.2008.09.009 PG 7 WC Surgery SC Surgery GA 404KU UT WOS:000263151200002 PM 19167967 ER PT J AU Oliver, A Greenberg, CC AF Oliver, Aundrea Greenberg, Caprice C. TI Measuring Outcomes in Oncology Treatment: The Importance of Patient-Centered Outcomes SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article DE Patient-centered outcomes; Patient satisfaction; Decision regret; Patient preference; Health-related quality of life; Survey instrument design ID QUALITY-OF-LIFE; HEALTH-STATE PREFERENCES; CLINICAL-TRIALS; PROSTATE-CANCER; SATISFACTION; REGRET; METHODOLOGY; POPULATION; VALIDATION; CHOICE AB An important component of quality healthcare is that it be patient-centered with a focus on the patient, including his or her preferences, values, and beliefs. The goal of this article is to provide a broad overview of patient-centered outcomes in oncologic research. It starts with an introduction to the different types of patient-centered measures including patient satisfaction, decision regret, patient preference, and health-related quality of life. It then offers an overview of survey instrument design and selection. Finally, it provides examples of existing approaches to measurement and previously validated instruments for each type of patient-centered outcome. C1 [Greenberg, Caprice C.] Brigham & Womens Hosp, Div Breast Surg Oncol, Dept Surg, Boston, MA 02115 USA. [Greenberg, Caprice C.] Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. [Greenberg, Caprice C.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. RP Oliver, A (reprint author), Brigham & Womens Hosp, Div Breast Surg Oncol, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM ccgreenberg@partners.org FU NCI NIH HHS [L30 CA123695] NR 28 TC 17 Z9 18 U1 3 U2 9 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD FEB PY 2009 VL 89 IS 1 BP 17 EP + DI 10.1016/j.suc.2008.09.015 PG 10 WC Surgery SC Surgery GA 415NB UT WOS:000263939400004 PM 19186228 ER PT J AU Refai, D Dunn, GP Santiago, P AF Refai, Daniel Dunn, Gavin P. Santiago, Paul TI Giant cell tumor of the thoracic spine: case report and review of the literature SO SURGICAL NEUROLOGY LA English DT Article DE Corpectomy; Embolization; Giant cell tumor; Thoracic; Spinal reconstruction ID RADIATION-THERAPY; BONE AB Background: Giant cell tumors are benign tumors of the bone that most commonly occur at the ends of the long bones; they are rarely found in the spine above the sacrum. The management of patients with giant cell tumors of the spine represents a challenge, and the clinical approach to this problem continues to evolve with improvements in surgical and adjunctive therapies. Case Description: A 19-year-old woman with localized back pain and a spinal compression deformity was found to harbor a giant cell tumor of the T7 vertebral body. The patient was first treated with arterial embolization of the hypervascular region observed on angiography. Subsequently, the patient underwent a one-stage transthoracic T7 corpectomy followed by anterior spinal reconstruction and stabilization. Postoperatively, the patient's kyphotic deformity was corrected. To optimize local disease control, the patient underwent IMRT delivered to the site of tumor resection. She remains neurologically intact at 1 year postoperatively without evidence of disease recurrence. Conclusion: The literature and approaches to the management of spinal giant cell tumors are reviewed. (C) 2009 Elsevier Inc. All rights reserved. C1 [Refai, Daniel; Santiago, Paul] Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA. [Dunn, Gavin P.] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Refai, D (reprint author), Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA. EM refaid@nsurg.wustl.edu NR 28 TC 11 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD FEB PY 2009 VL 71 IS 2 BP 228 EP 233 DI 10.1016/j.surneu.2007.07.056 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 400UY UT WOS:000262895900015 PM 18207522 ER PT J AU Walker, RH Koch, RJ Moore, C Meshul, CK AF Walker, Ruth H. Koch, Rick J. Moore, Cynthia Meshul, Charles K. TI Subthalamic Nucleus Stimulation and Lesioning Have Distinct State-Dependent Effects Upon Striatal Dopamine Metabolism SO SYNAPSE LA English DT Article DE deep brain stimulation; microdialysis; Parkinson's disease; rat; 6-hydroxydopamine ID HIGH-FREQUENCY STIMULATION; DEEP BRAIN-STIMULATION; NIGRA PARS RETICULATA; RAT SUBSTANTIA-NIGRA; INDUCED CELLULAR DEFECTS; MEDIAL FRONTAL-CORTEX; IN-VIVO MICRODIALYSIS; PARKINSONS-DISEASE; 6-HYDROXYDOPAMINE-LESIONED RATS; BASAL GANGLIA AB The mechanism by which deep brain stimulation (DBS) of the subthalamic nucleus (STN) achieves its effects in Parkinson's disease (PD) is not known. In animal models of PD, stimulation and lesioning of the STN have some effects which are the same, but others which differ, in reversing cellular and behavioral changes induced by dopamine depletion. We compared the effects of short-term STN stimulation and lesions upon extracellular levels of dopamine and metabolites using in vivo microdialysis of the dorsal striatum of awake, intact and unilateral 6-hydroxydopamine (60HDA)-lesioned rats. STN stimulation in control rats decreased striatal dopamine levels and caused a relative increase in dopamine metabolism, as expressed by HVA/dopamine and DOPAC/dopamine ratios. This suggests an increase in both vesicular dopamine release (metabolized to HVA), and release from the cytoplasmic dopamine pool (metabolized to DOPAC). STN lesions in control rats increased the HVA/dopamine ratio, also suggesting a relative increase in vesicular dopamine release. These results indicate that STN stimulation and lesioning can affect striatal dopamine metabolism in the intact system. In 60HDA-lesioned rats at baseline, metabolic ratios were markedly decreased as compared with controls. STN lesions of 60HDA-lesioned rats did not affect relative metabolic ratios as compared with baseline levels. In 6-OHDA-lesioned rats, STN stimulation decreased extracellular levels of dopamine, and, to a greater extent, metabolites, resulting in a decrease in metabolic ratios. This further decrease in dopamine turnover with STN stimulation would serve to maintain dopamine levels in the dopamine-depleted striatum, and may account for the therapeutic benefit of DBS in Parkinson's disease. Synapse 63:136-146, 2009. Published 2008 Wiley-Liss, Inc. C1 [Walker, Ruth H.; Koch, Rick J.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY 10468 USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Moore, Cynthia; Meshul, Charles K.] Oregon Hlth & Sci Univ, Vet Affairs Med Ctr, Neurocytol Lab, Res Serv, Portland, OR 97201 USA. [Meshul, Charles K.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Walker, RH (reprint author), James J Peters Vet Affairs Med Ctr, Dept Neurol 127, Bronx, NY 10468 USA. EM ruth.walker@mssm.edu FU Parkinson's Disease Foundation International Research; Department of Veterans Affairs Merit awards FX Parkinson's Disease Foundation International Research Grant, Department of Veterans Affairs Merit awards. NR 70 TC 12 Z9 12 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD FEB PY 2009 VL 63 IS 2 BP 136 EP 146 DI 10.1002/syn.20592 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 389EK UT WOS:000262073500006 PM 19021215 ER PT J AU Davis, AK Makar, RS Stowell, CP Kuter, DJ Dzik, WH AF Davis, Amanda K. Makar, Robert S. Stowell, Christopher P. Kuter, David J. Dzik, Walter H. TI ADAMTS13 binds to CD36: a potential mechanism for platelet and endothelial localization of ADAMTS13 SO TRANSFUSION LA English DT Article ID THROMBOTIC THROMBOCYTOPENIC PURPURA; VON-WILLEBRAND-FACTOR; FACTOR-CLEAVING PROTEASE; GLYCOPROTEIN-IV CD36; FACTOR MULTIMERS; IN-VIVO; THROMBOSPONDIN; PLASMA; IDENTIFICATION; RECEPTOR AB ADAMTS13 cleaves ultralarge von Willebrand factor (VWF) and plays a significant role in vascular biology and thrombotic thrombocytopenic purpura. CD36, a transmembrane protein present on endothelial cells and platelets (PLTs), binds to thrombospondin via three thrombospondin type 1 repeats. ADAMTS13 contains eight thrombospondin type 1 repeats. An enzyme-linked immunoassay was used to explore the binding of recombinant human CD36 (rHuCD36) to recombinant human ADAMTS13 (rHuADAMTS13). A competition assay between rHuADAMTS13 and recombinant human (rHu)-thrombospondin-2 for binding to CD36 was then performed. Subsequently, binding of rHuADAMTS13 to PLT membrane fragments expressing CD36 (PLT glycoprotein IV) and glycoprotein Ib/IX was assessed. To examine the functional significance of an ADAMTS13-CD36 interaction, ADAMTS13 activity measured by a fluorescence resonance energy transfer assay was investigated in the presence of either rHuCD36 or concentrated PLTs. rHuCD36 bound to rHuADAMTS13 in a dose-dependent fashion. rHu-thrombospondin-2 competed with ADAMTS13 for CD36 occupancy, but even high concentrations of rHu-thrombospondin-2 failed to completely block binding of rHuADAMTS13 to rHuCD36. rHuADAMTS13 bound to PLT membrane fragments expressing CD36 (PLT glycoprotein IV) in preference to PLT membrane fragments expressing glycoprotein Ib/IX. ADAMTS13 activity was not inhibited by the presence of either rHuCD36 or concentrated PLTs. rHuADAMTS13 binds to both rHuCD36 and PLT membrane CD36 in vitro. The binding of CD36 to rHuADAMTS13 with retention of its enzymatic activity is consistent with a proposed role for CD36 in localizing ADAMTS13 on the endothelial cell surface where it regulates the cleavage of VWF. C1 Massachusetts Gen Hosp, Dept Clin Hematol, Div Hematol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Blood Transfus Serv, Boston, MA 02114 USA. RP Davis, AK (reprint author), Alfred Hosp, Dept Hematol, Commercial Rd, Melbourne, Vic 3004, Australia. EM am.davis@alfred.org.au FU Evelyn and Robert Luick Memorial Fund FX This work was in part supported by research funding from Dr Louise Grochow and by donations from the Evelyn and Robert Luick Memorial Fund. NR 45 TC 17 Z9 21 U1 1 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 2009 VL 49 IS 2 BP 206 EP 213 DI 10.1111/j.1537-2995.2008.01978.x PG 8 WC Hematology SC Hematology GA 397XT UT WOS:000262696400006 PM 19389207 ER PT J AU Craddock, N Sklar, P AF Craddock, Nick Sklar, Pamela TI Genetics of bipolar disorder: successful start to a long journey SO TRENDS IN GENETICS LA English DT Review ID GENOME-WIDE ASSOCIATION; FAMILY-BASED ASSOCIATION; AMINO-ACID OXIDASE; CANDIDATE GENES; SCHIZOAFFECTIVE DISORDER; SUSCEPTIBILITY LOCI; SPECTRUM DISORDERS; SUGGESTIVE LINKAGE; PANIC DISORDER; INCREASE RISK AB Family and twin studies attest to the importance of genetic factors influencing susceptibility to bipolar disorder and to its genetic and phenotypic complexity. Although linkage and candidate gene association studies have repeatedly implicated some chromosome regions and certain genes, they have not produced the level of unambiguous support required to confirm the involvement of any specific gene or sequence variant in the pathogenesis of bipolar disorder. However, strong associations have recently been reported in meta-analyses of genome-wide association studies and the systematic study of structural variation is ongoing. These findings indicate that the study of large, phenotypically well-characterized samples will make an important contribution to delineating the etiology and pathogenesis of bipolar disorder and thereby pave the way for major improvements in clinical management. C1 [Craddock, Nick] Cardiff Univ, Sch Med, Dept Psychol Med, Cardiff CF14 4XN, S Glam, Wales. [Sklar, Pamela] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Sklar, Pamela] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Sklar, Pamela] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Sklar, Pamela] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Sklar, Pamela] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Sklar, Pamela] Broad Inst Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA. [Sklar, Pamela] MIT, Cambridge, MA 02142 USA. RP Craddock, N (reprint author), Cardiff Univ, Sch Med, Dept Psychol Med, Henry Wellcome Bldg,Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM craddockn@cardiff.ac.uk RI turton, miranda/F-4682-2011 FU WTCCC; STEP-BD FX We are grateful to many members of the WTCCC and STEP-BD consortia for helpful discussions and would particularly like to thank Mark McCarthy for discussions about the differing uses of susceptibility alleles. We are indebted to all those who have participated in, and helped with, genetic studies of bipolar disorder. NR 70 TC 84 Z9 88 U1 0 U2 19 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD FEB PY 2009 VL 25 IS 2 BP 99 EP 105 DI 10.1016/j.tig.2008.12.002 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 415IF UT WOS:000263926800007 PM 19144440 ER PT J AU Pieretti, RV Pieretti-Vanmarcke, R Pieretti, A AF Pieretti, Rafael V. Pieretti-Vanmarcke, Rafael Pieretti, Alberto TI Renal Abscess in Previously Healthy Girl SO UROLOGY LA English DT Article ID PERIRENAL ABSCESSES; CHILDHOOD; CHILDREN AB We describe the case of a previously healthy I I-year-old girl with a Staphylococcal aureus renal abscess. The diagnosis was confirmed by renal ultrasonography and abdominal computed tomography. We emphasize the need to obtain an abdominal ultrasound scan and computed tomography scan in patients with abdominal or flank pain, and laboratory evidences of infection to avoid diagnostic and therapeutic delays. UROLOGY 73: 297-298, 2009. Published by Elsevier Inc. C1 [Pieretti, Rafael V.] Massachusetts Gen Hosp, Dept Pediat Surg, Sect Pediat Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Cent Univ Caracas, Caracas, Venezuela. RP Pieretti, RV (reprint author), Massachusetts Gen Hosp, Dept Pediat Surg, Sect Pediat Urol, 55 Fruit Ave,Warren 1157, Boston, MA 02114 USA. EM rpieretti@partners.org NR 7 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2009 VL 73 IS 2 BP 297 EP 298 DI 10.1016/j.urology.2008.07.044 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 416XF UT WOS:000264038100020 PM 18950835 ER PT J AU Sher, DJ Mantzoros, C Jacobus, S Regan, MM Lee, GS Oh, WK AF Sher, David J. Mantzoros, Christos Jacobus, Susanna Regan, Meredith M. Lee, Gwo-Shu Oh, William K. TI Absence of Relationship Between Steroid Hormone Levels and Prostate Cancer Tumor Grade SO UROLOGY LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Society-for-Clinical-Oncology-Genitourinary-Cancer CY FEB 14-16, 2008 CL San Francisco, CA ID RADICAL PROSTATECTOMY; ANDROGEN SUPPRESSION; TRIAL; TESTOSTERONE; ASSOCIATION; RISK; PREVENTION; CARCINOMA; MEN AB OBJECTIVES To analyze the relationship between plasma testosterone and estradiol levels on prostate biopsy and radical prostatectomy Gleason scores in a cohort of patients with newly diagnosed prostate cancer. METHODS Patients with prostate cancer evaluated at the Dana-Farber Cancer Institute from 2001 to 2005 who were enrolled in a prospective sample banking protocol were eligible for this study. Stored plasma was processed for total testosterone, total estradiol, and sex hormone-binding globulin levels using enzyme-linked immunosorbent assays. The frequency of high-grade biopsy and radical prostatectomy Gleason scores (>6) was the primary endpoint. Univariate and multivariate logistic regression analyses were per-formed to determine the relationship between the hormone levels and high-grade Gleason scores while adjusting for sex hormone-binding globulin, age, body mass index, and prostate-specific antigen. RESULTS A total of 539 patients were included in this study, 199 of whom underwent radical prostatectomy. The median prostate-specific antigen level was 5.1 ng/dL, and 67% of the cancers were not palpable. The Gleason score was 2-6, 7, and 8-10 in 53%, 37%, and 10% of the cancers, respectively. On univariate analysis of the high-grade biopsy and radical prostatectomy Gleason score, the total testosterone, total estradiol, and estradiol-to-testosterone ratio were not significant as continuous or categorical variables. Adjusting these results for sex hormone-binding globulin level, body mass index, age, and prostate-specific antigen level did not change the conclusions, and these results were unchanged when categorizing high-grade prostate cancer as Gleason score 8-10. CONCLUSIONS No relationship was found between the circulating steroid hormone levels and the Gleason score in this cohort. UROLOGY 73: 356-361, 2009. (C) 2009 Published by Elsevier Inc. C1 [Oh, William K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 16 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2009 VL 73 IS 2 BP 356 EP 361 DI 10.1016/j.urology.2008.07.068 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 416XF UT WOS:000264038100038 PM 19036418 ER PT J AU Sher, DJ Oh, WK AF Sher, David J. Oh, William K. TI Absence of Relationship Between Steroid Hormone Levels and Prostate Cancer Tumor Grade REPLY SO UROLOGY LA English DT Editorial Material ID SERUM; TESTOSTERONE; ASSOCIATION; ANDROGENS C1 [Sher, David J.] Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Oh, William K.] Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RP Sher, DJ (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 8 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 0090-4295 J9 UROLOGY JI Urology PD FEB PY 2009 VL 73 IS 2 BP 362 EP 362 DI 10.1016/j.urology.2008.09.016 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 416XF UT WOS:000264038100040 ER PT J AU Schifferdecker, B Merchan, JA Ahmar, C Worthington, M Griben, A Schainfeld, RM Soukas, PA AF Schifferdecker, Branislav Merchan, Juan Andres Ahmar, Corinne Worthington, Michael Griben, Andre Schainfeld, Robert M. Soukas, Peter A. TI Endovascular treatment of septic thrombophlebitis: a case report of a rare complication and review of the literature SO VASCULAR MEDICINE LA English DT Article DE phlegmasia cerulea dolens; Salmonella; thrombectomy; venous thrombosis ID DEEP VENOUS THROMBOSIS; THROMBOLYTIC THERAPY; THROMBECTOMY; INFECTIONS; MANAGEMENT AB We report a case of severe deep venous thrombosis (DVT) treated with multi-modality therapy that was complicated by sepsis due to thrombus likely infected by Salmonella virchow. We review the current therapeutic options in the therapy of severe DVT and cardiovascular pathology associated with non-typhoid Salmonella. C1 [Schifferdecker, Branislav; Merchan, Juan Andres; Ahmar, Corinne; Worthington, Michael; Griben, Andre; Soukas, Peter A.] Caritas St Elizabeths Med Ctr, Div Cardiovasc Med, Brighton, MA 02135 USA. [Schifferdecker, Branislav] Oklahoma Heart Hosp, Oklahoma City, OK 73120 USA. [Schainfeld, Robert M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Soukas, PA (reprint author), Caritas St Elizabeths Med Ctr, Div Cardiovasc Med, 736 Cambridge St, Brighton, MA 02135 USA. EM peter.soukas@tufts.edu NR 14 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PD FEB PY 2009 VL 14 IS 1 BP 47 EP 50 DI 10.1177/1358863X08096517 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 394JQ UT WOS:000262443400006 PM 19144779 ER PT J AU Gore, JL Litwin, MS AF Gore, John L. Litwin, Mark S. CA Urologic Dis Amer Project TI Quality of care in bladder cancer: trends in urinary diversion following radical cystectomy SO WORLD JOURNAL OF UROLOGY LA English DT Article DE Bladder cancer; Quality of care; Urinary diversion ID ILEAL CONDUIT; ORTHOTOPIC NEOBLADDER; LIFE; RECONSTRUCTION; SUBSTITUTION; GUIDELINES; SPECIMENS; OUTCOMES; WOMEN AB Quality-of-care indicators have not yet been defined for patients with bladder cancer. Nonetheless, certain aspects of bladder cancer care can be evaluated to quantify the quality of care delivered. We sought to determine trends in continent urinary diversion to evaluate the adoption of this more optimal reconstruction. Subjects who underwent radical cystectomy for a primary diagnosis of bladder cancer were identified from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. We identified covariates independently associated with utilization of continent urinary diversion after radical cystectomy using multivariate logistic regression modeling. We then examined trends in diversion type based on patient and hospital characteristics and examined the impact of hospital volume on use of continent reconstruction. Our weighted sample included 5,075 subjects (14.3%) who underwent continent urinary diversion and 30,295 subjects (85.7%) who underwent an ileal conduit. Independent correlates of continent diversion included younger age, male gender, having private insurance, and undergoing surgery at an urban teaching hospital. Hospitals performing continent diversions on more than 40% of their cystectomies had a yearly cystectomy volume of 0.8 surgeries. Subjects treated at high-volume hospitals trended toward lower rates of comorbid conditions. We identified substantial disparities in continent diversion which, based on yearly trends, are unlikely to improve in the near future. Continent reconstructions are not the exclusive domain of high-volume cystectomy centers. Yet efforts to increase rates of this complex reconstruction must concentrate on technique dissemination and better definition of the quality-of-life detriments incurred by cystectomy patients. C1 [Gore, John L.; Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. [Gore, John L.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Gore, John L.] Univ Calif Los Angeles, Robert Wood Johnson Clin Scholars Program, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, Dept Hlth Serv, Sch Publ Hlth, Los Angeles, CA 90095 USA. [Litwin, Mark S.] Univ Calif Los Angeles, David Geffen Sch Med, Johnson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. [Litwin, Mark S.] RAND Corp, Santa Monica, CA USA. RP Gore, JL (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Box 951738, Los Angeles, CA 90095 USA. EM jgore@mednet.ucla.edu OI Gore, John/0000-0002-2847-5062 FU NIDDK NIH HHS [N01 DK012460] NR 21 TC 33 Z9 33 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD FEB PY 2009 VL 27 IS 1 BP 45 EP 50 DI 10.1007/s00345-008-0348-y PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 398AS UT WOS:000262704200008 PM 19020881 ER PT J AU Vale, AM Fujiwara, RT Neto, AFD Miret, JA Alvarez, DCC da Silva, JCF Campos-Neto, A Reed, S Mayrink, W Nascimento, E AF Vale, A. M. Fujiwara, R. T. da Silva Neto, A. F. Miret, J. A. Alvarez, D. C. C. da Silva, J. C. F. Campos-Neto, A. Reed, S. Mayrink, W. Nascimento, E. TI Identification of Highly Specific and Cross-Reactive Antigens of Leishmania Species by Antibodies from Leishmania (Leishmania) chagasi Naturally Infected Dogs SO ZOONOSES AND PUBLIC HEALTH LA English DT Article DE Visceral leishmaniasis; tegumentary leishmaniasis; dogs; cross-reactive Antigens; immunoblotting ID CANINE VISCERAL LEISHMANIASIS; WESTERN-BLOT-ANALYSIS; CUTANEOUS LEISHMANIASIS; IMMUNOBLOT ANALYSIS; RECOMBINANT ANTIGENS; INFANTUM ANTIGENS; IMMUNE-RESPONSES; SURFACE-ANTIGENS; TREATED DOGS; KALA-AZAR AB The Leishmania species present a genetic homology that ranges from 69 to 90%. Because of this homology, heterologous antigens have been used in the immunodiagnosis and vaccine development against Leishmania infections. In the current work, we describe the identification of species-specific and cross-reactive antigens among several New World Leishmania species, using symptomatic and asymptomatic naturally Leishmania chagasi-infected dog sera. Soluble antigens from five strains of New World Leishmania were separated by electrophoresis in SDS-PAGE and immunoblotted. Different proteins were uniquely recognized in the L. chagasi panel by either symptomatic or asymptomatic dog sera suggesting their use as markers for the progression of disease and diagnosis of the initial (sub-clinical) phase of the infection. Cross-reactive antigens were identified using heterologous antigenic panels (L. amazonensis strains PH8 and BH6, L. guyanensis and L. braziliensis). L. guyanensis panel showed the highest cross-reactivity against L. chagasi specific antibodies, suggesting that proteins from this extract might be suitable for the diagnosis of visceral canine leishmaniasis. Interestingly, the 51 and 97 kDa proteins of Leishmania were widely recognized (77.8% to 100%) among all antigenic panels tested, supporting their potential use for immunodiagnosis. Finally, we identified several leishmanial antigens that might be useful for routine diagnosis and seroepidemiological studies of the visceral canine leishmaniasis. C1 [Vale, A. M.; Fujiwara, R. T.; Miret, J. A.; Alvarez, D. C. C.; da Silva, J. C. F.; Mayrink, W.; Nascimento, E.] Univ Fed Minas Gerais, Dept Parasitol, Lab Leishmanioses & Vacinas, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, Brazil. [Vale, A. M.] Univ Fed Rio de Janeiro, Dept Imunol, Inst Microbiol Prof Paulo de Goes, BR-21941 Rio De Janeiro, Brazil. [da Silva Neto, A. F.; Campos-Neto, A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. [Reed, S.] Infect Dis Res Inst, Seattle, WA USA. RP Nascimento, E (reprint author), Univ Fed Minas Gerais, Dept Parasitol, Lab Leishmanioses & Vacinas, Inst Ciencias Biol, BR-31270901 Belo Horizonte, MG, Brazil. EM evaldo@icb.ufmg.br RI Fujiwara, Ricardo/J-7579-2012 OI Fujiwara, Ricardo/0000-0002-4713-575X FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq/Brazil) FX We thank Floriano de Souza Oliveira for technical assistance. We also thank Roberto Teodoro da Costa and Weverton Sampaio, both in memoriam, for their assistance and contribution to this work. We thank Guilherme Grossi Lopes Cancado for the help in the preparation of the manuscript. This research is part of the Master Degree's Dissertation in Parasitology (MSc) of AndrE Macedo Vale with fellowship from Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq/Brazil) in the Graduate Academic Program in Parasitology of the Instituto de Ciencias Biologicas of the Universidade Federal de Minas Gerais, Brazil. NR 55 TC 7 Z9 7 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1863-1959 EI 1863-2378 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PD FEB PY 2009 VL 56 IS 1 BP 41 EP 48 DI 10.1111/j.1863-2378.2008.01183.x PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 394VD UT WOS:000262478400006 PM 18990196 ER PT J AU Miller, TA Icli, B Cote, GM LeBrasseur, NK Borkan, SC Pimentel, DR Peng, XY Sawyer, DB AF Miller, Thomas A. Icli, Basak Cote, Gregory M. LeBrasseur, Nathan K. Borkan, Steve C. Pimentel, David R. Peng, Xuyang Sawyer, Douglas B. TI Palmitate alters neuregulin signaling and biology in cardiac myocytes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Lipotoxicity; Neuregulin; Heregulin; Palmitate; erbB2; erbB4; Heart; Apoptosis ID SATURATED FATTY-ACIDS; RAT VENTRICULAR MYOCYTES; BREAST-CANCER CELLS; INDUCED APOPTOSIS; SKELETAL-MUSCLE; INSULIN-RESISTANCE; RECEPTOR; ERBB2; EXPRESSION; CERAMIDE AB The saturated fatty acid palmitate alters normal cell function via disruption of cell signaling, and this effect has been implicated in the end-organ damage associated with dyslipidemia. Neuregulin-1 beta (NRG-1 beta) is a growth and survival factor in cardiac myocytes. We tested the hypothesis that palmitate alters NRG-1 beta signaling and biology in isolated neonatal rat cardiac myocytes. Palmitate treatment inhibited NRG-1 beta activation of the PI3-kinase/Akt pathway in myocytes. We found that the pro-apoptotic activity of palmitate was increased by NRG-1 beta treatment. The effects of palmitate on NRG-1 beta, signaling and Survival were reversed by the mono-unsaturated fatty acid oleate. Under control conditions NRG-1 beta decreases p53 expression in myocytes. In the presence of palmitate, NRG-1 beta caused an increase in p53 expression, bax multimer formation, concurrent with degradation of mdm2, a negative regulator of p53. Thus in the presence of palmitate NRG-1 beta activates pro-apoptotic, rather than pro-survival signaling in cardiac myocytes. (C) 2008 Elsevier Inc. All rights reserved. C1 [Peng, Xuyang; Sawyer, Douglas B.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. [Miller, Thomas A.; Icli, Basak; Cote, Gregory M.; LeBrasseur, Nathan K.; Borkan, Steve C.; Pimentel, David R.; Peng, Xuyang; Sawyer, Douglas B.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Miller, Thomas A.] Maine Med Ctr, Portland, ME 04102 USA. [Icli, Basak] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Cote, Gregory M.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Sawyer, DB (reprint author), Vanderbilt Univ, Sch Med, Dept Med, 383 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA. EM douglas.b.sawyer@vanderbilt.edu OI Borkan, Steven/0000-0003-3062-9486; LeBrasseur, Nathan/0000-0002-2002-0418; Cote, Gregory/0000-0003-0181-886X FU National Institutes of Health [HL068144]; American Heart Association; Juvenile Diabetes Research Foundation FX We thank Mark Marchionni and Acorda Therapeutics, Inc. for recombinant neuregulin-1 beta and Yasuo Ido for adenoviral ceramidase. This work was supported by grants HL068144 from the National Institutes of Health, an Established Investigator Award from the American Heart Association to DBS, and a grant from the Juvenile Diabetes Research Foundation. NR 47 TC 10 Z9 10 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 30 PY 2009 VL 379 IS 1 BP 32 EP 37 DI 10.1016/j.bbrc.2008.11.150 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 401DA UT WOS:000262917500007 PM 19070592 ER PT J AU Steiner, MK Syrkina, OL Kolliputi, N Mark, EJ Hales, CA Waxman, AB AF Steiner, M. Kathryn Syrkina, Olga L. Kolliputi, Narasaish Mark, Eugene J. Hales, Charles A. Waxman, Aaron B. TI Interleukin-6 Overexpression Induces Pulmonary Hypertension SO CIRCULATION RESEARCH LA English DT Article DE interleukin-6; pulmonary artery hypertension; proliferation ID SMOOTH-MUSCLE-CELLS; UP-REGULATES EXPRESSION; ARTERIAL-HYPERTENSION; PLEXIFORM LESIONS; ENDOTHELIAL-CELLS; INFLAMMATORY CYTOKINES; NEOINTIMAL FORMATION; VASCULAR STRUCTURE; GENE-EXPRESSION; TRANSGENIC MICE AB Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms. (Circ Res. 2009; 104: 236-244.) C1 [Steiner, M. Kathryn; Syrkina, Olga L.; Kolliputi, Narasaish; Hales, Charles A.; Waxman, Aaron B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm Crit Care Unit, Boston, MA USA. [Mark, Eugene J.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Steiner, MK (reprint author), Univ Massachusetts, Mem Med Ctr, Div Pulm Crit Care Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM marciakathryn.steiner@umassmemorial.org RI Kolliputi, Narasaiah/I-6050-2012 OI Kolliputi, Narasaiah/0000-0002-2654-1900 FU National Heart, Lung, and Blood Institute [HL074859, HL007874, HL039150] FX This work was supported by National Heart, Lung, and Blood Institute grants HL074859 (to A. B. W.) and HL007874 and HL039150 (to C. A. H.). NR 76 TC 210 Z9 228 U1 3 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD JAN 30 PY 2009 VL 104 IS 2 BP 236 EP U208 DI 10.1161/CIRCRESAHA.108.182014 PG 37 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 401AC UT WOS:000262909500015 PM 19074475 ER PT J AU Karmali, F Shelhamer, M AF Karmali, Faisal Shelhamer, Mark TI Compensating for camera translation in video eye-movement recordings by tracking a representative landmark selected automatically by a genetic algorithm SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Eye; Video; VOG; Video-oculography; Cross-correlation; Genetic algorithm ID VESTIBULOOCULAR REFLEX; PARABOLIC FLIGHT; OPTICAL-FLOW AB It is common in oculomotor and vestibular research to use video or still cameras to acquire data on eye movements. Unfortunately, such data are often contaminated by unwanted motion of the face relative to the camera, especially during experiments in dynamic motion environments. We develop a method for estimating the motion of a camera relative to a highly deformable surface, specifically the movement of a camera relative to the face and eyes. A small rectangular region of interest (ROI) on the face is automatically selected and tracked throughout a set of video frames as a measure of vertical camera translation. The specific goal is to present a process based on a genetic algorithm that selects a suitable ROI for tracking: one whose translation within the camera image accurately matches the actual relative motion of the camera. We find that co-correlation, a statistic describing the time series of a large group of ROIs, predicts the accuracy of the ROIs, and can be used to select the best ROI from a group. After the genetic algorithm finds the best ROIs from a group, it uses recombination to form a new generation of ROIs that inherit properties of the ROIs from the previous generation. We show that the algorithm can select an ROI that will estimate camera translation and determine the direction that the eye is looking with an average accuracy of 0.75 degrees, even with camera translations of 2.5 mm at a viewing distance of 120 mm, which Would cause an error of 11 degrees without correction. (C) 2008 Elsevier B.V. All rights reserved. C1 [Karmali, Faisal] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Karmali, Faisal; Shelhamer, Mark] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. [Shelhamer, Mark] Johns Hopkins Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. RP Karmali, F (reprint author), 243 Charles St,JVPL 421, Boston, MA 02114 USA. EM faisal_karmali@yahoo.com OI Karmali, Faisal/0000-0002-1140-4954 FU NIH [DC006090]; National Space Biomedical Research Institute (NASA/NSBRI); National Science and Engineering Research Council of Canada (NSERC). FX Supported by: NIH DC006090, National Space Biomedical Research Institute (NASA/NSBRI), National Science and Engineering Research Council of Canada (NSERC). We acknowledge the technical assistance and advice of Tiffany L. Chen, Dr. Jerry Prince, and Dr. Stefano Ramat. NR 24 TC 0 Z9 0 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 30 PY 2009 VL 176 IS 2 BP 157 EP 165 DI 10.1016/j.jneumeth.2008.09.010 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 398UX UT WOS:000262758100015 PM 18835407 ER PT J AU Zheng, B Jeong, JH Asara, JM Yuan, YY Granters, SR Chin, L Cantley, LC AF Zheng, Bin Jeong, Joseph H. Asara, John M. Yuan, Yuan-Ying Granters, Scott R. Chin, Lynda Cantley, Lewis C. TI Oncogenic B-RAF Negatively Regulates the Tumor Suppressor LKB1 to Promote Melanoma Cell Proliferation SO MOLECULAR CELL LA English DT Article ID ACTIVATED PROTEIN-KINASE; JEGHERS CANCER SYNDROME; METABOLIC CHECKPOINT; FUNCTIONAL-ANALYSIS; THERAPEUTIC TARGET; SIGNALING PATHWAYS; GLUCOSE-METABOLISM; SOMATIC MUTATION; DRUG DISCOVERY; GENE AB The LK131-AMPK signaling pathway serves as a critical cellular sensor coupling energy homeostasis to cell growth, proliferation, and survival. However, how tumor cells suppress this signaling pathway to gain growth advantage under conditions of energy stress is largely unknown. Here, we show that AMPK activation is suppressed in melanoma cells with the B-RAF V600E mutation and that downregulation of B-RAF signaling activates AMPK. We find that in these cells LKB1 is phosphorylated by ERK and Rsk, two kinases downstream of B-RAF, and that this phosphorylation compromises the ability of LKB1 to bind and activate AMPK. Furthermore, expression of a phosphorylation-deficient mutant of LKB1 allows activation of AMPK and inhibits melanoma cell proliferation and anchorage-independent cell growth. Our findings provide a molecular linkage between the LKB1-AMPK and the RAF-MEK-ERK pathways and suggest that suppression of LKB1 function by B-RAF V600E plays an important role in B-RAF V600E-driven tumorigenesis. C1 [Zheng, Bin; Asara, John M.; Yuan, Yuan-Ying; Cantley, Lewis C.] Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. [Zheng, Bin; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. [Asara, John M.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Jeong, Joseph H.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Granters, Scott R.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Zheng, B (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. EM bzheng@bidmc.harvard.edu; lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU National Institutes of Health [GM56203, CA102694, K99CA133245, UO1 CA84313, R01 CA93947] FX We thank Drs. Reuben Shaw, Nabeel Bardeesy, David Tuveson, and Melanie Cobb for reagents; Lisa Freimark for assistance with the mass spectrometry analysis; Li Zhang and Szexian Lee for technical assistance; and Dr. Yang-Oing Xu and members of the Cantley Lab for helpful discussion, We also would like to thank Shailender Nagpal for helping to create software for quantitative mass spectrometry analysis. B.Z. is supported by a Charles A. King Trust post-doctoral fellowship from the Charles A. King Trust, Bank of America, Co-Trustee. This work is supported by National Institutes of Health Grant GM56203 and CA102694 to L.C.C., K99CA133245 to B.Z.. and UO1 CA84313 and R01 CA93947 to L.C NR 61 TC 186 Z9 187 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 30 PY 2009 VL 33 IS 2 BP 237 EP 247 DI 10.1016/j.molcel.2008.12.026 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 405EC UT WOS:000263204500014 PM 19187764 ER PT J AU Hung, T Binda, O Champagne, KS Kuo, AJ Johnson, K Chang, HY Simon, MD Kutateladze, TG Gozani, O AF Hung, Tiffany Binda, Olivier Champagne, Karen S. Kuo, Alex J. Johnson, Kyle Chang, Howard Y. Simon, Matthew D. Kutateladze, Tatiana G. Gozani, Or TI ING4 Mediates Crosstalk between Histone H3 K4 Trimethylation and H3 Acetylation to Attenuate Cellular Transformation SO MOLECULAR CELL LA English DT Article ID SUPPRESSOR PROTEIN ING4; PHD FINGER; LYSINE-4 TRIMETHYLATION; H3K4ME3 RECOGNITION; PLANT HOMEODOMAIN; MOLECULAR-BASIS; METHYLATION; BINDING; GROWTH; GENE AB Aberrations in chromatin dynamics play a fundamental role in tumorigenesis, yet relatively little is known of the molecular mechanisms linking histone lysine methylation to neoplastic disease. ING4 (Inhibitor of Growth 4) is a native subunit of an HBO1 histone acetyltransferase (HAT) complex and a tumor suppressor protein. Here we show a critical role for specific recognition of histone H3 trimethylated at lysine 4 (H3K4me3) by the ING4 PHD finger in mediating ING4 gene expression and tumor suppressor functions. The interaction between ING4 and H3K4me3 augments HBO1 acetylation activity on H3 tails and drives H3 acetylation at ING4 target promoters. Further, ING4 facilitates apoptosis in response to genotoxic stress and inhibits anchorage-independent cell growth, and these functions depend on ING4 interactions with H3K4me3. Together, our results demonstrate a mechanism for brokering crosstalk between H3K4 methylation and H3 acetylation and reveal a molecular link between chromatin modulation and tumor suppressor mechanisms. C1 [Hung, Tiffany; Binda, Olivier; Kuo, Alex J.; Gozani, Or] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Champagne, Karen S.; Johnson, Kyle; Kutateladze, Tatiana G.] Univ Colorado Denver, Dept Pharmacol, Aurora, CO 80045 USA. [Chang, Howard Y.] Stanford Univ, Sch Med, Program Epithelial Biol, Stanford, CA 94305 USA. [Simon, Matthew D.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Gozani, O (reprint author), Stanford Univ, Dept Biol, Stanford, CA 94305 USA. EM ogozani@stanford.edu RI Binda, Olivier/A-5941-2009; OI Binda, Olivier/0000-0002-1539-0828; Glass, Karen/0000-0002-2761-733X FU NIH [R01 GM079641-01A1]; Helen Hay Whitney Fellowship; Genetech Foundation Predoctoral Fellowship; NIH NRSA Postdoctoral Fellowship; Searle Scholar Award FX We thank J. Cote for sharing unpublished data. We also thank K. Chua, X. Shi, C.L. Liu. R. Zhao. and P. Peha for helpful comments and M. van der Woerd and J. Nix for X-ray data collection. This work was supported in part by grants from the NIH to O.G. (R01 GM079641-01A1). T.G.K.. and H.Y.C. M.D.S. is supported by a Helen Hay Whitney Fellowship, A.J.K. by a Genetech Foundation Predoctoral Fellowship, and K.S.C. by an NIH NRSA Postdoctoral Fellowship. O.G. is a recipient of a Searle Scholar Award. NR 34 TC 106 Z9 111 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD JAN 30 PY 2009 VL 33 IS 2 BP 248 EP 256 DI 10.1016/j.molcel.2008.12.016 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 405EC UT WOS:000263204500015 PM 19187765 ER PT J AU Guidi, J Pender, M Hollon, SD Zisook, S Schwartz, FH Pedrelli, P Farabaugh, A Fava, M Petersen, TJ AF Guidi, Jenny Pender, Maribeth Hollon, Steven D. Zisook, Sidney Schwartz, Faye H. Pedrelli, Paola Farabaugh, Amy Fava, Maurizio Petersen, Timothy J. TI The prevalence of compulsive eating and exercise among college students: An exploratory study SO PSYCHIATRY RESEARCH LA English DT Article DE Prevention; Depression; Risk factors ID SELF-REPORT QUESTIONNAIRE; BULIMIA-NERVOSA; PSYCHIATRIC COMORBIDITY; DISORDER SYMPTOMS; YOUNG-ADULTS; INTERVIEW; WOMEN; DEPENDENCE; DEPRESSION; VALIDATION AB Eating disturbances continue to grow among college students, and researchers have begun to investigate factors that may lead to abnormal eating behaviors in this population. Recent research has also suggested that excessive exercise can become a compulsive behavior that may affect psychological health. The aim of this exploratory study was to evaluate the relationships between both compulsive eating and exercise, and demographic and clinical variables in a college population. Participants were 589 undergraduates (mean age 20 years) recruited during a mental health screening at two different campuses. Participants completed a screening package of measures including a questionnaire about socio-demographic data, the Beck Depression Inventory (BDI), the Beck Hopelessness Scale (BHS), the Consumptive Habits Questionnaire (CHQ), the Modified Overt Aggression Scale-Self-rated version (MOAS), and the Quality of Life Enjoyment and Satisfaction Questionnaire-Short version (QLESQ). A prevalence rate of 7.2% was found for compulsive eating and 18.1% for compulsive exercise, as measured by the CHQ. Only 11 participants (1.9%) reported both compulsive eating and exercise. There was no significant relationship between compulsive eating and compulsive exercise. The results suggest that college students may represent a group at high risk of developing abnormal eating behaviors and compulsive exercise. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Guidi, Jenny] Univ Bologna, Dept Psychol, I-40127 Bologna, Italy. [Guidi, Jenny; Pender, Maribeth; Schwartz, Faye H.; Pedrelli, Paola; Farabaugh, Amy; Fava, Maurizio; Petersen, Timothy J.] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Hollon, Steven D.] Vanderbilt Univ, Nashville, TN USA. [Zisook, Sidney] Univ Calif San Diego, San Diego, CA 92103 USA. RP Guidi, J (reprint author), Univ Bologna, Dept Psychol, Viale Berti Pichat 5, I-40127 Bologna, Italy. EM jenny.guidi@studio.unibo.it NR 40 TC 18 Z9 18 U1 3 U2 16 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 JAN 30 PY 2009 VL 165 IS 1-2 BP 154 EP 162 DI 10.1016/j.psychres.2007.10.005 PG 9 WC Psychiatry SC Psychiatry GA 401LM UT WOS:000262942200018 PM 19046604 ER PT J AU Flaumenhaft, R Dilks, JR Richardson, J Alden, E Patel-Hett, SR Battinelli, E Klement, GL Sola-Visner, M Italiano, JE AF Flaumenhaft, Robert Dilks, James R. Richardson, Jennifer Alden, Eva Patel-Hett, Sunita R. Battinelli, Elisabeth Klement, Giannoula L. Sola-Visner, Martha Italiano, Joseph E., Jr. TI Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles SO BLOOD LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; MARROW VASCULAR NICHE; PLASMA-MEMBRANE; P-SELECTIN; THROMBOCYTOPENIC PURPURA; MICROVESICLE GENERATION; BLEEDING DISORDER; BLOOD-PLATELETS; ACTIVATION; CYTOSKELETON AB Platelet microparticles are a normal constituent of circulating blood. Several studies have demonstrated positive correlations between thrombotic states and platelet microparticle levels. Yet little is known about the processes by which platelet microparticles are generated in vivo. We now characterize microparticles derived directly from megakaryocytes. Video microscopy of live mouse megakaryocytes demonstrated that microparticles form as submicron beads along the lengths of slender, unbranched micropodia. These microparticles are CD41(+), CD42b(+), and express surface phosphatidylserine. Megakaryocyte microparticle generation is resistant to inhibition of microtubule assembly, which is critical to platelet formation, and augmented by inhibition of actin polymerization. To determine whether circulating microparticles are derived primarily from activated platelets or megakaryocytes, we identified markers that distinguish between these 2 populations. CD62P and LAMP-1 were found only on mouse microparticles from activated platelets. In contrast, full-length filamin A was found in megakaryocyte-derived microparticles, but not microparticles from activated platelets. Circulating microparticles isolated from mice were CD62P(-), LAMP-1(-) and expressed fulllength filamin A, indicating a megakaryocytic origin. Similarly, circulating microparticles isolated from healthy volunteers were CD62P(-) and expressed full-length filamin A. Cultured human megakaryocytes elaborated microparticles that were CD41(+), CD42b(+), and express surface phosphatidylserine. These results indicate that direct production by megakaryocytes represents a physiologic means to generate circulating platelet microparticles. (Blood. 2009;113:1112-1121) C1 [Flaumenhaft, Robert] Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Dept Med, Boston, MA 02215 USA. [Richardson, Jennifer; Alden, Eva; Patel-Hett, Sunita R.; Battinelli, Elisabeth; Italiano, Joseph E., Jr.] Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Patel-Hett, Sunita R.; Klement, Giannoula L.; Italiano, Joseph E., Jr.] Childrens Hosp Boston, Dept Vasc Biol, Boston, MA USA. [Klement, Giannoula L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Sola-Visner, Martha] Childrens Hosp Boston, Div Newborn Med, Boston, MA USA. RP Flaumenhaft, R (reprint author), Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Dept Med, 330 Brookline Ave, Boston, MA 02215 USA. EM rflaumen@bidmc.harvard.edu FU National Institutes of Health [HL68130, HL63250]; American Society of Hematology Junior Faculty Scholars; American Heart Association; Bayer Healthcare FX This work was supported by National Institutes of Health (NIH, Bethesda, MD) grants HL68130 (J. E. I.) and HL63250 (R. F.). J. E. I. and R. F. are American Society of Hematology Junior Faculty Scholars. R. F. is a recipient of an Established Investigator Award from the American Heart Association (Dallas, TX) and a Special Project Award from Bayer Healthcare (Berkeley, CA). NR 56 TC 110 Z9 115 U1 4 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 29 PY 2009 VL 113 IS 5 BP 1112 EP 1121 DI 10.1182/blood-2008-06-163832 PG 10 WC Hematology SC Hematology GA 400RD UT WOS:000262885300019 PM 18802008 ER PT J AU Subak, LL Wing, R West, DS Franklin, F Vittinghoff, E Creasman, JM Richter, HE Myers, D Burgio, KL Gorin, AA Macer, J Kusek, JW Grady, D AF Subak, Leslee L. Wing, Rena West, Delia Smith Franklin, Frank Vittinghoff, Eric Creasman, Jennifer M. Richter, Holly E. Myers, Deborah Burgio, Kathryn L. Gorin, Amy A. Macer, Judith Kusek, John W. Grady, Deborah CA PRIDE Investigators TI Weight Loss to Treat Urinary Incontinence in Overweight and Obese Women. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; MIDDLE-AGED WOMEN; CARDIOVASCULAR-DISEASE; STRESS-INCONTINENCE; STYLE INTERVENTION; RISK-FACTORS; FOLLOW-UP; SURGERY; HEALTH AB Background: Obesity is an established and modifiable risk factor for urinary incontinence, but conclusive evidence for a beneficial effect of weight loss on urinary incontinence is lacking. Methods: We randomly assigned 338 overweight and obese women with at least 10 urinary-incontinence episodes per week to an intensive 6-month weight-loss program that included diet, exercise, and behavior modification (226 patients) or to a structured education program (112 patients). Results: The mean (+/-SD) age of the participants was 53+/-11 years. The body-mass index (BMI) (the weight in kilograms divided by the square of the height in meters) and the weekly number of incontinence episodes as recorded in a 7-day diary of voiding were similar in the intervention group and the control group at baseline (BMI, 36+/-6 and 36+/-5, respectively; incontinence episodes, 24+/-18 and 24+/-16, respectively). The women in the intervention group had a mean weight loss of 8.0% (7.8 kg), as compared with 1.6% (1.5 kg) in the control group (P<0.001). After 6 months, the mean weekly number of incontinence episodes decreased by 47% in the intervention group, as compared with 28% in the control group (P=0.01). As compared with the control group, the intervention group had a greater decrease in the frequency of stress-incontinence episodes (P=0.02), but not of urge-incontinence episodes (P=0.14). A higher proportion of the intervention group than of the control group had a clinically relevant reduction of 70% or more in the frequency of all incontinence episodes (P<0.001), stress-incontinence episodes (P=0.009), and urge-incontinence episodes (P=0.04). Conclusions: A 6-month behavioral intervention targeting weight loss reduced the frequency of self-reported urinary-incontinence episodes among overweight and obese women as compared with a control group. A decrease in urinary incontinence may be another benefit among the extensive health improvements associated with moderate weight reduction. (ClinicalTrials.gov number, NCT00091988.) N Engl J Med 2009;360:481-90. C1 [Subak, Leslee L.; Vittinghoff, Eric; Creasman, Jennifer M.; Macer, Judith; Grady, Deborah] Univ Calif San Francisco, Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. [Wing, Rena] Miriam Hosp, Providence, RI 02906 USA. [Wing, Rena; Myers, Deborah] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [West, Delia Smith] Univ Arkansas Med Sci, Coll Publ Hlth, Little Rock, AR 72205 USA. [Franklin, Frank; Richter, Holly E.; Burgio, Kathryn L.] Univ Alabama Birmingham, Birmingham, AL USA. [Burgio, Kathryn L.] Dept Vet Affairs, Ctr Geriatr Res Educ & Clin, Birmingham, AL USA. [Gorin, Amy A.] Univ Connecticut, Storrs, CT USA. [Kusek, John W.] NIDDKD, Bethesda, MD 20892 USA. [Grady, Deborah] San Francisco VA Med Ctr, San Francisco, CA USA. RP Subak, LL (reprint author), Univ Calif San Francisco, Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. EM subakl@obgyn.ucsf.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [U01 DK067860, U01 DK067861, U01 DK067862]; Office of Research on Women's Health; Pfizer; Bionovo; Astellas; GlaxoSmithKline FX Supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (U01 DK067860, U01 DK067861, and U01 DK067862) and from the Office of Research on Women's Health.; Dr. Subak reports serving on an advisory board for Pfizer and receiving grant support from Pfizer; Dr. Grady, receiving grant support from Bionovo; Dr. Kusek, owning stock in Eli Lilly, Pfizer, and deCODE Genetics; and Dr. Burgio, serving on an advisory board for Pfizer, receiving grant support from Pfizer, and receiving advisory-board fees from Astellas and GlaxoSmithKline. No other potential conflict of interest relevant to this article was reported.; The views expressed are those of the authors and do not necessarily represent the official views of the NIDDK or the National Institutes of Health. NR 36 TC 200 Z9 206 U1 1 U2 11 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2009 VL 360 IS 5 BP 481 EP 490 DI 10.1056/NEJMoa0806375 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 399PS UT WOS:000262812400007 PM 19179316 ER PT J AU Haynes, AB Weiser, TG Berry, WR Lipsitz, SR Breizat, AHS Dellinger, EP Herbosa, T Joseph, S Kibatala, PL Lapitan, MCM Merry, AF Moorthy, K Reznick, RK Taylor, B Gawande, AA AF Haynes, Alex B. Weiser, Thomas G. Berry, William R. Lipsitz, Stuart R. Breizat, Abdel-Hadi S. Dellinger, E. Patchen Herbosa, Teodoro Joseph, Sudhir Kibatala, Pascience L. Lapitan, Marie Carmela M. Merry, Alan F. Moorthy, Krishna Reznick, Richard K. Taylor, Bryce Gawande, Atul A. CA Safe Surgery Saves Lives Study Grp TI A Surgical Safety Checklist to Reduce Morbidity and Mortality in a Global Population. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANTIBIOTIC-PROPHYLAXIS; OPERATING-ROOM; SURGERY; RISK; INFECTIONS; ANESTHESIA; HOSPITALS; AUSTRALIA; TEAMWORK; NURSES AB Background: Surgery has become an integral part of global health care, with an estimated 234 million operations performed yearly. Surgical complications are common and often preventable. We hypothesized that a program to implement a 19-item surgical safety checklist designed to improve team communication and consistency of care would reduce complications and deaths associated with surgery. Methods: Between October 2007 and September 2008, eight hospitals in eight cities (Toronto, Canada; New Delhi, India; Amman, Jordan; Auckland, New Zealand; Manila, Philippines; Ifakara, Tanzania; London, England; and Seattle, WA) representing a variety of economic circumstances and diverse populations of patients participated in the World Health Organization's Safe Surgery Saves Lives program. We prospectively collected data on clinical processes and outcomes from 3733 consecutively enrolled patients 16 years of age or older who were undergoing noncardiac surgery. We subsequently collected data on 3955 consecutively enrolled patients after the introduction of the Surgical Safety Checklist. The primary end point was the rate of complications, including death, during hospitalization within the first 30 days after the operation. Results: The rate of death was 1.5% before the checklist was introduced and declined to 0.8% afterward (P=0.003). Inpatient complications occurred in 11.0% of patients at baseline and in 7.0% after introduction of the checklist (P<0.001). Conclusions: Implementation of the checklist was associated with concomitant reductions in the rates of death and complications among patients at least 16 years of age who were undergoing noncardiac surgery in a diverse group of hospitals. N Engl J Med 2009;360:491-9. C1 [Lipsitz, Stuart R.; Gawande, Atul A.] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Haynes, Alex B.; Weiser, Thomas G.; Berry, William R.; Gawande, Atul A.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Haynes, Alex B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Weiser, Thomas G.] Univ Calif Davis, Sacramento, CA 95817 USA. [Breizat, Abdel-Hadi S.] Prince Hamzah Hosp, Minist Hlth, Amman, Jordan. [Dellinger, E. Patchen] Univ Washington, Seattle, WA 98195 USA. [Herbosa, Teodoro] Univ Philippines, Coll Med, Manila, Philippines. [Joseph, Sudhir] St Stephens Hosp, New Delhi, India. [Kibatala, Pascience L.] St Francis Designated Dist Hosp, Ifakara, Tanzania. [Lapitan, Marie Carmela M.] Univ Philippines, Natl Inst Hlth, Manila, Philippines. [Merry, Alan F.] Univ Auckland, Auckland 1, New Zealand. [Merry, Alan F.] Auckland City Hosp, Auckland, New Zealand. [Moorthy, Krishna] Imperial Coll Healthcare Natl Hlth Serv Trust, London, England. [Reznick, Richard K.; Taylor, Bryce] Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. RP Gawande, AA (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM safesurgery@hsph.harvard.edu RI Haynes, Alex/K-1446-2013; OI Haynes, Alex/0000-0002-5731-329X; Merry, Alan/0000-0001-7100-009X FU World Health Organization FX Supported by grants from the World Health Organization. NR 29 TC 1707 Z9 1752 U1 31 U2 147 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2009 VL 360 IS 5 BP 491 EP 499 DI 10.1056/NEJMsa0810119 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 399PS UT WOS:000262812400008 PM 19144931 ER PT J AU Duff, P Barth, WH Post, MD Harris, NL Riley, LE AF Duff, Patrick Barth, William H., Jr. Post, Miriam D. Harris, Nancy Lee Riley, Laura E. TI A Pregnant Woman with Fever after a Trip to Africa Systemic congenital cytomegalovirus infection and cytomegalovirus placentitis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PRENATAL-DIAGNOSIS; WOMEN; IMMUNITY; DISEASE; FETAL C1 [Duff, Patrick] Univ Florida, Dept Obstet & Gynecol, Gainesville, FL 32611 USA. [Barth, William H., Jr.] Massachusetts Gen Hosp, Div Maternal Fetal Med, Boston, MA 02114 USA. [Post, Miriam D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Barth, William H., Jr.] Harvard Univ, Sch Med, Dept Obstet, Boston, MA USA. [Barth, William H., Jr.] Harvard Univ, Sch Med, Dept Gynecol, Boston, MA USA. [Barth, William H., Jr.] Harvard Univ, Sch Med, Dept Reprod Biol, Boston, MA USA. [Post, Miriam D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Duff, P (reprint author), Univ Florida, Dept Obstet & Gynecol, Gainesville, FL 32611 USA. NR 15 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 JAN 29 PY 2009 VL 360 IS 5 BP 508 EP 516 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 399PS UT WOS:000262812400013 PM 19179319 ER PT J AU Georgopoulos, K AF Georgopoulos, Katia TI Acute Lymphoblastic Leukemia -- On the Wings of IKAROS. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHROMATIN REMODELER MI-2-BETA; EXPRESSION C1 [Georgopoulos, Katia] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Georgopoulos, Katia] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Georgopoulos, K (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 12 TC 12 Z9 12 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 29 PY 2009 VL 360 IS 5 BP 524 EP 526 DI 10.1056/NEJMe0809819 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 399PS UT WOS:000262812400016 PM 19131438 ER PT J AU Lanoy, E Dores, GM Madeleine, MM Toro, JR Fraumeni, JF Engels, EA AF Lanoy, Emilie Dores, Graca M. Madeleine, Margaret M. Toro, Jorge R. Fraumeni, Joseph F., Jr. Engels, Eric A. TI Epidemiology of nonkeratinocytic skin cancers among persons with AIDS in the United States SO AIDS LA English DT Article DE AIDS; appendageal carcinoma; epidemiology; melanoma; Merkel cell carcinoma; sebaceous carcinoma; skin cancer ID HUMAN-IMMUNODEFICIENCY-VIRUS; MUIR-TORRE-SYNDROME; SQUAMOUS-CELL CARCINOMA; CUTANEOUS HUMAN PAPILLOMAVIRUSES; ORGAN TRANSPLANT RECIPIENTS; SEBACEOUS GLAND CARCINOMA; SUN-EXPOSED SKIN; MICROSATELLITE INSTABILITY; HIV-INFECTION; RISK-FACTORS AB Objective: Immunosuppression may increase risk for some skin cancers. We evaluated skin cancer epidemiology among persons with AIDS. Design: We linked data from population-based US AIDS and cancer registries to evaluate risk of nonkeratinocytic skin cancers (melanoma, Merkel cell carcinoma, and appendageal carcinomas, including sebaceous carcinoma) in 497 142 persons with AIDS. Methods: Standardized incidence ratios (SIRs) were calculated to relate skin cancer risk to that in the general population. We used logistic regression to compare risk according to demographic factors, CD4 cell count, and a geographic index of ultraviolet radiation exposure. Results: From 60 months before to 60 months after AIDS onset, persons with AIDS had elevated risks of melanoma (SIR=1.3, 95% confidence interval 1.1-1.4, n=292 cases) and, more strongly, of Merkel cell carcinoma (SIR=11, 95% confidence interval 6.3-17, n=17) and sebaceous carcinoma (SIR=8.1, 95% confidence interval 3.2-17, n=7). Risk for appendageal carcinomas increased with progressive time relative to AIDS onset (P trend 0.03). Risk of these skin cancers was higher in non-Hispanic whites than other racial/ethnic groups, and melanoma risk was highest among men who have sex with men. Melanoma risk was unrelated to CD4 cell count at AIDS onset (P=0.32). Risks for melanoma and appendageal carcinomas rose with increasing ultraviolet radiation exposure (P trend <10 (4) and P trend -10 (3), respectively). Conclusion: Among persons with AIDS, there is a modest excess risk of melanoma, which is not strongly related to immunosuppression and may relate to ultraviolet radiation exposure. In contrast, the greatly increased risks for Merkel cell and sebaceous carcinoma suggest an etiologic role for immunosuppression. (c) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Lanoy, Emilie; Dores, Graca M.; Toro, Jorge R.; Fraumeni, Joseph F., Jr.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. [Lanoy, Emilie] Univ Paris 06, INSERM, U720, Paris, France. [Lanoy, Emilie] Univ Paris 06, UPMC, UMR S720, Paris, France. [Dores, Graca M.] US Dept Vet Affairs, Med Ctr, Med Serv, Oklahoma City, OK USA. [Madeleine, Margaret M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Engels, EA (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7076, Rockville, MD 20892 USA. EM engelse@exchange.nih.gov RI Lanoy, Emilie/A-8541-2011 OI Lanoy, Emilie/0000-0002-4789-7770 FU Intramural Research Program of the National Cancer Institute FX We are grateful for the contributions of many staff members at the HIV/AIDS and cancer registries who collected the data, prepared data files for the mathces, and facilitated the record linkages.; E.L. and E.A.E. designed the study and conducted the statistical analyses. G.M.D., J.R.T, and J.F.F contributed expertise regarding, skin cancer. All authors contributed expertise regarding epidemiology methods and participated in the interpretation of the data. M.M.M. and E.A.E. provided data for the study. E.L. and E.A.E. drafted the article, and all authors contributed to critical revision of the article.; The study was supported by the Intramural Research Program of the National Cancer Institute. NR 42 TC 36 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 28 PY 2009 VL 23 IS 3 BP 385 EP 393 DI 10.1097/QAD.0b013e3283213046 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 406WH UT WOS:000263325100013 PM 19114864 ER PT J AU Oeffinger, KC Ford, JS Moskowitz, CS Diller, LR Hudson, MM Chou, JF Smith, SM Mertens, AC Henderson, TO Friedman, DL Leisenring, WM Robison, LL AF Oeffinger, Kevin C. Ford, Jennifer S. Moskowitz, Chaya S. Diller, Lisa R. Hudson, Melissa M. Chou, Joanne F. Smith, Stephanie M. Mertens, Ann C. Henderson, Tara O. Friedman, Debra L. Leisenring, Wendy M. Robison, Leslie L. TI Breast Cancer Surveillance Practices Among Women Previously Treated With Chest Radiation for a Childhood Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HEALTH BELIEF MODEL; LONG-TERM SURVIVORS; HODGKINS-DISEASE; YOUNG-WOMEN; SCREENING PRACTICES; OVARIAN-CANCER; UNITED-STATES; SUPRADIAPHRAGMATIC RADIATION; FEMALE SURVIVORS; ADULT SURVIVORS AB Context Women treated with chest radiation for a pediatric malignancy have a significantly increased risk of breast cancer at a young age and are recommended to have an annual screening mammogram starting at age 25 years or 8 years after radiation, whichever occurs last. Objective To characterize the breast cancer surveillance practices among female pediatric cancer survivors who were treated with chest radiation and identify correlates of screening. Design, Setting, and Participants Between June 2005 and August 2006, a 114-item questionnaire was administered to a random sample of 625 women aged 25 through 50 years who had survived pediatric cancer, who had been treated with chest radiation, and who were participating in the Childhood Cancer Survivor Study (CCSS), a North American cohort of long- term survivors diagnosed from 1970- 1986. Comparisons were made with similarly aged pediatric cancer survivors not treated with chest radiation ( n= 639) and the CCSS siblings cohort ( n= 712). Main Outcome Measure Screening mammogram within the previous 2 years. Results Of 1976 cancer survivors and siblings who were contacted, 87.9% participated. Among the 551 women with a history of chest radiation, 55% reported a screening mammogram in the past 2 years (ages 25- 39 years, 36.5%; 95% confidence interval [ CI], 31.0%-42.0%; ages 40- 50 years, 76.5%; 95% CI, 71.3%- 81.7%). In comparison, 40.5% of survivors without chest radiation and 37.0% of CCSS siblings reported a screening mammogram in the same time interval. Notably, among women with a history of chest radiation, 47.3% ( 95% CI; 41.6%- 53.0%) of those younger than 40 years had never had a mammogram and only 52.6% ( 95% CI; 46.4%- 58.8%) of women aged 40 through 50 years were being regularly screened ( 2 mammograms within 4 years). Screening rates were higher among women who reported a physician recommendation than those who did not ( ages 25- 39 years, 76.0% vs 17.6%; ages 40- 50 years, 87.3% vs 58.3%). In multivariate models, the association was particularly strong for younger women( ages25- 39 years, prevalence ratio [ PR], 3.0; 95% CI, 2.0- 4.0; ages 40- 50 years, PR, 1.3; 95% CI, 1.1- 1.6). Conclusions In this cohort of women who had childhood cancer treated with chest radiation, 63.5% of those aged 25 through 39 years and 23.5% of those aged 40 through 50 years had not had mammography screening for breast cancer within the previous 2 years despite a guideline recommendation that survivors of childhood cancer who were treated with chest radiation should undergo annual screening mammography. C1 [Oeffinger, Kevin C.; Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. [Moskowitz, Chaya S.; Chou, Joanne F.; Smith, Stephanie M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Diller, Lisa R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Hudson, Melissa M.] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Hudson, Melissa M.; Robison, Leslie L.] St Jude Childrens Hosp, Dept Epidemiol & Canc Control, Memphis, TN 38105 USA. [Mertens, Ann C.] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Henderson, Tara O.] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. [Friedman, Debra L.] Vanderbilt Ingram Canc Ctr, Dept Pediat, Nashville, TN USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Div, Seattle, WA 98104 USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. EM oeffingk@mskcc.org FU NCI NIH HHS [R21 CA106972-02, R21 CA106972, R21 CA106972-03, R21-CA-106972, U24 CA055727, U24 CA055727-06A1, U24 CA055727-07, U24 CA055727-08, U24 CA055727-09, R21 CA106972-01, U24 CA055727-10, U24 CA055727-11, U24 CA055727-11S1, U24 CA055727-11S2, U24 CA055727-12A1, U24 CA055727-13, U24 CA055727-14, U24-CA-55727] NR 58 TC 70 Z9 70 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 28 PY 2009 VL 301 IS 4 BP 404 EP 414 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 399CE UT WOS:000262777200020 PM 19176442 ER PT J AU N'Diaye, EN Branda, CS Branda, SS Nevarez, L Colonna, M Lowell, C Hamerman, JA Seaman, WE AF N'Diaye, Elsa-Noah Branda, Catherine S. Branda, Steven S. Nevarez, Lisette Colonna, Marco Lowell, Clifford Hamerman, Jessica A. Seaman, William E. TI TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TYROSINE KINASE; CUTTING EDGE; RHO-GTPASES; MACROPHAGES; SYK; MECHANISMS; DAP12; ACTIVATION; PROTEIN; FAMILY AB Phagocytosis, which is essential for the immune response to pathogens, is initiated by specific interactions between pathogens and cell surface receptors expressed by phagocytes. This study identifies triggering receptor expressed on myeloid cells 2 (TREM-2) and its signaling counterpart DAP12 as a molecular complex that promotes phagocytosis of bacteria. Expression of TREM-2-DAP12 enables nonphagocytic Chinese hamster ovary cells to internalize bacteria. This function depends on actin cytoskeleton dynamics and the activity of the small guanosine triphosphatases Rac and Cdc42. Internalization also requires src kinase activity and tyrosine phosphorylation. In bone marrow-derived macrophages, phagocytosis is decreased in the absence of DAP12 and can be restored by expression of TREM-2-DAP12. Depletion of TREM-2 inhibits both binding and uptake of bacteria. Finally, TREM-2-dependent phagocytosis is impaired in Syk-deficient macrophages. This study highlights a novel role for TREM-2-DAP12 in the immune response to bacterial pathogens. C1 [N'Diaye, Elsa-Noah; Nevarez, Lisette; Seaman, William E.] San Francisco VA Med Ctr, Macrophage Biol Lab, San Francisco, CA 94121 USA. [Branda, Catherine S.; Branda, Steven S.] Sandia Natl Labs, Livermore, CA 94550 USA. [Colonna, Marco] Washington Univ, Sch Med, St Louis, MO 63110 USA. [Lowell, Clifford] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Hamerman, Jessica A.] Benaroya Res Inst, Seattle, WA 98101 USA. RP Seaman, WE (reprint author), San Francisco VA Med Ctr, Macrophage Biol Lab, San Francisco, CA 94121 USA. EM bseaman@medicine.ucsf.edu OI Colonna, Marco/0000-0001-5222-4987 FU Laboratory Directed Research and Development program at Sandia National Laboratories; Lockheed Martin Company [DE-AC04-94AL85000]; National Institutes of Health [RO1 CA87922, GM062114] FX This work was supported by the Laboratory Directed Research and Development program at Sandia National Laboratories. Sandia is a multiprogram laboratory operated by Sandia Corporation, a Lockheed Martin Company, for the U. S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000. Additional support was provided by National Institutes of Health grant RO1 CA87922 (to W. E. Seaman), by National Institutes of Health grant GM062114 to the Alliance for Cellular Signaling, and by the Veterans Administration. NR 36 TC 78 Z9 79 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 28 PY 2009 VL 184 IS 2 BP 215 EP 223 DI 10.1083/jcb.200808080 PG 9 WC Cell Biology SC Cell Biology GA 404LO UT WOS:000263153900017 PM 19171755 ER PT J AU Yamamoto, M Beppu, H Takaoka, K Meno, C Li, E Miyazono, K Hamada, H AF Yamamoto, Masamichi Beppu, Hideyuki Takaoka, Katsuyoshi Meno, Chikara Li, En Miyazono, Kohei Hamada, Hiroshi TI Antagonism between Smad1 and Smad2 signaling determines the site of distal visceral endoderm formation in the mouse embryo SO JOURNAL OF CELL BIOLOGY LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; EARLY XENOPUS DEVELOPMENT; PRIMITIVE STREAK; FOREBRAIN DEVELOPMENT; ANTEROPOSTERIOR AXIS; VENTRALIZING FACTOR; NODAL ANTAGONISTS; MULTIPLE ROLES; BMP; GASTRULATION AB The anterior-posterior axis of the mouse embryo is established by formation of distal visceral endoderm (DVE) and its subsequent migration. The precise mechanism of DVE formation has remained unknown, however. Here we show that bone morphogenetic protein (BMP) signaling plays dual roles in DVE formation. BMP signaling is required at an early stage for differentiation of the primitive endoderm into the embryonic visceral endoderm (VE), whereas it inhibits DVE formation, restricting it to the distal region, at a later stage. A Smad2-activating factor such as Activin also contributes to DVE formation by generating a region of VE positive for the Smad2 signal and negative for Smad1 signal. DVE is thus formed at the distal end of the embryo, the only region of VE negative for the Smad1 signal and positive for Smad2 signal. An inverse relation between the level of phosphorylated Smad1 and that of phosphorylated Smad2 in VE suggests an involvement of antagonism between Smad1- and Smad2-mediated signaling. C1 [Yamamoto, Masamichi; Takaoka, Katsuyoshi; Meno, Chikara; Hamada, Hiroshi] Osaka Univ, Grad Sch Frontier Biosci, Dev Genet Grp, Suita, Osaka 5650871, Japan. [Yamamoto, Masamichi; Takaoka, Katsuyoshi; Hamada, Hiroshi] Japan Sci & Technol Corp, Suita, Osaka 5650871, Japan. [Beppu, Hideyuki] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. [Li, En] Novartis Inst Biomed Res, Epigenet Program, Cambridge, MA 02139 USA. [Miyazono, Kohei] Univ Tokyo, Grad Sch Med, Dept Mol Pathol, Tokyo 1130033, Japan. RP Yamamoto, M (reprint author), Osaka Univ, Grad Sch Frontier Biosci, Dev Genet Grp, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM myamamoto@fbs.osaka-u.ac.jp; hamada@fbs.osaka-u.ac.jp FU Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation; Ministry of Education, Culture, Sports, Science and Technology of Japan; Japan Society for the Promotion of Science for Japanese Junior Scientists FX This work was supported by a grant from Core Research for Evolutional Science and Technology of the Japan Science and Technology Corporation (to H. Hamada) as well as by a Grant-in-Aid for Scientific Research on Priority Areas and a Grant-in-Aid for Young Scientists (to M. Yamamoto) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. M. Yamamoto is also a recipient of a fellowship from the Japan Society for the Promotion of Science for Japanese Junior Scientists. NR 54 TC 50 Z9 50 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JAN 28 PY 2009 VL 184 IS 2 BP 323 EP 334 DI 10.1083/jcb.200808044 PG 12 WC Cell Biology SC Cell Biology GA 404LO UT WOS:000263153900025 PM 19153222 ER PT J AU Kong, W Mou, XY Liu, QZ Chen, ZX Vanderburg, CR Rogers, JT Huang, XD AF Kong, Wei Mou, Xiaoyang Liu, Qingzhong Chen, Zhongxue Vanderburg, Charles R. Rogers, Jack T. Huang, Xudong TI Independent component analysis of Alzheimer's DNA microarray gene expression data SO MOLECULAR NEURODEGENERATION LA English DT Article ID PROTEIN-KINASE-II; NERVOUS-SYSTEM; RHO GTPASES; DISEASE; CANCER; ACTIN; FILOPODIA; PROFILES; MODEL; RAC AB Background: Gene microarray technology is an effective tool to investigate the simultaneous activity of multiple cellular pathways from hundreds to thousands of genes. However, because data in the colossal amounts generated by DNA microarray technology are usually complex, noisy, high-dimensional, and often hindered by low statistical power, their exploitation is difficult. To overcome these problems, two kinds of unsupervised analysis methods for microarray data: principal component analysis (PCA) and independent component analysis (ICA) have been developed to accomplish the task. PCA projects the data into a new space spanned by the principal components that are mutually orthonormal to each other. The constraint of mutual orthogonality and second-order statistics technique within PCA algorithms, however, may not be applied to the biological systems studied. Extracting and characterizing the most informative features of the biological signals, however, require higher-order statistics. Results: ICA is one of the unsupervised algorithms that can extract higher-order statistical structures from data and has been applied to DNA microarray gene expression data analysis. We performed FastICA method on DNA microarray gene expression data from Alzheimer's disease (AD) hippocampal tissue samples and consequential gene clustering. Experimental results showed that the ICA method can improve the clustering results of AD samples and identify significant genes. More than 50 significant genes with high expression levels in severe AD were extracted, representing immunity-related protein, metal-related protein, membrane protein, lipoprotein, neuropeptide, cytoskeleton protein, cellular binding protein, and ribosomal protein. Within the aforementioned categories, our method also found 37 significant genes with low expression levels. Moreover, it is worth noting that some oncogenes and phosphorylation- related proteins are expressed in low levels. In comparison to the PCA and support vector machine recursive feature elimination (SVM-RFE) methods, which are widely used in microarray data analysis, ICA can identify more AD-related genes. Furthermore, we have validated and identified many genes that are associated with AD pathogenesis. Conclusion: We demonstrated that ICA exploits higher-order statistics to identify gene expression profiles as linear combinations of elementary expression patterns that lead to the construction of potential AD-related pathogenic pathways. Our computing results also validated that the ICA model outperformed PCA and the SVM-RFE method. This report shows that ICA as a microarray data analysis tool can help us to elucidate the molecular taxonomy of AD and other multifactorial and polygenic complex diseases. C1 [Kong, Wei; Mou, Xiaoyang; Huang, Xudong] Brigham & Womens Hosp, Biomed Informat & Cheminformat Grp, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, Boston, MA 02115 USA. [Kong, Wei; Mou, Xiaoyang; Huang, Xudong] Brigham & Womens Hosp, Dept Radiol, Ctr Adv Med Imaging, Boston, MA 02115 USA. [Kong, Wei; Mou, Xiaoyang; Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Kong, Wei] Shanghai Maritime Univ, Informat Engn Coll, Shanghai 200135, Peoples R China. [Liu, Qingzhong] New Mexico Inst Min & Technol, Dept Comp Sci, Socorro, NM 87801 USA. [Liu, Qingzhong] New Mexico Inst Min & Technol, Inst Complex Addit Syst Anal, Socorro, NM 87801 USA. [Chen, Zhongxue] Childrens Hosp Philadelphia, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Adv Tissue Resource Ctr, Charlestown, MA 02129 USA. [Vanderburg, Charles R.; Rogers, Jack T.; Huang, Xudong] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Rogers, Jack T.; Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Neurochem Lab, Charlestown, MA 02129 USA. RP Huang, XD (reprint author), Brigham & Womens Hosp, Biomed Informat & Cheminformat Grp, Conjugate & Med Chem Lab, Div Nucl Med & Mol Imaging, 75 Francis St, Boston, MA 02115 USA. EM wkong@bwh.harvard.edu; mou@bwh.harvard.edu; liuqzsc@nmt.edu; chenz@email.chop.edu; cvanderburg@partners.org; jtrogers@partners.org; xhuang3@partners.org FU Research Foundation of Shanghai Municipal Education Commission [06FZ012, 2008098]; National Natural Science Foundation of China [60801060]; Radiology Department of Brigham and Women's Hospital (BWH); NIA/NIH [5R21AG028850]; Alzheimer's Association [IIRG-07-60397]; BWH Radiology Department FX WK would like to express her gratitude for the supports from the Research Foundation of Shanghai Municipal Education Commission (No. 06FZ012 and No. 2008098), the National Natural Science Foundation of China (No. 60801060), and Radiology Department of Brigham and Women's Hospital (BWH). XH is supported by grants from the NIA/NIH (5R21AG028850), Alzheimer's Association (IIRG-07-60397), and the research funds from BWH Radiology Department. We thank Ms. Kimberly Lawson at BWH Radiology Department for her extremely helpful comments and editing of our manuscript. NR 50 TC 27 Z9 27 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD JAN 28 PY 2009 VL 4 AR 5 DI 10.1186/1750-1326-4-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 445PN UT WOS:000266063600001 PM 19173745 ER PT J AU Doshi, JA Zhu, JS Lee, BY Kimmel, SE Volpp, KG AF Doshi, Jalpa A. Zhu, Jingsan Lee, Bruce Y. Kimmel, Stephen E. Volpp, Kevin G. TI Impact of a Prescription Copayment Increase on Lipid-Lowering Medication Adherence in Veterans SO CIRCULATION LA English DT Article DE coronary disease; medication adherence; fees, pharmaceutical; statins; veterans ID ACUTE MYOCARDIAL-INFARCTION; PHARMACY BENEFITS; STATIN THERAPY; PERSISTENCE; COST; CHOLESTEROL; DATABASES; PROGRAM; DRUGS; CARE AB Background-In February 2002, the Department of Veterans Affairs (VA) increased copayments from $2 to $7 per 30-day drug supply of each medication for many veterans. We examined the impact of the copayment increase on lipid-lowering medication adherence. Methods and Results-This quasiexperimental study used electronic records of 5604 veterans receiving care at the Philadelphia VA Medical Center from November 1999 to April 2004. The all copayment group included veterans subject to copayments for all drugs with no annual cap. Veterans subject to copayments for drugs only if indicated for a non-service-connected condition with an annual cap of $840 for out-of-pocket costs made up the some copayment group. Veterans who remained copayment exempt formed a natural control group (no copayment group). Patients were identified as adherent if the proportion of days covered with lipid-lowering medications was >= 80%. Patients were identified as having a continuous gap if they had at least 1 continuous episode with no lipid-lowering medications for >= 90 days. A difference-in-difference approach compared changes in lipid-lowering medication adherence during the 24 months before and after copayment increase among veterans subject to the copayment change with those who were not. Adherence declined in all 3 groups after the copayment increase. However, the percentage of patients who were adherent (proportion of days covered >= 80%) declined significantly more in the all copayment (- 19.2%) and some copayment (- 19.3%) groups relative to the exempt group (- 11.9%). The incidence of a continuous gap increased significantly at twice the rate in both copayment groups (all copayment group, 24.6%; some copayment group, 24.1%) as the exempt group (11.7%). Compared with the exempt group, the odds of having a continuous gap in the after relative to the before period were significantly higher in both the all copayment group (odds ratio, 3.04; 95% confidence interval, 2.29 to 4.03) and the some copayment group (odds ratio, 1.85; 95% confidence interval, 1.43 to 2.40). Similar results were seen in subgroups of patients at high risk for coronary heart disease, high medication users, and elderly veterans. Conclusion-The copayment increase adversely affected lipid-lowering medication adherence among veterans, including those at high coronary heart disease risk. (Circulation. 2009; 119: 390-397.) C1 [Doshi, Jalpa A.; Zhu, Jingsan; Volpp, Kevin G.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Res & Promot, Philadelphia, PA USA. [Doshi, Jalpa A.; Zhu, Jingsan; Kimmel, Stephen E.; Volpp, Kevin G.] Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Kimmel, Stephen E.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Doshi, Jalpa A.; Volpp, Kevin G.] Univ Penn, Leonard Davis Inst Hlth Econ, Ctr Hlth Incent, Philadelphia, PA 19104 USA. [Volpp, Kevin G.] Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. [Lee, Bruce Y.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Lee, Bruce Y.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. RP Doshi, JA (reprint author), 1222 Blockley Hall, Philadelphia, PA 19104 USA. EM jdoshi@mail.med.upenn.edu FU VA Center for Health Equity Research and Promotion; American Heart Association Pharmaceutical Roundtable Award [0675066N]; Commonwealth of Pennsylvania [540625]; National Institute of Aging [R01 AG024451-01]; Penn Institute on Aging FX We are grateful for funding support from the VA Center for Health Equity Research and Promotion; the American Heart Association Pharmaceutical Roundtable Award (grant 0675066N); the Commonwealth of Pennsylvania (grant 540625); the National Institute of Aging (R01 AG024451-01); and the Penn Institute on Aging. The funding organizations or sponsors played no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. NR 24 TC 95 Z9 98 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 2009 VL 119 IS 3 BP 390 EP U53 DI 10.1161/CIRCULATIONAHA.108.783944 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 399EX UT WOS:000262784300007 PM 19139387 ER PT J AU Pokreisz, P Vandenwijngaert, S Bito, V Van den Bergh, A Lenaerts, I Busch, C Marsboom, G Gheysens, O Vermeersch, P Biesmans, L Liu, XS Gillijns, H Pellens, M Van Lommel, A Buys, E Schoonjans, L Vanhaecke, J Verbeken, E Sipido, K Herijgers, P Bloch, KD Janssens, SP AF Pokreisz, Peter Vandenwijngaert, Sara Bito, Virginie Van den Bergh, An Lenaerts, Ilse Busch, Cornelius Marsboom, Glenn Gheysens, Olivier Vermeersch, Pieter Biesmans, Liesbeth Liu, Xiaoshun Gillijns, Hilde Pellens, Marijke Van Lommel, Alfons Buys, Emmanuel Schoonjans, Luc Vanhaecke, Johan Verbeken, Erik Sipido, Karin Herijgers, Paul Bloch, Kenneth D. Janssens, Stefan P. TI Ventricular Phosphodiesterase-5 Expression Is Increased in Patients With Advanced Heart Failure and Contributes to Adverse Ventricular Remodeling After Myocardial Infarction in Mice SO CIRCULATION LA English DT Article DE phosphodiesterase-5; cyclic GMP; myocardial infarction; heart failure ID GUANYLYL CYCLASE; SARCOPLASMIC-RETICULUM; NATRIURETIC PEPTIDE; CGMP-BINDING; INHIBITION; MYOCYTES; CONTRACTILITY; SILDENAFIL; MOUSE; HYPERTROPHY AB Background-Ventricular expression of phosphodiesterase-5 (PDE5), an enzyme responsible for cGMP catabolism, is increased in human right ventricular hypertrophy, but its role in left ventricular (LV) failure remains incompletely understood. We therefore measured LV PDE5 expression in patients with advanced systolic heart failure and characterized LV remodeling after myocardial infarction in transgenic mice with cardiomyocyte-specific overexpression of PDE5 (PDE5-TG). Methods and Results-Immunoblot and immunohistochemistry techniques revealed that PDE5 expression was greater in explanted LVs from patients with dilated and ischemic cardiomyopathy than in control hearts. To evaluate the impact of increased ventricular PDE5 levels on cardiac function, PDE5-TG mice were generated. Confocal and immunoelectron microscopy revealed increased PDE5 expression in cardiomyocytes, predominantly localized to Z-bands. At baseline, myocardial cGMP levels, cell shortening, and calcium handling in isolated cardiomyocytes and LV hemodynamic measurements were similar in PDE5-TG and wild-type littermates. Ten days after myocardial infarction, LV cGMP levels had increased to a greater extent in wild-type mice than in PDE5-TG mice (P < 0.05). Ten weeks after myocardial infarction, LV end-systolic and end-diastolic volumes were larger in PDE5-TG than in wild-type mice (57 +/- 5 versus 39 +/- 4 and 65 +/- 6 versus 48 +/- 4 mu L, respectively; P < 0.01 for both). LV systolic dysfunction and diastolic dysfunction were more marked in PDE5-TG than in wild-type mice, associated with enhanced hypertrophy and reduced contractile function in isolated cardiomyocytes from remote myocardium. Conclusions-Increased PDE5 expression predisposes mice to adverse LV remodeling after myocardial infarction. Increased myocardial PDE5 expression in patients with advanced cardiomyopathy may contribute to the development of heart failure and represents an important therapeutic target. (Circulation. 2009; 119: 408-416.) C1 [Vanhaecke, Johan; Janssens, Stefan P.] Katholieke Univ Leuven, Div Clin Cardiol, B-3000 Louvain, Belgium. [Pokreisz, Peter; Vandenwijngaert, Sara; Marsboom, Glenn; Vermeersch, Pieter; Liu, Xiaoshun; Gillijns, Hilde; Pellens, Marijke; Schoonjans, Luc; Janssens, Stefan P.] Katholieke Univ Leuven VIB, Vesalius Res Ctr, Louvain, Belgium. [Gheysens, Olivier] Katholieke Univ Leuven, Dept Cardiovasc Med, B-3000 Louvain, Belgium. [Van Lommel, Alfons; Verbeken, Erik] Katholieke Univ Leuven, Dept Med Diagnost Sci, B-3000 Louvain, Belgium. [Busch, Cornelius; Buys, Emmanuel; Bloch, Kenneth D.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Busch, Cornelius; Buys, Emmanuel; Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Janssens, SP (reprint author), Katholieke Univ Leuven, Div Clin Cardiol, Campus Gasthuisberg,49 Herestr, B-3000 Louvain, Belgium. EM stefan.janssens@med.kuleuven.be RI Herijgers, Paul/B-8064-2013; Vermeersch, Pieter/M-8352-2016 FU Fund for Scientific Research-Flanders [G.0381.05, EWM-B4361-G.0442.06]; Flanders Institute for Biotechnology; National Institutes of Health [HL070896]; Research Fund K. U. Leuven [OT/05/55, GOA/2007/13]; European Union [LSHM-CT-2005-018833]; Astra-Zeneca FX This work was supported by the Fund for Scientific Research-Flanders G.0381.05 (Dr Herijgers), EWM-B4361-G.0442.06 (Dr Janssens), and the Flanders Institute for Biotechnology (VIB, to Dr Janssens); National Institutes of Health grant HL070896 (Dr Bloch); Research Fund K. U. Leuven OT/05/55 (Dr Herijgers) and GOA/2007/13 (Drs Sipido, Pokreisz, and Janssens); and European Union LSHM-CT-2005-018833, EUGeneHeart (Dr Bito). Dr Janssens is a Principal Investigator of Flanders Institute of Technology and is holder of a chair supported by Astra-Zeneca. NR 34 TC 105 Z9 108 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 JAN 27 PY 2009 VL 119 IS 3 BP 408 EP U93 DI 10.1161/CIRCULATIONAHA.108.822072 PG 28 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 399EX UT WOS:000262784300009 PM 19139381 ER PT J AU King, VL Lin, AY Kristo, F Anderson, TJT Ahluwalia, N Hardy, GJ Owens, AP Howatt, DA Shen, DX Tager, AM Luster, AD Daugherty, A Gerszten, RE AF King, Victoria L. Lin, Alexander Y. Kristo, Fjoralba Anderson, Thomas J. T. Ahluwalia, Neil Hardy, Gregory J. Owens, A. Phillip, III Howatt, Deborah A. Shen, Dongxiao Tager, Andrew M. Luster, Andrew D. Daugherty, Alan Gerszten, Robert E. TI Interferon-gamma and the Interferon-Inducible Chemokine CXCL10 Protect Against Aneurysm Formation and Rupture SO CIRCULATION LA English DT Article DE aneurysm; atherosclerosis; immunology; inflammation; mice, knockout ID ABDOMINAL AORTIC-ANEURYSMS; E-DEFICIENT MICE; ANGIOTENSIN-CONVERTING ENZYME; COLLAGEN-INDUCED ARTHRITIS; IFN-GAMMA; MOUSE MODEL; T-CELLS; TRANSFORMING GROWTH-FACTOR-BETA-1; PROMOTES ATHEROGENESIS; IMMUNE-RESPONSES AB Background-Vascular disease can manifest as stenotic plaques or ectatic aneurysms, although the mechanisms culminating in these divergent disease manifestations remain poorly understood. T-helper type 1 cytokines, including interferon-gamma and CXCL10, have been strongly implicated in atherosclerotic plaque development. Methods and Results-Here, we specifically examined their role in the formation of abdominal aortic aneurysms in the angiotensin II-induced murine model. Unexpectedly, we found increased suprarenal aortic diameters, abdominal aortic aneurysm incidence, and aneurysmal death in apolipoprotein E- and interferon-gamma-deficient (Apoe(-/-)/Ifng(-/-)) mice compared with Apoe(-/-) controls, although atherosclerotic luminal plaque formation was attenuated. The interferon-gamma-inducible T-cell chemoattractant CXCL10 was highly induced by angiotensin II infusion in Apoe(-/-) mice, but this induction was markedly attenuated in Apoe(-/-)/Ifng(-/-) mice. Apoe(-/-)/Cxcl10(-/-) mice had decreased luminal plaque but also increased aortic size, worse morphological grades of aneurysms, and a higher incidence of death due to aortic rupture than Apoe(-/-) controls. Furthermore, abdominal aortic aneurysms in Apoe(-/-)/Cxcl10(-/-) mice were enriched for non-T-helper type 1-related signals, including transforming growth factor-beta 1. Treatment of Apoe(-/-)/Cxcl10(-/-) mice with anti-transforming growth factor-beta neutralizing antibody diminished angiotensin II-induced aortic dilation. Conclusions-The present study defines a novel pathway in which interferon-gamma and its effector, CXCL10, contribute to divergent pathways in abdominal aortic aneurysm versus plaque formation, inhibiting the former pathology but promoting the latter. Thus, efforts to develop antiinflammatory strategies for atherosclerosis must carefully consider potential effects on all manifestations of vascular disease. (Circulation. 2009; 119: 426-435.) C1 [King, Victoria L.; Owens, A. Phillip, III; Howatt, Deborah A.; Daugherty, Alan] Univ Kentucky, Cardiovasc Res Ctr, Lexington, KY USA. [King, Victoria L.; Daugherty, Alan] Univ Kentucky, Grad Ctr Nutr Sci, Lexington, KY USA. [Owens, A. Phillip, III; Daugherty, Alan] Univ Kentucky, Grad Ctr Toxicol, Lexington, KY USA. [Lin, Alexander Y.; Kristo, Fjoralba; Anderson, Thomas J. T.; Ahluwalia, Neil; Hardy, Gregory J.; Shen, Dongxiao; Tager, Andrew M.; Luster, Andrew D.; Gerszten, Robert E.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [Lin, Alexander Y.; Kristo, Fjoralba; Anderson, Thomas J. T.; Ahluwalia, Neil; Hardy, Gregory J.; Shen, Dongxiao; Gerszten, Robert E.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gerszten, RE (reprint author), Massachusetts Gen Hosp E Campus, Div Cardiol, 149 13th St,Room 8307, Charlestown, MA 02129 USA. EM rgerszten@partners.org RI Daugherty, Alan/C-8282-2009; OI Kristo, Fjoralba/0000-0002-8045-9756; Anderson, Thomas/0000-0002-2762-6703 FU National Institutes of Health [HL62846, HL 80100, CA069212, HL65584]; American Heart Association; Donald W. Reynolds Foundation; Leducq Foundation FX The authors gratefully acknowledge support from the National Institutes of Health to Dr Daugherty (HL62846 and HL 80100), Dr Luster (CA069212), and Dr Gerszten (HL65584) and from the American Heart Association (Grant-in-Aid to Dr Gerszten). Dr Gerszten is also supported by the Donald W. Reynolds Foundation and the Leducq Foundation. NR 48 TC 58 Z9 60 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 27 PY 2009 VL 119 IS 3 BP 426 EP 435 DI 10.1161/CIRCULATIONAHA.108.785949 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 399EX UT WOS:000262784300011 PM 19139386 ER PT J AU Jaff, MR Dale, RA Creager, MA Lipicky, RJ Constant, J Campbell, LA Hiatt, WR AF Jaff, Michael R. Dale, Rita A. Creager, Mark A. Lipicky, Raymond John Constant, John Campbell, Lee Ann Hiatt, William R. TI Anti-Chlamydial Antibiotic Therapy for Symptom Improvement in Peripheral Artery Disease Prospective Evaluation of Rifalazil Effect on Vascular Symptoms of Intermittent Claudication and Other Endpoints in Chlamydia pneumoniae Seropositive Patients (PROVIDENCE-1) SO CIRCULATION LA English DT Article DE claudication; infection; peripheral vascular disease ID CORONARY-HEART-DISEASE; SMOOTH-MUSCLE-CELLS; SECONDARY PREVENTION; OCCLUSIVE DISEASE; CONTROLLED-TRIAL; INFECTION; AZITHROMYCIN; ASSOCIATION; ATHEROSCLEROSIS; METAANALYSIS AB Background-A potentially strong association exists between Chlamydia pneumoniae and atherosclerosis, but the clinical benefits of antibiotic therapy have not been demonstrated. Preliminary studies of antibiotic therapy in peripheral artery disease have shown a decreased need for revascularization and improved walking ability. The objective of this phase-III trial was to assess the effect of a potent anti-Chlamydial agent, rifalazil, on peak walking time in patients with symptomatic peripheral artery disease. Methods and Results-Patients with intermittent claudication secondary to peripheral artery disease who were seropositive for C pneumoniae were randomized to 25 mg rifalazil once weekly for 8 weeks or matching placebo. Two hundred ninety-seven patients were enrolled from 3 countries and were followed up for 1 year. The mean +/- SD ankle brachial index at baseline was 0.63 +/- 0.16. The primary end point, change from baseline in log peak walking time on a graded treadmill, was assessed 180 days after randomization. Secondary end points included changes in claudication onset time and quality of life, assessed with the Walking Impairment Questionnaire and the Short Form Medical Outcomes 36. No benefit of rifalazil therapy was found in the primary or any secondary end point among this cohort of patients with peripheral artery disease. The group treated with rifalazil improved their peak walking times by 23% (95% confidence interval, 15 to 31) from baseline to day 180, whereas the placebo group improved by 18% (95% confidence interval, 11 to 26; P = 0.38). Peak walking time, claudication onset time, Walking Impairment Questionnaire, and Short Form Medical Outcomes 36 showed no treatment-by-time interaction during the 360-day study period. Thirty-two adjudicated cardiovascular events occurred, 16 in each treatment group. Conclusions-Rifalazil did not improve exercise performance or quality of life in patients with intermittent claudication. No safety concerns were identified. Given the very small effect size, it is unlikely that larger studies would demonstrate a symptomatic benefit of this therapy in peripheral artery disease. (Circulation. 2009; 119: 452-458.) C1 [Jaff, Michael R.] Massachusetts Gen Hosp, Vasc Ctr, Boston, MA 02114 USA. [Dale, Rita A.; Hiatt, William R.] Colorado Prevent Ctr, Denver, CO USA. [Creager, Mark A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Lipicky, Raymond John] Lipicky LLC, N Potomac, MD USA. [Constant, John] PRA Int, Victoria, BC, Canada. [Campbell, Lee Ann] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Hiatt, William R.] Univ Colorado, Sch Med, Denver, CO USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ctr, GB 832,55 Fruit St, Boston, MA 02114 USA. EM mjaff@partners.org FU Genzyme; Sanofi-Aventis; Activbiotics; Sigma Tau; DNAVEC; Biomarin; Cardium Therapeutics; KOWA FX Dr Jaff has received grant support from Genzyme and has served as a consultant to Activbiotics. Dr Hiatt has received grant support from Genzyme, Sanofi-Aventis, Activbiotics, Sigma Tau, DNAVEC, Biomarin, Cardium Therapeutics, and KOWA and has served on the speaker's bureau for Sanofi-Aventis and Otsuka. Dr Creager has received grant support from Sanofi-Aventis; has served as a consultant to Genzyme, Sigma Tau, Sanofi-Aventis, and Activbiotics; and has been on the speaker's bureau for Bristol Myers Squibb-Sanofi Aventis. Drs Campbell, Lipicky, and Constant have served as consultants to Activbiotics. R. A. Dale reports no conflicts. NR 27 TC 17 Z9 19 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 JAN 27 PY 2009 VL 119 IS 3 BP 452 EP 458 DI 10.1161/CIRCULATIONAHA.108.815308 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 399EX UT WOS:000262784300014 PM 19139383 ER PT J AU Budoff, MJ Nasir, K McClelland, RL Detrano, R Wong, N Blumenthal, RS Kondos, G Kronmal, RA AF Budoff, Matthew J. Nasir, Khurram McClelland, Robyn L. Detrano, Robert Wong, Nathan Blumenthal, Roger S. Kondos, George Kronmal, Richard A. TI Coronary Calcium Predicts Events Better With Absolute Calcium Scores Than Age-Sex-Race/Ethnicity Percentiles MESA (Multi-Ethnic Study of Atherosclerosis) SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE atherosclerosis; cardiac CT; coronary calcium; prognosis ID COMPUTED-TOMOGRAPHY; ARTERY CALCIUM; RISK-FACTORS; CALCIFICATION; DISEASE AB Objectives In this study, we aimed to establish whether age-sex-specific percentiles of coronary artery calcium (CAC) predict cardiovascular outcomes better than the actual (absolute) CAC score. Background The presence and extent of CAC correlates with the overall magnitude of coronary atherosclerotic plaque burden and with the development of subsequent coronary events. Methods MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort study of 6,814 asymptomatic participants followed for coronary heart disease (CHD) events including myocardial infarction, angina, resuscitated cardiac arrest, or CHD death. Time to incident CHD was modeled with Cox regression, and we compared models with percentiles based on age, sex, and/or race/ethnicity to categories commonly used (0, 1 to 100, 101 to 400, 400 + Agatston units). Results There were 163 (2.4%) incident CHD events (median follow-up 3.75 years). Expressing CAC in terms of age- and sex-specific percentiles had significantly lower area under the receiver-operating characteristic curve (AUC) than when using absolute scores (women: AUC 0.73 versus 0.76, p = 0.044; men: AUC 0.73 versus 0.77, p < 0.001). Akaike's information criterion indicated better model fit with the overall score. Both methods robustly predicted events (> 90th percentile associated with a hazard ratio [HR] of 16.4, 95% confidence interval [CI]: 9.30 to 28.9, and score > 400 associated with HR of 20.6, 95% CI: 11.8 to 36.0). Within groups based on age-, sex-, and race/ethnicity-specific percentiles there remains a clear trend of increasing risk across levels of the absolute CAC groups. In contrast, once absolute CAC category is fixed, there is no increasing trend across levels of age-, sex-, and race/ethnicity-specific categories. Patients with low absolute scores are low-risk, regardless of age-, sex-, and race/ethnicity-specific percentile rank. Persons with an absolute CAC score of > 400 are high risk, regardless of percentile rank. Conclusions Using absolute CAC in standard groups performed better than age-, sex-, and race/ethnicity-specific percentiles in terms of model fit and discrimination. We recommend using cut points based on the absolute CAC amount, and the common CAC cut points of 100 and 400 seem to perform well. (J Am Coll Cardiol 2009; 53: 345-52) (C) 2009 by the American College of Cardiology Foundation C1 [Budoff, Matthew J.] Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Div Cardiol, Torrance, CA 90502 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Dept Radiol, Cardiac MRI PET CT Program, Boston, MA 02114 USA. [Nasir, Khurram] Harvard Univ, Sch Med, Boston, MA USA. [McClelland, Robyn L.; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Detrano, Robert; Wong, Nathan] Univ Calif Irvine, Div Cardiol, Irvine, CA USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. [Kondos, George] Univ Illinois, Div Cardiol, Chicago, IL USA. RP Budoff, MJ (reprint author), Univ Calif Los Angeles, Los Angeles Biomed Res Inst Harbor, Div Cardiol, 1124 W Carson St,RB2, Torrance, CA 90502 USA. EM Budoff@ucla.edu FU National Heart, Lung, and Blood Institute [R01 HL071739, N01-HC-95159, N01-HC-95165, N01 HC 95169] FX This research was supported by R01 HL071739 and contracts N01-HC-95159 through N01-HC-95165 and N01 HC 95169 from the National Heart, Lung, and Blood Institute. NR 16 TC 160 Z9 164 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 27 PY 2009 VL 53 IS 4 BP 345 EP 352 DI 10.1016/j.jacc.2008.07.072 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 396RF UT WOS:000262608100008 PM 19161884 ER PT J AU Viswanathan, A Rocca, WA Tzourio, C AF Viswanathan, Anand Rocca, Walter A. Tzourio, Christophe TI Vascular risk factors and dementia How to move forward? SO NEUROLOGY LA English DT Review ID WHITE-MATTER HYPERINTENSITIES; MIDLIFE BLOOD-PRESSURE; ALZHEIMERS-DISEASE; CEREBROVASCULAR-DISEASE; COGNITIVE DECLINE; CARDIOVASCULAR HEALTH; APOLIPOPROTEIN-E; SYSTOLIC HYPERTENSION; BRAIN INFARCTS; OLDER PERSONS AB In recent years, accumulating evidence has suggested that vascular risk factors contribute to Alzheimer disease ( AD). Vascular dementia had been traditionally considered secondary to stroke and vascular disease. It has been traditionally distinguished from AD, considered to be a purely neurodegenerative form of dementia. However, in light of this more recent literature, it appears that there is a spectrum: ranging from patients with pure vascular dementia to patients with pure AD and including a large majority of patients with contributions from both Alzheimer and vascular pathologies. In this article, we discuss the impact of vascular risk factors on AD and its consequences at the individual level and at the population level by highlighting the concept of attributable risk. We then discuss the key questions and next steps involved in designing a therapeutic trial to control vascular risk factors for the prevention of dementia. Neurology (R) 2009; 72:368-374 C1 [Viswanathan, Anand] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Viswanathan, Anand] Massachusetts Gen Hosp, Clin Trials Unit, Boston, MA 02114 USA. [Viswanathan, Anand] Harvard Univ, Sch Med, Boston, MA USA. [Rocca, Walter A.] Mayo Clin, Coll Med, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA. [Rocca, Walter A.] Mayo Clin, Coll Med, Dept Neurol, Rochester, MN USA. [Tzourio, Christophe] Univ Paris 06, F-75252 Paris, France. [Tzourio, Christophe] INSERM, Unit Neuroepidemiol 708, Paris, France. [Tzourio, Christophe] Hop Lariboisiere, Dept Neurol, F-75475 Paris, France. RP Tzourio, C (reprint author), Hop La Pitie Salpetriere, INSERM, U 708, 47 Blvd Hop, F-75651 Paris 13, France. EM aviswanathan1@partners.org; tzourio@chups.jussieu.fr RI Tzourio, christophe/B-4015-2009 OI Tzourio, christophe/0000-0002-6517-2984 FU ARNEVA (Association de Recherche en Neurologie Vasculaire), Hospital Lariboisiere, Paris, France FX Supported by ARNEVA (Association de Recherche en Neurologie Vasculaire), Hospital Lariboisiere, Paris, France. NR 54 TC 194 Z9 200 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 27 PY 2009 VL 72 IS 4 BP 368 EP 374 DI 10.1212/01.wnl.0000341271.90478.8e PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 399CK UT WOS:000262777800013 PM 19171835 ER PT J AU Schuh, LA Adair, JC Drogan, O Kissela, BM Morgenlander, JC Corboy, JR AF Schuh, L. A. Adair, J. C. Drogan, O. Kissela, B. M. Morgenlander, J. C. Corboy, J. R. TI Education Research: Neurology residency training in the new millennium SO NEUROLOGY LA English DT Editorial Material AB Objective: To survey adult neurology program directors (ANPD) to identify their most pressing needs at a time of dramatic change in neurology resident education. Methods: All US ANPD were surveyed in 2007 using an instrument adjusted from a 1999 survey instrument. The goal was to characterize current program content, the institution and evaluation of the core competencies, program director characteristics, program director support, the institution of work duty hour requirements, resident support, and the curriculum needs of program directors and programs. Results: A response rate of 82.9% was obtained. There is a significant disconnect between administration time spent by ANPD and departmental/institutional support of this, with ANPD spending approximately 35% of a 50-hour week on administration with only 16.7% salary support. Rearrangement of rotations or services has been the most common mode for ANPD to deal with work duty hour requirements, with few programs employing mid level providers. Most ANPD do not feel work duty hour reform has improved resident education. More residents are entering fellowships following graduation than documented in the past. Curriculum deficiencies still exist for ANPD to meet all Neurology Program Requirements, especially for nontraditional neurology topics outside the conventional bounds of clinical neurology (e. g., practice management). Nearly one quarter of neurology residency programs do not have a meeting or book fund for every resident in the program. Conclusions: Adult neurology program directors (ANPDs) face multiple important financial and organizational hurdles. At a time of increasing complexity in medical education, ANPDs need more institutional support. Neurology (R) 2009; 72: e15-e20 C1 [Schuh, L. A.] Henry Ford Hosp, Dept Neurol, Detroit, MI 48202 USA. [Adair, J. C.] Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. [Drogan, O.] Amer Acad Neurol Staff, St Paul, MN USA. [Kissela, B. M.] Univ Cincinnati, Dept Neurol, Cincinnati, OH 45221 USA. [Morgenlander, J. C.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Corboy, J. R.] Univ Colorado, Hlth Sci Ctr, Denver Vet Affairs Med Ctr, Denver, CO USA. [Corboy, J. R.] Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO USA. RP Schuh, LA (reprint author), Henry Ford Hosp, Dept Neurol, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM lschuh@neuro.hfh.edu OI Kissela, Brett/0000-0002-9773-4013 NR 4 TC 15 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 27 PY 2009 VL 72 IS 4 BP E15 EP E20 DI 10.1212/01.wnl.0000342389.60811.ca PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 399CK UT WOS:000262777800029 PM 19171823 ER PT J AU Kanellopoulou, C Muljo, SA Dimitrov, SD Chen, X Colin, C Plath, K Livingston, DM AF Kanellopoulou, Chryssa Muljo, Stefan A. Dimitrov, Stoil D. Chen, Xi Colin, Christian Plath, Kathrin Livingston, David M. TI X chromosome inactivation in the absence of Dicer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE embryonic stem cells; gene silencing; RNA interference; Xist ID EMBRYONIC STEM-CELLS; XIST RNA; ANTISENSE TRANSCRIPTION; DNA METHYLATION; TSIX TRANSCRIPTION; ENDOGENOUS SIRNAS; GENE-EXPRESSION; MOUSE OOCYTES; POLYCOMB; DIFFERENTIATION AB Dicer is central to the RNA interference (RNAi) pathway, because it is required for processing of double-stranded RNA (dsRNA) precursors into small RNA effector molecules. In principle, any long dsRNA could serve as a substrate for Dicer. The X inactive specific transcript (Xist) is an untranslated RNA that is required for dosage compensation in mammals. It coats and silences 1 of the 2 X chromosomes in female cells and initiates a chromosomewide change in chromatin structure that includes the recruitment of Polycomb proteins, but it is largely unknown how Xist RNA mediates these processes. To investigate a potential link between the RNAi pathway and X inactivation, we generated and analyzed Dicer-deficient embryonic stem (ES) cells. In the absence of Dicer, coating by Xist RNA, initiation of silencing, and recruitment of Polycomb proteins occur normally. Dicer ablation had modest effects on the steady-state levels of spliced Xist RNA. Together our data indicate that the RNAi machinery is not essential for the initiation of X inactivation. C1 [Plath, Kathrin] Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. [Kanellopoulou, Chryssa; Dimitrov, Stoil D.; Chen, Xi; Colin, Christian; Livingston, David M.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Muljo, Stefan A.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Muljo, Stefan A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Plath, K (reprint author), Univ Calif Los Angeles, Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA. EM kplath@mednet.ucla.edu; david_livingston@dfci.harvard.edu RI Muljo, Stefan/F-5671-2015; OI Muljo, Stefan/0000-0003-1013-446X; Plath, Kathrin/0000-0001-7796-3372 FU National Institutes of Health (NIH) [AI-064345]; Ruth L. Kirschstein National Research Service Award postdoctoral fellowship [AI-060302]; Claudia Adams Barr Foundation; V and Kimmel Scholar Award; NIH Director's DP2 Award; California Institute for Regenerative Medicine Young Investigator Award; Margaret E. Early Trust FX We thank Barbara Panning for the Xist promoter targeting vector, Klaus Rajewsky for supporting S. A. M. [via National Institutes of Health (NIH) RO1 Grant AI-064345], Dvora Ghitza in K. Rajewsky's laboratory for help with ES cell derivations, and Arie Otte for the Eed antibody. We are grateful to Velmurugan Soundarapandian, Kristine McKinney, and Jean Feunteun for critical reading of this manuscript and all other members of the Livingston laboratory for helpful suggestions. This work was supported by a Ruth L. Kirschstein National Research Service Award postdoctoral fellowship AI-060302 (to S. A. M.), Claudia Adams Barr Foundation (C. K.), V and Kimmel Scholar Award (K. P.), NIH Director's DP2 Award (to K. P.), California Institute for Regenerative Medicine Young Investigator Award and Margaret E. Early Trust (to K. P.). NR 51 TC 41 Z9 43 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 JAN 27 PY 2009 VL 106 IS 4 BP 1122 EP 1127 DI 10.1073/pnas.0812210106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 399XC UT WOS:000262831600031 PM 19164542 ER PT J AU Whitfield-Gabrieli, S Thermenos, HW Milanovic, S Tsuang, MT Faraone, SV McCarley, RW Shenton, ME Green, AI Nieto-Castanon, A LaViolette, P Wojcik, J Gabrieli, JDE Seidman, LJ AF Whitfield-Gabrieli, Susan Thermenos, Heidi W. Milanovic, Snezana Tsuang, Ming T. Faraone, Stephen V. McCarley, Robert W. Shenton, Martha E. Green, Alan I. Nieto-Castanon, Alfonso LaViolette, Peter Wojcik, Joanne Gabrieli, John D. E. Seidman, Larry J. TI Hyperactivity and hyperconnectivity of the default network in schizophrenia and in first-degree relatives of persons with schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE psychopathology; working memory; fMRI; functional connectivity; genetic risk ID FUNCTIONAL CONNECTIVITY; PREFRONTAL CORTEX; WORKING-MEMORY; BRAIN-FUNCTION; GENETIC RISK; YOUNG-ADULTS; MODE; FMRI; ADOLESCENTS; ATTENTION AB We examined the status of the neural network mediating the default mode of brain function, which typically exhibits greater activation during rest than during task, in patients in the early phase of schizophrenia and in young first-degree relatives of persons with schizophrenia. During functional MRI, patients, relatives, and controls alternated between rest and performance of working memory (WM) tasks. As expected, controls exhibited task-related suppression of activation in the default network, including medial prefrontal cortex (MPFC) and posterior cingulate cortex/precuneus. Patients and relatives exhibited significantly reduced task-related suppression in MPFC, and these reductions remained after controlling for performance. Increased task-related MPFC suppression correlated with better WM performance in patients and relatives and with less psychopathology in all 3 groups. For WM task performance, patients and relatives had greater activation in right dorsolateral prefrontal cortex (DLPFC) than controls. During rest and task, patients and relatives exhibited abnormally high functional connectivity within the default network. The magnitudes of default network connectivity during rest and task correlated with psychopathology in the patients. Further, during both rest and task, patients exhibited reduced anticorrelations between MPFC and DLPFC, a region that was hyperactivated by patients and relatives during WM performance. Among patients, the magnitude of MPFC task suppression negatively correlated with default connectivity, suggesting an association between the hyperactivation and hyperconnectivity in schizophrenia. Hyperactivation (reduced task-related suppression) of default regions and hyperconnectivity of the default network may contribute to disturbances of thought in schizophrenia and risk for the illness. C1 [Whitfield-Gabrieli, Susan; Nieto-Castanon, Alfonso; Gabrieli, John D. E.] Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Whitfield-Gabrieli, Susan; Nieto-Castanon, Alfonso; Gabrieli, John D. E.] Poitras Ctr Affect Disorders Res, Cambridge, MA 02139 USA. [Thermenos, Heidi W.; Milanovic, Snezana; McCarley, Robert W.; Wojcik, Joanne; Seidman, Larry J.] Harvard Univ, Massachusetts Mental Hlth Ctr, Beth Israel Deaconess Med Ctr, Dept Psychiat,Med Sch,Publ Psychiat Div, Boston, MA 02215 USA. [Thermenos, Heidi W.; Milanovic, Snezana; LaViolette, Peter; Seidman, Larry J.] Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Thermenos, Heidi W.; Tsuang, Ming T.; Seidman, Larry J.] Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. [Milanovic, Snezana; Seidman, Larry J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. [Tsuang, Ming T.] Univ Calif San Diego, Inst Behav Genet, Dept Psychiat, La Jolla, CA 92093 USA. [Faraone, Stephen V.] SUNY Syracuse, Genet Res Program, Syracuse, NY 13210 USA. [Faraone, Stephen V.] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [McCarley, Robert W.; Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA 02140 USA. [Shenton, Martha E.] Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp, Boston, MA 02115 USA. [Green, Alan I.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03755 USA. [Green, Alan I.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Pharmacol & Toxicol, Hanover, NH 03755 USA. [Thermenos, Heidi W.; Milanovic, Snezana; LaViolette, Peter; Seidman, Larry J.] Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Whitfield-Gabrieli, S (reprint author), Harvard Massachusetts Inst Technol, Div Hlth Sci & Technol, MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. EM swg@mit.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Faraone, Stephen/0000-0002-9217-3982 FU Mental Illness and Neuroscience Discovery Institute; National Association of Research in Schizophrenia and Depression Stone Award; National Institute of Mental Health [MH 43518, MH 65562, MH 63951, R25 MH 60485, MH 40799, MH 50740, MH 62157]; Commonwealth Research Center, Massachusetts Department of Mental Health; Poitras Center for Affective Disorders Research; National Center for Research Resources [P41RR14075] FX We thank the participants and their families and the project staff for their contributions to the study. Staff members included Ariel Brown, Ann Cousins, Lisa Gabel, Anthony Giuliano, Stephen Glatt, Jennifer Koch, Marc Korczykowski, Erica Lee, Nikos Makris, Virna Merino, Elon Mesholam, Raquelle Mesholam-Gately, Shay Moses, Caroline Patterson, Nicole Peace, Sari Reisner, William Stone, and Sharon White. We thank Anthony Wagner and Russell Poldrack for helping in the initial task design. This study was supported by a grant from the Mental Illness and Neuroscience Discovery Institute (to L. J. S.), by the National Association of Research in Schizophrenia and Depression Stone Award (to L. J. S.); by National Institute of Mental Health Grants MH 43518 and MH 65562 (to M. T. T. and L. J. S.), Grant MH 63951 (to L. J. S.), and Grant R25 MH 60485 (to H. W. T., Training Principal Investigator: Ming T. Tsuang, MD, PhD); by the Commonwealth Research Center, Massachusetts Department of Mental Health (L. J. S.); by the Poitras Center for Affective Disorders Research (S. W. G. and J. D. E. G.); and by National Institute of Mental Health Grant (to R. W. M.), Grant MH 50740 (to M. E. S.), and Grant MH 62157 (to A. I. G.). This work was also supported in part by the National Center for Research Resources (Grant P41RR14075). NR 38 TC 576 Z9 590 U1 9 U2 52 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 27 PY 2009 VL 106 IS 4 BP 1279 EP 1284 DI 10.1073/pnas.0809141106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 399XC UT WOS:000262831600058 PM 19164577 ER PT J AU Nardella, C Carracedo, A Alimonti, A Hobbs, RM Clohessy, JG Chen, ZB Egia, A Fornari, A Fiorentino, M Loda, M Kozma, SC Thomas, G Cordon-Cardo, C Pandolfi, PP AF Nardella, Caterina Carracedo, Arkaitz Alimonti, Andrea Hobbs, Robin M. Clohessy, John G. Chen, Zhenbang Egia, Ainara Fornari, Alessandro Fiorentino, Michelangelo Loda, Massimo Kozma, Sara C. Thomas, George Cordon-Cardo, Carlos Pandolfi, Pier Paolo TI Differential Requirement of mTOR in Postmitotic Tissues and Tumorigenesis SO SCIENCE SIGNALING LA English DT Article ID PROSTATE INTRAEPITHELIAL NEOPLASIA; STEM-CELLS; TRANSLATION INITIATION; CANCER; GROWTH; AKT; EXPRESSION; RAPAMYCIN; MODEL; PTEN AB The mammalian target of rapamycin (mTOR) is a crucial effector in a complex signaling network commonly disrupted in cancer. mTOR exerts its multiple functions in the context of two different multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate mTOR through AKT and represents one of the most frequent events in human prostate cancer. We show here that conditional inactivation of mTor in the adult mouse prostate is seemingly inconsequential for this postmitotic tissue. Conversely, inactivation of mTor leads to a marked suppression of Pten loss-induced tumor initiation and progression in the prostate. This suppression is more pronounced than that elicited by the sole pharmacological abrogation of mTORC1. Acute inactivation of mTor in vitro also highlights the differential requirement of mTor function in proliferating and transformed cells. Collectively, our data constitute a strong rationale for developing specific mTOR inhibitors targeting both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency and aberrant mTOR signaling. C1 [Nardella, Caterina; Carracedo, Arkaitz; Alimonti, Andrea; Hobbs, Robin M.; Clohessy, John G.; Chen, Zhenbang; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02115 USA. [Nardella, Caterina; Carracedo, Arkaitz; Alimonti, Andrea; Hobbs, Robin M.; Clohessy, John G.; Chen, Zhenbang; Egia, Ainara; Pandolfi, Pier Paolo] Harvard Univ, Sch Med, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Fornari, Alessandro; Fiorentino, Michelangelo; Loda, Massimo] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fornari, Alessandro] Univ Turin, Molinette Hosp, Dept Biomed Sci & Human Oncol, I-10126 Turin, Italy. [Loda, Massimo] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Kozma, Sara C.; Thomas, George] Univ Cincinnati, Dept Genome Sci, Genome Res Inst, Cincinnati, OH 45237 USA. [Cordon-Cardo, Carlos] Columbia Univ, Dept Pathol, New York, NY 10032 USA. RP Pandolfi, PP (reprint author), Harvard Univ, Sch Med, Canc Genet Program, Beth Israel Deaconess Canc Ctr,Dept Med, Boston, MA 02115 USA. EM ppandolf@bidmc.harvard.edu RI Carracedo, Arkaitz/F-7029-2011; Alimonti, Andrea/J-4150-2012; Thomas, George/K-9235-2014; OI Carracedo, Arkaitz/0000-0001-5957-1260; Thomas, George/0000-0003-3518-8149; Hobbs, Robin/0000-0002-3853-2614 FU NCI NIH HHS [U24 CA083084-10, P30 CA008748, P30 CA08748, R01 CA-82328, R01 CA082328, R01 CA082328-05, R01 CA082328-06, R01 CA082328-07, R01 CA082328-12, R24 CA083084, R24CA83084, U01 CA-84292, U01 CA084292, U01 CA084292-06, U01 CA084292-07, U01 CA084292-08, U01 CA084292-10, U24 CA083084]; NIMHD NIH HHS [R01 MD004038] NR 35 TC 45 Z9 46 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD JAN 27 PY 2009 VL 2 IS 55 AR ra2 DI 10.1126/scisignal.2000189 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 567UH UT WOS:000275471600005 PM 19176516 ER PT J AU Tolboom, H Pouw, RE Izamis, ML Milwid, JM Sharma, N Soto-Gutierrez, A Nahmias, Y Uygun, K Berthiaume, F Yarmush, ML AF Tolboom, Herman Pouw, Roos E. Izamis, Maria-Louisa Milwid, Jack M. Sharma, Nripen Soto-Gutierrez, Alejandro Nahmias, Yaakov Uygun, Korkut Berthiaume, Francois Yarmush, Martin L. TI Recovery of Warm Ischemic Rat Liver Grafts by Normothermic Extracorporeal Perfusion SO TRANSPLANTATION LA English DT Article DE Transplantation; Reperfusion injury; Machine perfusion; Preservation; Preconditioning ID HEART-BEATING DONOR; HYPOTHERMIC MACHINE PERFUSION; EX-VIVO; PRESERVATION SOLUTION; TRANSPLANTATION; POLYSOL; INJURY; DYSFUNCTION; VIABILITY; KIDNEYS AB Liver transplantation is currently the only established treatment of end-stage liver disease, but it is limited by a severe shortage of viable donor livers. Donors after cardiac death (DCD) are an untapped source that could significantly increase the pool of available livers. Preservation of these DCD livers by conventional static cold storage (SCS) is associated with an unacceptable risk of primary nonfunction and delayed graft failure. Normothermic extracorporeal liver perfusion (NELP) has been suggested as an improvement over SCS. Livers recovered from male Lewis rats were subjected to 1 hr of warm ischemia and preserved with 5 hr of SCS or NELP, and transplanted into syngeneic recipients. As additional controls, non-ischemic livers preserved with 6 hr of SCS or NELP and unpreserved ischemic livers were transplanted. After NELP, ischemically damaged livers could be orthotopically transplanted into syngeneic recipients with 92% survival (n = 13) after 4 weeks, which was comparable with control animals that received healthy livers preserved by SCS (n=9) or NELP (n=11) for 6 hr. On the other hand, animals from ischemia/SCS control group all died within 12 hr postoperatively (n=6). Similarly, animals that received ischemic livers without preservation all died within 24: hr after transplantation (n=6). These results suggest that NELP has the potential to reclaim warm ischemic livers that would not be transplantable otherwise. The rat model in this study is a useful platform to further optimize NELP as a method of recovery and preservation of DCD livers. C1 [Tolboom, Herman; Pouw, Roos E.; Izamis, Maria-Louisa; Milwid, Jack M.; Sharma, Nripen; Soto-Gutierrez, Alejandro; Nahmias, Yaakov; Uygun, Korkut; Berthiaume, Francois; Yarmush, Martin L.] Shriners Hosp Children, Boston, MA 02114 USA. [Tolboom, Herman; Pouw, Roos E.; Izamis, Maria-Louisa; Milwid, Jack M.; Sharma, Nripen; Soto-Gutierrez, Alejandro; Nahmias, Yaakov; Uygun, Korkut; Berthiaume, Francois; Yarmush, Martin L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med,Surg Serv, Boston, MA USA. RP Yarmush, ML (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. EM ireis@sbi.org RI Nahmias, Yaakov/H-4725-2013; OI Nahmias, Yaakov/0000-0002-6051-616X; Pouw, Roos/0000-0002-4707-1186 FU National Institutes of Health [R01 DK43371, R01 DK59766, K99 DK080942]; Shriners Hospitals for Children [8450, 8460, 8490]; Harvard University William F. Milton Fund FX This work was supported by the National Institutes of Health(R01 DK43371, R01 DK59766, and K99 DK080942), the Shriners Hospitals for Children (Grants 8450, 8460, and 8490), and the Harvard University William F. Milton Fund. NR 40 TC 43 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 27 PY 2009 VL 87 IS 2 BP 170 EP 177 DI 10.1097/TP.0b013e318192df6b PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 399AU UT WOS:000262773600004 PM 19155970 ER PT J AU Eliassen, AH Chen, WY Spiegelman, D Willett, WC Hunter, DJ Hankinson, SE AF Eliassen, A. Heather Chen, Wendy Y. Spiegelman, Donna Willett, Walter C. Hunter, David J. Hankinson, Susan E. TI Use of Aspirin, Other Nonsteroidal Anti-inflammatory Drugs, and Acetaminophen and Risk of Breast Cancer Among Premenopausal Women in the Nurses' Health Study II SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE-RECEPTOR STATUS; SERVICES-TASK-FORCE; PRIMARY PREVENTION; COLORECTAL-CANCER; PROSPECTIVE COHORT; COX-2 INHIBITORS; GENE-EXPRESSION; TUMOR CELLS; ASSOCIATION; CYCLOOXYGENASE AB Background: The use of aspirin and other nonsteroidal anti-inflammatory drugs ( NSAIDs) is widespread for treatment of common symptoms such as headaches, muscular pain, and inflammation. In addition, the chemopreventive use of NSAIDs is increasingly common for heart disease and colon cancer. Evidence of a protective association with breast cancer risk has been inconsistent, and few data exist for premenopausal women. Methods: We assessed the associations for use of aspirin, other NSAIDs, and acetaminophen with breast cancer risk among premenopausal women in the prospective Nurses' Health Study II. In total, 112 292 women, aged 25 to 42 years and free of cancer in 1989, were followed up until June 2003. Multivariate relative risks and 95% confidence intervals were calculated by Cox proportional hazards models, adjusting for age and other important breast cancer risk factors. Results: Overall, 1345 cases of invasive premenopausal breast cancer were documented. Regular use of aspirin (>= 2 times per week) was not significantly associated with breast cancer risk ( relative risk, 1.07; 95% confidence interval, 0.89-1.29). Regular use of either non-aspirin NSAIDs or acetaminophen also was not consistently associated with breast cancer risk. Results did not vary by frequency ( days per week), dose ( tablets per week), or duration of use. Furthermore, associations with each drug category did not vary substantially by estrogen and progesterone receptor status of the tumor. Conclusion: These data suggest that the use of aspirin, other NSAIDs, and acetaminophen is not associated with a reduced risk of breast cancer among premenopausal women. C1 [Eliassen, A. Heather; Chen, Wendy Y.; Willett, Walter C.; Hunter, David J.; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Eliassen, A. Heather; Spiegelman, Donna; Hunter, David J.; Hankinson, Susan E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chen, Wendy Y.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Eliassen, AH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Long Wood Ave, Boston, MA 02115 USA. EM heather.eliassen@channing.harvard.edu FU National Cancer Institute [CA50385, R25 CA098566-02]; R25 CA098566-02 FX This study was supported by research grant CA50385 from the National Cancer Institute. Dr Eliassen was supported by Cancer Education and Career Development Grant R25 CA098566-02 from the National Cancer Institute. NR 43 TC 25 Z9 25 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 26 PY 2009 VL 169 IS 2 BP 115 EP 121 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 399MB UT WOS:000262802900003 PM 19171806 ER PT J AU Martin, TM Bye, L Modi, N Stanford, MR Vaughan, R Smith, JR Wade, NK Mackensen, F Suhler, EB Rosenbaum, JT Wallace, GR AF Martin, Tammy M. Bye, Louise Modi, Neil Stanford, Miles R. Vaughan, Robert Smith, Justine R. Wade, N. Kevin Mackensen, Friederike Suhler, Eric B. Rosenbaum, James T. Wallace, Graham R. TI Genotype analysis of polymorphisms in autoimmune susceptibility genes, CTLA-4 and PTPN22, in an acute anterior uveitis cohort SO MOLECULAR VISION LA English DT Article ID LYMPHOID TYROSINE PHOSPHATASE; ANKYLOSING-SPONDYLITIS; INFLAMMATORY DISEASE; GRAVES-DISEASE; SPONDYLOARTHROPATHIES; ASSOCIATION; MANIFESTATION; INFLIXIMAB; HLA-B27; VARIANT AB Purpose: Acute anterior uveitis (AAU) is the most common form of uveitis and is thought to be autoimmune in nature. Recent studies have described genes that act as master controllers of autoimmunity. Protein tyrosine phosphatase type 22 (PTPN22) and Cytotoxic T lymphocyte antigen-4 (CTLA-4) are two of these genes, and single nucleotide polymorphisms (SNPs) in the genes encoding these molecules have been associated with several autoimmune diseases. In this study we have analyzed SNPs in PTPN22 and CTLA-4 in patients with AAU. Methods: The functional protein tyrosine phosphatase type 22 (PTPN22) SNP (R620W rs2476601, 1858C/T), and two CTLA-4 SNPs (rs5742909, -318C/T and rs231775, 49A/G) were analyzed in 140 patients with AAU and 92 healthy controls by sequence-specific primer-polymerase chain reaction (SSP-PCR). Data was analyzed by chi(2) analysis and Fisher's exact test. Results: There was no significant association between PTPN22 620W, CTLA-4 -318C/T, or CTLA-4 49A/G and AAU. Similarly, there was no association with the three SNPs when patients were classified by race or gender. Finally, there was no association with the presence of ankylosing spondylitis in the patient cohort. Conclusions: The data do not support an association between SNPs in PTPN22 and CTLA-4, genes regarded as genetic master switches of autoimmunity. This raises the issue of the etiology of AAU and the possibility that it should be regarded as an autoinflammatory rather than an autoimmune condition. C1 [Wallace, Graham R.] Univ Birmingham, Birmingham & Midland Eye Ctr, City Hosp, Acad Unit Ophthalmol, Birmingham B18 7QU, W Midlands, England. [Martin, Tammy M.; Smith, Justine R.; Suhler, Eric B.; Rosenbaum, James T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bye, Louise; Modi, Neil; Stanford, Miles R.; Vaughan, Robert] Kings Coll London, London WC2R 2LS, England. [Wade, N. Kevin] Kerrisdale Profess Ctr, Vancouver, BC, Canada. [Mackensen, Friederike] Heidelberg Univ, Heidelberg, Germany. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Wallace, GR (reprint author), Univ Birmingham, Birmingham & Midland Eye Ctr, City Hosp, Acad Unit Ophthalmol, Dudley Rd, Birmingham B18 7QU, W Midlands, England. EM g.r.wallace@bham.ac.uk FU Research to Prevent Blindness; National Institutes of Health [R01-EY-013139]; Birmingham Eye Foundation FX Supported by Research to Prevent Blindness awards to the Casey Eye Institute, and Drs. Martin, Smith and Rosenbaum; and National Institutes of Health R01-EY-013139. The Birmingham Eye Foundation (G. R. Wallace). The authors wish to thank the individuals with uveitis, referring physicians, and the Spondylitis Association of America for their cooperation. We appreciate the expert assistance of Carrie Austin, Trudy Doyle, Kelley Goodwin and Elli Kondeatis in subject enrollment and technical help. NR 28 TC 14 Z9 15 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD JAN 26 PY 2009 VL 15 IS 20-23 BP 208 EP 212 PG 5 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 421NC UT WOS:000264364600001 PM 19180256 ER PT J AU Kiln, T Leitner, JW Adochio, R Draznin, B AF Kiln, Toni Leitner, J. Wayne Adochio, Rebecca Draznin, Boris TI Knockdown of JNK rescues 3T3-L1 adipocytes from insulin resistance induced by mitochondrial dysfunction SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Insulin resistance; Mitochondrial dysfunction; JNK; 3T3-L1 adipocytes ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; TYPE-2 DIABETIC PARENTS; PROTEIN-KINASE-C; SKELETAL-MUSCLE; SERINE PHOSPHORYLATION; LIPID-CONTENT; FATTY-ACIDS; TRIGLYCERIDE; IRS-1; SPECTROSCOPY AB Mitochondrial dysfunction has been linked to etiology of insulin resistance, however the mechanism remains unknown. In this study we investigated whether mitochondrial dysfunction induced by cyanide p-trifluoromethoxyphenyl-hydrazone (FCCP) alters insulin sensitivity in 3T3-L1 adipocytes and which cellular signaling molecules might be involved. Fully differentiated 3T3-L1 adipocytes were treated with 10 mu M FCCP for 1 h, resulting in increased serine-307 phosphorylation of IRS-1 and decreased insulin-stimulated tyrosine phosphorylation, association of p85 alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase) with IRS-1, decreased insulin-stimulated PI 3-kinase activity and H-3-2-deoxyglucose (2DOG) uptake. A partial (46%) knockdown of JNK1 blocked FCCP-induced serine phosphorylation of IRS-1 and restored insulin-stimulated tyrosine phosphorylation of IRS-1, association of p85 alpha subunit of PI 3-kinase with IRS-1. activation of PI 3-kinase, and stimulation of 2DOG uptake. Thus, FCCP-induced mitochondrial dysfunction may cause insulin resistance that is ameliorated by reduction of JNK1 expression. (C) 2008 Elsevier Inc. All rights reserved. C1 [Adochio, Rebecca; Draznin, Boris] Univ Colorado, Denver Sch Med, Dept Med, Aurora, CO 80045 USA. [Leitner, J. Wayne; Draznin, Boris] Univ Colorado, Denver Sch Med, Denver VA Med Ctr, Res Serv, Aurora, CO 80045 USA. [Kiln, Toni] Univ Colorado, Denver Sch Med, Dept Pediat, Aurora, CO 80045 USA. RP Draznin, B (reprint author), Univ Colorado, Denver Sch Med, Dept Med, Mail Stop 8106,12631 E 17th Pl, Aurora, CO 80045 USA. EM Boris.Draznin@ucdenven.edu FU Research Service of the Department of Veterans Affairs FX This work was supported by the Research Service of the Department of Veterans Affairs. NR 32 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X EI 1090-2104 J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 23 PY 2009 VL 378 IS 4 BP 772 EP 776 DI 10.1016/j.bbrc.2008.11.121 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 394LE UT WOS:000262447400017 ER PT J AU Suchankova, G Nelson, LE Gerhart-Hines, Z Kelly, M Gauthier, MS Saha, AK Ido, Y Puigserver, P Ruderman, NB AF Suchankova, Gabriela Nelson, Lauren E. Gerhart-Hines, Zachary Kelly, Meghan Gauthier, Marie-Soleil Saha, Asish K. Ido, Yasuo Puigserver, Pere Ruderman, Neil B. TI Concurrent regulation of AMP-activated protein kinase and SIRT1 in mammalian cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE AMPK; Redox state; SIRT1; Resveratrol ID SACCHAROMYCES-CEREVISIAE; CALORIE RESTRICTION; SKELETAL-MUSCLE; RAT-LIVER; LIFE-SPAN; RESVERATROL; METABOLISM; PGC-1-ALPHA; MECHANISM; SIRTUINS AB We examined in HepG2 cells whether glucose-induced changes in AMP-activated protein kinase (AMPK) activity could be mediated by SIRT1, an NAD(+)-dependent histone/protein deacetylase that has been linked to the increase in longevity caused by caloric restriction. Incubation with 25 vs. 5 mM glucose for 6 h concurrently diminished the phosphorylation of AMPK (Thr 172) and ACC (Ser 79), increased lactate release, and decreased the abundance and activity of SIRT1. In contrast, incubation with pyruvate (0.1 and 1 mM) for 2 h increased AMPK phosphorylation and SIRT1 abundance and activity. The putative SIRT1 activators resveratrol and quercetin also increased AMPK phosphorylation. None of the tested compounds (low or high glucose, pyruvate, and resveratrol) significantly altered the AMP/ATP ratio. Collectively, these findings raise the possibility that glucose-induced changes in AMPK are linked to alterations in SIRT1 abundance and activity and possibly cellular redox state. (C) 2008 Elsevier Inc. All rights reserved. C1 [Suchankova, Gabriela; Nelson, Lauren E.; Kelly, Meghan; Gauthier, Marie-Soleil; Saha, Asish K.; Ido, Yasuo; Ruderman, Neil B.] Boston Med Ctr, Endocrinol Sect, Boston, MA 02118 USA. [Suchankova, Gabriela; Nelson, Lauren E.; Kelly, Meghan; Gauthier, Marie-Soleil; Saha, Asish K.; Ido, Yasuo; Ruderman, Neil B.] Boston Med Ctr, Dept Med, Boston, MA 02118 USA. [Suchankova, Gabriela; Nelson, Lauren E.; Kelly, Meghan; Gauthier, Marie-Soleil; Saha, Asish K.; Ido, Yasuo; Ruderman, Neil B.] Boston Med Ctr, Dept Physiol, Boston, MA 02118 USA. [Suchankova, Gabriela; Nelson, Lauren E.; Kelly, Meghan; Gauthier, Marie-Soleil; Saha, Asish K.; Ido, Yasuo; Ruderman, Neil B.] Boston Med Ctr, Dept Biochem, Boston, MA 02118 USA. [Gerhart-Hines, Zachary; Puigserver, Pere] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerhart-Hines, Zachary; Puigserver, Pere] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Ruderman, NB (reprint author), Boston Med Ctr, Endocrinol Sect, Boston, MA 02118 USA. EM nrude@bu.edu OI Saha, Asish/0000-0003-1001-5110; Ruderman, Neil/0000-0002-6589-6587 FU NIH [R01 DK19514, P01 HL08758, DK67509, T32DK07201-31]; ADA; NIDDK [F30DK082136] FX This work was supported by NIH Grants R01 DK19514, P01 HL08758, and DK67509 (N.R.). G.S. was the recipient of a mentor based grant from the ADA (N.R.). L.N. was supported by NIH Training Grant T32DK07201-31 and a Fellowship Award F30DK082136 from NIDDK. The authors would like to thank Jose Cacicedo and Fan Lan for helpful comments and technical advice. NR 29 TC 100 Z9 106 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 23 PY 2009 VL 378 IS 4 BP 836 EP 841 DI 10.1016/j.bbrc.2008.11.130 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 394LE UT WOS:000262447400029 PM 19071085 ER PT J AU Lee, JW Siegel, SM Oaklander, AL AF Lee, J. W. Siegel, S. M. Oaklander, A. L. TI EFFECTS OF DISTAL NERVE INJURIES ON DORSAL-HORN NEURONS AND GLIA: RELATIONSHIPS BETWEEN LESION SIZE AND MECHANICAL HYPERALGESIA SO NEUROSCIENCE LA English DT Article DE GABA; astrocyte; chronic pain; rat; axotomy; spinal cord ID REGIONAL PAIN SYNDROME; CHRONIC CONSTRICTION INJURY; RAT SCIATIC-NERVE; SPINAL-CORD; PERIPHERAL-NERVE; NEUROPATHIC PAIN; ANIMAL-MODEL; GABA-IMMUNOREACTIVITY; THERMAL HYPERALGESIA; SELECTIVE LOSS AB Penetrating limb injuries are common and usually heal without long-lasting effects, even when nerves are cut. However, rare nerve-injury patients develop prolonged and disabling chronic pain (neuralgia). When pain severity is disproportionate to severity of the inciting injury, physicians and insurers may suspect exaggeration and limit care or benefits, although the nature of the relationship between lesion-size and the development and persistence of neuralgia remains largely unknown. We compared cellular changes in the spinal dorsal-horn (the initial CNS pain-processing area) after partial or total tibial-nerve axotomies in male Sprague-Dawley rats to determine if these changes are proportional to the numbers of peripheral axons cut. Unoperated rats provided controls. Plantar hind-paw responses to touch, pin, and cold were quantitated bilaterally to identity hyperalgesic rats. We also compared data from nerve-injured rats with or without hyperalgesic responses to mechanical hind-paw stimulation to evaluate concordance between pain behaviors and dorsal-horn cellular changes. Hyperalgesia was no less prevalent or severe after partial than after total axotomy. L. spinal-cord sections from rats killed 7 days postoperatively were labeled for markers of primary afferents (substance P calcitonin gene-related peptide isolectin B4, gamma aminobutyric acid, and glial fibrillary acidic protein), then labeled cells were stereologically quantitated in somatotopically defined dorsal-horn regions. Total axotomy reduced markers of primary afferents more than partial axotomy. In contrast, GABA-immunoreactive profiles were similarly reduced after both lesions, and in rats with sensory loss versus hyperalgesia. Numbers of GFAP-immunoreactive astrocytes increased independently of lesion size and pain status. Small nerve injuries can thus have magnified and disproportionate effects on dorsal-horn neurons and glia, perhaps providing a biological correlate for the disproportionate pain of post-traumatic neuralgias (including complex regional pain syndrome-I) that follow seemingly minor nerve injuries. However, the presence of similar dorsal-horn changes in rats without pain behaviors suggests that not all transcellular responses to axotomy are pain-specific. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Oaklander, A. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Oaklander, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 275 Charles St,Warren 310, Boston, MA 02114 USA. EM aoaklander@partners.org FU Public Health Service [R01NS42866, K24NS059892, P30 EY 12196]; Beatrice and Roy Backus Foundation; RSDSA Rachel Tobias Young Investigator Award FX The technical assistance of Li Zheng, Ralph Gott, YangFeng Li, and statistical support of Dr. Yuchiao Chang are gratefully acknowledged. Supported in part by the Public Health Service (R01NS42866, K24NS059892, P30 EY 12196), the Beatrice and Roy Backus Foundation, and the RSDSA Rachel Tobias Young Investigator Award. Presented to the Society for Neuroscience in abstract form. NR 46 TC 15 Z9 16 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD JAN 23 PY 2009 VL 158 IS 2 BP 904 EP 914 DI 10.1016/j.neuroscience.2008.10.010 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 401RP UT WOS:000262959900053 PM 18992304 ER PT J AU Sabado, RL Kavanagh, DG Kaufmann, DE Fru, K Babcock, E Rosenberg, E Walker, B Lifson, J Bhardwaj, N Larsson, M AF Sabado, Rachel Lubong Kavanagh, Daniel G. Kaufmann, Daniel E. Fru, Karlhans Babcock, Ethan Rosenberg, Eric Walker, Bruce Lifson, Jeffrey Bhardwaj, Nina Larsson, Marie TI In Vitro Priming Recapitulates In Vivo HIV-1 Specific T Cell Responses, Revealing Rapid Loss of Virus Reactive CD4(+) T Cells in Acute HIV-1 Infection SO PLOS ONE LA English DT Article AB Background: The requirements for priming of HIV-specific T cell responses initially seen in infected individuals remain to be defined. Activation of T cell responses in lymph nodes requires cell-cell contact between T cells and DCs, which can give concurrent activation of T cells and HIV transmission. Methodology: The study aim was to establish whether DCs pulsed with HIV-1 could prime HIV-specific T cell responses and to characterize these responses. Both infectious and aldrithiol-2 inactivated noninfectious HIV-1 were compared to establish efficiencies in priming and the type of responses elicited. Findings: Our findings show that both infectious and inactivated HIV-1 pulsed DCs can prime HIV-specific responses from naive T cells. Responses included several CD4(+) and CD8(+) T cell epitopes shown to be recognized in vivo by acutely and chronically infected individuals and some CD4(+) T cell epitopes not identified previously. Follow up studies of acute and recent HIV infected samples revealed that these latter epitopes are among the earliest recognized in vivo, but the responses are lost rapidly, presumably through activation-induced general CD4(+) T cell depletion which renders the newly activated HIV-specific CD4(+) T cells prime targets for elimination. Conclusion: Our studies highlight the ability of DCs to efficiently prime naive T cells and induce a broad repertoire of HIV-specific responses and also provide valuable insights to the pathogenesis of HIV-1 infection in vivo. C1 [Babcock, Ethan; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10003 USA. [Kavanagh, Daniel G.; Kaufmann, Daniel E.; Rosenberg, Eric; Walker, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, PARC, Charlestown, MA USA. [Lifson, Jeffrey] NCI, NIH, SAIC Fredrick Inc, Frederick, MD USA. [Fru, Karlhans; Larsson, Marie] Linkoping Univ, Dept Clin & Expt Med, S-58183 Linkoping, Sweden. RP Sabado, RL (reprint author), NYU, Sch Med, New York, NY 10003 USA. EM marla@imk.liu.se FU The Swedish Research Council; The Swedish, Physicians against AIDS research Foundation; The Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University hospital research Fund; C ALF; The Swedish Society of Medicine; Emerald Foundation; Burroughs Wellcome; Elizabeth Glaser Pediatric AIDS Foundation; Bill and Melinda Gates Foundation; Center for HIV/AIDS Vaccine Initiative (CHAVI); NIH [AI52731, AI55274, AI61684, AI57127, AI44628]; National Cancer Institute, National Institutes of Health [N01-CO-12400] FX All below funders have provided funding for performing this study. This work has been supported by grants through: ML: AI52731, The Swedish Research Council, The Swedish, Physicians against AIDS research Foundation, The Swedish International Development Cooperation Agency; SIDA SARC, VINNMER for Vinnova, Linkoping University hospital research Fund, C ALF, and The Swedish Society of Medicine. NB: Emerald Foundation, Burroughs Wellcome, Elizabeth Glaser Pediatric AIDS Foundation, Bill and Melinda Gates Foundation and the Center for HIV/AIDS Vaccine Initiative (CHAVI) and NIH grants AI52731, AI55274, AI61684, AI57127, and AI44628. JL: with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views of policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 63 TC 24 Z9 24 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JAN 23 PY 2009 VL 4 IS 1 AR e4256 DI 10.1371/journal.pone.0004256 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437JD UT WOS:000265482400004 ER PT J AU Okawa, Y Hideshima, T Steed, P Vallet, S Hall, S Huang, K Rice, J Barabasz, A Foley, B Ikeda, H Raje, N Kiziltepe, T Yasui, H Enatsu, S Anderson, KC AF Okawa, Yutaka Hideshima, Teru Steed, Paul Vallet, Sonia Hall, Steven Huang, Ken Rice, John Barabasz, Amy Foley, Brianna Ikeda, Hiroshi Raje, Noopur Kiziltepe, Tanyel Yasui, Hiroshi Enatsu, Sotaro Anderson, Kenneth C. TI SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK SO BLOOD LA English DT Article ID NITRIC-OXIDE SYNTHASE; SMALL-MOLECULE INHIBITOR; ANTITUMOR-ACTIVITY; DRUG-RESISTANCE; SOLID TUMORS; PHASE-I; ACTIVATION; HEAT-SHOCK-PROTEIN-90; BONE; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN AB Heat-shock protein 90 (Hsp90) acts as a molecular chaperone required for maintaining the conformational stability of client proteins regulating cell proliferation, survival, and apoptosis. Here we investigate the biologic significance of Hsp90 inhibition in multiple myeloma (MM) and other hematologic tumors using an orally available novel small molecule inhibitor SNX-2112, which exhibits unique activities relative to 17-allyamino-17-demethoxy-geldanamycin (17-AAG). SNX-2112 triggers growth inhibition and is more potent than 17-AAG against MM and other malignancies. It induces apoptosis via caspase-8, -9, -3, and poly (ADP-ribose) polymerase cleavage. SNX-2112 inhibits cytokine-inducedAkt and extracellular signal-related kinase (ERK) activation and also overcomes the growth advantages conferred by interleukin-6, insulin-like growth factor-1, and bone marrow stromal cells. Importantly, SNX-2112 inhibits tube formation by human umbilical vein endothelial cells via abrogation of eNOS/Akt pathway and markedly inhibits osteoclast formation via down-regulation of ERK/c-fos and PU.1. Finally, SNX-2112, delivered by its prodrug SNX-5422, inhibits MM cell growth and prolongs survival in a xenograft murine model. Our results indicate that blockade of Hsp90 by SNX-2112 not only inhibitsMMcell growth but also acts in the bone marrow microenvironment to block angiogenesis and osteoclastogenesis. Taken together, our data provide the framework for clinical studies of SNX-2112 to improve patient outcome in MM and other hematologic malignancies. (Blood. 2009; 113:846-855) C1 [Okawa, Yutaka; Hideshima, Teru; Vallet, Sonia; Ikeda, Hiroshi; Raje, Noopur; Kiziltepe, Tanyel; Yasui, Hiroshi; Enatsu, Sotaro; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Okawa, Yutaka; Hideshima, Teru; Vallet, Sonia; Ikeda, Hiroshi; Raje, Noopur; Kiziltepe, Tanyel; Yasui, Hiroshi; Enatsu, Sotaro; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. [Okawa, Yutaka] Jikei Univ, Sch Med, Dept Internal Med, Div Clin Oncol & Hematol, Tokyo, Japan. [Steed, Paul; Hall, Steven; Huang, Ken; Rice, John; Barabasz, Amy; Foley, Brianna] Serenex, Durham, NC USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, LeBow Inst Myeloma Therapeut, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM yutaka_okawa@dfci.harvard.edu; kenneth_anderson@dfci.harvard.edu FU National Institutes of Health [IP50 CA10070-01, PO-1 CA78378, RO-1 CA50947]; Multiple Myeloma Research Foundation; LeBow Family Fund FX This study was supported by the National Institutes of Health Specialized Programs of Research Excellence (grants IP50 CA10070-01, PO-1 CA78378, and RO-1 CA50947), the Multiple Myeloma Research Foundation (T.H., K.C.A.), and the LeBow Family Fund to Cure Myeloma (K.C.A.). NR 50 TC 120 Z9 123 U1 1 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 22 PY 2009 VL 113 IS 4 BP 846 EP 855 DI 10.1182/blood-2008-04-151928 PG 10 WC Hematology SC Hematology GA 397EW UT WOS:000262646200013 PM 18948577 ER PT J AU Johnson, AD O'Donnell, CJ AF Johnson, Andrew D. O'Donnell, Christopher J. TI An Open Access Database of Genome-wide Association Results SO BMC MEDICAL GENETICS LA English DT Article ID CANDIDATE GENES; SUSCEPTIBILITY; DISEASE; POLYMORPHISMS; GENETICS; HAPMAP; OAS-1; LOCI; SNPS; TOOL AB Background: The number of genome-wide association studies (GWAS) is growing rapidly leading to the discovery and replication of many new disease loci. Combining results from multiple GWAS datasets may potentially strengthen previous conclusions and suggest new disease loci, pathways or pleiotropic genes. However, no database or centralized resource currently exists that contains anywhere near the full scope of GWAS results. Methods: We collected available results from 118 GWAS articles into a database of 56,411 significant SNP-phenotype associations and accompanying information, making this database freely available here. In doing so, we met and describe here a number of challenges to creating an open access database of GWAS results. Through preliminary analyses and characterization of available GWAS, we demonstrate the potential to gain new insights by querying a database across GWAS. Results: Using a genomic bin-based density analysis to search for highly associated regions of the genome, positive control loci (e. g., MHC loci) were detected with high sensitivity. Likewise, an analysis of highly repeated SNPs across GWAS identified replicated loci (e. g., APOE, LPL). At the same time we identified novel, highly suggestive loci for a variety of traits that did not meet genome-wide significant thresholds in prior analyses, in some cases with strong support from the primary medical genetics literature (SLC16A7, CSMD1, OAS1), suggesting these genes merit further study. Additional adjustment for linkage disequilibrium within most regions with a high density of GWAS associations did not materially alter our findings. Having a centralized database with standardized gene annotation also allowed us to examine the representation of functional gene categories (gene ontologies) containing one or more associations among top GWAS results. Genes relating to cell adhesion functions were highly over-represented among significant associations (p < 4.6 x 10(-14)), a finding which was not perturbed by a sensitivity analysis. Conclusion: We provide access to a full gene-annotated GWAS database which could be used for further querying, analyses or integration with other genomic information. We make a number of general observations. Of reported associated SNPs, 40% lie within the boundaries of a RefSeq gene and 68% are within 60 kb of one, indicating a bias toward gene-centricity in the findings. We found considerable heterogeneity in information available from GWAS suggesting the wider community could benefit from standardization and centralization of results reporting. C1 [Johnson, Andrew D.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP O'Donnell, CJ (reprint author), Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. EM johnsonad2@nhlbi.nih.gov; odonnellc@nhlbi.nih.gov RI Johnson, Andrew/G-6520-2013 FU NIH/NHLBI [N01-HC-25195] FX We would like to acknowledge the many thousands of international, anonymous participants of the GWAS included here for their contribution to human genetics. We thank Wolfgang Lieb, MD and Raghava Velagaleti, MD for their assistance as QC reviewers of the dataset. ADJ was supported by an intramural NHLBI IRTA fellowship award. This project was supported in part by the NHLBI's Framingham Heart Study (NIH/NHLBI Contract N01-HC-25195). We thank Teri Manolio, MD PhD for her comments on the manuscript. NR 33 TC 173 Z9 180 U1 2 U2 28 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JAN 22 PY 2009 VL 10 AR 6 DI 10.1186/1471-2350-10-6 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 418MS UT WOS:000264152900002 PM 19161620 ER PT J AU Muehlberger, N Schwarzer, R Lettmeier, B Sroczynski, G Zeuzem, S Siebert, U AF Muehlberger, Nikolai Schwarzer, Ruth Lettmeier, Beate Sroczynski, Gaby Zeuzem, Stefan Siebert, Uwe TI IHCV-related burden of disease in Europe: a systematic assessment of incidence, prevalence, morbidity, and mortality SO BMC PUBLIC HEALTH LA English DT Article ID CHRONIC HEPATITIS-C; QUALITY-OF-LIFE; VIRUS-INFECTION; COMBINATION THERAPY; PLUS RIBAVIRIN; LIVER-DISEASE; GLOBAL EPIDEMIOLOGY; UNITED-STATES; HEALTH; POPULATION AB Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods: Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results: HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3-8.8 million people (1.1-1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion: Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission. C1 [Zeuzem, Stefan] Univ Frankfurt, Dept Internal Med Gastroenterol Hepatol Pneumol &, Frankfurt, Germany. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Sch Med, Dept Hlth Policy & Management, Program Hlth Decis Sci, Boston, MA USA. EM nikolai.muehlberger@umit.at; ruth.schwarzer@umit.at; beate.lettmeier@umit.at; gaby.sroczynski@umit.at; zeuzem@em.uni-frankfurt.de; uwe.siebert@umit.at NR 90 TC 2 Z9 2 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD JAN 22 PY 2009 VL 9 AR 34 DI 10.1186/1471-2458-9-34 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 420KG UT WOS:000264288100001 ER PT J AU Wu, YC Navarro, F Lal, A Basar, E Pandey, RK Manoharan, M Feng, Y Lee, SJ Lieberman, J Palliser, D AF Wu, Yichao Navarro, Francisco Lal, Ashish Basar, Emre Pandey, Rajendra K. Manoharan, Muthiah Feng, Yang Lee, Sandra J. Lieberman, Judy Palliser, Deborah TI Durable Protection from Herpes Simplex Virus-2 Transmission Following Intravaginal Application of siRNAs Targeting Both a Viral and Host Gene SO CELL HOST & MICROBE LA English DT Article ID REPLICATION-DEFECTIVE MUTANT; RECEPTOR-RELATED PROTEIN-1; DNA-BINDING PROTEIN; POLIOVIRUS RECEPTOR; GLYCOPROTEIN-D; IN-VIVO; INFECTION; ENTRY; CELLS; INHIBITION AB A vaginal microbicide should prevent pathogen transmission without disrupting tissue barriers to infection. Ideally, it would not need to be applied immediately before sexual intercourse, when compliance is a problem. Intravaginal administration of small interfering RNA (siRNA) lipoplexes targeting Herpes Simplex Virus Type 2 (HSV-2) genes protects mice from HSV-2. However, protection is short-lived, and the transfection lipid on its own unacceptably enhances transmission. Here, we show that cholesterol-conjugated (chol)-siRNAs without lipid silence gene expression in the vagina without causing inflammation or inducing interferons. A viral siRNA prevents transmission within a day of challenge, whereas an siRNA targeting the HSV-2 receptor nectin-1 protects for a week, but protection is delayed for a few days until the receptor is down-modulated. Combining siRNAs targeting a viral and host gene protects mice from HSV-2 for a week, irrespective of the time of challenge. Therefore, intravaginal siRNAs could provide sustained protection against viral transmission. C1 [Wu, Yichao; Navarro, Francisco; Lal, Ashish; Basar, Emre; Lieberman, Judy; Palliser, Deborah] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Wu, Yichao; Navarro, Francisco; Lal, Ashish; Basar, Emre; Lieberman, Judy; Palliser, Deborah] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Pandey, Rajendra K.; Manoharan, Muthiah] Alnylam Pharmaceut, Cambridge, MA 02142 USA. [Feng, Yang; Lee, Sandra J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Palliser, Deborah] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. EM lieberman@idi.harvard.edu; dpallise@aecom.yu.edu RI Lieberman, Judy/A-2717-2015 FU NIH [AI070302]; amfAR Scholar Award; CFAR [AECOM/MMC 2P30AI051519] FX This work was supported by NIH grant AI070302 (J.L.), an amfAR Scholar Award (D.P.), and a CFAR pilot project grant AECOM/MMC 2P30AI051519 (D. P.). NR 35 TC 57 Z9 58 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD JAN 22 PY 2009 VL 5 IS 1 BP 84 EP 94 DI 10.1016/j.chom.2008.12.003 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 400RG UT WOS:000262885700011 PM 19154990 ER PT J AU Holick, MF Lim, R Dighe, AS Carroll, BC Rosenberg, ES Sherry, NA AF Holick, Michael F. Lim, Ruth Dighe, Anand S. Carroll, Bronwen C. Rosenberg, Eric S. Sherry, Nicole A. TI A 9-Month-Old Boy with Seizures Rickets due to vitamin D deficiency. Iron-deficiency anemia. Severe protein-calorie malnutrition. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NUTRITIONAL RICKETS; INFANTS; CHILDREN; SUPPLEMENTATION; RISK C1 [Holick, Michael F.] Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. [Holick, Michael F.] Boston Univ, Med Ctr, Dept Endocrinol, Boston, MA USA. [Holick, Michael F.] Boston Univ, Med Ctr, Dept Diabet, Boston, MA USA. [Lim, Ruth] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Dighe, Anand S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Holick, MF (reprint author), Boston Univ, Med Ctr, Dept Med, Boston, MA 02118 USA. FU Novartis; Bayer; Merck; Procter Gamble; Quest Diagnostics; National Dairy Council; UV Foundation FX Dr. Holick reports receiving consulting fees or serving on the paid advisory boards of Novartis, Bayer, Merck, Procter & Gamble, and Quest Diagnostics; lecture fees from Merck, Procter & Gamble, and Novartis; and grant support from the National Dairy Council and the UV Foundation. No other potential conflict of interest relevant to this article was reported. We thank Dr. Ian Michelow, the infectious-disease consultant on the case, and Dr. Nicole Sherry for their contributions to the development of this case study. NR 17 TC 13 Z9 13 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 JAN 22 PY 2009 VL 360 IS 4 BP 398 EP 407 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 395JH UT WOS:000262519900012 PM 19164191 ER PT J AU Bohn, P Clough, A Hazen, E Heering, A Rohlf, J Freeman, J Los, S Cascio, E Kuleshov, S Musienko, Y Piemonte, C AF Bohn, P. Clough, A. Hazen, E. Heering, A. Rohlf, J. Freeman, J. Los, S. Cascio, E. Kuleshov, S. Musienko, Y. Piemonte, C. TI Radiation damage studies of silicon photomultipliers SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE Silicon PM; SiPM; MRS; APD; HPD; Photodetector AB We report on the measurement of the radiation hardness of silicon photomultipliers (SiPMs) manufactured by Fondazione Bruno Kessler in Italy (1 and 6.2 mm(2)), Center of Perspective Technology and Apparatus in Russia (1 and 4.4 mm(2)), and Hamamatsu Corporation in Japan (1 mm(2)). The SiPMs were irradiated using a beam of 212 MeV protons at Massachusetts General Hospital, receiving fluences of up to 3 x 10(10) protons per cm(2) with the SiPMs at operating voltage. Leakage currents were read continuously during the irradiation. The delivery of the protons was paused periodically to record scope traces in response to calibrated light pulses to monitor the gains, photon detection efficiencies. and dark counts of the SiPMs. The leakage current and dark noise are found to increase with fluence. The leakage current is found to be proportional to the mean square deviation of the noise distribution, indicating the dark counts are due to increased random individual pixel activation, while SiPMs remain fully functional as photon detectors. The SiPMs are found to anneal at room temperature with a reduction in the leakage current by a factor of 2 in about 100 days. (c) 2008 Elsevier B.V. All rights reserved. C1 [Bohn, P.; Clough, A.; Hazen, E.; Heering, A.; Rohlf, J.] Boston Univ, Dept Phys, Boston, MA 02212 USA. [Freeman, J.; Los, S.] Fermilab Natl Accelerator Lab, Batavia, IL 60510 USA. [Cascio, E.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Kuleshov, S.] Inst Theoret & Expt Phys, Moscow 117259, Russia. [Musienko, Y.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Piemonte, C.] Fdn Bruno Kessler, I-38050 Trento, Italy. [Kuleshov, S.] Univ Tecn Federico Santa Maria, Dept Fis, Valparaiso, Chile. [Kuleshov, S.] Univ Tecn Federico Santa Maria, Ctr Estudios Subatom, Valparaiso, Chile. RP Rohlf, J (reprint author), Boston Univ, Dept Phys, Boston, MA 02212 USA. EM rohlf@bu.edu RI Kuleshov, Sergey/D-9940-2013 OI Kuleshov, Sergey/0000-0002-3065-326X FU U.S. National Science Foundation FX We acknowledge support of the U.S. National Science Foundation. NR 12 TC 13 Z9 13 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD JAN 21 PY 2009 VL 598 IS 3 BP 722 EP 736 DI 10.1016/j.nima.2008.10.027 PG 15 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 399UT UT WOS:000262825500010 ER PT J AU Mesquita, RC Huppert, TJ Boas, DA AF Mesquita, R. C. Huppert, T. J. Boas, D. A. TI Exploring neuro-vascular and neuro-metabolic coupling in rat somatosensory cortex SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BRAIN ELECTRICAL-ACTIVITY; CEREBRAL BLOOD-FLOW; HEMODYNAMIC-RESPONSE; OXYGEN-METABOLISM; BALLOON MODEL; ACTIVATION; FMRI; SPECTROSCOPY; DYNAMICS; DELIVERY AB The existence of a coupling between changes in neuronal activity, cerebral blood flow and blood oxygenation is well known. The explicit relationship between these systems, however, is complex and remains a subject of intense research. Here, we use direct electrophysiological recordings to predict blood flow and oxygenation changes measured with optical methods during parametric stimulation applied to the somatosensory cortex in rat brain. Using a multimodal model of the cerebral functional unit, we estimate a neurovascular and a neuro-metabolic transfer function relating the experimentally measured neural responses with the inputs to a vascular model predicting hemodynamic and blood oxygenation changes. We show that our model can accurately predict experimentally measured parametric hemodynamic evoked responses by using a single linear transfer function relationship with a reduced number of state parameters to relate the level of neural activity to evoked cerebral blood flow and oxygen metabolism changes. At the same time, we characterize the metabolic and vascular neural response functions and interpret their physiological significance. C1 [Mesquita, R. C.; Boas, D. A.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Mesquita, R. C.] Univ Estadual Campinas, Inst Phys, BR-13083970 Campinas, SP, Brazil. [Huppert, T. J.] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. RP Mesquita, RC (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM rickson@nmr.mgh.harvard.edu RI Mesquita, Rickson/N-9119-2013; Inst. of Physics, Gleb Wataghin/A-9780-2017 OI Mesquita, Rickson/0000-0003-1945-6713; FU CNPq [140273/2005-0]; CAPES [2860/06-6]; National Institutes of Health [R01-EB002482, R01-EB000790, R01NS051188, P41-RR14075] FX The authors would like to thank Drs Anna Devor, Rob Haslinger, Anders Dale and Roberto Covolan for helpful discussion of this text. RCM acknowledges funding from CNPq and CAPES agencies through 140273/2005-0 and 2860/06-6, respectively. This work was supported by the National Institutes of Health through R01-EB002482, R01-EB000790, R01NS051188 and P41-RR14075. NR 31 TC 6 Z9 6 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 21 PY 2009 VL 54 IS 2 BP 175 EP 185 DI 10.1088/0031-9155/54/2/001 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 393GG UT WOS:000262358700001 PM 19088392 ER PT J AU Eckman, MH Rosand, J Greenberg, SM Gage, BF AF Eckman, Mark H. Rosand, Jonathan Greenberg, Steven M. Gage, Brian F. TI Cost-Effectiveness of Using Pharmacogenetic Information in Warfarin Dosing for Patients With Nonvalvular Atrial Fibrillation SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ORAL ANTICOAGULANT TREATMENT; QUALITY-OF-LIFE; BLEEDING COMPLICATIONS; RISK-FACTORS; ANTITHROMBOTIC THERAPY; ORTHOPEDIC PATIENTS; INTRACEREBRAL HEMORRHAGE; INTRACRANIAL HEMORRHAGE; CYTOCHROME-P450 CYP2C9; DECISION-ANALYSIS AB Background: Variants in genes involved in warfarin metabolism and sensitivity affect individual warfarin requirements and the risk for bleeding. Testing for these variant alleles might allow more personalized dosing of warfarin during the induction phase. In 2007, the U. S. Food and Drug Administration changed the labeling for warfarin (Coumadin, Bristol-Myers Squibb, Princeton, New Jersey), suggesting that clinicians consider genetic testing before initiating therapy. Objective: To examine the cost-effectiveness of genotype-guided dosing versus standard induction of warfarin therapy for patients with nonvalvular atrial fibrillation. Design: Markov state transition decision model. Data Sources: MEDLINE searches and bibliographies from relevant articles of literature published in English. Target Population: Outpatients or inpatients requiring initiation of warfarin therapy. The base case was a man age 69 years with newly diagnosed nonvalvular atrial fibrillation and no contraindications to warfarin therapy. Time Horizon: Lifetime. Perspective: Societal. Intervention: Genotype-guided dosing consisting of genotyping for CYP2C9*2, CYP2C9*3, and/or VKORC1 versus standard warfarin induction. Outcome Measures: Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were in 2007 U. S. dollars. Results: In the base case, genotype-guided dosing resulted in better outcomes, but at a relatively high cost. Overall, the marginal cost-effectiveness of testing exceeded $170 000 per QALY. On the basis of current data and cost of testing (about $ 400), there is only a 10% chance that genotype-guided dosing is likely to be cost-effective (that is, <$50 000 per QALY). Sensitivity analyses revealed that for genetic testing to cost less than $ 50 000 per QALY, it would have to be restricted to patients at high risk for hemorrhage or meet the following optimistic criteria: prevent greater than 32% of major bleeding events, be available within 24 hours, and cost less than $200. Limitation: Few published studies describe the effect of genotype-guided dosing on major bleeding events, and although these studies show a trend toward decreased bleeding, the results are not statistically significant. Conclusion: Warfarin-related genotyping is unlikely to be cost-effective for typical patients with nonvalvular atrial fibrillation, but may be cost-effective in patients at high risk for hemorrhage who are starting warfarin therapy. C1 [Eckman, Mark H.] Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, St Louis, MO USA. RP Eckman, MH (reprint author), Univ Cincinnati, Med Ctr, POB 670535, Cincinnati, OH 45267 USA. EM mark.eckman@uc.edu FU The National Institute of Diabetes and Digestive and Kidney Diseases;; National Heart, Lung, and Blood Institute;; Foundation for Informed Medical Decision Making; National Institutes of Neurological Disorders and Stroke; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; American Heart Association FX The National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; Foundation for Informed Medical Decision Making; National Institutes of Neurological Disorders and Stroke; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke; and American Heart Association. NR 76 TC 177 Z9 180 U1 0 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 20 PY 2009 VL 150 IS 2 BP 73 EP U31 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 397ID UT WOS:000262655200002 PM 19153410 ER PT J AU Vetter, ML Cardillo, S Rickels, MR Iqbal, N AF Vetter, Marion L. Cardillo, Serena Rickels, Michael R. Iqbal, Nayyar TI Narrative Review: Effect of Bariatric Surgery on Type 2 Diabetes Mellitus SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID GASTRIC BYPASS-SURGERY; GLUCAGON-LIKE PEPTIDE-1; MORBIDLY OBESE SUBJECTS; BETA-CELL FUNCTION; INDUCED WEIGHT-LOSS; PLASMA GHRELIN; INHIBITORY POLYPEPTIDE; GLUCOSE-METABOLISM; GUT HORMONE; FOOD-INTAKE AB Bariatric surgery leads to substantial and durable weight reduction. Nearly 30% of patients who undergo bariatric surgery have type 2 diabetes, and for many of them, diabetes resolves after surgery (84% to 98% for bypass procedures and 48% to 68% for restrictive procedures). Glycemic control improves in part because of caloric restriction but also because gut peptide secretion changes. Gut peptides, which mediate the enteroinsular axis, include the incretins glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, as well as ghrelin and peptide YY. Bariatric surgery (particularly bypass procedures) alters secretion of these gut hormones, which results in enhanced insulin secretion and sensitivity. This review discusses the various bariatric procedures and how they alter the enteroinsular axis. Familiarity with these effects can help physicians decide among the different surgical procedures and avoid postoperative hypoglycemia. C1 [Vetter, Marion L.] Hosp Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Vetter, ML (reprint author), Hosp Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, 1 Maloney Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM marion.vetter@uphs.upenn.edu NR 94 TC 97 Z9 104 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 20 PY 2009 VL 150 IS 2 BP 94 EP U54 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 397ID UT WOS:000262655200004 PM 19153412 ER PT J AU Qaseem, A Snow, V Shekelle, P Hopkins, R Owens, DK AF Qaseem, Amir Snow, Vincenza Shekelle, Paul Hopkins, Robert, Jr. Owens, Douglas K. CA Clinical Efficacy Assessment Subco TI Screening for HIV in Health Care Settings: A Guidance Statement From the American College of Physicians and HIV Medicine Association SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; COST-EFFECTIVENESS; EMERGENCY-DEPARTMENT; RECOMMENDATIONS; TRANSMISSION; INFECTION; TESTS AB Description: The American College of Physicians (ACP) developed this guidance statement to present the available evidence on screening for HIV in health care settings. Methods: This guidance statement is derived from an appraisal of available guidelines on screening for HIV. Authors searched the National Guideline Clearinghouse to identify guidelines on screening for HIV in the United States and used the AGREE ( Appraisal of Guidelines Research and Evaluation) instrument to evaluate guidelines from the U. S. Preventive Services Task Force and the Centers for Disease Control and Prevention. Guidance Statement 1: ACP recommends that clinicians adopt routine screening for HIV and encourage patients to be tested. Guidance Statement 2: ACP recommends that clinicians determine the need for repeat screening on an individual basis. C1 [Qaseem, Amir] Amer Coll Physicians, Philadelphia, PA 19106 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. RAND Corp, Santa Monica, CA USA. Univ Arkansas, Little Rock, AR 72204 USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. Stanford Univ, Stanford, CA 94305 USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org FU ACP operating budget FX Financial support for the development of this guideline comes exclusively from the ACP operating budget. NR 42 TC 90 Z9 90 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 20 PY 2009 VL 150 IS 2 BP 125 EP U86 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 397ID UT WOS:000262655200007 PM 19047022 ER PT J AU Finnerty, JR Mazza, ME Jezewski, PA AF Finnerty, John R. Mazza, Maureen E. Jezewski, Peter A. TI Domain duplication, divergence, and loss events in vertebrate Msx paralogs reveal phylogenomically informed disease markers SO BMC EVOLUTIONARY BIOLOGY LA English DT Review ID WHOLE-GENOME DUPLICATION; SELECTIVE TOOTH AGENESIS; HOMEOBOX GENE CLUSTERS; RAY-FINNED FISHES; NEMATOSTELLA-VECTENSIS; NEURAL CREST; SEA-ANEMONE; TRANSCRIPTIONAL REPRESSION; EXPRESSION PATTERNS; ANNELID PLATYNEREIS AB Background: Msx originated early in animal evolution and is implicated in human genetic disorders. To reconstruct the functional evolution of Msx and inform the study of human mutations, we analyzed the phylogeny and synteny of 46 metazoan Msx proteins and tracked the duplication, diversification and loss of conserved motifs. Results: Vertebrate Msx sequences sort into distinct Msx1, Msx2 and Msx3 clades. The sister-group relationship between MSX1 and MSX2 reflects their derivation from the 4p/5q chromosomal paralogon, a derivative of the original "MetaHox" cluster. We demonstrate physical linkage between Msx and other MetaHox genes (Hmx, NK1, Emx) in a cnidarian. Seven conserved domains, including two Groucho repression domains (N- and C-terminal), were present in the ancestral Msx. In cnidarians, the Groucho domains are highly similar. In vertebrate Msx1, the N- terminal Groucho domain is conserved, while the C-terminal domain diverged substantially, implying a novel function. In vertebrate Msx2 and Msx3, the C-terminal domain was lost. MSX1 mutations associated with ectodermal dysplasia or orofacial clefting disorders map to conserved domains in a non-random fashion. Conclusion: Msx originated from a MetaHox ancestor that also gave rise to Tlx, Demox, NK, and possibly EHGbox, Hox and ParaHox genes. Duplication, divergence or loss of domains played a central role in the functional evolution of Msx. Duplicated domains allow pleiotropically expressed proteins to evolve new functions without disrupting existing interaction networks. Human missense sequence variants reside within evolutionarily conserved domains, likely disrupting protein function. This phylogenomic evaluation of candidate disease markers will inform clinical and functional studies. C1 [Jezewski, Peter A.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Finnerty, John R.; Mazza, Maureen E.] Boston Univ, Dept Biol, Boston, MA 02215 USA. [Jezewski, Peter A.] Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Jezewski, PA (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM jrf3@bu.edu; tmmazza@bu.edu; pjezewski@forsyth.org RI Finnerty, John/B-6564-2011 FU NIH/NIDCR [DE14528]; Harvard School of Dental Medicine FX We thank Dr. Michael Gribskov, of Purdue University, Departments of Biological Sciences and Computer Science for providing advice related to the MEME suite of software programs and for his suggestions on the manuscript. Thanks are also due to Dr. Jeffrey Murray, at the University of Iowa, Department of Pediatrics, for helpful discussions and the initial opportunity to pursue this work. We also acknowledge the suggestions of two anonymous reviewers that definitely improved this manuscript. This work was funded in part by an NIH/NIDCR K12 Faculty Transition Award (DE14528) from the Harvard School of Dental Medicine to P.A.J. NR 114 TC 19 Z9 20 U1 1 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JAN 20 PY 2009 VL 9 AR 18 DI 10.1186/1471-2148-9-18 PG 23 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 429OH UT WOS:000264929500001 PM 19154605 ER PT J AU Rudolph, JL Jones, RN Levkoff, SE Rockett, C Inouye, SK Sellke, FW Khuri, SF Lipsitz, LA Ramlawi, B Levitsky, S Marcantonio, ER AF Rudolph, James L. Jones, Richard N. Levkoff, Sue E. Rockett, Christopher Inouye, Sharon K. Sellke, Frank W. Khuri, Shukri F. Lipsitz, Lewis A. Ramlawi, Basel Levitsky, Sidney Marcantonio, Edward R. TI Derivation and Validation of a Preoperative Prediction Rule for Delirium After Cardiac Surgery SO CIRCULATION LA English DT Article DE aging; cardiac surgery; cognition; delirium; depression; prediction rule ID CONFUSION ASSESSMENT METHOD; GERIATRIC DEPRESSION SCALE; BYPASS GRAFT-SURGERY; RISK-FACTORS; POSTOPERATIVE DELIRIUM; PRECIPITATING FACTORS; HOSPITALIZED-PATIENTS; SERUM-ALBUMIN; MORTALITY; SYMPTOMS AB Background-Delirium is a common outcome after cardiac surgery. Delirium prediction rules identify patients at risk for delirium who may benefit from targeted prevention strategies, early identification, and treatment of underlying causes. The purpose of the present prospective study was to develop a prediction rule for delirium in a cardiac surgery cohort and to validate it in an independent cohort. Methods and Results-Prospectively, cardiac surgery patients >= 60 years of age were enrolled in a derivation sample (n = 122) and then a validation sample (n = 109). Beginning on the second postoperative day, patients underwent a standardized daily delirium assessment, and delirium was diagnosed according to the confusion assessment method. Delirium occurred in 63 (52%) of the derivation cohort patients. Multivariable analysis identified 4 variables independently associated with delirium: prior stroke or transient ischemic attack, Mini Mental State Examination score, abnormal serum albumin, and the Geriatric Depression Scale. Points were assigned to each variable: Mini Mental State Examination <= 23 received 2 points, and Mini Mental State Examination score of 24 to 27 received 1 point; Geriatric Depression Scale >4, prior stroke/transient ischemic attack, and abnormal albumin received 1 point each. In the derivation sample, the cumulative incidence of delirium for point levels of 0, 1, 2, and >= 3 was 19%, 47%, 63%, and 86%, respectively (C statistic, 0.74). The corresponding incidence of delirium in the validation sample was 18%, 43%, 60%, and 87%, respectively (C statistic, 0.75). Conclusions-Delirium occurs frequently after cardiac surgery. Using 4 preoperative characteristics, clinicians can determine cardiac surgery patients' risk for delirium. Patients at higher delirium risk could be candidates for close postoperative monitoring and interventions to prevent delirium. (Circulation. 2009;119:229-236.) C1 [Rudolph, James L.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. [Khuri, Shukri F.] Div Cardiac Surg, Boston, MA USA. [Jones, Richard N.; Rockett, Christopher; Inouye, Sharon K.; Lipsitz, Lewis A.] Inst Aging Res, Boston, MA USA. [Jones, Richard N.; Inouye, Sharon K.; Marcantonio, Edward R.] Aging Brain Ctr, Boston, MA USA. [Levkoff, Sue E.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. [Rudolph, James L.] Div Aging, Boston, MA USA. [Sellke, Frank W.; Levitsky, Sidney] Beth Israel Deaconess Med Ctr, Div Cardiac Surg, Boston, MA 02215 USA. [Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. [Levkoff, Sue E.; Lipsitz, Lewis A.; Marcantonio, Edward R.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. [Ramlawi, Basel] Columbia Univ, Columbia Presbyterian Med Ctr, Div Cardiothorac Surg, New York, NY 10032 USA. [Rudolph, James L.; Jones, Richard N.; Levkoff, Sue E.; Sellke, Frank W.; Khuri, Shukri F.; Lipsitz, Lewis A.; Levitsky, Sidney; Marcantonio, Edward R.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, 150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org RI Jones, Richard/J-3488-2013 OI Jones, Richard/0000-0002-1049-218X FU Harvard Older Americans Independence Center [AG08812-14]; National Institutes of Health [AG029861, AG00949, AG027549, AG026566, AG030618, AG028189, AG004390, AGO25193]; Veterans Administration Rehabilitation Career Development Award; Milton and Shirley Levy Family Chair. FX This work was funded by the Harvard Older Americans Independence Center AG08812-14 and National Institutes of Health grants (AG029861, AG00949, AG027549, AG026566, AG030618, AG028189, AG004390, and AGO25193). Dr Rudolph is supported by a Veterans Administration Rehabilitation Career Development Award. Dr Inouye is supported by the Milton and Shirley Levy Family Chair. NR 41 TC 152 Z9 156 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 20 PY 2009 VL 119 IS 2 BP 229 EP 236 DI 10.1161/CIRCULATIONAHA.108.795260 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XL UT WOS:000262625300007 PM 19118253 ER PT J AU Conrad, C Niess, H Huss, R Huber, S von Luettichau, I Nelson, PJ Ott, HC Jauch, KW Bruns, CJ AF Conrad, Claudius Niess, Hanno Huss, Ralf Huber, Stephan von Luettichau, Irene Nelson, Peter J. Ott, Harald C. Jauch, Karl-Walter Bruns, Christiane J. TI Multipotent Mesenchymal Stem Cells Acquire a Lymphendothelial Phenotype and Enhance Lymphatic Regeneration In Vivo SO CIRCULATION LA English DT Article DE lymphangiogenesis; Lyve-1; mesenchymal stem cell; Prox-1; VEGF ID GROWTH-FACTOR-C; ENDOTHELIAL PROGENITOR CELLS; BONE-MARROW; PERIPHERAL-BLOOD; PRECURSOR CELLS; POSTNATAL NEOVASCULARIZATION; TUMOR LYMPHANGIOGENESIS; DOWN-REGULATION; METASTASIS; EXPRESSION AB Background-The importance and therapeutic value of stem cells in lymphangiogenesis are poorly understood. We evaluated the potential of human and murine mesenchymal stem cells (MSCs) to acquire a lymphatic phenotype in vitro and to enhance lymphatic regeneration in vivo. Methods and Results-We assessed the lymphendothelial differentiation of human and murine MSCs after induction with supernatant derived from human dermal microvascular endothelial cells, isolated lymphatic endothelial cells, and purified vascular endothelial growth factor (VEGF)-C in vitro. We used human or murine progenitor MSC lines and then characterized the lymphatic phenotype by morphology, migratory capacity, and the expression of lymphatic markers such as Prox-1, podoplanin, Lyve-1, VEGF receptor-2, and VEGF receptor-3. Using a murine lymphatic edema model, we assessed the potential of these cells to form a functional lymphatic vasculature in vivo after injection of syngeneic MSCs. Incubation with supernatant from lymphatic endothelial cells induced an endothelium-like morphology and the expression of lymphendothelial markers in both human and murine MSCs in vitro. MSCs showed migratory activity along a VEGF-C gradient, which was enhanced by VEGF-C conditioning. In vivo, the local application of MSCs resulted in a significant decrease in edema formation (-20.1%; P<0.01 versus untreated tails) after 3 weekly cell injections and restored the drainage of intradermally injected methylene blue after 7 weekly injections. Conclusions-MSCs were capable of expressing a lymphatic phenotype when exposed to lymph-inductive media and purified VEGF-C. Migratory activity toward VEGF-C in vitro suggests homing capability in vivo. Restoration of lymphatic drainage after injection of MSCs in a lymphedema model indicates that MSCs play a role in lymphatic regeneration. The potential clinical application of MSC in wound healing and reduction of lymphatic edema warrants further research. (Circulation. 2009;119:281-289.) C1 [Conrad, Claudius; Ott, Harald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. [Niess, Hanno; Huber, Stephan; Jauch, Karl-Walter; Bruns, Christiane J.] Univ Munich Grosshadern, Dept Surg, Munich, Germany. [Huss, Ralf] Roche Diagnost GmbH, Penzberg, Germany. [von Luettichau, Irene] Tech Univ Munich, Dept Pediat, Munich, Germany. [Nelson, Peter J.] Univ Munich, Med Poliklin, D-8000 Munich, Germany. [Huss, Ralf] Univ Munich, Dept Pathol, Munich, Germany. RP Conrad, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. EM CConrad1@partners.org FU Deutsche Forschungsgemeinschaft [KFO 128/1-3, GU 489/3-1]; EU FX This research was supported by a grant of the clinical research group KFO 128/1-3 of the Deutsche Forschungsgemeinschaft and research grant GU 489/3-1 of the Deutsche Forschungsgemeinschaft of the Schwerpunktprogramm "The Tumor-Vessel Interface" and an EU grant INNOCHEM to Dr Nelson. NR 41 TC 50 Z9 58 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 20 PY 2009 VL 119 IS 2 BP 281 EP 289 DI 10.1161/CIRCULATIONAHA.108.793208 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 396XL UT WOS:000262625300013 PM 19118255 ER PT J AU Chi, SN Zimmerman, MA Yao, XP Cohen, KJ Burger, P Biegel, JA Rorke-Adams, LB Fisher, MJ Janss, A Mazewski, C Goldman, S Manley, PE Bowers, DC Bendel, A Rubin, J Turner, CD Marcus, KJ Goumnerova, L Ullrich, NJ Kieran, MW AF Chi, Susan N. Zimmerman, Mary Ann Yao, Xiaopan Cohen, Kenneth J. Burger, Peter Biegel, Jaclyn A. Rorke-Adams, Lucy B. Fisher, Michael J. Janss, Anna Mazewski, Claire Goldman, Stewart Manley, Peter E. Bowers, Daniel C. Bendel, Anne Rubin, Joshua Turner, Christopher D. Marcus, Karen J. Goumnerova, Liliana Ullrich, Nicole J. Kieran, Mark W. TI Intensive Multimodality Treatment for Children With Newly Diagnosed CNS Atypical Teratoid Rhabdoid Tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 13th International Symposium on Pediatric Neuro-Oncology CY JUN 29-JUL 02, 2008 CL Chicago, IL ID CENTRAL-NERVOUS-SYSTEM; TERATOID/RHABDOID TUMOR; RADIATION-THERAPY; CHILDHOOD; CHEMOTHERAPY; INFANCY; MEDULLOBLASTOMA; ATRT AB Purpose Atypical teratoid rhabdoid tumor (ATRT) of the CNS is a highly malignant neoplasm primarily affecting young children, with a historic median survival ranging from 6 to 11 months. Based on a previous pilot series, a prospective multi-institutional trial was conducted for patients with newly diagnosed CNS ATRT. Patients and Methods Treatment was divided into five phases: preirradiation, chemoradiation, consolidation, maintenance, and continuation therapy. Intrathecal chemotherapy was administered, alternating intralumbar and intraventricular routes. Radiation therapy (RT) was prescribed, either focal (54 Gy) or craniospinal (36 Gy, plus primary boost), depending on age and extent of disease at diagnosis. Results Between 2004 and 2006, 25 patients were enrolled; 20 were eligible for evaluation. Median age at diagnosis was 26 months (range, 2.4 months to 19.5 years). Gross total resection of the primary tumor was achieved in 11 patients. Fourteen patients had M0 disease at diagnosis, one patient had M2 disease, and five patients had M3 disease. Fifteen patients received radiation therapy: 11 focal and four craniospinal. Significant toxicities, in addition to the expected, included radiation recall (n = 2) and transverse myelitis (n = 1). There was one toxic death. Of the 12 patients who were assessable for chemotherapeutic response (pre-RT), the objective response rate was 58%. The objective response rate observed after RT was 38%. The 2-year progression-free and overall survival rates are 53% +/- 13% and 70% +/- 10%, respectively. Median overall survival has not yet been reached. Conclusion This intensive multimodality regimen has resulted in a significant improvement in time to progression and overall survival for patients with this previously poor-prognosis tumor. C1 [Chi, Susan N.] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Healthcare Atlanta, Atlanta, GA USA. Childrens Mem Med Ctr, Chicago, IL USA. Hasbro Childrens Hosp, Providence, RI USA. Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. Childrens Hosp, Minneapolis, MN USA. Clin Minnesota, Minneapolis, MN USA. Clin Minnesota, St Paul, MN USA. Childrens Hosp, St Paul, MN USA. Washington Univ, St Louis, MO USA. RP Chi, SN (reprint author), Childrens Hosp Boston, Dana Farber Canc Inst, 44 Binney St,SW331, Boston, MA 02115 USA. EM susan_chi@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [CA46274, R01 CA046274, R01 CA046274-17A2] NR 21 TC 136 Z9 140 U1 1 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 20 PY 2009 VL 27 IS 3 BP 385 EP 389 DI 10.1200/JCO.2008.18.7724 PG 5 WC Oncology SC Oncology GA 395CE UT WOS:000262499100012 PM 19064966 ER PT J AU Viswanathan, A Raj, S Greenberg, SM Stampfer, M Campbell, S Hyman, BT Irizarry, MC AF Viswanathan, A. Raj, S. Greenberg, S. M. Stampfer, M. Campbell, S. Hyman, B. T. Irizarry, M. C. TI Plasma A beta, homocysteine, and cognition The Vitamin Intervention for Stroke Prevention (VISP) trial SO NEUROLOGY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; WHITE-MATTER LESIONS; ALZHEIMER-DISEASE; RISK; DEMENTIA; HYPERHOMOCYSTEINEMIA; ASSOCIATION; IMPAIRMENT; FOLATE; MEN AB Background: Amyloid-beta protein (A beta) plays a key role in Alzheimer disease (AD) and is also implicated in cerebral small vessel disease. Serum total homocysteine (tHcy) is a risk factor for small vessel disease and cognitive impairment and correlates with plasma A beta levels. To determine whether this association results from a common pathophysiologic mechanism, we investigated whether vitamin supplementation-induced reduction of tHcy influences plasma A beta levels in the Vitamin Intervention in Stroke Prevention (VISP) study. Methods: Two groups of 150 patients treated with either the high-dose or low-dose formulation of pyridoxine, cobalamin, and folic acid in a randomized, double-blind fashion were selected among the participants in the VISP study without recurrent stroke during follow-up and in the highest 10% of the distribution for baseline tHcy levels. Concentrations of plasma A beta with 40 (A beta 40) and 42 (A beta 42) amino acids were measured at baseline and at the 2-year visit. Results: tHcy levels significantly decreased with vitamin supplementation in both groups. tHcy were strongly correlated with A beta 40 but not A beta 42 concentrations. There was no difference in the change in A beta 40, A beta 42 (p = 0.40, p = 0.35), or the A beta 42/A beta 40 ratio over time (p = 0.86) between treatment groups. A beta measures were not associated with cognitive change. Conclusions: This double-blind randomized controlled trial of vitamin therapy demonstrates a strong correlation between serum tHcy and plasma A beta 40 concentrations in subjects with ischemic stroke. Treatment with high dose vitamins does not, however, influence plasma levels of A beta, despite their effect on lowering tHcy. Our results suggest that although tHcy is associated with plasma A beta 40, they may be regulated by independent mechanisms. Neurology (R) 2009;72:268-272 C1 [Viswanathan, A.; Raj, S.; Greenberg, S. M.; Hyman, B. T.; Irizarry, M. C.] Massachusetts Gen Hosp, Memory Disorders Unit, Boston, MA 02114 USA. [Viswanathan, A.; Greenberg, S. M.] Massachusetts Gen Hosp, Stroke Serv, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. [Stampfer, M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Campbell, S.] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Stroke Prevent & Atherosclerosis Res Center, Chapel Hill, NC USA. RP Viswanathan, A (reprint author), Massachusetts Gen Hosp, Hemorrhag Stroke Res Program, Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM aviswanathan1@partners.org FU NIH [5K23NS046327-04, P50AG05134, 5R01AG026484-02, 5T32NS048005-05]; Massachusetts General Hospital; Harvard Center for Neurodegeneration and Repair FX Supported by NIH grants 5K23NS046327-04, P50AG05134, and 5R01AG026484-02 (Massachusetts General Hospital), the Harvard Center for Neurodegeneration and Repair, and NIH grant 5T32NS048005-05 (Harvard School of Public Health). NR 34 TC 20 Z9 24 U1 2 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 JAN 20 PY 2009 VL 72 IS 3 BP 268 EP 272 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 396XE UT WOS:000262624300012 PM 19153374 ER PT J AU Rozenblatt-Rosen, O Nagaike, T Francis, JM Kaneko, S Glatt, KA Hughes, CM LaFramboise, T Manley, JL Meyerson, M AF Rozenblatt-Rosen, Orit Nagaike, Takashi Francis, Joshua M. Kaneko, Syuzo Glatt, Karen A. Hughes, Christina M. LaFramboise, Thomas Manley, James L. Meyerson, Matthew TI The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3 ' mRNA processing factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HISTONE METHYLTRANSFERASE COMPLEX; POLYMERASE-II TRANSCRIPTION; HUMAN PAF COMPLEX; POLYADENYLATION FACTOR; ELONGATION-FACTORS; GENE-EXPRESSION; END FORMATION; PROTEIN; PARAFIBROMIN; HRPT2 AB The CDC73 tumor suppressor gene is mutationally inactivated in hereditary and sporadic parathyroid tumors. Its product, the Cdc73 protein, is a component of the RNA polymerase II and chromatin-associated human Paf1 complex (Paf1C). Here, we show that Cdc73 physically associates with the cleavage and polyadenylation specificity factor (CPSF) and cleavage stimulation factor (CstF) complexes that are required for the maturation of mRNA 3' ends in the cell nucleus. Immunodepletion experiments indicate that the Cdc73-CPSF-CstF complex is necessary for 3' mRNA processing in vitro. Microarray analysis of CDC73 siRNA-treated cells revealed INTS6, a gene encoding a subunit of the Integrator complex, as an in vivo Cdc73 target. Cdc73 depletion by siRNA resulted in decreased INTS6 mRNA abundance, and decreased association of CPSF and CstF subunits with the INTS6 locus. Our results suggest that Cdc73 facilitates association of 3' mRNA processing factors with actively-transcribed chromatin and support the importance of links between tumor suppression and mRNA maturation. C1 [Rozenblatt-Rosen, Orit; Francis, Joshua M.; Glatt, Karen A.; Hughes, Christina M.; LaFramboise, Thomas; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Rozenblatt-Rosen, Orit; Francis, Joshua M.; Glatt, Karen A.; Hughes, Christina M.; LaFramboise, Thomas; Meyerson, Matthew] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Nagaike, Takashi; Kaneko, Syuzo; Manley, James L.] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. RP Meyerson, M (reprint author), Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM matthew_meyerson@dfcl.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU Caring for Carcinoid Foundation; National Institutes of Health [GM28983] FX We thank J. Jaehning, S. Buratowski, and V. Runner for sharing unpublished results and discussions; S. Rozenblatt, and M. Keogh for discussions; A. Bass, S. A. Woo, W. Lin, and A. Alexander for critical reading of the manuscript; E. McIntush at Bethyl Laboratories for antibody design and preparation of polyclonal antibodies; R. Tomaino at Taplin Biological Mass Spectrometry Facility for mass spectrometric analysis; R. Luhrmann and C. Merz (Max Planck Institute, Gottingen, Germany) for providing plasmids; and S. Nannepaga for technical assistance. This work was supported by gifts from the Caring for Carcinoid Foundation and Drs. R. and B. Sackler (to M. M.) and National Institutes of Health Grant GM28983 (to J. L. M.). NR 39 TC 66 Z9 68 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 20 PY 2009 VL 106 IS 3 BP 755 EP 760 DI 10.1073/pnas.0812023106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 399OR UT WOS:000262809700017 PM 19136632 ER PT J AU Marzocchetti, A Lima, M Tompkins, T Kavanagh, DG Gandhi, RT O'Neill, DW Bhardwaj, N Koralnik, IJ AF Marzocchetti, Angela Lima, Marco Tompkins, Troy Kavanagh, Daniel. G. Gandhi, Rajesh T. O'Neill, David W. Bhardwaj, Nina Koralnik, Igor J. TI Efficient in vitro expansion of JC virus-specific CD8(+) T-cell responses by JCV peptide-stimulated dendritic cells from patients with progressive multifocal leukoencephalopathy SO VIROLOGY LA English DT Article DE JC virus; Progressive multifocal leukoencephalopathy; Dendritic cells ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; LYMPHOCYTES; SURVIVAL; IMMUNOTHERAPY; ASSOCIATION; PHENOTYPE; FREQUENCY; EPITOPE; CTL AB Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain caused by JC virus (JCV) for which there is no cure. PML patients who have JCV-specific CD8(+) cytotoxic T lymphocytes (CTL) in their blood have a better clinical outcome. We compared JCV-specific CTL responses in vitro elicited either by JCV peptide-loaded dendritic cells (DC) or by direct peptide stimulation of lymphocytes from 20 HLA-A*0201(+) healthy controls, HIV+ and PML patients. JCV peptide-loaded DC elicited a stronger CTL expansion in 13/15 responders. DC can induce a potent JCV-specific CTL response in vitro, and may constitute a promising approach for PML immunotherapy. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lima, Marco; Koralnik, Igor J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. [Marzocchetti, Angela; Lima, Marco; Tompkins, Troy; Koralnik, Igor J.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Cambridge, MA 02138 USA. [Kavanagh, Daniel. G.; Gandhi, Rajesh T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Cambridge, MA 02138 USA. [O'Neill, David W.; Bhardwaj, Nina] NYU, Sch Med, New York, NY 10003 USA. RP Koralnik, IJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, E CLS-1005,330 Brookline Ave, Boston, MA 02215 USA. EM ikoralni@bidmc.harvard.edu FU Public Health Service [R01 NS/Al 041198 NS 047029, K24 NS 060950] FX This work was supported in part by Public Health Service Grants R01 NS/Al 041198 NS 047029, and K24 NS 060950 to IJK. NR 24 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 20 PY 2009 VL 383 IS 2 BP 173 EP 177 DI 10.1016/j.virol.2008.10.046 PG 5 WC Virology SC Virology GA 396QH UT WOS:000262605700001 PM 19062062 ER PT J AU Miller, JC Blake, MA Boland, GWL AF Miller, J. C. Blake, M. A. Boland, G. W. L. TI Definitive characterisation of adrenal lesions SO BRITISH MEDICAL JOURNAL LA English DT Article ID CONTRAST-ENHANCED CT; MASSES; INCIDENTALOMA; PREVALENCE; MANAGEMENT; BENIGN C1 [Miller, J. C.; Blake, M. A.; Boland, G. W. L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. EM gboland@partners.org NR 16 TC 3 Z9 3 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD JAN 19 PY 2009 VL 338 AR a3092 DI 10.1136/bmj.a3092 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 405BO UT WOS:000263197300001 PM 19153128 ER PT J AU Zhao, WD Qin, WP Pan, JP Wu, Y Bauman, WA Cardozo, C AF Zhao, Weidong Qin, Weiping Pan, Jiangping Wu, Yong Bauman, William A. Cardozo, Christopher TI Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Glucocorticoids; Muscle atrophy; MAFbx; Atrogin-1; MuRF1; FOXO1; Akt; Glucocorticoiod receptor ID SKELETAL-MUSCLE ATROPHY; FOXO TRANSCRIPTION FACTORS; GROWTH-FACTOR-I; UBIQUITIN LIGASES; GENE-EXPRESSION; PATHWAY; DEGRADATION; MURF1; IDENTIFICATION; MECHANISMS AB The muscle ubiquitin ligases MAFbx and MuRF1 are upregulated in and promote muscle atrophy. Upregulation of MAFbx and MuRF1 by glucocorticoids has been linked to activation of FOXO1 and FOXO3A resulting from reduced Akt activity. We determined the requirements for the glucocorticoid receptor (GR) in these biological responses in C2C12 cells in which GR expression was knocked down by stable expression of an shRNA. Loss of GR prevented dexamethasone-induced increases in protein catabolism. Loss of GR. or inhibition of ligand binding to GR with RU486, prevented upregulation of MAFbx and MuRF1 by dexamethasone. Loss of GR also prevented dexamethasone-induced decreases in Akt phosphorylation, and increases in the fraction of FOXO1 that was unphosphorylated. The findings establish a requirement for the GR in activating molecular signals that promote muscle protein catabolism. Published by Elsevier Inc. C1 [Zhao, Weidong; Qin, Weiping; Pan, Jiangping; Wu, Yong; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. RP Cardozo, C (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences SCI, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [134162C, 133347K, 133522R] FX The research reported here was Supported by the Veterans Health Administration, Rehabilitation Research and Development Service (134162C, 133347K, 133522R). NR 24 TC 27 Z9 28 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 16 PY 2009 VL 378 IS 3 BP 668 EP 672 DI 10.1016/j.bbrc.2008.11.123 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 393AL UT WOS:000262343200066 PM 19059383 ER PT J AU von Boehmer, H AF von Boehmer, Harald TI Notch 1 Keeps Pro-T Cells on Track SO IMMUNITY LA English DT Editorial Material ID DELTA-LIKE 4 AB In this issue of Immunity, Feyerabend et al. (2009) report that Delta-like 4, acting on Notch 1, prevents pro-T cells from differentiating into dendritic cells and B cells. In addition, in the absence of Notch 1, B cells in the thymus arose from a cell-extrinsic pathway. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM harald_von_boehmer@dfci.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN 16 PY 2009 VL 30 IS 1 BP 5 EP 7 DI 10.1016/j.immuni.2008.12.008 PG 3 WC Immunology SC Immunology GA 398ZJ UT WOS:000262769900003 PM 19144311 ER PT J AU Lu, LF Thai, TH Calado, DP Chaudhry, A Kubo, M Tanaka, K Loeb, GB Lee, H Yoshimura, A Rajewsky, K Rudensky, AY AF Lu, Li-Fan Thai, To-Ha Calado, Dinis Pedro Chaudhry, Ashutosh Kubo, Masato Tanaka, Kentaro Loeb, Gabriel B. Lee, Hana Yoshimura, Akihiko Rajewsky, Klaus Rudensky, Alexander Y. TI Foxp3-Dependent MicroRNA155 Confers Competitive Fitness to Regulatory T Cells by Targeting SOCS1 Protein SO IMMUNITY LA English DT Article ID CYTOKINE SIGNALING-1; IMMUNE REGULATION; HIGH EXPRESSION; DIFFERENTIATION; DICER; SUPPRESSOR; MICE; AUTOIMMUNITY; LYMPHOMA; LINEAGE AB Foxp3(+) regulatory T (Treg) cells limit pathogenic immune responses to self-antigens and foreign antigens. An essential role for microRNA (miRNA) in the maintenance and function of Treg cells, revealed by the Treg cell-specific Dicer ablation, raised a question as to a specific miRNA contribution. We found that Foxp3 controlled the elevated miR155 expression required for maintaining Treg cell proliferative activity and numbers under nonlymphopenic conditions. Moreover, miR155 deficiency in Treg cells resulted in increased suppressor of cytokine signaling 1 (SOCS1) expression accompanied by impaired activation of signal transducer and activator of transcription 5 (STAT5) transcription factor in response to limiting amounts of interleukin-2. Our studies suggest that Foxp3-dependent regulation of miR155 maintains competitive fitness of Treg cells by targeting SOCS1, and they provide experimental support for a proposed role for miRNAs in ensuring the robustness of cellular phenotypes. C1 [Lu, Li-Fan; Chaudhry, Ashutosh; Loeb, Gabriel B.; Lee, Hana; Rudensky, Alexander Y.] Univ Washington, Dept Immunol, Seattle, WA 98195 USA. [Lu, Li-Fan; Chaudhry, Ashutosh; Loeb, Gabriel B.; Lee, Hana; Rudensky, Alexander Y.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. [Thai, To-Ha; Calado, Dinis Pedro; Rajewsky, Klaus] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Kubo, Masato] Riken Yokohama Inst, Riken Res Ctr Allergy & Immunol, Yokohama, Kanagawa 2300045, Japan. [Tanaka, Kentaro; Yoshimura, Akihiko] Kyushu Univ, Med Inst Bioregulat, Higashi Ku, Fukuoka 8128582, Japan. [Lu, Li-Fan; Thai, To-Ha; Calado, Dinis Pedro] Keio Univ, Sch Med, Dept Microbiol & Immunol, Shinjyuku Ku, Tokyo 1608582, Japan. RP Rudensky, AY (reprint author), Univ Washington, Dept Immunol, Box 357370, Seattle, WA 98195 USA. EM rudenska@mskcc.org RI Yoshimura, Akihiko/K-5515-2013; Kubo, Masato/A-5918-2016; OI Lu, Li-Fan/0000-0002-9727-0036; Chaudhry, Ashutosh/0000-0003-3379-5236 FU National Institutes of Health; European Union through MUGEN; Ministry of Education, Culture, Sports, Science, and Technology of Japan; Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation; Leukemia and Lymphoma Society; Portuguese Foundation for Science and Technology FX We thank S. Josefowicz for the help in key experiments, T. Chu, L. Karpik, and K. Forbush for superb technical assistance, and all members of our laboratory for discussions. This work was supported by grants from the National Institutes of Health (to A.Y.R. and K.R.), from the European Union through MUGEN (to K.R.), and from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (to A.Y.). L.L.F. is a Leukemia and Lymphoma Society Fellow. D.P.C. is supported by the Portuguese Foundation for Science and Technology (FCT-MCES). A.Y.R. is a Howard Hughes Medical Institute investigator. NR 39 TC 398 Z9 441 U1 1 U2 34 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JAN 16 PY 2009 VL 30 IS 1 BP 80 EP 91 DI 10.1016/j.immuni.2008.11.010 PG 12 WC Immunology SC Immunology GA 398ZJ UT WOS:000262769900012 PM 19144316 ER PT J AU Nakayama, M Hisatsune, J Yamasaki, E Isomoto, H Kurazono, H Hatakeyama, M Azuma, T Yamaoka, Y Yahiro, K Moss, J Hirayama, T AF Nakayama, Masaaki Hisatsune, Junzo Yamasaki, Eiki Isomoto, Hajime Kurazono, Hisao Hatakeyama, Masanori Azuma, Takeshi Yamaoka, Yoshio Yahiro, Kinnosuke Moss, Joel Hirayama, Toshiya TI Helicobacter pylori VacA-induced Inhibition of GSK3 through the PI3K/Akt Signaling Pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; GASTRIC EPITHELIAL-CELLS; BETA-CATENIN SIGNAL; AZ-521 CELLS; VACUOLATING TOXIN; WNT PATHWAY; ACTIVATION; PROTEIN; INDUCTION; CYTOTOXIN AB Helicobacter pylori VacA toxin contributes to the pathogenesis and severity of gastric injury. We found that incubation of AZ-521 cells with VacA resulted in phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3 beta (GSK3 beta) through a PI3K-dependent pathway. Following phosphorylation and inhibition of GSK3 beta,beta-catenin was released from a GSK3 beta/beta-catenin complex, with subsequent nuclear translocation. Methyl-beta-cyclodextrin (MCD) and phosphatidylinositol-specific phospholipase C (PIPLC), but not 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and bafilomycin A1, inhibited VacA-induced phosphorylation of Akt, indicating that it does not require VacA internalization and is independent of vacuolation. VacA treatment of AZ-521 cells transfected with TOPtkLuciferase reporter plasmid or control FOPtkLucifease reporter plasmid resulted in activation of TOPtkLuciferase, but not FOPtkLucifease. In addition, VacA transactivated the beta-catenin-dependent cyclin D1 promoter in a luciferase reporter assay. Infection of AZ-521 cells by a vacA mutant strain of H. pylori failed to induce phosphorylation of Akt and GSK3 beta, or release of beta-catenin from a GSK3 beta/beta-catenin complex. Taken together, these results support the conclusion that VacA activates the PI3K/Akt signaling pathway, resulting in phosphorylation and inhibition of GSK3 beta, and subsequent translocation of beta-catenin to the nucleus, consistent with effects of VacA on beta-catenin-regulated transcriptional activity. These data introduce the possibility that Wnt-dependent signaling might play a role in the pathogenesis of H. pylori infection, including the development of gastric cancer. C1 [Nakayama, Masaaki; Hisatsune, Junzo; Hirayama, Toshiya] Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan. [Yamasaki, Eiki; Kurazono, Hisao] Obihiro Univ Agr & Vet Med, Dept Appl Vet Med & Publ Hlth, Obihiro, Hokkaido 0808555, Japan. [Isomoto, Hajime] Nagasaki Univ, Dept Endoscopy, Sch Med, Nagasaki 8528523, Japan. [Hatakeyama, Masanori] Hokkaido Univ, Div Mol Oncol, Inst Med Genet, Sapporo, Hokkaido 0600815, Japan. [Azuma, Takeshi] Kobe Univ, Sch Med, Dept Gastroenterol, Kobe, Hyogo 6500017, Japan. [Yamaoka, Yoshio] Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. [Yamaoka, Yoshio] Baylor Coll Med, Houston, TX 77030 USA. [Yahiro, Kinnosuke; Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Hirayama, T (reprint author), Nagasaki Univ, Dept Bacteriol, Inst Trop Med, Nagasaki 8528523, Japan. EM hirayama@net.nagasaki-u.ac.jp FU Intramural Research Program of the NHLBI; National Institutes of Health; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This work was supported, in whole or in part, by the Intramural Research Program of the NHLBI, National Institutes of Health (to J. M.). This work was also supported by Grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan. 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 36 TC 56 Z9 59 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 16 PY 2009 VL 284 IS 3 BP 1612 EP 1619 DI 10.1074/jbc.M806981200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 392VK UT WOS:000262330100029 PM 18996844 ER PT J AU Cruz-Guilloty, F Pipkin, ME Djuretic, IM Levanon, D Lotem, J Lichtenheld, MG Groner, Y Rao, A AF Cruz-Guilloty, Fernando Pipkin, Matthew E. Djuretic, Ivana M. Levanon, Ditsa Lotem, Joseph Lichtenheld, Mathias G. Groner, Yoram Rao, Anjana TI Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HELPER TYPE-1 CELLS; IL4 SILENCER; BET; PERFORIN; DIFFERENTIATION; EOMESODERMIN; MEMORY; REPRESSION; HOMEOSTASIS; ACTIVATION AB Activation of naive CD8(+) T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) gamma expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-gamma, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs. C1 [Cruz-Guilloty, Fernando; Pipkin, Matthew E.; Djuretic, Ivana M.; Rao, Anjana] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cruz-Guilloty, Fernando; Pipkin, Matthew E.; Djuretic, Ivana M.; Rao, Anjana] Immune Dis Inst, Boston, MA 02115 USA. [Levanon, Ditsa; Lotem, Joseph; Groner, Yoram] Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. [Lichtenheld, Mathias G.] Univ Miami, Dept Microbiol & Immunol, Sylvester Comprehens Canc Ctr, Miller Sch Med, Miami, FL USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM arao@idi.harvard.edu FU NCI NIH HHS [F32 CA126247-01, CA42471, F32 CA126247, F32 CA126247-02, R01 CA042471, R37 CA042471]; NIAID NIH HHS [AI44432, P30 AI073961, R01 AI044432] NR 29 TC 166 Z9 171 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 16 PY 2009 VL 206 IS 1 BP 51 EP 59 DI 10.1084/jem.20081242 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VK UT WOS:000266008300008 PM 19139168 ER PT J AU Cariappa, A Takematsu, H Liu, HY Diaz, S Haider, K Boboila, C Kalloo, G Connole, M Shi, HN Varki, N Varki, A Pillai, S AF Cariappa, Annaiah Takematsu, Hiromu Liu, Haoyuan Diaz, Sandra Haider, Khaleda Boboila, Cristian Kalloo, Geetika Connole, Michelle Shi, Hai Ning Varki, Nissi Varki, Ajit Pillai, Shiv TI B cell antigen receptor signal strength and peripheral B cell development are regulated by a 9-O-acetyl sialic acid esterase SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID N-GLYCOLYLNEURAMINIC ACID; LYN-DEFICIENT MICE; ADHESION MOLECULE CD22-BETA; CD22-DEFICIENT MICE; INDEPENDENT RESPONSES; AUTOIMMUNE-DISEASE; NEGATIVE REGULATOR; O-ACETYLESTERASE; HUMORAL IMMUNITY; NATURAL LIGANDS AB We show that the enzymatic acetylation and deacetylation of a cell surface carbohydrate controls B cell development, signaling, and immunological tolerance. Mice with a mutation in sialate:O-acetyl esterase, an enzyme that specifically removes acetyl moieties from the 9-OH position of alpha 2-6-linked sialic acid, exhibit enhanced B cell receptor (BCR) activation, defects in peripheral B cell development, and spontaneously develop antichromatin autoantibodies and glomerular immune complex deposits. The 9-O-acetylation state of sialic acid regulates the function of CD22, a Siglec that functions in vivo as an inhibitor of BCR signaling. These results describe a novel catalytic regulator of B cell signaling and underscore the crucial role of inhibitory signaling in the maintenance of immunological tolerance in the B lineage. C1 [Cariappa, Annaiah; Liu, Haoyuan; Haider, Khaleda; Boboila, Cristian; Kalloo, Geetika; Shi, Hai Ning; Pillai, Shiv] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Takematsu, Hiromu; Diaz, Sandra; Varki, Nissi; Varki, Ajit] Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA. [Connole, Michelle] Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. RP Pillai, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL057345, P01HL057345]; NIAID NIH HHS [AI064930, R21 AI069458, R01 AI064930, AI069458]; NIDDK NIH HHS [P30 DK043351]; NIGMS NIH HHS [R01 GM032373, R37 GM032373, GM32373] NR 61 TC 60 Z9 61 U1 0 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 16 PY 2009 VL 206 IS 1 BP 125 EP 138 DI 10.1084/jem.20081399 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VK UT WOS:000266008300015 PM 19103880 ER PT J AU Mori, Y Iwasaki, H Kohno, K Yoshimoto, G Kikushige, Y Okeda, A Uike, N Niiro, H Takenaka, K Nagafuji, K Miyamoto, T Harada, M Takatsu, K Akashi, K AF Mori, Yasuo Iwasaki, Hiromi Kohno, Kentaro Yoshimoto, Goichi Kikushige, Yoshikane Okeda, Aki Uike, Naokuni Niiro, Hiroaki Takenaka, Katsuto Nagafuji, Koji Miyamoto, Toshihiro Harada, Mine Takatsu, Kiyoshi Akashi, Koichi TI Identification of the human eosinophil lineage-committed progenitor: revision of phenotypic definition of the human common myeloid progenitor SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MAST-CELL PROGENITORS; HEMATOPOIETIC PROGENITORS; MONOCLONAL-ANTIBODY; DEFICIENT MICE; BONE-MARROW; INTERLEUKIN-5; DIFFERENTIATION; GATA-1; FOG; GRANULOCYTE AB To establish effective therapeutic strategies for eosinophil-related disorders, it is critical to understand the developmental pathway of human eosinophils. In mouse hematopoiesis, eosinophils originate from the eosinophil lineage-committed progenitor (EoP) that has been purified downstream of the granulocyte/macrophage progenitor (GMP). We show that the EoP is also isolatable in human adult bone marrow. The previously defined human common myeloid progenitor (hCMP) population (Manz, M. G., T. Miyamoto, K. Akashi, and I.L. Weissman. 2002. Proc. Natl. Acad. Sci. USA. 99: 11872-11877) was composed of the interleukin 5 receptor alpha chain(+) (IL-5R alpha(+)) and IL-5R alpha(-) fractions, and the former was the hEoP. The IL5R alpha(+)CD34(+)CD38(+)IL-3R alpha(+)CD45RA(-) hEoPs gave rise exclusively to pure eosinophil colonies but never differentiated into basophils or neutrophils. The IL-5R alpha(-) hCMP generated the hEoP together with the hGMP or the human megakaryocyte/erythrocyte progenitor (hMEP), whereas hGMPs or hMEPs never differentiated into eosinophils. Importantly, the number of hEoPs increased up to 20% of the conventional hCMP population in the bone marrow of patients with eosinophilia, suggesting that the hEoP stage is involved in eosinophil differentiation and expansion in vivo. Accordingly, the phenotypic definition of hCMP should be revised to exclude the hEoP; an "IL-5R alpha-negative" criterion should be added to define more homogenous hCMP. The newly identified hEoP is a powerful tool in studying pathogenesis of eosinophilia and could be a therapeutic target for a variety of eosinophil-related disorders. C1 [Mori, Yasuo; Yoshimoto, Goichi; Kikushige, Yoshikane; Okeda, Aki; Niiro, Hiroaki; Takenaka, Katsuto; Nagafuji, Koji; Harada, Mine; Akashi, Koichi] Kyushu Univ, Grad Sch Med Sci, Fukuoka 8128582, Japan. [Iwasaki, Hiromi; Kohno, Kentaro; Miyamoto, Toshihiro; Akashi, Koichi] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. [Uike, Naokuni] Kyushu Natl Canc Ctr, Dept Hematol, Fukuoka 8111395, Japan. [Takatsu, Kiyoshi] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Immunol, Tokyo 1088639, Japan. [Akashi, Koichi] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Akashi, K (reprint author), Kyushu Univ, Grad Sch Med Sci, Fukuoka 8128582, Japan. EM akashi@med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 34 TC 62 Z9 63 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 16 PY 2009 VL 206 IS 1 BP 183 EP 193 DI 10.1084/jem.20081756 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 444VK UT WOS:000266008300019 PM 19114669 ER PT J AU Fu, KY Tan, YH Sung, B Mao, JR AF Fu, Kai-Yuan Tan, Yong-Hui Sung, Backil Mao, Jianren TI Peripheral formalin injection induces unique spinal cord microglial phenotypic changes SO NEUROSCIENCE LETTERS LA English DT Article DE Microglia; Formalin; CD45; OX-42; MHC class I; MHC class II ID CENTRAL-NERVOUS-SYSTEM; LONG-TERM HYPERALGESIA; RECEPTOR EXPRESSION; NEUROPATHIC PAIN; CELL-ACTIVATION; RAT; INFLAMMATION; INJURY; MODELS; IMMUNE AB Microglia are resident immune cells of brain and activated by peripheral tissue injury. In the present study, we investigated the possible induction of several microglial surface immunomolecules in the spinal cord, including leukocyte common antigen (LCA/CD45), MHC class I antigen, MHC class II antigen, Fc receptor, and CD11c following formalin injection into the rat's hind paw. CD45 and MHC class I were upregulated in the activated microglia, which was evident on day 3 with the peak expression on day 7 following peripheral formalin injection. There was a very low basal expression of MHC class II, CD11c, and the Fc receptor, which did not change after the formalin injection. These results, for the first time, indicate that peripheral formalin injection can induce phenotypic changes of microglia with distinct upregulation of CD45 and MHC class I antigen. The data suggest that phenotypic changes of the activated microglia may be a unique pattern of central changes following peripheral tissue injury. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Fu, Kai-Yuan; Tan, Yong-Hui] Peking Univ, Sch & Hosp Stomatol, Ctr TMD & Orofacial Pain, Beijing 100081, Peoples R China. [Sung, Backil; Mao, Jianren] Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Sch Med, MGH Ctr Translat Pain Res,Div Pain Med, Boston, MA 02114 USA. RP Fu, KY (reprint author), Peking Univ, Sch & Hosp Stomatol, Ctr TMD & Orofacial Pain, Beijing 100081, Peoples R China. EM kqkyfu@bjmu.edu.cn OI Fu, Kai-Yuan/0000-0001-7049-9888 FU New Century Excellent Talents in University (NCET); National Natural Science Foundation of China [30371544]; US PHS [DE18214, DE18538] FX The research was supported by the program for New Century Excellent Talents in University (NCET) and Project 30371544 by National Natural Science Foundation of China (K.Y.F.) as well as by the US PHS R01 grants DE18214 and DE18538 O.M.). NR 33 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JAN 16 PY 2009 VL 449 IS 3 BP 234 EP 239 DI 10.1016/j.neulet.2008.11.009 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 401SF UT WOS:000262961600018 PM 19015000 ER PT J AU Aqel, RA Hage, FG Ellipeddi, P Blackmon, L McElderry, HT Kay, GN Plumb, V Iskandrian, AE AF Aqel, Raed A. Hage, Fadi G. Ellipeddi, Pavani Blackmon, Linda McElderry, Hugh T. Kay, G. Neal Plumb, Vance Iskandrian, Ami E. TI Usefulness of Three Posterior Chest Leads for the Detection of Posterior Wall Acute Myocardial Infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ST-SEGMENT ELEVATION; PERCUTANEOUS CORONARY INTERVENTION; 12-LEAD ELECTROCARDIOGRAM; STANDARD; ECG; FIBRINOLYSIS; ANGIOPLASTY; DIAGNOSIS; REGISTRY; THERAPY AB A significant proportion of patients with myocardial infarction are missed upon initial presentation to the emergency department. The 12-lead electrocardiogram (ECG) has a low sensitivity for the detection of acute myocardial infarction, especially if the culprit lesion is in the left circumflex artery (LCA). This study was designed to evaluate the benefit of adding 3 posterior chest leads on top of the 12-lead ECG to detect ischemia resulting from LC disease, using a model of temporary balloon occlusion to produce ischemia. We studied 53 consecutive patients who underwent clinically indicated coronary interventions. At the time of coronary angiography, the balloon was inflated to produce complete occlusion of the proximal LCA. We recorded and analyzed the changes noted on the 15-lead ECG, which included 3 posterior leads in addition to the standard 12 leads. In response to acute occlusion of the LCA, the posterior chest leads showed more ST elevation than the other leads, and more patients had ST elevation in the posterior leads than in any other lead. The 15-lead ECG was able to detect >= 0.5 mm (74% vs 38%, p<0.0001) and >= 1 mm (62% vs 34%, p<0.0001) ST elevation in any 2 contiguous leads more frequently than the 12-lead ECG. In conclusion, the 15-lead ECG identified more patients with posterior myocardial wall ischemia because of temporary balloon occlusion of the LC than the 12-lead ECG. This information may enhance the detection of posterior MI in the emergency department and potentially facilitate early institution of reperfusion therapy. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:159-164) C1 [Aqel, Raed A.] Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. Univ Alabama, Dept Med, Div Cardiovasc Dis, Birmingham, AL 35294 USA. RP Aqel, RA (reprint author), Birmingham Vet Affairs Med Ctr, Div Cardiol, Birmingham, AL USA. EM raed.aqel@med.va.gov OI Hage, Fadi/0000-0002-1397-4942 NR 26 TC 10 Z9 11 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 JAN 15 PY 2009 VL 103 IS 2 BP 159 EP 164 DI 10.1016/j.amjcard.2008.09.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 396AJ UT WOS:000262564300003 PM 19121429 ER PT J AU Lewis, WR Fonarow, GC LaBresh, KA Cannon, CP Pan, W Super, DM Sororf, SA Schwamm, LH AF Lewis, William R. Fonarow, Gregg C. LaBresh, Kenneth A. Cannon, Christopher P. Pan, Wenqin Super, Dennis M. Sororf, Suzanne A. Schwamm, Lee H. TI Differential Use of Warfarin for Secondary Stroke Prevention in Patients With Various Types of Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RHYTHM CONTROL; RISK-FACTORS; THERAPY; CARE AB Anticoagulation therapy significantly reduces the incidence of thromboembolic events in patients with atrial fibrillation (AF), and warfarin therapy at discharge is a class I-indicated drug in patients with ischemic stroke with persistent or paroxysmal AF without contraindications. The aim was to determine whether participation in the Get With The Guidelines-Stroke (GWTG-S) quality improvement program would be associated with improved adherence to anticoagulation guidelines for patients with all types of AF. Adherence to warfarin treatment at hospital discharge was assessed in eligible patients with AF who presented with stroke or transient ischemic attack, based on type of AF. Of patients with stroke, 10.5% presented with some form of AF. When AF was documented using electrocardiography or telemetry (ECG) during the present admission, eligible patients were more likely to receive warfarin compared with patients for whom AF was reported using medical history only (78.8% vs 49.4%; p<0.0001). Improvement after GWTG-S participation in warfarin use was observed in patients with ECG-documented AF (73.8% at baseline vs 88.5% after the intervention; p<0.0001), but not patients using history only. Women and elderly patients were less likely to receive warfarin, and these gaps in treatment did not narrow during the quality improvement program for patients with ECG-documented AF and those with history only. In conclusion, anticoagulation for stroke prevention was underused in general for patients with AF, even in such high-risk groups as patients with stroke. GWTG-S was associated with improved adherence for patients with ECG-documented AF, but patients with a history of AF alone were largely untreated. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:227-231) C1 [Lewis, William R.; Super, Dennis M.; Sororf, Suzanne A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Los Angeles, CA USA. [LaBresh, Kenneth A.] Masspro, Waltham, MA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. [Cannon, Christopher P.] Harvard Univ, Sch Med, Boston, MA USA. [Pan, Wenqin] Duke Clin Res Inst, Durham, NC USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Lewis, WR (reprint author), Case Western Reserve Univ, MetroHlth Campus, Cleveland, OH 44106 USA. EM wlewis@metrohealth.org RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145 FU American Heart Association, Dallas Texas; National Center for Research Resources [M01 RR000080]; National Institutes of Health, Bethesda, Maryland; GlaxoSmithKline FX The data analysis of this study was performed by the Duke Clinical Research Institute, Durham, North Carolina, and funded by the American Heart Association, Dallas Texas. Dr. Super was supported by Grant No. M01 RR000080 from the National Center for Research Resources, National Institutes of Health, Bethesda, Maryland. Dr. Lewis has received speaker honoraria from Reliant Pharmaceuticals. Dr. Fonarow has received research grants from GlaxoSmithKline and honoraria from GlaxoSmithKline, Merck, Schering-Plough, and Bristol Myers Squibb and is or has been a consultant for Glaxo-Smith-Kline, Schering-Plough, Merck, and Bristol Myers Squibb. Dr. Cannon has received research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb, Glaxo Smith Kline, Merck, Sanofi-Aventis, and Schering Plough. NR 13 TC 21 Z9 22 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 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 15 PY 2009 VL 103 IS 2 BP 227 EP 231 DI 10.1016/j.amjcard.2008.08.062 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 396AJ UT WOS:000262564300015 PM 19121441 ER PT J AU Setty, AR Robinson, D AF Setty, Arathi R. Robinson, Dwight TI A 62-Year-Old Man With Wrist and Hand Pain SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID LIGHT-CHAIN AMYLOIDOSIS; FACTOR-X DEFICIENCY; RHEUMATOID-ARTHRITIS; MUSCULOSKELETAL MANIFESTATIONS; POLYMYALGIA-RHEUMATICA; CLINICAL PRESENTATION; SYSTEMIC AMYLOIDOSIS; AL AMYLOIDOSIS; PITTING EDEMA; DIAGNOSIS C1 [Setty, Arathi R.] Mt Auburn Hosp, Cambridge, MA USA. [Robinson, Dwight] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Setty, AR (reprint author), 300 Mt Auburn St,Suite 410, Cambridge, MA 02138 USA. EM asetty@mah.harvard.edu NR 41 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 JAN 15 PY 2009 VL 61 IS 1 BP 132 EP 138 DI 10.1002/art.24098 PG 7 WC Rheumatology SC Rheumatology GA 394BN UT WOS:000262420300019 PM 19116980 ER PT J AU Kramarenko, II Bunni, MA Morinelli, TA Raymond, JR Garnovskaya, MN AF Kramarenko, Inga I. Bunni, Marlene A. Morinelli, Thomas A. Raymond, John R. Garnovskaya, Maria N. TI Identification of functional bradykinin B-2 receptors endogenously expressed in HEK293 cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE G protein-coupled receptors; Signal transduction; Intracellular Ca2(+); Na+/H+ exchange; Extracellular signal-regulated protein kinase 1 and 2 ID ARACHIDONIC-ACID RELEASE; EPITHELIAL-CELLS; MESANGIAL CELLS; NA+/H+ EXCHANGE; SMOOTH-MUSCLE; NUCLEAR-LOCALIZATION; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; MIMCD-3 CELLS; MAP KINASE AB The human embryonic kidney (HEK) 293 cell line is widely used in cell biology research. Although HEK293 cells have been meticulously studied, our knowledge about endogenous G protein-coupled receptors (GPCR) in these cells is incomplete. While studying the effects of bradykinin (BK), a potent growth factor for renal cells, we unexpectedly discovered that BK activates extracellular signal-regulated protein kinase 1 and 2 (ERK) in HEK293 cells. Thus, we hypothesized that HEK293 cells possess endogenous BK receptors. RT-PCR demonstrated the presence of mRNAs for BK B-1 and BK B-2 receptors in HEK293 cells. Western blotting with BK B-1 and BK B-2 receptor antibodies confirmed this result at the protein level. To establish that BK receptors are functional, we employed fluorescent measurements of intracellular Ca2+, measured changes in extracellular acidification rate (ECAR) as a reflection of the Na+/H+ exchange (NHE) with a Cytosensor (TM) microphysiometer, and assessed ERK activation by Western blotting with a phospho-specific ERK antibody. Exposure of HEK293 cells to BK produced a concentration-dependent rise in intracellular Ca2+, (EC50 = 36.5 +/- 8.0 x 10 (9) M), a rapid increase in tyrosine phosphorylation of ERK (EC50 = 9.8 +/- 0.4 x 10 (9) M), and elevation in ECAR by similar to 20%. All of these signals were blocked by HOE-140 (B-2 receptor antagonist) but not by des-Arg(10)-HOE-140 (B-1 receptor antagonist). We conclude that HEK293 cells express endogenous functional BK B-2 receptors, which couple to the mobilization of intracellular Ca2+, increases in ECAR and increases in ERK phosphorylation. Published by Elsevier Inc. C1 [Kramarenko, Inga I.; Bunni, Marlene A.; Morinelli, Thomas A.; Raymond, John R.; Garnovskaya, Maria N.] Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. [Kramarenko, Inga I.; Bunni, Marlene A.; Morinelli, Thomas A.; Raymond, John R.; Garnovskaya, Maria N.] Ralph H Johnson Vet Affairs Med Ctr, Med & Res Serv, Charleston, SC 29401 USA. RP Garnovskaya, MN (reprint author), Med Univ S Carolina, Dept Med Nephrol, 96 Jonathan Lucas St,MSC 629, Charleston, SC 29425 USA. EM garnovsk@musc.edu FU Department of Veterans Affairs; AHA [GIA 0655445U]; National Institutes of Health [DK52448, GM63909]; M.U.S.C. Division of Nephrology and Dialysis Clinics, Incorporated FX This work was supported by grants from the Department of Veterans Affairs (Merit Awards and a REAP Award to MNG and JRR), AHA (GIA 0655445U to MNG), the National Institutes of Health (DK52448 and GM63909 to JRR), and a laboratory endowment jointly supported by the M.U.S.C. Division of Nephrology and Dialysis Clinics, Incorporated (JRR). NR 33 TC 12 Z9 12 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JAN 15 PY 2009 VL 77 IS 2 BP 269 EP 276 DI 10.1016/j.bcp.2008.09.027 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 394ZW UT WOS:000262492700014 PM 18938142 ER PT J AU Polter, A Yang, SF Zmijewska, AA van Groen, T Paik, JH DePinho, RA Peng, SL Jope, RS Li, XH AF Polter, Abigail Yang, Sufen Zmijewska, Anna A. van Groen, Thomas Paik, Ji-Hye DePinho, Ronald A. Peng, Stanford L. Jope, Richard S. Li, Xiaohua TI Forkhead Box, Class O Transcription Factors in Brain: Regulation and Behavioral Manifestation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Akt; antidepressant; anxiety; depression; FoxOs; serotonin ID PROTEIN-KINASE B; ANXIETY-LIKE BEHAVIORS; FACTOR FKHR; TUMOR SUPPRESSION; FACTOR FOXO3A; ALVEOLAR RHABDOMYOSARCOMA; SEROTONIN TRANSPORTER; SYMPATHETIC NEURONS; SIGNALING PATHWAY; OXIDATIVE STRESS AB Background: The mammalian forkhead box, class O (FoxO) transcription factors function to regulate diverse physiological processes. Emerging evidence that both brain-derived neurotrophic factor (BDNF) and lithium suppress FoxO activity suggests a potential role of FoxOs in regulating mood-relevant behavior. Here, we investigated whether brain FoxO1 and FoxO3a can be regulated by serotonin and antidepressant treatment and whether their genetic deletion affects behaviors. Methods: C57BL/6 mice were treated with D-fenfluramine to increase brain serotonergic activity or with the antidepressant imipramine. The functional status of brain FoxO1 and FoxO3a was audited by immunoblot analysis for phosphorylation and subcellular localization. The behavioral manifestations in FoxO1- and FoxO3a-deficient mice were assessed via the Elevated Plus Maze Test, Forced Swim Test, Tail Suspension Test, and Open Field Test. Results: Increasing serotonergic activity by D-fenfluramine strongly increased phosphorylation of FoxO1 and FoxO3a in several brain regions and reduced nuclear FoxO1 and FoxO3a. The effect Of D-fenfluramine was mediated by the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Chronic, but not acute, treatment with the antidepressant imipramine also increased the phosphorylation of brain FoxO1 and FoxO3a. When FoxO1 was selectively deleted from brain, mice displayed reduced anxiety. In contrast, FoxO3a-deficient mice presented with a significant antidepressant-like behavior. Conclusions: FoxOs may be a transcriptional target for anxiety and mood disorder treatment. Despite their physical and functional relatedness, FoxO1 and FoxO3a influence distinct behavioral processes linked to anxiety and depression. Findings in this study reveal important new roles of FoxOs in brain and provide a molecular framework for further investigation of how FoxOs may govern mood and anxiety disorders. C1 [Polter, Abigail; Yang, Sufen; Zmijewska, Anna A.; Jope, Richard S.; Li, Xiaohua] Univ Alabama, Dept Psychiat, Birmingham, AL 35294 USA. [Polter, Abigail] Univ Alabama, Dept Neurobiol, Birmingham, AL 35294 USA. [van Groen, Thomas] Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med Oncol, Ctr Appl Canc Sci, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. [Paik, Ji-Hye; DePinho, Ronald A.] Harvard Univ, Sch Med, Boston, MA USA. [Peng, Stanford L.] Roche Palo Alto, Palo Alto, CA USA. RP Li, XH (reprint author), Univ Alabama, Dept Psychiat & Behav Neurobiol, 1075 Sparks Ctr,1720 7th Ave S, Birmingham, AL 35294 USA. EM xili@uab.edu RI van Groen, Thomas/A-3150-2008 FU National Institutes of Health (NIH) [MH64555, MH73723, MH38752, CA84628, AI57571]; the University of Alabama at Birmingham [UAB] Behavioral Assessment Core [NS47466]; (the Alabama Neuroscience Blueprint Core Center [NS57098]; National Alliance for Research on Schizophrenia and Depression; Robert A. and Renee F. Belfer Foundation Institute for Innovative Cancer Science; Damon Runyon Cancer Research Foundation FX This study was supported by National Institutes of Health (NIH) Grants: MH64555 and MH73723 (XL), MH38752 (RSJ), CA84628 (RAD), AI57571 (SLP), and in part by NS47466 (the University of Alabama at Birmingham [UAB] Behavioral Assessment Core, principal investigator [PI], John Hablitz) and NS57098 (the Alabama Neuroscience Blueprint Core Center PI, Kevin A. Roth). XL is also supported by the National Alliance for Research on Schizophrenia and Depression independent investigator award. RAD is an American Cancer Society Research Professor and is supported by the Robert A. and Renee F. Belfer Foundation Institute for Innovative Cancer Science. J-HP is a Damon Runyon Fellows supported by the Damon Runyon Cancer Research Foundation. NR 79 TC 51 Z9 51 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 15 PY 2009 VL 65 IS 2 BP 150 EP 159 DI 10.1016/j.biopsych.2008.08.005 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 391KB UT WOS:000262231100009 PM 18823877 ER PT J AU Leleu, X Xu, L Jia, XY Sacco, A Farag, M Hunter, ZR Moreau, AS Ngo, HT Hatjiharissi, E Ho, AW Santos, DD Adamia, S O'Connor, K Ciccarelli, B Soumerai, J Manning, RJ Patterson, CJ Roccaro, AM Ghobrial, IM Treon, SP AF Leleu, Xavier Xu, Lian Jia, Xiaoying Sacco, Antonio Farag, Mena Hunter, Zachary R. Moreau, Anne-Sophie Ngo, Hai T. Hatjiharissi, Evdoxia Ho, Allen W. Santos, Daniel D. Adamia, Sofia O'Connor, Kelly Ciccarelli, Bryan Soumerai, Jacob Manning, Robert J. Patterson, Christopher J. Roccaro, Aldo M. Ghobrial, Irene M. Treon, Steven P. TI Endoplasmic reticulum stress is a target for therapy in Waldenstrom macroglobulinemia SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; MULTIPLE-MYELOMA CELLS; ER STRESS; IMMUNOGLOBULIN PRODUCTION; INTERNATIONAL WORKSHOP; TRANSCRIPTION FACTOR; IN-VITRO; B-CELLS; CASPASE-12; INHIBITION AB Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoma characterized by bone marrow (BM) involvement of IgM secreting lymphoplasmacytic cells. The induction of unfolded protein response (UPR) genes ("physiologic" UPR) enables cells to differentiate into professional secretory cells capable of production of high amounts of endoplasmic reticulum (ER)-processed proteins, such as immunoglobulins. Ultimately, the initially cytoprotective UPR triggers an apoptotic cascade if ER stress is not corrected, called proapoptotic/terminal UPR. We show that WM cells inherently express the physiologic UPR machinery compared with normal BM cells, and that increased ER stress leads to proapoptotic/terminal UPR in WM cells. We therefore examined tunicamycin, ER stress inducer, for potential antitumor effects in WM. Tunicamycin induced significant cytotoxicity, apoptosis and cell-cycle arrest, and inhibited DNA synthesis in WM cell lines and primary BM CD19(+) cells from patients with WM with an inhibitory concentration (IC(50)) of 0.5 mu g/mL to 1 mu g/mL, but not in healthy donor cells. Importantly, coculture of WM cells in the context of the BM microenvironment did not inhibit tunicamycin-induced cytotoxicity. Finally, we demonstrate that ER stress inducer synergizes with other agents used in the treatment of WM. These preclinical studies provide a framework for further evaluation of ER stress inducing agents as therapeutic agents in WM. (Blood. 2009; 113: 626-634) C1 [Treon, Steven P.] Dana Farber Canc Inst, Bing Program Waldenstrom Macroglobulinemia, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA 02115 USA. [Leleu, Xavier; Xu, Lian; Jia, Xiaoying; Sacco, Antonio; Farag, Mena; Hunter, Zachary R.; Ngo, Hai T.; Hatjiharissi, Evdoxia; Ho, Allen W.; Santos, Daniel D.; Adamia, Sofia; O'Connor, Kelly; Ciccarelli, Bryan; Soumerai, Jacob; Manning, Robert J.; Patterson, Christopher J.; Roccaro, Aldo M.; Ghobrial, Irene M.; Treon, Steven P.] Harvard Univ, Sch Med, Boston, MA USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Immunol Lab, Lille, France. [Jia, Xiaoying; Sacco, Antonio; Farag, Mena; Ngo, Hai T.; Roccaro, Aldo M.; Ghobrial, Irene M.] Dana Farber Canc Inst, Kirsch Lab Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Program Waldenstrom Macroglobulinemia, Bing Ctr Waldenstrom Macroglobulinemia, 44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvarrd.edu RI Ho, Allen/B-3017-2011; Hunter, Zachary/H-3018-2013; Sacco, Antonio/K-4681-2016; OI Hunter, Zachary/0000-0002-1689-1691; Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 FU Franco-American Fulbright Foundation; International Waldenstrom Macroglobulinemia Foundation FX X. L. was supported by a grant from the Franco-American Fulbright Foundation. This work was supported in part by the International Waldenstrom Macroglobulinemia Foundation. NR 44 TC 16 Z9 17 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 15 PY 2009 VL 113 IS 3 BP 626 EP 634 DI 10.1182/blood-2007-10-116848 PG 9 WC Hematology SC Hematology GA 394ZO UT WOS:000262491900020 PM 18981296 ER PT J AU Bergmeier, W Oh-hora, M McCarl, CA Roden, RC Bray, PF Feske, S AF Bergmeier, Wolfgang Oh-hora, Masatsugu McCarl, Christie-Ann Roden, R. Claire Bray, Paul F. Feske, Stefan TI R93W mutation in Orai1 causes impaired calcium influx in platelets SO BLOOD LA English DT Article ID CHANNEL FUNCTION; CA2+ CHANNELS; SENSOR STIM1; MICE LACKING; CRAC CHANNEL; ACTIVATION; ENTRY; CELL; INHIBITION; DEFICIENCY AB The intracellular Ca(2+) concentration of many nonexcitable cells is regulated by calcium store release and store-operated calcium entry (SOCE). In platelets, STIM1 was recently identified as the main calcium sensor expressed in the endoplasmic reticulum. To evaluate the role of the SOC channel moiety, Orai1, in platelet SOCE, we generated mice expressing a mutated, inactive form of Orai1 in blood cells only (Orai1(R93W)). Platelets expressing Orai1R93W were characterized by markedly reduced SOCE and impaired agonist-induced increases in [Ca(2+)](i). Orai1(R93W) platelets showed reduced integrin activation and impaired degranulation when stimulated with low agonist concentrations under static conditions. This defect, however, did not significantly affect the ability of Orai1(R93W) platelets to aggregate or to adhere to collagen under arterial flow conditions ex vivo. In contrast, these adherent Orai1(R93W) platelets were defective in surface phosphatidylserine exposure, suggesting that Orai1 is crucial for the platelets' procoagulant response rather than for other Ca(2+)- dependent cellular responses. (Blood. 2009; 113: 675-678) C1 [Bergmeier, Wolfgang; Roden, R. Claire; Bray, Paul F.] Thomas Jefferson Univ, Cardeza Fdn, Philadelphia, PA 19007 USA. [Bergmeier, Wolfgang; Oh-hora, Masatsugu; McCarl, Christie-Ann; Feske, Stefan] Immune Dis Inst, Boston, MA USA. [Bergmeier, Wolfgang; Oh-hora, Masatsugu; McCarl, Christie-Ann; Feske, Stefan] Harvard Univ, Sch Med, Boston, MA USA. [Bergmeier, Wolfgang; Roden, R. Claire; Bray, Paul F.] Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19007 USA. [McCarl, Christie-Ann; Feske, Stefan] NYU, Sch Med, New York, NY USA. RP Bergmeier, W (reprint author), Thomas Jefferson Univ, Cardeza Fdn, 803 Curtis,1015 Walnut St, Philadelphia, PA 19007 USA. EM wolfgang.bergmeier@jefferson.edu; feskes01@nyumc.org OI Feske, Stefan/0000-0001-5431-8178 FU National Institutes of Health (NIH) [AI066128, GM075256, R37-HL41002]; American Heart Association [Grant 0630044N]; March of Dimes Foundation; Uehara Memorial Foundation FX We thank Ying Jin for help with the RT-PCR assay and Peter Sims for providing DNA samples from a healthy volunteer and a Scott patient. We also thank Denisa Wagner and Anjana Rao for their support throughout the study and for use of their laboratory space. This work was supported by National Institutes of Health (NIH) grants AI066128 (S. F.), GM075256 (Anjana Rao), and R37-HL41002 (Denisa Wagner), a Scientist Development Grant 0630044N from the American Heart Association (W. B.), a March of Dimes Foundation grant (S. F.), and a Uehara Memorial Foundation research fellowship (M. O.). NR 27 TC 70 Z9 71 U1 1 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 JAN 15 PY 2009 VL 113 IS 3 BP 675 EP 678 DI 10.1182/blood-2008-08-174516 PG 4 WC Hematology SC Hematology GA 394ZO UT WOS:000262491900027 PM 18952890 ER PT J AU Nilsson, ME Maciejewski, PK Zhang, BH Wright, AA Trice, ED Muriel, AC Friedlander, RJ Fasciano, KM Block, SD Prigerson, HG AF Nilsson, Matthew E. Maciejewski, Paul K. Zhang, Baohui Wright, Alexi A. Trice, Elizabeth D. Muriel, Anna C. Friedlander, Robert J. Fasciano, Karen M. Block, Susan D. Prigerson, Holly G. TI Mental Health, Treatment Preferences, Advance Care Planning, Location, and Quality of Death in Advanced Cancer Patients With Dependent Children SO CANCER LA English DT Article DE cancer; dependent children; psychiatric illness; Do Not Resuscitate; hospice; end-of-life; advance care planning; quality-of-life ID OF-LIFE QUESTIONNAIRE; EARLY BREAST-CANCER; ADJUVANT CHEMOTHERAPY; INTERVENTIONS; WORTHWHILE; VALIDITY; PEACE; END AB BACKGROUND: Clinicians observe that advanced cancer patients with dependent children agonize over the impact their death will have on their children. The objective of this study was to determine empirically whether advanced cancer patients with and without dependent children differ in treatment preferences, mental health, and end-of-life (EOL) outcomes. METHODS: Coping with Cancer is a National Cancer Institute/National Institute of Mental Health-funded, multi-institutional, prospective cohort study of 668 patients with advanced cancer. Patients with and without dependent children were compared on rates of psychiatric disorders, advance care planning (ACID), EOL care, quality of their last week of life, and location of death. RESULTS: In adjusted analyses, patients with advanced cancer who had dependent children were more likely to meet panic disorder criteria (adjusted odds ratio [AOR], 5.41; 95% confidence interval [95% CI], 2,13-13.69), more likely to be worried (mean difference in standard deviations [delta], 0.09; P = .006), and more likely to prefer aggressive treatment over palliative care (AOR, 1.77; 95% Cl, 1.07-2.93). Patients with dependent children were less likely to engage in ACID (eg, do not resuscitate orders: AOR, 0.44; 95% Cl, 0.26-0.75) and had a worse quality of life in the last week of life (delta, 0.15; P - .007). Among spousal care-givers, those with dependent children were more likely to meet criteria for major depressive disorder (AOR, 4.53: 95% Cl, 1.47-14) and generalized anxiety disorder (AOR, 3.95; 95% Cl, 1.29-12.16). CONCLUSIONS: Patients with dependent children were more anxious, were less likely to engage in ACID, and were more likely to have a worse quality of life in their last week of life. Advanced cancer patients and spousal caregivers with dependent children represent a particularly distressed group that warrants further clinical attention, research, and support. Cancer 2009;115:399-409. (C) 2009 American Cancer Society. C1 [Nilsson, Matthew E.; Zhang, Baohui; Wright, Alexi A.; Trice, Elizabeth D.; Muriel, Anna C.; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 01225 USA. [Nilsson, Matthew E.; Zhang, Baohui; Wright, Alexi A.; Trice, Elizabeth D.; Fasciano, Karen M.; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 01225 USA. [Maciejewski, Paul K.] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. [Muriel, Anna C.] Massachusetts Gen Hosp, Canc Ctr Parenting Program, Boston, MA 02114 USA. [Muriel, Anna C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Friedlander, Robert J.] New Hampshire Oncol Hematol PA, Hooksett, NH USA. [Fasciano, Karen M.; Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. RP Nilsson, ME (reprint author), Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, 530 Shields Warren Bldg,44 Binney St, Boston, MA 01225 USA. FU National Institute of Mental Health [CA106370]; National Cancer Institute; Center For Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute FX Supported in part by the following grants to Dr. Prigerson: MH63892 from the National Institute of Mental Health, CA106370 from the National Cancer Institute, and the Center For Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. NR 30 TC 45 Z9 45 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD JAN 15 PY 2009 VL 115 IS 2 BP 399 EP 409 DI 10.1002/cncr.24002 PG 11 WC Oncology SC Oncology GA 401LJ UT WOS:000262941900020 PM 19110677 ER PT J AU Letai, A AF Letai, A. TI Harnessing apoptosis to kill breast cancer cells SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [Letai, A.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 61S EP 61S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200003 ER PT J AU Richardson, A Carey, L AF Richardson, A. Carey, L. TI Pathobiology: when the tumor is the target SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 62S EP 62S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200006 ER PT J AU Polyak, K Shipitsin, M Campbell, L Yao, J AF Polyak, K. Shipitsin, M. Campbell, L. Yao, J. TI Breast tumor evolution SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 SU S BP 64S EP 64S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200013 ER PT J AU Polyak, K Hu, M Shipitsin, M AF Polyak, K. Hu, M. Shipitsin, M. TI Microenvironmental changes in breast tumor progression: genetic or epigenetic? SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [Polyak, K.; Hu, M.; Shipitsin, M.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 SU S BP 64S EP 64S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200016 ER PT J AU Burstein, HJ Sun, Y Tan, AR Dirix, L Vermette, JJ Powell, C Zacharchuk, C Badwe, RA AF Burstein, H. J. Sun, Y. Tan, A. R. Dirix, L. Vermette, J. J. Powell, C. Zacharchuk, C. Badwe, R. A. TI Neratinib (HKI-272), an irreversible pan erbB receptor tyrosine kinase inhibitor: phase 2 results in patients with advanced HER2+breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Chinese Acad Med Sci, Canc Inst & Hosp, Beijing, Peoples R China. Canc Inst New Jersey, New Brunswick, NJ USA. Oncol Ctr AZ St Augustinus, Antwerp, Belgium. Wyeth Ayerst Res, Cambridge, MA USA. Tata Mem Hosp, Bombay 400012, Maharashtra, India. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 72S EP 73S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200039 ER PT J AU Ganz, PA Land, SR Geyer, CE Costantino, JP Pajon, ER Fehrenbacher, L Atkins, JN Polikoff, JA Vogel, VG Erban, JK Livingston, RB Perez, EA Mamounas, EP Wolmark, A Swain, SM AF Ganz, P. A. Land, S. R. Geyer, C. E. Costantino, J. P. Pajon, E. R. Fehrenbacher, L. Atkins, J. N. Polikoff, J. A. Vogel, V. G. Erban, J. K. Livingston, R. B. Perez, E. A. Mamounas, E. P. Wolmark, A. Swain, S. M. TI NSABP B-30: definitive analysis of quality of life (QOL) and menstrual history (MH) outcomes from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 NSABP, Pittsburgh, PA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Pittsburgh, Grad Sch Publ Hlth, NSABP Biostat Ctr, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Colarado Canc Res Prog, Denver, CO USA. Kaiser Permanente No Calif, Vallejo, CA USA. SE Canc Control Consortium CCOP, Goldsboro, NC USA. So Calif Kaiser Permanente, San Diego, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. ECOG, Philadelphia, PA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Univ Arizona, Arizona Canc Ctr, Arizona Hlth Sci Ctr, Ann Arbor, MI USA. NCCTG, Rochester, MN USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Aultman Hlth Fdn, Canton, OH USA. Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 81S EP 82S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200065 ER PT J AU Swain, SM Jeong, JH Geyer, CE Costantino, JP Pajon, ER Fehrenbacher, L Atkins, JN Polikoff, J Vogel, VG Erban, JK Livingston, RB Perez, EA Mamounas, EP Ganz, PA Land, SR Wolmark, N AF Swain, S. M. Jeong, J-H Geyer, C. E. Costantino, J. P. Pajon, E. R. Fehrenbacher, L. Atkins, J. N. Polikoff, J. Vogel, V. G. Erban, J. K. Livingston, R. B. Perez, E. A. Mamounas, E. P. Ganz, P. A. Land, S. R. Wolmark, N. TI NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 NSABP, Pittsburgh, PA USA. Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA. Univ Pittsburgh, NSABP Biostat Ctr, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Grad Sch Publ Hlth, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Colorado Canc Res Prog, Denver, CO USA. Kaiser Permanente No Calif, Vallejo, CA USA. SE Canc Control Consortium CCOP, Goldsboro, NC USA. So Calif Kaiser Permanente, San Diego, CA USA. Univ Pittsburgh, Pittsburgh, PA USA. ECOG, Philadelphia, PA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. SWOG, Ann Arbor, MI USA. Univ Arizona, Arizona Canc Ctr, Arizona Hlth Sci Ctr, Tucson, AZ USA. NCCTG, Rochester, NY USA. Mayo Clin, Jacksonville, FL 32224 USA. Aultman Hlth Fdn, Canton, OH USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 81S EP 81S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200064 ER PT J AU Ozanne, EM Cipriano, L Cameron, M Newman, T Esserman, LJ AF Ozanne, E. M. Cipriano, L. Cameron, M. Newman, T. Esserman, L. J. TI Cost-effectiveness of surgical interventions for BRCA gene mutation carriers: impact of delaying decision-making SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 94S EP 94S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200103 ER PT J AU Mayer, EL Isakoff, SJ Hannagan, K Savoie, J Beckman, J Klement, G Gelman, R Winer, EP Burstein, HJ AF Mayer, E. L. Isakoff, S. J. Hannagan, K. Savoie, J. Beckman, J. Klement, G. Gelman, R. Winer, E. P. Burstein, H. J. TI A phase I study of vandetanib and metronomic chemotherapy in advanced breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 105S EP 105S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200133 ER PT J AU Alexander, BM Sproll, K Wang, X DAndrea, AD Schnill, SJ Collins, LC Weaver, DT Garber, JE AF Alexander, B. M. Sproll, K. Wang, X. DAndrea, A. D. Schnill, S. J. Collins, L. C. Weaver, D. T. Garber, J. E. TI DNA repair protein biomarkers in triple negative breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Harvard Radiat Oncol Program, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. DNA Repair Company, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 124S EP 124S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200195 ER PT J AU Sgroi, D Goss, P Steffel, L Lester, S Brock, J Hameed, O Hattab, E Ma, XJ Erlander, M AF Sgroi, D. Goss, P. Steffel, L. Lester, S. Brock, J. Hameed, O. Hattab, E. Ma, X-J Erlander, M. TI Comparison of risk stratification by OncotypeDX versus HOXB13/IL17BR index and molecular grade index in 166 estrogen receptor positive patients from multiple institutions SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Alabama, Birmingham, AL USA. Indiana Univ, Indianapolis, IN 46204 USA. AviaraDx, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 127S EP 127S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200203 ER PT J AU Stadler, ZK Stoeckert, K Perez, A Regan, M Golshan, M Garber, JE AF Stadler, Z. K. Stoeckert, K. Perez, A. Regan, M. Golshan, M. Garber, J. E. TI Factors affecting surgical decision-making in patients undergoing BRCAI/2 testing at breast cancer diagnosis SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 134S EP 135S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200226 ER PT J AU Wang, Y Collins, L Schnitt, S Garber, J Tung, N AF Wang, Y. Collins, L. Schnitt, S. Garber, J. Tung, N. TI Characterization of estrogen receptor-positive breast cancers in BRCA1 mutation carriers SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Faber Canc Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 137S EP 137S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200236 ER PT J AU De Nicolo, A Pathania, S Parisini, E Branda, KJ Stoeckert, K Garber, JE AF De Nicolo, A. Pathania, S. Parisini, E. Branda, K. J. Stoeckert, K. Garber, J. E. TI BRCA1 c.5181_5183delGTT (p.Vall688del) is a true pathogenic mutation that affects both protein stability and function: implications for genetic counseling. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [De Nicolo, A.; Pathania, S.; Parisini, E.; Branda, K. J.; Stoeckert, K.; Garber, J. E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 138S EP 138S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200237 ER PT J AU Burga, LN Tung, N Troyan, SL Lee, BT Houlihan, MJ Pories, SE Staradub, V Tobias, A Come, SE Coffey, K Wulf, GM AF Burga, L. N. Tung, N. Troyan, S. L. Lee, B. T. Houlihan, M. J. Pories, S. E. Staradub, V Tobias, A. Come, S. E. Coffey, K. Wulf, G. M. TI A potential role of EGFR-inhibitors for the prevention of BRCA1-related breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Beth Isareal Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 139S EP 139S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200241 ER PT J AU Ligibel, JA Campbell, N Anita, GH Shockro, L Salinardi, T Winer, EP AF Ligibel, J. A. Campbell, N. Anita, G-H Shockro, L. Salinardi, T. Winer, E. P. TI impact of a home-based physical activity intervention upon exercise behaviors and anthropometric measures in women undergoing treatment for early stage breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [Ligibel, J. A.; Campbell, N.; Anita, G-H; Shockro, L.; Salinardi, T.; Winer, E. P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 141S EP 141S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200248 ER PT J AU Moy, B Tu, D Shepherd, LE Palmer, WJ Ingle, JN Goss, PE AF Moy, B. Tu, D. Shepherd, L. E. Palmer, W. J. Ingle, J. N. Goss, P. E. TI NCIC CTG MA.17: hormone receptor expression of in-breast recurrences and contralateral primary breast cancers arising on aromatase inhibitors SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON, Canada. Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 146S EP 146S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200264 ER PT J AU Anderson, KS Sibani, S Wong, J Hainsworth, E Mendoza, EA Eugene, R Raphael, J Logvinenko, T Ramachandran, N Godwin, A Marks, J Engstrom, P LaBaer, J AF Anderson, K. S. Sibani, S. Wong, J. Hainsworth, E. Mendoza, E. A. Eugene, R. Raphael, J. Logvinenko, T. Ramachandran, N. Godwin, A. Marks, J. Engstrom, P. LaBaer, J. TI Using custom protein microarrays to identify autoantibody biomarkers for the early detection of breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Inst Prote, Cambridge, MA USA. Tufts Med Ctr, Boston, MA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Duke Univ, Med Ctr, Durham, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 157S EP 157S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200297 ER PT J AU Dang, C Lin, N Moy, B Come, S Lake, D Theodoulou, M Troso-Sandoval, T Dickler, M Gorsky, M D'Andrea, G Modi, S Seidman, A Drullinsky, P Partridge, A Schapira, L Wulf, G Gilewski, T Atieh, D Mayer, E Isakoff, S Sugarman, S Fornier, M Traina, T Bromberg, J Currie, V Robson, M Burstein, H Overmoyer, B Ryan, P Kuter, I Younger, J Schumer, S Tung, N Zarwan, C Schnipper, L Chen, C Winer, E Norton, L Hudis, C AF Dang, C. Lin, N. Moy, B. Come, S. Lake, D. Theodoulou, M. Troso-Sandoval, T. Dickler, M. Gorsky, M. D'Andrea, G. Modi, S. Seidman, A. Drullinsky, P. Partridge, A. Schapira, L. Wulf, G. Gilewski, T. Atieh, D. Mayer, E. Isakoff, S. Sugarman, S. Fornier, M. Traina, T. Bromberg, J. Currie, V Robson, M. Burstein, H. Overmoyer, B. Ryan, P. Kuter, I Younger, J. Schumer, S. Tung, N. Zarwan, C. Schnipper, L. Chen, C. Winer, E. Norton, L. Hudis, C. TI Dose-dense (DD) doxorubicin and cyclophosphamide (AC) followed by weekly paclitaxel (P) with trastuzumab (T) and lapatinib (L) in HER2/neu-positive breast cancer is not feasible due to excessive diarrhea: updated results. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Fornier, Monica/F-5899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 189S EP 189S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583200396 ER PT J AU Goss, PE Njar, VCO Qi, S Hu, H Gediya, LK Puranik, P Khandelwal, A AF Goss, P. E. Njar, V. C. O. Qi, S. Hu, H. Gediya, L. K. Puranik, P. Khandelwal, A. TI Effects of novel retinoic acid metabolism blocking agent (VN/14-1) on N-methyl-N-nitrosourea (MNU)-induced mammary carcinoma and uterus in the rat model. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Puranik, Purushottamachar/A-9725-2008 OI Puranik, Purushottamachar/0000-0001-9540-067X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 196S EP 196S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201004 ER PT J AU Ryan, PD Neven, P Dirix, LY Barrios, CH Miller, WH Fenton, D Abraham, MF Paccagnella, L Gualberto, A Goss, PE AF Ryan, P. D. Neven, P. Dirix, L. Y. Barrios, C. H. Miller, W. H. Fenton, D. Abraham, M. F. Paccagnella, L. Gualberto, A. Goss, P. E. TI Safety of the anti-IGF-1R antibody CP-751,871 in combination with exemestane in patients with advanced breast cancer. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Multidisciplinair Borstcentrum Gynecol, UZ Gasthuisberg, Louvain, Belgium. Oncol Centrum, AZ Sint Augustinus, Antwerp, Belgium. Hosp Sao Lucas PUCRS, Ctr Pesquisa & Oncol, Porto Alegre, RS, Brazil. Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Inst Invest Clin, Santa Fe, Argentina. Pfizer Global Res & Dev, New London, CT USA. RI Barrios, Carlos/G-8525-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 197S EP 197S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201007 ER PT J AU Ozanne, EM Shorko, J Drohon, B Grinstein, G Hughes, KS AF Ozanne, E. M. Shorko, J. Drohon, B. Grinstein, G. Hughes, K. S. TI Identification of high-risk lesions through automated natural language processing (NLP) of pathology reports SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Massachusetts, Lowell, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 205S EP 205S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201029 ER PT J AU Xu, Y Watlers, A Leibovich, SJ Mann, D Rueda, BR Gonzalez, RR AF Xu, Y. Watlers, A. Leibovich, S. J. Mann, D. Rueda, B. R. Gonzalez, R. R. TI Molecular mechanisms for leptin regulation of VEGF in breast cancer cells. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Morehouse Sch Med, Atlanta, GA 30310 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Cardiovasc Res Ctr, Newark, NJ 07103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 225S EP 225S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201096 ER PT J AU Kaur, H Silverman, P Singh, D Fu, P Farag, R Wang, N Cooper, BW Krishnamurthi, S Dumadog, L Lyons, J Remick, S Overmoyer, B AF Kaur, H. Silverman, P. Singh, D. Fu, P. Farag, R. Wang, N. Cooper, B. W. Krishnamurthi, S. Dumadog, L. Lyons, J. Remick, S. Overmoyer, B. TI Phase II study of weekly administration of docetaxel (D) in combination with the epidermal growth factor receptor (EGFR) inhibitor erlotinib (E) in metastatic breast cancer (MBC) SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 ICC, Cleveland, OH USA. WVU, Morgantown, WV USA. DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 239S EP 239S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201142 ER PT J AU Mayer, E Kozloff, M Qamar, R Klencke, B Balkissoon, J Parmar, H Samant, M Burstein, HJ AF Mayer, E. Kozloff, M. Qamar, R. Klencke, B. Balkissoon, J. Parmar, H. Samant, M. Burstein, H. J. TI SABRE-B: a randomized phase II trial evaluating the safety and efficacy of combining sunitinib (S) with paclitaxel (P) plus bevacizumab (B) as first-line treatment for HER2-negative metastatic breast cancer (MBC): final results SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, San Francisco, CA 94080 USA. RI qamar, raheel/D-4543-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 239S EP 240S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201144 ER PT J AU Krop, IE Mita, M Burris, HA Birkner, M Girish, S Tibbitts, J Holden, SN Lutzker, SG Modi, S AF Krop, I. E. Mita, M. Burris, H. A. Birkner, M. Girish, S. Tibbitts, J. Holden, S. N. Lutzker, S. G. Modi, S. TI A phase I study of weekly dosing of trastuzumab-DM1 (T-DM1) in patients with advanced HER2+breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Drug Dev, San Antonio, TX USA. Sarah Cannon Res Inst, Nashville, TN USA. Genentech Inc, San Francisco, CA 94080 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 3 Z9 3 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 243S EP 243S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201154 ER PT J AU Tolaney, SM Najita, J Chen, W Savoie, J Fornier, M Krop, IE Winer, EP Bunnell, C AF Tolaney, S. M. Najita, J. Chen, W. Savoie, J. Fornier, M. Krop, I. E. Winer, E. P. Bunnell, C. TI A phase II study of ixabepilone plus trastuzumab for metastatic HER2-positive breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Mem Sloan Kettering Canc Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Fornier, Monica/F-5899-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 243S EP 243S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201155 ER PT J AU Gavenonis, SC Lee, JM Halpern, EF Rafferty, EA AF Gavenonis, S. C. Lee, J. M. Halpern, E. F. Rafferty, E. A. TI Positive predictive value of breast MRI in cancer detection. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [Gavenonis, S. C.; Lee, J. M.; Halpern, E. F.; Rafferty, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 253S EP 254S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201184 ER PT J AU Vachon, C Sasano, H Ghosh, K Brandt, K Santen, R Watson, D Lingle, W Goss, P Hartmann, L Reynolds, C Pankratz, VS Ingle, J AF Vachon, C. Sasano, H. Ghosh, K. Brandt, K. Santen, R. Watson, D. Lingle, W. Goss, P. Hartmann, L. Reynolds, C. Pankratz, V. S. Ingle, J. TI Evaluation of aromatase expression in mammographically dense and non-dense regions of the breast in healthy women. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Mayo Clin, Rochester, MN USA. Tohoku Univ, Sch Med, Tohoku, Japan. Univ Virginia, Charlottesville, VA 22903 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 261S EP 262S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201209 ER PT J AU Morris, PG Dickler, M McArthur, H Traina, T Godfrey, L Steingart, R Rugo, H Lin, N Moy, B Come, S Sugarman, S Norton, L Hudis, CA Dang, C AF Morris, P. G. Dickler, M. McArthur, H. Traina, T. Godfrey, L. Steingart, R. Rugo, H. Lin, N. Moy, B. Come, S. Sugarman, S. Norton, L. Hudis, C. A. Dang, C. TI Adjuvant dose-dense doxorubicin-cyclophosphamide x 4 with or without bevacizumab is safe: no evidence of short-term changes in left ventricular ejection fraction. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual Meeting of the San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 SU S BP 281S EP 281S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201270 ER PT J AU Garwood, ER Kumar, AS Baehner, F Garber, JE Troyan, S Olopade, OI Moore, D Au, A Flowers, C Campbell, M Hylton, N Esserman, LJ Rush-Port, E AF Garwood, E. R. Kumar, A. S. Baehner, F. Garber, J. E. Troyan, S. Olopade, O., I Moore, D. Au, A. Flowers, C. Campbell, M. Hylton, N. Esserman, L. J. Rush-Port, E. TI Fluvastatin has biologic effects on stage 0 and 1 breast cancer SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 UCSF, San Francisco, CA USA. UC E Bay, Oakland, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Chicago, Chicago, IL 60637 USA. MSKCC, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 287S EP 287S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201289 ER PT J AU Anderson, KS Hodi, FS Sasada, T Canning, C Hassett, M Mayer, E Hannagan, K Wong, J Colson, Y Shoji, B Najita, J Sibani, S LaBaer, J Winer, EP Dranoff, G AF Anderson, K. S. Hodi, F. S. Sasada, T. Canning, C. Hassett, M. Mayer, E. Hannagan, K. Wong, J. Colson, Y. Shoji, B. Najita, J. Sibani, S. LaBaer, J. Winer, E. P. Dranoff, G. TI A phase I study of an autologous GM-CSF-secreting breast cancer vaccine SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA USA. Harvard Inst Prote, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 288S EP 288S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201291 ER PT J AU Rimm, DL Broadwater, G Friedman, P Berry, D Seidman, A Hudis, C Winer, E Harris, L Thor, A AF Rimm, D. L. Broadwater, G. Friedman, P. Berry, D. Seidman, A. Hudis, C. Winer, E. Harris, L. Thor, A. TI Uniformly positive (> 80%) HER2 expression maximizes sensitivity and specificity for prediction of response to trastuzumab in CALGB 9840. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Yale Univ, Sch Med, New Haven, CT USA. Duke Univ, Med Ctr, Durham, NC USA. CALGB, Chicago, IL USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Colorado, Denver, CO 80202 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 360S EP 360S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201515 ER PT J AU Rugo, HS Carey, LA Mayer, E Marcom, PK Liu, M Ma, C Storniolo, AM Forero, A Esteva, FJ Wolff, AC Hobday, T Ferraro, M Davidson, NE Winer, EP Moore, D Scott, J Park, JW AF Rugo, H. S. Carey, L. A. Mayer, E. Marcom, P. K. Liu, M. Ma, C. Storniolo, A. M. Forero, A. Esteva, F. J. Wolff, A. C. Hobday, T. Ferraro, M. Davidson, N. E. Winer, E. P. Moore, D. Scott, J. Park, J. W. TI Assays of circulating tumor cells and outcome in the triple-negative breast cancer trial TBCRC001. SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. UNC, Chapel Hill, NC USA. DFCI, Boston, MA USA. Duke Univ, Durham, NC 27706 USA. Washington Univ, St Louis, MO 63130 USA. Indiana Univ, Indianapolis, IN 46204 USA. UAB, Birmingham, AL USA. MDACC, Houston, TX USA. JHU, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 SU S BP 360S EP 361S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201517 ER PT J AU Ozanne, EM Cipriano, L Cameron, M Newman, T Esserman, LJ AF Ozanne, E. M. Cipriano, L. Cameron, M. Newman, T. Esserman, L. J. TI Cost-effectiveness of genetic testing for BRCA1 and BRCA2 mutations SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UCSF Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 377S EP 377S PG 1 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201563 ER PT J AU Yang, XH Zou, L AF Yang, Xiaohong H. Zou, Lee TI Dual functions of DNA replication forks in checkpoint signaling and PCNA ubiquitination SO CELL CYCLE LA English DT Article DE DNA damage; checkpoint; replication fork; PCNA; ATR; Chk1; ubiquitination ID S-PHASE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; MONOUBIQUITINATED PCNA; INTERACTING PROTEIN; MAMMALIAN-CELLS; STRANDED-DNA; MRC1; PROGRESSION; POLYMERASE; COMPLEX AB During cell proliferation, DNA damage inflicted by intrinsic or extrinsic genotoxic stresses impose a thereat to DNA replication. The stability of the DNA replication forks that encounter DNA damage is crucial for genomic integrity. Both the ATR-regulated checkpoint pathway and the translesion DNA synthesis mediated by the ubiquitinated PCNA are important for continuous replication of damaged DNA. We have recently shown that Chk1, a key effector kinase of ATR in checkpoint response, is required for efficient PCNA ubiquitination after DNA damage. Surprisingly, the ubiquitination of PCNA is independent of ATR, but regulated by Claspin, a replication protein that mediates the activation of Chk1 by ATR. Like Claspin, Timeless and Rad17, two other Chk1 regulators at stressed replication forks, are also implicated in PCNA ubiquitination. These findings suggest that while ATR signaling and PCNA ubiquitination are two independent processes, they are mediated by a common group of proteins including Chk1 and it regulators at replication forks. Furthermore, these data raise the possibility that Chk1 and its regulators may constitute a functional module at replication forks to enable multiple stress responses. C1 [Yang, Xiaohong H.; Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Bldg 149-7404,13th St, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU NIH [GM076388]; Ellison Medical Foundation; Susan G. Komen for the Cure FX The Zou laboratory is supported by grants from the NIH (GM076388), Susan G. Komen for the Cure, and the Ellison Medical Foundation. NR 43 TC 23 Z9 25 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2009 VL 8 IS 2 BP 191 EP 194 DI 10.4161/cc.8.2.7357 PG 4 WC Cell Biology SC Cell Biology GA 396WT UT WOS:000262622800005 PM 19158510 ER PT J AU Chen, Y Craigen, WJ Riley, DJ AF Chen, Yumay Craigen, William J. Riley, Daniel J. TI Nek1 regulates cell death and mitochondrial membrane permeability through phosphorylation of VDAC1 SO CELL CYCLE LA English DT Article DE cytochrome c; polycystic kidney disease; kat mouse; Nek1; VDAC1; apoptosis; DNA damage ID DEPENDENT ANION CHANNEL; POLYCYSTIC KIDNEY-DISEASE; DNA-DAMAGE RESPONSE; PROTEIN-KINASE; TRANSITION PORE; CYCLOPHILIN-D; CYTOCHROME-C; ASPERGILLUS-NIDULANS; HEXOKINASE-I; APOPTOSIS AB The mammalian NIMA-related protein kinase 1 (Nek1) is important for keeping cells alive after DNA damage, but the mechanism by which injured cells die without functional Nek1 has not yet been demonstrated. Here we show that Nek1 regulates the pathway to mitochondrial cell death through phosphorylation of voltage dependent anion channel 1 (VDAC1) on serine 193. Nek1 associates with VDAC1 in a yeast two-hybrid system, as well as by GST pull-down assays and by reciprocal immunoprecipitation. A portion of Nek1 in cells also localizes at mitochondria. Ectopic expression of a kinase-dead Nek1 mutant results in cell death, which is immediately preceded by loss of the Nek1-dependent VDAC1-S193 phosphorylation. UV irradiation of Nek1-deficient cells or silencing of endogenous Nek1 expression similarly results in loss of the specific S193 phosphorylation before cells die. Nek1-deficient cells are characterized by exaggerated mitochondrial membrane permeability (MMP) and accelerated cell death. Ectopic expression of a VDAC1-Ser193Ala mutant, which cannot be phosphorylated by Nek1, also results in cell death. A VDAC1-Ser193Glu mutant, designed to mimic constitutive phosphorylation by Nek1, rescues exaggerated MMP and keeps cells alive after DNA damaging injury, but only transiently. The direct interaction between Nek1 and VDAC1 provides a mechanism to explain how Nek1 prevents excessive cell death, as well as the first direct evidence that a specific kinase regulates VDAC1 activity. C1 [Chen, Yumay; Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. [Riley, Daniel J.] Univ Texas Hlth Sci Ctr San Antonio, Transplant Ctr, Dept Surg, San Antonio, TX 78229 USA. [Craigen, William J.] Baylor Coll Med, Dept Mol & Human Genet, San Antonio, TX USA. [Riley, Daniel J.] S Texas Vet Hlth Care Syst, Audie L Murphy Div, Renal Res Div, San Antonio, TX USA. RP Chen, Y (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Nephrol, Dept Med, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM cheny@uthscsa.edu FU PKD Foundation; American Society of Nephrology; National Kidney Foundation; NIH [RO1-DK067339, P50-DK061597, RO1-DK61626] FX This work was supported by grants from the PKD Foundation, the American Society of Nephrology, the National Kidney Foundation, and the NIH (RO1-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. (RO1-DK61626). We thank Rosaria Polci, Patricia Litchfield, and Sergio Garcia for assistance with early stages of the project and with technical matters; and a Veterans Administration Renal Research Excellence Award Program to the South Texas Veterans Health Care System, Audie L. Murphy Division for core facility support. NR 54 TC 27 Z9 27 U1 2 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 15 PY 2009 VL 8 IS 2 BP 257 EP 267 DI 10.4161/cc.8.2.7551 PG 11 WC Cell Biology SC Cell Biology GA 396WT UT WOS:000262622800016 PM 19158487 ER PT J AU Russo, AL Kwon, HC Burgan, WE Carter, D Beam, K Weizheng, X Zhang, J Slusher, BS Chakravarti, A Tofilon, PJ Camphausen, K AF Russo, Andrea L. Kwon, Hyuk-Chan Burgan, William E. Carter, Donna Beam, Katie Weizheng, Xu Zhang, Jie Slusher, Barbara S. Chakravarti, Arnab Tofilon, Philip J. Camphausen, Kevin TI In vitro and In vivo Radiosensitization of Glioblastoma Cells by the Poly (ADP-Ribose) Polymerase Inhibitor E7016 SO CLINICAL CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; POLY(ADP-RIBOSE) POLYMERASE; 3-AMINOBENZAMIDE; TEMOZOLOMIDE; LINES AB Purpose: Poly (ADP-ribose) polymerase (PARP) inhibitors are undergoing clinical evaluation for cancer therapy, Because PARP inhibition has been shown to enhance tumor cell sensitivity to radiation, we investigated the in vitro and in vivo effects of the novel PARP inhibitor E7016. Experimental Design: The effect of E7016 on the in vitro radiosensitivity of tumor cell lines was evaluated using clonogenic survival. DNA damage and repair were measured using gamma H2AX foci and neutral comet assay. Mitotic catastrophe was determined by immunostaining. Tumor growth delay was evaluated in mice for the effect of E7016 on in vivo (U251) tumor radiosensitivity. Results: Cell lines exposed to E7016 preirradiation yielded an increase in radiosensitivity with dose enhancement factors at a surviving fraction of 0.1 from 1.4 to 1.7. To assess DNA double-strand breaks repair, gamma H2AX measured at 24 hours postirradiation had significantly more foci per cell in the E7016/irradiation group versus irradiation alone. Neutral comet assay further suggested unrepaired double-strand breaks with significantly greater DNA damage at 6 hours postirradiation in the combination group versus irradiation alone. Mitotic catastrophe staining revealed a significantly greater number of cells staining positive at 24 hours postirradiation in the combination group. In vivo, mice treated with E7016/irradiation/temozolomide had an additional growth delay of six days compared with the combination of temozolomide and irradiation. Conclusions: These results indicate that E7016 can enhance tumor cell radiosensitivity in vitro and in vivo through the inhibition of DNA repair. Moreover, enhanced growth delay with the addition of E7016 to temozolomide and radiotherapy in a glioma mouse model suggests a potential role for this drug in the treatment of glioblastoma multiforme. C1 [Russo, Andrea L.; Kwon, Hyuk-Chan; Camphausen, Kevin] NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. [Burgan, William E.; Carter, Donna; Beam, Katie] NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. [Russo, Andrea L.] Howard Hughes Med Inst NIH Res Scholar, Bethesda, MD USA. [Burgan, William E.; Carter, Donna; Beam, Katie] NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. [Weizheng, Xu; Zhang, Jie; Slusher, Barbara S.] Eisai Res Inst, Baltimore, MD USA. [Chakravarti, Arnab] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Tofilon, Philip J.] Univ S Florida, H Lee Moffitt Canc Ctr, Drug Discovery Program, Tampa, FL 33682 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, 10 Ctr Dr 3B42, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov FU NIH; National Cancer Institute FX Grant support: Intramural Research Program of the NIH, National Cancer Institute. 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 22 TC 97 Z9 102 U1 2 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 JAN 15 PY 2009 VL 15 IS 2 BP 607 EP 612 DI 10.1158/1078-0432.CCR-08-2079 PG 6 WC Oncology SC Oncology GA 397VD UT WOS:000262689300023 PM 19147766 ER PT J AU Wu, JD Atteridge, CL Wang, XJ Seya, T Plymate, SR AF Wu, Jennifer D. Atteridge, Catherine L. Wang, Xuanjun Seya, Tsukasa Plymate, Stephen R. TI Obstructing Shedding of the Immunostimulatory MHC Class I Chain-Related Gene B Prevents Tumor Formation SO CLINICAL CANCER RESEARCH LA English DT Article ID ACTIVATING IMMUNORECEPTOR NKG2D; CELL-MEDIATED REJECTION; NK CELLS; RETINOIC-ACID; DOWN-REGULATION; CUTTING EDGE; LIGANDS; EXPRESSION; RECEPTOR; MICA AB Purpose: Clinical observations have suggested that shedding of the MHC class I chain - related molecule (MIC) may be one of the mechanisms by which tumors evade host immunosurveillance and progress. However, this hypothesis has never been proven. In this study, we tested this hypothesis using a prostate tumor model and investigated the effect of shedding of MIC on tumor development. Experimental Design: We generated a shedding-resistant noncleavable form of MICB (MICB.A2). We overexpressed MICB.A2, the wild-type MICB, and the recombinant soluble MICB (rsMICB) in mouse prostate tumor TRAMP-C2 (TC2) cells and implanted these cells into severe combined immunodeficient mice. Results: No tumors were developed in animals that were implanted with TC2-MICB.A2 cells, whereas all the animals that were implanted with TC2, TC2-MICB, or TC2-rsMICB cells developed tumors. When a NKG2D-specific antibody CX5 or purified rsMICB was administered to animals before tumor implantation, all animals that were implanted with TC2-MICB.A2 cells developed tumors. In vitro cytotoxicity assay revealed the loss of NKG2D-mediated natural killer cell function in these prechallenged animals, suggesting that persistent levels of soluble MICB in the serum can impair natural killer cell function and thus allow tumor growth. Conclusions: These data suggest that MIC shedding may contribute significantly to tumor formation by transformed cells and that inhibition of MIC shedding to sustain the NKG2D receptor-MIC ligand recognition may have potential clinical implication in targeted cancer treatment. C1 [Wu, Jennifer D.; Atteridge, Catherine L.; Wang, Xuanjun; Plymate, Stephen R.] Univ Washington, Dept Med, Seattle, WA 98104 USA. [Plymate, Stephen R.] Vet Affairs Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. [Seya, Tsukasa] Hokkaido Univ, Dept Microbiol & Immunol, Grad Sch Med, Sapporo, Hokkaido, Japan. RP Wu, JD (reprint author), Univ Washington, Dept Med, 325 9th Ave,Box 359625, Seattle, WA 98104 USA. EM wuj@u.washington.edu RI Seya, Tsukasa/A-4336-2012; OI wang, xuanjun/0000-0003-1211-506X FU DOD-USMRC New Investigators [W81XWH-04-1-0577]; IDEA Development [W81XWH-06-1-0014]; W Prostate SPORE Program; NIH [1K01CA116002] FX Grant support: DOD-USMRC New Investigators Grant W81XWH-04-1-0577 and IDEA Development Award W81XWH-06-1-0014, NW Prostate SPORE Program, and NIH Temin Award 1K01CA116002 (J.D.Wu). NR 41 TC 30 Z9 30 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 15 PY 2009 VL 15 IS 2 BP 632 EP 640 DI 10.1158/1078-0432.CCR-08-1305 PG 9 WC Oncology SC Oncology GA 397VD UT WOS:000262689300026 PM 19147769 ER PT J AU Lo Re, V Amorosa, VK Localio, AR O'Flynn, R Teal, V Dorey-Stein, Z Kostman, JR Gross, R AF Lo Re, Vincent, III Amorosa, Valerianna K. Localio, A. Russell O'Flynn, Rose Teal, Valerie Dorey-Stein, Zachariah Kostman, Jay R. Gross, Robert TI Adherence to Hepatitis C Virus Therapy and Early Virologic Outcomes SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 24th International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 17-20, 2008 CL Copenhagen, DENMARK ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; ANTIRETROVIRAL THERAPY; COMBINATION THERAPY; SUSTAINED RESPONSE; PHARMACY RECORDS; VIRAL LOAD; MANAGEMENT; INFECTION; IMPACT AB Background. Suboptimal drug exposure attributable to physician-directed dosage reductions of pegylated interferon and/or ribavirin are associated with decreased sustained virologic response rates. However, data are limited with regard to suboptimal drug exposure that is attributable to missed doses by patients with chronic hepatitis C virus (HCV) infection. We examined the relationship between adherence to pegylated interferon and ribavirin therapy, measured by pharmacy refill, and HCV suppression during the initial 12 weeks of therapy. Methods. We conducted a cohort study involving 188 patients with chronic HCV infection who were treated with pegylated interferon plus ribavirin. Adherence was calculated using pharmacy refill data and could exceed 100%. The primary outcome was decrease in HCV load at 12 weeks; early virologic response was a secondary outcome. Mixed-effects regression models estimated the association between adherence and HCV suppression during the initial 12 weeks. Subanalyses were performed among patients who received optimal weight-based dosages. Results. The mean decrease in HCV load at 12 weeks was 0.66 log IU/mL greater for patients with >= 85% adherence than for those with < 85% adherence (3.23 vs. 2.57 log IU/mL;). When patients who received Pp. 04 a suboptimal ribavirin dosage were excluded, the decrease in viral load was 1.00 log IU/mL greater for persons with >= 85% adherence (3.32 vs. 2.32 log IU/mL;). Early virologic response was more common among Pp. 01 patients with >= 85% adherence than it was among those with < 85% adherence to treatment with pegylated interferon (73% vs. 29%; P=.02) and ribavirin (73% vs. 55%; P=.08 Conclusions. Adherence of >= 85% to pegylated interferon and ribavirin treatment was associated with increased HCV suppression. Decreases in HCV load became greater when patients with >= 85% adherence to their regimen continued to receive their recommended weight-based ribavirin dosage. C1 [Lo Re, Vincent, III; Localio, A. Russell; Teal, Valerie; Gross, Robert] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Amorosa, Valerianna K.; Dorey-Stein, Zachariah; Kostman, Jay R.; Gross, Robert] Univ Penn, Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Localio, A. Russell; Teal, Valerie; Gross, Robert] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Localio, A. Russell; Gross, Robert] Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. [Lo Re, Vincent, III; Amorosa, Valerianna K.; O'Flynn, Rose; Gross, Robert] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Lo Re, V (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 809 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM vincentl@mail.med.upenn.edu RI Lo Re, Vincent/N-7817-2015; OI Teal, Valerie/0000-0001-7116-5353 FU AHRQ HHS [HS 10399, U18 HS010399]; NIAID NIH HHS [K01 AI070001-02, K01 AI 070001, K01 AI070001] NR 17 TC 29 Z9 31 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 15 PY 2009 VL 48 IS 2 BP 186 EP 193 DI 10.1086/595685 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 389JJ UT WOS:000262088400009 PM 19086908 ER PT J AU Dalmau, J Puertas, MC Azuara, M Marino, A Frahm, N Mothe, B Izquierdo-Useros, N Buzon, MJ Paredes, R Matas, L Allen, TM Brander, C Rodrigo, C Clotet, B Martinez-Picado, J AF Dalmau, Judith Puertas, Maria Carmen Azuara, Marta Marino, Ana Frahm, Nicole Mothe, Beatriz Izquierdo-Useros, Nuria Buzon, Maria Jose Paredes, Roger Matas, Lourdes Allen, Todd M. Brander, Christian Rodrigo, Carlos Clotet, Bonaventura Martinez-Picado, Javier TI Contribution of Immunological and Virological Factors to Extremely Severe Primary HIV Type 1 Infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSES; DISEASE PROGRESSION; AIDS; HLA; INDIVIDUALS; SEROCONVERSION; TRANSMISSION; ASSOCIATION; RESISTANT AB Background. During acute human immunodeficiency virus (HIV) infection, high viral loads and the induction of host immune responses typically coincide with the onset of clinical symptoms. However, clinically severe presentations during acute HIV type 1 (HIV-1) infection, including AIDS-defining symptoms, are unusual. Methods. Virus isolates were tested for clade, drug susceptibility, coreceptor use, and growth rate in 2 case reports of sexual transmission of HIV-1 infection. Human leukocyte antigen (HLA) genotype was determined, and HIV-1-specific cytotoxic T lymphocyte responses to an overlapping peptide set spanning the entire HIV clade A and clade B proteome were assayed. Results. The viruses isolated in the 2 unrelated case reports of severe primary HIV-1 infection showed R5/X4 dual-mixed tropism, belonged to clade B and CRF02-AG, and were highly replicative in peripheral blood mononuclear cell culture. Impaired humoral responses were paralleled by a profound absence of HIV-1-specific cytotoxic T lymphocyte responses to the entire viral proteome in the 2 case reports. In 1 case report for which the virus source was available, there was a remarkable HLA similarity between the 2 patients involved in the transmission event, because 3 of 4 HLA-A and HLA-B alleles had matched HLA supertype for both patients. Conclusions. The data suggest that concurrence of viral and host factors contributes to the clinical severity of primary HIV-1 infection and that patients infected with highly replicative, dual-tropic viruses are more prone to develop AIDS-defining symptoms during acute infection if they are unable to mount humoral and cellular HIV-1-specific immune responses. The presence of concordant HLA supertypes might facilitate the preferential transmission of HLA-adapted viral variants, further accelerating disease progression. C1 [Dalmau, Judith; Puertas, Maria Carmen; Mothe, Beatriz; Izquierdo-Useros, Nuria; Buzon, Maria Jose; Paredes, Roger; Brander, Christian; Clotet, Bonaventura; Martinez-Picado, Javier] Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Badalona 08916, Spain. [Azuara, Marta; Rodrigo, Carlos] Hosp Badalona Germans Trias & Pujol, Pediat Unit, Badalona 08916, Spain. [Matas, Lourdes] Hosp Badalona Germans Trias & Pujol, Microbiol Unit, Badalona 08916, Spain. [Marino, Ana] Hosp Arquitecto Marcide, El Ferol, Spain. [Brander, Christian; Martinez-Picado, Javier] Inst Catalana Recerca & Estudis Avancats ICREA, Barcelona, Spain. [Frahm, Nicole; Allen, Todd M.; Brander, Christian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA USA. RP Martinez-Picado, J (reprint author), Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Ctra Canyet S-N, Badalona 08916, Spain. EM jmpicado@irsicaixa.es RI Martinez-Picado, Javier/G-5507-2012; Allen, Todd/F-5473-2011; Buzon, Maria J/G-8286-2015; Izquierdo-Useros, Nuria/G-2534-2016; Puertas, Maria /G-3251-2016; Dalmau, Judith/I-7065-2016; Matas, Lurdes/L-2466-2015; OI Martinez-Picado, Javier/0000-0002-4916-2129; Rodrigo, Carlos/0000-0003-1140-2585; Buzon, Maria J/0000-0003-4427-9413; Izquierdo-Useros, Nuria/0000-0002-1039-1821; Puertas, Maria /0000-0002-6750-2318; Dalmau, Judith/0000-0001-7513-3711; Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [R01 AI054178, R01 AI054178-05] NR 43 TC 25 Z9 26 U1 0 U2 5 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 JAN 15 PY 2009 VL 48 IS 2 BP 229 EP 238 DI 10.1086/595704 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 389JJ UT WOS:000262088400015 PM 19093810 ER PT J AU Fujino, A Arango, NA Zhan, Y Manganaro, TF Li, XL MacLaughlin, DT Donahoe, PK AF Fujino, Akihiro Arango, Nelson A. Zhan, Yong Manganaro, Thomas F. Li, Xianlin MacLaughlin, David T. Donahoe, Patricia K. TI Cell migration and activated PI3K/AKT-directed elongation in the developing rat Mullerian duct SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Mullerian duct; Cell migration; Duct elongation; PI3K/AKT pathway; LY294002; Phosphorylated AKT; Wolffian duct; Coelomic epithelium; Tubulerization ID FEMALE REPRODUCTIVE-TRACT; ORGAN-CULTURE ASSAY; INHIBITING SUBSTANCE; WOLFFIAN DUCT; UROGENITAL DEVELOPMENT; BRANCHING MORPHOGENESIS; MOLECULAR-MECHANISMS; BUD MORPHOGENESIS; FETAL MOUSE; REGRESSION AB In vertebrates, the Mullerian duct elongates along the Wolffian duct, a mesonephric structure that is required for Mullerian duct formation. Recently, several genes required for initial Mullerian duct formation have been identified. However, the precise mechanism of Mullerian duct elongation remains to be elucidated. In this Study, we investigated dynamic morphological changes in the elongating Mullerian duct in rat urogenital ridges in organ culture manipulated by microincision and/or chemical inhibitors. Mechanical division of the developing Mullerian duct showed that epithelial cells of the Mullerian duct actively migrate along the anterior-posterior axis independent of the proliferative expansion of the anterior portion of the duct. We found that the PI3K/AKT signaling pathway is activated in the Mullerian duct epithelium and is required for elongation of the tip of the duct; however, migration of Mullerian duct epithelial cells proximal to the tip remains intact when PI3K/AKT is inactivated. Although much is known about the molecular and cellular mechanisms leading to Mullerian duct regression, the present findings provide a fuller understanding of the mechanisms contributing to Mullerian duct fort-nation and to the general process of early tubulogenesis. (C) 2008 Published by Elsevier Inc. C1 [Donahoe, Patricia K.] Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Dept Surg, Pediat Surg Res Labs, 185 Cambridge St,CPZN 6100, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NIH [NICHD-HD-32112, NCI R01CA 137393, NCI C1105009] FX We would like to thank Dr. Ronny Drapkin for providing the anti-PAX8 antibody, Drs. Jose Teixeira, Allan Goldstein and Liz Perkins for suggestions and critical review of the manuscript, Drs. Maria Loscertales, Henry L. Chang, Rafael V. Pieretti, and Paul P. Szotek for sharing techniques and reagents, and members of the Donahoe laboratory for helpful discussions. This work was supported by a grant from the NIH (NICHD-HD-32112 and NCI R01CA 137393 to P. K. D. and D. T. M. and NCI C1105009 Ovarian Cancer SPORE grant, Principal Investigator, Daniel Cramer). NR 62 TC 14 Z9 14 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 15 PY 2009 VL 325 IS 2 BP 351 EP 362 DI 10.1016/j.ydbio.2008.10.027 PG 12 WC Developmental Biology SC Developmental Biology GA 396KA UT WOS:000262589400005 PM 19013450 ER PT J AU Riley, DE Krieger, JN AF Riley, Donald E. Krieger, John N. TI Embryonic nervous system genes predominate in searches for dinucleotide simple sequence repeats flanked by conserved sequences SO GENE LA English DT Article DE Highly conserved elements; HCEs; Simple sequence repeats; SSRs; Dinucleotide simple sequence repeats; diSSRs; Microsatellites; Nervous system; Development ID BINDING PROTEIN; ULTRACONSERVED ELEMENTS; SYNAPTIC VESICLES; MESSENGER-RNAS; HUMAN GENOME; EXPRESSION; EVOLUTION; BRAIN; MOUSE; REGIONS AB To study evolution of dinucleotide simple sequence repeats (diSSRs) we searched recently available mammalian genomes for UTR-localized diSSRs with conserved upstream flanking sequences (CFS). There were 252 reported Homo sapiens genes containing the repeats (AC)n, (GT)n, (AG)n or (CT)n in their UTRs including 22 (8.7%) with diSSR-upstream flanking sequences conserved comparing divergent mammalian lineages represented by Homo sapiens and the marsupial, Monodelphis domestica. Of these 22 genes, 19 had known functions including 18 (95%) that proved critical for mammalian nervous systems (Fishers exact test, P<0.0001). The remaining gene, Cd2ap, proved critical for development of kidney podocytes, cells that have multiple similarities to neurons. Gene functions included voltage and chloride channels, synapse-associated proteins, neurotransmitter receptors, axon and dendrite pathfinders, a NeuroD potentiator and other neuronal activities. Repeat length polymorphism was confirmed for 68% of CFS diSSRs even though these repeats were nestled among highly conserved sequences. This finding supports a hypothesis that SSR polymorphism has functional implications. A parallel study was performed on the self-complementary diSSRs (AT)n and (GC)n. When flanked by conserved sequences, the self-complementary diSSR (AT)n was also associated with genes expressed in the developing nervous system. Our findings implicate functional roles for diSSRs in nervous system development. Published by Elsevier B.V. C1 [Riley, Donald E.; Krieger, John N.] Univ Washington, Dept Urol, Seattle, WA 98195 USA. [Riley, Donald E.; Krieger, John N.] VA Puget Sound Hlth Care Syst, Dept Res, Seattle, WA 98012 USA. RP Riley, DE (reprint author), Puget Sound Hlth Care Syst VA, Room 517,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. FU NIDDK NIH HHS [R01 DK038955-15] NR 57 TC 13 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 15 PY 2009 VL 429 IS 1-2 BP 74 EP 79 DI 10.1016/j.gene.2008.09.025 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 399CL UT WOS:000262777900011 PM 18952158 ER PT J AU Riley, DE Krieger, JN AF Riley, Donald E. Krieger, John N. TI UTR dinucleotide simple sequence repeat evolution exhibits recurring patterns including regulatory sequence motif replacements SO GENE LA English DT Article DE SSR, simple sequence repeat; HCE, highly conserved element; STR, short tandem repeats; Microsatellites; Nervous system; Development; Post-transcriptional regulation; ARE, AU-rich elements ID MESSENGER-RNA TRAFFICKING; 3'-UNTRANSLATED REGION; ELEMENTS; MULTIPLE; PROTEINS; HUR; MICROSATELLITES; STABILIZATION; EXPRESSION; ALIGNMENT AB New genome sequence information was used to study evolution of 22 dinucleotide simple sequence repeat (diSSR) sites whose upstream flanking sequences were shown to be conserved comparing Homo sapiens with the marsupial, Monodelphis domestica. Among mammals, most of these diSSR sites were conserved both upstream and downstream of the diSSR. However, individual diSSRs were frequently replaced by alternative repeats. Conserved among mammals examined, the Vsnl1 gene's 3' UTR-localized (AC)n repeat replaced an A-rich tract in non-mammalian vertebrates examined. The Sema6D gene's (GT)n was also well conserved among mammals examined. Such conservation provides evidence of a functional role. The UTR-localized diSSRs of other genes evolved by replacing alternative diSSRs, by replacing mononucleotide-rich tracts and, in fewer cases, by expansion from short repeating sequences. Extension of the study to less conserved diSSR sites revealed that some diSSRs replaced post-transcriptional regulatory motifs, such as AU-rich elements (AREs) and C-rich tracts. The Mtap2 gene's UTR-localized (AC)n was located within a known dendritic targeting element. These evolutionary replacements suggest that some diSSRs belong to a broader group of weak-folding repetitive sequences with potential regulatory roles. Published by Elsevier B.V. C1 Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Res, Seattle, WA 98012 USA. RP Riley, DE (reprint author), Sound Hlth Care Syst VA, Room 517,Bldg 1,1660 S Columbian Way, Seattle, WA 98108 USA. EM dri@u.washington.edu FU NIDDK NIH HHS [R01 DK038955-15] NR 28 TC 17 Z9 19 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JAN 15 PY 2009 VL 429 IS 1-2 BP 80 EP 86 DI 10.1016/j.gene.2008.09.030 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 399CL UT WOS:000262777900012 PM 18955121 ER PT J AU Schmucker, D Chen, B AF Schmucker, Dietmar Chen, Brian TI Dscam and DSCAM: complex genes in simple animals, complex animals yet simple genes SO GENES & DEVELOPMENT LA English DT Review DE Dscam; immunoglobulin receptor; alternative splicing; neural circuit formation ID CELL-ADHESION-MOLECULE; HOMOPHILIC INTERCELLULAR-ADHESION; PRE-MESSENGER-RNA; IMMUNOGLOBULIN SUPERFAMILY; DROSOPHILA-DSCAM; AXON GUIDANCE; C-ELEGANS; WIRING SPECIFICITY; SELF-RECOGNITION; STRUCTURAL BASIS AB Cadherins and the immunoglobulin (Ig) proteins give rise to a multitude of surface receptors, which function as diverse cell adhesion molecules (CAMs) or signal-transducing receptors. These functions are often interdependent, and rely on a high degree of specificity in homophilic binding as well as heterophilic interactions. The Drosophila receptor Dscam is an exceptional example of homophilic binding specificity involved in a number of important biological processes, such as neural wiring and innate immunity. Combinatorial use of alternatively spliced Ig-domains enables the generation of an estimated 18,000 isoform-specific homophilic receptor pairs. Although isoform diversity of Dscam is unique to arthropods, recent genetic analysis of vertebrate DSCAM( Down Syndrome Cell Adhesion Molecule) genes has revealed an intriguing conservation of molecular functions underlying neural wiring. This review covers the multiple functions of Dscam across different species highlighting its remarkable versatility as well as its conserved basic functions in neural development. We discuss how an unprecedented expansion of complex alternative splicing has been uniquely employed by arthropods to generate diverse surface receptors, important for cell-cell communication, molecular self-recognition in neurons, and innate immune defenses. We end with a speculative hypothesis reconciling the striking differences in Dscam and DSCAM gene structures with their conserved functions in molecular recognition underlying neural circuit formation. C1 [Schmucker, Dietmar] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Schmucker, Dietmar] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Chen, Brian] McGill Univ, Ctr Hlth, Ctr Res Neurosci, Montreal, PQ H3G 1A4, Canada. [Chen, Brian] Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. RP Schmucker, D (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM dietmar_schmucker@dfci.harvard.edu NR 53 TC 79 Z9 80 U1 1 U2 14 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD JAN 15 PY 2009 VL 23 IS 2 BP 147 EP 156 DI 10.1101/gad.1752909 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 399JR UT WOS:000262796700004 PM 19171779 ER PT J AU Paintlia, AS Paintlia, MK Singh, I Skoff, RB Singh, AK AF Paintlia, Ajaib S. Paintlia, Manjeet K. Singh, Inderjit Skoff, Robert B. Singh, Avtar K. TI Combination Therapy of Lovastatin and Rolipram Provides Neuroprotection and Promotes Neurorepair in Inflammatory Demyelination Model of Multiple Sclerosis SO GLIA LA English DT Article DE combination therapy; EAE/MS; demyelination; inflammation ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; COA REDUCTASE INHIBITOR; TRAUMATIC BRAIN-INJURY; GLATIRAMER ACETATE; SPINAL-CORD; PHOSPHODIESTERASE INHIBITOR; AXONAL REGENERATION; NEUROTROPHIC FACTOR; NEURITE OUTGROWTH AB Drug combination therapies for central nervous system (CNS) demyelinating diseases including multiple sclerosis (MS) are gaining momentum over monotherapy. Over the past decade, both in vitro and in vivo studies established that statins (HMG-CoA reductase inhibitors) and rolipram (phosphodiesterase-4 inhibitor; blocks the degradation of intracellular cyclic AMP) can prevent the progression of MS in affected individuals via different mechanisms of action. In this study, we evaluated the effectiveness of lovastatin (LOV) and rolipram (RLP) in combination therapy to promote neurorepair in an inflammatory CNS demyelination model of MS, experimental autoimmune encephalomyelitis (EAE). Combination treatment with suboptimal doses of these drugs in an established case of EAE (clinical disease score >= 2.0) significantly attenuated the infiltration of inflammatory cells and protected myelin sheath and axonal integrity in the CNS. It was accompanied with elevated level of cyclic AMP and activation of its associated protein kinase A. Interestingly, combination treatment with these drugs impeded neurodegeneration and promoted neurorepair in established EAE animals (clinical disease score >= 3.5) as verified by quantitative real-time polymerase chain reaction, immunohistochemistry and electron microscopic analyses. These effects of combination therapy were minimal and/or absent with either drug alone in these settings. Together, these data suggest that combination therapy with LOV and RLP has the potential to provide neuroprotection and promote neurorepair in MS, and may have uses in other related CNS demyelinating diseases. (C) 2008 Wiley-Liss, Inc. C1 [Paintlia, Ajaib S.; Paintlia, Manjeet K.; Singh, Inderjit; Singh, Avtar K.] Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. [Skoff, Robert B.] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA. [Singh, Avtar K.] Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. [Singh, Avtar K.] Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. RP Singh, AK (reprint author), Med Univ S Carolina, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM paintlia@musc.edu; singhi@musc.edu OI Paintlia, Ajaib/0000-0003-4525-5333 FU NIH [NS-22576, NS-34741, NS-37766, NS-40144, NS-038236, C06-RR015455, C06-RR018823]; Merck Company FX NIH; Grant number: NS-22576, NS-34741, NS-37766, NS-40144, NS-038236, C06-RR015455, C06-RR018823; Grant sponsor; Merck & Company. NR 65 TC 35 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD JAN 15 PY 2009 VL 57 IS 2 BP 182 EP 193 DI 10.1002/glia.20745 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 383OA UT WOS:000261681700005 PM 18720408 ER PT J AU Wen, Y Feng, J Scott, DR Marcus, EA Sachs, G AF Wen, Yi Feng, Jing Scott, David R. Marcus, Elizabeth A. Sachs, George TI The pH-Responsive Regulon of HP0244 (FlgS), the Cytoplasmic Histidine Kinase of Helicobacter pylori SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HP0165-HP0166 2-COMPONENT SYSTEM; ALPHA-CARBONIC ANHYDRASE; SIGNAL-TRANSDUCTION; RALSTONIA-EUTROPHA; ACID ACCLIMATION; GENE-EXPRESSION; RESISTANCE DETERMINANT; ALCALIGENES-EUTROPHUS; NUCLEOTIDE-SEQUENCE; H-2 SENSOR AB Helicobacter pylori colonizes the acidic gastric environment, in contrast to all other neutralophiles, whose acid resistance and tolerance responses allow only gastric transit. This acid adaptation is dependent on regulation of gene expression in response to pH changes in the periplasm and cytoplasm. The cytoplasmic histidine kinase, HP0244, which until now was thought only to regulate flagellar gene expression via its cognate response regulator, HP0703, was found to generate a response to declining medium pH. Although not required for survival at pH 4.5, HP0244 is required for survival at pH 2.5 with 10 mM urea after 30 min. Transcriptional profiling of a HP0244 deletion mutant grown at pH 7.4 confirmed the contribution of HP0244 to sigma(54) activation via HP0703 to coordinate flagellar biosynthesis by a pH-independent regulon that includes 14 flagellar genes. Microarray analysis of cells grown at pH 4.5 without urea revealed an additional 22 genes, including 4 acid acclimation genes (ureA, ureB, ureI, and amiE) that are positively regulated by HP0244. Additionally, 86 differentially expressed genes, including 3 acid acclimation genes (ureF, rocF [arginase], and ansB [asparaginase]), were found in cells grown at pH 2.5 with 30 mM urea. Hence, HP0244 has, in addition to the pH-independent flagellar regulon, a pH-dependent regulon, which allows adaptation to a wider range of environmental acid conditions. An acid survival study using an HP0703 mutant and an electrophoretic mobility shift assay with in vitro-phosphorylated HP0703 showed that HP0703 does not contribute to acid survival and does not bind to the promoter regions of several genes in the HP0244 pH-dependent regulon, suggesting that there is a pathway outside the HP0703 regulon which transduces the acid-responsive signal sensed by HP0244. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Membrane Biol Lab, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Wen, Y (reprint author), 11301 Wilshire Blvd,Bldg 113,Rm 324, Los Angeles, CA 90073 USA. EM ywen@ucla.edu FU U.S. Veterans Administration; NIH [DK46917, 53462, 58333]; The CURE Digestive Diseases Research Center at UCLA FX This work was supported by U.S. Veterans Administration and NIH grants DK46917, 53462, and 58333 and by a pilot and feasibility grant from The CURE Digestive Diseases Research Center at UCLA. NR 52 TC 25 Z9 27 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN 15 PY 2009 VL 191 IS 2 BP 449 EP 460 DI 10.1128/JB.01219-08 PG 12 WC Microbiology SC Microbiology GA 389TP UT WOS:000262117700001 PM 18978046 ER PT J AU Shaffer, MH Dupree, RS Zhu, PM Saotome, I Schmidt, RF McClatchey, AI Freedman, BD Burkhardt, JK AF Shaffer, Meredith H. Dupree, Renell S. Zhu, Peimin Saotome, Ichiko Schmidt, Richard F. McClatchey, Andrea I. Freedman, Bruce D. Burkhardt, Janis K. TI Ezrin and Moesin Function Together to Promote T Cell Activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EZRIN/RADIXIN/MOESIN ERM PROTEINS; MEMBRANE-MICROFILAMENT LINKER; IMMUNE SYNAPSE FORMATION; IMMUNOLOGICAL SYNAPSE; TYROSINE PHOSPHORYLATION; RECEPTOR MICROCLUSTERS; CYTOPLASMIC DOMAIN; AMINO-ACID; LIPID RAFT; CYTOSKELETON AB The highly homologous proteins ezrin, radixin, and moesin link proteins to the actin cytoskeleton. The two family members expressed in T cells, ezrin and moesin, are implicated in promoting T cell activation and polarity. To elucidate the contributions of ezrin and moesin, we conducted a systematic analysis of their function during T cell activation. In response to TCR engagement, ezrin and moesin were phosphorylated in parallel at the regulatory threonine, and both proteins ultimately localized to the distal pole complex (DPC). However, ezrin exhibited unique behaviors, including tyrosine phosphorylation and transient localization to the immunological synapse before movement to the DPC. To ask whether these differences reflect unique requirements for ezrin vs moesin in T cell signaling, we generated mice with conditional deletion of ezrin in mature T cells. Ezrin(-/-) T cells exhibited normal immunological synapse organization based upon localization of protein kinase C-theta, talin, and phospho-ZAP70. DPC localization of CD43 and RhoGDP dissociation inhibitor, as well as the novel DPC protein Src homology region 2 domain-containing phosphatase-1, was also unaffected. However, recruitment of three novel DPC proteins, ezrin binding protein of 50 kDa, Csk binding protein, and the p85 subunit of PI3K was partially perturbed. Biochemical analysis of ezrin(-/-) T cells or T cells suppressed for moesin using small interfering RNA showed intact early TCR signaling, but diminished levels of IL-2. The defects in IL-2 production were more pronounced in T cells deficient for both ezrin and moesin. These cells also exhibited diminished phospholipase C-gamma 1 phosphorylation and calcium flux. We conclude that despite their unique movement and phosphorylation patterns, ezrin and moesin function together to promote T cell activation. The Journal of Immunology, 2009, 182: 1021-1032. C1 [Shaffer, Meredith H.; Dupree, Renell S.; Schmidt, Richard F.; Burkhardt, Janis K.] Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Zhu, Peimin; Freedman, Bruce D.] Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. [Saotome, Ichiko; McClatchey, Andrea I.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Saotome, Ichiko; McClatchey, Andrea I.] Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA 02129 USA. RP Burkhardt, JK (reprint author), Childrens Hosp Philadelphia, Dept Pathol & Lab Med, 816D Abramson Res Ctr,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM jburkhar@mail.med.upenn.edu FU National Institutes of Health [R01 A150098, P01 CA093615, T32-HD07516-09, T32-GM7229-29] FX This work was supported by National Institutes of Health Grants R01 A150098 and P01 CA093615 (to J.K.B.) and by National Institutes of Health Training Grants T32-HD07516-09 and T32-GM7229-29 (to M.H.S.). NR 53 TC 61 Z9 61 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2009 VL 182 IS 2 BP 1021 EP 1032 PG 12 WC Immunology SC Immunology GA 393RO UT WOS:000262390600031 PM 19124745 ER PT J AU Jiang, YF Borrelli, L Bacskai, BJ Kanaoka, Y Boyce, JA AF Jiang, Yongfeng Borrelli, Laura Bacskai, Brian J. Kanaoka, Yoshihide Boyce, Joshua A. TI P2Y6 Receptors Require an Intact Cysteinyl Leukotriene Synthetic and Signaling System to Induce Survival and Activation of Mast Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GENE DISRUPTION REVEALS; SMOOTH-MUSCLE-CELLS; CYSLT(1) RECEPTOR; VASCULAR-PERMEABILITY; EXTRACELLULAR NUCLEOTIDES; INTERLEUKIN-8 PRODUCTION; INFLAMMATORY RESPONSES; CYTOKINE GENERATION; ASTHMATIC SUBJECTS; P2Y(6) RECEPTORS AB Cysteinyl Ieukotrienes (cys-LTs) induce inflammatory responses through type 1 (CysLT(1)R) and type 2 (CysLT(2)R) cys-LT receptors and activate mast cells in vitro. We previously demonstrated that cys-LTs cross-desensitized IL-4-primed primary human mast cells (hMCs) to stimulation with the nucleotide uridine diphosphate (UDP). We now report that hMCs, mouse bone marrow-derived mast cells (mBMMCs), and the human MC line LAD2 all express UDP-selective P2Y6 receptors that cooperate with CysLT(1)R to promote cell survival and chemokine generation by a pathway involving reciprocal ligand-mediated cross-talk. Leukotriene (LT) D(4), the most potent CysLT, R ligand, and UDP both induced phosphorylation of ERK and prolonged the survival of cytokine-starved hMCs and mBMMCs. ERK activation and cytoprotection in response to either ligand were attenuated by treatment of the cells with a selective P2Y6 receptor antagonist (MRS2578), which did not interfere with signaling through recombinant CysLT(1)R. Surprisingly, both UDP and LTD(4)-mediated ERK activation and cytoprotection were absent in mBMMCs lacking CysLT(1)R and the biosynthetic enzyme LTC(4) synthase, implying a requirement for a cys-LT-mediated autocrine loop. In IL-4-primed LAD2 cells, LTD(4) induced the generation of MIP-1 beta, a response blocked by short hairpin RNA-mediated knockdown of CysLT(1)R or P2Y6 receptors, but not of CysLT(2)R. Thus, CysLT(1)R and P2Y6 receptors, which are coexpressed on many cell types of innate immunity, reciprocally amplify one another's function in mast cells through endogenous ligands. The Journal of Immunology, 2009, 182: 1129-1137. C1 [Jiang, Yongfeng; Kanaoka, Yoshihide; Boyce, Joshua A.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Boyce, Joshua A.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Boyce, Joshua A.] Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Borrelli, Laura; Bacskai, Brian J.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02115 USA. RP Boyce, JA (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, 1 Jimmy Fund Way,Smith Bldg,Room 626, Boston, MA 02115 USA. EM jboyce@rics.bwh.harvard.edu FU National Institutes of Health [AI-48802, AI-52353, AI-31599, HL-36110, EB-00768]; Charles Dana Foundation; Vinik Family Fund for Research in Allergic Diseases FX This work was supported by National Institutes of Health Grants AI-48802, AI-52353, AI-31599, HL-36110, and EB-00768 and by grants from the Charles Dana Foundation and the Vinik Family Fund for Research in Allergic Diseases. NR 58 TC 25 Z9 26 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2009 VL 182 IS 2 BP 1129 EP 1137 PG 9 WC Immunology SC Immunology GA 393RO UT WOS:000262390600042 PM 19124756 ER PT J AU Lipe, H Bird, T AF Lipe, Hillary Bird, Thomas TI Late onset Huntington Disease: Clinical and genetic characteristics of 34 cases SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Huntington Disease; Late onset; Neurogenetics; CAG repeat expansion ID AGE; PROGRESSION; DURATION; REPEAT AB We performed a retrospective observational study of thirty-four persons with late onset of Huntington Disease (HD) (onset range 60-79 years). CAG trinucleotide expansion size ranged from 38-44 repeats. Even at this late age a significant negative correlation (r = -0.421, p < 0.05) was found between the length of repeat and age of onset. important characteristics of these older subjects were: (1) Most (68%) were the first in the family to have a diagnosis of HD, (2) Motor problems were the initial symptoms at onset, (3) Disability increased and varied from mild to severe (4) Disease duration was somewhat shorter (12 years) than that reported for mid life onset, (5) Death was often related to diseases of old age, Such as cancer and cerebrovascular disease, (6) Serious falls were a major risk and (7) Global dementia may be associated with coincident Alzheimer disease. Recognizing these characteristics will help physicians and other health care providers better identify and follow the late onset presentation of this disease. Published by Elsevier B.V. C1 [Lipe, Hillary; Bird, Thomas] VA Puget Sound Hlth Care Syst, Geriat Res & Clin Ctr, Seattle, WA 98109 USA. [Bird, Thomas] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Bird, Thomas] Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Bird, T (reprint author), VA Puget Sound Hlth Care Syst, Geriat Res & Clin Ctr, 1660 S Columbian Way,S-182 GRECC, Seattle, WA 98109 USA. EM tomnroz@u.washington.edu FU Department of Veterans Affairs research funds; Huntington's Disease Society of America FX Supported by the Department of Veterans Affairs research funds and the Huntington's Disease Society of America. Our appreciation to Our colleagues and the staff of the Medical Genetics clinic at the University of Washington for identifying late onset cases. Thanks to DG Cook and S Elmore for assistance with the figures. NR 17 TC 22 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JAN 15 PY 2009 VL 276 IS 1-2 BP 159 EP 162 DI 10.1016/j.jns.2008.09.029 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 404BH UT WOS:000263125200035 PM 18977004 ER PT J AU Mahalanabis, M Jayaraman, P Miura, T Pereyra, F Chester, EM Richardson, B Walker, B Haigwood, NL AF Mahalanabis, Madhumita Jayaraman, Pushpa Miura, Toshiyuki Pereyra, Florencia Chester, E. Michael Richardson, Barbra Walker, Bruce Haigwood, Nancy L. TI Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naive Human Immunodeficiency Virus Controllers SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; MULTIPLE SEQUENCE ALIGNMENT; ORIGINAL ANTIGENIC SIN; TYPE-1 INFECTION; HIV-INFECTION; RESPONSES; EVOLUTION; ENVELOPE; PROGRESSION; VARIANTS AB We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naive subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous env evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive variants dominated in subjects with intermittent viral blips, while neutralization-resistant variants predominated in elite controllers. By sequence analysis of this panel of autologous variants with various sensitivities to neutralization, we identified more than 30 residues in envelope proteins (Env) associated with resistance or sensitivity to ANAbs. The appearance of new sensitive variants is consistent with a model of continuous selection and turnover. Strong ANAb responses directed against autologous Env variants are present in long-term chronically infected individuals, suggesting a role for these responses in contributing to the durable control of HIV replication. C1 [Mahalanabis, Madhumita; Haigwood, Nancy L.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Haigwood, Nancy L.] Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. [Richardson, Barbra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Chester, E. Michael] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Miura, Toshiyuki; Pereyra, Florencia; Walker, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02129 USA. [Miura, Toshiyuki; Pereyra, Florencia; Walker, Bruce] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. [Jayaraman, Pushpa; Haigwood, Nancy L.] Seattle Biomed Res Inst, Seattle, WA 98109 USA. RP Haigwood, NL (reprint author), Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA. EM haigwoon@ohsu.edu FU PHS [NIH-P01-AI054564]; Center for AIDS; University of Washington [P30 AI27757]; James B. Pendleton Charitable Trust; Murdock Charitable Trust FX The work was supported by PHS grant NIH-P01-AI054564, the Immunology Core of the Center for AIDS and STD at the University of Washington (P30 AI27757), and generous gifts from the James B. Pendleton Charitable Trust and the Murdock Charitable Trust. NR 39 TC 75 Z9 76 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 15 PY 2009 VL 83 IS 2 BP 662 EP 672 DI 10.1128/JVI.01328-08 PG 11 WC Virology SC Virology GA 388UO UT WOS:000262045000016 PM 18987151 ER PT J AU Prado, JG Honeyborne, I Brierley, I Puertas, MC Martinez-Picado, J Goulder, PJR AF Prado, Julia G. Honeyborne, Isobella Brierley, Ian Puertas, Maria Carmen Martinez-Picado, Javier Goulder, Philip J. R. TI Functional Consequences of Human Immunodeficiency Virus Escape from an HLA-B*13-Restricted CD8(+) T-Cell Epitope in p1 Gag Protein SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL LOAD; HIV-1 GAG; LYMPHOCYTE RESPONSE; IN-VIVO; VACCINE DESIGN; POL PRECURSOR; TYPE-1; REPLICATION; HLA; MUTATIONS AB The observed association between HLA-B*13 and control of human immunodeficiency virus type 1 (HIV-1) infection has been linked to the number of Gag-specific HLA-B*13-restricted cytotoxic T-cell (CTL) responses identified. To date, the Gag escape mutations described that result in an in vitro fitness cost to the virus have been located within structural protein p24 only. Here we investigated the hypothesis that CTL escape mutations within other regions of HIV Gag may also reduce viral fitness and contribute to immune control. We analyzed an HLA-B*13-restricted CTL response toward an epitope in p1 Gag, RQANFLGKI(429-437) (RI9), where amino acid variation at Gag residues 436 and 437 is associated with HLA-B*13 expression. In this work, we assessed the impact of amino acid substitutions at these positions on CTL recognition and on HIV-1 fitness. We demonstrated that substitutions I437L and I437M largely abrogate CTL recognition and reduce viral fitness while variants K436R and I437V have only a marginal effect on recognition and fitness. Examination of the patterns of protein synthesis indicated that the loss of fitness in the I437L and I437M mutants is associated with the accumulation of unprocessed Gag precursors. A significant reduction in ribosomal frameshifting efficiency was observed with I437M, suggesting that this mechanism contributes to the observed reduced fitness of this virus. These studies illustrate the apparent trade-off available to the virus between evasion of CTL recognition in p1 Gag and the functional consequences for viral fitness. C1 [Prado, Julia G.; Honeyborne, Isobella; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford OX1 3SY, England. [Brierley, Ian] Univ Cambridge, Dept Pathol, Div Virol, Cambridge CB2 1QP, England. [Puertas, Maria Carmen; Martinez-Picado, Javier] Hosp Badalona Germans Trias & Pujol, Fundacio IrsiCaixa, Badalona, Spain. [Martinez-Picado, Javier] ICREA, Barcelona, Spain. [Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Congella, South Africa. [Goulder, Philip J. R.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. RP Goulder, PJR (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res,S Parks Rd, Oxford OX1 3SY, England. EM philip.goulder@paediatrics.ox.ac.uk RI Martinez-Picado, Javier/G-5507-2012; Puertas, Maria /G-3251-2016 OI Martinez-Picado, Javier/0000-0002-4916-2129; Puertas, Maria /0000-0002-6750-2318 FU Wellcome Trust; IEF [41811]; Biotechnology and Biological Sciences Research Council; HIVACAT FX This work was supported by the Wellcome Trust (P.J.R.G.), Marie Curie program IEF contract 41811 (J.G.P), the Biotechnology and Biological Sciences Research Council (I.B.), and the HIVACAT project (J.M.P.). NR 51 TC 35 Z9 37 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 15 PY 2009 VL 83 IS 2 BP 1018 EP 1025 DI 10.1128/JVI.01882-08 PG 8 WC Virology SC Virology GA 388UO UT WOS:000262045000048 PM 18945768 ER PT J AU Wu, L Fossum, E Joo, CH Inn, KS Shin, YC Johannsen, E Hutt-Fletcher, LM Hass, J Jung, JU AF Wu, Liguo Fossum, Even Joo, Chul Hyun Inn, Kyung-Soo Shin, Young Chul Johannsen, Eric Hutt-Fletcher, Lindsey M. Hass, Juergen Jung, Jae U. TI Epstein-Barr Virus LF2: an Antagonist to Type I Interferon SO JOURNAL OF VIROLOGY LA English DT Article ID REGULATORY FACTOR; ANTIVIRAL RESPONSE; IMMUNE EVASION; ACTIVATION; PROTEIN; IRF-7; INDUCTION; GENES; INFECTION; DISTINCT AB Upon viral infection, the major defense mounted by the host immune system is activation of the interferon (IFN)-mediated antiviral pathway, which is mediated by IFN regulatory factors (IRFs). In order to complete their life cycle, viruses must modulate host IFN-mediated immune responses. Despite its association with significant human health problems, activities of Epstein-Barr virus (EBV), a human tumor-inducing herpesvirus, to evade host IFN-mediated innate immunity have not been well characterized. To search for EBV genes that block IFN signal transduction, we carried out a screening of EBV open reading frames for their abilities to block IFN-alpha/beta-mediated luciferase expression upon Sendai virus infection. This screening demonstrates that EBV LF2 tegument protein specifically interacts with the central inhibitory association domain of IRF7, and this interaction leads to inhibition of the dimerization of IRF7, which suppresses IFN-alpha production and IFN-mediated immunity. This demonstrates a novel immune evasion mechanism of EBV LF2 in blocking cellular IRF7-mediated innate immunity. C1 [Wu, Liguo; Inn, Kyung-Soo; Shin, Young Chul; Jung, Jae U.] Harvard Univ, Sch Med, New England Primate Res Ctr, Dept Microbiol & Mol Genet,Tumor Virol Div, Southborough, MA 01772 USA. [Wu, Liguo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Immunol & Inflammatory Dis, Charlestown, MA 02129 USA. [Inn, Kyung-Soo; Jung, Jae U.] Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, Los Angeles, CA 93300 USA. [Fossum, Even] Forschungszentrum Karlsruhe, Inst Genet, D-76021 Karlsruhe, Germany. [Fossum, Even; Hass, Juergen] Univ Ulsan, Coll Med, Dept Microbiol, Seoul 138736, South Korea. [Johannsen, Eric] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Johannsen, Eric] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Hutt-Fletcher, Lindsey M.] Louisiana State Univ, Hlth Sci Ctr, Dept Microbiol & Immunol, Ctr Mol & Tumor Virol, Shreveport, LA 71130 USA. [Hutt-Fletcher, Lindsey M.] Louisiana State Univ, Hlth Sci Ctr, Feist Weiller Canc Ctr, Shreveport, LA 71130 USA. RP Jung, JU (reprint author), Univ So Calif, Keck Sch Med, Dept Mol Microbiol & Immunol, 2011 Zonal Ave,HMR Rm 401, Los Angeles, CA 90033 USA. EM jaeujung@usc.edu FU U. S. Public Health Service [CA106156, CA82057, CA91819, RR00168]; Korea Research Foundation [KRF-2004-037-C00104] FX We thank P. Palese and J. Hiscott for providing reagents. NR 40 TC 28 Z9 35 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN 15 PY 2009 VL 83 IS 2 BP 1140 EP 1146 DI 10.1128/JVI.00602-08 PG 7 WC Virology SC Virology GA 388UO UT WOS:000262045000060 PM 18987133 ER PT J AU Raffel, GD Chu, GC Jesneck, JL Cullen, DE Bronson, RT Bernard, OA Gilliland, DG AF Raffel, Glen D. Chu, Gerald C. Jesneck, Jonathan L. Cullen, Dana E. Bronson, Roderick T. Bernard, Olivier A. Gilliland, D. Gary TI Ott1 (Rbm15) Is Essential for Placental Vascular Branching Morphogenesis and Embryonic Development of the Heart and Spleen SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LEFT-RIGHT AXIS; HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL GROWTH-FACTOR; CHORIOALLANTOIC PLACENTA; SIGNALING PATHWAY; DIGEORGE-SYNDROME; ALAGILLE-SYNDROME; BINDING-PROTEIN; CRITICAL REGION; SPLIT-ENDS AB The infant leukemia-associated gene Ott1 (Rbm15) has broad regulatory effects within murine hematopoiesis. However, germ line Ott1 deletion results in fetal demise prior to embryonic day 10.5, indicating additional developmental requirements for Ott1. The spen gene family, to which Ott1 belongs, has a transcriptional activation/repression domain and RNA recognition motifs and has a significant role in the development of the head and thorax in Drosophila melanogaster. Early Ott1-deficient embryos show growth retardation and incomplete closure of the notochord. Further analysis demonstrated placental defects in the spongiotrophoblast and syncytiotrophoblast layers, resulting in an arrest of vascular branching morphogenesis. The rescue of the placental defect using a conditional allele with a trophoblast-sparing cre transgene allowed embryos to form a normal placenta and survive gestation. This outcome showed that the process of vascular branching morphogenesis in Ott1-deficient animals was regulated by the trophoblast compartment rather than the fetal vasculature. Mice surviving to term manifested hyposplenia and abnormal cardiac development. Analysis of global gene expression of Ott1-deficient embryonic hearts showed an enrichment of hypoxia-related genes and a significant alteration of several candidate genes critical for cardiac development. Thus, Ott1-dependent pathways, in addition to being implicated in leukemogenesis, may also be important for the pathogenesis of placental insufficiency and cardiac malformations. C1 [Raffel, Glen D.; Cullen, Dana E.; Gilliland, D. Gary] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. [Chu, Gerald C.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Jesneck, Jonathan L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Jesneck, Jonathan L.] Broad Inst Harvard, Canc Program, Cambridge, MA 02141 USA. [Jesneck, Jonathan L.] MIT, Cambridge, MA 02141 USA. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Bernard, Olivier A.] INSERM, E0210, Paris, France. [Bernard, Olivier A.] Univ Paris 05, Paris, France. [Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Raffel, GD (reprint author), Univ Massachusetts, Sch Med, Div Hematol Oncol, LRB306,364 Plantat St, Worcester, MA 01605 USA. EM glen.raffel@umassmed.edu; ggilliland@rics.bwh.harvard.edu RI Bernard, Olivier/E-5721-2016 FU National Institutes of Health [K08 CA111399, P01 CA66996]; Leukemia and Lymphoma Society FX This work was supported in part by National Institutes of Health grants K08 CA111399 ( G. D. R.) and P01 CA66996 ( D. G. G.) and the Leukemia and Lymphoma Society. D. G. G. is an Investigator for the Howard Hughes Medical Institute. We report no relevant conflicts of interest. NR 67 TC 16 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN 15 PY 2009 VL 29 IS 2 BP 333 EP 341 DI 10.1128/MCB.00370-08 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 388UW UT WOS:000262045800004 PM 18981216 ER PT J AU Princen, F Bard, E Sheikh, F Zhang, SS Wang, J Zago, WM Wu, DM Trelles, RD Bailly-Maitre, B Kahn, CR Chen, Y Reed, JC Tong, GG Mercola, M Chen, J Feng, GS AF Princen, Frederic Bard, Emilie Sheikh, Farah Zhang, Sharon S. Wang, Jing Zago, Wagner M. Wu, Dongmei Trelles, Ramon Diaz Bailly-Maitre, Beatrice Kahn, C. Ronald Chen, Yan Reed, John C. Tong, Gary G. Mercola, Mark Chen, Ju Feng, Gen-Sheng TI Deletion of Shp2 Tyrosine Phosphatase in Muscle Leads to Dilated Cardiomyopathy, Insulin Resistance, and Premature Death SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; HEART-FAILURE; CARDIAC-HYPERTROPHY; SIGNALING PATHWAYS; RECEPTOR SUBSTRATE-1; GENE-EXPRESSION; PTPN11 SHP2; CARDIOMYOCYTES; MOUSE; MECHANISM AB The intracellular signaling mechanisms underlying the pathogenesis of cardiac diseases are not fully understood. We report here that selective deletion of Shp2, an SH2-containing cytoplasmic tyrosine phosphatase, in striated muscle results in severe dilated cardiomyopathy in mice, leading to heart failure and premature mortality. Development of cardiomyopathy in this mouse model is coupled with insulin resistance, glucose intolerance, and impaired glucose uptake in striated muscle cells. Shp2 deficiency leads to upregulation of leukemia inhibitory factor-stimulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes. Insulin resistance and impaired glucose uptake in Shp2-deficient mice are at least in part due to impaired protein kinase C-zeta/lambda and AMP-kinase activities in striated muscle. Thus, we have generated a mouse line modeling human patients suffering from cardiomyopathy and insulin resistance. This study reinforces a concept that a compound disease with multiple cardiovascular and metabolic disturbances can be caused by a defect in a single molecule such as Shp2, which modulates multiple signaling pathways initiated by cytokines and hormones. C1 [Princen, Frederic; Bard, Emilie; Zhang, Sharon S.; Wang, Jing; Zago, Wagner M.; Wu, Dongmei; Trelles, Ramon Diaz; Bailly-Maitre, Beatrice; Reed, John C.; Tong, Gary G.; Mercola, Mark; Feng, Gen-Sheng] Burnham Inst Med Res, La Jolla, CA 92037 USA. [Sheikh, Farah; Chen, Ju] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Tong, Gary G.] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Chen, Yan] Chinese Acad Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China. [Feng, Gen-Sheng] Xiamen Univ, Inst Biomed Res, Xiamen 361005, Peoples R China. RP Feng, GS (reprint author), Burnham Inst Med Res, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM gfeng@burnham.org RI Bard-Chapeau, Emilie/H-6091-2011; Chen, Ju/E-5579-2011; OI Diaz Trelles, Ramon/0000-0002-2666-9728 FU NIH [R01DK73945, R01HL082902, R01HL059502]; American Heart Association; AHA National Scientist Development FX This study was supported by NIH grants R01DK73945 to G.-S. F., R01HL082902 to J. C., and R01HL059502 to M. M. R. D. T. is a recipient of a postdoctoral fellowship from American Heart Association. F. S. is a recipient of the AHA National Scientist Development Grant. NR 48 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JAN 15 PY 2009 VL 29 IS 2 BP 378 EP 388 DI 10.1128/MCB.01661-08 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 388UW UT WOS:000262045800007 PM 19001090 ER PT J AU Szumski, NR Cheng, EM AF Szumski, Nicholas R. Cheng, Eric M. TI Optimizing Algorithms to Identify Parkinson's Disease Cases Within an Administrative Database SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; ICD-9-CM codes; administrative data; predictive value; sensitivity; specificity ID INTERNATIONAL CLASSIFICATION; ACCURACY; CODES; DIAGNOSIS; ICD-9-CM AB Patients assigned file diagnostic ICD-9-CM code for Parkinson's disease (PD) in an administrative database may not truly carry that diagnosis because Of the Various error sources. Improved ability to identify PD cases within databases may facilitate specific research goals. Experienced chart reviewers abstracted the working diagnosis of all 577 patients assigned diagnostic code 332.0 (PD) during 1 year at it VA Healthcare System. We then tested the ability of various algorithms making use of PD and non-PD diagnostic codes, specialty of clinics visited, and medication prescription data to predict the abstracted working diagnosis. Chart review determined 436 (75.6%) patients to be PD or Possibly PD, and 141 (24.4%) to lie Not PD. Our tiered consensus algorithm preferentially used data from specialists over nonspecialists improved PPV to 83.2% (P = 0.003 vs. baseline). When presence of a PD prescription was an additional criterion, PPV increased further to 88.2% (P = 0.04 vs. without medication criterion), but sensitivity decreased from 87.4 to 77.1% (P = 0.0001). We demonstrate that algorithms provide better identification of PD cases than using a single Occurrence of the diagnostic code for PD, and modifications of such algorithms can be tuned to maximize parameters that best meet the goals of a particular database query. 0 2008 Movement Disorder Society C1 [Szumski, Nicholas R.; Cheng, Eric M.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. [Szumski, Nicholas R.; Cheng, Eric M.] SW Parkinsons Dis Res Educ & Clin Ctr PADRECC, Los Angeles, CA USA. [Szumski, Nicholas R.; Cheng, Eric M.] VA Greater Los Angeles Healthcare Syst, Dept Neurol, Los Angeles, CA USA. RP Szumski, NR (reprint author), Univ Calif Los Angeles, Dept Neurol, 710 Westwood Plaza,RNRC A-153, Los Angeles, CA 90095 USA. EM nszumski@mednet.ucla.edu FU Southwest Parkinson's Disease Research, Education, and Clinical Center [PADRECC]; NINDS career development award [K23NS058571] FX Research supported by the Southwest Parkinson's Disease Research, Education, and Clinical Center (PADRECC). Dr. Cheng is supported by an NINDS career development award (K23NS058571). We thank Stefanie D. Vassar for her help in compiling data and performing statistical analyses. NR 15 TC 17 Z9 18 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JAN 15 PY 2009 VL 24 IS 1 BP 51 EP 56 DI 10.1002/mds.22283 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 402CW UT WOS:000262992800006 PM 18816696 ER PT J AU Stoodley, CJ Schmahmann, JD AF Stoodley, Catherine J. Schmahmann, Jeremy D. TI Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies SO NEUROIMAGE LA English DT Review DE Cerebellum; Cognition; Motor; Emotion; Topography; Functional imaging ID POSITRON-EMISSION-TOMOGRAPHY; VERBAL WORKING-MEMORY; COGNITIVE-AFFECTIVE SYNDROME; POSTERIOR-FOSSA TUMORS; BLOOD-FLOW CHANGES; HUMAN BRAIN; HORSERADISH-PEROXIDASE; MOTOR IMAGERY; CORTICOPONTOCEREBELLAR PATHWAY; SOMATOTOPIC ORGANIZATION AB Clinical, experimental and neuroimaging studies indicate that the cerebellum is involved in neural processes beyond the motor domain. Cerebellar somatotopy has been shown for motor control, but topographic organization of higher-order functions has not yet been established. To determine whether existing literature supports the hypothesis of functional topography in the human cerebellum, we conducted an activation likelihood estimate (ALE) meta-analysis of neuroimaging studies reporting cerebellar activation in selected task categories: motor (n=7 studies), somatosensory (n=2), language (n=11), verbal working memory (n=8), spatial (n=8), executive function (n= 8) and emotional processing (n= 9). In agreement with previous investigations, sensorimotor tasks activated anterior lobe (lobule V) and adjacent lobule VI, with additional foci in lobule VIII. Motor activation was in VIIIA/B; somatosensory activation was confined to VIIIB. The posterior lobe was involved in higher-level tasks. ALE peaks were identified in lobule VI and Crus I for language and verbal working memory; lobule VI for spatial tasks; lobules VI, Crus I and VIIB for executive functions; and lobules VI, Crus I and medial VII for emotional processing. Language was heavily right-lateralized and spatial peaks left-lateralized, reflecting crossed cerebro-cerebellar projections. Language and executive tasks activated regions of Crus I and lobule VII proposed to be involved in prefrontal-cerebellar loops. Emotional processing involved vermal lobule VII, implicated in cerebellar-limbic circuitry. These data provide support for an anterior sensorimotor vs. posterior cognitive/emotional dichotomy in the human cerebellum. Prospective studies of multiple domains within single individuals are necessary to better elucidate neurobehavioral structure-function correlations in the cerebellar posterior lobe. (C) 2008 Elsevier Inc. All rights reserved. C1 [Stoodley, Catherine J.] Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stoodley, CJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Cognit Behav Neurol Unit, Ataxia Unit, 175 Cambridge St,Suite 340, Boston, MA 02114 USA. EM cstoodley@partners.org RI Stoodley, Catherine/P-2081-2016 OI Stoodley, Catherine/0000-0003-2629-0213 FU Birmingham Foundation FX Grant support was provided by the Birmingham Foundation, and a Fund for Medical Discovery fellowship award to C. Stoodley from the MGH Executive Committee on Research. We would like to thank Jason MacMore and Joseph DiNunzio for their technical assistance, and acknowledge the work of Amy Hurwitz, Russell Loeber and Jennifer Marjani on a previous version of this project. NR 160 TC 580 Z9 595 U1 6 U2 64 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2009 VL 44 IS 2 BP 489 EP 501 DI 10.1016/j.neuroimage.2008.08.039 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KH UT WOS:000262301100019 PM 18835452 ER PT J AU Agam, Y Hyun, JS Danker, JF Zhou, F Kahana, MJ Sekuler, R AF Agam, Yigal Hyun, Joo-Seok Danker, Jared F. Zhou, Feng Kahana, Michael J. Sekuler, Robert TI Early neural signatures of visual short-term memory SO NEUROIMAGE LA English DT Article ID POSTERIOR PARIETAL CORTEX; WORKING-MEMORY; PREFRONTAL CORTEX; INDIVIDUAL-DIFFERENCES; OBJECT RECOGNITION; BRAIN; REPETITION; CAPACITY; HUMANS; SPEED AB Visual short-term memory (VSTM) relies on a distributed network including sensory-related, posterior regions of the brain and frontal areas associated with attention and cognitive control. To characterize the. ne temporal details of processing within this network, we recorded event-related potentials (ERPs) while human subjects performed a recognition-memory task. The task's difficulty was graded by varying the perceptual similarity between the items held in memory and the probe used to access memory. The evaluation of VSTM's contents against a test stimulus produced clear similarity-dependent differences in ERPs as early as 156 ms after probe onset. Posterior recording sites were the first to reflect the difficulty of the analysis, preceding their frontal counterparts by about 50 ms. Our results suggest an initial feed-forward interaction underlying stimulus-memory comparisons, consistent with the idea that visual areas contribute to temporary storage of visual information for use in ongoing tasks. This study provides a first look into early neural activity underlying the processing of visual information in short-term memory. (C) 2008 Elsevier Inc. All rights reserved. C1 [Agam, Yigal] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. [Hyun, Joo-Seok] Chung Ang Univ, Dept Psychol, Seoul 156756, South Korea. [Danker, Jared F.] Carnegie Mellon Univ, Dept Psychol, Pittsburgh, PA 15213 USA. [Zhou, Feng; Sekuler, Robert] Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02254 USA. [Kahana, Michael J.] Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Agam, Y (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02138 USA. EM yigal@nmr.mgh.harvard.edu FU NIH [MH68404] FX Supported by NIH grant MH68404. NR 44 TC 5 Z9 7 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JAN 15 PY 2009 VL 44 IS 2 BP 531 EP 536 DI 10.1016/j.neuroimage.2008.09.018 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392KH UT WOS:000262301100023 PM 18930156 ER PT J AU Tonino, PAL De Bruyne, B Pijls, NHJ Siebert, U Ikeno, F van 't Veer, M Klauss, V Manoharan, G Engstrom, T Oldroyd, KG Lee, PNV MacCarthy, PA Fearon, WF AF Tonino, Pim A. L. De Bruyne, Bernard Pijls, Nico H. J. Siebert, Uwe Ikeno, Fumiaki van 't Veer, Marcel Klauss, Volker Manoharan, Ganesh Engstrom, Thomas Oldroyd, Keith G. Lee, Peter N. Ver MacCarthy, Philip A. Fearon, William F. CA FAME Study Investigators TI Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID DRUG-ELUTING STENTS; OPTIMAL MEDICAL THERAPY; ARTERY-DISEASE; MYOCARDIAL-INFARCTION; MULTIVESSEL DISEASE; RANDOMIZED-TRIALS; CLINICAL-OUTCOMES; BLOOD-FLOW; FOLLOW-UP; REVASCULARIZATION AB Background In patients with multivessel coronary artery disease who are undergoing percutaneous coronary intervention ( PCI), coronary angiography is the standard method for guiding the placement of the stent. It is unclear whether routine measurement of fractional flow reserve ( FFR; the ratio of maximal blood flow in a stenotic artery to normal maximal flow), in addition to angiography, improves outcomes. Methods In 20 medical centers in the United States and Europe, we randomly assigned 1005 patients with multivessel coronary artery disease to undergo PCI with implantation of drug- eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography- guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR- guided PCI underwent stenting of indicated lesions only if the FFR was 0.80 or less. The primary end point was the rate of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. Results The mean (+/- SD) number of indicated lesions per patient was 2.7+/- 0.9 in the angiography group and 2.8+/- 1.0 in the FFR group ( P = 0.34). The number of stents used per patient was 2.7+/- 1.2 and 1.9+/- 1.3, respectively ( P< 0.001). The 1- year event rate was 18.3% ( 91 patients) in the angiography group and 13.2% ( 67 patients) in the FFR group ( P = 0.02). Seventy- eight percent of the patients in the angiography group were free from angina at 1 year, as compared with 81% of patients in the FFR group ( P = 0.20). Conclusions Routine measurement of FFR in patients with multivessel coronary artery disease who are undergoing PCI with drug- eluting stents significantly reduces the rate of the composite end point of death, nonfatal myocardial infarction, and repeat revascularization at 1 year. (ClinicalTrials.gov number, NCT00267774.). C1 [Tonino, Pim A. L.; Pijls, Nico H. J.; van 't Veer, Marcel] Catharina Hosp, Dept Cardiol, NL-5623 EJ Eindhoven, Netherlands. [De Bruyne, Bernard] Cardiovasc Ctr Aalst, Aalst, Belgium. [Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Hall In Tirol, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Ikeno, Fumiaki; Fearon, William F.] Palo Alto Vet Affairs Hlth Care Syst, Stanford, CA USA. [Klauss, Volker] Univ Hosp Munich, Med Poliklin, Munich, Germany. [Manoharan, Ganesh] Royal Victoria Hosp, Ctr Heart, Belfast BT12 6BA, Antrim, North Ireland. [Engstrom, Thomas] Rigshosp, DK-2100 Copenhagen, Denmark. [Oldroyd, Keith G.] Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. [Lee, Peter N. Ver] NE Cardiol Assoc, Bangor, ME USA. [MacCarthy, Philip A.] Kings Coll Hosp London, London, England. RP Pijls, NHJ (reprint author), Catharina Hosp, Dept Cardiol, Michelangelolaan 2, NL-5623 EJ Eindhoven, Netherlands. EM nico.pijls@inter.nl.net FU Radi Medical Systems; Stichting Vrienden van het Hart Zuidoost Brabant; Medtronic; Catharina Hospital Eindhoven from Radi Medical Systems; Nycomed Denmark; Boston Scientific; Cordis; Abbott Vascular FX Supported by unrestricted research grants from Radi Medical Systems and Stichting Vrienden van het Hart Zuidoost Brabant. Medtronic provided limited financial support to some centers by tailoring the price of the Endeavor stents to the local reimbursement system.; Dr. Pijls reports receiving an institutional research grant for the Catharina Hospital Eindhoven from Radi Medical Systems; Dr. Engstrom, lecture fees from Nycomed Denmark; Dr. Oldroyd, consulting fees from Radi Medical Systems, Boston Scientific, and Cordis and lecture fees and grant support from Boston Scientific; Dr. Ver Lee, lecture fees from Radi Medical Systems; and Dr. Fearon, consulting fees from Abbott Vascular. No other potential conflict of interest relevant to this article was reported. NR 39 TC 1266 Z9 1336 U1 9 U2 46 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2009 VL 360 IS 3 BP 213 EP 224 DI 10.1056/NEJMoa0807611 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 394GR UT WOS:000262434500004 PM 19144937 ER PT J AU Filbin, MR Ring, DC Wessels, MR Avery, LL Kradin, RL Binder, WD AF Filbin, Michael R. Ring, David C. Wessels, Michael R. Avery, Laura L. Kradin, Richard L. Binder, William D. TI A Man with Pain and Swelling of the Right Hand and Hypotension Necrotizing fasciitis and the toxic shock syndrome, caused by group A streptococcal infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BLACK-TAR HEROIN; STREPTOLYSIN-S; PYOGENES; THERAPY; SEPSIS; RISK C1 [Filbin, Michael R.] Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. [Ring, David C.] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. [Avery, Laura L.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Kradin, Richard L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wessels, Michael R.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Filbin, Michael R.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Ring, David C.] Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. [Wessels, Michael R.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Avery, Laura L.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Kradin, Richard L.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kradin, Richard L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Filbin, MR (reprint author), Massachusetts Gen Hosp, Dept Emergency Serv, Boston, MA 02114 USA. FU Biosite; Small Bone Innovations; Smith and Nephew Richards; Wright Medical Technology; Joint Active Systems; Biomet; Medical Modeling; Tornier; Acumed; Hand Innovations FX Dr. Filbin reports receiving grant support from Biosite for a sepsis biomarker study and serving as an expert witness for litigation involving sepsis. Dr. Ring reports receiving unrestricted research grants from Small Bone Innovations, Smith and Nephew Richards, Wright Medical Technology, Joint Active Systems, Biomet, Medical Modeling, Tornier, and Acumed, receiving consulting fees from Smith and Nephew Richards, Wright Medical, Tornier, and Acumed, receiving royalties from Hand Innovations, and having stock options in Illuminos, MiMedx, and Simplicity Orthopedic Solutions. No other potential conflict of interest relevant to this article was reported. NR 19 TC 7 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 15 PY 2009 VL 360 IS 3 BP 281 EP 290 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 394GR UT WOS:000262434500012 PM 19144944 ER PT J AU Boisgerault, F Liu, Y Anosova, N Dana, R Benichou, G AF Boisgerault, Florence Liu, Ying Anosova, Nathalle Dana, Reza Benichou, Gilles TI Differential Roles of Direct and Indirect Allorecognition Pathways in the Rejection of Skin and Corneal Transplants SO TRANSPLANTATION LA English DT Article DE Skin graft; Corneal transplantation; T cells; Indirect allorecognition; Cytokines ID CYTOTOXIC T-LYMPHOCYTES; CLASS-I PEPTIDES; MHC CLASS-II; ALLOGRAFT-REJECTION; INDIRECT RECOGNITION; GRAFT-REJECTION; DENDRITIC CELLS; CD4(+); MICE; ANTIGENS AB Background. It is generally accepted that all transplants are not rejected in the same fashion. However, the extrinsic and intrinsic factors that control the recognition and rejection of a particular allograft by the host are not well characterized. Methods. We compared the mechanisms underlying the response with donor antigens by T cells activated after transplantation of fully allogeneic skin and corneal grafts in mice. Results. In corneal-transplanted mice, the CD4(+) T-cell response was exclusively mediated by T cells recognizing minor antigens in an indirect fashion and producing low levels of interleukin-2. In contrast, skin grafts elicited both direct and indirect CD4(+) T-cell responses primarily directed to major histocompatibility complex antigens and characterized by high interleukin-2 levels. Although CD8(+) T-cells producing gamma interferon were activated directly in both skin-and cortical-grafted mice, only CD8(+) T cells from skin-transplanted mice Mounted a cytotoxic response. Next, we investigated whether failure of corneal transplants to induce a CD4(+) direct alloresponse is due to their poor immunogenicity or due to the site of placement (eye). We observed that corneas transplanted under the skin and splenocytes transplanted in the eye were both capable of inducing direct CD4(+) T-cell alloreactivity. Conclusions. This shows that failure of orthotopic corneal allotransplants to elicit a CD4(+) T-cell direct alloresponse is associated with the combination of two factors, their low immunogenicity and the immune-privileged properties of the eye. C1 [Boisgerault, Florence; Anosova, Nathalle; Benichou, Gilles] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Surg, Transplantat Unit,Cellular & Mol Immunol Lab, Boston, MA 02114 USA. [Liu, Ying; Dana, Reza] Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. RP Benichou, G (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Surg, Transplantat Unit,Cellular & Mol Immunol Lab, 55 Fruit St,Thier 807, Boston, MA 02114 USA. EM gbenichou@partners.org FU NEI NIH HHS [R01 EY13310, R01 EY12963, R01 EY013310, R01 EY012963-08, R01 EY012963]; NIAID NIH HHS [K02 AI053103-05, R01 AI054976-03, K02 AI053103, R01 AI054976] NR 47 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 2009 VL 87 IS 1 BP 16 EP 23 DI 10.1097/TP.0b013e318191b38b PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 394WL UT WOS:000262483700004 PM 19136886 ER PT J AU Streeck, H Jessen, H Kuecherer, C Li, B Jessen, AB Dupke, S Baumgarten, A Stahmer, I van Lunzen, J Altfeld, M Walker, BD Allen, TM AF Streeck, Hendrik Jessen, Heiko Kuecherer, Claudia Li, Bin Jessen, Arne B. Dupke, Stephan Baumgarten, Axel Stahmer, Ingrid van Lunzen, Jan Altfeld, Marcus Walker, Bruce D. Allen, Todd M. TI Epidemiologically linked transmission of HIV-1 illustrates the impact of host genetics on virological outcome SO AIDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; T-CELL RESPONSES; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; TYPE-1 INFECTION; VIRAL CONTROL; ESCAPE; DISCONTINUATION; SELECTION; MUTATION AB The diversity of HIV-1 and human genetics complicates our ability to determine the impact of treatment during primary HIV-1 infection on disease outcome. Here, we show, in a small group infected with virtually identical HIV-1 strains and treated during primary HIV-1 infection, that patients expressing protective human leucocyte antigen alleles had lower viral loads following treatment discontinuation. These data suggest that genetic factors play an important role in the outcome of HIV-1 infection despite early therapy. C1 [Streeck, Hendrik; Li, Bin; Altfeld, Marcus; Walker, Bruce D.; Allen, Todd M.] Harvard Univ, Partners AIDS Res Ctr, Div Infect Dis, Massachusetts Gen Hosp,Med Sch, Charlestown, MA USA. [Jessen, Heiko; Jessen, Arne B.] HIV Clin Dres Jessen, Berlin, Germany. [Kuecherer, Claudia] Robert Koch Inst, D-1000 Berlin, Germany. [Dupke, Stephan; Baumgarten, Axel] HIV Clin Baumgarten, Berlin, Germany. [Stahmer, Ingrid; van Lunzen, Jan] Univ Med Ctr Hamburg Eppendorf, Infect Dis Unit, Hamburg, Germany. [Walker, Bruce D.] Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Allen, TM (reprint author), MGH E, CNY 6625,149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [U01-AI052403, R01-AI054178, U01 AI052403, U01 AI052403-04, R01 AI054178, R01 AI054178-04] NR 25 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 14 PY 2009 VL 23 IS 2 BP 259 EP 262 DI 10.1097/QAD.0b013e328315a78b PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 400OB UT WOS:000262876600015 PM 19098497 ER PT J AU Millett, PJ Braun, S Gobezie, R Pacheco, IH AF Millett, Peter J. Braun, Sepp Gobezie, Reuben Pacheco, Ivan H. TI Acromioclavicular joint reconstruction with coracoacromial ligament transfer using the docking technique SO BMC MUSCULOSKELETAL DISORDERS LA English DT Article ID COMPLETE DISLOCATION; INJURIES; SEPARATIONS; SHOULDER; COMPLEX; REPAIR AB Background: Symptomatic Acromioclavicular (AC) dislocations have historically been surgically treated with Coracoclavicular (CC) ligament reconstruction with transfer of the Coracoacromial (CA) ligament. Tensioning the CA ligament is the key to success. Methods: Seventeen patients with chronic, symptomatic Type III AC joint or acute Type IV and V injuries were treated surgically. The distal clavicle was resected and stabilized with CC ligament reconstruction using the CA ligament. The CA ligament was passed into the medullary canal and tensioned, using a modified 'docking' technique. Average follow-up was 29 months (range 12-57). Results: Postoperative ASES and pain significantly improved in all patients ( p = 0.001). Radiographically, 16 (94%) maintained reduction, and only 1 (6%) had a recurrent dislocation when he returned to karate 3 months postoperatively. His ultimate clinical outcome was excellent. Conclusion: The docking procedure allows for tensioning of the transferred CA ligament and healing of the ligament in an intramedullary bone tunnel. Excellent clinical results were achieved, decreasing the risk of recurrent distal clavicle instability. C1 [Millett, Peter J.; Braun, Sepp] Steadman Hawkins Res Fdn, Vail, CO USA. [Gobezie, Reuben; Pacheco, Ivan H.] Case Western Reserve Univ, Sch Med, Case Shoulder & Elbow Serv, Cleveland, OH USA. [Pacheco, Ivan H.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Sch Med,Harvard Shoulder Serv, Boston, MA 02115 USA. RP Millett, PJ (reprint author), Steadman Hawkins Res Fdn, 181 W Meadow Dr,Suite 1000, Vail, CO USA. EM drmillett@steadman-hawkins.com; sebra16@mac.com; Reuben.Gobezie@UHhospitals.org; ihpacheco@yahoo.com NR 39 TC 15 Z9 20 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2474 J9 BMC MUSCULOSKEL DIS JI BMC Musculoskelet. Disord. PD JAN 14 PY 2009 VL 10 AR 6 DI 10.1186/1471-2474-10-6 PG 8 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 405MZ UT WOS:000263230200002 PM 19144190 ER PT J AU Kaplan, GB Leite-Morris, KA Klufas, MA Fan, WY AF Kaplan, Gary B. Leite-Morris, Kimberly A. Klufas, Michael A. Fan, WenYing TI Intra-VTA adenosine A(1) receptor activation blocks morphine stimulation of motor behavior and cortical and limbic Fos immunoreactivity SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE Adenosine A1 receptor; c-Fos; Morphine; Opioid; Ventral tegmental area ID VENTRAL TEGMENTAL AREA; RAT NUCLEUS-ACCUMBENS; MIDBRAIN DOPAMINE NEURONS; IN-VIVO MICRODIALYSIS; MU-OPIOID RECEPTORS; OPIATE WITHDRAWAL; EXTRACELLULAR DOPAMINE; PRESYNAPTIC INHIBITION; A(2A) RECEPTORS; BASAL GANGLIA AB Drugs of abuse produce psychomotor stimulation as one of their characteristic behavioral effects. Single administration of opiates stimulates motor activity via effects on gamma-aminobutyric acid (GABA) and dopamine transmission in the ventral tegmental area (VTA). Adenosine A(1) receptor agonists inhibit VTA GABAergic and dopaminergic transmission and are predicted to alter the behavioral effects of opiates. This study examined the effects of intra-VTA administration of selective adenosine A(1) receptor agonist N-6-cyclopentyladenosine (CPA) and antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT) on morphine-induced motor stimulation in C57BL/6 mice. It also examined the effects of CPA on morphine's activation of VTA neurons projecting to limbic and cortical regions including the nucleus accumbens (NAc), anterior cingulate cortex (ACg) and prelimbic cortex (PrL) via quantitation of immediate-early gene c-Fos protein in these regions. Mice received subcutaneous morphine and intra-VTA administration of CPA and then automated motor activity was measured. Morphine treatment induced both motor activity and Fos immunoreactivity in the NAc, ACg and PrL suggesting that behavioral stimulation is produced by neural activation in these regions. Intra-VTA CPA administration produced a dose-dependent inhibition of morphine-induced motor stimulation and blocked c-Fos induction in all three regions. Intra-VTA CPT treatment had no effects on motor activity or on morphine-induced motor stimulation. VTA adenosine A(1) agonist inhibition of morphine's effects on motor activity and of neural activation of VTA projections suggests that these neurons and their regulation are critical to morphine's stimulant effects. Adenosine A(1) receptor agonists and purinergic modulators may represent useful treatment approaches for blocking the behavioral effects of opiates. Published by Elsevier B.V. C1 [Kaplan, Gary B.] VA Boston Healthcare Syst, Mental Hlth Serv, Boston, MA 02130 USA. [Leite-Morris, Kimberly A.; Fan, WenYing] VA Boston Healthcare Syst, Res Serv, Boston, MA 02130 USA. [Kaplan, Gary B.; Leite-Morris, Kimberly A.; Fan, WenYing] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02130 USA. [Kaplan, Gary B.; Leite-Morris, Kimberly A.; Fan, WenYing] Boston Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02130 USA. [Kaplan, Gary B.] Vet Affairs Med Ctr, Mental Hlth Serv, Providence, RI 02908 USA. [Leite-Morris, Kimberly A.; Klufas, Michael A.] Vet Affairs Med Ctr, Res Serv, Providence, RI 02908 USA. RP Kaplan, GB (reprint author), VA Boston Healthcare Syst, Mental Hlth Serv, 150 S Huntington Ave, Boston, MA 02130 USA. EM Gary.Kaplan@va.gov; kleitemo@bu.edu OI Leite-Morris, Kimberly/0000-0003-3407-7375 FU Department of Veterans Affairs FX This work was supported by a Merit Review Grant from the Department of Veterans Affairs (G.B.K). We acknowledge the technical assistance of Jessie W. Janowski and Lauren Moran in the present study. NR 45 TC 3 Z9 4 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JAN 14 PY 2009 VL 602 IS 2-3 BP 268 EP 276 DI 10.1016/j.ejphar.2008.10.052 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 402MD UT WOS:000263016900013 PM 19027733 ER PT J AU Liu, CY Hsu, YH Wu, MT Pan, PC Ho, CK Su, L Xu, X Li, Y Christiani, DC AF Liu, Chen-yu Hsu, Yi-Hsiang Wu, Ming-Tsang Pan, Pi-Chen Ho, Chi-Kung Su, Li Xu, Xin Li, Yi Christiani, David C. CA Kaohsiung Leukemia Res Grp TI Cured meat, vegetables, and bean-curd foods in relation to childhood acute leukemia risk: A population based case-control study SO BMC CANCER LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; UNITED-STATES; EXPERIMENTAL CARCINOGENESIS; CANCER PREVENTION; BREAST-CANCER; DIET; SOY; CONSUMPTION; NITRITE; FRUIT AB Background: Consumption of cured/smoked meat and fish leads to the formation of carcinogenic N-nitroso compounds in the acidic stomach. This study investigated whether consumed cured/smoked meat and fish, the major dietary resource for exposure to nitrites and nitrosamines, is associated with childhood acute leukemia. Methods: A population-based case-control study of Han Chinese between 2 and 20 years old was conducted in southern Taiwan. 145 acute leukemia cases and 370 age-and sex-matched controls were recruited between 1997 and 2005. Dietary data were obtained from a questionnaire. Multiple logistic regression models were used in data analyses. Results: Consumption of cured/smoked meat and fish more than once a week was associated with an increased risk of acute leukemia (OR = 1.74; 95% CI: 1.15-2.64). Conversely, higher intake of vegetables (OR = 0.55; 95% CI: 0.37-0.83) and bean-curd (OR = 0.55; 95% CI: 0.34-0.89) was associated with a reduced risk. No statistically significant association was observed between leukemia risk and the consumption of pickled vegetables, fruits, and tea. Conclusion: Dietary exposure to cured/smoked meat and fish may be associated with leukemia risk through their contents of nitrites and nitrosamines among children and adolescents, and intake of vegetables and soy-bean curd may be protective. C1 [Liu, Chen-yu; Su, Li; Xu, Xin; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Med, Hebrew Rehabil Ctr, Inst Aging Res, Boston, MA 02115 USA. [Hsu, Yi-Hsiang] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA. [Wu, Ming-Tsang] Kaohsiung Med Univ, Dept Family Med, Kaohsiung, Taiwan. [Wu, Ming-Tsang] Kaohsiung Med Univ, Grad Inst Occupat Safety & Hlth, Kaohsiung, Taiwan. [Wu, Ming-Tsang] Kaohsiung Med Univ, Ctr Excellence & Environm Med, Kaohsiung, Taiwan. [Pan, Pi-Chen] Yuh Ing Jr Coll Hlth Care & Management, Dept Nursing, Kaohsiung, Taiwan. [Ho, Chi-Kung] Kaohsiung Med Univ, Sch Publ Hlth, Kaohsiung, Taiwan. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Yi] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Christiani, David C.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave, Boston, MA 02115 USA. EM cliu@hsph.harvard.edu; yhhsu@hsph.harvard.edu; e_encourage@yahoo.com; pcpan@ms.yuhing.edu.tw; kmco6849@ms14.hinet.net; LISU@hohp.harvard.edu; xin_xu@harvard.edu; yili@jimmy.harvard.edu; DCHRIS@hsph.harvard.edu RI Wu, Ming-Tsang/D-2385-2009; OI LIU, CHEN-YU/0000-0002-4693-5667 FU National Institutes of Health [ES09723, ES00002] FX The members of the Kaohsiung Leukemia Research Group were as follows: Kaohsiung Medical University Chung-Ho Memorial Hospital - Tai-Tsung Chang, Sheng-Fung Lin, Shyh-Shin Chiou, Ren-Chin Jang, Hui-Hua Hsiao, Ta-Chih Liu, and Pei-Chin Lin; Kaohsiung Chang Gung Memorial Hospital Chih-Cheng Hsiao, Jiunn-Ming Sheen, Ching-Yuan Kuo, Ming-Chung Wang, Cheng-Hua Huang, and Chung-Bin Huang; and Kaohsiung Veterans General Hospital - Yuk-Cheung Wong, Hung-Bo Wu, Shyh-Jer Lin, Yu-Ming Sun, Kai-Sheng Hsieh, and Yu-Hsiang Chang. NR 48 TC 10 Z9 10 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD JAN 13 PY 2009 VL 9 AR 15 DI 10.1186/1471-2407-9-15 PG 9 WC Oncology SC Oncology GA 417DE UT WOS:000264054800001 PM 19144145 ER PT J AU Diercks, DB Kontos, MC Chen, AY Pollack, CV Wiviott, SD Rumsfeld, JS Magid, DJ Gibler, WB Cannon, CP Peterson, ED Roe, MT AF Diercks, Deborah B. Kontos, Michael C. Chen, Anita Y. Pollack, Charles V., Jr. Wiviott, Stephen D. Rumsfeld, John S. Magid, David J. Gibler, W. Brian Cannon, Christopher P. Peterson, Eric D. Roe, Matthew T. CA NCDR ACTION Registry Participants TI Utilization and Impact of Pre-Hospital Electrocardiograms for Patients With Acute ST-Segment Elevation Myocardial Infarction Data From the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE myocardial infarction; pre-hospital electrocardiogram; reperfusion ID TO-BALLOON TIMES; CARE AB Objectives This study sought to determine the association of pre-hospital electrocardiograms (ECGs) and the timing of reperfusion therapy for patients with ST-segment elevation myocardial infarction (STEMI). Background Pre-hospital ECGs have been recommended in the management of patients with chest pain transported by emergency medical services (EMS). Methods We evaluated patients with STEMI from the NCDR (National Cardiovascular Data Registry) ACTION (Acute Coronary Treatment and Intervention Outcomes Network) registry who were transported by EMS from January 1, 2007, through December 31, 2007. Patients were stratified by the use of pre-hospital ECGs, and timing of reperfusion therapy was compared between the 2 groups. Results A total of 7,098 of 12,097 patients (58.7%) utilized EMS, and 1,941 of these 7,098 EMS transport patients (27.4%) received a pre-hospital ECG. Among the EMS transport population, primary percutaneous coronary intervention was performed in 92.1% of patients with a pre-hospital ECG versus 86.3% with an in-hospital ECG, whereas fibrinolytic therapy was used in 4.6% versus 4.2% of patients. Median door-to-needle times for patients receiving fibrinolytic therapy (19 min vs. 29 min, p = 0.003) and median door-to-balloon times for patients undergoing primary percutaneous coronary intervention (61 min vs. 75 min, p < 0.0001) were significantly shorter for patients with a pre-hospital ECG. A suggestive trend for a lower risk of in-hospital mortality was observed with pre-hospital ECG use (adjusted odds ratio: 0.80, 95% confidence interval: 0.63 to 1.01). Conclusions Only one-quarter of these patients transported by EMS receive a pre-hospital ECG. The use of a pre-hospital ECG was associated with a greater use of reperfusion therapy, faster reperfusion times, and a suggested trend for a lower risk of mortality. (J Am Coll Cardiol 2009; 53: 161-6) (C) 2009 by the American College of Cardiology Foundation C1 [Diercks, Deborah B.] Univ Calif Davis, Med Ctr, Dept Emergency Med, Sacramento, CA 95661 USA. [Kontos, Michael C.] Virginia Commonwealth Univ Hlth Syst, Richmond, VA USA. [Chen, Anita Y.; Peterson, Eric D.; Roe, Matthew T.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Pollack, Charles V., Jr.] Penn Hosp, Philadelphia, PA 19107 USA. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Rumsfeld, John S.; Magid, David J.] Univ Colorado, Med Ctr, Denver, CO 80202 USA. [Gibler, W. Brian] Univ Cincinnati Hosp, Cincinnati, OH USA. RP Diercks, DB (reprint author), Univ Calif Davis, Med Ctr, Dept Emergency Med, 2315 Stockton Blvd,PSSB 2100, Sacramento, CA 95661 USA. EM dbdiercks@ucdavis.edu NR 9 TC 110 Z9 118 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 13 PY 2009 VL 53 IS 2 BP 161 EP 166 DI 10.1016/j.jacc.2008.09.030 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 394AV UT WOS:000262418500003 PM 19130984 ER PT J AU Semigran, M AF Semigran, Marc TI Myocardial Effects of PDE5 Inhibition More Function With Less Mass SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material DE PDE5; hypertrophy; remodeling; heart; molecular ID LEFT-VENTRICULAR MASS; CARDIAC-HYPERTROPHY C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Semigran, M (reprint author), Massachusetts Gen Hosp, Div Cardiol, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org FU NHLBI NIH HHS [K24 HL004021-05, K24 HL004021] NR 8 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 13 PY 2009 VL 53 IS 2 BP 216 EP 217 DI 10.1016/j.jacc.2008.09.036 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 394AV UT WOS:000262418500010 PM 19130991 ER PT J AU Qin, W Ho, L Wang, J Peskind, E Pasinetti, GM AF Qin, Weiping Ho, Lap Wang, Jun Peskind, Elaine Pasinetti, Giulio Maria TI S100A7, a Novel Alzheimer's Disease Biomarker with Non-Amyloidogenic alpha-Secretase Activity Acts via Selective Promotion of ADAM-10 SO PLOS ONE LA English DT Article AB Alzheimer's disease (AD) is the most common cause of dementia among older people. At present, there is no cure for the disease and as of now there are no early diagnostic tests for AD. There is an urgency to develop a novel promising biomarker for early diagnosis of AD. Using surface-enhanced laser desorption ionization-mass spectrometry SELDI-(MS) proteomic technology, we identified and purified a novel 11.7-kDa metal-binding protein biomarker whose content is increased in the cerebrospinal fluid (CSF) and in the brain of AD dementia subjects as a function of clinical dementia. Following purification and protein-sequence analysis, we identified and classified this biomarker as S100A7, a protein known to be involved in immune responses. Using an adenoviral- S100A7 expression system, we continued to examine the potential role of S100A7 in AD amyloid neuropathology in in vitro model of AD. We found that the expression of exogenous S100A7 in primary cortico-hippocampal neuron cultures derived from Tg2576 transgenic embryos inhibits the generation of beta-amyloid (A beta)(1-42) and A beta(1-40) peptides, coincidental with a selective promotion of "non- amyloidogenic'' alpha-secretase activity via promotion of ADAM (a disintegrin and metalloproteinase)-10. Finally, a selective expression of human S100A7 in the brain of transgenic mice results in significant promotion of alpha-secretase activity. Our study for the first time suggests that S100A7 may be a novel biomarker of AD dementia and supports the hypothesis that promotion of S100A7 expression in the brain may selectively promote alpha-secretase activity in the brain of AD precluding the generation of amyloidogenic peptides. If in the future we find that S1000A7 protein content in CSF is sensitive to drug intervention experimentally and eventually in the clinical setting, S100A7 might be developed as novel surrogate index (biomarker) of therapeutic efficacy in the characterization of novel drug agents for the treatment of AD. C1 [Qin, Weiping; Ho, Lap; Wang, Jun; Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. [Pasinetti, Giulio Maria] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Ho, Lap; Wang, Jun; Pasinetti, Giulio Maria] James J Peters Vet Affairs Med Ctr, GCRC, Bronx, NY USA. [Peskind, Elaine] Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Qin, W (reprint author), Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. EM giulio.pasinetti@mssm.edu FU James J. Peters VA GRECC Program; NIA [AG02219] FX These studies were supported by James J. Peters VA GRECC Program and NIA AG02219 to GMP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 41 TC 34 Z9 35 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 JAN 13 PY 2009 VL 4 IS 1 AR e4183 DI 10.1371/journal.pone.0004183 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437IE UT WOS:000265479600002 PM 19159013 ER PT J AU Perera, SA Li, DA Shimamura, T Raso, MG Ji, HB Chen, LA Borgman, CL Zaghlul, S Brandstetter, KA Kubo, S Takahashi, M Chirieac, LR Padera, RF Bronson, RT Shapiro, GI Greulich, H Meyerson, M Guertler, U Chesa, PG Solca, F Wistuba, II Wong, KK AF Perera, Samanthi A. Li, Danan Shimamura, Takeshi Raso, Maria G. Ji, Hongbin Chen, Liang Borgman, Christa L. Zaghlul, Sara Brandstetter, Kathleyn A. Kubo, Shigeto Takahashi, Masaya Chirieac, Lucian R. Padera, Robert F. Bronson, Roderick T. Shapiro, Geoffrey I. Greulich, Heidi Meyerson, Matthew Guertler, Ulrich Chesa, Pilar Garin Solca, Flavio Wistuba, Ignacio I. Wong, Kwok-Kin TI HER2(YVMA) drives rapid development of adenosquamous lung tumors in mice that are sensitive to BIBW2992 and rapamycin combination therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE lung cancer; murine model ID HER2 KINASE DOMAIN; ERBB RECEPTORS; CANCER; EGFR; MUTATIONS; TRASTUZUMAB; ADENOCARCINOMAS; ACTIVATION; INHIBITORS; CARCINOMA AB Mutations in the HER2 kinase domain have been identified in human clinical lung cancer specimens. Here we demonstrate that inducible expression of the most common HER2 mutant (HER2(YVMA)) in mouse lung epithelium causes invasive adenosquamous carcinomas restricted to proximal and distal bronchioles. Continuous expression of HER2YVMA is essential for tumor maintenance, suggesting a key role for HER2 in lung adenosquamous tumorigenesis. Preclinical studies assessing the in vivo effect of erlotinib, trastuzumab, BIBW2992, and/or rapamycin on HER2(YVMA) transgenic mice or H1781 xenografts with documented tumor burden revealed that the combination of BIBW2992 and rapamycin is the most effective treatment paradigm causing significant tumor shrinkage. Immunohistochemical analysis of lung tumors treated with BIBW2992 and rapamycin combination revealed decreased phosphorylation levels for proteins in both upstream and downstream arms of MAPK and Akt/mTOR signaling axes, indicating inhibition of these pathways. Based on these findings, clinical testing of the BIBW2992/rapamycin combination in non-small cell lung cancer patients with tumors expressing HER2 mutations is warranted. C1 [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. [Raso, Maria G.; Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. [Wistuba, Ignacio I.] Univ Texas MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Ji, Hongbin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China. [Kubo, Shigeto] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02115 USA. [Chirieac, Lucian R.; Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Dept Pathol, Boston, MA 02115 USA. [Greulich, Heidi; Meyerson, Matthew] Broad Inst MIT & Harvard, Boston, MA 02115 USA. [Guertler, Ulrich; Chesa, Pilar Garin; Solca, Flavio] Boehringer Ingelheim GmbH & Co KG, Dept Pharmacol, A-1120 Vienna, Austria. RP Wong, KK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Lowe Ctr Thorac Oncol, 44 Binney St,D810, Boston, MA 02115 USA. EM kwong1@partners.org RI Meyerson, Matthew/E-7123-2012; OI wong, kwok kin/0000-0001-6323-235X FU Cecily and Robert Harris Foundation; Joan Scarangello Foundation to Conquer Lung Cancer; Flight Attendant Medical Research Institute; National Institutes of Health [R01 AG2400401, R01 CA122794, P20 CA90578, R01 CA90687]; Career Development Award; Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Lung Cancer FX We thank Dr. Jeffrey Whitsett (Cincinnati Children's Hospital Medical Center, Cincinnati, OH) for providing the CCSP-rtTA transgenic mice. Wealso thank Eva Strauss, Astrid Jeschko, Stefan Fischer, Christine Lam, and Mei Zheng for technical support. This work was supported by the Cecily and Robert Harris Foundation (K.-K.W.); the Joan Scarangello Foundation to Conquer Lung Cancer (K.-K.W.); the Flight Attendant Medical Research Institute (K.- K. W.); and National Institutes of Health Grants R01 AG2400401 (to K.- K. W.), R01 CA122794 (to K.- K. W.), P20 CA90578 (to K.- K. W., G. I. S., and L. R. C.), and R01 CA90687 (to G. I. S.). T. S. is supported by a Career Development Award as part of the Dana-Farber/Harvard Cancer Center Specialized Program of Research Excellence in Lung Cancer and National Institutes of Health Grant P20 CA90578. NR 22 TC 80 Z9 84 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2009 VL 106 IS 2 BP 474 EP 479 DI 10.1073/pnas.0808930106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 399MM UT WOS:000262804000023 PM 19122144 ER PT J AU Rahdar, M Inoue, T Meyer, T Zhang, J Vazquez, F Devreotes, PN AF Rahdar, Meghdad Inoue, Takanari Meyer, Tobias Zhang, Jin Vazquez, Francisca Devreotes, Peter N. TI A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE iRAP; phosphatase; PI3K; PIP2; PIP3 ID PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SIGNALING PATHWAY; CELL-SURVIVAL; BINDING MOTIF; PROTEIN; PHOSPHATASE; GENE; INACTIVATION; INHIBITION; PROGRESSION AB The PI 3-phosphatase PTEN (phosphatase and tensin homologue deleted on chromosome 10), one of the most important tumor suppressors, must associate with the plasma membrane to maintain appropriate steady-state levels of phosphatidylinositol 3,4,5triphosphate. Yet the mechanism of membrane binding has received little attention and the key determinants that regulate localization, a phosphatidylinositol 4,5-bisphosphate (PIP2) binding motif and a cluster of phosphorylated C-terminal residues, were not included in the crystal structure. We report that membrane binding requires PIP2 and show that phosphorylation regulates an intramolecular interaction. A truncated version of the enzyme, PTEN1-351, bound strongly to the membrane, an effect that was reversed by co-expression of the remainder of the molecule, PTEN352-403. The separate fragments associated in vitro, an interaction dependent on phosphorylation of the C-terminal cluster, a portion of the PIP2 binding motif, integrity of the phosphatase domain, and the CBR3 loop. Our investigation provides direct evidence for a model in which PTEN switches between open and closed states and phosphorylation favors the closed conformation, thereby regulating localization and function. Small molecules targeting these interactions could potentially serve as therapeutic agents in antagonizing Ras or PI3K-driven tumors. The study also stresses the importance of determining the structure of the native enzyme. C1 [Vazquez, Francisca] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Rahdar, Meghdad; Inoue, Takanari; Devreotes, Peter N.] Johns Hopkins Univ, Sch Med, Dept Cell Biol, Baltimore, MD 21205 USA. [Rahdar, Meghdad; Zhang, Jin] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Meyer, Tobias] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Vazquez, F (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM francisca_vazquez@dfci.harvard.edu; pnd@jhmi.edu FU National Institutes of Health [GM 28007, GM 34933, GM 71920] FX The authors wish to acknowledge members of the Devreotes lab, particularly Yoichiro Kamimura, Jonathan Franca-Koh, and Stacey Willard, for helpful discussion and advice. We also wish to thank MoiraMcMahon for critical reading of this manuscript and helpful advice. This work was supported by National Institutes of Health Grants GM 28007, GM 34933, and GM 71920. NR 37 TC 112 Z9 114 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 13 PY 2009 VL 106 IS 2 BP 480 EP 485 DI 10.1073/pnas.811212106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 399MM UT WOS:000262804000024 PM 19114656 ER PT J AU Noble, VE Lamhaut, L Capp, R Bosson, N Liteplo, A Marx, JS Carli, P AF Noble, Vicki E. Lamhaut, Lionel Capp, Roberta Bosson, Nichole Liteplo, Andrew Marx, Jean-Sebastian Carli, Pierre TI Evaluation of a thoracic ultrasound training module for the detection of pneumothorax and pulmonary edema by prehospital physician care providers SO BMC MEDICAL EDUCATION LA English DT Article ID EXTRAVASCULAR LUNG WATER; ALVEOLAR-INTERSTITIAL SYNDROME; CONGESTIVE-HEART-FAILURE; COMET-TAIL ARTIFACT; SIGN; DIAGNOSIS; PATIENT; COPD AB Background: While ultrasound (US) has continued to expedite diagnosis and therapy for critical care physicians inside the hospital system, the technology has been slow to diffuse into the pre-hospital system. Given the diagnostic benefits of thoracic ultrasound (TUS), we sought to evaluate image recognition skills for two important TUS applications; the identification of B-lines (used in the US diagnosis of pulmonary edema) and the identification of lung sliding and comet tails (used in the US diagnosis of pneumothorax). In particular we evaluated the impact of a focused training module in a pre-hospital system that utilizes physicians as pre-hospital providers. Methods: 27 Paris Service D'Aide Medicale Urgente (SAMU) physicians at the Hopital Necker with varying levels of US experience were given two twenty-five image recognition pre-tests; the first test had examples of both normal and pneumothorax lung US and the second had examples of both normal and pulmonary edema lung US. All 27 physicians then underwent the same didactic training modules. A post-test was administered upon completing the training module and results were recorded. Results: Pre and post-test scores were compared for both the pneumothorax and the pulmonary edema modules. For the pneumothorax module, mean test scores increased from 10.3 +/- 4.1 before the training to 20.1 +/- 3.5 after (p < 0.0001), out of 25 possible points. The standard deviation decreased as well, indicating a collective improvement. For the pulmonary edema module, mean test scores increased from 14.1 +/- 5.2 before the training to 20.9 +/- 2.4 after (p < 0.0001), out of 25 possible points. The standard deviation decreased again by more than half, indicating a collective improvement. Conclusion: This brief training module resulted in significant improvement of image recognition skills for physicians both with and without previous ultrasound experience. Given that rapid diagnosis of these conditions in the pre-hospital system can change therapy, especially in systems where physicians can integrate this information into treatment decisions, the further diffusion of this technology would seem to be beneficial and deserves further study. C1 [Noble, Vicki E.; Capp, Roberta; Bosson, Nichole; Liteplo, Andrew] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Lamhaut, Lionel; Marx, Jean-Sebastian; Carli, Pierre] Hop Necker Enfants Malad, SAMU Paris, F-75743 Paris 15, France. RP Noble, VE (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. EM vnoble@partners.org; lamhautl@gmail.com; rcapp@partners.org; nichole.bosson@gmail.com; aliteplo@partners.org; jean-sebastien.marx@nck.aphp.fr; pcarli.secretariat@nck.aphp.fr OI Lamhaut, Lionel/0000-0003-4160-9456 NR 14 TC 43 Z9 43 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6920 J9 BMC MED EDUC JI BMC Med. Educ. PD JAN 12 PY 2009 VL 9 AR 3 DI 10.1186/1472-6920-9-3 PG 5 WC Education & Educational Research; Education, Scientific Disciplines SC Education & Educational Research GA 686NL UT WOS:000284702900002 PM 19138397 ER PT J AU Wolpin, BM Meyerhardt, JA Chan, AT Ng, K Chan, JA Wu, K Pollak, MN Giovannucci, EL Fuchs, CS AF Wolpin, Brian M. Meyerhardt, Jeffrey A. Chan, Andrew T. Ng, Kimmie Chan, Jennifer A. Wu, Kana Pollak, Michael N. Giovannucci, Edward L. Fuchs, Charles S. TI Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID IGF-BINDING-PROTEINS; SERUM C-PEPTIDE; PHYSICAL-ACTIVITY QUESTIONNAIRE; III COLON-CANCER; BODY-MASS INDEX; FACTOR-I; DIETARY PATTERNS; BREAST-CANCER; RECTAL CANCERS; COLLEGE ALUMNI AB Purpose Obesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models. Patients and Methods Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3. Results Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors. Conclusion Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection. C1 [Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. McGill Univ, Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal, PQ, Canada. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org RI Pollak, Michael/G-9094-2011 OI Pollak, Michael/0000-0003-3047-0604 FU National Cancer Institute, National Institutes of Health, Bethesda, MD [CA118553, CA87969, CA108341, CA127003-01, CA09001] FX Supported by Grants No. CA118553, CA87969, CA108341, CA127003-01, and CA09001 from the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 66 TC 108 Z9 111 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2009 VL 27 IS 2 BP 176 EP 185 DI 10.1200/JCO.2008.17.9945 PG 10 WC Oncology SC Oncology GA 392QW UT WOS:000262318300006 PM 19064975 ER PT J AU Wolpin, BM Hezel, AF Abrams, T Blaszkowsky, LS Meyerhardt, JA Chan, JA Enzinger, PC Allen, B Clark, JW Ryan, DP Fuchs, CS AF Wolpin, Brian M. Hezel, Aram F. Abrams, Thomas Blaszkowsky, Lawrence S. Meyerhardt, Jeffrey A. Chan, Jennifer A. Enzinger, Peter C. Allen, Brittany Clark, Jeffrey W. Ryan, David P. Fuchs, Charles S. TI Oral mTOR Inhibitor Everolimus in Patients With Gemcitabine-Refractory Metastatic Pancreatic Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 30-JUN 03, 2008 CL Chicago, IL SP Amer Soc Clin Oncol ID PHASE-III TRIAL; COOPERATIVE-ONCOLOGY-GROUP; ADVANCED SOLID TUMORS; MAMMALIAN TARGET; DUCTAL ADENOCARCINOMA; CELL-PROLIFERATION; 2ND-LINE THERAPY; ACTIVATED AKT; IN-VIVO; RAPAMYCIN AB Purpose The PI3K/Akt/mTOR pathway is activated in the majority of pancreatic cancers, and inhibition of this pathway has antitumor effects in preclinical studies. We performed a multi-institutional, single-arm, phase II study of RAD001(everolimus), an oral inhibitor of mTOR, in patients who experienced treatment failure on first-line therapy with gemcitabine. Patients and Methods Thirty-three patients with gemcitabine-refractory, metastatic pancreatic cancer were treated continuously with RAD001 at 10 mg daily. Prior treatment with fluorouracil in the perioperative setting was allowed. Patients were observed for toxicity, treatment response, and survival. Results Treatment with single-agent RAD001 was well-tolerated; the most common adverse events were mild hyperglycemia and thrombocytopenia. No patients were removed from the study because of drug-related adverse events. No complete or partial treatment responses were noted, and only seven patients (21%) had stable disease at the first restaging scans performed at 2 months. Median progression-free survival and overall survival were 1.8 months and 4.5 months, respectively. One patient (3%) had a biochemical response, defined as >= 50% reduction in serum CA19-9. Conclusion Although well-tolerated, RAD001 administered as a single-agent had minimal clinical activity in patients with gemcitabine-refractory, metastatic pancreatic cancer. Future studies in metastatic pancreatic cancer should assess the combination of mTOR inhibitors with other agents and/or examine inhibitors of other components of the PI3K/Akt/mTOR pathway. C1 [Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM bwolpin@partners.org FU NCI NIH HHS [P50 CA127003, P01 CA124908, P01 CA55075, P01 CA87969, T32 CA09001] NR 49 TC 150 Z9 153 U1 1 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2009 VL 27 IS 2 BP 193 EP 198 DI 10.1200/JCO.2008.18.9514 PG 6 WC Oncology SC Oncology GA 392QW UT WOS:000262318300008 PM 19047305 ER PT J AU Ozanne, EM Braithwaite, D Sepucha, K Moore, D Esserman, L Belkora, J AF Ozanne, Elissa M. Braithwaite, Dejana Sepucha, Karen Moore, Dan Esserman, Laura Belkora, Jeffrey TI Sensitivity to Input Variability of the Adjuvant! Online Breast Cancer Prognostic Model SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 4th International Conference on Shared Decision Making CY MAY 30-JUN 02, 2007 CL Freiburg, GERMANY ID THERAPY DECISIONS; COMPUTER-PROGRAM; COMORBIDITY; ASSIST; VALIDATION; SURVIVAL; AID AB Purpose Adjuvant! Online (www.adjuvantonline.org) is a software model that predicts the benefit of adjuvant therapy for women with early-stage breast cancer. The model has been validated, is widely consulted, and has been shown to influence patient choices in the clinical setting. Adjuvant! requires the clinician to input patient age, tumor size, grade, hormone receptor status, number of positive lymph nodes, and comorbidity level. Because comorbidity is strongly and independently associated with survival, this study tested the hypothesis that Adjuvant! predictions would be sensitive to comorbidity inputs. Methods Investigators used single-variable deterministic sensitivity analysis to evaluate the effect of varying each input of the model independently for three representative case examples based on National Comprehensive Cancer Network guidelines (NCCN). The main outcome of interest was 10-year mortality prediction. Results The analyses show that Adjuvant!'s 10-year mortality predictions are most sensitive to patients' comorbidity levels and the extent of nodal involvement for the cases, particularly among older women. Comorbidity was the most influential input except in younger women, aged 40 years. Conclusion The Adjuvant! model is sensitive to patient comorbidity, and impact on the model outputs are significant enough that they are likely to affect physician recommendations and patients' treatment choices. For example, incorrect assessments of comorbidities could lead physicians to overtreat or undertreat a patient who is in a gray zone relative to the NCCN guidelines. These results point to the importance of accurately assessing comorbidities in patients with breast cancer when using Adjuvant! and highlight the need for a standardized process of comorbidity ascertainment. C1 [Ozanne, Elissa M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Biostat & Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. RP Ozanne, EM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Fl, Boston, MA 02114 USA. EM elissa@mgh-ita.org NR 20 TC 15 Z9 16 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 JAN 10 PY 2009 VL 27 IS 2 BP 214 EP 219 DI 10.1200/JCO.2008.17.3914 PG 6 WC Oncology SC Oncology GA 392QW UT WOS:000262318300011 PM 19047286 ER PT J AU Leleu, X Soumerai, J Roccaro, A Hatjiharissi, E Hunter, ZR Manning, R Ciccarelli, BT Sacco, A Ioakimidis, L Adamia, S Moreau, AS Patterson, CJ Ghobrial, IM Treon, SP AF Leleu, Xavier Soumerai, Jacob Roccaro, Aldo Hatjiharissi, Evdoxia Hunter, Zachary R. Manning, Robert Ciccarelli, Bryan T. Sacco, Antonio Ioakimidis, Leukothea Adamia, Sophia Moreau, Anne-Sophie Patterson, Christopher J. Ghobrial, Irene M. Treon, Steven P. TI Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenstrom Macroglobulinemia Treated With Nucleoside Analogs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC-LYMPHOCYTIC-LEUKEMIA; INTERNATIONAL WORKSHOP; MYELOID-LEUKEMIA; FLUDARABINE; THERAPY; LYMPHOMA; CYCLOPHOSPHAMIDE; RECOMMENDATIONS; CHEMOTHERAPY; CHLORAMBUCIL AB Purpose Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenstrom macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM. Patients and Methods We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years. Results Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months. Conclusion These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs. C1 [Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Ctr Hosp Reg Univ, Hop Claude Huriez, Serv Malad Sang, Lille, France. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013; Sacco, Antonio/K-4681-2016; OI Hunter, Zachary/0000-0002-1689-1691; Sacco, Antonio/0000-0003-2945-9416; Roccaro, Aldo/0000-0002-1872-5128 NR 20 TC 87 Z9 87 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 JAN 10 PY 2009 VL 27 IS 2 BP 250 EP 255 DI 10.1200/JCO.2007.15.1530 PG 6 WC Oncology SC Oncology GA 392QW UT WOS:000262318300016 PM 19064987 ER PT J AU Schapira, L Moynihan, TJ von Gunten, CF Smith, TJ AF Schapira, Lidia Moynihan, Timothy J. von Gunten, Charles F. Smith, Thomas J. TI Phase I Versus Palliative Care: Striking the Right Balance SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CANCER-PATIENTS; LIFE; END C1 [Schapira, Lidia] Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. San Diego Hosp, San Diego, CA USA. Virginia Commonwealth Univ, Div Hematol Oncol & Palliat Care, Dept Med, Richmond, VA USA. RP Schapira, L (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM lschapira@partners.org NR 8 TC 10 Z9 10 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 JAN 10 PY 2009 VL 27 IS 2 BP 307 EP 308 DI 10.1200/JCO.2008.20.7803 PG 2 WC Oncology SC Oncology GA 392QW UT WOS:000262318300024 PM 19064948 ER PT J AU Conway, JB Weingart, SN AF Conway, James B. Weingart, Saul N. TI Leadership: Assuring respect and compassion to clinicians involved in medical error SO SWISS MEDICAL WEEKLY LA English DT Editorial Material C1 [Conway, James B.] Inst Healthcare Improvement, Cambridge, MA USA. [Conway, James B.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Weingart, Saul N.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Weingart, Saul N.] Dana Farber Canc Inst, Ctr Patient Safety, Boston, MA 02115 USA. RP Conway, JB (reprint author), Inst Healthcare Improvement, Cambridge, MA USA. EM jconway@ihi.org NR 1 TC 8 Z9 8 U1 0 U2 2 PU E M H SWISS MEDICAL PUBLISHERS LTD PI MUTTENZ PA FARNSBURGERSTR 8, CH-4132 MUTTENZ, SWITZERLAND SN 1424-7860 J9 SWISS MED WKLY JI Swiss Med. Wkly. PD JAN 10 PY 2009 VL 139 IS 1-2 BP 3 EP 3 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 395UW UT WOS:000262550000002 PM 19142749 ER PT J AU Chow, CY Landers, JE Bergen, SK Sapp, PC Grant, AE Jones, JM Everett, L Lenk, GM McKenna-Yasek, DM Weisman, LS Figlewicz, D Brown, RH Meisler, MH AF Chow, Clement Y. Landers, John E. Bergen, Sarah K. Sapp, Peter C. Grant, Adrienne E. Jones, Julie M. Everett, Lesley Lenk, Guy M. McKenna-Yasek, Diane M. Weisman, Lois S. Figlewicz, Denise Brown, Robert H. Meisler, Miriam H. TI Deleterious Variants of FIG4. a Phosphoinositide Phosphatase, in Patients with ALS SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; HUMAN-DISEASE GENES; NUCLEOTIDE STRUCTURE; COMPUTATIONAL TOOLS; MUTATION PATTERN; EXCHANGE FACTOR; NEURODEGENERATION; GENETICS; PREDICT AB Mutations of the lipid phosphatase FIG4 that regulates PI(3,5)P(2) are responsible for the recessive peripheral-nerve disorder CMT4J. We now describe nonsynonymous variants of FIG4 in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases. C1 [Chow, Clement Y.; Bergen, Sarah K.; Grant, Adrienne E.; Jones, Julie M.; Everett, Lesley; Lenk, Guy M.; Meisler, Miriam H.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Landers, John E.; Sapp, Peter C.; McKenna-Yasek, Diane M.; Brown, Robert H.] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Boston, MA 02114 USA. [Landers, John E.; Sapp, Peter C.; McKenna-Yasek, Diane M.; Brown, Robert H.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01605 USA. [Weisman, Lois S.] Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. [Weisman, Lois S.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. [Figlewicz, Denise] Univ Michigan, Dept Neurol, Ann Arbor, MI 48109 USA. [Sapp, Peter C.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Meisler, MH (reprint author), Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. EM meislerm@umich.edu RI Lenk, Guy/Q-1226-2016 OI Lenk, Guy/0000-0001-8092-1405 FU National Institutes of Health [GM24872, NS050557, NS050641, T32 GM007544, NS064015]; ALS Association; ALS Therapy Alliance; Angel Fund; Pierre L. de Bourgknecht AUS Research Foundation; Al-Athel ALS Foundation FX This study was supported by National Institutes of Health grants GM24872-(M.H.M.), NS050557 (R.H.B.), NS050641 (R.H.B.), T32 GM007544 (C.Y.C.), and NS064015 (L.S.W.) and by the ALS Association (M.H.M. and R.H.B.), the ALS Therapy Alliance, Project ALS, the Angel Fund, the Pierre L. de Bourgknecht AUS Research Foundation, and the Al-Athel ALS Foundation. We thank Emily Kauffman for assistance in development of the yeast-vacuole assay. P.S. is supported through the auspices of H. Robert Horvitz, an Investigator of the Howard Hughes Medical Institute. DNA panels from the NINDS Human Genetics Resource Center DNA and Cell Line Repository (http://ccr.coriell.org/ninds), as well as clinical data, were used in this study. The submitters that contributed samples are acknowledged in detailed descriptions of each panel: NDPT025, NDPT026, NDPT029, NDPT006, and NDPT009. NR 20 TC 152 Z9 160 U1 6 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN 9 PY 2009 VL 84 IS 1 BP 85 EP 88 DI 10.1016/j.ajhg.2008.12.010 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 397RJ UT WOS:000262679500011 PM 19118816 ER PT J AU Liu, J He, CW Zhou, KA Wang, JD Kang, JX AF Liu, Jing He, Chengwei Zhou, Keyuan Wang, Jingdong Kang, Jing X. TI Coptis extracts enhance the anticancer effect of estrogen receptor antagonists on human breast cancer cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Breast cancer; Estrogen receptor antagonist; Coptis; Gene expression; Cell growth ID INTERFERON-BETA; MEDICINAL HERB; TAMOXIFEN; RESISTANCE; BERBERINE; FULVESTRANT; INHIBITION; APOPTOSIS; BCL-2; CYCLOOXYGENASE-2 AB Estrogen receptor (ER) antagonists have been widely used for breast cancer treatment, but the efficacy and drug resistance remain to be clinical concerns. The purpose of this Study was to determine whether the extracts of coptis, an anti-inflammatory herb, improve the anticancer efficacy of ER antagonists. The results showed that the combined treatment of ER antagonists and the crude extract of coptis or its purified compound berberine conferred synergistic growth inhibitory effect on MCF-7 cells (ER+), but not On MDA-MB-231 cells (ER-). Similar results were observed in the combined treatment of fulvestrant, a specific aromatase antagonist. Analysis of the expression of breast cancer related genes indicated that EGFR, HER2. bcl-2, and COX-2 were significantly downregulated, while IFN-beta and p21 were remarkably upregulated by berberine. Our results Suggest that coptis extracts could be promising adjuvant to ER antagonists in ER positive breast cancer treatment through regulating expression Of Multiple genes. (C) 2008 Elsevier Inc. All rights reserved. C1 [Liu, Jing; He, Chengwei; Wang, Jingdong; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [Liu, Jing; He, Chengwei; Wang, Jingdong; Kang, Jing X.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [He, Chengwei; Zhou, Keyuan] Guangdong Med Coll, Inst Biochem & Mol Biol, Zhanjiang 524023, Guangdong, Peoples R China. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu FU Starr Foundation; NIH [CA113605]; National Natural Science Foundation of China [30672741] FX We thank J. Wan for assistance in cell viability assay and data analysis. This work was supported by the Starr Foundation. (J.X.K.), the NIH grant CA113605 (J.X.K.), and the National Natural Science Foundation of China 30672741 (K.Z.). NR 25 TC 43 Z9 45 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JAN 9 PY 2009 VL 378 IS 2 BP 174 EP 178 DI 10.1016/j.bbrc.2008.10.169 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 389AU UT WOS:000262063100006 PM 19000652 ER PT J AU Xiao, CC Rajewsky, K AF Xiao, Changchun Rajewsky, Klaus TI MicroRNA Control in the Immune System: Basic Principles SO CELL LA English DT Review ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; T-CELL PROLIFERATION; BREAST-CANCER; C-MYB; MALIGNANT-LYMPHOMA; TUMOR SUPPRESSORS; INHIBITOR P21; CYCLE CONTROL; B-CELLS AB MicroRNA (miRNA) control has emerged as a critical regulatory principle in the mammalian immune system. Genetic ablation of the miRNA machinery, as well as loss or deregulation of certain individual miRNAs, severely compromises immune development and response and can lead to immune disorders like autoimmunity and cancer. Although individual miRNAs modulate protein output from hundreds of target genes, they may impact physiological processes by regulating the concentrations of just a few key cellular proteins that may be components of a single or of functionally interrelated pathways in a given cellular context. C1 [Xiao, Changchun; Rajewsky, Klaus] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu FU National Institutes of Health; European Union, through MUGEN; Cancer Research Institute; Joint Program in Hematology and Transfusion Medicine at Harvard Medical School FX We thank H. von Boehmer and N. Rajewsky for critical reading of this manuscript. K. R. is supported by grants from the National Institutes of Health and the European Union, through MUGEN. C. X. was supported by a Cancer Research Institute postdoctoral fellowship and a T32 training grant awarded to the Joint Program in Hematology and Transfusion Medicine at Harvard Medical School. NR 115 TC 513 Z9 555 U1 6 U2 85 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 9 PY 2009 VL 136 IS 1 BP 26 EP 36 DI 10.1016/j.cell.2008.12.027 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 392QX UT WOS:000262318400012 PM 19135886 ER PT J AU Dejardin, J Kingston, RE AF Dejardin, Jerome Kingston, Robert E. TI Purification of Proteins Associated with Specific Genomic Loci SO CELL LA English DT Article ID BINDING PROTEINS; HUMAN TELOMERES; HUMAN-CELLS; AFFINITY PURIFICATION; MAMMALIAN-CELLS; NUCLEIC-ACID; CHROMATIN; DNA; RECOMBINATION; COMPLEX AB Eukaryotic DNA is bound and interpreted by numerous protein complexes in the context of chromatin. A description of the full set of proteins that regulate specific loci is critical to understanding regulation. Here, we describe a protocol called proteomics of isolated chromatin segments (PICh) that addresses this issue. PICh uses a specific nucleic acid probe to isolate genomic DNA with its associated proteins in sufficient quantity and purity to allow identification of the bound proteins. Purification of human telomeric chromatin using PICh identified the majority of known telomeric factors and uncovered a large number of novel associations. We compared proteins found at telomeres maintained by the alternative lengthening of telomeres (ALT) pathway to proteins bound at telomeres maintained by telomerase. We identified and validated several proteins, including orphan nuclear receptors, that specifically bind to ALT telomeres, establishing PICh as a useful tool for characterizing chromatin composition. C1 [Kingston, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Kingston, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM kingston@molbio.mgh.harvard.edu FU EMBO Long term fellowship; NIH [GM48405] FX We would like to thank Mike Blower for suggestions on the metaphase spread experiments, Matthew Simon, Rebecca Dunn, and Karim Bouazoune for critically reading the manuscript, the National Cell Culture Center for providing large-scale HeLa S3 cultures, Titia de Lange for providing the HeLa 1.2.11 cell line, Elliott Kieff for providing the HA-NXP2 construct, Joe Garlick for technical assistance, and the Taplin Mass Spectrometric Facility (Ross Tomaino) at Harvard Medical School for protein identifications. J.D. was supported by an EMBO Long term fellowship. This work is supported by NIH grant #GM48405 to R. E. K. This work is dedicated to the memory of Wolfram Horz, a gentleman and scientist. NR 51 TC 225 Z9 231 U1 1 U2 41 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD JAN 9 PY 2009 VL 136 IS 1 BP 175 EP 186 DI 10.1016/j.cell.2008.11.045 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 392QX UT WOS:000262318400024 PM 19135898 ER PT J AU Shen, XH Orkin, SH AF Shen, Xiaohua Orkin, Stuart H. TI Glimpses of the Epigenetic Landscape SO Cell Stem Cell LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; GENOME; METHYLATION; PLURIPOTENT C1 [Shen, Xiaohua; Orkin, Stuart H.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu NR 10 TC 9 Z9 9 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD JAN 9 PY 2009 VL 4 IS 1 BP 1 EP 2 DI 10.1016/j.stem.2008.12.006 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 395YN UT WOS:000262559500001 PM 19128786 ER PT J AU Chi, AS Bernstein, BE AF Chi, Andrew S. Bernstein, Bradley E. TI DEVELOPMENTAL BIOLOGY Pluripotent Chromatin State SO SCIENCE LA English DT Editorial Material ID EMBRYONIC STEM-CELLS; POLYCOMB; TRANSCRIPTION; REGULATORS C1 [Chi, Andrew S.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. [Chi, Andrew S.; Bernstein, Bradley E.] Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. [Chi, Andrew S.; Bernstein, Bradley E.] Broad Inst Harvard & Massachusetts Inst Technol, Cambridge, MA 02139 USA. [Chi, Andrew S.] Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. [Bernstein, Bradley E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Chi, AS (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA. EM bernstein.bradley@mgh.harvard.edu FU NHGRI NIH HHS [U54 HG004570-01, U54 HG004570] NR 17 TC 37 Z9 37 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 9 PY 2009 VL 323 IS 5911 BP 220 EP 221 DI 10.1126/science.1166261 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 392GG UT WOS:000262290600027 PM 19131621 ER PT J AU Chang, JJ Altfeld, M AF Chang, J. Judy Altfeld, Marcus TI TLR-mediated immune activation in HIV SO BLOOD LA English DT Editorial Material C1 [Chang, J. Judy; Altfeld, Marcus] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chang, JJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 8 TC 15 Z9 18 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 8 PY 2009 VL 113 IS 2 BP 269 EP 270 DI 10.1182/blood-2008-10-184598 PG 2 WC Hematology SC Hematology GA 392QZ UT WOS:000262318600001 PM 19131556 ER PT J AU Yu, J Kindy, MS Gattoni-Celli, S AF Yu, Jin Kindy, Mark S. Gattoni-Celli, Sebastiano TI Semi-allogeneic vaccines and tumor-induced immune tolerance SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID REGULATORY T-CELLS; HYBRIDS; CANCER; IMMUNOTHERAPY; EXPRESSION AB Experimental results from studies with inbred mice and their syngeneic tumors indicated that the inoculation of semi-allogeneic cell hybrids (derived from the fusion between syngeneic tumor cells and an allogeneic cell line) protects the animal host from a subsequent lethal challenge with unmodified syngeneic tumor cells. Semi-allogeneic somatic cell hybrids were generated by the fusion of EL-4 T lymphoma cells (H-2(b)) and BALB/c-derived renal adenocarcinoma RAG cells (H-2(d)). Cell hybrids were injected intra-peritoneally (i.p.) in C57BL/6 mice (H-2(b)) before challenging the mice with a tumorigenic dose of EL-4 cells. Semi-allogeneic tumor cell hybrids could not form a tumor in the animal host because they expressed allogeneic determinants (H-2(d)) and were rejected as a transplant. However, they conferred protection against a tumorigenic challenge of EL-4 cells compared to control mice that were mock-vaccinated with i.p.-injected phosphate-buffered saline (PBS) and in which EL-4 lymphomas grew rapidly to a large size in the peritoneal cavity. Screening of spleen-derived RNA by means of focused microarray technology showed up-regulation of genes involved in the Th-1-type immune response and in the activation of dendritic antigen-presenting cells (APC). The results of our studies confirm the role of APC in mediating the immune protection induced by semi-allogeneic vaccines by activating a Th-1 response; these studies also reveal that semi-allogeneic vaccines are able to interfere with or even block the tumor-mediated induction of immune tolerance, a key mechanism underlying the suppression of antitumor immunity in the immune competent host. C1 [Yu, Jin; Kindy, Mark S.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. [Gattoni-Celli, Sebastiano] Med Univ S Carolina, Dept Radiat Oncol, Charleston, SC 29425 USA. [Kindy, Mark S.; Gattoni-Celli, Sebastiano] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. [Kindy, Mark S.; Gattoni-Celli, Sebastiano] SemiAlloGen Inc, Mt Pleasant, SC 29466 USA. RP Gattoni-Celli, S (reprint author), Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. EM yujin@musc.edu; kindyms@musc.edu; gattonis@musc.edu FU National Science Foundation [EPS-0132573, EPS-0447660]; Veterans Administration Merit Review; SCLaunch FX The authors wish to acknowledge support by the National Science Foundation EPSCoR grants (MSK, EPS-0132573 and EPS-0447660), Veterans Administration Merit Review (MSK) and support from SCLaunch to Semi-AlloGen. NR 16 TC 1 Z9 1 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JAN 8 PY 2009 VL 7 AR 3 DI 10.1186/1479-5876-7-3 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 409WZ UT WOS:000263537800001 PM 19133135 ER PT J AU Costello, DJ Eichler, FS Grant, PE Auluck, PK Bianchi, MT AF Costello, Daniel J. Eichler, Florian S. Grant, P. Ellen Auluck, Pavan K. Bianchi, Matthew T. TI A Man with Progressive Cognitive Decline Adult cerebral form of X-linked adrenoleukodystrophy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TOXIC LEUKOENCEPHALOPATHY; HALF-TRANSPORTERS; BRAIN; DEMENTIA C1 [Costello, Daniel J.; Eichler, Florian S.] Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. [Grant, P. Ellen] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Auluck, Pavan K.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Costello, Daniel J.; Eichler, Florian S.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Grant, P. Ellen] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Auluck, Pavan K.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Costello, DJ (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RI Auluck, Pavan/A-1160-2010 FU Shire Pharmaceuticals FX Dr. Eichler reports receiving lecture fees from Shire Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 23 TC 3 Z9 4 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 JAN 8 PY 2009 VL 360 IS 2 BP 171 EP U116 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 391UG UT WOS:000262258300012 PM 19129531 ER PT J AU Greene, MF AF Greene, Michael F. TI Making Small Risks Even Smaller SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID 3RD-TRIMESTER AMNIOCENTESIS; CESAREAN-SECTION; DELIVERY; LABOR C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 9 TC 8 Z9 8 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 8 PY 2009 VL 360 IS 2 BP 183 EP 184 DI 10.1056/NEJMe0810120 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 391UG UT WOS:000262258300013 PM 19129532 ER PT J AU Segar, TM Kasckow, JW Welge, JA Herman, JP AF Segar, Tracy M. Kasckow, John W. Welge, Jeffrey A. Herman, James P. TI Heterogeneity of neuroendocrine stress responses in aging rat strains SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE Aging; Stress; HPA; ACTH; Corticosterone; Homoscedasticity ID PITUITARY-ADRENAL AXIS; INDIVIDUAL-DIFFERENCES; BROWN-NORWAY; AGE; BRAIN; CORTICOSTERONE; MEMORY; IMPAIRMENT; RESPONSIVENESS; HIPPOCAMPUS AB Hyperactivity of the hypothalamo-pituitary-adrenocortical (HPA) axis is linked with age-related decrements in cognition and neuronal survival. However. the nature and extent of age-related HPA axis deficits vary considerably across and indeed, within strains. The current study was designed to assess variance in HPA axis function using two rodent models commonly used in aging Studies: Fischer 344 (F344) and F344/Brown-Norway F1 hybrid rats (F344/BN). We examined both basal and stress-induced ACTH and corticosterone (CORT) release in two stress contexts thought to differ in intensity: novel environment ('mild') and restraint ('intense'). Variability of the data was tested with a modification of the Brown-Forsythe test of homoscedasticity. The results indicated that F344 rats exhibit greater peak HPA responses. Furthermore, in most cases variability was increased in aged rats relative to young and middle-aged rats of the same strain, indicative of the emergence of individual differences in stress responsivity amongst older rats. The results suggest that these older rat strains may be useful models to further assess individual differences in neuroendocrine aging. Published by Elsevier Inc. C1 VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15206 USA. [Segar, Tracy M.; Welge, Jeffrey A.; Herman, James P.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45237 USA. [Kasckow, John W.] Univ Pittsburgh, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. RP Kasckow, JW (reprint author), VA Pittsburgh Hlth Care Syst, Behav Hlth 116A,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM kasckowjw@upmc.edu RI Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU VA Pittsburgh VISN 4 MIRECC [AG12962, AG10836] FX This research was supported by AG12962 and AG10836 (JPH) as well as the VA Pittsburgh VISN 4 MIRECC site (JWK). We Would also like to thank Ben Packard, Amy Bruestle, Amy Furay, Michelle Ostrander, Yve Ulrich-Lai, Helmer Figueiredo, Nancy Mueller, Nate Evanson and Ingrid Thomas for their expertise and assistance. NR 43 TC 17 Z9 19 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD JAN 8 PY 2009 VL 96 IS 1 BP 6 EP 11 DI 10.1016/j.physbeh.2008.07.024 PG 6 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 402LA UT WOS:000263014000002 PM 18722394 ER PT J AU Tam, J Fukumura, D Jain, RK AF Tam, Joshua Fukumura, Dai Jain, Rakesh K. TI A Mathematical Model of Murine Metabolic Regulation by Leptin: Energy Balance and Defense of a Stable Body Weight SO CELL METABOLISM LA English DT Article ID DIET-INDUCED OBESITY; FOOD-INTAKE; OB/OB MICE; MOUSE; RESISTANCE; EXPENDITURE; HOMEOSTASIS; TRANSPORT; DYNAMICS; HUMANS AB We have developed a physiologically based mathematical model, with parameters derived from published experimental data, to simulate the regulatory effects of the leptin pathway on murine energy homeostasis. Model outcomes are consistent with data reported in the literature and reproduce key characteristics of the energy regulatory system, including compensatory responses that counteract changes in body weight and the failure of this ability when the leptin pathway is disrupted. Our model revealed the possibility of multiple steady states for body weight. It also provided a unified theoretical framework for two historically antagonistic hypotheses regarding body weight regulation ("set-point" versus "settling point"). Finally, our model has identified potential avenues for future investigations. C1 [Tam, Joshua; Fukumura, Dai; Jain, Rakesh K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edwin L Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. [Tam, Joshua] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Edwin L Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu FU NIH [CA80124, CA85140, CA96915, CA115767] FX The authors would like to thank H. Kim, B. Seed (Department of Genetics, Massachusetts General Hospital), T. Stylianopoulos, M. Dupin, G. Cheng, and G.D. Duda for valuable advice. This study is supported in part by NIH grants to R.K.J. and D.F. (CA80124, CA85140, CA96915, and CA115767). NR 42 TC 20 Z9 20 U1 0 U2 4 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 JAN 7 PY 2009 VL 9 IS 1 BP 52 EP 63 DI 10.1016/j.cmet.2008.11.005 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 392WN UT WOS:000262333000009 PM 19117546 ER PT J AU Gaziano, JM Glynn, RJ Christen, WG Kurth, T Belanger, C MacFadyen, J Bubes, V Manson, JE Sesso, HD Buring, JE AF Gaziano, J. Michael Glynn, Robert J. Christen, William G. Kurth, Tobias Belanger, Charlene MacFadyen, Jean Bubes, Vadim Manson, Joann E. Sesso, Howard D. Buring, Julie E. TI Vitamins E and C in the Prevention of Prostate and Total Cancer in Men The Physicians' Health Study II Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BETA-CAROTENE SUPPLEMENTATION; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; LUNG-CANCER; ANTIOXIDANT VITAMINS; COLORECTAL-CANCER; WOMENS HEALTH; MORTALITY; SELENIUM AB Context Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large- scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer. Objective To evaluate whether long- term vitamin E or C supplementation decreases risk of prostate and total cancer events among men. Design, Setting, and Participants The Physicians' Health Study II is a randomized, double- blind, placebo- controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14 641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled. Intervention Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. Main Outcome Measures Prostate and total cancer. Results During a mean follow- up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer ( active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person- years; hazard ratio [ HR], 0.97; 95% confidence interval [ CI], 0.85- 1.09; P=. 58) or total cancer ( active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person- years; HR, 1.04; 95% CI, 0.95- 1.13; P=. 41). There was also no significant effect of vitamin C on total cancer ( active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person- years; HR, 1.01; 95% CI, 0.92- 1.10; P=. 86) or prostate cancer ( active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person- years; HR, 1.02; 95% CI, 0.90- 1.15; P=. 80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site- specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow- up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk. Conclusions In this large, long- term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle- aged and older men. Trial Registration clinicaltrials. gov Identifier: NCT00270647. C1 [Gaziano, J. Michael; Glynn, Robert J.; Christen, William G.; Kurth, Tobias; Belanger, Charlene; MacFadyen, Jean; Bubes, Vadim; Manson, Joann E.; Sesso, Howard D.; Buring, Julie E.] Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02120 USA. [Gaziano, J. Michael; Kurth, Tobias; Sesso, Howard D.; Buring, Julie E.] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02120 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Div Cardiovasc Dis, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Glynn, Robert J.; Kurth, Tobias; Manson, Joann E.; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02115 USA. RP Gaziano, JM (reprint author), Brigham & Womens Hosp, Div Prevent Med, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU National Institutes of Health (Bethesda, Maryland) [CA 97193, CA 34944, CA 40360, HL 26490, HL 34595]; BASF Corporation (Florham Park, New Jersey) FX This work was supported by grants CA 97193, CA 34944, CA 40360, HL 26490, and HL 34595 from the National Institutes of Health (Bethesda, Maryland) and an investigator-initiated grant from BASF Corporation (Florham Park, New Jersey). Study agents and packaging were provided by BASF Corporation, Wyeth Pharmaceuticals (Madison, New Jersey), and DSM Nutritional Products Inc (formerly Roche Vitamins) (Parsippany, New Jersey). NR 34 TC 245 Z9 256 U1 3 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 2009 VL 301 IS 1 BP 52 EP 62 DI 10.1001/jama.2008.862 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 391FY UT WOS:000262220400020 PM 19066368 ER PT J AU Weaver, FM Follett, K Stern, M Hur, K Harris, C Marks, WJ Rothlind, J Sagher, O Reda, D Moy, CS Pahwa, R Burchiel, K Hogarth, P Lai, EC Duda, JE Holloway, K Samii, A Horn, S Bronstein, J Stoner, G Heemskerk, J Huang, GD AF Weaver, Frances M. Follett, Kenneth Stern, Matthew Hur, Kwan Harris, Crystal Marks, William J., Jr. Rothlind, Johannes Sagher, Oren Reda, Domenic Moy, Claudia S. Pahwa, Rajesh Burchiel, Kim Hogarth, Penelope Lai, Eugene C. Duda, John E. Holloway, Kathryn Samii, Ali Horn, Stacy Bronstein, Jeff Stoner, Gatana Heemskerk, Jill Huang, Grant D. CA CSP 468 Study Grp TI Bilateral Deep Brain Stimulation vs Best Medical Therapy for Patients With Advanced Parkinson Disease A Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID QUALITY-OF-LIFE; SUBTHALAMIC STIMULATION; MOTOR FLUCTUATIONS; ADVERSE EVENTS; FOLLOW-UP; MULTICENTER; NUCLEUS; METAANALYSIS; VALIDATION AB Context Deep brain stimulation is an accepted treatment for advanced Parkinson disease ( PD), although there are few randomized trials comparing treatments, and most studies exclude older patients. Objective To compare 6- month outcomes for patients with PD who received deep brain stimulation or best medical therapy. Design, Setting, and Patients Randomized controlled trial of patients who received either deep brain stimulation or best medical therapy, stratified by study site and patient age ( < 70 years vs >= 70 years) at 7 Veterans Affairs and 6 university hospitals between May 2002 and October 2005. A total of 255 patients with PD ( Hoehn and Yahr stage >= 2 while not taking medications) were enrolled; 25% were aged 70 years or older. The final 6- month follow- up visit occurred in May 2006. Intervention Bilateral deep brain stimulation of the subthalamic nucleus ( n= 60) or globus pallidus ( n= 61). Patients receiving best medical therapy ( n= 134) were actively managed by movement disorder neurologists. Main Outcome Measures The primary outcome was time spent in the "on" state ( good motor control with unimpeded motor function) without troubling dyskinesia, using motor diaries. Other outcomes included motor function, quality of life, neurocognitive function, and adverse events. Results Patients who received deep brain stimulation gained a mean of 4.6 h/ d of on time without troubling dyskinesia compared with 0 h/ d for patients who received best medical therapy ( between group mean difference, 4.5 h/ d [ 95% CI, 3.7- 5.4 h/ d]; P <. 001). Motor function improved significantly ( P <. 001) with deep brain stimulation vs best medical therapy, such that 71% of deep brain stimulation patients and 32% of best medical therapy patients experienced clinically meaningful motor function improvements ( >= 5 points). Compared with the best medical therapy group, the deep brain stimulation group experienced significant improvements in the summary measure of quality of life and on 7 of 8 PD quality- of- life scores ( P <. 001). Neurocognitive testing revealed small decrements in some areas of information processing for patients receiving deep brain stimulation vs best medical therapy. At least 1 serious adverse event occurred in 49 deep brain stimulation patients and 15 best medical therapy patients ( P <. 001), including 39 adverse events related to the surgical procedure and 1 death secondary to cerebral hemorrhage. Conclusion In this randomized controlled trial of patients with advanced PD, deep brain stimulation was more effective than best medical therapy in improving on time without troubling dyskinesias, motor function, and quality of life at 6 months, but was associated with an increased risk of serious adverse events. Trial Registration clinicaltrials. gov Identifier: NCT00056563. C1 [Weaver, Frances M.] Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, Hines, IL 60141 USA. [Hur, Kwan; Reda, Domenic] Edward Hines Jr VA Hosp, Cooperat Studies Coordinating Ctr, Hines, IL 60141 USA. [Weaver, Frances M.] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. [Follett, Kenneth] Univ Nebraska, Dept Neurosurg, Omaha, NE 68182 USA. [Stern, Matthew; Duda, John E.; Horn, Stacy] Univ Penn Hlth Syst, Dept Neurol, Philadelphia, PA USA. [Stern, Matthew; Duda, John E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Harris, Crystal] Clin Res Pharm, VA Cooperat Studies Program, Albuquerque, NM USA. [Marks, William J., Jr.; Rothlind, Johannes] San Francisco VA Med Ctr, San Francisco, CA USA. [Marks, William J., Jr.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Rothlind, Johannes] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Sagher, Oren] Univ Michigan, Med Ctr, Dept Neurosurg, Ann Arbor, MI 48109 USA. [Moy, Claudia S.; Heemskerk, Jill] NINDS, Rockville, MD USA. [Pahwa, Rajesh] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. [Burchiel, Kim; Hogarth, Penelope] Portland VA Med Ctr, Portland, OR USA. [Burchiel, Kim] Oregon Hlth & Sci Univ, Dept Neurosurg, Portland, OR 97201 USA. [Hogarth, Penelope] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Lai, Eugene C.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Lai, Eugene C.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. [Holloway, Kathryn] Richmond VA Med Ctr, Richmond, VA USA. [Holloway, Kathryn] Virginia Commonwealth Univ, Dept Neurosurg, Richmond, VA USA. [Samii, Ali] Puget Sound Hlth Care Syst, Seattle, WA USA. [Bronstein, Jeff] W Los Angeles VA Med Ctr, Los Angeles, CA USA. [Stoner, Gatana] Univ Iowa Health Care, Dept Neurosurg, Iowa City, IA USA. [Huang, Grant D.] VA Off Res & Dev, Dept Vet Affairs, Cooperat Studies Program Cent Off, Washington, DC USA. RP Weaver, FM (reprint author), Edward Hines Jr VA Hosp, Ctr Management Complex Chron Care, 5000 S 5th Ave 151H, Hines, IL 60141 USA. EM Frances.Weaver@va.gov FU The Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; National Institute of Neurological Disorders and Stroke; Medtronic Neuromodulation FX The Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development, the National Institute of Neurological Disorders and Stroke, and Medtronic Neuromodulation provided financial support for this study. NR 31 TC 542 Z9 557 U1 7 U2 50 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 2009 VL 301 IS 1 BP 63 EP 73 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 391FY UT WOS:000262220400021 PM 19126811 ER PT J AU Bortfeld, T Webb, S AF Bortfeld, Thomas Webb, Steve TI Single-Arc IMRT? SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; CONFORMAL RADIOTHERAPY; PLAN QUALITY; THERAPY; TOMOTHERAPY; DELIVERY; COMPENSATION; OPTIMIZATION; COLLIMATION AB The idea of delivering intensity-modulated radiation therapy (IMRT) with a multileaf collimator in a continuous dynamic mode during a single rotation of the gantry has recently gained momentum both in research and industry. In this note we investigate the potential of this Single-Arc IMRT technique at a conceptual level. We consider the original theoretical example case from Brahme et al that got the field of IMRT started. Using analytical methods, we derive deliverable intensity 'landscapes' for Single-Arc as well as standard IMRT and Tomotherapy. We find that Tomotherapy provides the greatest flexibility in shaping intensity landscapes and that it allows one to deliver IMRT in a way that comes close to the ideal case in the transverse plane. Single-Arc and standard IMRT make compromises in different areas. Only in relatively simple cases that do not require substantial intensity modulation will Single-Arc be dosimetrically comparable to Tomotherapy. Compared with standard IMRT, Single-Arc could be dosimetrically superior in certain cases if one is willing to accept the spreading of low dose values over large volumes of normal tissue. In terms of treatment planning, Single-Arc poses a more challenging optimization problem than Tomotherapy or standard IMRT. We conclude that Single-Arc holds potential as an efficient IMRT technique especially for relatively simple cases. In very complex cases, Single-Arc may unduly compromise the quality of the dose distribution, if one tries to keep the treatment time below 2 min or so. As with all IMRT techniques, it is important to explore the tradeoff between plan quality and the efficiency of its delivery carefully for each individual case. C1 [Bortfeld, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bortfeld, Thomas] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Webb, Steve] Inst Canc Res, Joint Dept Phys, Sutton SM2 5PT, Surrey, England. [Webb, Steve] Royal Marsden NHS Fdn Trust, Sutton SM2 5PT, Surrey, England. RP Bortfeld, T (reprint author), Massachusetts Gen Hosp, 30 Fruit St, Boston, MA 02114 USA. FU Cancer Research UK [10588]; NCI NIH HHS [CA103904, CA118200] NR 24 TC 100 Z9 108 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD JAN 7 PY 2009 VL 54 IS 1 BP N9 EP N20 DI 10.1088/0031-9155/54/1/N02 PG 12 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 382HS UT WOS:000261597400013 PM 19075362 ER PT J AU Ellenbogen, JM Hulbert, JC Jiang, Y Stickgold, R AF Ellenbogen, Jeffrey M. Hulbert, Justin C. Jiang, Ying Stickgold, Robert TI The Sleeping Brain's Influence on Verbal Memory: Boosting Resistance to Interference SO PLOS ONE LA English DT Article ID SLOW-WAVE SLEEP; DECLARATIVE MEMORY; CONSOLIDATION; HIPPOCAMPUS; PLASTICITY; SYSTEMS; WAKING; CORTEX AB Memories evolve. After learning something new, the brain initiates a complex set of post-learning processing that facilitates recall (i.e., consolidation). Evidence points to sleep as one of the determinants of that change. But whenever a behavioral study of episodic memory shows a benefit of sleep, critics assert that sleep only leads to a temporary shelter from the damaging effects of interference that would otherwise accrue during wakefulness. To evaluate the potentially active role of sleep for verbal memory, we compared memory recall after sleep, with and without interference before testing. We demonstrated that recall performance for verbal memory was greater after sleep than after wakefulness. And when using interference testing, that difference was even more pronounced. By introducing interference after sleep, this study confirms an experimental paradigm that demonstrates the active role of sleep in consolidating memory, and unmasks the large magnitude of that benefit. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Hulbert, Justin C.] Univ St Andrews, St Andrews, Fife, Scotland. [Jiang, Ying] Dartmouth Coll, Hanover, NH 03755 USA. [Stickgold, Robert] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Ellenbogen, JM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. EM jeffrey_ellenbogen@hms.harvard.edu OI Hulbert, Justin/0000-0002-2889-0901 FU National Institutes of Health [R01-MH048832, K30-HL04095, T32-HL007901] FX This work was supported by the National Institutes of Health: NIH-R01-MH048832 (RS); NIH-K30-HL04095 (JME); and NIH-T32-HL007901 (JME). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 42 Z9 42 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 JAN 7 PY 2009 VL 4 IS 1 AR e4117 DI 10.1371/journal.pone.0004117 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 437FX UT WOS:000265473300003 PM 19127287 ER PT J AU Kwong, LN Chin, L AF Kwong, Lawrence N. Chin, Lynda TI The Metastasis Problem Gets Stickier SO CANCER CELL LA English DT Editorial Material ID CANCER METASTASIS; LUNG METASTASIS AB The enormity and complexity of cancer genome data present significant challenges in downstream validation of novel oncogenes and tumor suppressors. In this issue of Cancer Cell, Hu at al. evaluate candidate oncogenes in a recurrent amplification in poor-prognosis breast cancers. They identify and validate the prometastatic gene metadherin (MTDH) as a key modulator of endothelial adhesion and chemoresistance. C1 [Kwong, Lawrence N.; Chin, Lynda] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chin, Lynda] Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. [Chin, Lynda] Harvard Univ, Sch Med, Dept Dermatol, 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 FU NCI NIH HHS [R01 CA093947-08, R01 CA093947] NR 8 TC 9 Z9 11 U1 0 U2 3 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 JAN 6 PY 2009 VL 15 IS 1 BP 1 EP 2 DI 10.1016/j.ccr.2008.12.007 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 392XF UT WOS:000262334800001 PM 19111873 ER PT J AU Lieb, W Larson, MG Benjamin, EJ Yin, X Tofler, GH Selhub, J Jacques, PF Wang, TJ Vita, JA Levy, D Vasan, RS Mitchell, GF AF Lieb, Wolfgang Larson, Martin G. Benjamin, Emelia J. Yin, Xiaoyan Tofler, Geoffrey H. Selhub, Jacob Jacques, Paul F. Wang, Thomas J. Vita, Joseph A. Levy, Daniel Vasan, Ramachandran S. Mitchell, Gary F. TI Multimarker Approach to Evaluate Correlates of Vascular Stiffness The Framingham Heart Study SO CIRCULATION LA English DT Article DE epidemiology; biomarkers; renin-angiotensin-aldosterone system; C-reactive protein; plasminogen activator inhibitor 1 ID PULSE-WAVE VELOCITY; ANGIOTENSIN-CONVERTING ENZYME; C-REACTIVE PROTEIN; CROSS-SECTIONAL RELATIONS; MIDDLE-AGED WOMEN; ARTERIAL STIFFNESS; AORTIC STIFFNESS; RISK-FACTORS; ESSENTIAL-HYPERTENSION; NATRIURETIC PEPTIDE AB Background-Arterial stiffness increases with age and contributes to the pathogenesis of systolic hypertension and cardiovascular disease in the elderly. Knowledge about the pathophysiological processes that determine arterial stiffness may help guide therapeutic approaches. Methods and Results-We related 7 circulating biomarkers representing distinct biological pathways (C-reactive protein, aldosterone-to-renin ratio, N-terminal proatrial natriuretic peptide and B-type natriuretic peptide, plasminogen activator inhibitor-1, fibrinogen, and homocysteine) to 5 vascular function measures (central pulse pressure, carotid-femoral pulse-wave velocity, mean arterial pressure, forward pressure wave amplitude [all measures of conduit artery stiffness], and augmented pressure, an indicator of wave reflection) in 2000 Framingham Offspring Study participants (mean age, 61 years; 55% women). Tonometry measures were obtained on average 3 years after the biomarkers were measured. In multivariable linear regression models adjusting for covariates, the biomarker panel was significantly associated with all 5 vascular measures (P < 0.003 for all). On backward elimination, the aldosterone-to-renin ratio was positively associated with each stiffness measure (P <= 0.002 for all). In addition, C-reactive protein was positively related to augmented pressure (P = 0.0003), whereas plasminogen activator inhibitor-1 was positively associated with mean arterial pressure (P = 0.003), central pulse pressure (P = 0.001), and forward pressure wave (P = 0.01). Conclusions-Our cross-sectional data on a community-based sample suggest a distinctive pattern of positive associations of biomarkers of renin-angiotensin-aldosterone system activation with pan-arterial vascular stiffness, plasminogen activator inhibitor-1 with central vascular stiffness indices, and C-reactive protein with wave reflection. These observations support the notion of differential influences of biological pathways on vascular stiffness measures. (Circulation. 2009; 119: 37-43.) C1 [Lieb, Wolfgang; Larson, Martin G.; Benjamin, Emelia J.; Wang, Thomas J.; Levy, Daniel; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Larson, Martin G.; Yin, Xiaoyan] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vita, Joseph A.; Vasan, Ramachandran S.] Boston Univ, Cardiol Div & Prevent Med, Boston, MA 02215 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Epidemiol Sect, Boston, MA USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Sydney, NSW, Australia. [Selhub, Jacob; Jacques, Paul F.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA 02062 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA USA. EM vasan@bu.edu; GaryFMitchell@mindspring.com RI Lieb, Wolfgang/C-1990-2012; OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195]; National Heart, Lung, and Blood Institute [2K24HL04334, HL080124]; National Institutes of Health [HL60040, HL70100, HL076784, AG028321]; Donald W. Reynolds Foundation FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract N01-HC-25195: and grants 2K24HL04334 and HL080124 (both to Dr Vasan) from the National Heart, Lung, and Blood Institute. The project also was supported by National Institutes of Health grants HL60040, HL70100, HL076784, and AG028321 and the Donald W. Reynolds Foundation. NR 42 TC 69 Z9 75 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 JAN 6 PY 2009 VL 119 IS 1 BP 37 EP 43 DI 10.1161/CIRCULATIONAHA.108.816108 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 390YT UT WOS:000262200300008 PM 19103986 ER PT J AU Schwamm, LH Fonarow, GC Reeves, MJ Pan, W Frankel, MR Smith, EE Ellrodt, G Cannon, CP Liang, L Peterson, E LaBresh, KA AF Schwamm, Lee H. Fonarow, Gregg C. Reeves, Mathew J. Pan, Wenqin Frankel, Michael R. Smith, Eric E. Ellrodt, Gray Cannon, Christopher P. Liang, Li Peterson, Eric LaBresh, Kenneth A. TI Get With the Guidelines-Stroke Is Associated With Sustained Improvement in Care for Patients Hospitalized With Acute Stroke or Transient Ischemic Attack SO CIRCULATION LA English DT Article DE cerebral ischemia; risk factors; stroke; thrombolysis ID ACUTE CORONARY SYNDROMES; MEDICARE BENEFICIARIES; OUTCOMES; REGISTRY; QUALITY; RECOMMENDATIONS; ESTABLISHMENT; MANAGEMENT; ADHERENCE; PROGRAM AB Background-Adherence to evidence-based guidelines for treatment of stroke or transient ischemic attack is suboptimal. We sought to establish whether participation in Get With the Guidelines-Stroke was associated with improvements in adherence. Methods and Results-This prospective, nonrandomized, national quality improvement program measured adherence to guideline recommendations in 322 847 hospitalized patients discharged with a diagnosis of ischemic stroke or transient ischemic attack. A volunteer sample of 790 US academic and community hospitals participated from 2003 through 2007. The main outcome measures were change in adherence over time to 7 prespecified performance measures and a composite measure (total number of interventions provided in eligible patients divided by total number of care opportunities among eligible patients). Generalized estimating equations were used to identify factors associated with improvement. Participation in Get With the Guidelines-Stroke was associated with improvements in the 7 individual and 1 composite measures from baseline to the fifth year: intravenous thrombolytics (42.09% versus 72.84%), early antithrombotics (91.46% versus 97.04%), deep vein thrombosis prophylaxis (73.79% versus 89.54%), discharge antithrombotics (95.68% versus 98.88%), anticoagulation for atrial fibrillation (95.03% versus 98.39%), lipid treatment for low-density lipoprotein >100 mg/dL (73.63% versus 88.29%), smoking cessation (65.21% versus 93.61%), and composite (83.52% versus 93.97%) (P < 0.0001 for all comparisons). Multivariate analysis showed that time in Get With the Guidelines-Stroke was associated with a 1.18-fold yearly increase in the odds of fulfilling care opportunities that was independent of secular trends. Conclusions-Get With the Guidelines-Stroke participation was associated with increased adherence to all stroke performance measures. Markedly improved stroke care was seen in all hospitals regardless of size, geography, and teaching status. (Circulation. 2009; 119: 107-115.) C1 [Schwamm, Lee H.; Smith, Eric E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Reeves, Mathew J.] Michigan State Univ, E Lansing, MI 48824 USA. [Pan, Wenqin; Liang, Li; Peterson, Eric] Duke Clin Res Inst, Durham, NC USA. [Frankel, Michael R.] Emory Univ, Atlanta, GA 30322 USA. [Ellrodt, Gray] Berkshire Med Ctr, Pittsfield, MA USA. [Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [LaBresh, Kenneth A.] Masspro, Waltham, MA USA. RP Schwamm, LH (reprint author), Massachusetts Gen Hosp, ACC720,55 Fruit St, Boston, MA 02114 USA. EM lschwamm@partners.org RI LaBresh, Kenneth/A-6995-2017; OI LaBresh, Kenneth/0000-0001-9040-1956; Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668 FU AHA; American Stroke Association; Pfizer Inc, New York, NY; Merck-Schering Plough Partnership (North Wales, Pa) FX GWTG-Stroke is funded by the AHA and the American Stroke Association. The program is also supported in part by unrestricted educational grants to the AHA by Pfizer Inc, New York, NY, and the Merck-Schering Plough Partnership (North Wales, Pa), which did not participate in the design, analysis, manuscript preparation, or approval. NR 33 TC 256 Z9 259 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 6 PY 2009 VL 119 IS 1 BP 107 EP U206 DI 10.1161/CIRCULATIONAHA.108.783688 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 390YT UT WOS:000262200300016 PM 19075103 ER PT J AU Minniti, AN Rebolledo, DL Grez, PM Fadic, R Aldunate, R Volitakis, I Cherny, RA Opazo, C Masters, C Bush, AI Inestrosa, NC AF Minniti, Alicia N. Rebolledo, Daniela L. Grez, Paula M. Fadic, Ricardo Aldunate, Rebeca Volitakis, Irene Cherny, Robert A. Opazo, Carlos Masters, Colin Bush, Ashley I. Inestrosa, Nibaldo C. TI Intracellular amyloid formation in muscle cells of A beta-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification SO MOLECULAR NEURODEGENERATION LA English DT Article ID INCLUSION-BODY MYOSITIS; NEURONAL OXIDATIVE STRESS; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; IN-VIVO; NEUROMUSCULAR-JUNCTIONS; PROTOFIBRIL FORMATION; SUPEROXIDE-DISMUTASE; SENILE PLAQUES; RNA OXIDATION AB Background: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine A beta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that A beta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that A beta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly. Results: In the present work, we found that intracellular A beta aggregation in muscle cells of Caenorhabditis elegans overexpressing A beta peptide is affected by two single amino acid substitutions, E22G (Arctic) and V18A (NIC). Both variations show decrease intracellular amyloidogenesis compared to wild type A beta. We show that intracellular amyloid aggregation of wild type A beta is accelerated by Cu(2+) and diminished by copper chelators. Moreover, we demonstrate through toxicity and behavioral assays that A beta-transgenic worms display a higher tolerance to Cu(2+) toxic effects and that this resistance may be linked to the formation of amyloid aggregates. Conclusion: Our data show that intracellular A beta amyloid aggregates may trap excess of free Cu(2+) buffering its cytotoxic effects and that accelerated intracellular A beta aggregation may be part of a cell protective mechanism. C1 [Minniti, Alicia N.; Rebolledo, Daniela L.; Grez, Paula M.; Aldunate, Rebeca; Inestrosa, Nibaldo C.] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Ctr Regulac Celular & Patol Joaquin V Luco, MIFAB,CARE, Santiago 8331010, Chile. [Fadic, Ricardo] Pontificia Univ Catolica Chile, Dept Neurol, Fac Med, Santiago 8331010, Chile. [Volitakis, Irene; Cherny, Robert A.; Masters, Colin; Bush, Ashley I.] Univ Melbourne, Oxidat Disorders Lab, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. [Volitakis, Irene; Cherny, Robert A.; Masters, Colin; Bush, Ashley I.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. [Opazo, Carlos] Univ Concepcion, Lab Neurobiomet, Dept Fisiol, Fac Ciencias Biol, Concepcion, Chile. [Bush, Ashley I.] Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Sch Med, Charlestown, MA USA. RP Inestrosa, NC (reprint author), Pontificia Univ Catolica Chile, Fac Ciencias Biol, Ctr Regulac Celular & Patol Joaquin V Luco, MIFAB,CARE, Alameda 340, Santiago 8331010, Chile. EM aminniti@bio.puc.cl; dvreboll@puc.cl; pgrez@indiana.edu; rfadic@med.puc.cl; raldunat@bio.puc.cl; ivolitakis@mhri.edu.au; rcherny@mhri.edu.au; carlosopazo@udec.cl; c.masters@unimelb.edu.au; bush@helix.mgh.harvard.edu; ninestrosa@bio.puc.cl RI Fadic, Ricardo/E-9488-2013; Bush, Ashley/A-1186-2007; OI Bush, Ashley/0000-0001-8259-9069; Volitakis, Irene/0000-0003-0766-817X FU NIH National Center for Research Resources (NCRR); International Copper Association (ICA, New York, N.Y.); FONDAP-Biomedicine [13980001]; Millennium Institute of Fundamental and Applied Biology (MIFAB); Center for Aging and Regeneration (CARE) [PFB 12/2007]; Base Financing Program for Scientific and Technological Centers of Excellence; CONICYT; Alzheimer's Association; NHMRC; NIA [R01AG12686] FX Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the NIH National Center for Research Resources (NCRR). This work was supported by the International Copper Association (ICA, New York, N.Y.), FONDAP-Biomedicine grant No 13980001, Millennium Institute of Fundamental and Applied Biology (MIFAB), the Center for Aging and Regeneration (CARE), PFB 12/2007, Base Financing Program for Scientific and Technological Centers of Excellence, CONICYT, the Alzheimer's Association, the NHMRC and the NIA (R01AG12686 to AIB). NR 74 TC 21 Z9 23 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1750-1326 J9 MOL NEURODEGENER JI Mol. Neurodegener. PD JAN 6 PY 2009 VL 4 AR 2 DI 10.1186/1750-1326-4-2 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 445PK UT WOS:000266063200002 PM 19126228 ER PT J AU Bird, TD AF Bird, Thomas D. TI A new disease mimicking Refsum syndrome SO NEUROLOGY LA English DT Editorial Material C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Bird, TD (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. EM tomnroz@u.washington.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 6 PY 2009 VL 72 IS 1 BP 13 EP 13 DI 10.1212/01.wnl.0000334358.71615.fd PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 390KL UT WOS:000262162600003 PM 19005173 ER PT J AU Waldron, TT Springer, TA AF Waldron, Travis T. Springer, Timothy A. TI Transmission of allostery through the lectin domain in selectin-mediated cell adhesion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cell rolling; mechanochemistry; vasculature ID CATCH BONDS; P-SELECTIN; LIGAND RECOGNITION; BACTERIAL ADHESION; SHEAR; FORCE; FLOW; RECEPTOR; BINDING AB The selectins are cell adhesion proteins that must resist applied forces to mediate leukocyte tethering and rolling along the endothelium and have 2 conformational states. Selectin-ligand bond dissociation increases only modestly with applied force, and exhibits catch bond behavior in a low-force regime where bond lifetimes counterintuitively increase with increasing force. Both allosteric and sliding-rebinding models have emerged to explain catch bonds. Here, we introduce a large residue into a cleft that opens within the lectin domain to stabilize the more extended, high-affinity selectin conformation. This mutation stabilizes the high-affinity state, but surprisingly makes rolling less stable. The position of the mutation in the lectin domain provides evidence for an allosteric pathway through the lectin domain, connecting changes at the lectin-EGF interface to the distal binding interface. C1 [Waldron, Travis T.; Springer, Timothy A.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, 200 Longwood Ave,WAB Room 240, Boston, MA 02115 USA. EM springer@idi.harvard.edu FU National Institutes of Health [HL-48675]; Kirschstein National Research Service Award FX We thank Drs. Larry Shapiro, Wendy Thomas, and William Somers for reviewing this manuscript. This work was supported by National Institutes of Health Grant HL-48675 and a Kirschstein National Research Service Award. NR 24 TC 33 Z9 35 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2009 VL 106 IS 1 BP 85 EP 90 DI 10.1073/pnas.0810620105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391WC UT WOS:000262263900019 PM 19118202 ER PT J AU Springer, TA AF Springer, Timothy A. TI Structural basis for selectin mechanochemistry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID P-SELECTIN; CATCH BONDS; MONOCLONAL-ANTIBODIES; LIGAND RECOGNITION; CELL-ADHESION; DOMAIN; FORCE; RECEPTOR; SHEAR; FLOW AB Selectins are adhesion molecules that resist large tensile forces applied by hydrodynamic forces to leukocytes binding to vessel walls. In crystals, the liganded (high-affinity) and unliganded (low-affinity) conformations differ in orientation between their tandem lectin and EGF domains. I examine how tensile force exerted on a selectin-ligand complex in vivo could favor the more extended, high-affinity conformation. Allostery is transmitted from the EGF-lectin domain interface to the ligand-binding interface on the lectin domain, 30 angstrom away. Trp-1 of the lectin domain and the long axis of the EGF domain form an L-shaped prybar that is welded together by hydrogen bonds to the Trp-1 alpha-amino group. Pivoting of the prybar induced by force demolishes an interface between the Trp-1 side chain and the lectin domain at a switch1 region. These changes are transmitted by rigid body movement of the switch2 region to rearrangements in the switch3 region at the ligand binding site. Another switch region corresponds to a single residue in the EGF domain with large effects on ligand binding and rolling adhesion. Allostery in selectins, and the alignment of tensile force on a selectin-ligand complex with the transition pathway for conformational change, explain much of the structural basis for selectin mechanochemistry. C1 Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu FU National Institutes of Health [HL-48675] FX I thank Drs. Larry Shapiro, Wendy Thomas, and William Somers for reviewing this manuscript. This work was supported by National Institutes of Health Grant HL-48675. NR 24 TC 43 Z9 44 U1 2 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 JAN 6 PY 2009 VL 106 IS 1 BP 91 EP 96 DI 10.1073/pnas.0810784105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391WC UT WOS:000262263900020 PM 19118197 ER PT J AU Zhang, LL Lee, SY Beznoussenko, GV Peters, PJ Yang, JS Gilbert, HY Brass, AL Elledge, SJ Isaacs, SN Moss, B Mironov, A Hsu, VW AF Zhang, Leiliang Lee, Stella Y. Beznoussenko, Galina V. Peters, Peter J. Yang, Jia-Shu Gilbert, Hui-ya Brass, Abraham L. Elledge, Stephen J. Isaacs, Stuart N. Moss, Bernard Mironov, Alexander Hsu, Victor W. TI A role for the host coatomer and KDEL receptor in early vaccinia biogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE COPI; morphogenesis ID FUNCTIONAL GENOMIC SCREEN; ENDOPLASMIC-RETICULUM; COPI VESICLES; MEMBRANE; VIRUS; PROTEIN; TRANSPORT; REVEALS; ARF1; MORPHOGENESIS AB Members of the poxvirus family have been investigated for their applications as vaccines and expression vectors and, more recently, because of concern for their potential as biological weapons. Vaccinia virus, the prototypic member, evolves through multiple forms during its replication. Here, we show a surprising way by which vaccinia hijacks coatomer for early viral biogenesis. Whereas coatomer forms COPI vesicles in the host early secretory system, vaccinia formation bypasses this role of coatomer, but instead, depends on coatomer interacting with the host KDEL receptor. To gain insight into the viral roles of these two host proteins, we have detected them on the earliest recognized viral forms. These findings not only suggest insights into early vaccinia biogenesis but also reveal an alternate mechanism by which coatomer acts. C1 [Zhang, Leiliang; Lee, Stella Y.; Yang, Jia-Shu; Gilbert, Hui-ya; Hsu, Victor W.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. [Zhang, Leiliang; Lee, Stella Y.; Yang, Jia-Shu; Gilbert, Hui-ya; Hsu, Victor W.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Beznoussenko, Galina V.; Mironov, Alexander] Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy. [Peters, Peter J.] Netherlands Canc Inst, Div Cell Biol, NL-1066 CX Amsterdam, Netherlands. [Brass, Abraham L.; Elledge, Stephen J.] Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Genet, Howard Hughes Med Inst,Ctr Genet & Genom, Boston, MA 02115 USA. [Brass, Abraham L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Isaacs, Stuart N.] Univ Penn, Sch Med, Div Infect Dis, Dept Med, Philadelphia, PA 19104 USA. [Moss, Bernard] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Hsu, VW (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. EM vhsu@rics.bwh.harvard.edu FU National Institutes of Health; Telethon Italy; Harvard University Center for AIDS Research FX We thank Jian Li and Ming Bai for advice and Erik Bos for technical assistance. This work was supported by grants from the National Institutes of Health ( to V. W. H. and S.N.I.), Telethon Italy ( to A. M.), and the Harvard University Center for AIDS Research ( to A. L. B.). S. J. E. is an Investigator of the Howard Hughes Medical Institute. NR 29 TC 15 Z9 17 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 6 PY 2009 VL 106 IS 1 BP 163 EP 168 DI 10.1073/pnas.0811631106 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 391WC UT WOS:000262263900032 PM 19109439 ER PT J AU Wang, Y Samuels, JF Chang, YC Grados, MA Greenberg, BD Knowles, JA McCracken, JT Rauch, SL Murphy, DL Rasmussen, SA Cullen, B Hoehn-Saric, R Pinto, A Fyer, AJ Piacentini, J Pauls, DL Bienvenu, OJ Riddle, M Shugart, YY Liang, KY Nestadt, G AF Wang, Y. Samuels, J. F. Chang, Y. C. Grados, M. A. Greenberg, B. D. Knowles, J. A. McCracken, J. T. Rauch, S. L. Murphy, D. L. Rasmussen, S. A. Cullen, B. Hoehn-Saric, R. Pinto, A. Fyer, A. J. Piacentini, J. Pauls, D. L. Bienvenu, O. J. Riddle, M. Shugart, Y. Y. Liang, K. Y. Nestadt, G. TI Gender Differences in Genetic Linkage and Association on 11p15 in Obsessive-Compulsive Disorder Families SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; linkage; association; OCD; gender ID TANDEM DUPLICATION POLYMORPHISM; COMPLEX SEGREGATION ANALYSIS; DOPAMINE-D4 RECEPTOR GENE; DRD4 GENE; CHILDREN; ADHD; SUSCEPTIBILITY; LOCUS; IDENTIFICATION; ADOLESCENTS AB Several clinical and genetic studies have reported gender differences in obsessive-compulsive disorder (OCD). Previously, we conducted a linkage genome scan using multipoint allele-sharing methods to test for linkage in 219 families participating in the OCD Collaborative Genetics Study. When these families were stratified by proband's gender, suggestive linkage to chromosome 11p15 at marker D11S2362 (KAC(all) = 2.92, P = 0.00012) was detected in families with male probands, but not in the ones with female probands. We have since conducted fine mapping with a denser microsatellite marker panel in the region of 11p15, and detected a significant linkage signal at D11S4146 (KAC(all) = 5.08, P < 0.00001) in the families of male probands. Subsequently, 632 SNPs were genotyped spanning a 4.0 Mb region of the 1 LOD unit interval surrounding the linkage peak in the original families and an additional 165 families. Six SNPs were associated with OCD (P < 0.001): two SNPs were identified when all the families were included, and four SNPs only in male proband families. No SNP showed significant association with the OCD phenotype only in the families with a female proband. The results suggest a possible gender effect in the etiology of OCD. (c) 2008 Wiley-Liss, Inc. C1 [Wang, Y.; Samuels, J. F.; Grados, M. A.; Hoehn-Saric, R.; Bienvenu, O. J.; Riddle, M.; Nestadt, G.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Chang, Y. C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Greenberg, B. D.; Rasmussen, S. A.] Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. [Knowles, J. A.] Univ So Calif, Dept Psychiat, Los Angeles, CA 90089 USA. [McCracken, J. T.; Piacentini, J.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Massachusetts Gen Hosp, Neurodev Genet Unit, Boston, MA 02114 USA. [Rauch, S. L.; Pauls, D. L.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Murphy, D. L.] NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. [Pinto, A.; Fyer, A. J.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. [Shugart, Y. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. [Liang, K. Y.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 109, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Piacentini, John/C-4645-2011; Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU National Institute of Mental Health NIMH [R01 MH50214, K23MH64543, 7K23MHO66284]; James E. Marshall OCD Foundation; NIH [OPD-GCRC RR 00052]; NCRR FX This study is supported by NIMH R01 MH50214 to GN, K23MH64543 to OJB, and 7K23MHO66284 to MAG from the National Institute of Mental Health, and funding from the James E. Marshall OCD Foundation, and NIH, NCRR, OPD-GCRC RR 00052 from the National Institutes of Health. We are grateful to the numerous individuals and families who generously donated their time and resources. We thank David Houseman, MID, Kathleen Merikangas, PhD, Ann Pulver, PhD, and Alec Wilson, Phl), for consultation; and clinicians and coordinators at each site: Providence (Maria Mancebo, Phl), Richard Marsland, RN, Shirley Yen, PhD); New York (Rence Goodwin, PhD, Joshua Lipsitz, PhD); Baltimore (Laura Eisen, BS; Karan Lamb, PsyD, Tracey Lichner, PhD, Yungmei Leong, Phl); Krista Vermillion, BA); Boston (Dan Geller, MD, Anne Chosak, Phl), Michelle Wedig, BS, Evelyn Stewart, MD, Michael Jenike, MD, Beth Gershuny, Phl), Sabine Wilhelm, PhD); Bethesda (Lucy Justement, Diane Kazuba, V Holland LaSafle-Ricci, Theresa B DeGuzman); Los Angeles (R Lindsey Bergman, PhD, Susanna Chang, PhD, Audra Langley, Phl), Arnanda Pearlrnan, BA). NR 66 TC 16 Z9 17 U1 3 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4841 EI 1552-485X J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JAN 5 PY 2009 VL 150B IS 1 BP 33 EP 40 DI 10.1002/ajmg.b.30760 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 402XR UT WOS:000263046900004 PM 18425788 ER PT J AU Gorlero, M Wieczorek, R Adamala, K Giorgi, A Schinina, ME Stano, P Luisi, PL AF Gorlero, Macha Wieczorek, Rafal Adamala, Katarzyna Giorgi, Alessandra Schinina, Maria Eugenia Stano, Pasquale Luisi, Pier Luigi TI Ser-His catalyses the formation of peptides and PNAs SO FEBS LETTERS LA English DT Article DE Organocatalysis; Peptide condensation; Fragment condensation; Origins of life; Prebiotic chemistry ID PREBIOTIC CONDITIONS; HISTIDYL-HISTIDINE; BOND FORMATION; ACID; OLIGOPEPTIDES; GLYCINE; EVOLUTION; DNA AB The dipeptide seryl-histidine (Ser-His) catalyses the condensation of esters of amino acids, peptide fragments, and peptide nucleic acid (PNA) building blocks, bringing to the formation of peptide bonds. Di-, tri- or tetra-peptides can be formed with yields that vary from 0.5% to 60% depending on the nature of the substrate and on the conditions. Other simpler peptides as Gly-Gly, or Gly-Gly-Gly are also effective, although less efficiently. We discuss the results from the viewpoint of primitive chemistry and the origin of long macromolecules by stepwise fragment condensations. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved. C1 [Gorlero, Macha; Wieczorek, Rafal; Stano, Pasquale; Luisi, Pier Luigi] Univ RomaTre, Dept Biol, Rome, Italy. [Wieczorek, Rafal] Univ Ca Foscari, European Ctr Living Technol, Venice, Italy. [Adamala, Katarzyna] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Giorgi, Alessandra; Schinina, Maria Eugenia] Univ Roma La Sapienza, Dept Biochem Sci, I-00185 Rome, Italy. [Schinina, Maria Eugenia] Univ Roma La Sapienza, Lab Funct Genom & Prote Model Organisms, I-00185 Rome, Italy. RP Luisi, PL (reprint author), Univ RomaTre, Dept Biol, Viale G Marconi 446, Rome, Italy. EM luisi@mat.ethz.ch OI Wieczorek, Rafal/0000-0003-0172-8063; Adamala, Kate/0000-0003-1066-7207 FU EC FP6 [043359]; Human Frontier Science Program; Italian Space Agency FX Research conducted in the P. L. L.'s laboratory (Chemical Synthetic Biology) is supported by the EC FP6 (contract # 043359), the Human Frontier Science Program, and the Italian Space Agency. NR 25 TC 31 Z9 34 U1 3 U2 32 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JAN 5 PY 2009 VL 583 IS 1 BP 153 EP 156 DI 10.1016/j.febslet.2008.11.052 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 387JT UT WOS:000261949200027 PM 19071124 ER PT J AU Murthy, V Maison, SF Taranda, J Haque, N Bond, CT Elgoyhen, AB Adelman, JP Liberman, MC Vetter, DE AF Murthy, Vidya Maison, Stephane F. Taranda, Julian Haque, Nadeem Bond, Chris T. Belen Elgoyhen, A. Adelman, John P. Charles Liberman, M. Vetter, Douglas E. TI SK2 channels are required for function and long-term survival of efferent synapses on mammalian outer hair cells SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article DE Cochlea; Small conductance potassium channels; Nicotinic receptors; Synaptic degeneration; Synaptogenesis ID ACTIVATED POTASSIUM CHANNELS; CA2+-ACTIVATED K+ CHANNEL; SMALL-CONDUCTANCE; DEVELOPMENTAL EXPRESSION; ACETYLCHOLINE-RECEPTOR; SURFACE EXPRESSION; RAT COCHLEA; INHIBITION; RESPONSES; MOUSE AB Cochlear hair cells use SK2 Currents to shape responses to cholinergic efferent feedback from the brain. Using SK2(-/-) mice, we demonstrate that, in addition to their previously defined role in modulating hair cell membrane potentials, SK2 channels are necessary for long-term survival of olivocochlear fibers and synapses. Loss of the SK2 gene also results a loss of electrically driven olivocochlear effects in vivo. and down regulation of ryanodine receptors involved in calcium-induced calcium release, the main inducer of nAChR evoked SK2 activity. Generation Of double-null mice lacking both the alpha 10 nAChR gene, loss of which results in hypertrophied olivocochlear terminals, and the SK2 gene, recapitulates the SK2(-/-) synaptic phenotype and gene expression, and also leads to clown regulation of alpha 9 nAChR gene expression. The data suggest a hierarchy of activity necessary to maintain early olivocochlear synapses at then, targets, with SK2 serving an epistatic, upstream, role to the nAChRs. (C) 2008 Elsevier Inc. All rights reserved C1 [Murthy, Vidya; Taranda, Julian; Vetter, Douglas E.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Maison, Stephane F.; Charles Liberman, M.] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA USA. [Maison, Stephane F.; Charles Liberman, M.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. [Taranda, Julian; Belen Elgoyhen, A.] Consejo Nacl Invest Cient & Tecn, Inst Invest Ingn Genet & Biol Mol, RA-1033 Buenos Aires, DF, Argentina. [Haque, Nadeem] Univ Notre Dame, Notre Dame, IN 46556 USA. [Adelman, John P.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR USA. RP Vetter, DE (reprint author), Tufts Univ, Sch Med, Dept Neurosci, 136 Harrison Ave, Boston, MA 02111 USA. EM douglas.vetter@tufts.edu FU NIH [R01 DC006258, R01 DC0188, P30 DC 05209]; The Tufts Center for Neuroscience Research Imaging Core and Genomics Core [P30 NS047243] FX This work was supported by: NIH R01 DC006258 (DEV), R01 DC0188 (MCL), P30 DC 05209 (MCL). and The Tufts Center for Neuroscience Research Imaging Core and Genomics Core P30 NS047243. NR 42 TC 25 Z9 25 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JAN 5 PY 2009 VL 40 IS 1 BP 39 EP 49 DI 10.1016/j.mcn.2008.08.011 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 394CK UT WOS:000262422700004 PM 18848895 ER PT J AU Sung, YJ Choi, W Fang-Yen, C Badizadegan, K Dasari, RR Feld, MS AF Sung, Yongjin Choi, Wonshik Fang-Yen, Christopher Badizadegan, Kamran Dasari, Ramachandra R. Feld, Michael S. TI Optical diffraction tomography for high resolution live cell imaging SO OPTICS EXPRESS LA English DT Article ID DIGITAL HOLOGRAPHIC MICROSCOPY; PHASE MICROSCOPY; REFRACTIVE-INDEX; LIVING CELLS; MORPHOMETRY; SCATTERING; DYNAMICS; CONTRAST AB We report the experimental implementation of optical diffraction tomography for quantitative 3D mapping of refractive index in live biological cells. Using a heterodyne Mach-Zehnder interferometer, we record complex field images of light transmitted through a sample with varying directions of illumination. To quantitatively reconstruct the 3D map of complex refractive index in live cells, we apply optical diffraction tomography based on the Rytov approximation. In this way, the effect of diffraction is taken into account in the reconstruction process and diffraction-free high resolution 3D images are obtained throughout the entire sample volume. The quantitative refractive index map can potentially serve as an intrinsic assay to provide the molecular concentrations without the addition of exogenous agents and also to provide a method for studying the light scattering properties of single cells. (C) 2008 Optical Society of America C1 [Sung, Yongjin; Choi, Wonshik; Fang-Yen, Christopher; Badizadegan, Kamran; Dasari, Ramachandra R.; Feld, Michael S.] MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. [Badizadegan, Kamran] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. [Badizadegan, Kamran] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Choi, W (reprint author), MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. EM wonshik@mit.edu OI Fang-Yen, Christopher/0000-0002-4568-3218 FU National Institutes of Health [P41-RR02594-18]; National Science Foundation [DBI-0754339]; Hamamatsu Corporation; Kwanjeong Educational Foundation FX This work was funded by the National Center for Research Resources of the National Institutes of Health (P41-RR02594-18), the National Science Foundation (DBI-0754339) and Hamamatsu Corporation. Yongjin Sung was supported in part by a fellowship from the Kwanjeong Educational Foundation. NR 25 TC 160 Z9 162 U1 2 U2 31 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD JAN 5 PY 2009 VL 17 IS 1 BP 266 EP 277 DI 10.1364/OE.17.000266 PG 12 WC Optics SC Optics GA 391FX UT WOS:000262220300030 PM 19129896 ER PT J AU Mocroft, A Wyatt, C Szczech, L Neuhaus, J El-Sadr, W Tracy, R Kuller, L Shlipak, M Angus, B Klinker, H Ross, M AF Mocroft, Amanda Wyatt, Christina Szczech, Lynda Neuhaus, Jacquie El-Sadr, Wafaa Tracy, Russell Kuller, Lewis Shlipak, Michael Angus, Brian Klinker, Harting Ross, Michael CA Insight Smart Study Grp TI Interruption of antiretroviral therapy is associated with increased plasma cystatin C SO AIDS LA English DT Article DE cystatin C; randomized trial; treatment interruption ID GLOMERULAR-FILTRATION-RATE; CHRONIC KIDNEY-DISEASE; IMMUNODEFICIENCY-VIRUS-INFECTION; TUBULAR EPITHELIAL-CELLS; CARDIOVASCULAR-DISEASE; SERUM CREATININE; RENAL-FUNCTION; HIV-1-ASSOCIATED NEPHROPATHY; REFERENCE RANGES; HIV-1 INFECTION AB Background: Cystatin C has been proposed as an alternative marker of renal function. We sought to determine whether participants randomized to episodic use of antiretroviral therapy guided by CD4(+) cell count (drug conservation) had altered cystatin C levels compared with those randomized to Continuous antiretroviral therapy (viral suppression) in the Strategies for Management of Antiretroviral Therapy trial, and to identify factors associated with increased cystatin C. Methods: Cystatin C was measured in plasma collected at randomization, 1, 2, 4, 8 and 12 months after randomization in a random sample of 249 and 250 participants in the drug conservation and viral suppression groups, respectively. Logistic regression was used to model the odds of at least 0.15 mg/dl increase in cystatin C (1 SD) in the first month after randomization, adjusting for demographic and clinical characteristics. Results: At randomization, mean (SD) cystatin C level was 0.99 (0.26 mg/dl) and 1.01 (0.28 mg/dl) in the drug conservation and viral Suppression arms, respectively (P = 0.29). In the first month after randomization, 21.8 and 10.6% had at least 0.15 mg/dl increase in cystatin C in the drug conservation and viral suppression arms, respectively (P=0.0008). The difference in cystatin C between the treatment arms was maintained through 1 year after randomization. After adjustment, participants in the viral suppression arm had significantly reduced odds of at least 0.15 mg/dl increase in cystatin C in the first month (odds ratio 0.42; 95% confidence interval 0.23-0.74, P = 0.0023). Conclusion: These results demonstrate that interruption of antiretroviral therapy is associated with an increase in cystatin C, which may reflect worsened renal function. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins C1 [Mocroft, Amanda] UCL, Sch Med, Res Dept Infect & Populat Hlth, London NW3 2PF, England. [Wyatt, Christina; Ross, Michael] Mt Sinai Sch Med, New York, NY USA. [Szczech, Lynda] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Neuhaus, Jacquie] Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. [El-Sadr, Wafaa] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. [El-Sadr, Wafaa] Columbia Univ, New York, NY USA. [Tracy, Russell] Univ Vermont, Coll Med, Burlington, VT 05405 USA. [Kuller, Lewis] Univ Pittsburgh, Pittsburgh, PA USA. [Shlipak, Michael] San Francisco VA Med Ctr, San Francisco, CA USA. [Shlipak, Michael] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Angus, Brian] Univ Oxford, Nuffield Dept Med, Oxford OX1 2JD, England. [Angus, Brian] MRC, HIV Clin Trials Unit, London, England. [Klinker, Harting] Klinikum Univ Wurzburg, Wurzburg, Germany. RP Mocroft, A (reprint author), UCL, Sch Med, Res Dept Infect & Populat Hlth, Royal Free Campus,Rowland Hill St, London NW3 2PF, England. EM a.mocroft@pcps.ucl.ac.uk RI Mocroft, Amanda/C-1527-2008; Mocroft, Amanda/G-8748-2011; SHCS, int. coll. B/G-4090-2011; SHCS, all/G-4072-2011; Pulido, Federico/B-8417-2009; Brites, Carlos/D-1353-2013; OI Magenta, Lorenzo/0000-0002-7644-3647; Okhuysen, Pablo/0000-0002-1596-3411; Angus, Brian/0000-0003-3598-7784; Pulido, Federico/0000-0002-7414-8812; Koirala, Janak/0000-0002-3608-474X; Brites, Carlos/0000-0002-4673-6991; Gayet-Ageron, Angele/0000-0002-6164-9693 FU NIAID; NIH [U01AI042170, U01A1068641, U01A146362] FX This study was supported by NIAID, NIH grants U01AI042170, U01A1068641 and U01A146362 Clinical Trials.gov identifier: NCT00027352. NR 44 TC 36 Z9 38 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JAN 2 PY 2009 VL 23 IS 1 BP 71 EP 82 DI 10.1097/QAD.0b013e32831cc129 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 390XS UT WOS:000262197600010 PM 19050388 ER PT J AU Bhattacharya, A Muller, FL Liu, YH Sabia, M Liang, HY Song, W Jang, YC Ran, QT Van Remmen, H AF Bhattacharya, Arunabh Muller, Florian L. Liu, Yuhong Sabia, Marian Liang, Hanyu Song, Wook Jang, Youngmok C. Ran, Qitao Van Remmen, Holly TI Denervation Induces Cytosolic Phospholipase A(2)-mediated Fatty Acid Hydroperoxide Generation by Muscle Mitochondria SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; AGING SKELETAL-MUSCLE; GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; SELENOORGANIC COMPOUND; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; BIOLOGICAL-SYSTEMS; INDUCED APOPTOSIS; MICE DEFICIENT AB Previously, we demonstrated that mitochondria from denervated muscle exhibited dramatically higher Amplex Red dependent fluorescence (thought to be highly specific for hydrogen peroxide) compared with control muscle mitochondria. We now demonstrate that catalase only partially inhibits the Amplex Red signal in mitochondria from denervated muscle. In contrast, ebselen (a glutathione peroxidase mimetic and inhibitor of fatty acid hydroperoxides) significantly inhibits the Amplex Red signal. This suggests that the majority of the Amplex Red signal in mitochondria from denervated muscle is not derived from hydrogen peroxide. Because Amplex Red cannot react with substrates in the lipid environment, we hypothesize that lipid hydroperoxides formed within the mitochondrial lipid bilayer are released as fatty acid hydroperoxides and react with the Amplex Red probe. We also suggest that the release of fatty acid hydroperoxides from denervated muscle mitochondria may be an important determinant of muscle atrophy. In support of this, muscle atrophy and the Amplex Red signal are inhibited in caloric restricted mice and in transgenic mice that overexpress the lipid hydroperoxide-detoxifying enzyme glutathione peroxidase 4. Finally, we propose that cytosolic phospholipase A(2) may be a potential source of these hydroperoxides. C1 [Bhattacharya, Arunabh; Liu, Yuhong; Liang, Hanyu; Song, Wook; Ran, Qitao; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Bhattacharya, Arunabh; Muller, Florian L.; Liu, Yuhong; Liang, Hanyu; Jang, Youngmok C.; Ran, Qitao; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. [Sabia, Marian; Ran, Qitao; Van Remmen, Holly] S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP Van Remmen, H (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, Texas Res Pk Campus,15355 Lambda Dr, San Antonio, TX 78245 USA. EM vanremmen@uthscsa.edu RI Liang, Hanyu/A-1066-2010 FU National Institutes of Health [AG20591]; Muscular Dystrophy Association [MDA 3879]; Veterans Affairs merit grant FX This work was supported, in whole or in part, by National Institutes of Health Grant AG20591 (to H. V. R.). This work was also supported by Muscular Dystrophy Association Grant MDA 3879 (to H. V. R.) and a Veterans Affairs merit grant (to H. V. R.). 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 30 Z9 30 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 2 PY 2009 VL 284 IS 1 BP 46 EP 55 DI 10.1074/jbc.M806311200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 387TP UT WOS:000261974800006 PM 19001413 ER PT J AU Clay, NK Adio, AM Denoux, C Jander, G Ausubel, FM AF Clay, Nicole K. Adio, Adewale M. Denoux, Carine Jander, Georg Ausubel, Frederick M. TI Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response SO SCIENCE LA English DT Article ID GLUTATHIONE-DEFICIENT MUTANT; METAL-BINDING PEPTIDES; NONHOST RESISTANCE; DISEASE RESISTANCE; PHYTOCHELATIN SYNTHASE; ABC TRANSPORTER; ABSCISIC-ACID; CELL WALL; THALIANA; BIOSYNTHESIS AB The perception of pathogen or microbe- associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity and is defined partly by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen- triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4- methoxy- indol- 3- ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen- triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens. C1 [Clay, Nicole K.; Denoux, Carine; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Clay, Nicole K.; Denoux, Carine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Clay, Nicole K.; Denoux, Carine; Ausubel, Frederick M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Adio, Adewale M.; Jander, Georg] Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. RP Ausubel, FM (reprint author), Harvard Univ, Sch Med, Dept Genet, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu FU NIH National Research Service Award-Kirschstein Postdoctoral Fellowship [R37-GM48707]; NSF [IOS-0718733, DBI-0500550, MCB-0519898] FX We thank S. Abel for ugt74B1-2; J.L. Celenza for atr1-3, atr4-1/cyp83B1, cyp79B2 cyp79B3, and trp3-1; C.S. Cobbett for cad1-3/pcs1 and cad2-1/gsh1; P.L. Conklin for vtc1-1 and vtc2-1; R. Blum for pcs1-1, pcs2-1, and pcs1-1 pcs2-1; S. C. Somerville for pcs1-2; and Arabidopsis Biological Resource Center for insertion lines. Ph. D. stipend support to N.K.C. comes from NIH National Research Service Award-Kirschstein Postdoctoral Fellowship. Support to A.M.A. and G.J. comes from NSF grants IOS-0718733 and DBI-0500550. Support to F.M.A. comes from NSF grant MCB-0519898 and NIH grant R37-GM48707. NR 59 TC 411 Z9 435 U1 19 U2 138 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 2 PY 2009 VL 323 IS 5910 BP 95 EP 101 DI 10.1126/science.1164627 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 389OL UT WOS:000262104100048 PM 19095898 ER PT S AU Akilov, OE Kosaka, S Hasan, T AF Akilov, Oleg E. Kosaka, Sachiko Hasan, Tayyaba BE Kessel, DH TI Photochemistry-based immune modulation in the treatment of cutaneous leishmaniasis SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE photodynamic therapy; photosensitizer; Leishmania; Th1; immunomodulation ID REGULATORY T-CELLS; PHOTODYNAMIC THERAPY; VISCERAL LEISHMANIASIS; RESISTANCE; INFLAMMATION; MILTEFOSINE; MACROPHAGES; GENERATION; INFECTION; REFUGEE AB The destruction of infectious pathogens by photodynamic therapy (PDT) is an emerging modality. We demonstrated the efficacy of PDT for the management of cutaneous leishmaniasis in our previous studies. However, much remains to be done for the improvement of PDT regimens. The modulation of the immune response by photochemistry is an exciting but under-explored area of PDT research. The goal of this study is to understand the mechanisms of the augmentation of the host immune response after PDT of cutaneous leishmaniasis (CL). We found that PDT with phenoxiazine analogues was capable for induction of Th1 immune response due to stimulation of IL-12 production by dendritic cells. Single PDT treatment facilitated fast healing of the CL lesions due to effective parasite eradication and augmentation of the immune system. Comparative study with different photosensitizers (PS) (porphyrins, pehnoxiazines) demonstrated different immunomodulating properties of PDT depending on chemical class of PS. Knowing the particular profiles and immunomodulating properties of the pertinent PSs allows us to select the optimal PS with regards to both the photodestructive and immunostimulating potential. C1 [Akilov, Oleg E.; Kosaka, Sachiko] Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard Med Sch, Boston, MA 02114 USA. [Akilov, Oleg E.; Kosaka, Sachiko] Harvard Med Sch, Dept Dermatol, Boston, MA 02114 USA. RP Akilov, OE (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Harvard Med Sch, Boston, MA 02114 USA. EM thasan@partners.org FU Department of Defense Medical Free Electron Laser Program [FA9550- 04-1-0079] FX We are grateful to Dr. Mary Ann McDowell (Department of Biological Science, University of Notre Dame, Notre Dame, IN, USA) for providing the L. major strain V1 and strain LV39. Our thanks to Prof. Stanley Brown (Photopharmica, Leeds, UK) for providing us with the PPA904 compound. This work was supported by the Department of Defense Medical Free Electron Laser Program Grant No. FA9550- 04-1-0079 (to T. Hasan). NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73803G DI 10.1117/12.827041 PG 10 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100055 ER PT S AU Dai, TH Tegos, GP Lu, ZS Zhiyentayev, T Huang, LY Franklin, MJ Baer, DG Hamblin, MR AF Dai, Tianhong Tegos, George P. Lu, Zongshun Zhiyentayev, Timur Huang, Liyi Franklin, Michael J. Baer, David G. Hamblin, Michael R. BE Kessel, DH TI Antimicrobial photodynamic therapy in a mouse model of Acinetobacter baumannii burn infection SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Antimicrobial photodynamic therapy; photosensitizer; mouse model; Acinetobacter baumannii; infection ID GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA; MICE; TRANSLOCATION; WOUNDS AB Multi-drug resistant Acinetobacter baumanii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment using traditional antibiotics can be extremely difficult and new antimicrobial approaches are being investigated. One of these antimicrobial alternatives could be the combination of non-toxic photosensitizers (PS) and visible light known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by covalent conjugation chlorin(e6) to polyethylenimine followed by illumination of the burn surface with red light. Application of 10 8 A. baumannii cells to the surface of 10-second burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted on average 22 days characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after applying bacteria gave over three logs of loss of bacterial luminescence in a light exposure dependent manner, while PDT carried out on day 1 and day 2 gave approximately a 1.7-log reduction. Application of PS dissolved in 10% or 20% DMSO without light gave only modest reduction in bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multi-drug resistant localized A. baumannii infections. C1 [Dai, Tianhong; Tegos, George P.; Lu, Zongshun; Zhiyentayev, Timur; Huang, Liyi; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Dai, Tianhong; Tegos, George P.; Huang, Liyi; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA USA. [Lu, Zongshun] Tianjin Med Univ Gen Hosp, Dept Gastroenterol, Tianjin, Peoples R China. [Zhiyentayev, Timur] M Lomonosov Moscow State Univ, Dept Chem, Moscow, Russia. [Huang, Liyi] Guangxi Med Univ, Dept Infect Dis, First Affiliated Coll Hosp, Nanning, Peoples R China. [Franklin, Michael J.] Montana State Univ, Dept Microbiol, Bozeman, MT USA. [Baer, David G.] US Army Inst Surg Res, Ft Sam Houston, TX USA. [Hamblin, Michael R.] Harvard Div Hlth Sci & Technol, Cambridge, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 FU US Air Force MFEL [FA9550-04-1-0079]; NIH [AI050875] FX This work was supported by the US Air Force MFEL program (contract FA9550-04-1-0079) and the NIH (grant AI050875).. We are grateful to Victoria Hamrahi for assistance with bacterial identification and to Christopher H. Contag, Tayyaba Hasan, Albert T. McManus for helpful advice and discussion. NR 24 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 738037 DI 10.1117/12.823065 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100049 ER PT S AU Lee, S Galbally-Kinney, K Hinds, MF O'Hara, JA Pogue, BW Liang, A Hasan, T Davis, SJ AF Lee, S. Galbally-Kinney, K. Hinds, M. F. O'Hara, J. A. Pogue, B. W. Liang, A. Hasan, T. Davis, S. J. BE Kessel, DH TI A singlet oxygen monitor as an in vivo photodynamic therapy dosimeter SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Photodynamic therapy; singlet oxygen; dosimetry ID LUMINESCENCE; TESTS AB In this paper we describe the development and testing of instruments to measure singlet molecular oxygen produced by the photodynamic process. Singlet oxygen is an active species in photodynamic therapy, and we are developing two instruments for PDT researchers with the goal of a real-time dosimeter for singlet oxygen. We discuss both an ultra-sensitive point sensor, and an imaging system that provides simultaneous 2D maps of the photosensitizer fluorescence and the singlet oxygen emission. Results of in vitro tests to characterize the sensors and preliminary in vivo results are presented. C1 [Lee, S.; Galbally-Kinney, K.; Hinds, M. F.; Davis, S. J.] Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. [O'Hara, J. A.; Pogue, B. W.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. [Liang, A.; Hasan, T.] Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM lee@psicorp.com FU National Cancer Institute of the National Institutes of Health under NIH SBIR [4R44CA128364-02, 2R44CA119486-02] FX This work was supported by the National Cancer Institute of the National Institutes of Health under NIH SBIR Grant No. 4R44CA128364-02 and 2R44CA119486-02. We appreciate D. H. Vu, A. Liang and J. Polex for their technical assistance and Dr. J. A. O'Hara for her valuable discussions and animal study. NR 20 TC 2 Z9 3 U1 1 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 738046 DI 10.1117/12.823030 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100071 ER PT S AU Mroz, P Huang, YY Janjua, S Zhiyentayev, T Ruzie, C Borbas, KE Fan, DZ Krayer, M Balasubramanian, T Yang, EK Kee, HL Holten, D Lindsey, JS Hamblin, MR AF Mroz, Pawel Huang, Ying-Ying Janjua, Sahar Zhiyentayev, Timur Ruzie, Christian Borbas, K. Eszter Fan, Dazhong Krayer, Michael Balasubramanian, Thiagarajan Yang, Eun Kyung Kee, Hooi Ling Holten, Dewey Lindsey, Jonathan S. Hamblin, Michael R. BE Kessel, DH TI New stable synthetic bacteriochlorins for photodynamic therapy of melanoma SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE melanoma; photodynamic therapy; multidrug resistance; melanosomes; bacteriochlorins ID B16 PIGMENTED MELANOMA; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA; CANCER-CELLS; MTT ASSAYS; IN-VITRO; PHOTOSENSITIZERS; MELANOGENESIS; MELANOSOMES; METASTASES AB Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and has afforded highly encouraging results in skin cancers such as basal cell carcinoma. However, pigmented melanoma remains a notable exception from the range of tumors treated by PDT largely due to the fact that melanin has high absorption of light in wavelength regions where most clinically approved photosensitizers (PS) absorb light (600-690 nm). Moreover, melanoma cells sequester exogenous molecules including photosensitizers inside melanosomes. The aforementioned drawbacks of the clinically used PS have motivated us to search for new classes of PS with improved spectral properties, such as bacteriochlorins (BC) to be used in PDT of melanoma. To overcome the PDT-resistance mechanisms of melanoma, particularly the high optical absorption of melanin, three near-infrared (NIR) absorbing synthetic stable BC were used in PDT treatment of melanoma. Dose and fluence dependent cell killing, intracellular localization (particularly in melanosomes), and correlation between the melanin level and cell death were examined. Intracellular melanosomes are ruptured after illumination as shown by electron microscopy. The best in vitro performing BC were tested upon delivery in micellar nanoparticles against a mouse pigmented melanoma. Two of the BC were effective at significantly lower concentrations (<0.5 mu M) than common photosensitizers in present use. C1 [Mroz, Pawel; Huang, Ying-Ying; Janjua, Sahar; Zhiyentayev, Timur; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA USA. [Janjua, Sahar] Aga Khan Med Coll, Karachi, Pakistan. [Zhiyentayev, Timur] M Lomonosov Moscow State Univ, Dept Chem, Moscow, Russia. [Ruzie, Christian; Borbas, K. Eszter; Fan, Dazhong; Krayer, Michael; Lindsey, Jonathan S.] North Carolina State Univ, Dept Chem, Raleigh, NC USA. [Balasubramanian, Thiagarajan] NIRvana Pharmaceut Inc, Raleigh, NC USA. [Yang, Eun Kyung; Kee, Hooi Ling; Holten, Dewey] Washington Univ, Dept Chem, St Louis, MO USA. [Hamblin, Michael R.] Harvard Div Hlth Sci & Technol, Cambridge, MA USA. RP Mroz, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Lindsey, Jonathan/J-7761-2012; OI Hamblin, Michael/0000-0001-6431-4605 FU NIH [R01GM36238, R01AI050875]; BurroughsWellcome fellowship; National Institute of Allergy and Infectious Diseases to NIRvana Pharmaceuticals [R41AI072854] FX This work was supported by grants from the NIH (R01GM36238 to J.S.L. and R01AI050875 to M.R.H.), a BurroughsWellcome fellowship to M.K., and the Jimmy V.NCSU Cancer Therapeutics Training Program. P.M. and T.B. were supported by a grant (R41AI072854) from the National Institute of Allergy and Infectious Diseases to NIRvana Pharmaceuticals, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIAID or the NIH. We are grateful to Pharmacyclics, Inc. for the gift of LuTex, and to QLT, Inc. for the gift of Photofrin. NR 61 TC 1 Z9 1 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73802S DI 10.1117/12.823060 PG 14 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100041 ER PT S AU Mroz, P Hamblin, MR AF Mroz, Pawel Hamblin, Michael R. BE Kessel, DH TI Combination of PDT and a DNA demethylating agent produces anti-tumor immune response in a mouse tumor model SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE tumor antigens; photodynamic therapy; MAGE; epigenetics; 5-aza-deoxycytidine ID HISTONE DEACETYLASE INHIBITORS; HEAT-SHOCK PROTEINS; PHOTODYNAMIC THERAPY; METHYLTRANSFERASE INHIBITORS; MELANOMA-CELLS; CANCER-THERAPY; IN-VIVO; EXPRESSION; ANTIGEN; METHYLATION AB Epigenetic mechanisms, which involve DNA methylation and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. However, these changes must be actively maintained after each cell division rendering them a promising target for pharmacologic inhibition. DNA methyltransferase inhibitors like 5-aza-deoxycytidine (5-aza-dC) induce and/or up-regulate the expression of MAGE-type antigens in human and mice cancer cells. Photodynamic therapy (PDT) has been shown to be an effective locally ablative anti-cancer treatment that has the additional advantage of stimulating tumor-directed immune response. We studied the effects of a new therapy that combined the demethylating agent 5-aza-dC with PDT in the breast cancer model 4T1 syngenic to immunocompetent BALB/c mice. PDT was used as a locally ablating tumor treatment that is capable of eliciting strong and tumor directed immune response while 5-aza-dC pretreatment was used promote de novo induction of the expression of P1A. protein. This is the mouse homolog of human MAGE family antigens and is reported to function as a tumor rejection antigen in certain mouse tumors. This strategy led to an increase in PDT-mediated immune response and better treatment outcome. These results strongly suggest that the MAGE family antigens are important target for PDT mediated immune response but that their expression can be silenced by epigenetic mechanisms. Therefore the possibility that PDT can be combined with epigenetic strategies to elicit anti-tumor immunity in MAGE-positive tumor models is highly clinically significant and should be studied in detail. C1 [Mroz, Pawel; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Mroz, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. OI Hamblin, Michael/0000-0001-6431-4605 NR 41 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73800H DI 10.1117/12.823005 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100007 ER PT S AU Mroz, P Castano, AP Wu, MX Kung, AL Hamblin, MR AF Mroz, Pawel Castano, Ana P. Wu, Mei X. Kung, Andrew L. Hamblin, Michael R. BE Kessel, DH TI Anti-tumor immune response after photodynamic therapy SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE photodynamic therapy; colon cancer; tumor-associated antigen; cytotoxic T cells; regulatory T-cells; low dose cyclophosphamide ID TUMOR-ASSOCIATED ANTIGEN; LOW-DOSE CYCLOPHOSPHAMIDE; RECOMBINANT VACCINIA; T-CELLS; MODEL; IMMUNOTHERAPY; TOLERANCE; CANCER AB Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naive T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26. CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26. CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26. CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26. CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26. CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26. CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp3+) and potentiate immune response after PDT in the case of tumors that express self-antigens. These data suggest that PDT alone will stimulate a strong immune response when tumors express a robust antigen, and in cases where tumors express a self-antigen, T-reg depletion can unmask the immune response after PDT. C1 [Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Hamblin, Michael R.] Harvard Med Sch, Dept Dermatol, Boston, MA USA. [Wu, Mei X.; Hamblin, Michael R.] Harvard Div Hlth Sci & Technol, Cambridge, MA USA. [Kung, Andrew L.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM Hamblin@helix.mgh.harvard.edu OI Kung, Andrew/0000-0002-9091-488X; Hamblin, Michael/0000-0001-6431-4605 FU US NIH National Cancer Institute [R01CA/ AI838801, R01AI050875]; Department of Defense CDMRP Breast Cancer Research Grant [W81XWH- 041- 0676] FX This work was supported by the US NIH National Cancer Institute ( grants R01CA/ AI838801 and R01AI050875 to MRH). Ana P Castano was supported by Department of Defense CDMRP Breast Cancer Research Grant ( W81XWH- 041- 0676). We are grateful to QLT Inc ( Vancouver, Canada) for the generous gift of BPD. NR 20 TC 0 Z9 0 U1 1 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73800F DI 10.1117/12.822994 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100006 ER PT S AU O'Hara, J Samkoe, KS Chen, A Hoopes, PJ Rizvi, I Hasan, T Pogue, BW AF O'Hara, Julia Samkoe, Kimberley S. Chen, Alina Hoopes, P. Jack Rizvi, Imran Hasan, Tayyaba Pogue, Brian W. BE Kessel, DH TI Uptake of Verteporfin by Orthotopic Xenograft Pancreas Models with Different Levels of Aggression SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Verteporfin; photodynamic therapy; xenograft orthotopic pancreas tumors; dosimetry; contrast; ASPC-1; fluorescence; PANC-1 ID GUIDED PHOTODYNAMIC THERAPY; TUMOR AB Pancreatic cancer is an aggressive disease with a poor prognosis, usually treated with chemoradiation therapy. Interstitial photodynamic therapy is a potentially effective adjuvant treatment that is under development. In the current study, two orthotopic pancreatic cancer models (AsPC-1 and Panc-1), have been characterized with respect to growth rates, morphology and liposomal drug (Verteporfin) uptake and distribution in SCID mice. Fluorescence of Verteporfin was measured in liver and tumor in vivo using a PDT fluorescence dosimeter with measurements taken before and up to one hour after tail vein injection. Fluorescence reached a plateau by about 15 minutes and did not decrease over the first hour. At time points from 15 minutes to 24 hrs, the internal organs (kidney, spleen, pancreas, tumor, muscle, lung, liver, and skin were excised and scanned on a Typhoon imager. The ratio of fluorescence in tumor versus normal tissues was analyzed with image processing, calculated at each time point and compared to in vivo results. Tissue distribution of Verteporfin in relation to functional vasculature marked by DiOc7 was carried out on frozen sections. Final analysis will result in determination of the ideal time point to administer light to achieve maximum tumor destruction while preserving normal tissue. C1 [O'Hara, Julia; Samkoe, Kimberley S.; Chen, Alina; Rizvi, Imran; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. [Hoopes, P. Jack] Dartmouth Med Sch, Dept Surg, Lebanon, NH 03756 USA. [Rizvi, Imran; Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP O'Hara, J (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. FU NIH [P01CA84203] FX This work has been funded by NIH grant P01CA84203. NR 9 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73805F DI 10.1117/12.823214 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100092 ER PT S AU Rai, P Chang, SK Mai, ZM Neuman, D Hasan, T AF Rai, Prakash Chang, Sung K. Mai, Zhiming Neuman, Daniel Hasan, Tayyaba BE Kessel, DH TI Nanotechnology-based combination therapy improves treatment response in cancer models SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Photodynamic Therapy; nanocell; nanoparticles; liposomes; anti-angiogenic therapy; pancreatic cancer ID ENDOTHELIAL GROWTH-FACTOR; MEDIATED PHOTODYNAMIC THERAPY; PANCREATIC-CANCER; TUMOR-CELLS; VEGF; NANOPARTICLES; ANGIOGENESIS; BEVACIZUMAB; EXPRESSION; CARCINOMA AB Pancreatic cancer (PanCa) has a poor prognosis with a 5-year survival rate of only 5%. Photodynamic therapy (PDT) has shown promising results in treating PanCa. Mechanism-based combinations with PDT have enhanced treatment outcome. Agents tested with PDT include Avastin, an antibody against vascular endothelial growth factor (VEGF) which is approved for treating various cancers. Simultaneous delivery of drugs in nano-constructs could improve the treatment response of mechanism based combination therapies. Here, we investigate the effect of neutralizing VEGF using nanotechnology for the delivery of Avastin in combination with PDT. For this we used a construct called "nanocells" in which the photosensitizer was trapped inside polymer nanoparticles and these, with Avastin, were then encapsulated inside liposomes. In vitro, nanocells containing Avastin (NCA) significantly enhanced cytotoxicity in PanCa cells. NCA based PDT also significantly improved treatment response in mice that were orthotopically implanted with PanCa. Avastin delivered extracellularly in combination with PDT did not show any improvement. Here we propose a new paradigm for Avastin-based therapy by combining intracellular delivery of the antibody and PDT using nanotechnology for treating PanCa. C1 [Rai, Prakash; Chang, Sung K.; Mai, Zhiming; Neuman, Daniel; Hasan, Tayyaba] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Rai, P (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM thasan@partners.org NR 51 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73800W DI 10.1117/12.828402 PG 11 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100014 ER PT S AU Sallum, UW Zheng, X Verma, S Hasan, T AF Sallum, Ulysses W. Zheng, Xiang Verma, Sarika Hasan, Tayyaba BE Kessel, DH TI Exploiting bacterial drug resistance: a single construct for the diagnosis and treatment of drug resistant infections SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ ID SOFT-TISSUE INFECTIONS; BETA-LACTAMASES; SKIN AB beta-lactamase enzyme-activated photosensitizer (beta-LEAP). We aim to exploit drug resistance mechanisms to selectively release photosensitizers (PSs) for a specific photodynamic antimicrobial effect and reduced host tissue damage. Consequently, the fluorescence emission intensity of the PSs increases and allows for the detection of enzyme activity. In this work we sought to evaluate beta-LEAP for use as a sensitive molecular probe. We have reported the enzyme specific antibacterial action of beta-LEAP. Here we report the use of beta-LEAP for the rapid functional definition of a beta-lactamase. C1 [Sallum, Ulysses W.; Zheng, Xiang; Verma, Sarika; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Sallum, UW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73806R DI 10.1117/12.828202 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100115 ER PT S AU Samkoe, KS Davis, SC Srinivasan, S O'Hara, JA Hasan, T Pogue, BW AF Samkoe, Kimberley S. Davis, Scott C. Srinivasan, Subhadra O'Hara, Julia A. Hasan, Tayyaba Pogue, Brian W. BE Kessel, DH TI A Study of MRI-Guided Diffuse Fluorescence Molecular Tomography for Monitoring PDT Effects in Pancreas Cancer SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE magnetic resonance imaging; diffuse fluorescence tomography; xenograft orthotopic pancreas tumor; verteporfin photodynamic therapy ID PHOTODYNAMIC THERAPY; GEMCITABINE AB Over the last several decades little progress has been made in the therapy and treatment monitoring of pancreas adenocarcinoma, a devastating and aggressive form of cancer that has a 5-year patient survival rate of 3%. Currently, investigations for the use of interstitial Verteporfin photodynamic therapy (PDT) are being undertaken in both orthotopic xenograft mouse models and in human clinical trials. In the mouse models, magnetic resonance (MR) imaging has been used as a measure of surrogate response to Verteporfin PDT; however, MR imaging alone lacks the molecular information required to assess the metabolic function and growth rates of the tumor immediately after treatment. We propose the implementation of MR-guided fluorescence tomography in conjunction with a fluorescently labeled (IR-Dye 800 CW, LI-COR) epidermal growth factor (EGF) as a molecular measure of surrogate response. To demonstrate the effectiveness of MR-guided diffuse fluorescence tomography for molecular imaging, we have used the AsPC-1 (+EGFR) human pancreatic adenocarcinoma in an orthotopic mouse model. EGF IRDye 800CW was injected 48 hours prior to imaging. MR image sequences were collected simultaneously with the fluorescence data using a MR-coupled diffuse optical tomography system. Image reconstruction was performed multiple times with varying abdominal organ segmentation in order to obtain a optimal tomographic image. It is shown that diffuse fluorescence tomography of the orthotopic pancreas model is feasible, with consideration of confounding fluorescence signals from the multiple organs and tissues surrounding the pancreas. MR-guided diffuse fluorescence tomography will be used to monitor EGF response after photodynamic therapy. Additionally, it provide the opportunity to individualize subsequent therapies based on response to PDT as well as to evaluate the success of combination therapies, such as PDT with chemotherapy, antibody therapy or even radiation. C1 [Samkoe, Kimberley S.; Davis, Scott C.; Srinivasan, Subhadra; O'Hara, Julia A.; Pogue, Brian W.] Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. [Hasan, Tayyaba; Pogue, Brian W.] Massachusetts Gen Hosp, Wellman Ctr Photomedicine, Boston, MA 02114 USA. RP Samkoe, KS (reprint author), Dartmouth Coll, Thayer Sch Engn, 8000 Cummings Hall, Hanover, NH 03755 USA. FU NIH [P01 CA84203] FX This work has been funded by NIH grant P01 CA84203. NR 12 TC 0 Z9 0 U1 1 U2 6 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73803M DI 10.1117/12.823079 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100059 ER PT S AU Spring, BQ Celli, JP Evans, CL Zhong, W Rizvi, I Mai, ZM Mertz, J Yun, SH Hasan, T AF Spring, Bryan Q. Celli, Jonathan P. Evans, Conor L. Zhong, Wei Rizvi, Imran Mai, Zhiming Mertz, Jerome Yun, Seok H. Hasan, Tayyaba BE Kessel, DH TI Intravital, fiber-optic fluorescence imaging for monitoring ovarian carcinoma progression & treatment response SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Ovarian Cancer; Fluorescence Microendoscopy; Photodynamic Therapy; Treatment Monitoring ID STRUCTURED ILLUMINATION; EPITHELIAL ACINI; CANCER; MICROSCOPE; GROWTH; MODEL AB Our laboratory has constructed a custom fluorescence microendoscope for detecting and monitoring tumor nodules in a mouse model of metastatic ovarian carcinoma (OVCA). The microendoscope is being applied for tumor recognition and for quantifying tumor burden reduction following photodynamic therapy (PDT). Benzoporphyrin derivative monoacid ring A (BPD-MA), a photosensitizing agent for PDT, is administered to the mice and imaged with the microendoscope prior to PDT. BPD-MA fluorescence is a convenient means for locating tumor sites and quantifying tumor burden (despite the fact that BPD-MA is a non-targeted contrast agent). The miniature, flexible microendoscope probe is delivered via a 14-gauge catheter for imaging metastases along the outer surfaces of the internal organs and the inner walls of the peritoneal cavity. The minimal invasiveness of this approach facilitates frequent imaging of the mice in order to monitor cancer progression and treatment response. We present promising data for intravital imaging of treatment response following PDT and new developments in the microendoscope instrumentation for improved image quality. C1 [Spring, Bryan Q.; Celli, Jonathan P.; Evans, Conor L.; Zhong, Wei; Rizvi, Imran; Mai, Zhiming; Yun, Seok H.; Hasan, Tayyaba] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. [Mertz, Jerome] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. RP Spring, BQ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. EM bspring@partners.org NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73800L DI 10.1117/12.828206 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100008 ER PT S AU Upadya, MH Tegos, G Hamblin, M Kishen, A AF Upadya, M. H. Tegos, G. Hamblin, M. Kishen, A. BE Kessel, DH TI Influence of Bacterial Interactions on the Susceptibility to Photodynamic Inactivation SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Enterococcus faecalis; biofilm; photodynamic therapy; efflux pump inhibitor ID MULTIDRUG-RESISTANCE; SODIUM-HYPOCHLORITE; ENTEROCOCCUS-FAECALIS; DENTIN AB Photodynamic therapy has emerged as a possible supplement to the existing protocols for endodontic disinfection. Microbes are known to gain significant ecological advantage when they survive as coaggregates and biofilms in an infected tissue. Such microbial coaggregates and biofilms have been confirmed to play a key role in the pathogenicity of many infections. So far, not many studies have correlated the efficacy of antimicrobial photodynamic inactivation (APDI) to the different modes of bacterial growth. This study aims to evaluate the APDI of 3 strains of Enterococcus faecalis in planktonic phase, in a co-aggregated suspension and in a 4-day old biofilm. The results showed that the biofilm mode of growth offered the greatest resistance to APDI and the inclusion of an efflux pump inhibitor significantly increased the APDI of biofilm bacteria. From this study, we conclude that APDI of bacteria in biofilms is the most challenging and that the use of bacterial efflux pump inhibitors enhances its photodynamic anti-biofilm efficacy. C1 [Upadya, M. H.; Kishen, A.] Natl Univ Singapore, Fac Dent, Dept Restorat Dent, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. [Tegos, G.; Hamblin, M.] Massachusetts Gen Hosp, Wellman Ctr Photomedicine, Boston, MA 02114 USA. RP Upadya, MH (reprint author), Natl Univ Singapore, Fac Dent, Dept Restorat Dent, 5 Lower Kent Ridge Rd, Singapore 119074, Singapore. RI Upadya, Megha/N-2235-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU Faculty of dentistry (National University of Singapore) strategic research initiative: Dental Biophotonics and Biomaterials Programme (DBBP) [C-221-000-304- 001]; National University of Singapore ARF [R-224-000-029-112] FX This study is supported by the Faculty of dentistry (National University of Singapore) strategic research initiative: Dental Biophotonics and Biomaterials Programme (DBBP): C-221-000-304- 001 and the National University of Singapore ARF Grant number R-224-000-029-112. The authors are grateful to Dr. Eleutherios Mylonakis, Division of Infectious Diseases, Massachusetts General Hospital, Boston MA. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73803D DI 10.1117/12.822851 PG 9 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100052 ER PT S AU Verma, S Sallum, U Zheng, X Hasan, T AF Verma, Sarika Sallum, Ulysses Zheng, Xiang Hasan, Tayyaba BE Kessel, DH TI Strategies for targeted antimicrobial photodynamic therapy SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE photosensitizers; molecular modifications; targeted PDT ID ENDOTHELIAL GROWTH-FACTOR; CANCER; EFFICACY AB The photophysics and mechanisms of cell killing by photodynamic therapy (PDT) have been extensively studied in recent years, and PDT has received regulatory approval for the treatment of a number of diseases worldwide. As the application of this treatment modality expands with regard to both anatomical sites and diseases, it is important to develop strategies for enhancing PDT outcomes. Our group has focused on developing targeting strategies to enhance PDT for both cancerous as well as anti-microbial applications. In this article, we will discuss photosensitizer modification and conjugation strategies for targeted antimicrobial photodynamic therapy. C1 [Verma, Sarika; Sallum, Ulysses; Zheng, Xiang; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Verma, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73803J DI 10.1117/12.828203 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100058 ER PT S AU Zheng, X Verma, S Sallum, UW Hasan, T AF Zheng, Xiang Verma, Sarika Sallum, Ulysses W. Hasan, Tayyaba BE Kessel, DH TI Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT SO 12TH WORLD CONGRESS OF THE INTERNATIONAL PHOTODYNAMIC ASSOCIATION: PHOTODYNAMIC THERAPY: BACK TO THE FUTURE SE Proceedings of SPIE LA English DT Proceedings Paper CT 12th World Congress of the International-Photodynamic-Association (IPA) on Photodynamic Therapy - Back to the Future CY JUN 11-15, 2009 CL Seattle, WA SP Int Photodynam Assoc (IPA), SPIE, AF Off Sci Res, Axcan Pharma Inc, Covidien Imaging Solut, Ondine Biopharma Corp, Photocure ASA, QinetiQ N Amer, Wellman Ctr PhotoMed, Wayne State Univ DE Photodynamic therapy; photosensitizer; beta-lactamase; methicillin-resistant Staphylococcus aureus ID PHOTODYNAMIC THERAPY; STANDARD; YIELD; SKIN; RED AB Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed. C1 [Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Zheng, X (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, 40 Blossom St, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7660-9 J9 PROC SPIE PY 2009 VL 7380 AR 73802H DI 10.1117/12.824500 PG 8 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BDM00 UT WOS:000313709100037 ER PT S AU Heering, AH Bohn, P Clough, A Hazen, E Rohlf, J Los, S Freeman, J Cascio, E Musienko, Y Piemonte, C AF Heering, A. H. Bohn, P. Clough, A. Hazen, E. Rohlf, J. Los, S. Freeman, J. Cascio, E. Musienko, Y. Piemonte, C. GP IEEE TI Radiation Damage Studies on SiPMs for Calorimetry at the Super LHC SO 2008 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (2008 NSS/MIC), VOLS 1-9 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2008 CL Dresden, GERMANY SP IEEE Nucl & Plasma Sci Soc, Natl Nucl Secur Adm, US Def Threat Reduct Agcy, ICx Radiat GmbH, ORTEC, Hamamatsu, European Phys Journal, Hilger Crystals, SAFC Hitech, ATOMTEX, Canberra, SensL, ASP, Brookhaven Natl Lab, CEA, CERN, DESY, Forschungszentrum Julich GmbH, Int Atom Energy Agcy, Lawrence Livermore Natl Lab AB A typical scintillating the sampling calorimeter consists of multiple layers of scintillators coupled to wavelength shifting fibers viewed by a suitable photo-detector. Long clear fibers are used to connect the tiles to the readout modules. We have investigated the use of silicon photomultipliers (SiPMs) at the Super Lagre Hadron Collider (SLHC). Because radiation hardness is the main concern, two sets of radiation data were taken using a 212 MeV proton beam at Massachusetts General Hospital. In the first data set we radiated up to a dose of 3x10(10) protons per cm(2) using diodes from three different manufactures (i.e., FBK, CPTA and Hamamatsu). At a dose of 3x10(10) protons per cm(2) only small effects of PDE loss were detected due to very high dark count always occupying one or more cells in a multi-cell SiPM. A second set of data up to 10(13) protons per cm(2) using very high pixel density MAPDs with upto 40,000 cells per mm(2). After each small radiation dose multiple scope traces were taken to look at the PDE and dark count of the devices. The increase in dark count due to the radiation was compared to the DC leakage current. Also a comparison was made between multi-cell and single-cell samples of the FBK-IRST diodes. C1 [Heering, A. H.; Bohn, P.; Clough, A.; Hazen, E.; Rohlf, J.] Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. [Los, S.; Freeman, J.] Fermilab Natl Accelerator Lab, Batavia, IL USA. [Cascio, E.] Massachusetts Gen Hosp, Francis H Burr Therapy Ctr, Boston, MA USA. [Musienko, Y.] Northeastern Univ, Dept Phys, Boston, MA USA. [Piemonte, C.] Fondazione Bruno Kessler, Trenton, NJ USA. RP Heering, AH (reprint author), Boston Univ, Dept Phys, 590 Commonwealth Ave, Boston, MA 02215 USA. FU U.S. National Science Foundation FX Manuscript received November 14, 2008. We acknowledge support of the U.S. National Science Foundation NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-2714-7 J9 IEEE NUCL SCI CONF R PY 2009 BP 798 EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BKN17 UT WOS:000268656000176 ER PT B AU Zollei, L Wells, WM AF Zoellei, Lilla Wells, William M. GP IEEE TI ON THE OPTIMALITY OF MUTUAL INFORMATION AS AN IMAGE REGISTRATION OBJECTIVE FUNCTION SO 2009 16TH IEEE INTERNATIONAL CONFERENCE ON IMAGE PROCESSING, VOLS 1-6 LA English DT Proceedings Paper CT 16th IEEE International Conference on Image Processing CY NOV 07-10, 2009 CL Cairo, EGYPT SP IEEE DE mutual information; optimum; pair-wise registration AB We model images and the anatomy that they are derived from as stationary and jointly ergodic random processes. Using an empirically-observed property of anatomy, and data processing inequality arguments, we arrive at optimality criteria for mutual information in the ensemble domain. Using ergodicity, we transfer the criteria to single pairs of images in the spatial domain, where it applies to the popular mutual information-based registration approach that is used in practice. C1 [Zoellei, Lilla] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Wells, William M.] Brigham & Womens Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02115 USA. RP Zollei, L (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. FU NAC; NCRR [NCRR P41RR13218, NCRR P41-RR14075, NIH R01 RR16594-01A1]; NCRR BIRN Morphometric Project [BIRN002, U24 RR021382]; NIBIB [R01 EB001550, R01EB006758]; NINDS as well as the MIND Institute [R01 NS052585-01]; NIH through the NIH Roadmap for Medical Research [U54 EB005149] FX Support for this research was provided in part by the NAC, NCRR grants (NCRR P41RR13218, NCRR P41-RR14075, NIH R01 RR16594-01A1 and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the NIBIB (R01 EB001550, R01EB006758), the NINDS (R01 NS052585-01) as well as the MIND Institute, and is part of the NAMIC, funded by the NIH through the NIH Roadmap for Medical Research, Grant U54 EB005149. NR 12 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5653-6 PY 2009 BP 189 EP + DI 10.1109/ICIP.2009.5414178 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BQA01 UT WOS:000280464300048 ER PT B AU Kelly, SK Shire, DB Doyle, P Gingerich, MD Drohan, WA Rizzo, JF Theogarajan, LS Cogan, SF Chen, JH Wyatt, JL AF Kelly, Shawn K. Shire, Douglas B. Doyle, Patrick Gingerich, Marcus D. Drohan, William A. Rizzo, Joseph F., III Theogarajan, Luke S. Cogan, Stuart F. Chen, Jinghua Wyatt, John L. GP IEEE TI The Boston Retinal Prosthesis A 15-Channel Hermetic Wireless Neural Stimulator SO 2009 2ND INTERNATIONAL SYMPOSIUM ON APPLIED SCIENCES IN BIOMEDICAL AND COMMUNICATION TECHNOLOGIES (ISABEL 2009) LA English DT Proceedings Paper CT 2nd International Symposium on Applied Sciences in Biomedical and Communication Technologies CY NOV 24-27, 2009 CL Bratislava, SLOVAKIA DE biomedical engineering; biomedical electrodes; bioelectric potentials; neuromuscular stimulation; iridium; integrated circuit design; telemetry ID CHARGE-INJECTION LIMITS; IRIDIUM OXIDE AIROF; ELECTRICAL-STIMULATION; DEGENERATION; IMPLANTATION; ELECTRODES; RESPONSES AB A miniaturized, hermetically-encased, wirelessly-operated retinal prosthesis has been developed for pre-clinical studies in Yucatan minipig animal models. The prosthesis attaches conformally to the outside of the eye and drives a microfabricated thin-film polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially-designed ab externo surgical technique that uses the retina to hold the array in place while leaving the bulk of the prosthesis outside the eye. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete circuit components. Feedthroughs from the case connect to secondary power- and data-receiving coils. In addition, long-term in vitro pulse testing was performed on the electrodes to ensure that their lifetime would match that of the hermetic case. The final assembly was tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a custom graphical user interface. Operation of the retinal implant has been verified in vivo in two pigs for up to five and a half months by measuring stimulus artifact on the eye surface using a contact lens electrode. C1 [Kelly, Shawn K.; Shire, Douglas B.; Doyle, Patrick; Gingerich, Marcus D.; Drohan, William A.; Rizzo, Joseph F., III] Boston VA Healthcare Syst, Boston, MA 02130 USA. [Chen, Jinghua] Massachusetts Eye & Ear Infirm, Boston, MA USA. [Theogarajan, Luke S.] Univ Calif Santa Barbara, Santa Barbara, CA USA. [Cogan, Stuart F.] EIC Labs, Norwood, MA USA. [Wyatt, John L.] MIT, Cambridge, MA USA. RP Kelly, SK (reprint author), Boston VA Healthcare Syst, Boston, MA 02130 USA. EM skkelly@alum.mit.edu FU Boston VA Center for Innovative Visual Rehabilitation, NIH [EY016674-01]; NSF [IIS-0515134]; Catalyst Foundation; MOSIS Service FX This work was supported in part by the Boston VA Center for Innovative Visual Rehabilitation, NIH (EY016674-01) , NSF (IIS-0515134), the Catalyst Foundation, and the MOSIS Service NR 21 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4640-7 PY 2009 BP 151 EP + PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Electrical & Electronic; Telecommunications SC Computer Science; Engineering; Telecommunications GA BOU33 UT WOS:000277624100030 ER PT B AU Chen, Z Brown, EN Barbieri, R AF Chen, Zhe Brown, Emery N. Barbieri, Riccardo GP IEEE TI A Unified Point Process Framework for Assessing Heartbeat Dynamics and Cardiovascular Control SO 2009 35TH ANNUAL NORTHEAST BIOENGINEERING CONFERENCE LA English DT Proceedings Paper CT 35th Annual Northeast Bioengineering Conference CY APR 03-05, 2009 CL Cambridge, MA AB We present a unified probabilistic point process framework to estimate and monitor the instantaneous heartbeat dynamics as related to specific cardiovascular control mechanisms and hemodynamics. Assessment of the model's statistics is established through the Wiener-Volterra theory and a multivariate autoregressive (AR) structure. A variety of instantaneous cardiovascular metrics, such as heart rate (HR), heart rate variability (HRV), respiratory sinus arrhythmia (RSA), and baroreceptor-cardiac reflex (baroreflex), can be rigorously derived within a parametric framework and instantaneously updated with an adaptive algorithm. Nonlinearity metrics, as well as the bispectrum of heartbeat intervals, can also be derived. We have applied the proposed point process framework to a number of recordings under different experimental protocols. Results reveal interesting dynamic trends across different posture/pharmacological/age/heart disease conditions, pointing at our mathematical approach as a promising monitoring tool for an accurate, noninvasive assessment of a large spectrum of cardiovascular diseases and disorders, including hypertension and congestive heart disease. C1 [Chen, Zhe; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, MIT, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. EM zhechen@neurostat.mgh.harvard.edu; brown@neurostat.mgh.harvard.edu; barbieri@neurostat.mgh.harvard.edu NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4362-8 PY 2009 BP 105 EP 106 PG 2 WC Engineering, Biomedical SC Engineering GA BKP77 UT WOS:000268886300049 ER PT S AU Kelly, SK Shire, DB Chen, JH Doyle, P Gingerich, MD Drohan, WA Theogarajan, LS Cogan, SF Wyatt, JL Rizzo, JF AF Kelly, Shawn K. Shire, Douglas B. Chen, Jinghua Doyle, Patrick Gingerich, Marcus D. Drohan, William A. Theogarajan, Luke S. Cogan, Stuart F. Wyatt, John L. Rizzo, Joseph F., III GP IEEE TI Realization of a 15-Channel, Hermetically-Encased Wireless Subretinal Prosthesis for the Blind SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID CHARGE-INJECTION LIMITS; IRIDIUM OXIDE AIROF; ELECTRICAL-STIMULATION; HUMAN RETINA; DEGENERATION; IMPLANTATION; ELECTRODES; RESPONSES AB A miniaturized, hermetically-encased, wirelessly-operated retinal prosthesis has been developed for implantation and pre-clinical studies in Yucatan mini-pig animal models. The prosthesis conforms to the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially-designed ab externo surgical technique that affixes the bulk of the prosthesis to the surface of the sclera. The implanted device includes a hermetic titanium case containing a 15-channel stimulator chip and discrete power supply components. Feedthroughs from the case connect to secondary power- and data-receiving coils. In addition, long-term in vitro pulse testing was performed on the electrodes to ensure their stability for the long lifetime of the hermetic case. The final assembly was tested in vitro to verify wireless operation of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation pulse strength, duration and frequency were programmed wirelessly using a custom graphical user interface. Operation of the retinal implant has been verified in vivo in one pig for more than three months by measuring stimulus artifacts on the eye surface using a contact lens electrode. C1 [Kelly, Shawn K.; Drohan, William A.] VABHS, MIT, Cambridge, MA 02139 USA. [Shire, Douglas B.; Gingerich, Marcus D.] Cornell Univ, VABHS, Ithaca, NY 14853 USA. [Chen, Jinghua] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Doyle, Patrick] MIT, Boston Res Inst, Cambridge, MA 02139 USA. [Theogarajan, Luke S.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Cogan, Stuart F.] EIC Labs Inc, Norwood, MA 02062 USA. [Wyatt, John L.] MIT, Cambridge, MA 02139 USA. [Rizzo, Joseph F., III] VABHS, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kelly, SK (reprint author), VABHS, MIT, Cambridge, MA 02139 USA. EM skkelly@alum.mit.edu; dbs6@cornell.edu; jinghua_chen@meei.harvard.edu; wpd@mit.edu; mdg37@cornell.edu; billd@mit.edu; ltheogar@ece.ucsb.edu; scogan@eiclabs.com; jlw@mit.edu; joseph_rizzo@meei.harvard.edu OI Kelly, Shawn/0000-0003-3533-5268 FU VA Center for Innovative Visual Rehabilitation; NIH [EY016674-01, IIS-0515134]; Catalyst Foundation; MOSIS Service FX This work was supported in part by the VA Center for Innovative Visual Rehabilitation, NIH (EY016674-01), NSF (IIS-0515134), the Catalyst Foundation, and the MOSIS Service. NR 18 TC 3 Z9 3 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 200 EP + DI 10.1109/IEMBS.2009.5333619 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543600054 ER PT S AU Yip, M He, DD Winokur, E Balderrama, AG Sheridan, R Ma, HS AF Yip, Marcus He, David Da Winokur, Eric Balderrama, Amanda Gaudreau Sheridan, Robert Ma, Hongshen GP IEEE TI A Flexible Pressure Monitoring System for Pressure Ulcer Prevention SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB Pressure ulcers are painful sores that arise from prolonged exposure to high pressure points, which restricts blood flow and leads to tissue necrosis. This is a common occurrence among patients with impaired mobility, diabetics and the elderly. In this work, a flexible pressure monitoring system for pressure ulcer prevention has been developed. The prototype consists of 99 capacitive pressure sensors on a 17-cm x 22-cm sheet which is flexible in two dimensions. Due to its low cost, the sensor sheet can be disconnected from the reusable electronics and be disposed of after use, suitable for a clinical setting. Each sensor has a resolution of better than 2-mmHg and a range of 50-mmHg and offset is calibrated in software. Real-time pressure data is displayed on a computer. A maximum sampling rate of 12-Hz allows for continuous monitoring of pressure points. C1 [Yip, Marcus; He, David Da; Winokur, Eric; Balderrama, Amanda Gaudreau] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Sheridan, Robert] Massachusetts Gen Hosp, Shriners Hosp Children Bostan, Boston, MA 02114 USA. [Ma, Hongshen] Univ British Columbia, Dept Engn Mech, Vancouver, BC V6T 1Z4, Canada. RP Yip, M (reprint author), MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. EM yipm@mit.edu; davidhe@mit.edu; ewinokur@mit.edu; adgaud@mit.edu; hongma@interchange.ubc.ca FU Center for Integration of Medicine and Innovative Technology, Boston, MA FX This work was supported by the Center for Integration of Medicine and Innovative Technology, Boston, MA. NR 6 TC 9 Z9 9 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 1212 EP + DI 10.1109/IEMBS.2009.5333964 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543601035 ER PT S AU Dauwels, J Eskandar, E Cash, S AF Dauwels, Justin Eskandar, Emad Cash, Sydney GP IEEE TI Localization of Seizure Onset Area from Intracranial Non-Seizure EEG by Exploiting Locally Enhanced Synchrony SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID EPILEPSY; COHERENCE; ENTROPY AB For as many as 30% of epilepsy patients, seizures are poorly controlled with medication alone. For some of these patients surgery may be an option: the brain region responsible for seizure onset may be removed surgically. However, this requires accurate delineation of the seizure onset region. Currently, the key to making this determination is seizure EEG. Therefore, EEG recordings must continue until enough seizures are obtained to determine the onset region; this may take about 5 days to several weeks. In some cases these recordings must be done using invasive electrodes, a procedure that includes substantial risk, discomfort and cost. In this paper, techniques are developed that use periods of intracranial non-seizure ("rest") EEG to localize epileptogenic networks. Analysis of intracranial EEG (recorded by surface and/or depth electrodes) of 6 epileptic patients shows that certain EEG channels and hence cortical regions are consistently more synchronous ("hypersynchronous") compared to others. It is shown that hypersynchrony seems to strongly correlate with the seizure onset zone; this phenomenon may in the long term allow to determine the seizure onset area(s) from non-seizure EEG, which in turn would enable shorter hospitalizations or even avoidance of semi-chronic implantations all-together. C1 [Dauwels, Justin] MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. [Eskandar, Emad] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. [Eskandar, Emad; Cash, Sydney] Harvard Med Sch, Cambridge, MA USA. [Cash, Sydney] Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Dauwels, J (reprint author), MIT, Informat & Decis Syst Lab, Cambridge, MA 02139 USA. EM justin@dauwels.com RI Dauwels, .Justin /A-5034-2011 NR 15 TC 10 Z9 10 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 2180 EP + DI 10.1109/IEMBS.2009.5332447 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543601279 ER PT S AU Iftimia, N Hammer, DX Mujat, M Desphande, V Cizginer, S Brugge, W AF Iftimia, N. Hammer, D. X. Mujat, M. Desphande, V Cizginer, S. Brugge, W. GP IEEE TI Optical coherence tomography imaging for cancer diagnosis and therapy guidance SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID FINE-NEEDLE-ASPIRATION; CYSTIC NEOPLASMS; PANCREAS; BIOPSY; ACCURACY; LESIONS; BENIGN AB Optical Coherence Tomography (OCT) is an emerging optical technology that has shown great promise for early cancer detection. Using backreflected light to visualize tissue microstructure, OCT can provide information on nuclear size and shape, nuclear-to-cytoplasmic ratio, and the organization and structure of glands. It can also provide functional information, like blood flow, tissue birefringence, etc. These capabilities could potentially be employed in three ways: as a primary diagnostic test to replace biopsy, as a screening tool to direct biopsy, and as a diagnostic tool to guide therapy and monitor therapy response. In this paper we present an application of OCT for pancreatic cancer diagnosis and therapy guidance. C1 [Iftimia, N.; Hammer, D. X.; Mujat, M.] Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. [Desphande, V; Cizginer, S.; Brugge, W.] Massachusetts Gen Hosp, Boston, MA 02214 USA. RP Iftimia, N (reprint author), Phys Sci Inc, 20 New England Business Ctr, Andover, MA 01810 USA. EM iftimia@psicorp.com; hammerr@psicorp.com; mujat@psicorp.com; VDESHPANDE@PARTNERS.ORG; SCIZGINERI@PARTNERS.ORG; WBRUGGE@PARTNERS.ORG FU NIH/NCI [5R43CA117218-02] FX This work was supported by the NIH/NCI grant 5R43CA117218-02. NR 14 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 4067 EP + DI 10.1109/IEMBS.2009.5333198 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543603109 ER PT S AU Wu, W Chen, Z Gao, SK Brown, EN AF Wu, Wei Chen, Zhe Gao, Shangkai Brown, Emery N. GP IEEE TI A Probabilistic Framework for Learning Robust Common Spatial Patterns SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID FILTERS; EEG AB Robustness in signal processing is crucial for the purpose of reliably interpreting physiological features from noisy data in biomedical applications. We present a robust algorithm based on the reformulation of a well-known spatial filtering and feature extraction algorithm named Common Spatial Patterns (CSP). We cast the problem of learning CSP into a probabilistic framework, which allows us to gain insights into the algorithm. To address the overfitting problem inherent in CSP, we propose an expectation-maximization (EM) algorithm for learning robust CSP using from a Student-t distribution. The efficacy of the proposed robust algorithm is validated with both simulated and real EEG data. C1 [Wu, Wei; Chen, Zhe; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. [Wu, Wei; Gao, Shangkai] Tsinghua Univ, Dept Biomed Engn, Beijing 100084, Peoples R China. [Wu, Wei; Chen, Zhe; Brown, Emery N.] Massachusetts Gen Hosp, Harward Med Sch, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Wu, W (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM weiwu@neurostat.mit.edu OI Chen, Zhe/0000-0002-6483-6056 FU NIH [DP1-OD003646]; National Natural Science Foundation of China [30630022] FX This work was supported by NIH Grants DP1-OD003646 and the National Natural Science Foundation of China under Grant 30630022. NR 12 TC 2 Z9 2 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 4658 EP + DI 10.1109/IEMBS.2009.5332646 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543603260 ER PT S AU Chen, Z Putrino, DF Ba, DE Ghosh, S Barbieri, R Brown, EN AF Chen, Zhe Putrino, David F. Ba, Demba E. Ghosh, Soumya Barbieri, Riccardo Brown, Emery N. GP IEEE TI A Regularized Point Process Generalized Linear Model for Assessing the Functional Connectivity in the Cat Motor Cortex SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID NEURAL SPIKING ACTIVITY; TRAIN DATA; FRAMEWORK; ENSEMBLE AB Identification of multiple simultaneously recorded neural spike train recordings is an important task in understanding neuronal dependency, functional connectivity, and temporal causality in neural Systems. An assessment of the functional connectivity in a group of ensemble cells was performed using a regularized point process generalized linear model (GLM) that incorporates temporal smoothness or contiguity of the solution. An efficient convex optimization algorithm was then developed for the regularized solution. The point process model was applied to an ensemble of neurons recorded from the cat motor cortex during a skilled reaching task. The implications of this analysis to the coding of skilled movement in primary motor cortex is discussed. C1 [Chen, Zhe; Putrino, David F.; Ba, Demba E.; Ghosh, Soumya; Barbieri, Riccardo; Brown, Emery N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 NR 16 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5006 EP 5009 DI 10.1109/IEMBS.2009.5334610 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543603344 ER PT S AU Chen, Z Purdon, PL Pierce, ET Harrell, G Walsh, J Salazar, AF Tavares, CL Brown, EN Barbieri, R AF Chen, Zhe Purdon, Patrick L. Pierce, Eric T. Harrell, Grace Walsh, John Salazar, Andres F. Tavares, Casie L. Brown, Emery N. Barbieri, Riccardo GP IEEE TI Linear and Nonlinear Quantification of Respiratory Sinus Arrhythmia during Propofol General Anesthesia SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID HEART-RATE-VARIABILITY; PREDICTS AB Quantitative evaluation of respiratory sinus arrhythmia (RSA) may provide important information in clinical practice of anesthesia and postoperative care. In this paper, we apply a point process method to assess dynamic RSA during propofol general anesthesia. Specifically, an inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by a linear or bilinear bivariate regression on the previous R-R intervals and respiratory measures. The estimated second-order bilinear interaction allows us to evaluate the nonlinear component of the RSA. The instantaneous RSA gain and phase can be estimated with an adaptive point process filter. The algorithm's ability to track non-stationary dynamics is demonstrated using one clinical recording. Our proposed statistical indices provide a valuable quantitative assessment of instantaneous cardiorespiratory control and heart rate variability (HRV) during general anesthesia. C1 [Chen, Zhe; Purdon, Patrick L.; Pierce, Eric T.; Harrell, Grace; Walsh, John; Salazar, Andres F.; Tavares, Casie L.; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@mit.edu OI Barbieri, Riccardo/0000-0001-9381-3833; Chen, Zhe/0000-0002-6483-6056 NR 20 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5336 EP 5339 DI 10.1109/IEMBS.2009.5332693 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543604061 ER PT S AU Aoi, M Gremaud, P Tran, HT Novak, V Olufsen, MS AF Aoi, Mikio Gremaud, Pierre Tran, Hien T. Novak, Vera Olufsen, Mette S. GP IEEE TI Modeling cerebral blood flow and regulation SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID PRESSURE AB Cerebral autoregulation is a homeostatic mechanism which maintains blood flow despite changes in blood pressure in order to meet local metabolic demands. Several mechanisms play a role in cerebral autoregulation in order to adjust vascular tone and caliber of the cerebral vessels, but the exact etiology of the dynamics of these mechanism is not well understood. In this study, we discuss two patient specific models predicting cerebral blood flow velocity during postural change from sitting to standing. One model characterises cerebral autoregulation, the other describes the beat-to-beat distribution of blood flow to the major regions of the brain. Both models have been validated against experimental data from a healthy young subject. C1 [Aoi, Mikio] North Carolina State Univ, Biomath Program, Raleigh, NC 27695 USA. [Gremaud, Pierre; Tran, Hien T.; Olufsen, Mette S.] North Carolina State Univ, Dept Math, Raleigh, NC 27695 USA. [Novak, Vera] Harvard Med Sch, Beth Isreal Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA. RP Aoi, M (reprint author), North Carolina State Univ, Biomath Program, Raleigh, NC 27695 USA. EM mcaoi@ncsu.edu; gremaud@ncsu.edu; tran@ncsu.edu; vnovak@bidmc.harvard.edu; msolufse@ncsu.edu FU National Science Foundation [NSF/DMS-0616597]; [NIH-NIA-1-T32-AG023480-04] FX This work was supported in part by the National Science Foundation through grant awarded by NSF/DMS-0616597. M. Aoi was supported by NIH-NIA-1-T32-AG023480-04 during the summer 2008. NR 11 TC 2 Z9 3 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5470 EP + DI 10.1109/IEMBS.2009.5334057 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543604095 ER PT S AU Chen, LY Reisner, AT Reifman, J AF Chen, Liangyou Reisner, Andrew T. Reifman, Jaques GP IEEE TI Automated Beat Onset and Peak Detection Algorithm for Field-Collected Photoplethysmograms SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID PULSE OXIMETRY; SIGNAL AB Recent reports suggest that photoplethysmography (PPG), which is a component of routine pulse oximetry, may be useful for detecting hypovolemia. An essential step in extracting and analyzing common PPG features is the robust identification of onset and peak locations of the vascular beats, despite varying beat morphologies and major oscillations in the baseline. Some prior reports used manual analysis of the PPG waveform; however, for systematic widespread use, an automated method is required. In this paper, we report an algorithm that automatically detects beat onsets and peaks from noisy field-collected PPG waveforms. We validated the algorithm by clinician evaluation of 100 randomly selected PPG waveform samples. For 99% of the beats, the algorithm was able to credibly identify the onsets and peaks of vascular beats, although the precise locations were ambiguous, given the very noisy data from actual clinical operations. The algorithm appears promising, and future consideration of its diagnostic capabilities and limitations is warranted. C1 [Reifman, Jaques] USAMRMC, TATRC, Bioinformat Cell, ATTN,MCMR TT, Bldg 363 Miller Dr, Ft Detrick, MD 21702 USA. [Chen, Liangyou; Reisner, Andrew T.] USAMRMC, TATRC, Bioinformat Cell, Ft Detrick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Reifman, J (reprint author), USAMRMC, TATRC, Bioinformat Cell, ATTN,MCMR TT, Bldg 363 Miller Dr, Ft Detrick, MD 21702 USA. EM lchen@bioanalysis.org; areisner@partners.org; jaques.reifman@us.army.mil FU U.S. Army Medical Research and Materiel Command (USAMRMC) FX This work was supported in part by the Combat Casualty Care Research Area Directorate of the U.S. Army Medical Research and Materiel Command (USAMRMC), Fort Detrick, Maryland. NR 8 TC 3 Z9 3 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5689 EP + DI 10.1109/IEMBS.2009.5333542 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543604149 ER PT S AU Rohde, CB Gilleland, C Samara, C Norton, S Haggarty, S Yanik, MF AF Rohde, Christopher B. Gilleland, Cody Samara, Chrysanthi Norton, Stephanie Haggarty, Stephen Yanik, Mehmet Fatih GP IEEE TI Microfluidic in vivo Screen Identifies Compounds Enhancing Neuronal Regeneration SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID LASER AXOTOMY AB Compound screening is a powerful tool to identify new therapeutic targets, drug leads, and elucidate the fundamental mechanisms of biological processes. We report here the results of the first in vivo small-molecule screens for compounds enhancing neuronal regeneration. These screens are enabled by the microfluidic devices we have developed for C. elegans. The devices enable rapid and repeatable animal immobilization which allows high-throughput and precise surgery. Following surgery, animals are exposed to the contents of a small-molecule library and assayed for neuronal regeneration. Using this screening method we have identified several compounds that enhance neural regeneration in vivo. C1 [Rohde, Christopher B.; Gilleland, Cody; Samara, Chrysanthi; Yanik, Mehmet Fatih] MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Norton, Stephanie; Haggarty, Stephen] Massachusetts Gen Hosp, Harvard Med Sch, Ctr Human Genet Res, Boston, MA 02142 USA. RP Rohde, CB (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM yanik@mit.edu FU NIH Director's New Innovator Award Program [1-DP2-OD00298901]; NIH Roadmap for Medical Research; MIT-Merck Graduate Fellowship; National Science Foundation Graduate Fellowship FX This work was supported in part by the NIH Directors New Innovator Award Program (1-DP2-OD00298901), part of the NIH Roadmap for Medical Research. C. B. Rohde was supported by the MIT-Merck Graduate Fellowship. C. Gilleland was supported by the National Science Foundation Graduate Fellowship. NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 5950 EP + DI 10.1109/IEMBS.2009.5334771 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543604213 ER PT S AU Vichare, VV Wall, C Balkwill, MD Sienko, KH AF Vichare, V. V. Wall, C., III Balkwill, M. D. Sienko, K. H. GP IEEE TI Assessing the effect of vibrotactile feedback during continuous multidirectional platform motion: A frequency domain approach SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID BALANCE PROSTHESIS; POSTURAL CONTROL; VESTIBULAR LOSS; DEFICITS; SWAY AB This study uses frequency domain techniques to demonstrate the effect of vibrotactile feedback during continuous multidirectional perturbations of a support platform. Eight subjects with bilateral or unilateral vestibular loss were subjected to two-axis pseudo random surface platform motion while donning a multi-axis feedback balance aid that mapped body tilt estimates onto their trunks via a 3-row by 16-column array of tactile vibrators (tactors). Four tactor display configurations with spatial resolutions ranging between 22.5 degrees and 90 degrees, in addition to the tactors off configuration, were evaluated. Power spectral density (PSD) functions of body sway in the anterior-posterior (A/P) and medial-lateral (M/L) directions were computed at frequencies ranging from 0.0178 Hz to 3.56 Hz. Transfer functions between the platform motion and body sway were also computed. Vibrotactile feedback produced significant decreases in A/P and M/L spectral power, decreased transfer function gains up to a frequency of 1.8 Hz and 0.6 Hz in the A/P and M/L directions, respectively, and increased phase leads above 0.3 Hz. The lack of a consistent difference among tactor configurations argue in favor of the simplest 4-column configuration during multidirectional continuous surface perturbations. C1 [Vichare, V. V.; Sienko, K. H.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. [Wall, C., III; Balkwill, M. D.] Massachusetts Eye & Ear Infirm, Harvard Med Sch, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Vichare, VV (reprint author), Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA. EM vvichare@umich.edu; cwall@mit.edu; dbalkwill@meei.harvard.edu; sienko@umich.edu FU National Institutes of Health (NIH) [NIDCD R01 DC6201] FX Manuscript received on April 7, 2009. This work was supported by the National Institutes of Health (NIH NIDCD R01 DC6201). NR 10 TC 5 Z9 5 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6910 EP + DI 10.1109/IEMBS.2009.5333618 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605185 ER PT S AU Stamoulis, C Betensky, RA Mohapatra, G Louis, DN AF Stamoulis, Catherine Betensky, Rebecca A. Mohapatra, Gayatry Louis, David N. GP IEEE TI Application of Signal Processing Techniques for Estimating Regions of Copy Number Variations in Human Meningioma DNA SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID COMPARATIVE GENOMIC HYBRIDIZATION; ARRAY CGH DATA; CANCER; MICROARRAYS; MODEL AB We applied mode-decomposition and matched-filtering, both signal processing techniques used to increase the signal-to-noise ratio (SNR), to array CGH data of human meningioma DNA, in order to extract genomic regions of copy-number changes potentially associated with tumor progression. DNA segments from different chromosomes were decomposed into a small number of dominant components (modes), and low-amplitude modes were eliminated. The SNR of the entire segment was increased and it was possible to identify local changes in the data spatial structure, previously indistinguishable due to noise. We applied matched-filtering to the mode-reduced signals, using a normal DNA sequences (averaged over 50 healthy donors) as the template. The residual signals from this process were analyzed to identify disease-related copy number changes. We were able to identify distinct local changes at different chromosomes in patients with recurrent versus primary meningiomas. C1 [Stamoulis, Catherine] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Betensky, Rebecca A.] Harvard Sch Publ Health, Dept Biostat, Boston, MA 02115 USA. [Mohapatra, Gayatry] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. [Louis, David N.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Stamoulis, C (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Neurol, Boston, MA 02215 USA. EM cstamoul@bidmc.harvard.edu; betensky@hsph.harvard.edu; gmohapatra@partners.org; dlouis@partners.org NR 17 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 6973 EP + DI 10.1109/IEMBS.2009.5333851 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605200 ER PT S AU Malik, WQ Schummers, J Sur, M Brown, EN AF Malik, Wasim Q. Schummers, James Sur, Mriganka Brown, Emery N. GP IEEE TI A Statistical Model for Multiphoton Calcium Imaging of the Brain SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID VISUAL-CORTEX; IN-VIVO AB Multiphoton calcium fluorescence imaging has gained prominence as a valuable tool for the study of brain cells, but the corresponding analytical regimes remain rather naive. In this paper, we develop a statistical framework that facilitates principled quantitative analysis of multiphoton images. The proposed methods discriminate the stimulus-evoked response of a neuron from the background firing and image artifacts. We develop a harmonic regression model with colored noise, and estimate the model parameters with computationally efficient algorithms. We apply this model to in vivo characterization of cells from the ferret visual cortex. The results demonstrate substantially improved tuning curve fitting and image contrast. C1 [Malik, Wasim Q.; Brown, Emery N.] MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. [Schummers, James; Sur, Mriganka] MIT, Dept Brain & Cognit Sci, Picower Inst Learning & Memory, E25-618, Cambridge, MA 02139 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. RP Malik, WQ (reprint author), MIT, Dept Brain & Cognit Sci, E25-618, Cambridge, MA 02139 USA. EM wqm@mit.edu; schummej@mit.edu; msur@mit.edu; enbrown1@mit.edu RI Malik, Wasim/C-9982-2011 FU NIH [DP1 OD003646, EY07023] FX This work was supported by NIH Grants DP1 OD003646 and EY07023. NR 13 TC 1 Z9 1 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 7002 EP + DI 10.1109/IEMBS.2009.5333848 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543605207 ER PT B AU Sundara-Rajan, K Rowe, GI Simon, AJ Klute, GK Ledoux, WR Mamishev, AV AF Sundara-Rajan, Kishore Rowe, Gabriel I. Simon, Anthony J. Klute, Glenn K. Ledoux, William R. Mamishev, Alexander V. BE Evans, BM TI Shear Sensor for Lower Limb Prosthetic Applications SO 2009 FIRST ANNUAL ORNL BIOMEDICAL SCIENCE & ENGINEERING CONFERENCE: EXPLORING THE INTERSECTIONS OF INTERDISCIPLINARY BIOMEDICAL RESEARCH LA English DT Proceedings Paper CT 1st Annual ORNL Biomedical Science and Engineering Conference CY MAR 18-19, 2009 CL Oak Ridge, TN SP Oak Ridge Natl Lab AB Lower limb amputees using a prosthetic device often suffer from mechanically-induced skin injuries. Shear stresses are believed to play a significant role in the formation of these skin injuries. The work presented in this paper is aimed at creating a new class of adaptive prosthetic and orthotic interfaces involving a capacitive shear stress sensor. The sensor design and transfer function are discussed. A few preliminary test results demonstrating the functionality of the sensor are also presented. C1 [Sundara-Rajan, Kishore; Rowe, Gabriel I.; Simon, Anthony J.; Mamishev, Alexander V.] Univ Washington, Dept Elect Engn, Sensors Energy & Automat Lab, Seattle, WA 98195 USA. [Klute, Glenn K.; Ledoux, William R.] VA Puget Sound Hlth Care Syst, Ctr Excellence Limb Loss Prevent & Prosthet Engn, Seattle, WA USA. [Klute, Glenn K.; Ledoux, William R.] Univ Washington, Dept Engn Mech, Seattle, WA USA. RP Sundara-Rajan, K (reprint author), Univ Washington, Dept Elect Engn, Sensors Energy & Automat Lab, Seattle, WA 98195 USA. EM kishore@u.washington.edu FU U.S. National Institute of Health under Grant [R21HD052109-02]; Department of Veterans Affairs Grant [A4843C] FX This work was supported in part by the U.S. National Institute of Health under Grant R21HD052109-02 and the Department of Veterans Affairs Grant A4843C. NR 11 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3837-2 PY 2009 BP 61 EP + PG 2 WC Engineering, Biomedical SC Engineering GA BMB15 UT WOS:000271720900011 ER PT S AU Shi, F Yap, PT Fan, Y Cheng, JZ Wald, LL Gerig, G Lin, WL Shen, DG AF Shi, Feng Yap, Pew-Thian Fan, Yong Cheng, Jie-Zhi Wald, Lawrence L. Gerig, Guido Lin, Weili Shen, Dinggang GP IEEE TI Cortical Enhanced Tissue Segmentation of Neonatal Brain MR Images Acquired by a Dedicated Phased Array Coil SO 2009 IEEE COMPUTER SOCIETY CONFERENCE ON COMPUTER VISION AND PATTERN RECOGNITION WORKSHOPS (CVPR WORKSHOPS 2009), VOLS 1 AND 2 SE IEEE Conference on Computer Vision and Pattern Recognition LA English DT Proceedings Paper CT IEEE-Computer-Society Conference on Computer Vision and Pattern Recognition Workshops CY JUN 20-25, 2009 CL Miami Beach, FL SP IEEE Comp Soc ID AUTOMATIC SEGMENTATION; RECONSTRUCTION; REGISTRATION AB The acquisition of high quality MR images of neonatal brains is largely hampered by their characteristically small head size and low tissue contrast. As a result, subsequent image processing and analysis, especially for brain tissue segmentation, are often hindered To overcome this problem, a dedicated phased array neonatal head coil is utilised to improve MR image qualify by effectively combing images obtained from 8 coil elements without lengthening data acquisition time. In addition, a subject-specific atlas based tissue segmentation algorithm is specifically developed for the delineation of fine structures in the acquired neonatal brain MR images. The proposed tissue segmentation method first enhances the sheet-like cortical gray matter (GM) structures in neonatal images with a Hessian filter for generation of cortical GM prior. Then, the prior is combined with our neonatal population atlas to form a cortical enhanced hybrid atlas, which we refer to as the subject-specific atlas. Various experiments are conducted to compare the proposed method with manual segmentation results, as well as with additional two population atlas based segmentation methods. Results show that the proposed method is capable of segmenting the neonatal brain with the highest accuracy, compared to other two methods. C1 [Shi, Feng; Yap, Pew-Thian; Fan, Yong; Cheng, Jie-Zhi; Shen, Dinggang] Univ N Carolina, IDEA Lab, Dept Radiol & BRIC, Chapel Hill, NC 27515 USA. [Lin, Weili] Univ N Carolina, MRI Lab, Dept Radiol & BRIC, Chapel Hill, NC 27515 USA. [Wald, Lawrence L.] Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Dept Radiol, Boston, MA USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA USA. [Gerig, Guido] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA. RP Shi, F (reprint author), Univ N Carolina, IDEA Lab, Dept Radiol & BRIC, Chapel Hill, NC 27515 USA. EM fengshi@med.unc.edu; ptyap@med.unc.edu; yfan@med.unc.edu; jzcheng@med.unc.edu; wald@nmr.mgh.harvard.edu; gerig@sci.utah.edu; weili_lin@med.unc.edu; dgshen@med.unc.edu RI Wald, Lawrence/D-4151-2009 FU [1R01EB006733]; [1R03EB008760]; [R01EB008374] FX This work was supported in part by grants 1R01EB006733, 1R03EB008760 and R01EB008374. NR 23 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1063-6919 BN 978-1-4244-3994-2 J9 PROC CVPR IEEE PY 2009 BP 102 EP + PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BNL85 UT WOS:000274887100014 ER PT S AU Chen, Z Purdon, PL Pierce, ET Harrell, G Brown, EN Barbieri, R AF Chen, Zhe Purdon, Patrick L. Pierce, Eric T. Harrell, Grace Brown, Emery N. Barbieri, Riccardo GP IEEE TI Assessment of Baroreflex Control of Heart Rate During General Anesthesia Using a Point Process Method SO 2009 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS 1- 8, PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech and Signal Processing CY APR 19-24, 2009 CL Taipei, TAIWAN SP IEEE, IEEE Signal Proc Soc DE point processes; adaptive filters; Volterra series; bilinear systems; baroreflex control ID RECOVERY AB Evaluation of baroreflex control of heart rate (HR) has important implications in clinical practice of anesthesia and postoperative care. In this paper, we present a point process method to assess the dynamic baroreflex gain using a closed-loop model of the cardiovascular system. Specifically, the inverse Gaussian probability distribution is used to model the heartbeat interval, whereas the instantaneous mean is identified by a linear or bilinear bivariate regression on the previous R-R intervals and blood pressure (BP) measures. The instantaneous baroreflex gain is estimated in the feedback loop with a point process filter, while the RR -> BP feedforward frequency response is estimated by a Kalman filter. In addition, the instantaneous cross-spectrum and cross-bispectrum (as well as their ratio) can also be estimated. All statistical indices provide a valuable quantitative assessment of the interaction between heartbeat dynamics and hemodynamics during general anesthesia. C1 [Chen, Zhe; Purdon, Patrick L.; Pierce, Eric T.; Harrell, Grace; Brown, Emery N.; Barbieri, Riccardo] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. RP Chen, Z (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosci Stat Res Lab, Boston, MA 02114 USA. EM zhechen@mit.edu OI Chen, Zhe/0000-0002-6483-6056 NR 16 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4244-2353-8 J9 INT CONF ACOUST SPEE PY 2009 BP 333 EP 336 DI 10.1109/ICASSP.2009.4959588 PG 4 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BKQ01 UT WOS:000268919200084 ER PT S AU Colby, G Heaton, JT Gilmore, LD Sroka, J Deng, YB Cabrera, J Roy, S De Luca, CJ Meltzner, GS AF Colby, Glen Heaton, James T. Gilmore, L. Donald Sroka, Jason Deng, Yunbin Cabrera, Joao Roy, Serge De Luca, Carlo J. Meltzner, Geoffrey S. GP IEEE TI SENSOR SUBSET SELECTION FOR SURFACE ELECTROMYOGRAPY BASED SPEECH RECOGNITION SO 2009 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS 1- 8, PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech and Signal Processing CY APR 19-24, 2009 CL Taipei, TAIWAN SP IEEE, IEEE Signal Proc Soc DE Electromyography; speech recognition AB The authors previously reported speaker-dependent automatic speech recognition accuracy for isolated words using eleven surface-electromyographic (sEMG) sensors in fixed recording locations on the face and neck. The original array of sensors was chosen to ensure ample coverage of the muscle groups known to contribute to articulation during speech production. In this paper we systematically analyzed speech recognition performance from sensor subsets with the goal of reducing the number of sensors needed and finding the best combination of sensor locations to achieve word recognition rates comparable to the full set. We evaluated each of the different possible subsets by its mean word recognition rate across nine speakers using HMM modeling of MFCC and co-activation features derived from the subset of sensor signals. We show empirically that five sensors are sufficient to achieve a recognition rate to within a half a percentage point of that obtainable from the full set of sensors. C1 [Colby, Glen; Sroka, Jason; Deng, Yunbin; Cabrera, Joao; Meltzner, Geoffrey S.] BAE Syst Adv Informat Technol, Burlington, MA USA. [Heaton, James T.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabilitat, Boston, MA USA. [Gilmore, L. Donald; Roy, Serge; De Luca, Carlo J.] Altec Inc, Boston, MA USA. RP Colby, G (reprint author), BAE Syst Adv Informat Technol, Burlington, MA USA. FU United States Defense Advanced Research Projects Agency Defense Advanced Research Projects Agency (DARPA) Information Processing Technology Office (IPTO) Program Advanced Speech Encoding [W15P7T-06-C-P437] FX This study was sponsored by the United States Defense Advanced Research Projects Agency Defense Advanced Research Projects Agency (DARPA) Information Processing Technology Office (IPTO) Program Advanced Speech Encoding, under contract W15P7T-06-C-P437. The views and conclusions in this document are those of the authors and should not be interpreted as representing the official policies, either expressly or implied, of DARPA or the U.S. Government. NR 5 TC 0 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4244-2353-8 J9 INT CONF ACOUST SPEE PY 2009 BP 473 EP + DI 10.1109/ICASSP.2009.4959623 PG 2 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BKQ01 UT WOS:000268919200119 ER PT S AU Shimazaki, H Amari, SI Brown, EN Grun, S AF Shimazaki, Hideaki Amari, Shun-ichi Brown, Emery N. Gruen, Sonja GP IEEE TI STATE-SPACE ANALYSIS ON TIME-VARYING CORRELATIONS IN PARALLEL SPIKE SEQUENCES SO 2009 IEEE INTERNATIONAL CONFERENCE ON ACOUSTICS, SPEECH, AND SIGNAL PROCESSING, VOLS 1- 8, PROCEEDINGS SE International Conference on Acoustics Speech and Signal Processing ICASSP LA English DT Proceedings Paper CT IEEE International Conference on Acoustics, Speech and Signal Processing CY APR 19-24, 2009 CL Taipei, TAIWAN SP IEEE, IEEE Signal Proc Soc DE State space methods; Point processes; Generalized linear model; Correlation; Information geometry ID ENSEMBLE; EVENTS; DISTRIBUTIONS; MODEL AB A state-space method for simultaneously estimating time-dependent rate and higher-order correlation underlying parallel spike sequences is proposed. Discretized parallel spike sequences are modeled by a conditionally independent multivariate Bernoulli process using a log-linear link function, which contains a state of higher-order interaction factors. A nonlinear recursive filtering formula is derived from a log-quadratic approximation to the posterior distribution of the state. Together with a fixed-interval smoothing algorithm, time-dependent log-linear parameters are estimated. The smoothed estimates are optimized via EM-algorithm such that their prior covariance matrix maximizes the expected complete data log-likelihood. In addition, we perform model selection on the hierarchical log-linear state-space models to avoid over-fitting. Application of the method to simultaneously recorded neuronal spike sequences is expected to contribute to uncover dynamic cooperative activities of neurons in relation to behavior. C1 [Shimazaki, Hideaki; Amari, Shun-ichi; Gruen, Sonja] RIKEN Brain Sci Inst, Theoret Neurosci Grp, Wako, Saitama, Japan. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. [Brown, Emery N.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA USA. RP Shimazaki, H (reprint author), RIKEN Brain Sci Inst, Theoret Neurosci Grp, Wako, Saitama, Japan. RI Shimazaki, Hideaki/C-8606-2009; Grun, Sonja/I-6321-2013 OI Shimazaki, Hideaki/0000-0001-7794-3064; Grun, Sonja/0000-0003-2829-2220 FU JSPS Research Fellowship [R01 MH59733 / DP1 OD 003646]; RIKEN Strategic Programs for RD FX This work was supported in part by JSPS Research Fellowships for Young Scientists (HS), R01 MH59733 / DP1 OD 003646 (EB), and RIKEN Strategic Programs for R&D (SG). NR 17 TC 6 Z9 6 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1520-6149 BN 978-1-4244-2353-8 J9 INT CONF ACOUST SPEE PY 2009 BP 3501 EP + DI 10.1109/ICASSP.2009.4960380 PG 2 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA BKQ01 UT WOS:000268919201415 ER PT B AU Betti, A Fiori, G Iannaccone, G Mao, Y AF Betti, A. Fiori, G. Iannaccone, G. Mao, Y. GP IEEE TI Physical insights on graphene nanoribbon mobility through atomistic simulations SO 2009 IEEE INTERNATIONAL ELECTRON DEVICES MEETING SE International Electron Devices Meeting LA English DT Proceedings Paper CT IEEE International Electron Devices Meeting (IEDM 2009) CY DEC 07-09, 2009 CL Baltimore, MD SP IEEE Electron Devices Soc ID LIMITED MOBILITY; DEVICES AB We present an investigation of the main mechanisms which limit mobility in GNR-FETs, by means of atomistic simulations based on the NEGF formalism. In particular, we focus on i) line edge roughness (LER), single defects; iii) ionized impurities, iv) acoustic and optical phonons. Results show that the effect of ionized impurities is negligible, while phonons, LER and defects largely limits carrier mobility, especially for narrower GNRs. C1 [Betti, A.; Fiori, G.; Iannaccone, G.] Univ Pisa, Dipartimento Ingn Informaz, Via Caruso, I-56122 Pisa, Italy. [Mao, Y.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Betti, A (reprint author), Univ Pisa, Dipartimento Ingn Informaz, Via Caruso, I-56122 Pisa, Italy. EM alessandro.betti@iet.unipi.it RI Iannaccone, Giuseppe/C-4866-2008; Fiori, Gianluca/F-1092-2014 FU EC 7FP through Network of Excellence NANOSIL [216171]; GRAND [215752]; European Science Foundation EUROCORES Programme Fundamentals of Nanoelectronics through CNR; EC 6FP [ERASCT- 2003-980409] FX Authors thank Dr. M. Lemme and Prof. P. Palestri for useful discussions, CINECA Super-Computing Center, Bologna, and www.nanohub.org for the provided computational resources. This work was supported in part by the EC 7FP through the Network of Excellence NANOSIL (Contract 216171), by the Project GRAND (Contract 215752) and by the European Science Foundation EUROCORES Programme Fundamentals of Nanoelectronics, through funding from the CNR (awarded to IEEIIT-PISA) and the EC 6FP, under Project Dewint (Contract ERASCT- 2003-980409). NR 14 TC 3 Z9 3 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5639-0 J9 INT EL DEVICES MEET PY 2009 BP 837 EP + PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BPM79 UT WOS:000279343900215 ER PT B AU Mosher, JC Hamalainen, MS Pantazis, D Hui, HB Burgess, RC Leahy, RM AF Mosher, John C. Hamalainen, Matti S. Pantazis, Dimitrios Hui, Hua Brian Burgess, Richard C. Leahy, Richard M. GP IEEE TI GENERALIZED SIDELOBE CANCELLER FOR MAGNETOENCEPHALOGRAPHY ARRAYS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Array signal processing; magnetoencephalography; spatial filters; adaptive arrays ID BRAIN; MEG; LOCALIZATION; EEG AB In the last decade, large arrays of sensors for magnetoencephalography (MEG) (and electroencephalography (EEG)) have become more commonplace, allowing new opportunities for the application of beamforming techniques to the joint problems of signal estimation and noise reduction. We introduce a new approach to noise cancellation, the generalized sidelobe canceller (GSC), itself an alternative to the linearly constrained minimum variance (LCMV) algorithm. The GSC framework naturally fits within the other noise reduction techniques that employ real or virtual reference arrays. Using expository human subject data with strong environmental and biological artifacts, we demonstrate a straightforward sequence of steps for practical noise filtering, applicable to any large array sensor design. C1 [Mosher, John C.; Burgess, Richard C.] Cleveland Clin, Neurol Inst, Epilepsy Ctr, Cleveland, OH 44106 USA. [Hamalainen, Matti S.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Pantazis, Dimitrios; Hui, Hua Brian; Leahy, Richard M.] Univ Southern Calif, Signal & Image Processing Inst, Los Angeles, CA USA. RP Mosher, JC (reprint author), Cleveland Clin, Neurol Inst, Epilepsy Ctr, Cleveland, OH 44106 USA. FU National Institute of Biomedical Imaging and BioEngineering [R01-EB002010, R01-EB006572, R01-EB009048]; National Center for Research Resources [P41-RR14075] FX This work was supported in part by the National Institute of Biomedical Imaging and BioEngineering, grants R01-EB002010, R01-EB006572, and R01-EB009048, and the National Center for Research Resources, grant P41-RR14075. NR 14 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 149 EP + DI 10.1109/ISBI.2009.5193005 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400037 ER PT B AU Jang, B Kaeli, D Do, S Pien, H AF Jang, Byunghyun Kaeli, David Do, Synho Pien, Homer GP IEEE TI MULTI GPU IMPLEMENTATION OF ITERATIVE TOMOGRAPHIC RECONSTRUCTION ALGORITHMS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Iterative reconstruction; GPU; Computed tomography AB Although iterative reconstruction techniques (IRTs) have been shown to produce images of superior quality over conventional filtered back projection (FBP) based algorithms, the use of IRT in a clinical setting has been hampered by the significant computational demands of these algorithms. In this paper we present results of our efforts to overcome this hurdle by exploiting the combined computational power of multiple graphical processing units (GPUs). We have implemented forward and backward projection steps of reconstruction on an NVIDIA Tesla S870 hardware using CUDA. We have been able to accelerate forward projection by 71x and backward projection by 137x. We generate these results with no perceptible difference in image quality between the GPU and serial CPU implementations. This work illustrates the power of using commercial off-the-shelf relatively low-cost GPUs, potentially allowing IRT tomographic image reconstruction to be run in near real time, lowering the barrier to entry of IRT, and enabling deployment in the clinic. C1 [Jang, Byunghyun; Kaeli, David] Northeastern Univ, Dept ECE, Boston, MA 02115 USA. [Do, Synho; Pien, Homer] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Jang, B (reprint author), Northeastern Univ, Dept ECE, Boston, MA 02115 USA. FU CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the NSF [EEC-9986821]; nVidia FX This work was supported in part by CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the NSF (Award Number EEC-9986821), and by equipment donations from nVidia. NR 7 TC 15 Z9 16 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 185 EP + DI 10.1109/ISBI.2009.5193014 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400046 ER PT B AU Iwaki, S Bonmassar, G Belliveau, JW AF Iwaki, Sunao Bonmassar, Giorgio Belliveau, John W. GP IEEE TI NEURAL DYNAMICS OF 3-D OBJECT PERCEPTION ASSESSED BY COMBINED MEG/FMRI IMAGING TECHNIQUE SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE MEG; fMRI; multimodal brain imaging; 3-D object perception ID SURFACE-BASED ANALYSIS; STRUCTURE-FROM-MOTION; CORTICAL SURFACE; COORDINATE SYSTEM; GLOBAL MOTION; HUMAN BRAIN; MAGNETOENCEPHALOGRAPHY; NEURONS; CORTEX; FMRI AB Here, we used both the neuromagnetic (MEG) and the hemodynamic (fMRI) measures to visualize the spatiotemporal brain dynamics during 3-D structure perception from 2D motion (3D-SFM). The coherence of the random-dot motion stimuli was parametrically controlled to infer the changes of the brain dynamics corresponding to different 3-D percepts. The results of the fMRI analysis were used to impose plausible constraints on the MEG inverse calculation using the 'weighted' minimum-norm approach to improve spatial resolution of the spatiotemporal activity estimates. The inferior-temporal, the parieto-occipital, and the intraparietal regions showed increased neural activity in the highly coherent motion conditions in which subjects perceived robust 3-D object structure at different latencies. These results are in agreement with the previous fMRI studies and add further insight into the temporal dynamics of the neural activities in the multiple brain regions along both the dorsal and the ventral visual processing streams during 3D-SFM. C1 [Iwaki, Sunao] Natl Inst Adv Ind Sci & Technol, Tokyo, Japan. [Iwaki, Sunao; Bonmassar, Giorgio; Belliveau, John W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Iwaki, S (reprint author), Natl Inst Adv Ind Sci & Technol, Tokyo, Japan. EM s.iwaki@aist.go.jp RI Iwaki, Sunao/B-1079-2011 OI Iwaki, Sunao/0000-0002-7123-7203 NR 20 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 205 EP + DI 10.1109/ISBI.2009.5193019 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400051 ER PT B AU Do, S Cho, S Karl, WC Kalra, MK Brady, TJ Pien, H AF Do, Synho Cho, Sanghee Karl, W. Clem Kalra, Mannudeep K. Brady, Thomas J. Pien, Homer GP IEEE TI ACCURATE MODEL-BASED HIGH RESOLUTION CARDIAC IMAGE RECONSTRUCTION IN DUAL SOURCE CT SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE model-based imaging; iterative method; cardiac; dual source CT ID QUALITY; SCANNER AB Cardiac imaging represents one of the most challenging imaging problems, requiring high spatial and temporal resolutions along with good tissue contrast. One of the newest clinical cardiac CT scanners incorporates two source-detector pairs in order to improve the temporal resolution by two-fold. To achieve the highest spatial resolution, reconstructions using iterative techniques may be desired. Yet the complexity of the dual-source geometry makes accurate system modeling a challenge. In this paper, we present a model-based iterative reconstruction algorithm for the dual-source CT. We demonstrate, using a total variation formulation, the results of our reconstructions. To accelerate the processing and enhance the quality of the result, we also incorporate a simplified detector response function in the forward projector. A segment of heavily-calcified coronary artery is used to demonstrate the spatial and temporal C1 [Do, Synho; Cho, Sanghee; Kalra, Mannudeep K.; Brady, Thomas J.; Pien, Homer] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karl, W. Clem] Boston Univ, Dept Elect & Comp Engn, Boston, MA 02215 USA. RP Do, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. FU NIH T-32 Cardiac Imaging Training Fellowship FX This research was funded in part by the NIH T-32 Cardiac Imaging Training Fellowship. NR 14 TC 4 Z9 4 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 330 EP + DI 10.1109/ISBI.2009.5193051 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400083 ER PT B AU Gurjar, R Seetamraju, M Kolodziejski, N Koo, YEL Kumar, ATN Kopelman, R AF Gurjar, Rajan Seetamraju, Madhavi Kolodziejski, Noah Koo, Yong-Eun L. Kumar, Anand T. N. Kopelman, Raoul GP IEEE TI DIFFUSED OPTICAL TOMOGRAPHY USING OXYGEN-SENSITIVE LUMINESCENT CONTRAST AGENT SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Oxygen sensitive phosphor; solid-state photomultiplier; diffuse phosphorescence lifetime imaging AB We present results of diffused phosphorescence lifetime tomography performed on tissue-simulating phantoms for high contrast imaging of hypoxic breast tumors. Oxygen sensitive phosphor embedded in a versatile nanoparticle matrix was used as contrast agent to identify simulated hypoxic tumors in phantoms. The surface of these nanoparticles was decorated with F3 peptide that targets cell surface receptors that is often overexpressed in aggressive breast tumors. The surface functionalization did not interfere with the embedded phosphor's characteristics. The phosphorescence intensity and lifetime was measured using single photon sensitive multi-pixel photon counting (MPPC) detectors in box-car geometry. The detection technique has a large dynamic range, high sensitivity and good resolution in oxygen concentration. C1 [Gurjar, Rajan; Seetamraju, Madhavi; Kolodziejski, Noah] Radiat Monitoring Devices Inc, 44 Hunt St, Watertown, MA 02472 USA. [Koo, Yong-Eun L.; Kopelman, Raoul] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. [Kumar, Anand T. N.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. RP Gurjar, R (reprint author), Radiat Monitoring Devices Inc, 44 Hunt St, Watertown, MA 02472 USA. EM RGurjar@rmdinc.com NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 767 EP + DI 10.1109/ISBI.2009.5193162 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400194 ER PT B AU Nappi, J Cai, W Yoshida, H AF Nappi, J. Cai, W. Yoshida, H. GP IEEE TI COMPUTER-AIDED DETECTION OF COLORECTAL LESIONS FOR CATHARTIC-FREE CT COLONOGRAPHY SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE computer aided analysis; biomedical image processing; object detection; x-ray tomography; cancer ID TOMOGRAPHIC COLONOGRAPHY; CANCER; PERFORMANCE; POLYPS AB Cathartic bowel preparation is a major barrier in implementing clinically feasible colorectal screening programs. We developed a fully automated computer-aided detection (CAD) scheme for a cathartic-free computed tomographic colonography (CTC) examination. In a pilot evaluation with 46 clinical cathartic-free CTC cases, the proposed scheme detected 100% (4/4) of large >= 10 mm lesions with 3.7 false-positive (FP) detections per patient (per two volumetric CT scans) and 90% (9/10) of >= 6 mm lesions with 5.0 FP detections per patient, on average. The results indicate that CAD can be used to detect clinically significant lesions with high accuracy in cathartic-free CTC examinations. C1 [Nappi, J.] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. RP Nappi, J (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. FU U.S.Public Health Service [CA095279]; American Cancer Society [RSG-05-088-01-CCE] FX This study was supported in part by grant no CA095279 from the U.S.Public Health Service and by research scholar grant RSG-05-088-01-CCE from the American Cancer Society. We thank Drs. Philippe Lefere and Stefaan Gryspeerdt (Stedelijk Ziekenhuis, Roeselare, Belgium), and Dr. Michael Zalis (Massachusetts General Hospital and Harvard Medical School, Boston, USA), for providing clinical cases for this study. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 911 EP + DI 10.1109/ISBI.2009.5193201 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400233 ER PT B AU Yoshida, H Nappi, J Cai, WL AF Yoshida, H. Nappi, J. Cai, Wenli GP IEEE TI COMPUTER-AIDED DETECTION OF POLYPS IN CT COLONOGRAPHY: PERFORMANCE EVALUATION IN COMPARISON WITH HUMAN READERS BASED ON LARGE MULTICENTER CLINICAL TRIAL CASES SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE computer-aided analysis; biomedical image processing; object detection; x-ray tomography; cancer ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COLONIC POLYPS; FALSE POSITIVES; CAD; REDUCTION; FEATURES AB CT colonography (CTC), also known as virtual colonoscopy, is a promising alternative technique for providing mass screening for colorectal carcinoma. In this study, we developed a high-performance CAD scheme that automatically detects suspicious polyps in CTC data, and retrospectively compared its performance with that of prospective unaided human CTC reading in the detection of clinically significant adenomas/carcinomas by use of CTC database consisting of cases from two large multicenter clinical trials. C1 [Yoshida, H.] Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. RP Yoshida, H (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400C, Boston, MA 02114 USA. NR 16 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 919 EP + DI 10.1109/ISBI.2009.5193203 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400235 ER PT B AU Ambwani, S Cho, S Karl, WC Tawakol, A Pien, H AF Ambwani, Sonal Cho, Sanghee Karl, W. Clem Tawakol, Ahmed Pien, Homer GP IEEE TI A FEASIBILITY STUDY OF JOINT RESPIRATORY AND CARDIAC MOTION CORRECTION FOR CORONARY PET/CT IMAGING SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Atherosclerosis; Inflammation; PET/CT; Super-resolution; Blind deconvolution ID MYOCARDIAL-PERFUSION; SUPERRESOLUTION; RECONSTRUCTION AB Coronary artery disease (CAD) or atherosclerosis is a leading cause of death in industrialized nations. Such diseases are marked by development of chronic vascular inflammation in coronary arteries. Accurate assessment, characterization and localization of this inflammation through non-invasive methods is an important Step towards the treatment of CAD. It has been shown that positron emission tomography (PET) is capable of detecting large vessel inflammation via activated macrophage uptake of FDG. However, respiratory and cardiac motion during image acquisition leads to severe blurring of the resulting images thereby rendering the spatial resolution inadequate for detection of inflammation in coronary arteries. The objective of this paper is to demonstrate the potential of producing high resolution PET images to enable imaging of coronary artery inflammation. In this paper, we propose a novel method for joint cardiac and respiratory motion correction in PET/CT called Cardiac Shape Tracking with Adjustment for Respiration (CSTAR). It uses a sequential cardiac and respiratory motion correction scheme by decoupling the two, and also features the use of all acquired data for SNR preservation. CT images are primarily used for cardiac shape tracking through the estimation of cardiac motion. Cardiac motion correction is incorporated in a super-resolution framework, followed by adjustment for the residual respiratory motion blur using blind deconvolution. We investigated the feasibility of this technique on simulated cardiac PET/CT data using XCAT and the preliminary results show a marked qualitative and quantitative improvement when compared to conventional PET reconstruction. C1 [Ambwani, Sonal; Karl, W. Clem] Boston Univ, Boston, MA 02215 USA. [Cho, Sanghee; Tawakol, Ahmed; Pien, Homer] Massachusetts Gen Hosp, Boston, MA 02215 USA. RP Ambwani, S (reprint author), Boston Univ, Boston, MA 02215 USA. FU CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the National Science Foundation FX This work was supported in part by CenSSIS, the Center for Subsurface Sensing and Imaging Systems, under the Engineering Research Centers Program of the National Science Foundation. NR 13 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 935 EP + DI 10.1109/ISBI.2009.5193207 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400239 ER PT B AU Peroni, M Spadea, MF Riboldi, M Baroni, G Chen, GTY Sharp, GC AF Peroni, M. Spadea, M. F. Riboldi, M. Baroni, G. Chen, G. T. Y. Sharp, G. C. GP IEEE TI VALIDATION OF AN AUTOMATIC CONTOUR PROPAGATION METHOD FOR LUNG CANCER 4D ADAPTIVE RADIATION THERAPY SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Contour Propagation; Deformable Registration; Adaptive Radiation Therapy; 4D Treatment Planning; Re-planning ID REGISTRATION AB The objective of this work is to validate a fast and reliable 4D-based adaptive treatment planning procedure for the Radiation Oncology clinic. A non-rigid B-Spline based registration is per-formed between CT scans at different respiratory phases. Radiotherapy contours drawn on a reference phase are than propagated to the target phase. We present results from two novel validation methods: a validation study using a 4D anthropomorphic computational phantom, and a patient data analysis comparing auto-rater versus inter-rater variability. For the phantom study, the overlap was greater than 90%, while the diameter variation was 5.1% at exhale and 3.4% at inhale. For the patient dataset, pairwise auto-rater Dice coefficient values exceeded inter-rater values for 9 of 15 structures. Though subject to inaccuracies caused by residual motion artifacts, and manual contouring variations, the reliability of the method suggests it could be soon introduced in the clinical practice. C1 [Peroni, M.; Spadea, M. F.; Riboldi, M.; Baroni, G.] Politecn Milano Univ, Dept Bioengn, Milan, Italy. [Spadea, M. F.] Magna Graecia Univ Catanzaro, Dept Expt & Clin Med, Catanzaro, Italy. [Chen, G. T. Y.; Sharp, G. C.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Chen, G. T. Y.; Sharp, G. C.] Harvard Med Sch, Boston, MA USA. RP Peroni, M (reprint author), Politecn Milano Univ, Dept Bioengn, Milan, Italy. RI Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU "Progetto Rocca" foundation; MIT and Politecnico di Milano FX This work was supported in part by the Progetto Rocca foundation, a collaboration program between MIT and Politecnico di Milano. NR 6 TC 1 Z9 1 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 1071 EP + DI 10.1109/ISBI.2009.5193241 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400273 ER PT B AU Fang, QQ Boas, DA AF Fang, Qianqian Boas, David A. GP IEEE TI TETRAHEDRAL MESH GENERATION FROM VOLUMETRIC BINARY AND GRAY-SCALE IMAGES SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Mesh generation; Finite element analysis; Medical image AB We report a general purpose mesh generator for creating finite-element surface or volumetric mesh from 3D binary or gray-scale medical images. This toolbox incorporates a number of existing free mesh processing utilities and enables researchers to perform a range of mesh processing tasks for image-based mesh generation, including raw image processing, surface mesh extraction, surface re-sampling, and multi-scale/adaptive tetrahedral mesh generation. We also implemented robust algorithms for meshing open-surfaces and sub-region labeling. Atomic meshing utilities for each processing step can be accessed with simple interfaces, which can be streamlined or executed independently. The toolbox is compatible with Matlab or GNU Octave. We demonstrate the applications of this toolbox for meshing a range of challenging geometries including complex vessel network, human brain and breast. C1 [Fang, Qianqian; Boas, David A.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Fang, QQ (reprint author), Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. NR 9 TC 151 Z9 151 U1 1 U2 8 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 1142 EP 1145 DI 10.1109/ISBI.2009.5193259 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400291 ER PT B AU He, L Orten, BB Do, S Karl, WC Kambadakone, A Sahani, DV Pien, H AF He, L. Orten, B. B. Do, S. Karl, W. C. Kambadakone, A. Sahani, D. V. Pien, H. GP IEEE TI SPATIO-TEMPORAL DECONVOLUTION OF PERFUSION CT DATA IN RECTAL TUMOR PATIENTS SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE DE Spatio-temporal deconvolution; truncated singular value decomposition (TSVD); perfusion computed tomography (CTp); rectal tumor ID FLOW AB Anatomical imaging modalities such as MR and CT produce high resolution images that are essential in modern health care. Anatomical imaging, however, can be supplemented with functional imaging to provide additional insights into the status and progression of disease. In perfusion imaging, a bolus of contrast entering a tissue region of interest is carefully monitored in order to derive hemodynamic parameters. While useful, perfusion parameter maps tend to be noisy, in part because the parameters of every voxel are computed independently of its neighboring voxels. A spatio-temporally correlated approach to estimating perfusion parameters has been previously introduced. In this paper, we expand upon this earlier formulation and demonstrate its functionality on a set of rectal tumor patients undergoing CT perfusion (CTp) studies. Our results show that our spatio-temporal deconvolution approach is less noisy than conventional singular value deconvolution approach, and show greater separation between normal and cancerous regions. C1 [He, L.; Do, S.; Kambadakone, A.; Sahani, D. V.; Pien, H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Orten, B. B.; Karl, W. C.] Boston Univ, Dept Elect & Comp Engn, Boston, MA USA. RP He, L (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. FU Center for Integration of Medicine and Innovative Technology (CIMIT); U.S. Army Medical Research FX This work was supported in part by a grant from the Center for Integration of Medicine and Innovative Technology (CIMIT), U.S. Army Medical Research. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 1231 EP + DI 10.1109/ISBI.2009.5193284 PG 2 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400315 ER PT B AU Cascio, EW Gottschalk, B AF Cascio, Ethan W. Gottschalk, Bernard GP IEEE TI A Simplified Vacuumless Faraday Cup for the Experimental Beamline at the Francis H. Burr Proton Therapy Center SO 2009 IEEE RADIATION EFFECTS DATA WORKSHOP, WORKSHOP RECORD LA English DT Proceedings Paper CT IEEE Radiation Effects Data Workshop CY JUL 20-24, 2009 CL Quebec, CANADA SP IEEE, IEEE Nuclear & Plasma Sci Soc, IEEE Nuclear & Space Radiat Effects Conf, Defense Threat Reduct Agcy AB We describe a simplified vacuumless, Faraday cup and compare it with a traditional Faraday cup under various beam conditions. We show that the new design agrees with the traditional design to an accuracy of 1% to 5%. C1 [Cascio, Ethan W.] Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. [Gottschalk, Bernard] Harvard Univ, Lab Particle Phys & Cosmotol, Cambridge, MA 02138 USA. RP Cascio, EW (reprint author), Massachusetts Gen Hosp, Francis H Burr Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM ecascio@partners.org; bgottsch@fas.harvard.edu NR 8 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5092-3 PY 2009 BP 161 EP + DI 10.1109/REDW.2009.5336294 PG 2 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA BNK62 UT WOS:000274805100029 ER PT B AU Meydan, C Sezerman, U Otu, H AF Meydan, Cem Sezerman, Ugur Otu, Hasan BE Zhang, J Li, GZ Yang, JY TI Prediction Of Peptides Binding To MHC Class I Alleles By Partial Periodic Pattern Mining SO 2009 INTERNATIONAL JOINT CONFERENCE ON BIOINFORMATICS, SYSTEMS BIOLOGY AND INTELLIGENT COMPUTING, PROCEEDINGS LA English DT Proceedings Paper CT International Joint Conference on Bioinformatics, Systems Biology and Intelligent Computing CY AUG 03-05, 2009 CL Shanghai, PEOPLES R CHINA SP IEEE Computer Soc, Conf Publish Serv DE motif mining; periodic pattern mining; major histocompatibility complex; machine learning AB MHC (Major Histocompatibility Complex) is a key player in the immune response of an organism. It is important to be able to predict which antigenic peptides will bind to a specific MHC allele and which will not, creating possibilities for controlling immune response and for the applications of immunotherapy. however, a problem for MHC class I is the presence of bulges and loops in the peptides, changing the total length. Most machine learning methods in use today require the sequences to be of same length to successfully mine the binding motifs. We propose the use of time-based data mining methods in motif mining to be able to mine motifs position-independently. Also, the information for both binding and nonbinding peptides is used on the contrary to the other methods which only rely on binding peptides. The prediction results are between 60-95% for the tested alleles. C1 [Meydan, Cem; Sezerman, Ugur] Sabanci Univ, Biol Sci & Bioengn Dept, Istanbul, Turkey. [Otu, Hasan] BIDMC Genom Ctr, Harvard Med Sch, Boston, MA USA. RP Meydan, C (reprint author), Sabanci Univ, Biol Sci & Bioengn Dept, Istanbul, Turkey. EM ugur@sabanciuniv.edu; hotu@bidmc.harvard.edu NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-3739-9 PY 2009 BP 315 EP + DI 10.1109/IJCBS.2009.122 PG 2 WC Computer Science, Artificial Intelligence; Mathematical & Computational Biology SC Computer Science; Mathematical & Computational Biology GA BRI88 UT WOS:000282797800055 ER PT B AU Theogarajan, L Shire, D Kelly, S Wyatt, JL Rizzo, J AF Theogarajan, Luke Shire, Doug Kelly, Shawn Wyatt, John L. Rizzo, Joseph, III GP IEEE TI Visual Prostheses: Current Progress and Challenges SO 2009 INTERNATIONAL SYMPOSIUM ON VLSI DESIGN, AUTOMATION AND TEST (VLSI-DAT), PROCEEDINGS OF TECHNICAL PROGRAM LA English DT Proceedings Paper CT International Symposium on VLSI Design, Automation and Test CY APR 28-30, 2009 CL Hsinchu, TAIWAN SP Ind Technol Res Inst, IEEE ID STIMULATION; THRESHOLDS; ELECTRODE; IMPLANTS; SYSTEM; CHIP C1 [Theogarajan, Luke] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. [Shire, Doug] Cornell Univ, Ithaca, NY 14853 USA. [Kelly, Shawn; Wyatt, John L.] MIT, Cambridge, MA 02139 USA. [Rizzo, Joseph, III] Massachusetts Eye & Ear Infirmary, Boston, MA 02114 USA. [Shire, Doug; Kelly, Shawn; Rizzo, Joseph, III] Vet Adm, Boston, MA USA. RP Theogarajan, L (reprint author), Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA. OI Kelly, Shawn/0000-0003-3533-5268 FU MOSIS; especially Cesar Pina and Wes Hansford; chip fabrication; Catalyst Foundation and the VA Boston FX The authors would like to thank MOSIS, especially Cesar Pina and Wes Hansford, for their generosity with the chip fabrication, the Catalyst Foundation and the VA Boston for supporting this work.; The authors are grateful to Greg Swider, Bill Drohan and Jinghua Chen for their help in obtaining the experimental results. NR 17 TC 0 Z9 0 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-2781-9 PY 2009 BP 126 EP + DI 10.1109/VDAT.2009.5158111 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BMD77 UT WOS:000271941200032 ER PT S AU Lapinski, M Berkson, E Gill, T Reinold, M Paradiso, JA AF Lapinski, Michael Berkson, Eric Gill, Thomas Reinold, Mike Paradiso, Joseph A. GP IEEE Computer Society TI A Distributed Wearable, Wireless Sensor System for Evaluating Professional Baseball Pitchers and Batters SO 2009 INTERNATIONAL SYMPOSIUM ON WEARABLE COMPUTERS, PROCEEDINGS SE IEEE International Symposium on Wearable Computers LA English DT Proceedings Paper CT 13th International Symposium on Wearable Computers CY SEP 04-07, 2009 CL Linz, AUSTRIA AB This paper introduces a compact, wireless, wearable system that measures signals indicative of forces, torques and other descriptive and evaluative features that the human body undergoes during bursts of extreme physical activity (such as during athletic performance). Standard approaches leverage highspeed camera systems, which need significant infrastructure and provide limited update rates and dynamic accuracy. This project uses 6 degree-of-freedom inertial measurement units worn on various segments of an athlete's body to directly make these dynamic measurements. A combination of low and high range sensors enables sensitivity for both slow and fast motion, and the addition of a compass helps in tracking joint angles. Data from the battery-powered nodes is acquired using a custom wireless protocol over an RF link and analyzed offline. Several professional pitchers and batters were instrumented with the system and data was gathered over many pitches and swings. We show some biomechanically descriptive parameters extracted from this data, and highlight ongoing work and system improvements. C1 [Lapinski, Michael; Paradiso, Joseph A.] MIT, Media Lab, Respons Environm Grp, 77 Massachusetts Ave, Cambridge, MA 02139 USA. [Berkson, Eric; Gill, Thomas; Reinold, Mike] Massachusetts Gen Hosp, Dept Orthopaed Surg, Sports Med Serv, Boston, MA 02114 USA. RP Lapinski, M (reprint author), MIT, Media Lab, Respons Environm Grp, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mtl@media.mit.edu; eberkson@partners.org; tgill@partners.org; mreinold@partners.org; joep@media.mit.edu FU Boston Red Sox Foundation; MIT Media Laboratory FX We thank many of our colleagues and collaborators who helped in this work. In particular, Mark Feldmeier, Mat Laibowitz, Dan Hyatt, and Ryan Aylward from the Responsive Environments Group gave valuable aid in hardware and software design and testing. Wed also like to thank Jim Zachazewski and Tom Gill III from MGH Sports Medicine and Paolo Bonato from Spaulding Rehab for many important discussions regarding biomechanics, measurement techniques, and logistics that were crucial to this project. This work was supported by a gift from the Boston Red Sox Foundation and the sponsors of the MIT Media Laboratory. NR 29 TC 12 Z9 12 U1 1 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA SN 1550-4816 BN 978-0-7695-3779-5 J9 IEEE INT SYM WRBL CO PY 2009 BP 131 EP + DI 10.1109/ISWC.2009.27 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BLR64 UT WOS:000270891900019 ER PT J AU Bhide, P AF Bhide, P. BE Baron, A Chneiweiss, H TI Neurovascular interactions in the embryonic brain SO 9TH EUROPEAN MEETING ON GLIAL CELLS IN HEALTH AND DISEASE LA English DT Proceedings Paper CT 9th European Meeting on Glial Cells in Health and Disease CY SEP 08-12, 2009 CL Paris, FRANCE ID VASCULOGENESIS; ANGIOGENESIS AB Angiogenesis in the embryonic brain was long considered to be a passive process principally occurring in response to metabolic demands placed growing neuronal populations. The brain vasculature develops concomitant with neuronal development, which is regulated by compartment-specific cell autonomous factors. Yet, cell autonomous patterning signals were not considered to regulate brain angiogenesis. We show that angiogenesis in the mouse telencephalon occurs in an orderly, ventral-to-dorsal gradient regulated cell-autonomously by compartment-specific homeo-box transcription factors. These transcription factors also regulate compartmental identities of telencephalic neurons and progenitor populations. Thus, our data offer now perspectives on neurovascular interactions and compartmental identities in the embryonic telencephalon. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Bhide, P (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-521-3 PY 2009 BP 7 EP 10 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BVP38 UT WOS:000292191900002 ER PT J AU Zerzan, JT Hess, R Schur, E Phillips, RS Rigotti, N AF Zerzan, Judy T. Hess, Rachel Schur, Ellen Phillips, Russell S. Rigotti, Nancy TI Making the Most of Mentors: A Guide for Mentees SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med ID GENERAL INTERNAL-MEDICINE; ACADEMIC MEDICINE; JUNIOR FACULTY; STUDENTS; CAREER AB Effective mentorship is likely one of the most important determinants of success in academic medicine and research. Many papers focus on mentoring from the mentor's perspective, but few give guidance to mentees forging these critically important relationships. The authors apply "managing up," a corporate concept, to academic medical settings both to promote effective, successful mentoring and to make a mentor's job easier. Managing up requires the mentee to take responsibility for his or her part in the collaborative alliance and to be the leader of the relationship by guiding and facilitating the mentor's efforts to create a satisfying and productive relationship for both parties. The authors review the initiation and cultivation of a mentoring relationship from the perspective of a mentee at any stage (student through junior faculty), and they propose specific strategies for mentee success. C1 [Zerzan, Judy T.] Univ Colorado, Div Gen Internal Med, Sch Med, Dept Med, Aurora, CO 80045 USA. [Hess, Rachel] Univ Pittsburgh, Sch Med, Dept Med & Epidemiol, Div Gen Internal Med, Pittsburgh, PA USA. [Schur, Ellen] Univ Washington, Harborview Med Ctr, Div Gen Internal Med, Seattle, WA 98104 USA. [Phillips, Russell S.] Harvard Univ, Div Gen Med & Primary Care, Dept Med, Sch Med, Boston, MA 02215 USA. [Phillips, Russell S.] Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Med, Sch Med, Boston, MA 02215 USA. [Rigotti, Nancy] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Zerzan, JT (reprint author), Univ Colorado, Div Gen Internal Med, Sch Med, Dept Med, 12631 E 17th Ave,B180,POB 6511, Aurora, CO 80045 USA. EM Judy.Zerzan@ucdenver.edu NR 24 TC 78 Z9 80 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JAN PY 2009 VL 84 IS 1 BP 140 EP 144 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 466IN UT WOS:000267654900028 PM 19116494 ER PT J AU Co, JPT MacDonald, E Yucel, RM Ferris, TG AF Co, John Patrick T. MacDonald, Ellie Yucel, Recai M. Ferris, Timothy G. TI Practice Variation in Parental Assessment of Pediatric Ambulatory Care SO ACADEMIC PEDIATRICS LA English DT Article DE ambulatory care; children; patient surveys; primary care; quality of care ID CHILDRENS HEALTH-CARE; QUALITY; CONTINUITY; ACCESS AB Objective.-To assess parental experience of pediatric primary care at the level of physician practice and to determine what variation exists among practices. Methods.-This cross-sectional survey assessed 7 pediatric primary care practices in eastern Massachusetts. Parents of children aged <= 12 years who received care between July 1999 and June 2000 were surveyed. Parents assessed practice performance in 6 areas of quality: access to care, patient education and information, patient/physician relationship, coordination and Continuity of care, office Staff Courtesy and helpfulness. and specialty care experience. Results.-Surveys were returned by 744 parents (response rate 50%). Practices performed best in the domains of patient education and access to care, and performed poorest in coordination/continuity and specialty care experience. Practice performance varied in the included domains, with significant interpractice variation in specialty care experience (range 61-83 on 100-point scale), coordination and continuity (range 64-84), and access to care (range 80-92). Items with significant variation included the physician/nurse being informed about specialist care, file physician/nurse knowing the parent/child as people, staff helpfulness, and the physician/nurse knowing what worried the parent about the child's health. Conclusions.-Parent reports of specific experiences of care revealed priorities for improvement in several areas. including coordination and continuity. specialty care experience, and interpersonal aspects of care. Performance differed among practices, providing an Opportunity for practices to learn from each other. survey-based measures of quality can help identify variation in performance and Priorities for improving quality of care. C1 [Co, John Patrick T.; Ferris, Timothy G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. [MacDonald, Ellie; Ferris, Timothy G.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Yucel, Recai M.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY USA. RP Co, JPT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM jco@partners.org NR 33 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1876-2859 J9 ACAD PEDIATR JI Acad. Pediatr. PD JAN-FEB PY 2009 VL 9 IS 1 BP 47 EP 52 PG 6 WC Pediatrics SC Pediatrics GA 572ZW UT WOS:000275878900010 PM 19329091 ER PT J AU Bhuvaneswar, C Stern, T Beresin, E AF Bhuvaneswar, Chaya Stern, Theodore Beresin, Eugene TI Using the Technique of Journal Writing to Learn Emergency Psychiatry SO ACADEMIC PSYCHIATRY LA English DT Article ID DISCLOSURE AB Objective: The authors discuss journal writing in learning emergency psychiatry. Methods: The journal of a psychiatry intern rotating through an emergency department is used as sample material for analysis that could take place in supervision or a resident support group. A range of articles are reviewed that illuminate the relevance of journal writing for the learning process, including articles about resident resilience, "autognosis," the learning process in psychiatry, and " limbic music." Results: Journal writing is a useful tool in consolidating knowledge, and can be used along with traditional exercises for learning psychiatry such as writing chart notes, process notes, and completing required studies for examinations. Conclusion: Psychiatry training should continue to explore the use of journals as residents continue to write them. C1 [Bhuvaneswar, Chaya] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Stern, Theodore; Beresin, Eugene] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Bhuvaneswar, C (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,2nd Floor, Philadelphia, PA 19104 USA. EM Bhuvaneswaren@uphs.upenn.edu NR 19 TC 3 Z9 3 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JAN-FEB PY 2009 VL 33 IS 1 BP 43 EP 46 PG 4 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 429NF UT WOS:000264926700009 PM 19349443 ER PT J AU Iannucci, R Sanders, K Greenfield, SF AF Iannucci, Rocco Sanders, Kathy Greenfield, Shelly F. TI A 4-Year Curriculum on Substance Use Disorders for Psychiatry Residents SO ACADEMIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th Annual Medcial Education Day CY NOV, 2006 CL Boston, MA ID POSITION STATEMENT; ABUSE; EDUCATION AB Objective: The authors describe an addiction psychiatry curriculum integrated in a general psychiatry training program to demonstrate comprehensive and practical approaches to educating general psychiatric residents on the recognition and treatment of substance use disorders. Methods: The Massachusetts General Hospital/McLean Hospital adult psychiatric residency training program provides training in addiction psychiatry in multiple treatment settings during the 4 years of residency. Addiction specialists, nonspecialty psychiatrists, and residents and fellows provide training. Results: Adult psychiatric residencies can provide comprehensive addiction psychiatry training that spans multiple treatment settings and postgraduate years by training general staff psychiatrists, senior residents, and fellows to assist core addiction faculty in providing addiction psychiatry education. Conclusion: Substance use disorders are common among patients presenting to general psychiatry treatment settings, and thus it is important that all psychiatric residents be well trained in the screening, diagnosis, and treatment of outpatients with these problems. C1 [Iannucci, Rocco] Berkshire Med Ctr Pittsfield, Dept Psychiat, Pittsfield, MA USA. [Sanders, Kathy] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Greenfield, Shelly F.] McLean Hosp, Alcohol & Drug Abuse Treatment Program, Belmont, MA 02178 USA. RP Greenfield, SF (reprint author), McLean Hosp Harvard, 115 Mill St, Belmont, MA 02478 USA. EM sgreenfield@mclean.harvard.edu FU NIDA NIH HHS [K24 DA019855, K24 DA019855-01] NR 18 TC 7 Z9 8 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1042-9670 J9 ACAD PSYCHIATR JI Acad. Psych. PD JAN-FEB PY 2009 VL 33 IS 1 BP 60 EP 66 PG 7 WC Education & Educational Research; Psychiatry SC Education & Educational Research; Psychiatry GA 429NF UT WOS:000264926700013 PM 19349447 ER PT J AU Tokuda, J Schmitt, M Sun, YP Patz, S Tang, Y Mountford, CE Hata, N Wald, LL Hatabu, H AF Tokuda, Junichi Schmitt, Melanie Sun, Yanping Patz, Samuel Tang, Yi Mountford, Carolyn E. Hata, Nobuhiko Wald, Lawrence L. Hatabu, Hiroto TI Lung Motion and Volume Measurement by Dynamic 3D MRI Using a 128-Channel Receiver Coil SO ACADEMIC RADIOLOGY LA English DT Article DE Lung; magnetic resonance imaging; image segmentation; lung volume measurement ID HUMAN DIAPHRAGM SHAPE; HEALTHY-SUBJECTS; RADIOTHERAPY; EMPHYSEMA; RECONSTRUCTION; VARIABILITY; MECHANICS; CANCER; TUMORS AB Rationale and Objectives. The authors present their initial experience using a 3-T whole-body scanner equipped with a 128-channel coil applied to lung motion assessment. Recent improvements in fast magnetic resonance imaging (MRI) technology have enabled several trials of free-breathing three-dimensional (313) imaging of the lung. A large number of image frames necessarily increases the difficulty of image analysis and therefore warrants automatic image processing. However, the intensity homogeneities of images of prior dynamic 3D lung MRI studies have been insufficient to use such methods. In this study, initial data were obtained at 3 T with a 128-channel coil that demonstrate the feasibility of acquiring multiple sets of 3D pulmonary scans during free breathing and that have sufficient quality to be amenable to automatic segmentation. Materials and Methods. Dynamic 3D images of the lungs of two Volunteers were acquired with acquisition times of 0.62 to 0.76 frames/s and an image matrix of 128 X 128, with 24 to 30 slice encodings. The volunteers were instructed to take shallow and deep breaths during the scans. The variation Of lung volume was measured from the segmented images. Results. Dynamic 3D images were successfully acquired for both respiratory conditions for each subject. The images showed whole-lung motion, including lifting of the chest wall and the displacement of the diaphragm, with sufficient contrast to distinguish these structures from adjacent tissues. The average time to complete segmentation for one 3D image was 4.8 seconds. The tidal volume measured was consistent with known tidal volumes for healthy subjects performing deep-breathing maneuvers. The temporal resolution was insufficient to measure tidal volumes for shallow breathing Conclusion. This initial experience with a 3-T whole-body scanner and a 128-channel coil showed that the scanner and imaging protocol provided dynamic 3D images with spatial and temporal resolution sufficient to delineate the diaphragmatic domes and chest wall during active breathing. In addition, the intensity homogeneities and signal-to-noise ratio were adequate to perform automatic segmentation. C1 [Tokuda, Junichi; Sun, Yanping; Patz, Samuel; Tang, Yi; Mountford, Carolyn E.; Hata, Nobuhiko; Hatabu, Hiroto] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Tokuda, Junichi; Sun, Yanping; Patz, Samuel; Tang, Yi; Mountford, Carolyn E.; Hata, Nobuhiko; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. [Schmitt, Melanie] Massachusetts Gen Hosp, Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Wald, Lawrence L.] Harvard MIT Div Hlth Sci Technol, Cambridge, MA USA. RP Hatabu, H (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM hhatabu@partners.org RI Patz, Samuel/I-2879-2012; Hata, Nobuhiko/L-5221-2014; Wald, Lawrence/D-4151-2009; OI Hata, Nobuhiko/0000-0002-6818-7700; Patz, Samuel/0000-0002-4500-1918 FU National Institutes of Health, Bethesda, MD [R21CA116271-02] FX This work was supported in part by grant R21CA116271-02 from the National Institutes of Health, Bethesda, MD. NR 25 TC 21 Z9 21 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JAN PY 2009 VL 16 IS 1 BP 22 EP 27 DI 10.1016/j.acra.2008.07.021 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 388LP UT WOS:000262021600004 PM 19064208 ER PT B AU MacDonald, SM Gierga, DP Napolitano, B Taghian, AG AF MacDonald, Shannon M. Gierga, David P. Napolitano, Brian Taghian, Alphonse G. BE Wazer, DE Arthur, DW Vicini, FA TI APBI 3D Conformal External Beam: The MGH Technique SO ACCELERATED PARTIAL BREAST IRRADIATION: TECHNIQUES AND CLINICAL IMPLEMENTATION, SECOND EDITION LA English DT Article; Book Chapter ID PARTIAL-BREAST IRRADIATION; INITIAL DOSIMETRIC EXPERIENCE; RADIATION-THERAPY; CLINICAL-EXPERIENCE; PROTON-BEAMS; PHOTONS; CANCER; IMRT C1 [MacDonald, Shannon M.; Gierga, David P.; Napolitano, Brian] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Taghian, Alphonse G.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP MacDonald, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 100 Blossom St Cox Bldg 302, Boston, MA 02114 USA. EM ataghian@partners.org NR 25 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-3-540-88005-9 PY 2009 BP 315 EP 326 DI 10.1007/978-3-540-88006-6_18 D2 10.1007/978-3-540-88006-6 PG 12 WC Oncology SC Oncology GA BLO25 UT WOS:000270664000018 ER PT J AU Oberaigner, W Siebert, U AF Oberaigner, Willi Siebert, Uwe TI Are survival rates for Tyrol published in the Eurocare studies biased? SO ACTA ONCOLOGICA LA English DT Article DE Cancer registry; record linkage; survival; survival status ID PROSTATE-CANCER MORTALITY; PATIENT SURVIVAL; RECORD LINKAGE; ASCERTAINMENT; COMPLETENESS; REDUCTION; REGISTRY; AUSTRIA AB Objective. To investigate whether survival rates published in the EUROCARE studies for Tyrol are distorted, we evaluated data quality in the Cancer Registry of Tyrol. Material and methods. Potential errors in completeness of Tyrolean incidence data were assessed by applying semi-quantitative and quantitative methods, in part by comparing indices for Tyrol with those of neighboring countries published in Cancer Incidence in Five Continents. Validity of patient survival status was checked for all cancer patients diagnosed in 1997 (n = 2 556). For all 1 026 of these patients still alive at end of 2007, we reassessed survival status. Finally, we re-abstracted date of diagnosis for a subset of 295 patients. Results. Quality indices on completeness showed no greater bias with the exception of borderline ovarian cancer, which was in part miscoded in the early nineties. Some differences for bladder cancer and prostate cancer between Tyrol and neighboring countries are due to PSA testing and pathology diagnosis. Concerning patient survival status, four cases were erroneously assessed as alive, five cases died outside Austria, three cases were proven not to belong to the population of Tyrol at time of diagnosis and 21 cases emigrated. Absolute errors in survival rates were less than 0.5 for up to five-year survival rates and less than 1.0 for ten year survival rates. Conclusions. Evaluation of data quality in the Cancer Registry of Tyrol demonstrated that the survival rates published for Tyrol are only minimally biased by registration or analysis procedures. However, access to data on emigration, which until now is not possible because of data protection restrictions, would reduce the bias in patient survival status, bearing in mind that the extent of emigration of cancer patients is expected to increase in Austria over the coming years. C1 [Oberaigner, Willi] Tyrolean State Hosp Ltd, Dept Clin Epidemiol, Canc Registry Tyrol, Innsbruck, Austria. [Oberaigner, Willi; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Informat Syst & Hlth Technol Asses, Hall In Tirol, Austria. [Oberaigner, Willi; Siebert, Uwe] Innsbruck Med Univ, Oncotyrol Ctr Personalized Canc Med, Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Ctr Hlth Decis Sci, Boston, MA 02115 USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Oberaigner, W (reprint author), TILAK GmbH, Canc Registry Tyrol, Anichstr 35, Innsbruck, Austria. EM willi.oberaigner@iet.at NR 26 TC 11 Z9 11 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA KARL JOHANS GATE 5, NO-0154 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PY 2009 VL 48 IS 7 BP 984 EP 991 DI 10.1080/02841860903188635 PG 8 WC Oncology SC Oncology GA 512EV UT WOS:000271228400006 PM 19714522 ER PT J AU Yehuda, R Schmeidler, J Labinsky, E Bell, A Morris, A Zemelman, S Grossman, RA AF Yehuda, R. Schmeidler, R. Labinsky, E. Bell, A. Morris, A. Zemelman, S. Grossman, R. A. TI Ten-year follow-up study of PTSD diagnosis, symptom severity and psychosocial indices in aging holocaust survivors SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE holocaust survivors; longitudinal course; post-traumatic stress disorder; morale; traumatic loss ID POSTTRAUMATIC-STRESS-DISORDER; WORLD-WAR-II; FORMER PRISONERS; LONGITUDINAL ASSESSMENT; LIFETIME TRAUMA; COMBAT VETERANS; IMPACT; SCALE AB Objective: We performed a longitudinal study of holocaust survivors with and without post-traumatic stress disorder ( PTSD) by assessing symptoms and other measures at two intervals, approximately 10 years apart. Method: The original cohort consisted of 63 community-dwelling subjects, of whom 40 were available for follow-up. Results: There was a general diminution in PTSD symptom severity over time. However, in 10% of the subjects (n = 4), new instances of delayed onset PTSD developed between time 1 and time 2. Self-report ratings at both assessments revealed a worsening of trauma-related symptoms over time in persons without PTSD at time 1, but an improvement in those with PTSD at time 1. Conclusion: The findings suggest that a nuanced characterization of PTSD trajectory over time is more reflective of PTSD symptomatology than simple diagnostic status at one time. The possibility of delayed onset trajectory complicates any simplistic overall trajectory summarizing the longitudinal course of PTSD. C1 [Yehuda, R.; Schmeidler, R.; Labinsky, E.; Bell, A.; Morris, A.; Zemelman, S.; Grossman, R. A.] Mt Sinai Sch Med, Dept Psychiat, Div Traumat Stress Studies, New York, NY USA. [Yehuda, R.; Schmeidler, R.; Labinsky, E.; Bell, A.; Morris, A.; Zemelman, S.; Grossman, R. A.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. RP Yehuda, R (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@va.gov FU NIMH [R01 MH 64675-01, 5 M01 RR00071]; National Institute of Health FX This work was supported by NIMH R01 MH 64675-01 entitled 'Biology of Risk and PTD in Holocaust Survivor spring' and in part by a grant (5 M01 RR00071) for the Mount Sinai General Clinical Research Center from the National Institute of Health. The authors acknowledge Ms Shira Kaufman and Mr William Blair for research coordination, and Drs Lisa Tischler and Alicia Hirsch for diagnostic evaluations and consensus conferencing. The authors report no financial or other relationship relevant to the subject of this article. NR 30 TC 26 Z9 26 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2009 VL 119 IS 1 BP 25 EP 34 DI 10.1111/j.1600-0447.2008.01248.x PG 10 WC Psychiatry SC Psychiatry GA 394LX UT WOS:000262449300004 PM 18785948 ER PT J AU Shankar, S Dundamadappa, SK Karam, AR Stay, RM van Sonnenberg, E AF Shankar, S. Dundamadappa, S. K. Karam, A. R. Stay, R. M. van Sonnenberg, E. TI Imaging of Gastrointestinal Stromal Tumors before and after Imatinib Mesylate Therapy SO ACTA RADIOLOGICA LA English DT Review DE Abdomen/GI; metastases; neoplasms; primary; staging ID RESPONSE EVALUATION; CT; RECURRENCE; SURVIVAL; EFFICACY; PATTERNS; GLEEVEC; SAFETY; PET AB Gastrointestinal stromal tumors (GISTs) account for the majority of gastrointestinal mesenchymal tumors. Recent advances in treatment using the molecular targeting agent imatinib mesylate have shown startling response rates and variegated imaging findings. We present the various imaging appearances of GIST on computed tomography (CT) and magnetic resonance imaging (MRI), both before and after treatment. C1 [Shankar, S.; Dundamadappa, S. K.; Karam, A. R.] Univ Massachusetts, Dept Radiol, Med Ctr, Worcester, MA 01655 USA. [Stay, R. M.] Univ Virginia, Dept Radiol, Charlottesville, VA USA. [van Sonnenberg, E.] Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Dundamadappa, SK (reprint author), Univ Massachusetts, Dept Radiol, Med Ctr, 55 Lake Ave N, Worcester, MA 01655 USA. EM vsnewton@yahoo.com NR 28 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0284-1851 J9 ACTA RADIOL JI Acta Radiol. PY 2009 VL 50 IS 8 BP 837 EP 844 DI 10.1080/02841850903059423 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 502KV UT WOS:000270459200002 PM 19735005 ER PT S AU Moss, M Thompson, BT AF Moss, Marc Thompson, B. Taylor BE Choi, AMK TI Definitions and Clinical Risk Factors SO Acute Respiratory Distress Syndrome, 2nd Edition SE Lung Biology in Health and Disease LA English DT Article; Book Chapter ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; MECHANICALLY VENTILATED PATIENTS; PULMONARY VASCULAR-PERMEABILITY; END-EXPIRATORY PRESSURE; CHRONIC ALCOHOL-ABUSE; INTEROBSERVER VARIATION; ORGAN FAILURE; SEPTIC SHOCK; TIDAL VOLUME C1 [Moss, Marc] Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80204 USA. [Thompson, B. Taylor] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Thompson, B. Taylor] Harvard Univ, Sch Med, Boston, MA USA. RP Moss, M (reprint author), Univ Colorado, Hlth Sci Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80204 USA. NR 77 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 0362-3181 BN 978-1-4200-8841-0; 978-1-4200-8840-3 J9 LUNG BIOL HEALTH DIS PY 2009 VL 233 BP 1 EP 16 PG 16 WC Respiratory System SC Respiratory System GA BD6KI UT WOS:000362321700004 ER PT S AU Matute-Bello, G Martin, TR AF Matute-Bello, Gustavo Martin, Thomas R. BE Choi, AMK TI Apoptosis in the Pathogenesis and Resolution of Acute Lung Injury SO Acute Respiratory Distress Syndrome, 2nd Edition SE Lung Biology in Health and Disease LA English DT Article; Book Chapter ID RESPIRATORY-DISTRESS-SYNDROME; ENDOTHELIAL-CELL APOPTOSIS; ALVEOLAR EPITHELIAL-CELLS; COLONY-STIMULATING FACTOR; FAS-INDUCED APOPTOSIS; NEUTROPHIL APOPTOSIS; IN-VIVO; PULMONARY INFLAMMATION; FIBROBLAST APOPTOSIS; CASPASE INHIBITOR C1 [Matute-Bello, Gustavo; Martin, Thomas R.] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Martin, Thomas R.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Matute-Bello, G (reprint author), Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. NR 80 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 0362-3181 BN 978-1-4200-8841-0; 978-1-4200-8840-3 J9 LUNG BIOL HEALTH DIS PY 2009 VL 233 BP 93 EP 108 PG 16 WC Respiratory System SC Respiratory System GA BD6KI UT WOS:000362321700010 ER PT S AU Gong, MN Christiani, DC AF Gong, Michelle Ng Christiani, David C. BE Choi, AMK TI Current Approaches and Recent Advances in the Genetic Epidemiology of Acute Lung Injury/Acute Respiratory Distress Syndrome SO Acute Respiratory Distress Syndrome, 2nd Edition SE Lung Biology in Health and Disease LA English DT Article; Book Chapter ID COLONY-ENHANCING FACTOR; TUMOR-NECROSIS-FACTOR; CHAIN KINASE GENE; INSERTION/DELETION POLYMORPHISM; INTERLEUKIN-10 POLYMORPHISM; POPULATION STRATIFICATION; MOLECULAR EPIDEMIOLOGY; HAPLOTYPE BLOCKS; FALSE DISCOVERY; CONFER RISK C1 [Gong, Michelle Ng] Montefiore Med Ctr, Dept Med, Crit Care Med, Bronx, NY 10467 USA. [Gong, Michelle Ng] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Christiani, David C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. [Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Gong, MN (reprint author), Montefiore Med Ctr, Dept Med, Crit Care Med, 111 E 210th St, Bronx, NY 10467 USA. NR 83 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 0362-3181 BN 978-1-4200-8841-0; 978-1-4200-8840-3 J9 LUNG BIOL HEALTH DIS PY 2009 VL 233 BP 196 EP 219 PG 24 WC Respiratory System SC Respiratory System GA BD6KI UT WOS:000362321700015 ER PT S AU Anzueto, A Gattinoni, L AF Anzueto, Antonio Gattinoni, Luciano BE Choi, AMK TI Prone Position in ARDS SO Acute Respiratory Distress Syndrome, 2nd Edition SE Lung Biology in Health and Disease LA English DT Article; Book Chapter ID RESPIRATORY-DISTRESS-SYNDROME; ACUTE LUNG INJURY; INHALED NITRIC-OXIDE; END-EXPIRATORY PRESSURE; PULMONARY BLOOD-FLOW; MECHANICAL VENTILATION; REGIONAL DISTRIBUTION; VERTICAL-DISTRIBUTION; AIRWAY PRESSURE; INSPIRED GAS C1 [Anzueto, Antonio] South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. [Anzueto, Antonio] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Gattinoni, Luciano] Osped Maggiore Policlin, Milan, Italy. RP Anzueto, A (reprint author), South Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. NR 80 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL ST, LONDON, EC2A 4LQ, ENGLAND SN 0362-3181 BN 978-1-4200-8841-0; 978-1-4200-8840-3 J9 LUNG BIOL HEALTH DIS PY 2009 VL 233 BP 313 EP 334 PG 22 WC Respiratory System SC Respiratory System GA BD6KI UT WOS:000362321700020 ER PT J AU Geller, DA Brown, TE AF Geller, Daniel A. Brown, Thomas E. BE Brown, TE TI ADHD WITH OBSESSIVE-COMPULSIVE DISORDER SO ADHD COMORBIDITIES: HANDBOOK FOR ADHD COMPLICATIONS IN CHILDREN AND ADULTS LA English DT Article; Book Chapter ID FAMILIAL RISK ANALYSIS; PSYCHIATRIC DIAGNOSES; SPECTRUM DISORDERS; FOLLOW-UP; CHILDREN; ADOLESCENTS; SCALE; PHARMACOTHERAPY; METAANALYSIS; COMORBIDITY C1 [Geller, Daniel A.] Massachusetts Gen Hosp, Pediat Obsess Compuls Disorder Program, Boston, MA 02114 USA. [Geller, Daniel A.] Harvard Univ, Sch Med, Boston, MA USA. [Brown, Thomas E.] Yale Clin Attent & Related Disorders, New Haven, CT USA. [Brown, Thomas E.] Yale Univ, Sch Med, New Haven, CT USA. RP Geller, DA (reprint author), Massachusetts Gen Hosp, Pediat Obsess Compuls Disorder Program, Boston, MA 02114 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-158-3 PY 2009 BP 177 EP 187 PG 11 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA BCE56 UT WOS:000309972600012 ER PT J AU Wilens, TE AF Wilens, Timothy E. BE Brown, TE TI ADHD WITH SUBSTANCE USE DISORDERS SO ADHD COMORBIDITIES: HANDBOOK FOR ADHD COMPLICATIONS IN CHILDREN AND ADULTS LA English DT Article; Book Chapter ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SEEKING COCAINE ABUSERS; FAMILIAL RISK ANALYSIS; ADOLESCENT DRUG-USE; 15-YEAR FOLLOW-UP; PSYCHIATRIC-DISORDERS; YOUNG-ADULTS; CONDUCT DISORDER; ALCOHOL-USE C1 [Wilens, Timothy E.] Pediat Psychopharmacol Clin, Boston, MA USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Subst Abuse Serv, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. RP Wilens, TE (reprint author), Pediat Psychopharmacol Clin, Boston, MA USA. NR 157 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-158-3 PY 2009 BP 249 EP 263 PG 15 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA BCE56 UT WOS:000309972600015 ER PT J AU Prince, JB Wilens, TE AF Prince, Jefferson B. Wilens, Timothy E. BE Brown, TE TI PHARMACOTHERAPY OF ADHD AND COMORBIDITIES SO ADHD COMORBIDITIES: HANDBOOK FOR ADHD COMPLICATIONS IN CHILDREN AND ADULTS LA English DT Article; Book Chapter ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; DEFICIT-HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; MIXED AMPHETAMINE SALTS; PLACEBO-CONTROLLED TRIAL; OPPOSITIONAL DEFIANT DISORDER; DISRUPTIVE BEHAVIOR DISORDERS; PEDIATRIC BIPOLAR DISORDER; RANDOMIZED CONTROLLED-TRIAL; POSTTRAUMATIC-STRESS-DISORDER C1 [Prince, Jefferson B.] N Shore Med Ctr, Boston, MA USA. [Prince, Jefferson B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Wilens, Timothy E.] Pediat Psychopharmacol Clin, Boston, MA USA. [Wilens, Timothy E.] Massachusetts Gen Hosp, Subst Abuse Serv, Boston, MA 02114 USA. [Wilens, Timothy E.] Harvard Univ, Sch Med, Boston, MA USA. RP Prince, JB (reprint author), N Shore Med Ctr, Boston, MA USA. NR 434 TC 0 Z9 0 U1 5 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-158-3 PY 2009 BP 339 EP 384 PG 46 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA BCE56 UT WOS:000309972600021 ER PT S AU Regan, MM AF Regan, Meredith M. BE Castiglione, M Piccart, MJ TI Statistical Issues and Challenges SO ADJUVANT THERAPY FOR BREAST CANCER SE Cancer Treatment and Research LA English DT Article; Book Chapter ID NEGATIVE BREAST-CANCER; GENE-EXPRESSION; ADJUVANT CHEMOTHERAPY; RANDOMIZED TRIAL; FOREST PLOTS; SIGNATURE; SUBSETS; THERAPY; RESPONSIVENESS; TRASTUZUMAB C1 [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat, IBCSG Stat Ctr, Boston, MA 02115 USA. [Regan, Meredith M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, IBCSG Stat Ctr, Boston, MA 02115 USA. RP Regan, MM (reprint author), Dana Farber Canc Inst, Dept Biostat & Computat, IBCSG Stat Ctr, Boston, MA 02115 USA. EM meredith_regan@dfci.harvard.edu NR 37 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-0-387-75114-6 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 BP 77 EP 90 DI 10.1007/978-0-387-75115-3_6 D2 10.1007/978-0-387-75115-3 PG 14 WC Oncology SC Oncology GA BLV65 UT WOS:000271182800006 ER PT S AU Ruddy, KJ Partridge, AH AF Ruddy, K. J. Partridge, A. H. BE Castiglione, M Piccart, MJ TI Fertility SO ADJUVANT THERAPY FOR BREAST CANCER SE Cancer Treatment and Research LA English DT Article; Book Chapter ID BREAST-CANCER PATIENTS; CRYOPRESERVED OVARIAN TISSUE; ADJUVANT CHEMOTHERAPY; YOUNG-WOMEN; PREMENOPAUSAL WOMEN; CHILDHOOD-CANCER; EMBRYO CRYOPRESERVATION; PRESERVE FERTILITY; PROGNOSTIC IMPACT; HODGKINS-DISEASE C1 [Ruddy, K. J.; Partridge, A. H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Partridge, AH (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM kruddy@partners.org; ahpartridge@partners.org NR 75 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0927-3042 BN 978-0-387-75114-6 J9 CANCER TREAT RES JI Canc. Treat. Res. PY 2009 BP 367 EP 385 DI 10.1007/978-0-387-75115-3_23 D2 10.1007/978-0-387-75115-3 PG 19 WC Oncology SC Oncology GA BLV65 UT WOS:000271182800023 ER PT B AU Boland, GWL AF Boland, G. W. L. BE Blake, MA Boland, GWL TI The Adrenals in Oncology SO ADRENAL IMAGING SE Contemporary Medical Imaging LA English DT Article; Book Chapter ID ADRENOCORTICAL CARCINOMA; CORTICAL CARCINOMA; MALIGNANT PHEOCHROMOCYTOMA; FAMILIAL PHEOCHROMOCYTOMA; PROGNOSTIC-FACTORS; RADIATION-THERAPY; P53 MUTATIONS; TUMORS; CANCER; MITOTANE C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. EM gboland@partners.org NR 74 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-86-2 J9 CONTEMP MED IMAG PY 2009 BP 65 EP 76 DI 10.1007/978-1-59745-560-2_4 D2 10.1007/978-1-59745-560-2 PG 12 WC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BJZ80 UT WOS:000267545500004 ER PT B AU Stephen, AE AF Stephen, A. E. BE Blake, MA Boland, GWL TI Adrenal Surgery SO ADRENAL IMAGING SE Contemporary Medical Imaging LA English DT Article; Book Chapter ID PRIMARY ALDOSTERONISM; INCIDENTALOMA; TUMOR C1 Massachusetts Gen Hosp, Div Surg Oncol, Ctr Canc, Boston, MA 02114 USA. RP Stephen, AE (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Ctr Canc, 55 Fruit St,YAW 7, Boston, MA 02114 USA. NR 29 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-86-2 J9 CONTEMP MED IMAG PY 2009 BP 77 EP 89 DI 10.1007/978-1-59745-560-2_5 D2 10.1007/978-1-59745-560-2 PG 13 WC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BJZ80 UT WOS:000267545500005 ER PT B AU Scott, JA AF Scott, J. A. BE Blake, MA Boland, GWL TI Single Photon Imaging of the Adrenal Gland SO ADRENAL IMAGING SE Contemporary Medical Imaging LA English DT Article; Book Chapter ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; METAIODOBENZYLGUANIDINE; PHEOCHROMOCYTOMA; MANAGEMENT; TUMORS; INDIUM-111-PENTETREOTIDE; EXPERIENCE; THERAPY C1 Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. RP Scott, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02114 USA. EM jscott2@partners.org NR 18 TC 11 Z9 11 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-86-2 J9 CONTEMP MED IMAG PY 2009 BP 157 EP 171 DI 10.1007/978-1-59745-560-2_10 D2 10.1007/978-1-59745-560-2 PG 15 WC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BJZ80 UT WOS:000267545500010 ER PT B AU Blake, MA AF Blake, M. A. BE Blake, MA Boland, GWL TI PET and PET-CT Imaging of Adrenal Lesions SO ADRENAL IMAGING SE Contemporary Medical Imaging LA English DT Article; Book Chapter ID POSITRON-EMISSION-TOMOGRAPHY; 11-BETA-HYDROXYLASE TRACER C-11-METOMIDATE; STANDARDIZED UPTAKE VALUES; F-18-FDG PET/CT; FDG-PET; ADRENOCORTICAL CARCINOMA; COMPUTED-TOMOGRAPHY; CHEMICAL-SHIFT; DIAGNOSTIC LOCALIZATION; LUNG-CANCER C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. EM Mblake2@partners.org; Mblake2@partners.org NR 69 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-934115-86-2 J9 CONTEMP MED IMAG PY 2009 BP 173 EP 191 DI 10.1007/978-1-59745-560-2_11 D2 10.1007/978-1-59745-560-2 PG 19 WC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Endocrinology & Metabolism; Pathology; Radiology, Nuclear Medicine & Medical Imaging GA BJZ80 UT WOS:000267545500011 ER PT S AU Barrett, LF Bliss-Moreau, E AF Barrett, Lisa Feldman Bliss-Moreau, Eliza BE Zanna, MP TI AFFECT AS A PSYCHOLOGICAL PRIMITIVE SO ADVANCES IN EXPERIMENTAL SOCIAL PSYCHOLOGY, VOL 41 SE ADVANCES IN EXPERIMENTAL SOCIAL PSYCHOLOGY LA English DT Article; Book Chapter ID VENTROMEDIAL PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS DOPAMINE; SPONTANEOUS TRAIT INFERENCES; HUMAN ORBITOFRONTAL CORTEX; UNKNOWN DISTANCE FUNCTION; HUMAN AMYGDALA; RHESUS-MONKEY; FACIAL EXPRESSIONS; DECISION-MAKING; INDIVIDUAL-DIFFERENCES AB In this article, we discuss the hypothesis that affect is a fundamental, psychologically irreducible property of the human mind. We begin by presenting historical perspectives on the nature of affect. Next, we proceed with a more contemporary discussion of core affect as a basic property of the mind that is realized within a broadly distributed neuronal workspace. We then present the affective circumplex, a mathematical formalization for representing core affective states, and show that this model can be used to represent individual differences in core affective feelings that are linked to meaningful variation in emotional experience. Finally, we conclude by suggesting that core affect has psychological consequences that reach beyond the boundaries of emotion, to influence learning and consciousness. C1 [Barrett, Lisa Feldman] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Program, Chestnut Hill, MA USA. [Barrett, Lisa Feldman] Boston Coll, Dept Psychol, Martinos Imaging Ctr, Dept Radiol, Chestnut Hill, MA 02167 USA. [Bliss-Moreau, Eliza] Univ Calif Davis, Dept Psychiat & Behav Sci, Sacramento, CA 95817 USA. RP Barrett, LF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Psychiat Neuroimaging Program, Chestnut Hill, MA USA. FU NIA NIH HHS [R01 AG030311-03, R01 AG030311]; NIH HHS [DP1 OD003312, DP1 OD003312-02]; NIMH NIH HHS [K02 MH001981] NR 279 TC 106 Z9 106 U1 4 U2 23 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2601 BN 978-0-12-374472-2 J9 ADV EXP SOC PSYCHOL JI Adv. Exp. Soc. Psychol. PY 2009 VL 41 BP 167 EP 218 DI 10.1016/S0065-2601(08)00404-8 PG 52 WC Psychology, Experimental; Psychology, Social SC Psychology GA BJD08 UT WOS:000264874200004 PM 20552040 ER PT S AU Petrocca, F Lieberman, J AF Petrocca, Fabio Lieberman, Judy BE Alt, FW Austen, KF Honjo, T Melchers, F Uhr, JW Unanue, ER TI Micromanagers of Immune Cell Fate and Function SO ADVANCES IN IMMUNOLOGY, VOL 102 SE Advances in Immunology LA English DT Review; Book Chapter ID TARGET MESSENGER-RNAS; MICRORNA TARGETS; POSTTRANSCRIPTIONAL REGULATION; ENCODED MICRORNAS; PROTEIN-SYNTHESIS; SYSTEMATIC IDENTIFICATION; CAENORHABDITIS-ELEGANS; MAMMALIAN-CELLS; LET-7 MICRORNA; IN-VIVO AB MicroRNAs (miRNAs) regulate cell fate during development and in response to environmental cues. Here, we review the emerging story of how miRNAs regulate immune cell development and function. C1 [Petrocca, Fabio] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Petrocca, F (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI070302] NR 99 TC 9 Z9 9 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-374801-0 J9 ADV IMMUNOL JI Adv.Immunol. PY 2009 VL 102 BP 227 EP 244 DI 10.1016/S0065-2776(09)01204-8 PG 18 WC Immunology SC Immunology GA BJW04 UT WOS:000267288200004 PM 19477322 ER PT S AU Djuretic, IM Cruz-Guilloty, F Rao, A AF Djuretic, Ivana M. Cruz-Guilloty, Fernando Rao, Anjana BE Alt, FW Austen, KF Honjo, T Melchers, F Uhr, JW Unanue, ER TI Regulation of Gene Expression in Peripheral T Cells by Runx Transcription Factors SO ADVANCES IN IMMUNOLOGY, VOL 104 SE Advances in Immunology LA English DT Review; Book Chapter ID ROR-GAMMA-T; HELPER TYPE-1 CELLS; TGF-BETA; OSTEOBLAST DIFFERENTIATION; NONCODING RNAS; HUMAN LEUKEMIA; IL4 SILENCER; HUMAN GENOME; DNA-BINDING; CBF-BETA AB Members of the Runx family of transcription factors, Runx1-3, are essential regulators of the immune system: a deficiency in one of the members, Runx1, results in complete ablation of hematopoiesis, and all three Runx proteins play important, nonredundant roles in immune system development and function. Here, we review gene regulation by Runx proteins in T lymphocytes, with a focus on their recently emerging roles in the development and function of peripheral CD4(+) and CD8(+) T lineages. C1 [Djuretic, Ivana M.; Cruz-Guilloty, Fernando; Rao, Anjana] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Djuretic, Ivana M.; Cruz-Guilloty, Fernando; Rao, Anjana] Childrens Hosp, Immune Dis Inst, Boston, MA 02115 USA. [Djuretic, Ivana M.; Cruz-Guilloty, Fernando; Rao, Anjana] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. RP Djuretic, IM (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. FU NCI NIH HHS [CA42471]; NIAID NIH HHS [AI44432, AI70788] NR 102 TC 13 Z9 13 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 978-0-12-375031-0 J9 ADV IMMUNOL JI Adv.Immunol. PY 2009 VL 104 BP 1 EP 23 DI 10.1016/S0065-2776(08)04001-7 PG 23 WC Immunology SC Immunology GA BMI38 UT WOS:000272437100001 PM 20457114 ER PT S AU Payne, RP Matthews, PC Prado, JG Goulder, PJR AF Payne, Rebecca P. Matthews, Philippa C. Prado, Julia G. Goulder, Philip J. R. BE Webster, JP TI HLA-Mediated Control of HIV and HIV Adaptation to HLA SO ADVANCES IN PARASITOLOGY, VOL 68: NATURAL HISTORY OF HOST-PARASITE INTERACTIONS SE Advances in Parasitology LA English DT Review; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; VIRAL LOAD; IMMUNE ESCAPE; CELL RESPONSES; AIDS VACCINE; GENETIC DIVERSITY; TYPE-1 INFECTION; RHESUS MACAQUES; FITNESS COST AB The human immunodeficiency virus (HIV) epidemic provides a rare opportunity to examine in detail the initial stages of a host-pathogen co-evolutionary struggle in humans. The genes encoding the human leukocyte antigen (HLA) class I molecules have a critical influence in the success or failure of the immune response against HIV. The particular HLA class I molecules expressed by each individual defines the type of cytotoxic T-lymphocyte (CTL) response that is made against the virus. This chapter describes the role of HLA class I and the CTL response in controlling HIV replication, and discusses the extent to which HIV has already adapted to those HLA class I molecules and CTL responses that are most effective in viral suppression. It is evident that viral mutations that enable HIV to evade the CTL response are indeed already accumulating in populations where the selecting HLA molecules are highly prevalent, indicating the dynamic and shifting nature of the evolutionary interplay between HIV and human populations. C1 [Payne, Rebecca P.; Matthews, Philippa C.; Prado, Julia G.; Goulder, Philip J. R.] Univ Oxford, Dept Paediat, Oxford, England. [Goulder, Philip J. R.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Goulder, Philip J. R.] Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. RP Payne, RP (reprint author), Univ Oxford, Dept Paediat, Peter Medawar Bldg Pathogen Res, Oxford, England. OI Matthews, Philippa/0000-0002-4036-4269 FU Medical Research Council [G0501777] NR 78 TC 5 Z9 6 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-308X BN 978-0-12-374787-7 J9 ADV PARASIT JI Adv.Parasitol. PY 2009 VL 68 BP 1 EP + DI 10.1016/S0065-308X(08)00601-5 PG 21 WC Parasitology SC Parasitology GA BJI66 UT WOS:000266158900001 PM 19289188 ER PT J AU Gleason, CE Carlsson, CM Barnet, JH Meade, SA Setchell, KDR Atwood, CS Johnson, SC Ries, ML Asthana, S AF Gleason, Carey E. Carlsson, Cynthia M. Barnet, Jodi H. Meade, Sarah A. Setchell, Kenneth D. R. Atwood, Craig S. Johnson, Sterling C. Ries, Michele L. Asthana, Sanjay TI A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women SO AGE AND AGEING LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; HEALTH INITIATIVE MEMORY; POSTMENOPAUSAL WOMEN; PHARMACOKINETICS; CONSUMPTION; FREQUENCY; LIPIDS; SERUM; EQUOL AB Background: a small number of reports exist on the cognitive effects of soy isoflavones, the findings from which are mixed. Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons. Of particular interest is the production of the metabolite, equol, which is dependent upon intestinal microflora and an integrous digestive system, both being altered by age and age-associated conditions. Unfortunately, few studies enrolled adults over the age of 70, and none included older men. Objective: we examined safety, feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women (age 62-89 years). Design and Methods: in this randomised, placebo-controlled, double-blind pilot study, subjects ingested either 100 mg/day soy isoflavones (glycoside weight) or matching placebo tablets for 6 months. Results: active and placebo-treated subjects exhibited a comparable side-effect profile. Plasma levels of genistein and daidzein (P < 0.001), but not equol, increased with isoflavone administration. While similar at baseline, the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered. Isoflavone-treated subjects improved on tests of visual-spatial memory (P < 0.01) and construction (P = 0.01), verbal fluency (P < 0.01) and speeded dexterity (P = 0.04). Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function (P < 0.05). Conclusions: these data suggest that administration of 100 mg/day of isoflavones was well tolerated. Plasma genistein and daidzein levels, but not equol, increased with isoflavone administration. Finally, data support the potential cognitive effects of soy isoflavones in older adults. C1 [Gleason, Carey E.; Carlsson, Cynthia M.; Meade, Sarah A.; Atwood, Craig S.; Johnson, Sterling C.; Ries, Michele L.; Asthana, Sanjay] Univ Wisconsin, Dept Med, Madison VA GRECC 11G, Sect Geriatr & Gerontol, Madison, WI 53705 USA. [Gleason, Carey E.; Carlsson, Cynthia M.; Atwood, Craig S.; Johnson, Sterling C.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. [Barnet, Jodi H.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53792 USA. [Meade, Sarah A.] Univ Wisconsin, Wisconsin Alzheimers Inst, Madison, WI 53719 USA. [Setchell, Kenneth D. R.] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45267 USA. [Setchell, Kenneth D. R.] Cincinnati Childrens Hosp, Med Ctr, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. RP Gleason, CE (reprint author), Univ Wisconsin, Dept Med, Madison VA GRECC 11G, Sect Geriatr & Gerontol, 2500 Overlook Terrace, Madison, WI 53705 USA. EM ceg@medicine.wisc.edu FU UW General Clinical Research Center from the National Center for Research Resources, National Institutes of Health [M01 RR03186]; NIH/NIA [K23 AG024302] FX Work was supported by grants: M01 RR03186 awarded to The UW General Clinical Research Center from the National Center for Research Resources, National Institutes of Health and K23 AG024302 NIH/NIA (C.E.G.). Archer Daniels Midland provided Novasoy brand isoflavones tablets and matching placebo. Sponsors of the project played no role in the design, execution, analysis or interpretation of the data or writing of the study. NR 32 TC 30 Z9 31 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD JAN PY 2009 VL 38 IS 1 BP 86 EP 93 DI 10.1093/ageing/afn227 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 395IP UT WOS:000262518100017 PM 19054783 ER PT J AU Taft, CT Bryant-Davis, T Woodward, HE Tillman, S Torres, SE AF Taft, Casey T. Bryant-Davis, Thema Woodward, Halley E. Tillman, Shaquita Torres, Sandra E. TI Intimate partner violence against African American women: An examination of the socio-cultural context SO AGGRESSION AND VIOLENT BEHAVIOR LA English DT Article DE African Americans; Intimate partner violence ID POSTTRAUMATIC-STRESS-DISORDER; DOMESTIC VIOLENCE; MENTAL-HEALTH; INTERVENTION PROGRAM; DEPRESSIVE SYMPTOMS; CAUCASIAN BATTERERS; COLLECTIVE EFFICACY; STRUCTURAL FACTORS; ABUSIVE PARTNERS; RACIAL IDENTITY AB Intimate partner violence (IPV) is a significant public health concern that affects an alarmingly high percentage of women. There is evidence to Suggest that African American women are impacted by IPV at higher rates than are Caucasian women, yet little of the IPV literature addresses the cultural and structural factors that differentially affect African American and Caucasian couples. The present paper reviews the existing literature on IPV towards African American women, including prevalence, theories, risk factors for victimization, victims' psychological sequelae, barriers to service utilization. coping strategies. and interventions for survivors and perpetrators of IPV. Recommendations for counseling, research, and policy are explored. Published by Elsevier Ltd. C1 [Taft, Casey T.; Woodward, Halley E.] VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. [Taft, Casey T.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. [Bryant-Davis, Thema; Tillman, Shaquita] Pepperdine Univ, Grad Sch Educ & Psychol, Malibu, CA USA. [Torres, Sandra E.] VA Boston Healthcare Syst, Womens Hlth Sci Div, Natl Ctr PTSD, Boston, MA 02130 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Behav Sci Div, Natl Ctr PTSD, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM Casey.Taft@va.gov NR 91 TC 30 Z9 30 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-1789 J9 AGGRESS VIOLENT BEH JI Aggress. Violent Behav. PD JAN-FEB PY 2009 VL 14 IS 1 BP 50 EP 58 DI 10.1016/j.avb.2008.10.001 PG 9 WC Criminology & Penology; Psychology, Multidisciplinary SC Criminology & Penology; Psychology GA 407TS UT WOS:000263387800006 ER PT J AU Paukert, AL LeMaire, A Cully, JA AF Paukert, Amber Lynn LeMaire, Ashley Cully, Jeffrey A. TI Predictors of depressive symptoms in older veterans with heart failure SO AGING & MENTAL HEALTH LA English DT Article DE depression; locus of control; illness intrusiveness; anxiety; geriatric ID PERCEIVED SOCIAL SUPPORT; QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES; MULTIDIMENSIONAL SCALE; ILLNESS INTRUSIVENESS; ELDERLY-PATIENTS; HEALTH-STATUS; PREVALENCE; VALIDATION; DISEASE AB Objectives: This study collected data on demographic factors, heart failure physical limitations, perception of heart failure intrusiveness, coping mechanisms, locus of control, self-efficacy and social support for 104 older veterans with heart failure (HF) to determine the factors' relative importance in predicting depressive symptoms. Method: Participants were veterans at least 60 years of age with HF who were screened for depression and anxiety with the Geriatric Depression Scale and Geriatric Anxiety Inventory, respectively, so that the final sample consisted of equal numbers with and without significant levels of anxiety and depression. Other measures included the Kansas City Cardiomyopathy Questionnaire, Heart Failure Illness Intrusiveness Rating Scale, Brief-COPE, Multidimensional Health Locus of Control Scale, Chronic Disease Self-Efficacy and Multidimensional Scale of Perceived Social Support. Results: Correlational analyses indicated that depressive symptoms were significantly associated with physical limitations from HF, HF perceptions of intrusiveness, maladaptive coping, attributing locus of control to chance and HF self-efficacy. Including these variables in one regression equation predicting depressive symptoms indicated that perceptions of intrusiveness from HF and attributing locus of control to chance were the only variables to predict depressive symptoms independent of the influence of other significant bivariate predictors. Conclusion: Even if physical limitations, maladaptive coping and self-efficacy are held constant, decreasing perceptions of HF intrusiveness and locus of control to chance reduce depressive symptoms. These two cognitive/perceptual factors may play a salient role in treatment of depression among older HF patients. C1 [Paukert, Amber Lynn] Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Paukert, Amber Lynn; LeMaire, Ashley; Cully, Jeffrey A.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Paukert, Amber Lynn; Cully, Jeffrey A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Cully, Jeffrey A.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. RP Paukert, AL (reprint author), Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. EM Amber.Paukert@VA.gov NR 65 TC 25 Z9 25 U1 4 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1360-7863 J9 AGING MENT HEALTH JI Aging Ment. Health PY 2009 VL 13 IS 4 BP 601 EP 610 AR PII 913279815 DI 10.1080/13607860802459823 PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 474JP UT WOS:000268279900013 PM 19629786 ER PT J AU Selesniemi, K Lee, HJ Niikura, T Tilly, JL AF Selesniemi, Kaisa Lee, Ho-Joon Niikura, Teruko Tilly, Jonathan L. TI Young adult donor bone marrow infusions into female mice postpone age-related reproductive failure and improve offspring survival SO AGING-US LA English DT Article DE stem cell; bone marrow; ovary; fertility; aging; reproduction; menopause ID STEM-CELL TRANSPLANTATION; ADVANCED CHRONOLOGICAL AGE; TOTAL-BODY IRRADIATION; GERM-CELLS; PERIPHERAL-BLOOD; PROGENITOR CELLS; LIFE-SPAN; CHEMOTHERAPY; FERTILITY; OOCYTES AB The female reproductive axis is the first major organ system of the body to fail with advancing age. In addition to a permanent cessation of fertile potential, the loss of cyclic ovarian function in humans heralds the onset of menopause, which in turn underlies the emergence of a diverse spectrum of health issues in aging women. Recently, it was reported that bone marrow (BM) transplantation (BMT) into adult female mice conditioned a week earlier with highly cytotoxic drugs rescues ovarian function and fertility. Herein we show in mice receiving no prior conditioning regimen that once monthly infusions of BM-derived cells retrieved from young adult female donors bearing an enhanced green fluorescent protein (EGFP) transgene sustain the fertile potential of aging wild-type females long past their time of normal reproductive senescence. The fertility-promoting effects of female donor BM are observed regardless whether the infusions are initiated in young adult or middle-aged females. Although the mechanism by which BM infusions benefit the reproductive performance of aging females remains to be elucidated, the absence of EGFP-expressing offspring suggests that it does not depend on development of mature eggs derived from germline-committed cells in the donor marrow. However, donor BM-derived somatic cells accumulate in the recipients, indicating efficient donor cell engraftment without prior conditioning. These findings provide a strong impetus to further explore development of adult stem cell-based technologies to safely extend function of the female reproductive axis into advanced age without the need for toxic preconditioning protocols routinely used in other models of stem cell delivery. C1 [Selesniemi, Kaisa; Lee, Ho-Joon; Niikura, Teruko; Tilly, Jonathan L.] Harvard Univ, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Massachusetts Gen Hosp,Med Sch, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Vincent Ctr Reprod Biol, Vincent Obstet & Gynecol Serv, Massachusetts Gen Hosp,Med Sch, 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; Vincent Memorial Research Funds FX We thank L. Prickett and K. Folz-Donahue (Harvard Stem Cell Institute Flow Cytometry Core Facility) for technical assistance with analysis of EGFP chimerism in BM. 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, and Vincent Memorial Research Funds. NR 40 TC 19 Z9 19 U1 0 U2 5 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1945-4589 J9 AGING-US JI Aging-US PD JAN PY 2009 VL 1 IS 1 BP 49 EP 57 PG 9 WC Cell Biology SC Cell Biology GA 579DK UT WOS:000276347200008 ER PT J AU Dryden-Peterson, S Sunpath, H Gandhi, RT AF Dryden-Peterson, Scott Sunpath, Henry Gandhi, Rajesh T. BE Kaufmann, SHE Walker, BD TI Clinical Issues in the Diagnosis and Management of HIV Infection SO AIDS AND TUBERCULOSIS: A DEADLY LIAISON LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; SUB-SAHARAN AFRICA; REVERSE-TRANSCRIPTASE INHIBITORS; SEXUALLY-TRANSMITTED-DISEASES; CENTRAL-NERVOUS-SYSTEM; HIGH-INCOME COUNTRIES; HEPATITIS-B-VIRUS; COST-EFFECTIVENESS; HIV-1-INFECTED PATIENTS C1 [Dryden-Peterson, Scott; Gandhi, Rajesh T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Sunpath, Henry] McCord Hosp, Dept Med, ZA-4067 Durban, Kwazulu Natal, South Africa. RP Dryden-Peterson, S (reprint author), Massachusetts Gen Hosp, Div Infect Dis, GRJ 504, Boston, MA 02114 USA. NR 138 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-527-32270-1 PY 2009 BP 157 EP 190 D2 10.1002/9783527627905 PG 34 WC Immunology; Infectious Diseases; Pharmacology & Pharmacy SC Immunology; Infectious Diseases; Pharmacology & Pharmacy GA BUA18 UT WOS:000288599200008 ER PT J AU Pinkerton, SD Bogart, LM Howerton, D Snyder, S Becker, K Asch, SM AF Pinkerton, Steven D. Bogart, Laura M. Howerton, Devery Snyder, Susan Becker, Kirsten Asch, Steven M. TI Cost of OraQuick oral fluid rapid HIV testing at 35 community clinics and community-based organizations in the USA SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE HIV; rapid testing; cost; community-based organizations ID UNITED-STATES; PREVENTION; INFECTION; VIRUS AB The US Centers for Disease Control and Prevention recommends the expanded use of rapid HIV antibody tests in community settings to increase the proportion of persons who are aware of their HIV status. The cost of providing rapid testing services in these settings is not known. We conducted a cost survey of non-profit community clinics and community-based organizations (CBOs). The final study sample for the cost analyses included 28 community clinics and seven CBOs that offered rapid HIV testing, all of which used OraSure's OraQuick oral fluid assay. Overall, the mean per-client rapid testing cost was $36.68 for HIV-negative clients (2006 dollars, provider perspective) and $44.22 for preliminary-positive clients. Personnel costs accounted for 55.6% of overall testing costs for negative clients and 63.2% for preliminary-positive clients. This study contributes unique empirical data about the costs of OralQuick rapid testing that can be used by clinic and CBO directors to assess the economic impact of implementing rapid testing at their sites. The findings also could be used to inform discussions regarding national and local HIV testing policies. C1 [Pinkerton, Steven D.] Med Coll Wisconsin, Dept Psychiat & Behav Med, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. [Bogart, Laura M.; Becker, Kirsten; Asch, Steven M.] RAND Corp, Hlth Program, Santa Monica, CA USA. [Bogart, Laura M.] Harvard Univ, Sch Med, Childrens Hosp Boston, Cambridge, MA 02138 USA. [Howerton, Devery; Snyder, Susan] Ctr Dis Control & Prevent, Div Lab Syst, Lab Practice Evaluat & Genom Branch, Atlanta, GA USA. [Asch, Steven M.] VA Greater Los Angeles Healthcare Network, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Pinkerton, SD (reprint author), Med Coll Wisconsin, Dept Psychiat & Behav Med, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. EM pinkrton@mcw.edu FU NIMH NIH HHS [P30-MH52776]; PHS HHS [U65/CCU924523-01] NR 20 TC 7 Z9 7 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2009 VL 21 IS 9 BP 1157 EP 1162 DI 10.1080/09540120902729940 PG 6 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 515MX UT WOS:000271477000010 PM 20024775 ER PT J AU Reisner, SL Mimiaga, MJ Safren, SA Mayer, KH AF Reisner, Sari L. Mimiaga, Matthew J. Safren, Steven A. Mayer, Kenneth H. TI Stressful or traumatic life events, post-traumatic stress disorder (PTSD) symptoms, and HIV sexual risk taking among men who have sex with men SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article DE stressful life events; PTSD; HIV; STD; MSM; syndemics ID BISEXUAL MEN; CAGE QUESTIONNAIRE; HIDDEN POPULATIONS; GAY MEN; DEPRESSION; CHILDHOOD; ABUSE; BEHAVIOR; COMORBIDITY; VULNERABILITY AB The present study assessed the presence of post-traumatic stress disorder (PTSD) symptoms in response to stressful or traumatic life events and their impact on HIV risk behaviors and associated psychosocial variables among men who have sex with men (MSM). Participants (n = 189; 60% HIV-infected) who were recruited by notices posted in a community health clinic and via a modified respondent-driven sampling technique completed a behavioral assessment survey. Sixty percentage of participants screened positive for having PTSD symptoms using the startle, physiological arousal, anger, and numbness screening instrument. After controlling for race, sexual self-identification, and HIV status, multivariable logistic regression analyses revealed that screening in for having PTSD symptoms was significantly associated with having engaged in unprotected anal (insertive or receptive) sex in the past 12 months, over and above any effects of whether or not a traumatic/stressful event occurred during the year (adjusted odds ratio [OR] = 2.72; p < 0.02; 95% confidence interval [CI] = 1.19-6.20). In addition, MSM with PTSD symptoms were more likely to have clinically significant depressive symptoms (adjusted OR = 3.50; p < 0.001) and/or symptoms of social anxiety (adjusted OR = 2.87; p < 0.01; 95% CI = 1.48-5.62). The current study, in the context of other research documenting the high rates of co-occurring psychosocial issues facing MSM, points to the importance of incorporating coping with these issues in HIV and sexually transmitted disease prevention and care interventions. C1 [Reisner, Sari L.; Mimiaga, Matthew J.; Safren, Steven A.; Mayer, Kenneth H.] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mayer, Kenneth H.] Miriam Hosp, Brown Med Sch, Providence, RI 02906 USA. RP Reisner, SL (reprint author), Fenway Community Hlth, Fenway Inst, Boston, MA USA. EM sreisner@fenwayhealth.org NR 51 TC 33 Z9 34 U1 6 U2 15 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2009 VL 21 IS 12 BP 1481 EP 1489 DI 10.1080/09540120902893258 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 535YU UT WOS:000273008700001 PM 20024727 ER PT J AU Rodriguez, M Daniels, B Gunawardene, S Robbins, GK AF Rodriguez, M. Daniels, B. Gunawardene, S. Robbins, G. K. TI High Frequency of Vitamin D Deficiency in Ambulatory HIV-Positive Patients SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; BONE-MINERAL DENSITY; D SUPPLEMENTATION; HIV-1-INFECTED PATIENTS; YOUNG-ADULTS; PREVALENCE; CALCIUM; OSTEOPENIA; WOMEN AB Several reports have suggested an increased prevalence of osteopenia and osteoporosis in HIV-infected individuals. Vitamin D deficiency may be a risk factor for osteoporosis and bone fractures. We aimed to determine the prevalence of vitamin D insufficiency in an outpatient HIV clinic in Boston. We collected serum levels of 25-OH vitamin D and evaluated calcium and vitamin D intake in adult HIV-positive outpatients during the winter and spring of 2005. Fifty-seven subjects were enrolled. The prevalence of moderate (<= 20 and >10 ng/ml) and severe (<= 10 ng/ml) 25-OH vitamin D deficiency was 36.8% and 10.5%, respectively. Lower vitamin D intake was significantly associated with severe 25-OH vitamin D deficiency (p = 0.01). Lactose intolerance tended to be associated with severe vitamin D deficiency (p = 0.08). Antiretroviral use and low daily calcium intake were significantly associated with elevated parathyroid hormone levels (p = 0.01 and 0.03, respectively). Vitamin D deficiency was frequent in ambulatory HIV-positive patients. HIV-infected individuals living in areas with low exposure to ultraviolet light during winter may benefit from vitamin D supplementation. C1 [Rodriguez, M.] Univ Alabama, Dept Med, Montgomery Hlth Ctr, Montgomery, AL 36116 USA. [Rodriguez, M.; Daniels, B.; Gunawardene, S.; Robbins, G. K.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Rodriguez, M.; Daniels, B.; Robbins, G. K.] Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. [Gunawardene, S.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Rodriguez, M (reprint author), Univ Alabama, Dept Med, Montgomery Hlth Ctr, 4371 Narrow Lane Rd,Suite 200, Montgomery, AL 36116 USA. EM Mrodri2@uab.edu FU Bristol-Myers Squibb Virology Fellows Research [1K01AI062435-032]; Harvard Medical School Center for AIDS Research [P30 AI 60354]; NIH [5R21DK67905-2] FX Presented in part at the 43rd Infectious Disease Society of America Meeting, San Francisco, 2005. The study was supported by the Bristol-Myers Squibb Virology Fellows Research Program (M. R.), 1K01AI062435-032 (G. K. R.), and the Harvard Medical School Center for AIDS Research (P30 AI 60354). A portion of the data was provided by the ongoing study, Acid-Base Balance and Bone Resorption in HIV-Infected Individuals, and Dr. Robert Neer, supported by NIH Grant 5R21DK67905-2. We thank the patients who volunteered to participate in this study, Jane Hubbard, R. D., who provided the calcium and vitamin D intake questionnaire, and the providers and nurses from our Infectious Disease Clinic, who helped recruit patients and obtain blood samples. NR 46 TC 76 Z9 78 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN PY 2009 VL 25 IS 1 BP 9 EP 14 DI 10.1089/aid.2008.0183 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 402GZ UT WOS:000263003500002 PM 19108690 ER PT J AU Savas, LS White, DL Wieman, M Daci, K Fitzgerald, S Smith, SL Tan, G Graham, DP Cully, JA El-Serag, HB AF Savas, L. S. White, D. L. Wieman, M. Daci, K. Fitzgerald, S. Smith, S. Laday Tan, G. Graham, D. P. Cully, J. A. El-Serag, H. B. TI Irritable bowel syndrome and dyspepsia among women veterans: prevalence and association with psychological distress SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FUNCTIONAL GASTROINTESTINAL DISORDERS; DEPRESSION INVENTORY-II; PSYCHOSOCIAL-ASPECTS; ABDOMINAL-PAIN; HEALTH-STATUS; RISK-FACTORS; POPULATION; SYMPTOMS; DISEASE AB Background The burden of functional GI disorders and their associations with psychological distress in women veterans is unclear. Aim To examine 1-year prevalence of irritable bowel syndrome (IBS) and dyspepsia symptoms and their associations with anxiety, depression and post-traumatic stress disorder (PTSD) among women veterans receiving primary care at a Veteran Affairs Medical Center Women's Clinic. Methods Irritable bowel syndrome, dyspepsia and psychological distress were assessed using the validated self-administered Bowel Disorder Questionnaire, the Beck Depression and Anxiety Inventories, as well as the Mississippi Scale for Combat-Related Post-Traumatic Stress Disorder Questionnaire. Results We enrolled 248 women (84% participation rate). Ninety-three (38%) reported IBS and 51 (21%) dyspepsia symptoms. Women with IBS and dyspepsia reported higher mean scores of anxiety (IBS: 24 vs. 12, P < 0.0005 and dyspepsia: 26 vs. 12, P < 0.0005), depression (IBS: 22 vs. 11, P = 0.0005 and dyspepsia: 23 vs. 11, P < 0.0005) and PTSD (IBS: 87 vs. 69, P < 0.001 and dyspepsia: 86 vs. 69, P < 0.0005). Age-and ethnicity-adjusted logistic regression analyses showed a 3-to 46-fold increase in odds of IBS and dyspepsia among women with anxiety, depression or PTSD. Conclusion Women veterans have high prevalence of IBS and dyspepsia symptoms, both of which are highly associated with presence of depression, anxiety and PTSD. C1 [Savas, L. S.; White, D. L.; Wieman, M.; Fitzgerald, S.; Cully, J. A.; El-Serag, H. B.] Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. [Savas, L. S.] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. [White, D. L.; Wieman, M.; Graham, D. P.; Cully, J. A.; El-Serag, H. B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev Serv, Houston, TX USA. [White, D. L.; Daci, K.; El-Serag, H. B.] Baylor Coll Med, Gastroenterol Sect, Houston, TX 77030 USA. [White, D. L.; Daci, K.; El-Serag, H. B.] Michael E DeBakey Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. [Smith, S. Laday] Michael E DeBakey Dept Vet Affairs Med Ctr, Omen Vet Program, Houston, TX USA. [Smith, S. Laday] Baylor Coll Med, Dept Anesthesiol & Phys Med & Rehabil, Houston, TX 77030 USA. [Graham, D. P.; Cully, J. A.] Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Cully, J. A.] Vet Affairs S Cent Mental Illness Res Educ & Clin, Houston, TX USA. RP El-Serag, HB (reprint author), Houston VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu RI Graham, David /J-1158-2014 FU Novartis pharmaceuticals; National Institute of Health [K-24 DK07815403]; Health Resources and Services [5 T32 HP10031-09]; Veterans Health Administration, HSR D Service [CDA-2; 05-288] FX Declaration of personal interests: Hashim El-Serag has served as a consultant and an advisory board member for Novartis Pharmaceuticals. None of the authors is an employee, owns stocks or shares, or has patents that constitute a conflict of interest. Hashem B. El-Serag was responsible for the study design. Hashem B. El-Serag, Donna L. White and Lara S. Savas were responsible for the interpretation of results and manuscript. Data analysis was done by Lara S. Savas. All authors reviewed and revised the manuscript of the paper and approved its final version. All analyses and writing was conducted solely by the listed authors. There are no conflicts of interest. Declaration of funding interests: This material is based upon work supported in part by Health Services Research and Development (HSR& D) Service, Office of Research and Development, Department of Veterans Affairs. This study is partly funded by a grant from Novartis pharmaceuticals to Dr El-Serag. Dr El-Serag is supported by National Institute of Health grant K-24 DK07815403. Dr Savas is supported by the National Research Service Award 5 T32 HP10031-09 funded by the Health Resources and Services. Dr Cully is supported by a Career Development Award (CDA-2; 05-288) from the Veterans Health Administration, HSR& D Service. NR 58 TC 32 Z9 33 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD JAN 1 PY 2009 VL 29 IS 1 BP 115 EP 125 DI 10.1111/j.1365-2036.2008.03847.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 384ZB UT WOS:000261781600013 PM 18785989 ER PT J AU Castaldo, A Lumry, W Caballero, T Vernon, M Blaustein, M Wilson, D AF Castaldo, A. Lumry, W. Caballero, T. Vernon, M. Blaustein, M. Wilson, D. TI Humanistic burden of hereditary angioedema: health-related quality of life, depression, productivity, and social consequences SO ALLERGY LA English DT Meeting Abstract CT 28th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2009 CL Warsaw, POLAND SP European Acad Allergy & Clin Immunol C1 [Castaldo, A.] US Hereditary Angioedema Assoc, New Bedford, MA USA. [Lumry, W.] AARA Res Ctr, Dallas, TX USA. [Caballero, T.] Univ Hosp La Paz, Secc Alergia, Madrid, Spain. [Vernon, M.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. [Blaustein, M.] Dyax Corp, Alliance Management, Cambridge, MA USA. [Wilson, D.] Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Clin Invest, Boston, MA 02114 USA. NR 0 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 0105-4538 J9 ALLERGY JI Allergy PY 2009 VL 64 MA 567 BP 232 EP 232 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 447DJ UT WOS:000266171500548 ER PT J AU Wilson, D Bork, K Cicardi, M Rentz, A Castaldo, A Blaustein, M AF Wilson, D. Bork, K. Cicardi, M. Rentz, A. Castaldo, A. Blaustein, M. TI Resource utilisation associated with acute and chronic management of hereditary angioedema SO ALLERGY LA English DT Meeting Abstract CT 28th Congress of the European-Academy-of-Allergy-and-Clinical-Immunology CY JUN 06-10, 2009 CL Warsaw, POLAND SP European Acad Allergy & Clin Immunol C1 [Wilson, D.] Massachusetts Gen Hosp, Inst Hlth Profess, Grad Program Clin Invest, Boston, MA 02114 USA. [Bork, K.] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Cicardi, M.] Univ Milan, Inst Internal Med, L Sacco Hosp, I-20122 Milan, Italy. [Rentz, A.] United BioSource Corp, Ctr Hlth Outcomes Res, Bethesda, MD USA. [Castaldo, A.] US Hereditary Angioedema Assoc, New Bedford, MA USA. [Blaustein, M.] Dyax Corp, Alliance Management, Cambridge, MA USA. NR 0 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 0105-4538 J9 ALLERGY JI Allergy PY 2009 VL 64 MA 1076 BP 412 EP 412 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 447DJ UT WOS:000266171501042 ER PT J AU Banerji, A Sheffer, AL AF Banerji, Aleena Sheffer, Albert L. TI The spectrum of chronic angioedema SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article CT Meeting of the Eastern-Allergy-Society CY MAY 04, 2008 CL Naples, FL SP Eastern Allergy Soc DE ACE inhibitors; androgens; angioneurotic; bradykinin; C1 inhibitor; hereditary; idiopathic; kallikrein; swelling ID INHIBITOR-ASSOCIATED ANGIOEDEMA; HEREDITARY ANGIONEUROTIC-EDEMA; CAPILLARY LEAK SYNDROME; KALLIKREIN-KININ SYSTEMS; 1ST COMPLEMENT COMPONENT; OF-THE-LITERATURE; EPISODIC ANGIOEDEMA; ACE-INHIBITOR; SERUM-LEVELS; EOSINOPHILIA AB This article focuses specifically on angioedema. Chronic angiodema represents a wide range of diseases and call be categorized into several forms including hereditary, acquired, drug induced, and idiopathic. Hereditary and acquired angioedema are known to be a result of abnormalities in C1 inhibitor protein while the mechanism of drug-induced and idiopathic angiodema is less clear. Significant advances have been made in recent years with regard to diagnosis and management of these patients leading to a significant reduction in morbidity and mortality. Several novel therapies are in clinical trials and should be available in the United States within the next year. There is still a lot to learn about the pathophysiology, diagnosis, and treatment of patients with chronic angioedema. This review will hopefully provide more information to the readers who care for patients with these disorders and also stimulate further interest and research into the pathophysiology of these conditions. C1 [Banerji, Aleena] Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sheffer, Albert L.] Harvard Univ, Div Rheumatol Allergy & Immunol, Brigham & Womens Hosp, Sch Med, Boston, MA 02114 USA. RP Banerji, A (reprint author), Harvard Univ, Sch Med, Div Rheumatol Allergy & Immunol, Massachusetts Gen Hosp, 100 Blossom St,Cox 201, Boston, MA 02114 USA. EM abanerji@partners.org NR 53 TC 22 Z9 22 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD JAN-FEB PY 2009 VL 30 IS 1 BP 11 EP 16 DI 10.2500/aap.2009.30.3188 PG 6 WC Allergy SC Allergy GA 414HG UT WOS:000263853900002 PM 19331715 ER PT J AU Reifel, N Bayhylle, R Harada, N Villa, V AF Reifel, Nancy Bayhylle, Ruth Harada, Nancy Villa, Valentine TI American Indian Veterans' Views about Their Choices in Health Care: VA, IHS, and Medicare SO AMERICAN INDIAN CULTURE AND RESEARCH JOURNAL LA English DT Article ID SYSTEM; SERVICES; HISTORY C1 [Bayhylle, Ruth] Univ Calif Los Angeles, Dept Informat Studies, Los Angeles, CA 90024 USA. [Bayhylle, Ruth] Native Amer Vet Grp, Los Angeles, CA USA. [Harada, Nancy] Vet Adm Greater Los Angeles Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Hlth Serv Res, Los Angeles, CA USA. [Villa, Valentine] Calif State Coll, Los Angeles, CA USA. [Villa, Valentine] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. NR 22 TC 0 Z9 0 U1 1 U2 2 PU U C L A, AMER INDIAN STUDIES CENTER PI LOS ANGELES PA 3220 CAMPBELL HALL, BOX 951548, LOS ANGELES, CA 90095-1548 USA SN 0161-6463 J9 AM INDIAN CULT RES J JI Am. Indian Cult. Res. J. PY 2009 VL 33 IS 3 BP 23 EP 33 PG 11 WC History SC History GA 502NB UT WOS:000270466000003 ER PT J AU Naik, A Dyer, C Kunik, M McCullough, L AF Naik, Aanand D. Dyer, Carmel B. Kunik, Mark E. McCullough, Laurence B. TI Patient Autonomy for the Management of Chronic Conditions: A Two-Component Re-Conceptualization SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE autonomy; decision-making; capacity; executive control functions; older adults; functional assessment ID EXECUTIVE CONTROL FUNCTIONS; INFORMED CONSENT; DECISION-MAKING; ELDERLY PERSONS; CARE; IMPAIRMENT; COMPETENCE; INSTRUMENT; LITERACY; CAPACITY AB The clinical application of the concept of patient autonomy has centered on the ability to deliberate and make treatment decisions (decisional autonomy) to the virtual exclusion of the capacity to execute the treatment plan (executive autonomy). However, the one-component concept of autonomy is problematic in the context of multiple chronic conditions. Adherence to complex treatments commonly breaks down when patients have functional, educational, and cognitive barriers that impair their capacity to plan, sequence, and carry out tasks associated with chronic care. The purpose of this article is to call for a two-component re-conceptualization of autonomy and to argue that the clinical assessment of capacity for patients with chronic conditions should be expanded to include both autonomous decision-making and autonomous execution of the agreed-upon treatment plan. We explain how the concept of autonomy should be expanded to include both decisional and executive autonomy, describe the biopsychosocial correlates of the two-component concept of autonomy, and recommend diagnostic and treatment strategies to support patients with deficits in executive autonomy. C1 [Naik, Aanand D.; Kunik, Mark E.] Houston Ctr Qual Care Utilizat Studies, Baylor Coll Med, Michael DeBakey VA Med Ctr, Houston, TX USA. [McCullough, Laurence B.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Dyer, Carmel B.] Univ Texas Houston, Sch Med, Houston, TX USA. RP Naik, A (reprint author), Michael E DeBakey VA Med Ctr 152, Houston Ctr Qual Care & Utilizat Studies, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM anaik@bcm.tmc.edu FU Houston Center for Quality of Care & Utilization Studies; Michael E. DeBakey Veterans Affairs Medical Center; Consortium for Research in Elder Self-Neglect of Texas (NIH) [P20-RR020626]; Greenwall Foundation; National Institute of Aging [K23AG027144]; [FP90-020] FX This article is the result of work supported with resources and the use of facilities at the Houston Center for Quality of Care & Utilization Studies (FP90-020), Michael E. DeBakey Veterans Affairs Medical Center, the Consortium for Research in Elder Self-Neglect of Texas (NIH P20-RR020626), and a bioethics grant from the Greenwall Foundation. Dr. Naik is also supported by the National Institute of Aging (K23AG027144). The authors would like to thank Sonora Hudson for her careful review of a prior version of the manuscript. NR 47 TC 34 Z9 34 U1 1 U2 6 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 2 BP 23 EP 30 AR PII 908346820 DI 10.1080/15265160802654111 PG 8 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 400ZG UT WOS:000262907300011 PM 19180389 ER PT J AU Celone, K Stern, C AF Celone, Kim Stern, Chantal TI A Neuroimaging Perspective on the Use of Functional Magnetic Resonance Imaging (fMRI) in Educational and Legal Systems SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material ID NEUROSCIENCE C1 [Celone, Kim; Stern, Chantal] Boston Univ, Silvio O Conte Ctr Memory & Brain, Boston, MA 02143 USA. [Celone, Kim; Stern, Chantal] Massachusetts Gen Hosp, Ctr Biomed Imaging, Boston, MA 02114 USA. RP Stern, C (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St,Room 105, Boston, MA 02143 USA. EM chantal@bu.edu NR 9 TC 2 Z9 2 U1 2 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2009 VL 9 IS 1 BP 28 EP 29 DI 10.1080/15265160802617985 PG 2 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 400ZD UT WOS:000262907000009 PM 19132617 ER PT J AU McClelland, RL Nasir, K Budoff, M Blumenthal, RS Kronmal, RA AF McClelland, Robyn L. Nasir, Khurram Budoff, Matthew Blumenthal, Roger S. Kronmal, Richard A. TI Arterial Age as a Function of Coronary Artery Calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA]) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK-ASSESSMENT; CHOLESTEROL; PLAQUE; CT AB It has been proposed that coronary artery calcium (CAC) can be used to estimate arterial age in adults. Supporting this concept is that chronologic age, as used in cardiovascular risk assessment, is a surrogate for atherosclerotic burden. This measure can provide patients with a more understandable version of their CAC scores (e.g., "You are 55 years old, but your arteries are more consistent with an arterial age of 65 years"). The aim of this study was to describe a method of calculating arterial age by equating estimated coronary heart disease (CHD) risk for observed age and CAC. Arterial age is then the risk equivalent of CAC. Data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of 6,814 participants free of clinical cardiovascular disease and followed for an average of 4 years, were used. Estimated arterial age was obtained as a simple linear function of log-transformed CAC. In a model for incident CHD risk controlling for age and arterial age, only arterial age was significant, indicating that observed age does not provide additional information after controlling for arterial age. Framingham risk calculated using this arterial age was more predictive of short-term incident coronary events than Framingham risk on the basis of observed age (area under the receiver-operating characteristic curve 0.75 for Framingham risk on the basis of observed age and 0.79 using arterial age, p = 0.006). In conclusion, arterial age provides a convenient transformation of CAC from Agatston units to a scale more easily appreciated by patients and treating physicians. (C) 2009 Elsevier Inc. (Am J Cardiol 2009;103:59-63) C1 [McClelland, Robyn L.; Kronmal, Richard A.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Budoff, Matthew] Harbor UCLA Med Ctr, Div Cardiol, Los Angeles, CA USA. [Blumenthal, Roger S.] Johns Hopkins Univ, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP McClelland, RL (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM rmcclell@u.washington.edu FU National Heart, Lung, and Blood Institute, Bethesda, Maryland [N01-HC-95159, N01-HC-95165, N01-HC-95169] FX This research was supported by Contracts N01-HC-95159 through N01-HC-95165 and N01-HC-95169 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. NR 15 TC 36 Z9 40 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2009 VL 103 IS 1 BP 59 EP 63 DI 10.1016/j.amjcard.2008.08.031 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 394CB UT WOS:000262421700011 PM 19101230 ER PT J AU Fernandez, AB Keyes, MJ Pencina, M D'Agostino, R O'Donnell, CJ Thompson, PD AF Fernandez, Antonio B. Keyes, Michelle J. Pencina, Michael D'Agostino, Ralph O'Donnell, Christopher J. Thompson, Paul D. TI Relation of Corneal Arcus to Cardiovascular Disease (from the Framingham Heart Study Data Set) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; RISK-FACTORS; SERUM-LIPIDS; FOLLOW-UP; ASSOCIATION; SENILIS AB Corneal arcus is a lipid-rich deposit at the corneoscleral limbus that shares some similarities with the lipid deposition of atherosclerosis. Epidemiologic studies examining the association between corneal arcus and coronary artery disease (CAD) have yielded mixed results. This study was conducted to determine if corneal arcus is an independent risk factor for cardiovascular disease (CVD) and CAD. A prospective analysis was performed using Cox proportional-hazards regression models in the Framingham Heart Study Original Cohort and Offspring Cohort database. This cohort included 23,376 patient-examinations, during 3,890 (17%) of which corneal arcus was identified. Corneal arcus was a predictor of CVD, and CAD at 4 years (hazard ratios [HRs] 2.28 and 1.99, respectively) and 8 years (HRs 2.52 and 2.35, respectively) of follow-up (p <0.0001 for all). Corneal arcus was no longer predictive of either CVD or CAD, however, after adjustment for age and gender at 4 years (HRs 1.07 and 1.01, respectively) and 8 years (HRs 1.18 and 1.17, respectively) of follow-up (p >0.05 for all). In conclusion, corneal arcus predicted CVD and CAD in the community-based Framingham Heart Study cohort because of the strong association of corneal arcus with increasing age. To date, this is the largest and lengthiest population-based cohort study examining the direct association between corneal arcus and CVD and CAD. (C) 2009 Published by Elsevier Inc. (Am J Cardiol 2009;103:64-66) C1 [Fernandez, Antonio B.; Thompson, Paul D.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Keyes, Michelle J.; Pencina, Michael; D'Agostino, Ralph] Boston Univ, Dept Math, Boston, MA 02215 USA. [Keyes, Michelle J.; Pencina, Michael; D'Agostino, Ralph] Boston Univ, Dept Stat, Boston, MA 02215 USA. [Keyes, Michelle J.; D'Agostino, Ralph; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Thompson, Paul D.] Hartford Hosp, Henry Low Heart Ctr, Div Cardiol, Hartford, CT 06115 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Thompson, PD (reprint author), Univ Connecticut, Ctr Hlth, Farmington, CT USA. EM pthomps@harthosp.org FU National Heart, Lung and Blood Institute, Bethesda, Maryland [N01-HC-25195]; Framingham Heart Study FX This work was supported by Contract No. N01-HC-25195 from the the National Heart, Lung and Blood Institute, Bethesda, Maryland, Framingham Heart Study. NR 25 TC 12 Z9 12 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2009 VL 103 IS 1 BP 64 EP 66 DI 10.1016/j.amjcard.2008.08.030 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 394CB UT WOS:000262421700012 PM 19101231 ER PT J AU Ho, SGY Chan, HHL AF Ho, Stephanie G. Y. Chan, Henry H. L. TI The Asian Dermatologic Patient Review of Common Pigmentary Disorders and Cutaneous Diseases SO AMERICAN JOURNAL OF CLINICAL DERMATOLOGY LA English DT Review ID INTENSE PULSED-LIGHT; Q-SWITCHED RUBY; OTA-LIKE MACULES; ACQUIRED BILATERAL NEVUS; NONMELANOMA SKIN-CANCER; ND-YAG LASERS; HYPOPIGMENTED MYCOSIS-FUNGOIDES; HYPERTROPHIC STERNOTOMY SCARS; RANDOMIZED CONTROLLED-TRIAL; BASAL-CELL CARCINOMA AB The Asian patient with Fitzpatrick skin types III-V is rarely highlighted in publications on cutaneous disorders or cutaneous laser surgery. However, with changing demographics, Asians will become all increasingly important group in this context. Although high melanin content confers better photoprotection, photodamage in the form of pigmentary disorders is common. Melasma, freckles, and lentigines are the epidermal disorders commonly seen, whilst nevus of Ota and acquired bilateral nevus of Ota-like macules are common dermal pigmentary disorders. Post-inflammatory hyperpigmentation (PIH) occurring, after cutaneous injury remains a hallmark of skin of color. With increasing use of lasers and light sources in Asians, prevention and management of PIH is of great research interest. Bleaching agents, chemical peels, intense Pulsed light (IPL) treatments, and fractional skin resurfacing have all been used with some Success for the management of melasma. Q-switched (QS) lasers are effective for the management of epidermal pigmentation but are associated with a high risk of PIH. Long-pulsed neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers and IPL Sources pose less of a PIH risk but require a greater number of treatment sessions. Dermal pigmentary disorders are better targeted by QS ruby QS alexandrite, and QS 1064-nm Nd:YAG lasers, but hyper- and hypopigmentation may Occur. Non-ablative skin rejuvenation using a combination approach with different lasers and light sources in conjunction with cooling devices allows different skin chromophores to be targeted and optimal results to be achieved, even in skin of color. Deep-tissue heating using radiofrequency and infra-red light Sources affects the deep dermis and achieves enhanced skin tightening, resulting in eyebrow elevation, rhytide reduction, and contouring of the lower face and jawline. For management of severe degrees of photoaging, fractional resurfacing is useful for wrinkle and pigment reduction. as well as acne scarring. Acne, which is common in Asians, can be treated with topical and oral antibacterials, hormonal treatments, and isotretinoin. Infra-red diode lasers used with a low-fluence, multiple-pass approach have also been shown to be effective with few complications. Fractional skin resurfacing is very useful for improving the appearance of acne scarring. Hypertrophic and keloid scarring, another common condition seen in Asians, can be treated with the combined used of intralesional triamcinolone and fluorouracil, followed by pulsed-dye laser. Esthetic enhancement procedures such as botulinum toxin type A and Fillers are becoming increasingly popular. These are effective for rhytide improvement and facial or body contouring. We highlight the differences between Asian skin and other skin types and review conditions common in skin of color together with treatment strategies. C1 [Ho, Stephanie G. Y.; Chan, Henry H. L.] Univ Hong Kong, Dept Med, Div Dermatol, Hong Kong, Hong Kong, Peoples R China. [Chan, Henry H. L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. [Chan, Henry H. L.] Fudan Univ, Dept Dermatol, Huashan Hosp, Shanghai 200433, Peoples R China. RP Chan, HHL (reprint author), 13F Club Lusitano,16 Ice House St, Hong Kong, Hong Kong, Peoples R China. EM hhlchan@hkucc.hku.hk RI Ho, Stephanie /A-4576-2012; Chan, Henry Hin Lee/L-2267-2013 NR 125 TC 47 Z9 51 U1 3 U2 16 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1175-0561 EI 1179-1888 J9 AM J CLIN DERMATOL JI Am. J. Clin. Dermatol. PY 2009 VL 10 IS 3 BP 153 EP 168 PG 16 WC Dermatology SC Dermatology GA 440XV UT WOS:000265733900002 PM 19354330 ER PT J AU Stoelb, BL Jensen, MP Tackett, MJ AF Stoelb, Brenda L. Jensen, Mark P. Tackett, M. Jan TI Hypnotic Analgesia for Combat-Related Spinal Cord Injury Pain: A Case Study SO AMERICAN JOURNAL OF CLINICAL HYPNOSIS LA English DT Article DE Spinal cord injury; pain; chronic pain; hypnosis; self-hypnosis training ID VETERANS; HYPNOTHERAPY; NONVETERANS; PREVALENCE; DISABILITY; HYPNOSIS; SAMPLE; MEN AB A U.S. Army soldier stationed in Iraq developed myriad pain problems after sustaining a high-level spinal cord injury (SCI) from a gunshot wound. These problems were negatively impacting his ability to participate fully in his physical rehabilitation and care. Ten sessions of self-hypnosis training were administered to the patient over a 5-week period to help him address these problems. Both the patient and his occupational therapist reported a substantial reduction in pain over the course of treatment, which allowed the patient to actively engage in his therapies. Six months post treatment, the patient reported continued use of the hypnosis strategies taught, which effectively reduced his experience of pain. This case study demonstrates the efficacy of hypnotic analgesia treatment for U.S. military veterans who are experiencing pain problems due to traumatic or combat-related SCIs. C1 [Stoelb, Brenda L.; Jensen, Mark P.] Univ Washington, Dept Rehabil Med, Sch Med, Seattle, WA 98195 USA. [Tackett, M. Jan] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Stoelb, BL (reprint author), Univ Washington, Dept Rehabil Med, Sch Med, 1959 NE Pacific St,Box 356490, Seattle, WA 98195 USA. EM bstoelb@u.washington.edu NR 25 TC 1 Z9 1 U1 0 U2 7 PU AMER SOC CLINICAL HYPNOSIS PI BLOOMINGDALE PA 140 N BLOOMINGDALE RD, BLOOMINGDALE, IL 60108-1017 USA SN 0002-9157 J9 AM J CLIN HYPN JI Am. J. Clin. Hypn. PD JAN PY 2009 VL 51 IS 3 BP 273 EP 280 PG 8 WC Psychology, Clinical SC Psychology GA 397SB UT WOS:000262681300005 PM 19216212 ER PT J AU Perez-Martinez, P Corella, D Shen, J Arnett, DK Yiannakouris, N Tai, ES Orho-Melander, M Tucker, KL Tsai, M Straka, RJ Province, M Kai, CS Perez-Jimenez, F Lai, CQ Lopez-Miranda, J Guillen, M Parnell, LD Borecki, I Kathiresan, S Ordovas, JM AF Perez-Martinez, Pablo Corella, Dolores Shen, Jian Arnett, Donna K. Yiannakouris, Nikos Tai, E. Syong Orho-Melander, Marju Tucker, Katherine L. Tsai, Michael Straka, Robert J. Province, Michael Kai, Chew Suok Perez-Jimenez, Francisco Lai, Chao-Qiang Lopez-Miranda, Jose Guillen, Marisa Parnell, Laurence D. Borecki, Ingrid Kathiresan, Sekar Ordovas, Jose M. TI Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID TRIGLYCERIDE-RICH LIPOPROTEINS; METABOLIC SYNDROME; CORONARY INFARCT; RISK-FACTORS; DIETARY; OVEREXPRESSION; CHOLESTEROL; HEALTHY; DISEASE; GLUCOSE AB Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C -> T, APOA5 -1131T -> C, and APOA5 56C -> G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = `1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes). Results: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend < 0.001). Conclusions: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment. Am J Clin Nutr 2009;89:391-9. Clin Nutr 2009; 89: 391-9. C1 [Perez-Martinez, Pablo; Perez-Jimenez, Francisco; Lopez-Miranda, Jose] Reina Sofia Univ Hosp, Lipids & Atherosclerosis Res Unit, Cordoba 14004, Spain. [Perez-Martinez, Pablo; Perez-Jimenez, Francisco; Lopez-Miranda, Jose] Univ Cordoba, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Cordoba, Spain. [Perez-Martinez, Pablo; Corella, Dolores; Shen, Jian; Lai, Chao-Qiang; Parnell, Laurence D.; Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Boston, MA 02111 USA. [Tucker, Katherine L.] Tufts Univ, Dietary Assessment & Epidemiol Res Program, Jean Mayer US Dept Agr Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Corella, Dolores; Guillen, Marisa] Univ Valencia, Genet & Mol Epidemiol Unit, Valencia, Spain. [Corella, Dolores; Guillen, Marisa] Univ Valencia, CIBER Fisiopatol Obesidad & Nutr CIBEROBN, Sch Med, Valencia, Spain. [Arnett, Donna K.] Univ Alabama, Dept Epidemiol, Birmingham, AL USA. [Yiannakouris, Nikos] Harokopio Univ Athens, Athens, Greece. [Tai, E. Syong] Singapore Gen Hosp, Dept Endocrinol, Singapore 0316, Singapore. [Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo Univ Hosp, Clin Res Ctr, Malmo, Sweden. [Tsai, Michael] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Straka, Robert J.] Univ Minnesota, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. [Province, Michael; Borecki, Ingrid] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Kai, Chew Suok] Minist Hlth, Epidemiol & Dis Control Div, Singapore, Singapore. [Kathiresan, Sekar] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Dis Prevent Ctr,Dept Med,Cardiol Div, Boston, MA USA. RP Perez-Martinez, P (reprint author), Reina Sofia Univ Hosp, Lipids & Atherosclerosis Res Unit, Avda Menendez Pidal S-N, Cordoba 14004, Spain. EM pablopermar@yahoo.es RI Tucker, Katherine/A-4545-2010; OI Perez Jimenez, Francisco/0000-0001-9808-1280; Perez-Jimenez, Francisco/0000-0001-7499-7681; Parnell, Laurence/0000-0001-9718-1335; Perez Martinez, Pablo/0000-0001-7716-8117; Tucker, Katherine/0000-0001-7640-662X; Ordovas, Jose/0000-0002-7581-5680; Tai, E Shyong/0000-0003-2929-8966 FU US Department of Agriculture Agricultural Research Service [53-K06-5-10 and 58-1950-9-001]; NIH Heart, Lung, and Blood Institute [U 01 HL72524]; Genetic and Environmental Determinants of Triglycerides; NIH, National Institute on Aging [5P01AG023394-02, RD07/0067/0006, PR2008-0268]; Instituto de Salud Carlos III, Spain [CIBEROBN03/06, PI070954] FX Supported by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Agricultural Research Service; NIH Heart, Lung, and Blood Institute grant U 01 HL72524, Genetic and Environmental Determinants of Triglycerides; NIH, National Institute on Aging, grant 5P01AG023394-02; RD07/0067/0006 (ISCIII) and PR2008-0268 (MICIN); and CIBEROBN03/06 and PI070954 from the Instituto de Salud Carlos III, Spain. NR 32 TC 34 Z9 36 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN 1 PY 2009 VL 89 IS 1 BP 391 EP 399 DI 10.3945/ajcn.2008.26363 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 391VM UT WOS:000262262300049 PM 19056598 ER PT J AU Al-Ghananeem, AM Herman, BH Abbassi, M Yu, E Miotto, K O'Brien, CP Ling, W Montgomery, A Walsh, R AF Al-Ghananeem, Abeer M. Herman, Barbara H. Abbassi, Maggie Yu, Elmer Miotto, Karen O'Brien, Charles P. Ling, Walter Montgomery, Ann Walsh, Robert TI Urine and Plasma Pharmacokinetics of Lofexidine after Oral Delivery in Opiate-Dependent Patients SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE Clinical trial; lofexidine; oral delivery; pharmacokinetics; urine AB Objectives: The objective of this study was to investigate lofexidine urine and plasma pharmacokinetics using three different dosing regimens in opioid dependent subjects. To date, there have been no published studies on lofexidine appearance and excretion in urine of opioid dependent subjects. Methods: Subjects were stabilized with 100 mg morphine sulphate on days 3-8 of the study. The dosing regimens of lofexidine hydrochloride were .8 mg twice a day (BID), 1.2 mg BID, or .8 mg three times a day (TID) on days 9 through 16 of the study. Plasma and urine samples were collected at appropriate time points. Area under the concentration-time curve (AUC), maximum concentration in plasma (C(max)), time when maximum concentration was reached (T(max)) and fraction excreted unchanged in urine (Fe) were calculated. Results: The average half-life obtained from all profiles was 12.1 +/- 6.3 hr. Steady-state (SS) was reached by study day 15. The plasma pharmacokinetic parameters for 1.2 mg BID and .8 mg TID dosing regimens did not seem to be different at steady state (day 15). T(max) was not statistically significantly different across dosing regimens. Fe values ranged between .01% and 34% with high variability within the same dosing regimen. For the total dose of 2.4 mg/day the two dosing regimens that were evaluated, namely 1.2 mg BID and .8 mg TID, did not show a significant statistical difference in plasma and urine pharmacokinetic parameters. Conclusion: Although preliminary due to the limited number of subjects, these findings are the first to document lofexidine urine pharmacokinetics in opiate addicts using a highly sensitive liquid chromatography tandem mass spectrometric analysis. C1 [Al-Ghananeem, Abeer M.; Abbassi, Maggie] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA. [Herman, Barbara H.; Montgomery, Ann; Walsh, Robert] Natl Inst Drug Abuse, DPMCDA, NIH, Bethesda, MD USA. [Yu, Elmer; O'Brien, Charles P.] Univ Penn, Philadelphia, PA 19104 USA. [Yu, Elmer; O'Brien, Charles P.] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. [Miotto, Karen; Ling, Walter] Univ Calif Los Angeles, David Geffen Sch Med, Long Beach Vet Affairs Med Ctr, Los Angeles, CA 90095 USA. RP Al-Ghananeem, AM (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 927 Rose St, Lexington, KY 40536 USA. EM amalg0@email.uky.edu NR 17 TC 0 Z9 0 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PY 2009 VL 35 IS 5 BP 311 EP 315 DI 10.1080/00952990903060135 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 562EG UT WOS:000275031700009 PM 19637105 ER PT J AU Manini, AF Dannemann, N Brown, DF Butter, J Bamberg, F Nagurney, JT Nichols, JH Hoffmann, U AF Manini, Alex F. Dannemann, Nina Brown, David F. Butter, Javed Bamberg, Fabian Nagurney, John T. Nichols, John H. Hoffmann, Udo CA Rule-Out Myocardial Infarction Usi TI Limitations of risk score models in patients with acute chest pain SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ELEVATION MYOCARDIAL-INFARCTION; MULTIDETECTOR COMPUTED-TOMOGRAPHY; AMERICAN-HEART-ASSOCIATION; ACUTE CORONARY SYNDROMES; EMERGENCY-DEPARTMENT; NONDIAGNOSTIC ELECTROCARDIOGRAM; PRACTICAL IMPLEMENTATION; UNSTABLE ANGINA; GUIDELINES; CARDIOLOGY AB Objectives: Cardiac multidetector computed tomography (CMCT) has potential to be used as a screening test for patients with acute chest pain, but several tools are already used to risk-stratify this population. Risk models exist that stratify need for intensive care (Goldman), short-term prognosis (Thrombolysis in Myocardial Infarction, TIMI), and 1-year events (Sanchis). We applied these cardiovascular risk models to candidates for CMCT and assessed sensitivity for prediction of in-hospital acute coronary syndrome (ACS). We hypothesized that none of the models would achieve a sensitivity of 90% or greater, thereby justifying use of CMCT in patients with acute chest pain. Methods: We analyzed TIMI, Goldman, and Sanchis in 148 consecutive patients with chest pain, nondiagnostic electrocardiogram, and negative initial cardiac biomarkers who previously met inclusion and exclusion criteria for the Rule-Out Myocardial Infarction Using Coronary Artery Tomography Study. ACS was adjudicated, and risk scores were categorized based on established criteria. Risk score agreement was assessed with weighted kappa statistics. Results: Overall, 17 (11%) of 148 patients had ACS. For all risk models, sensitivity was poor (range, 35%-53%), and 95% confidence intervals did not cross above 77%. Agreement to risk-classify patients was poor to moderate (weighted kappa range, 0.18-0.43). Patients categorized as "low risk" had nonzero rates of ACS using all 3 scoring models (range, 8%-9%). Conclusions: Available risk scores had poor sensitivity to detect ACS in patients with acute chest pain. Because of the small number of patients in this data set, these findings require confirmation in larger studies. (C) 2009 Elsevier Inc. All rights reserved. C1 [Manini, Alex F.] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Dannemann, Nina; Butter, Javed; Bamberg, Fabian; Nichols, John H.; Hoffmann, Udo] Harvard Univ, Sch Med, Cardiac MR PET CT Program, Boston, MA USA. [Brown, David F.; Nagurney, John T.] Harvard Univ, Sch Med, Dept Emergency Med, Boston, MA USA. [Brown, David F.; Nagurney, John T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Manini, AF (reprint author), 455 1st Ave,Room 123, New York, NY 10016 USA. EM alex.mamini@nyumc.org FU National Institutes of Health [R01 HL080053]; Massachusetts General Hospital Department of Emergency Medicine FX Funding: Supported by National Institutes of Health R01 grant HL080053 (Principal Investigator: Dr. Hoffmann) and a Departmental Award from the Massachusetts General Hospital Department of Emergency Medicine (Principal Investigator: Dr. Manini). NR 23 TC 28 Z9 28 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD JAN PY 2009 VL 27 IS 1 BP 43 EP 48 DI 10.1016/j.ajem.2008.01.022 PG 6 WC Emergency Medicine SC Emergency Medicine GA 385NP UT WOS:000261821200006 PM 19041532 ER PT J AU Karlamangla, AS Sarkisian, CA Kado, DM Dedes, H Liao, DH Kim, S Reuben, DB Greendale, GA Moore, AA AF Karlamangla, Arun S. Sarkisian, Catherine A. Kado, Deborah M. Dedes, Howard Liao, Diana H. Kim, Sungjin Reuben, David B. Greendale, Gail A. Moore, Alison A. TI Light to Moderate Alcohol Consumption and Disability: Variable Benefits by Health Status SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; BODY-MASS INDEX; UNITED-STATES; OLDER PERSONS; FOLLOW-UP; LATE-LIFE; AGED 65; DRINKING; WOMEN; RISK AB In adults, light to moderate alcohol consumption is associated with lower risks for heart disease, diabetes, and mortality. This study examined whether light to moderate alcohol use is also associated with lower risk of incident physical disability over two 5-year periods in 4,276 noninstitutionalized adults in the United States, aged 50 years or older, by using data from 3 waves of the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study surveys from 1982 to 1992. Light/moderate drinking (< 15 drinks per week and < 5 per drinking day or 4 per drinking day for women) was associated with reduced risk for incident disability or death over 5 years, compared with abstention (adjusted odds ratio = 0.77; P = 0.008). Among survivors, light/moderate drinking was associated with lower risk for incident disability, compared with abstention (adjusted odds ratio = 0.75; P = 0.009). In stratified analyses, disability risk decreased with light/moderate drinking in a dose-dependent fashion in men and women with good or better self-reported health but not in men or women with fair or worse self-reported health. Alcohol consumption in moderation might reduce the risk of developing physical disability in older adults in good health but not in those in poor health. C1 [Karlamangla, Arun S.; Kado, Deborah M.; Dedes, Howard; Liao, Diana H.; Kim, Sungjin; Reuben, David B.; Greendale, Gail A.; Moore, Alison A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Sarkisian, Catherine A.] VA Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. RP Moore, AA (reprint author), Div Geriatr, 10945 Le Conte Ave,Suite 2339, Los Angeles, CA 90095 USA. EM aamoore@mednet.ucla.edu FU John A. Hartford Foundation/American Federation for Aging Research Medical Student Geriatric Scholars Program; National Institute on Alcohol Abuse and Alcoholism [R01-AA-013937, R01-AA-013990, R01-DA-020944]; Claude D. Pepper Older Americans Independence Center; National Institute on Aging [5P30 AG028748] FX This work was supported by the John A. Hartford Foundation/American Federation for Aging Research Medical Student Geriatric Scholars Program (to H. D.); the National Institute on Alcohol Abuse and Alcoholism (grants R01-AA-013937, R01-AA-013990, and R01-DA-020944 to A. A. M.); and the Claude D. Pepper Older Americans Independence Center, National Institute on Aging (grant 5P30 AG028748 to A. S. K.). NR 45 TC 24 Z9 24 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2009 VL 169 IS 1 BP 96 EP 104 DI 10.1093/aje/kwn294 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 390GL UT WOS:000262152200012 PM 19022829 ER PT J AU Muddana, V Whitcomb, DC Khalid, A Slivka, A Papachristou, GI AF Muddana, Venkata Whitcomb, David C. Khalid, Asif Slivka, Adam Papachristou, Georgios I. TI Elevated Serum Creatinine as a Marker of Pancreatic Necrosis in Acute Pancreatitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INTRAVENOUS CONTRAST-MEDIUM; NECROTIZING PANCREATITIS; COMPUTED-TOMOGRAPHY; RISK-FACTOR; HEMOCONCENTRATION; SEVERITY; MICROCIRCULATION; ANTIPROTEASES; IMPAIRMENT; FAILURE AB OBJECTIVES: Pancreatic necrosis is a serious complication of acute pancreatitis. The identification of simple laboratory tests to detect subjects at risk of pancreatic necrosis may direct management and improve outcome. This study focuses on the association between routine laboratory tests and the development of pancreatic necrosis in patients with acute pancreatitis. METHODS: In a cohort of 185 patients with acute pancreatitis prospectively enrolled in the Severity of Acute Pancreatitis Study, patients with contrast-enhanced computerized tomography performed were selected (n = 129). Serum hematocrit, creatinine, and urea nitrogen on admission and peak values within 48 h of admission were analyzed. The volume of intravenous fluid resuscitation was calculated for each patient. RESULTS: Of 129 patients, 35 (27%) had evidence of pancreatic necrosis. Receiver operating characteristic curves for pancreatic necrosis revealed an area under the curve of 0.79 for admission hematocrit, 0.77 for peak creatinine, and 0.72 for peak urea nitrogen. Binary logistic regression yielded that all three tests were significantly associated with pancreatic necrosis (P < 0.0001), with the highest odds ratio, 34.5, for peak creatinine. The volume of intravenous fluid resuscitation was similar in patients with and without necrosis. Low admission hematocrit (= 44.8%) yielded a negative predictive value of 89%; elevated peak creatinine (> 1.8 mg/dl) within 48 h yielded a positive predictive value of 93%. CONCLUSIONS: We confirm that a low admission hematocrit indicates a low risk of pancreatic necrosis (PNec) in patients with acute pancreatitis. In contrast, an increase in creatinine within the first 48 h is strongly associated with the development of PNec. This finding may have important clinical implications and warrants further investigation. C1 [Muddana, Venkata; Whitcomb, David C.; Khalid, Asif; Slivka, Adam; Papachristou, Georgios I.] Univ Pittsburgh, Sch Med, Dept Med, UPMC Presbyterian Hosp,Div Gastroenterol Hepatol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA. [Khalid, Asif; Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Div Gastroenterol, Dept Med, Pittsburgh, PA USA. RP Papachristou, GI (reprint author), Univ Pittsburgh, Sch Med, Dept Med, UPMC Presbyterian Hosp,Div Gastroenterol Hepatol, Mezzanine Level 2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. EM papachristoug@dom.pitt.edu FU VA Stars and Stripes Healthcare Network 2007 Competitive Pilot Project Fund (GIP); NIH [R01 DK61451] FX This work was supported by the VA Stars and Stripes Healthcare Network 2007 Competitive Pilot Project Fund (GIP) and NIH R01 DK61451 (DCW). NR 32 TC 47 Z9 53 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2009 VL 104 IS 1 BP 164 EP 170 DI 10.1038/ajg.2008.66 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 391WV UT WOS:000262265800027 PM 19098865 ER PT J AU Brandt, LJ Chey, WD Foxx-Orenstein, AE Quigley, EMM Schiller, LR Schoenfeld, PS Spiegel, BM Talley, NJ Moayyedi, P AF Brandt, Lawrence J. Chey, William D. Foxx-Orenstein, Amy E. Quigley, Eamonn M. M. Schiller, Lawrence R. Schoenfeld, Philip S. Spiegel, Brennan M. Talley, Nicholas J. Moayyedi, Paul TI An Evidence-Based Position Statement on the Management of Irritable Bowel Syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID RANDOMIZED-CONTROLLED-TRIAL; QUALITY-OF-LIFE; PLACEBO-CONTROLLED TRIAL; INTESTINAL BACTERIAL OVERGROWTH; DOUBLE-BLIND TRIAL; 5-HT3 RECEPTOR ANTAGONIST; PREDOMINANCE IBS-D; CORTICOTROPIN-RELEASING HORMONE; CHRONIC IDIOPATHIC CONSTIPATION; COST-EFFECTIVENESS ANALYSIS C1 [Brandt, Lawrence J.; Moayyedi, Paul] Montefiore Med Ctr, Div Gastroenterol, Bronx, NY 10467 USA. [Chey, William D.] Univ Michigan Hlth Syst, Div Gastroenterol, Ann Arbor, MI USA. [Foxx-Orenstein, Amy E.] Mayo Clin, Dept Internal Med, Div Gastroenterol & Hepatol, Rochester, MN USA. [Quigley, Eamonn M. M.] Cork Univ Hosp, Dept Med, Cork, Ireland. [Schiller, Lawrence R.] Baylor Univ, Med Ctr, Digest Hlth Associates Texas, Dallas, TX USA. [Schoenfeld, Philip S.] Vet Affairs Ann Arbor Healthcare Syst, Div Gastroenterol, Ann Arbor, MI USA. [Spiegel, Brennan M.] Univ Calif Los Angeles, David Geffen Sch Med, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. [Talley, Nicholas J.] Mayo Clin, Dept Med, Jacksonville, FL 32224 USA. [Moayyedi, Paul] McMaster Univ, Med Ctr, Div Gastroenterol, Dept Med, Hamilton, ON, Canada. RP Brandt, LJ (reprint author), Montefiore Med Ctr, Div Gastroenterol, 111 E 210 St, Bronx, NY 10467 USA. RI Talley, nicholas/D-5399-2013 OI Talley, nicholas/0000-0003-2537-3092 NR 320 TC 300 Z9 314 U1 9 U2 26 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JAN PY 2009 VL 104 SU 1 BP S1 EP S36 DI 10.1038/ajg.2008.122 PG 36 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 391XB UT WOS:000262266400001 ER PT J AU Frick, KD Burton, LC Clark, R Mader, SI Naughton, WB Burl, JB Greenough, WB Steinwachs, DM Leff, B AF Frick, Kevin D. Burton, Lynda C. Clark, Rebecca Mader, Scott I. Naughton, W. Bruce Burl, Jeffrey B. Greenough, William B., III Steinwachs, Donald M. Leff, Bruce TI Substitutive Hospital at Home for Older Persons: Effects on Costs SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; MINIMIZATION ANALYSIS; EARLY DISCHARGE; INPATIENT INTERVENTIONS; CARE; HEALTH; PROGRAM AB Objective:To compare the cost of substitutive Hospital at Home care versus traditional inpatient care for older patients with community-acquired pneumonia, exacerbation of chronic obstructive pulmonary disease, exacerbation of congestive heart failure, or cellulitis. Study Design: Prospective nonrandomized clinical trial involving 455 community-dwelling older patients in 3 Medicare managed care health systems and at a Department of Veterans Affairs medical center. Methods: Costs were analyzed across all patients, within each of the separate health systems, and by condition. Generalized linear models controlling for confounders and using a log link and gamma family specification were used to make inferences about the statistical significance of cost differences. tTests were used to make inferences regarding differences in follow-up utilization. Results: The costs of the Hospital at Home intervention were significantly lower than those of usual acute hospital care (mean [SD], $5081 [$4427] vs $7480 [$8113]; P<.001). Laboratory and procedure expenditures were lower across all study sites and at each site individually. There were minimal significant differences in health service utilization between the study groups during the 8 weeks after the index hospitalization. As-treated analysis results were consistent with Hospital at Home costs being lower. Conclusions: Total costs seem to be lower when substitutive Hospital at Home care is available for patients with congestive heart failure or chronic obstructive pulmonary disease. This result may be related to the study-based requirement for continuous nursing input. Savings may be possible, particularly for care of conditions that typically use substantial laboratory tests and procedures in traditional acute settings. C1 [Frick, Kevin D.; Burton, Lynda C.; Clark, Rebecca; Naughton, W. Bruce; Steinwachs, Donald M.; Leff, Bruce] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Mader, Scott I.] Portland VA Med Ctr, Portland, OR USA. [Mader, Scott I.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Naughton, W. Bruce] SUNY Buffalo, Buffalo, NY 14260 USA. [Burl, Jeffrey B.] Fallon Clin Inc, Worcester, MA USA. [Naughton, W. Bruce; Leff, Bruce] Johns Hopkins Sch Med, Baltimore, MD USA. RP Frick, KD (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, 624 N Broadway,Rm 606, Baltimore, MD 21205 USA. EM kfrick@jhsph.edu FU John A. Hartford Foundation of New York [98309-G]; Department of Veterans Affairs New Clinical Initiative [99-027a] FX This study was supported by grant 98309-G from the John A. Hartford Foundation of New York and was supplemented at Portland Veterans Affairs Medical Center by Department of Veterans Affairs New Clinical Initiative Program grant 99-027a. NR 32 TC 9 Z9 9 U1 1 U2 1 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD JAN PY 2009 VL 15 IS 1 BP 49 EP 56 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 400HA UT WOS:000262857400005 PM 19146364 ER PT J AU Smith, MEB Desai, SS Allen, ES Saha, S Hunter, AJ AF Smith, M. E. Beth Desai, Sima S. Allen, Elizabeth S. Saha, Somnath Hunter, Alan J. TI Impact of Shorter Inpatient Faculty Rotations on Resident Learning Experience SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT National Meeting of the Alliance-for-Academic-Internal-Medicine CY OCT, 2006 CL New Orleans, LA SP Alliance Acad Internal Med ID MEDICAL-EDUCATION; FACTORIAL VALIDATION; PHYSICIAN BURNOUT; INTERNAL-MEDICINE; CARE; STRATEGIES; FRAMEWORK; PROGRAM; NIH C1 [Smith, M. E. Beth] Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, Portland, OR 97239 USA. [Desai, Sima S.; Hunter, Alan J.] Oregon Hlth & Sci Univ, Div Hosp Med, Dept Med, Portland, OR 97239 USA. [Allen, Elizabeth S.; Saha, Somnath] Portland VA Med Ctr, Div Gen Med & Geriatr, Portland, OR USA. RP Smith, MEB (reprint author), Oregon Hlth & Sci Univ, Div Gen Med & Geriatr, 3181 SW Sam Jackson Pk Rd,Mail Code CH9G, Portland, OR 97239 USA. EM smithbet@ohsu.edu NR 21 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JAN PY 2009 VL 122 IS 1 BP 96 EP 100 DI 10.1016/j.amjmed.2008.09.031 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 387XZ UT WOS:000261986200018 PM 19114177 ER PT J AU Shlipak, MG Katz, R Kestenbaum, B Fried, LF Newman, AB Siscovick, DS Stevens, L Sarnak, MJ AF Shlipak, Michael G. Katz, Ronit Kestenbaum, Bryan Fried, Linda F. Newman, Anne B. Siscovick, David S. Stevens, Lesley Sarnak, Mark J. TI Rate of Kidney Function Decline in Older Adults: A Comparison Using Creatinine and Cystatin C SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Glomerular filtration rate; Creatinine; Cystatin C; Chronic kidney disease ID GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; STAGE RENAL-DISEASE; CARDIOVASCULAR EVENTS; MORTALITY RISK; SERUM CREATININE; PROGRESSION; GFR; FAILURE; DEATH AB Background/Aims: The aim of this study was to determine the decline in the estimated glomerular filtration rate (eGFR) in elderly persons and to compare estimates based on creatinine and cystatin C. Methods: In the Cardiovascular Health Study, GFR changes in an elderly cohort were estimated from serum creatinine and cystatin C measured at baseline, year 3 and year 7 in 4,380 participants (age 72 +/- 5 years at entry). Outcomes were mean eGFR decline, incident chronic kidney disease (CKD) and rapid decline in eGFR (annual loss >3 ml/min/1.73 m(2)). Results: Mean annual eGFR loss as estimated from creatinine was 0.4 +/- 3.6 ml/min/1.73 m(2), with 16% of the participants experiencing a rapid decline. Mean eGFR loss as estimated from cystatin C was 1.8 +/- 2.6, with 25% of the participants experiencing a rapid decline (p<0.001 for both). Among participants without baseline CKD, incident CKD was detected at year 7 in 10% (n=263) using creatinine and 19% (n=544) using cystatin C (p<0.001). Increasing age was the strongest predictor of rapid decline; adjusted odds ratios were 1.38 (1.16-1.65), 1.62 (1.31-1.99) and 2.96 (2.28-3.84) for participants aged 70-74, 75-79 and 80+ at baseline, compared with those aged 65-69. Conclusion: In elderly persons, cystatin C estimated substantially larger declines in kidney function than creatinine did. Defining the optimal measurement of kidney function in elderly persons should be a high priority for future research. Copyright (C) 2009 S. Karger AG, Basel C1 [Shlipak, Michael G.] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Dept Biostat, Seattle, WA 98195 USA. [Kestenbaum, Bryan] Univ Washington, Sch Med, Div Nephrol, Seattle, WA USA. [Fried, Linda F.] Univ Pittsburgh, Grad Sch Publ Hlth, Renal Sect, Med Serv,VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Newman, Anne B.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Stevens, Lesley; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Dept Med, Boston, MA USA. RP Shlipak, MG (reprint author), VA Med Ctr 111A1, Gen Internal Med Sect, 4150 Clement St, San Francisco, CA 94121 USA. EM michael.shlipak@ucsf.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung and Blood Institute (NHLBI) [R01 HL073208-01, R01 DK066488]; National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health [R01AG027002, K24DK078204-01]; NHLBI [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01 HC-15103] FX This work was supported by contracts R01 HL073208-01 and R01 DK066488 from the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases, respectively. In addition, this work was supported by the American Federation for Aging Research by a Paul Beeson Scholars Program award and R01AG027002 and K24DK078204-01 from the National Institutes of Health. The CHS is supported by contracts N01-HC-85079 through N01-HC-85086, N01-HC-35129, and N01 HC-15103 from the NHLBI. This study was funded through contracts with the NHLBI and included substantial NHLBI involvement in data collection, analysis and interpretation, as well as manuscript preparation. A full list of participating CHS investigators and institutions can be found at http://www.chs-nhlbi.org. NR 27 TC 60 Z9 63 U1 1 U2 4 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 30 IS 3 BP 171 EP 178 DI 10.1159/000212381 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 485PN UT WOS:000269136000001 PM 19349699 ER PT J AU Williams, ME Lacson, E Teng, M Hakim, RM Lazarus, JM AF Williams, M. E. Lacson, E., Jr. Teng, M. Hakim, R. M. Lazarus, J. M. TI Extremes of Glycemic Control (HbA(1c)) Increase Hospitalization Risk in Diabetic Hemodialysis Patients in the USA SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE End-stage renal disease, hospitalization; Diabetes mellitus; Glycemic control ID CHRONIC-RENAL-FAILURE; CARDIOVASCULAR-DISEASE; GLYCATED HEMOGLOBIN; MAINTENANCE HEMODIALYSIS; GLYCOSYLATED HEMOGLOBIN; MELLITUS; COMPLICATIONS; SURVIVAL; GLUCOSE; DIALYSIS AB Background/Aims: Because the relation between glycemic control and clinical outcomes found in the general diabetic population has not been established in diabetic hemodialysis patients, we evaluated the association between glycemic control and hospitalization risk. Methods: We performed a primary retrospective data analysis on 23,829 hemodialysis patients with diabetes mellitus. Hemoglobin A(1c) at baseline and hospitalization events over the subsequent 12 months were analyzed and logistic regression models constructed for unadjusted, case mix-adjusted and case mix plus lab-adjusted data. Models were also constructed for cardiovascular, vascular access and sepsis hospitalizations. Results: Eighty percent had type 2DM, 5% type 1 and 14% not specified. The groups had similar mean HbA(1c) levels, 6.8 +/- 1.6%. Among all patients, the mean HbA(1c) values were > 7% in 35%. The odds ratio of hospitalizations grouped by baseline HbA(1c) was significant at extremes of < 5% and > 11%. Similar relationships were evident for the subset of type 2DM and in the analysis for hospitalizations due to sepsis. Conclusion: Extremely high and low HbA(1c) values are associated with hospitalization risk in diabetic hemodialysis patients. Prospective studies are needed to determine whether meeting recommended HbA(1c) targets might improve outcomes without posing additional risks in this population. Copyright (C) 2008 S. Karger AG, Basel C1 [Williams, M. E.] Joslin Diabet Ctr, Renal Unit, Boston, MA 02215 USA. [Lacson, E., Jr.; Teng, M.; Hakim, R. M.; Lazarus, J. M.] Fresenius Med Care, Lexington, MA USA. RP Williams, ME (reprint author), Joslin Diabet Ctr, Renal Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM mark.williams@joslin.harvard.edu NR 45 TC 19 Z9 19 U1 1 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 1 BP 54 EP 61 DI 10.1159/000151276 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 366CN UT WOS:000260458300008 PM 18689979 ER PT J AU Fried, LF Katz, R Cushman, M Sarnak, M Shlipak, MG Kuller, L Newman, AB AF Fried, Linda F. Katz, Ronit Cushman, Mary Sarnak, Mark Shlipak, Michael G. Kuller, Lewis Newman, Anne B. TI Change in Cardiovascular Risk Factors with Progression of Kidney Disease SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 46th Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 02-05, 2006 CL Phoenix, AZ SP Amer Heart Assoc, Natl Heart, Lung & Blood Inst DE Cardiovascular risk factors; Chronic kidney disease; Disease progression; Inflammation; Lipids ID C-REACTIVE PROTEIN; RENAL-INSUFFICIENCY; VENOUS THROMBOEMBOLISM; ELDERLY PERSONS; CYSTATIN-C; MORTALITY; HEALTH; ATHEROSCLEROSIS; INFLAMMATION; CLEARANCE AB Background: Prior studies evaluating the relationship of kidney disease with cardiovascular risk factors have been limited by their cross-sectional design. We evaluated the change in lipids, inflammatory and procoagulant biomarkers with decline in kidney function in a nested case-cohort study in the Cardiovascular Health Study, a community-based study of adults aged >65 years. Methods: Individuals with an increase in serum creatinine >= 0.3 mg/dl (baseline to 3 years later, n = 207) were matched to controls of similar age, race, gender, diabetes and baseline serum creatinine, but whose change in creatinine was <0.3 mg/dl. Baseline and change in risk factors were analyzed with conditional logistic regression. Results: Changes in C-reactive protein were similar. In contrast, cases had larger increases in fibrinogen (OR 1.38 per standard deviation, 95% confidence interval 1.08-1.76) and factor VIII [1.38 (1.10-1.72)] and larger decreases in HDL [OR 0.80 (0.64, 1.00)]. Change in interleukin-6 was greater in cases than controls, but this did not persist after multivariate adjustment. However, in linear regression, change in interleukin-6 was correlated with change in creatinine. Conclusion: Cardiovascular risk factors and kidney function may change concurrently. This could lead to an increased risk of cardiovascular disease as kidney function worsens. Copyright (C) 2008 S. Karger AG, Basel C1 [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr Div, Pittsburgh, PA 15240 USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. [Fried, Linda F.; Kuller, Lewis; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Katz, Ronit] Univ Washington, Coordinating Ctr, Seattle, WA 98195 USA. [Cushman, Mary] Univ Vermont, Dept Med, Thrombosis & Hemostasis Program, Burlington, VT 05401 USA. [Sarnak, Mark] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA USA. [Shlipak, Michael G.] Univ Calif San Francisco, Gen Internal Med Sect, San Francisco Vet Affairs Med Ctr, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Univ Dr Div, Mailstop 111F-U, Pittsburgh, PA 15240 USA. EM linda.fried@va.gov RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01 HC-55222, N01 HC015103, N01 HC035129, N01 HC045133, N01-HC-75150, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086, N01HC55222, N01HC75150, N01HC85079, N01HC85086, U01 HL080295]; NIA NIH HHS [R01 AG027002] NR 31 TC 7 Z9 8 U1 1 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 4 BP 334 EP 341 DI 10.1159/000166598 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 375RX UT WOS:000261132100007 PM 18948687 ER PT J AU Patel, T Hirter, A Kaufman, J Keithi-Reddy, SR Reda, D Singh, A AF Patel, Tejas Hirter, Angie Kaufman, James Keithi-Reddy, Sai Ram Reda, Domenic Singh, Ajay TI Route of Epoetin Administration Influences Hemoglobin Variability in Hemodialysis Patients SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Hemoglobin variability; Anemia; Subcutaneous epoetin; Bundling of dialysis service ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; STAGE RENAL-DISEASE; LEVEL VARIABILITY; ANEMIA MANAGEMENT; MORTALITY; ASSOCIATIONS; ESRD AB Background: Compared to the intravenous route, subcutaneous administration of epoetin requires lower dose and will be an attractive option for cost containment when bundling for dialysis is implemented. Hemoglobin variability defined as fluctuation of hemoglobin over time has not been well studied with respect to the route of administration. Methods: 157 prevalent-hemodialysis subjects were analyzed from an open-label, randomized study that compared the intravenous to the subcutaneous route of epoetin with identical weight-based dosing algorithm. Hemoglobin variability was defined as the number of weeks hemoglobin is outside the target range of 10-11 g/dl. Sensitivity analysis was performed. Results: 78 subjects in the intravenous and 79 in the subcutaneous group entered the 24-week dose maintenance phase. Baseline covariates were similar in both groups except for the dose of epoetin (lower in subcutaneous) and dialysis vintage (longer in intravenous). Patients on subcutaneous epoetin were outside the target range more weeks (p = 0.04) and had higher standard deviation of hemoglobin (p = 0.01) compared to the intravenous group. Conclusions: The subcutaneous route of epoetin was associated with modestly higher hemoglobin variability, probably reflecting greater sensitivity of the subcutaneous route and/or identical epoetin-dosing algorithm employed in both the arms. This study could serve as an important guide when bundling for dialysis services is implemented as switching from intravenous to subcutaneous administration is likely to occur. Copyright (c) 2008 S. Karger AG, Basel C1 [Patel, Tejas; Keithi-Reddy, Sai Ram; Singh, Ajay] Harvard Univ, Div Renal, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hirter, Angie; Reda, Domenic] Hines VA Hosp, Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. [Kaufman, James] VA Boston Healthcare Syst, Renal Sect, Boston, MA USA. RP Singh, A (reprint author), Harvard Univ, Div Renal, Brigham & Womens Hosp, Sch Med, MRB 4,75 Francis St, Boston, MA 02115 USA. EM asingh@partners.org OI Hirter, Angie/0000-0001-6616-2123 FU Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development; [T32-DK007527-23] FX Dr. Patel was supported by T32-DK007527-23. The analysis for the present study was supported in part by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development. NR 14 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 6 BP 532 EP 537 DI 10.1159/000187649 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 442SP UT WOS:000265861200006 PM 19088467 ER PT J AU Hilliard, LM Russo, LM Comper, WD AF Hilliard, Lucinda M. Russo, Leileata M. Comper, Wayne D. TI Hypertension-Mediated Albuminuria Is Associated with Reduced Lysosomal Activity in the Kidney and the Heart SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Cardiac fibrosis; Cardiac hypertrophy; Lysosomal activity; Ramipril; Renal albumin degradation pathway; beta ig-h3 expression ID GROWTH-FACTOR-BETA; STREPTOZOTOCIN-DIABETIC RATS; MATRIX GENE-EXPRESSION; SMOOTH-MUSCLE-CELLS; TGF-BETA; CARDIAC-HYPERTROPHY; ANGIOTENSIN-II; ACE-INHIBITOR; MYOCARDIAL FIBROSIS; MESANGIAL CELLS AB Background: Recent studies suggest that expression of the transforming growth factor-beta (TGF-beta)-inducible gene-h3 (beta ig-h3) and its anti-lysosomal activity may be responsible for the development of albuminuria and cardiovascular disease associated with hypertension. Methods: We evaluated the proposed linkage using the spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat models. The kidney and left ventricular weight/body weight ratios were measured and cardiac collagen deposition was analyzed by Masson's trichrome stain. Renal and cardiac TGF-beta(1) and beta ig-h3 expression were determined by real-time reverse transcription-polymerase chain reaction, and renal and cardiac cathepsin B and L activities were measured as an indicator of lysosomal proteolytic activity. Results: SHR exhibited increased levels of intact urinary albumin without significant change in total albumin (intact plus albumin-derived material) excretion. This was accompanied by renal hypertrophy, increased renal beta ig-h3 expression, and reduced renal cathepsin B and L activities. At the same time, increased cardiac TGF-beta(1) and beta ig-h3 expression and reduced cardiac cathepsin B activity was identified in SHR in addition to cardiac hypertrophy and increased collagen deposition. All these changes could be ameliorated with ramipril treatment. Conclusions: These findings implicate for the first time beta ig-h3 expression and lysosomal activity as a key factor in the induction of albuminuria and cardiovascular disease associated with hypertension. Copyright (c) 2008 S. Karger AG, Basel C1 [Hilliard, Lucinda M.; Comper, Wayne D.] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. [Russo, Leileata M.] Harvard Univ, Sch Med, Boston, MA USA. [Russo, Leileata M.] Massachusetts Gen Hosp, Program Membrane Biol, Renal Unit, Boston, MA 02114 USA. RP Comper, WD (reprint author), Monash Univ, Dept Biochem & Mol Biol, Wellington Rd, Clayton, Vic 3800, Australia. EM wcomper@hotmail.com NR 61 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 5 DI 10.1159/000176535 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 428SO UT WOS:000264870200016 PM 19023196 ER PT J AU Jolly, SE Li, S Chen, SC Narva, AS Jurkovitz, CT Norris, KC Shlipak, MG AF Jolly, Stacey E. Li, Suying Chen, Shu-Cheng Narva, Andrew S. Jurkovitz, Claudine T. Norris, Keith C. Shlipak, Michael G. TI Risk Factors for Chronic Kidney Disease among American Indians and Alaska Natives - Findings from the Kidney Early Evaluation Program SO AMERICAN JOURNAL OF NEPHROLOGY LA English DT Article DE Chronic kidney disease; Risk factors; American Indians; Alaska Natives ID GLOMERULAR-FILTRATION-RATE; TYPE-2 DIABETES-MELLITUS; SERUM CREATININE VALUES; STAGE RENAL-DISEASE; UNITED-STATES; COLLABORATIVE APPROACH; NATIONAL-HEALTH; HEART-FAILURE; PIMA-INDIANS; FOLLOW-UP AB Background: American Indians and Alaska Natives (AIAN) have a high incidence of end-stage renal disease. Less is known about chronic kidney disease (CKD) among AIAN and whether risk factors differ for low estimated glomerular filtration rate (eGFR) versus albuminuria with a normal eGFR. Methods: Cross-sectional study examining the associations of age, sex, smoking, obesity, diabetes, hypertension, family history, and geographic region with CKD among a screened population of AIAN participants in the Kidney Early Evaluation Program from 2000 to 2006. CKD was defined by the presence of either a low eGFR, < 60 ml/min/1.73 m(2), or albuminuria, a urine albumin/creatinine ratio >= 30 mg/g. Results: The prevalence of any CKD was 29%, of low eGFR was 17%, and of albuminuria with a normal eGFR was 12%. Older age was the strongest predictor of low eGFR (61+ years OR 8.42, 95% Cl 5.92-11.98), followed by hypertension (OR 2.38, 95% Cl 1.74-3.26). In contrast, diabetes (OR 2.04, 95% Cl 1.57-2.64) and hypertension (OR 2.63, 95% Cl 1.93-3.59) were the only predictors of albuminuria among persons with a normal eGFR. Conclusion: The burden of CKD was high among this screened population of AIAN, and different risk factor patterns were associated with low eGFR and albuminuria. Innovative programs and longitudinal research are needed to address CKD among AIAN. Copyright (c) 2008 S. Karger AG, Basel C1 [Jolly, Stacey E.; Shlipak, Michael G.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. [Li, Suying; Chen, Shu-Cheng] Minneapolis Med Res Fdn Inc, Chron Dis Res Grp, Minneapolis, MN USA. [Narva, Andrew S.] NIDDK, Bethesda, MD USA. [Jurkovitz, Claudine T.] Christiana Care Hlth Syst, Ctr Outcomes Res, Newark, DE USA. [Norris, Keith C.] Charles R Drew Univ, Dept Internal Med, Los Angeles, CA USA. [Shlipak, Michael G.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Jolly, SE (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, Campus Mailbox 1364, San Francisco, CA 94143 USA. EM stacey.jolly@ucsf.edu FU Health Resources and Services Administration Faculty Development [D55HP05165]; American Heart Association's Established Investigator; [R01-DK066488]; [R01-AG027002] FX Dr. Jolly was supported by Health Resources and Services Administration Faculty Development in Primary Care Grant D55HP05165 for this study. Dr. Shlipak's effort on this paper was supported by R01-DK066488, R01-AG027002, and the American Heart Association's Established Investigator Award. NR 32 TC 9 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-8095 J9 AM J NEPHROL JI Am. J. Nephrol. PY 2009 VL 29 IS 5 DI 10.1159/000174857 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 428SO UT WOS:000264870200014 PM 19011277 ER PT J AU Nogueira, RG Lev, MH Roccatagliata, L Hirsch, JA Gonzalez, RG Ogilvy, CS Halpern, EF Rordorf, GA Rabinov, JD Pryor, JC AF Nogueira, R. G. Lev, M. H. Roccatagliata, L. Hirsch, J. A. Gonzalez, R. G. Ogilvy, C. S. Halpern, E. F. Rordorf, G. A. Rabinov, J. D. Pryor, J. C. TI Intra-Arterial Nicardipine Infusion Improves CT Perfusion-Measured Cerebral Blood Flow in Patients with Subarachnoid Hemorrhage-induced Vasospasm SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID COOPERATIVE ANEURYSM; RANDOMIZED-TRIAL; TOMOGRAPHY; NIMODIPINE; PREVENTION; EXPERIENCE; MANAGEMENT; THERAPY AB BACKGROUND AND PURPOSE: Our aim was to determine the effects of intra-arterial (IA) nicardipine infusion on the cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm by using first-pass quantitative cine CT perfusion (CTP). MATERIALS AND METHODS: Six patients post-aSAH with clinical and transcranial Doppler findings suggestive of vasospasm were evaluated by CT angiography and CTP immediately before angiography for possible vasospasm treatment, CTP was repeated immediately following IA nicardipine infusion. Maps of mean transit time (MITT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were constructed and analyzed in a blinded manner. Corresponding regions of interest on these maps from the bilateral middle cerebral artery territories and, when appropriate, the bilateral anterior or posterior cerebral artery territories, were selected from the pre- and posttreatment scans. Normalized values were compared by repeated measures analysis of variance. RESULTS: Angiographic vasospasm was confirmed in all patients. In 5 of the 6 patients, both CBF and MTT improved significantly in affected regions in response to nicardipine therapy (mean increase in CBF, 41 +/- 43%; range, -9%-162%, P = .0004; mean decrease in MTT, 26 +/- 24%; range, 0%-70%, P = .0002). In I patient, we were unable to quantify improvement in flow parameters due to section-selection differences between the pre- and posttreatment examinations. CONCLUSIONS: IA nicardipine improves CBF and MTT in ischemic regions in patients with aSAH-induced vasospasm. Our data provide a tissue-level complement to the favorable effects of IA nicardipine reported on prior angiographic studies. CTP may provide a surrogate marker for monitoring the success of treatment strategies in patients with aSAH-induced vasospasm. C1 [Nogueira, R. G.; Hirsch, J. A.; Rabinov, J. D.; Pryor, J. C.] Harvard Univ, Sch Med, Endovasc Neurosurg Intervent Neuroradiol Sect, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02115 USA. [Nogueira, R. G.; Hirsch, J. A.; Rabinov, J. D.; Pryor, J. C.] Harvard Univ, Sch Med, Endovasc Neurosurg Intervent Neuroradiol Sect, Massachusetts Gen Hosp,Dept Neurosurg, Boston, MA 02115 USA. [Nogueira, R. G.; Rordorf, G. A.] Harvard Univ, Sch Med, Neurocrit Care & Vasc Neurol Sect, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02115 USA. [Lev, M. H.; Roccatagliata, L.; Gonzalez, R. G.; Halpern, E. F.] Harvard Univ, Sch Med, Diagnost Neuroradiol Sect, Massachusetts Gen Hosp,Dept Radiol, Boston, MA 02115 USA. [Ogilvy, C. S.] Harvard Univ, Sch Med, Vasc Neurosurg Sect, Massachusetts Gen Hosp,Dept Neurosurg, Boston, MA 02115 USA. RP Nogueira, RG (reprint author), Massachusetts Gen Hosp, Dept Intervent Neuroradiol & Endovasc Neurosurg, 55 Fruit St,GRB 2-241, Boston, MA 02114 USA. EM RNOGUEIRA@PARTNERS.ORG NR 26 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2009 VL 30 IS 1 BP 160 EP 164 DI 10.3174/ajnr.A1275 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 396AV UT WOS:000262565500032 PM 18945790 ER PT J AU Lew, HL Gray, M Poole, JH AF Lew, Henry L. Gray, Max Poole, John H. TI Simultaneous Measurement of Perceptual and Motor Cortical Potentials Implications for Assessing Information Processing in Traumatic Brain Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Motor Potential; P300; Reaction Time; Processing Speed; Traumatic Brain Injury ID EVENT-RELATED POTENTIALS; FINGER MOVEMENTS; CLINICAL UTILITY; REACTION-TIME; HEAD-INJURY; P300; ACTIVATION; ATTENTION; RECOVERY AB Objective: Psychomotor slowing is a common manifestation of traumatic brain injury. Previous electrophysiological studies of traumatic brain injury have focused on abnormal attentional and perceptual responses to incoming stimuli. We hypothesize that traumatic brain injury is also associated with abnormal cortical components of motor execution. Design: To test this hypothesis, we analyzed event-related potentials of 22 subjects (11 with a history of severe traumatic brain injury and 11 age-matched healthy subjects) during oddball discrimination tasks. In addition to the usual stimulus-locked averaging of electrophysiological data to reveal cognitive components, such as the P300, we also analyzed subjects' response-locked data to reveal motor potential waveforms. To focus on generalized effects across modality, analyses were performed on composite measures from both auditory and visual event-related potentials. Results: (1) Traumatic brain injury subjects had abnormal P300 responses (with reduced amplitude and prolonged latency) in both sensory modalities. (2) Traumatic brain injury subjects' motor potential waveforms showed significantly reduced amplitude in both sensory modalities. (3) Abnormalities in P300 latency, amplitude, and motor potential amplitude (effect sizes = 1.2-1.5 SID) were greater than behavioral slowing, as measured by reaction times (0.7 SD). (4) P300 latency and motor potential amplitude together accounted for much of the reaction time prolongation (r = 0.73). Conclusions: This study demonstrates the value of concurrently analyzing stimulus-locked and response-locked event-related potential data to evaluate cortical components of perceptual and motor processing. The present findings indicate that patients with traumatic brain injury have impairments in both the perceptual interpretation of incoming stimuli and the execution of motor responses and that both abnormalities contribute to psychomotor slowing in patients with traumatic brain injury. C1 [Lew, Henry L.] VA Boston Healthcare Syst, Phys Med & Rehabil Serv, Boston, MA USA. [Lew, Henry L.] Harvard Univ, Sch Med, Boston, MA USA. [Gray, Max; Poole, John H.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. RP Lew, HL (reprint author), VA Boston Healthcare Syst, Phys Med & Rehabil Serv, 150 S Huntington Ave, Boston, MA USA. FU Department of Veterans Affairs, ARCD [B3262K] FX Supported by Department of Veterans Affairs, ARCD Grant B3262K. NR 21 TC 6 Z9 6 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2009 VL 88 IS 1 BP 1 EP 6 DI 10.1097/PHM.0b013e3181911102 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 388NS UT WOS:000262027100001 PM 19096287 ER PT J AU Slack, D Nelson, L Patterson, D Burns, S Hakimi, K Robinson, L AF Slack, David Nelson, Lonnie Patterson, David Burns, Stephen Hakimi, Kevin Robinson, Lawrence TI The Feasibility of Hypnotic Analgesia in Ameliorating Pain and Anxiety Among Adults Undergoing Needle Electromyography SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Electromyography (EMG); Hypnosis; Hypnotic Analgesia ID HYPNOSIS; PERCEPTION; ABSORPTION; DISTRESS; OPENNESS; CANCER AB Objective: Our hypothesis was that hypnotic analgesia reduces pain and anxiety during electromyography (EMG). Design: We performed a prospective randomized, controlled clinical trial at outpatient electrodiagnostic clinics in teaching hospitals. Just before EMG, 26 subjects were randomized to one of three 20-min audio programs: education about EMG (EDU) (n = 8); hypnotic induction without analgesic suggestion (n = 10); or hypnotic induction with analgesic suggestion (n = 8). The blinded electromyographer provided a posthypnotic suggestion at the start of EMG. After EMG, subjects rated worst and average pain and anxiety using visual analog scales. Results: Mean values for the EDU, hypnotic induction without analgesic suggestion, and hypnotic induction with analgesic suggestion groups were not significantly different (mean +/- SD): worst pain 67 +/- 25, 42 +/- 18, and 49 +/- 30; average pain 35 +/- 26, 27 +/- 14, and 25 +/- 22; and anxiety 44 +/- 41, 42 +/- 23, and 22 +/- 24. When hypnosis groups were merged (n = 18) and compared with the EDU condition (n = 8), average and worst pain and anxiety were less for the hypnosis group than EDU, but this was statistically significant only for worst pain (hypnosis, 46 +/- 24 vs. EDU, 67 +/- 35; P = 0.049) with a 31% average reduction. Conclusions: A short hypnotic induction seems to reduce worst pain during electromyography. C1 [Nelson, Lonnie; Patterson, David; Burns, Stephen; Hakimi, Kevin; Robinson, Lawrence] Univ Washington, Harborview Med Ctr, Sch Med,Dept Rehabil Med, Electrodiagnost Clin, Seattle, WA 98195 USA. [Slack, David] Vet Affairs Puget Sound Hlth Care Syst, Rehabil Care Serv, Electrodiagnost Clin, Seattle, WA USA. RP Robinson, L (reprint author), Univ Washington, Harborview Med Ctr, Sch Med,Dept Rehabil Med, Electrodiagnost Clin, Box 356380, Seattle, WA 98195 USA. FU National Institutes of Health [R01 GM42725-09A1] FX This study was supported in part by grant R01 GM42725-09A1 from the National Institutes of Health. NR 24 TC 10 Z9 10 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2009 VL 88 IS 1 BP 21 EP 29 DI 10.1097/PHM.0b013e31818e00bd PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 388NS UT WOS:000262027100004 PM 18971768 ER PT J AU Morse, LR Geller, A Battaglino, RA Stolzmann, KL Matthess, K Lazzari, AA Garshick, E AF Morse, Leslie R. Geller, Andrew Battaglino, Ricardo A. Stolzmann, Kelly L. Matthess, Kirby Lazzari, Antonio A. Garshick, Eric TI Barriers to Providing Dual Energy X-ray Absorptiometry Services to Individuals with Spinal Cord Injury SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Spinal Cord Injury; Osteoporosis; Bone Mineral Density; Fracture ID BONE-MINERAL DENSITY; OSTEOPOROSIS; ALENDRONATE; LIFE AB To assess barriers to bone mineral density testing in individuals with chronic spinal cord injury, a cross-sectional study of 20 individuals with spinal cord injury was conducted with assessment of physical and logistical barriers to dual energy x-ray absorptiometry scanning. We identified several barriers, including scanner design and configuration in the scanning room that limited accessibility, increased typical scanning time, and made additional staff necessary. For dual energy x-ray absorptiometry to become a routine component of ongoing care in spinal cord injury medicine, we recommend the following changes: (1) install ceiling-mounted hydraulic lifts and grab bars to facilitate transfers in the scanning room; (2) increase staffing during scans; (3) increase time allotment for scans; (4) install the scanner in an adequately-sized room; and (5) partner with administrators and staff to raise awareness of access issues faced by individuals with spinal cord injury. C1 [Morse, Leslie R.] Harvard Univ, Sch Med, Forsyth Inst, Dept Phys Med & Rehabil, Boston, MA 02118 USA. [Geller, Andrew] Univ Massachusetts, Sch Med, Worcester, MA USA. [Stolzmann, Kelly L.; Matthess, Kirby; Lazzari, Antonio A.; Garshick, Eric] VA Boston Healthcare Syst, Dept Vet Affairs, Res & Dev Serv, Boston, MA USA. [Stolzmann, Kelly L.; Matthess, Kirby] Harvard Univ, Sch Med, Programs Res VA Boston, Boston, MA 02118 USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Primary Care Sect, Boston, MA 02118 USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02118 USA. [Lazzari, Antonio A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. [Garshick, Eric] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02118 USA. [Garshick, Eric] VA Boston Healthcare Syst, Med Serv, Pulm & Crit Care Med Sect, Boston, MA USA. RP Morse, LR (reprint author), Harvard Univ, Sch Med, Forsyth Inst, Dept Phys Med & Rehabil, 140 Fenway, Boston, MA 02118 USA. RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU Department of Veterans Affairs, Veterans Health Administration, Health Services Research; Development Services Quality Enhancement Research Initiative [RRP-07-312] FX The project reported/outlined here was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Services Quality Enhancement Research Initiative RRP-07-312. Dr. Garshick is the Associate Chief of Pulmonary and Critical Care Medicine at VA Boston Healthcare System. The views expressed in this article are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. All authors have no conflict of interest. NR 15 TC 7 Z9 7 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2009 VL 88 IS 1 BP 57 EP 60 DI 10.1097/PHM.0b013e31818a5f87 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 388NS UT WOS:000262027100008 PM 18824888 ER PT J AU Quinn, LS Anderson, BG Strait-Bodey, L Stroud, AM Argiles, JM AF Quinn, LeBris S. Anderson, Barbara G. Strait-Bodey, Lena Stroud, Ashley M. Argiles, Josep M. TI Oversecretion of interleukin-15 from skeletal muscle reduces adiposity SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE adipose tissue; obesity; cytokines; adipokines; myokines; bone; skeletal muscle; interleukin-15; body composition ID MECHANISMS LINKING OBESITY; TUMOR-BEARING RATS; INSULIN-RESISTANCE; BODY-COMPOSITION; TRANSGENIC MICE; NATURAL-KILLER; ENERGY-BALANCE; CRUCIAL ROLE; FAT; IL-15 AB Quinn LS, Anderson BG, Strait-Bodey L, Stroud AM, Argiles JM. Oversecretion of interleukin-15 from skeletal muscle reduces adiposity. Am J Physiol Endocrinol Metab 296: E191-E202, 2009. First published November 11, 2008; doi: 10.1152/ajpendo.90506.2008.-Obesity is a risk factor for development of insulin resistance, type 2 diabetes, cardiovascular disease, osteoarthritis, and some forms of cancer. Many of the adverse health consequences of excess fat deposition are caused by increased secretion of proinflammatory adipokines by adipose tissue. Reciprocal muscle-to-fat signaling factors, or myokines, are starting to be identified. Interleukin-15 (IL-15) is a cytokine that is highly expressed in muscle tissue and that, on the basis of cell culture experiments, has been proposed to act as a circulating myokine that inhibits adipose tissue deposition. To test this hypothesis in vivo, two lines of transgenic mice that overexpressed IL-15 mRNA and protein in skeletal muscle tissue were constructed. By substitution of the inefficient native IL-15 signal peptide with a more efficient signal peptide, one of the transgenic mouse lines also exhibited elevated secretion of IL-15 in the circulation. Overexpression of IL-15 in muscle tissue without secretion in the bloodstream resulted in no differences in body composition. Elevated circulating levels of IL-15 resulted in significant reductions in body fat and increased bone mineral content, without appreciably affecting lean body mass or levels of other cytokines. Elevated circulating levels of IL-15 also inhibited adiposity induced by consumption of a high-fat/high-energy diet in male, but not female, transgenic mice. Female mice with elevated serum IL-15 exhibited increased deposition of lean body mass on a low-fat/low-energy diet and a high-fat/high-energy diet. These findings indicate that muscle-derived circulating IL-15 can modulate adipose tissue deposition and support addition of IL-15 to the growing list of potential myokines that are increasingly being implicated in regulation of body composition. C1 [Quinn, LeBris S.] VA Puget Sound Hlth Care Syst, Amer Lake Div 151, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. [Strait-Bodey, Lena; Stroud, Ashley M.] VA Puget Sound Hlth Care Syst, Res Serv, Tacoma, WA 98493 USA. [Quinn, LeBris S.; Anderson, Barbara G.] Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. [Quinn, LeBris S.; Stroud, Ashley M.] Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Argiles, Josep M.] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, Barcelona, Spain. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div 151, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. EM quinnL@u.washington.edu FU United States Department of Agriculture Cooperative State Research, Education [2005-35206-15264]; National Institute on Aging (NIA) [RO1AG-024136, 5P30AG-013280]; National Institute of Diabetes and Digestive and Kidney Diseases [5P30DK-17047] FX This work was supported by National Research Initiative Competitive Grant no. 2005-35206-15264 from the United States Department of Agriculture Cooperative State Research, Education, and Extension Service Animal Growth and Nutrient Utilization Program to L. S. Quinn, National Institute on Aging (NIA) Grant RO1AG-024136 ( L. S. Quinn), the Transgenic Resource Core of the University of Washington Nathan Shock Center of Excellence in the Basic Biology of Aging (NIA Grant 5P30AG-013280), the Molecular Genetics Core of the University of Washington Diabetes Endocrinology Research Center ( National Institute of Diabetes and Digestive and Kidney Diseases Grant 5P30DK-17047), and by use of resources and facilities at the Veterans Affairs Puget Sound Health Care System, Seattle/Tacoma, WA. NR 74 TC 73 Z9 79 U1 0 U2 12 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2009 VL 296 IS 1 BP E191 EP E202 DI 10.1152/ajpendo.90506.2008 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 388XU UT WOS:000262054400022 PM 19001550 ER PT J AU Chao, W AF Chao, Wei TI Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Review DE apoptosis; cardiomyocytes; inflammation; innate immune; interleukin-1 receptor-associated kinase; ischemia-reperfusion; myeloid differentiation primary-response gene 88 adapter-like protein; myocardial infarction; nuclear factor-kappa B; remodeling ID MYOCARDIAL REPERFUSION INJURY; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; CARDIOMYOCYTES IN-VITRO; DORSAL-VENTRAL POLARITY; LPS BINDING-PROTEIN; PERFUSED RAT-HEART; CARDIAC MYOCYTES; INDUCED APOPTOSIS; ISCHEMIA/REPERFUSION INJURY AB Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart. Am J Physiol Heart Circ Physiol 296: H1-H12, 2009. First published November 14, 2008; doi: 10.1152/ajpheart.00995.2008. - Toll-like receptors (TLRs) represent the first line of host defense against microbial infection and play a pivotal role in both innate and adaptive immunity. TLRs recognize invading pathogens through molecular pattern recognition, transduce signals via distinct intracellular pathways involving a unique set of adaptor proteins and kinases, and ultimately lead to the activation of transcription factors and inflammatory responses. Among 10 TLRs identified in humans, at least two exist in the heart, i.e., TLR2 and TLR4. In addition to the critical role of these in mediating cardiac dysfunction in septic conditions, emerging evidence suggests that the TLRs can also recognize endogenous ligands and may play an important role in modulating cardiomyocyte survival and in ischemic myocardial injury. In animal models of ischemia-reperfusion injury or in hypoxic cardiomyocytes in vitro, the administration of a sublethal dose of lipopolysaccharide, which signals through TLR4, reduces subsequent myocardial infarction, improves cardiac functions, and attenuates cardiomyocyte apoptosis. By contrast, a systemic deficiency of TLR2, TLR4, or myeloid differentiation primary-response gene 88, an adaptor critical for all TLR signaling, except TLR3, leads to an attenuated myocardial inflammation, a smaller infarction size, a better preserved ventricular function, and a reduced ventricular remodeling after ischemic injury. These loss-of-function studies suggest that both TLRs contribute to myocardial inflammation and ischemic injury in the heart although the exact contribution of cardiac (vs. circulatory cell) TLRs remains to be defined. These recent studies demonstrate an emerging role for TLRs as a critical modulator in both cell survival and tissue injury in the heart. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Anesthesia Ctr Crit C, Boston, MA 02114 USA. RP Chao, W (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 wchao@partners.org FU Foundation for Anesthesia Education and Research; American Society of Anesthesiologists; American Heart Association [0755890T]; The William Milton Foundation of Harvard University; National Institutes of Health [HL-04336, GM-080906] FX This work was supported by the Foundation for Anesthesia Education and Research and American Society of Anesthesiologists, an American Heart Association Grant 0755890T, The William Milton Foundation of Harvard University, and National Institutes of Health Grants HL-04336 and GM-080906. NR 170 TC 119 Z9 129 U1 3 U2 23 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JAN PY 2009 VL 296 IS 1 BP H1 EP H12 DI 10.1152/ajpheart.00995.2008 PG 12 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 389ND UT WOS:000262099100001 PM 19011041 ER PT J AU Bem, RA van Woensel, JBM Bos, AP Koski, A Farnand, AW Domachowske, JB Rosenberg, HF Martin, TR Matute-Bello, G AF Bem, Reinout A. van Woensel, Job B. M. Bos, Albert P. Koski, Amy Farnand, Alex W. Domachowske, Joseph B. Rosenberg, Helene F. Martin, Thomas R. Matute-Bello, Gustavo TI Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE respiratory syncytial virus; acute lung injury ID RESPIRATORY SYNCYTIAL VIRUS; EPITHELIAL-CELL APOPTOSIS; TIDAL VOLUME VENTILATION; DISTRESS-SYNDROME; PNEUMONIA VIRUS; ORGAN DYSFUNCTION; VIRAL BRONCHIOLITIS; CYTOKINE RESPONSE; FAS LIGAND; RAT LUNGS AB Bem RA, van Woensel JB, Bos AP, Koski A, Farnand AW, Domachowske JB, Rosenberg HF, Martin TR, Matute-Bello G. Mechanical ventilation enhances lung inflammation and caspase activity in a model of mouse pneumovirus infection. Am J Physiol Lung Cell Mol Physiol 296: L46-L56, 2009. First published November 7, 2008; doi:10.1152/ajplung.00467.2007.-Severe infection with respiratory syncytial virus (RSV) in children can progress to respiratory distress and acute lung injury (ALI). Accumulating evidence suggests that mechanical ventilation (MV) is an important cofactor in the development of ALI by modulating the host immune responses to bacteria. This study investigates whether MV enhances the host response to pneumonia virus of mice (PVM), a mouse pneumovirus that has been used as a model for RSV infection in humans. BALB/c mice were inoculated intranasally with diluted clarified lung homogenates from mice infected with PVM strain J3666 or uninfected controls. Four days after inoculation, the mice were subjected to 4 h of MV (tidal volume, 10 ml/kg) or allowed to breathe spontaneously. When compared with that of mice inoculated with PVM only, the administration of MV to PVM-infected mice resulted in increased bronchoalveolar lavage fluid concentrations of the cytokines macrophage inflammatory protein (MIP)-2, MIP-1 alpha (CCL3), and IL-6; increased alveolar-capillary permeability to high molecular weight proteins; and increased caspase-3 activity in lung homogenates. We conclude that MV enhances the activation of inflammatory and caspase cell death pathways in response to pneumovirus infection. We speculate that MV potentially contributes to the development of lung injury in patients with RSV infection. C1 [Bem, Reinout A.; van Woensel, Job B. M.; Bos, Albert P.] Univ Amsterdam, Acad Med Ctr, Pediat Intens Care Unit, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands. [Koski, Amy; Martin, Thomas R.] Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Farnand, Alex W.; Matute-Bello, Gustavo] Univ Washington, Sch Med, Dept Med, Ctr Lung Biol,Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Domachowske, Joseph B.] SUNY Upstate Med Univ, Syracuse, NY USA. [Rosenberg, Helene F.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Matute-Bello, G (reprint author), Univ Washington Med, S Lake Union Campus,815 Mercer St,Box 358052, Seattle, WA 98109 USA. FU National Heart, Lung, and Blood Institute [HL-083044, HL-073996]; American Lung Association FX This work was supported in part by National Heart, Lung, and Blood Institute Grants HL-083044 and HL-073996 and by the American Lung Association. NR 57 TC 21 Z9 22 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2009 VL 296 IS 1 BP L46 EP L56 DI 10.1152/ajplung.00467.2007 PG 11 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 388YR UT WOS:000262056900007 PM 18996903 ER PT J AU Figlewicz, DP Benoit, SC AF Figlewicz, Dianne P. Benoit, Stephen C. TI Insulin, leptin, and food reward: update 2008 SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Review DE motivation; food intake; dopamine ID CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; MELANIN-CONCENTRATING HORMONE; HYPOTHALAMIC NEUROPEPTIDE-Y; VENTRAL TEGMENTAL AREA; OBESE ZUCKER RATS; CONDITIONED PLACE PREFERENCE; RECEPTOR MESSENGER-RNA; AGOUTI-RELATED PEPTIDE; MODERATE-FAT DIET AB Figlewicz DP, Benoit SC. Insulin, leptin, and food reward: update 2008. Am J Physiol Regul Integr Comp Physiol 296: R9-R19, 2009. First published October 22, 2008; doi:10.1152/ajpregu.90725.2008.- The hormones insulin and leptin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis at medial hypothalamic sites. In a previous review, we described new research demonstrating that, in addition to these direct homeostatic actions at the hypothalamus, CNS circuitry that subserves reward and motivation is also a direct and an indirect target for insulin and leptin action. Specifically, insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward, i.e., midbrain dopamine and opioidergic pathways. Here we summarize new behavioral, systems, and cellular evidence in support of this hypothesis and in the context of research into the homeostatic roles of both hormones in the CNS. We discuss some current issues in the field that should provide additional insight into this hypothetical model. The understanding of neuroendocrine modulation of food reward, as well as food reward modulation by diet and obesity, may point to new directions for therapeutic approaches to overeating or eating disorders. C1 [Figlewicz, Dianne P.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. [Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Benoit, Stephen C.] Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU Department of Veterans Affairs; National Institute of Diabetes and Digestive and Kidney Diseases [DK-40963, DK-066223] FX This work is supported by a Career Scientist Award from the Department of Veterans Affairs and National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-40963 (D. P. Figlewicz, Lattemann) and DK-066223 (S. C. Benoit). NR 198 TC 101 Z9 103 U1 4 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 2009 VL 296 IS 1 BP R9 EP R19 DI 10.1152/ajpregu.90725.2008 PG 11 WC Physiology SC Physiology GA 388YM UT WOS:000262056300002 PM 18945945 ER PT J AU Nazeer, K Janech, MG Lin, JJC Ryan, KJ Arthur, JM Budisavljevic, MN AF Nazeer, Khurram Janech, Michael G. Lin, Jim J. -C. Ryan, Kevin J. Arthur, John M. Budisavljevic, Milos N. TI Changes in protein profiles during course of experimental glomerulonephritis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE two-dimensional electrophoresis; mass spectrometry; anti-Thy-1 glomerulonephritis; tropomyosin ID MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS; SMOOTH MUSCLE ACTIN; TROPOMYOSIN ISOFORMS; EXPRESSION; CELLS; CYTOSKELETON; PROGRESSION; MICROARRAY; NEPHRITIS; INJURY AB Nazeer K, Janech MG, Lin JJ, Ryan KJ, Arthur JM, Budisavljevic MN. Changes in protein profiles during course of experimental glomerulonephritis. Am J Physiol Renal Physiol 296: F186-F193, 2009. First published November 5, 2008; doi: 10.1152/ajprenal.90222.2008. Better characterization of the molecular mechanisms underlying glomerular cell proliferation may improve our understanding of the pathogenesis of glomerulonephritis and yield disease-specific markers. We used two-dimensional gel electrophoresis (2DE) and mass spectrometry (MS) to generate expression profiles of glomerular proteins in the course of anti-Thy-1 nephritis. Glomeruli were isolated from Wistar rats by sieving, and proteins were separated by 2DE. In preliminary studies using normal rats, we identified known glomerular proteins from microfilaments [tropomyosin (Tm)] and intermediate filaments (vimentin and lamin A), proteins involved in assembly (alpha-actinin-4, F-actin capping protein) and membrane cytoskeletal linking (ezrin), as well as several enzymes (protein disulfide isomerase, ATP synthase, and aldehyde dehydrogenase). Comparison of glomerular protein abundance between normal rats and rats in the early phase of anti-Thy-1 nephritis yielded 28 differentially expressed protein spots. MS analysis identified 16 differentially expressed proteins including Tm. Altered Tm abundance in the course of anti-Thy-1 nephritis was confirmed, and specific isoforms were characterized by Western blotting. We demonstrated a complex change in Tm isoform abundance in the course of anti-Thy-1 nephritis. The early mesangiolytic phase of the disease was characterized by decreased abundance of low-molecular-weight isoforms Tm5a/5b and increased abundance of high-molecular-weight isoforms Tm6, Tm1, Tm2, and Tm3. The late proliferative phase of the disease was associated with increased abundance of isoforms Tm5a/5b, Tm6, and Tm1 and decreased abundance of Tm3. Isoforms Tm4 and Tm5 remained unchanged in the course of this model of experimental glomerulonephritis. Characterization of Tm isoform abundance in the course of clinical glomerulonephritis may identify disease-specific markers. C1 [Janech, Michael G.; Ryan, Kevin J.; Arthur, John M.; Budisavljevic, Milos N.] Med Univ S Carolina, Div Nephrol, Dept Med, Charleston, SC 29425 USA. [Nazeer, Khurram] Univ Louisville, Dept Med, Louisville, KY 40292 USA. [Lin, Jim J. -C.] Univ Iowa, Dept Biol Sci, Iowa City, IA USA. [Janech, Michael G.; Arthur, John M.; Budisavljevic, Milos N.] Ralph H Johnson Dept Vet Affairs Med Ctr, Dept Med, Charleston, SC USA. RP Budisavljevic, MN (reprint author), Med Univ S Carolina, Div Nephrol, Dept Med, 96 Jonathan Lucas St,POB 250623, Charleston, SC 29425 USA. EM budisamn@musc.edu OI Janech, Michael/0000-0002-3202-4811 FU Department of Veterans Affairs; Dialysis Clinics, Inc [DCI 2340] FX Support for this project came from the Department of Veterans Affairs and Grant DCI 2340 from Dialysis Clinics, Inc. NR 20 TC 8 Z9 10 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2009 VL 296 IS 1 BP F186 EP F193 DI 10.1152/ajprenal.90222.2008 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 389NU UT WOS:000262101200021 PM 18987115 ER PT J AU Raychowdhury, MK Ramos, AJ Zhang, P McLaughin, M Dai, XQ Chen, XZ Montalbetti, N Cantero, MD Ausiello, DA Cantiello, HF AF Raychowdhury, Malay K. Ramos, Arnolt J. Zhang, Peng McLaughin, Margaret Dai, Xiao-Qing Chen, Xing-Zhen Montalbetti, Nicolas Cantero, Maria del Rocio Ausiello, Dennis A. Cantiello, Horacio F. TI Vasopressin receptor-mediated functional signaling pathway in primary cilia of renal epithelial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE apical vasopressin; cystic kidney disease; cAMP production; polycystin-2; ciliary function ID POLYCYSTIC KIDNEY-DISEASE; PERMEABLE CATION CHANNELS; SOLUBLE ADENYLYL-CYCLASE; ACTIVATED PROTEIN-KINASE; CONDUCTANCE K+ CHANNELS; CYCLIC-AMP; NEURONAL CILIA; NA+ CHANNELS; V2 RECEPTOR; MDCK CELLS AB Raychowdhury MK, Ramos AJ, Zhang P, McLaughlin M, Dai, XQ, Chen XZ, Montalbetti N, Cantero MR, Ausiello DA, Cantiello HF. Vasopressin receptor-mediated functional signaling pathway in primary cilia of renal epithelial cells. Am J Physiol Renal Physiol 296: F87-F97, 2009. First published October 22, 2008; doi: 10.1152/ajprenal.90509.2008.-The primary cilium of renal epithelial cells is a nonmotile sensory organelle, implicated in mechanosensory transduction signals. Recent studies from our laboratory indicate that renal epithelial primary cilia display abundant channel activity; however, the presence and functional role of specific membrane receptors in this organelle are heretofore unknown. Here, we determined a functional signaling pathway associated with the type 2 vasopressin receptor (V2R) in primary cilia of renal epithelial cells. Besides their normal localization on basolateral membrane, V2R was expressed in primary cilia of LLC-PK(1) renal epithelial cells. The presence of V2R in primary cilia was determined by spontaneous fluorescence of a V2R-gfp chimera and confirmed by immunocytochemical analysis of wild-type LLC-PK(1) cells stained with anti-V2R antibodies and in LLC-PK(1) cells overexpressing the V2R-Flag, with anti-Flag antibody. Ciliary V2R colocalized with adenylyl cyclase (AC) type V/VI in all cell types tested. Functional coupling of the receptors with AC was confirmed by measurement of cAMP production in isolated cilia and by testing AVP-induced cation-selective channel activity either in reconstituted lipid bilayers or subjected to membrane-attached patch clamping. Addition of either 10 mu M AVP (trans) or forskolin (cis) in the presence but not the absence of ATP (1 mM, cis) stimulated cation-selective channel activity in ciliary membranes. This channel activity was reduced by addition of the PKA inhibitor PKI. The data provide the first demonstration for the presence of V2R in primary cilia of renal epithelial cells, and a functional cAMP-signaling pathway, which targets ciliary channel function and may help control the sensory function of the primary cilium. C1 [Raychowdhury, Malay K.; Ramos, Arnolt J.; Zhang, Peng; McLaughin, Margaret; Ausiello, Dennis A.; Cantiello, Horacio F.] Massachusetts Gen Hosp, Dept Med, Nephrol Div & Electrophysiol Core, Charlestown, MA USA. [Raychowdhury, Malay K.; Ramos, Arnolt J.; Zhang, Peng; McLaughin, Margaret; Ausiello, Dennis A.; Cantiello, Horacio F.] Harvard Univ, Sch Med, Charlestown, MA USA. [McLaughin, Margaret; Ausiello, Dennis A.] Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. [Dai, Xiao-Qing; Chen, Xing-Zhen] Univ Alberta, Dept Physiol, Edmonton, AB, Canada. [Montalbetti, Nicolas; Cantero, Maria del Rocio; Cantiello, Horacio F.] UBA CONICET, ININCA, Lab Canales Ion, Buenos Aires, DF, Argentina. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp E, Nephrol Div & Electrophysiol Core, 149 13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu OI Montalbetti, Nicolas/0000-0003-2897-9540 FU Polycystic Kidney Disease (PKD) Foundation; Canadian Institutes for Health Research and the Alberta Heritage Foundation; Mathers Foundation; PKD Foundation FX H. F. Cantiello was partially funded by the Polycystic Kidney Disease (PKD) Foundation. The Canadian Institutes for Health Research and the Alberta Heritage Foundation for Medical Research supported X.- Z. Chen and his group. M. K. Raychowdhury was partially supported by the G. Harold and Leila V. Mathers Foundation, and A. J. Ramos kindly acknowledges the PKD Foundation for a postdoctoral fellowship. NR 46 TC 30 Z9 33 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2009 VL 296 IS 1 BP F87 EP F97 DI 10.1152/ajprenal.90509.2008 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 389NU UT WOS:000262101200010 PM 18945824 ER PT J AU North, CS Suris, AM Davis, M Smith, RP AF North, Carol S. Suris, Alina M. Davis, Miriam Smith, Rebecca P. TI Toward Validation of the Diagnosis of Posttraumatic Stress Disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID PSYCHIATRIC-DISORDERS; DSM-III; TERRORIST ATTACKS; OKLAHOMA-CITY; SEPTEMBER 11; CRITERION-A; PTSD; TRAUMA; INTRUSION; EPIDEMIOLOGY AB Unlike most psychiatric diagnoses, post-traumatic stress disorder (PTSD) is defined in relation to a potentially etiologic event (the traumatic "stressor criterion") that is fundamental to its conceptualization. The diagnosis of PTSD thus inherently depends on two separate but confounded processes: exposure to trauma and development of a specific pattern of symptoms that appear following the trauma. Attempts to define the range of trauma exposure inherent in the diagnosis of PTSD have generated controversy, as reflected in successive revisions of the criterion from DSM-III onward. It is still not established whether or not there are specific types of traumatic events and levels of exposure to them that are associated with a syndrome that is cohesive in clinical characteristics, biological correlates, familial patterns, and longitudinal diagnostic stability. On the other hand, the symptomatic description of PTSD is becoming more clear. Of three categories of symptoms associated with PTSD-intrusive memories, avoidance and numbing, and hyperarousal-avoidance and numbing appear to be the most specific for identification of PTSD. Research is now poised to answer questions about the relevance of traumatic events based on their relationship to symptomatic outcome. The authors recommend that future research begin with existing diagnostic criteria, testing and further refining them in accordance with the classic Robins and Guze strategy for validation of psychiatric diagnoses. In this process, diligent adherence to the criteria under examination is paramount to successful PTSD research, and changes in criteria are driven by empirical data rather than theory. Collaborations among trauma research biologists, epidemiologists, and nosologists to map the correspondence between the clinical and biological indicators of psychopathology are necessary to advance validation and further understanding of PTSD. C1 VA N Texas Hlth Care Syst, Dallas, TX USA. Univ Texas SW Med Ctr Dallas, Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Texas SW Med Ctr Dallas, Dept Surg, Div Emergency Med, Dallas, TX 75390 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mt Sinai Sch Med, New York, NY USA. RP North, CS (reprint author), Dallas VAMC, Program Trauma & Disaster, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM carol.north@utsouthwestern.edu FU NIMH; NIAAA; VA; VA, Dallas VA Research Corporation; NARSAD; NIH National Center for Research Resources; NIMH [068853] FX This work was supported by NIMH grant number 068853 to Dr. North. NR 51 TC 70 Z9 72 U1 7 U2 15 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JAN PY 2009 VL 166 IS 1 BP 34 EP 41 DI 10.1176/appi.ajp.2008.08050644 PG 8 WC Psychiatry SC Psychiatry GA 390OJ UT WOS:000262173300010 PM 19047323 ER PT J AU Eisenman, DP Glik, D Ong, M Zhou, Q Tseng, CH Long, A Fielding, J Asch, S AF Eisenman, David P. Glik, Deborah Ong, Michael Zhou, Qiong Tseng, Chi-Hong Long, Anna Fielding, Jonathan Asch, Steven TI Terrorism-Related Fear and Avoidance Behavior in a Multiethnic Urban Population SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SEPTEMBER 11; ATTACKS; BIOTERRORISM; PREPAREDNESS; STRESS; HEALTH; EXPERIENCES; RISK AB Objectives. We sought to determine whether groups traditionally most vulnerable to disasters would be more likely than would be others to perceive population level risk as high (as measured by the estimated color-coded alert level) would worry more about terrorism, and would avoid activities because of terrorism concerns. Methods. We conducted a random digit dial survey of the Los Angeles County population October 2004 through January 2005 in 6 languages. We asked respondents what color alert level the country was under, how often they worry about terrorist attacks, and how often they avoid activities because of terrorism. Multivariate regression modeled correlates of worry and avoidance, including mental illness, disability, demographic factors, and estimated color-coded alert level. Results. Persons who are mentally ill, those who are disabled, African Americans, Latinos, Chinese Americans, Korean Americans, and non-US citizens were more likely to perceive population-level risk as high, as measured by the estimated color-coded alert level. These groups also reported more worry and avoidance behaviors because of concerns about terrorism. Conclusions. Vulnerable populations experience a disproportionate burden of the psychosocial impact of terrorism threats and our national response. Further studies should investigate the specific behaviors affected and further elucidate disparities in the disaster burden associated with terrorism and terrorism policies. (Am J Public Health. 2009;99:168-174. doi:10.2105/AJPH. 2007.124206) C1 [Eisenman, David P.] Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, Los Angeles, CA 90095 USA. [Eisenman, David P.; Asch, Steven] RAND Corp, Santa Monica, CA USA. [Glik, Deborah; Fielding, Jonathan] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Asch, Steven] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Asch, Steven] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Long, Anna; Fielding, Jonathan] Los Angeles Cty Dept Publ Hlth, Los Angeles, CA USA. RP Eisenman, DP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Gen Internal Med, 911 Broxton Plaza, Los Angeles, CA 90095 USA. EM deisenman@mednet.ucla.edu RI Ong, Michael/F-7397-2013 FU Centers for Disease Control and Prevention [UB90/CCU917012-06, K01-CD000049-02] FX Funding for this study was provided to D. P. Eisenman through a grant to the Los Angeles County Department of Public Health from the Centers for Disease Control and Prevention (UB90/CCU917012-06) and from another award to D. P. Eisenman from the Centers for Disease Control and Prevention (K01-CD000049-02). NR 45 TC 20 Z9 21 U1 1 U2 8 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 JAN PY 2009 VL 99 IS 1 BP 168 EP 174 DI 10.2105/AJPH.2007.124206 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 391OA UT WOS:000262241400027 PM 19008521 ER PT J AU Aledia, AS Shelley, D Venegas, J Harris, RS Winkler, T George, SC AF Aledia, A. S. Shelley, D. Venegas, J. Harris, R. S. Winkler, T. George, S. C. TI Effect of Methacholine-Induced Bronchoconstriction on Exhaled Nitric Oxide in Mild Asthmatics. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Aledia, A. S.; George, S. C.] Univ Calif Irvine, Dept Biomed Engr, Irvine, CA USA. [Shelley, D.; George, S. C.] Univ Calif Irvine, Irvine, CA USA. [Venegas, J.; Harris, R. S.; Winkler, T.] Mass Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5184 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104648 ER PT J AU Alexander, LEC Buschman, HM Timmer, AM Nizet, V AF Alexander, L. E. Crotty Buschman, H. M. Timmer, A. M. Nizet, V. TI Group A Streptococcal Pilus Protein spy0128 Stimulates Host Inflammatory Responses, Leading to Decreased Virulence in Pneumonia and Necrotizing Fasciitis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Alexander, L. E. Crotty; Buschman, H. M.; Timmer, A. M.; Nizet, V.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Alexander, L. E. Crotty] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lecrotty@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3270 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102505 ER PT J AU Alexander, LEC Vega, VL De Maio, A Nizet, V AF Alexander, L. E. Crotty Vega, V. L. De Maio, A. Nizet, V. TI Changes in Bactericidal Capacity of Macrophages in Response to Fever. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Alexander, L. E. Crotty; Vega, V. L.; De Maio, A.; Nizet, V.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Alexander, L. E. Crotty] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM lecrotty@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3237 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102472 ER PT J AU Badesch, DB Feldman, J Keogh, A Mathier, MA Oudiz, RJ Shapiro, S Farber, H McGoon, M Frost, A Rubin, LJ AF Badesch, D. B. Feldman, J. Keogh, A. Mathier, M. A. Oudiz, R. J. Shapiro, S. Farber, H. McGoon, M. Frost, A. Rubin, L. J. CA ARIES-3 Study Grp TI ARIES-3: Ambrisentan Therapy in a Diverse Population of Patients with Pulmonary Hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Badesch, D. B.] Univ Colorado, Denver, CO 80202 USA. [Feldman, J.] Arizona Pulm Specialists Ltd, Phoenix, AZ USA. [Keogh, A.] St Vincents Hosp, Sydney, NSW 2010, Australia. [Mathier, M. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Oudiz, R. J.] Harbor UCLA, LA Biomed Res Inst, Torrance, CA USA. [Shapiro, S.] VA Greater LA Healthcare Syst, Los Angeles, CA USA. [Shapiro, S.] David Geffen UCLA Sch Med, Los Angeles, CA USA. [Farber, H.] Boston Univ, Sch Med, Boston, MA 02118 USA. [McGoon, M.] Mayo Clin, Rochester, MN USA. [Frost, A.] Baylor Coll Med, Houston, TX 77030 USA. [Rubin, L. J.] UCSD, La Jolla, CA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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. PY 2009 VL 179 MA A3357 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102592 ER PT J AU Bajwa, EK Januzzi, JL Gong, MN Thompson, BT Christiani, DC AF Bajwa, E. K. Januzzi, J. L. Gong, M. N. Thompson, B. T. Christiani, D. C. TI Plasma Levels of Interleukin Receptor ST2 and Mortality and Organ Failure in ARDS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bajwa, E. K.; Januzzi, J. L.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gong, M. N.] Mt Sinai Sch Med, New York, NY USA. EM ebajwa@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4635 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104100 ER PT J AU Bajwa, EK Khan, UA Januzzi, JL Gong, MN Thompson, BT Christiani, DC AF Bajwa, E. K. Khan, U. A. Januzzi, J. L. Gong, M. N. Thompson, B. T. Christiani, D. C. TI Plasma C-Reactive Protein Levels Are Associated with Improved Outcome in Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bajwa, E. K.; Khan, U. A.; Januzzi, J. L.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gong, M. N.] Mt Sinai Sch Med, New York, NY USA. EM ebajwa@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4629 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104094 ER PT J AU Bhattacharya, S Basu, A Mariani, TJ AF Bhattacharya, S. Basu, A. Mariani, T. J. TI An Expression Profiling Data Repository for Lung Disease Gene Discovery SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bhattacharya, S.; Mariani, T. J.] Univ Rochester, Dept Pediat, Rochester, NY USA. [Basu, A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM soumyaroop_bhattacharya@URMC.rochester.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1890 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101009 ER PT J AU Bilal, S Haworth, O Wu, L Weylandt, KH Levy, BD Kang, JX AF Bilal, S. Haworth, O. Wu, L. Weylandt, K. H. Levy, B. D. Kang, J. X. TI Fat-1 Mice Are Protected against Allergic Airway Inflammation. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Bilal, S.; Weylandt, K. H.; Kang, J. X.] Massachusetts Gen Hosp, Charlestown, MA USA. [Haworth, O.; Levy, B. D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bilal, S.; Weylandt, K. H.] Charite, D-13353 Berlin, Germany. [Wu, L.] Resolvyx, Bedford, MA USA. EM sbilal@gmx.de NR 3 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4224 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103577 ER PT J AU Calfee, CS Ware, LB Glidden, DV Eisner, MD Parsons, PE Thompson, BT Matthay, MA AF Calfee, C. S. Ware, L. B. Glidden, D. V. Eisner, M. D. Parsons, P. E. Thompson, B. T. Matthay, M. A. CA ARDS Network TI Combining Multiple Biomarkers Improves Risk Prediction in Patients with ALI in Both Derivation and Replication Cohorts SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ware, L. B.] Vanderbilt Univ, Nashville, TN USA. [Parsons, P. E.] Univ Vermont, Burlington, VT 05405 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM carolyn.calfee@ucsf.edu NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A4626 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104091 ER PT J AU Chandrasena, AR Ho, G Araujo, L Mao, Y Pan, J Frank, JA AF Chandrasena, A. R. Ho, G. Araujo, L. Mao, Y. Pan, J. Frank, J. A. TI Regulation of Paracellular Transport by Differential Claudin Expression in Alveolar Epithelial Cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Chandrasena, A. R.; Ho, G.; Araujo, L.; Pan, J.; Frank, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chandrasena, A. R.; Frank, J. A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mao, Y.; Frank, J. A.] NCIRE VHRI, San Francisco, CA USA. EM anita.chandrasena@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3560 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102794 ER PT J AU Choi, WI Syrkina, O Garg, HG Hales, CA AF Choi, W. I. Syrkina, O. Garg, H. G. Hales, C. A. TI Hyaluronan Improves Survival in Endotoxemic Rats. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Choi, W. I.; Syrkina, O.; Garg, H. G.; Hales, C. A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. EM wchoi@partners.org NR 0 TC 0 Z9 0 U1 1 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. PY 2009 VL 179 MA A5555 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105146 ER PT J AU Conhaim, RL Watson, KE Dovi, WF Harms, BA AF Conhaim, R. L. Watson, K. E. Dovi, W. F. Harms, B. A. TI Microthrombus Formation Continues in Rat Lungs for up to 24 Hours Following Acute Hemorrhage SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Conhaim, R. L.; Watson, K. E.; Harms, B. A.] Univ Wisconsin, Sch Med, Madison, WI USA. [Dovi, W. F.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3870 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103223 ER PT J AU Coppersmith, JC Gylys-Colwell, IM Dougherty, CM Schneider, C Hunziker, J Short, V Sablinsky, M Steele, BG AF Coppersmith, J. C. Gylys-Colwell, I. M. Dougherty, C. M. Schneider, C. Hunziker, J. Short, V. Sablinsky, M. Steele, B. G. TI Combined Rehabilitation Program for Chronic Obstructive Pulmonary Disease (COPD) and Heart Failure (HF). SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Coppersmith, J. C.; Gylys-Colwell, I. M.; Schneider, C.; Hunziker, J.; Short, V.; Sablinsky, M.; Steele, B. G.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Dougherty, C. M.] Univ Washington, Sch Nursing, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2370 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101489 ER PT J AU Danilack, VA Stolzmann, KL Gagnon, DR Brown, R Tun, CG Garshick, E AF Danilack, V. A. Stolzmann, K. L. Gagnon, D. R. Brown, R. Tun, C. G. Garshick, E. TI Current and Future Chest Illness in Chronic Spinal Cord Injury SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Danilack, V. A.; Stolzmann, K. L.; Gagnon, D. R.; Tun, C. G.; Garshick, E.] VA Boston Healthcare Syst, Boston, MA USA. [Garshick, E.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Gagnon, D. R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Brown, R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Danilack, V. A.; Stolzmann, K. L.; Brown, R.; Tun, C. G.; Garshick, E.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4212 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103565 ER PT J AU de Molina, RMM Mortensen, EM Copeland, LA Pugh, MJV Anzueto, A Restrepo, MI AF de Molina, R. M. Malo Mortensen, E. M. Copeland, L. A. Pugh, M. J. V. Anzueto, A. Restrepo, M. I. TI Outpatient Inhaled Corticosteroid (ICS) Therapy Decreases Mortality in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [de Molina, R. M. Malo; Anzueto, A.; Restrepo, M. I.] Univ Texas Hlth Care Syst, San Antonio, TX USA. [de Molina, R. M. Malo; Mortensen, E. M.; Copeland, L. A.; Pugh, M. J. V.; Restrepo, M. I.] S Texas Vet Hlth Care Syst VERDICT, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A6115 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105706 ER PT J AU Eikermann, M Zaremba, S Fassbender, P Jordan, AS Rosow, C Malhotra, A Chamberlin, NL AF Eikermann, M. Zaremba, S. Fassbender, P. Jordan, A. S. Rosow, C. Malhotra, A. Chamberlin, N. L. TI Pentobarbital's Respiratory Depressant Effect Spares Upper Airway Muscle Activity during Anesthesia in Rats SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Eikermann, M.; Rosow, C.] Massachusetts Gen Hosp, Dpt Anesthesia & Crit Care, Boston, MA 02114 USA. [Eikermann, M.; Zaremba, S.; Fassbender, P.; Jordan, A. S.; Malhotra, A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Zaremba, S.; Fassbender, P.; Chamberlin, N. L.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. EM meikermann@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5401 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104865 ER PT J AU Eikermann, M Jordan, AS Eckert, DJ Chamberlin, NL Zaremba, S Rosow, C Malhotra, A AF Eikermann, M. Jordan, A. S. Eckert, D. J. Chamberlin, N. L. Zaremba, S. Rosow, C. Malhotra, A. TI Effects of Pentobarbital on Genioglossus Muscle Activity and Upper Airway Collapsibility during Sleep. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Eikermann, M.; Rosow, C.] Massachusetts Gen Hosp, Dpt Anesthesia & Crit Care, Boston, MA 02114 USA. [Eikermann, M.; Jordan, A. S.; Eckert, D. J.; Zaremba, S.; Malhotra, A.] Brigham & Womens Hosp, Div Sleep Med, Boston, MA 02115 USA. [Chamberlin, N. L.] Beth Israel Deaconess Med Ctr, Dpt Neurol, Boston, MA 02215 USA. EM meikermann@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3593 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102826 ER PT J AU Fan, VS Udris, EM Au, DH AF Fan, V. S. Udris, E. M. Au, D. H. TI Factors Associated with Self-Efficacy in COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Fan, V. S.; Udris, E. M.; Au, D. H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A1077 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100078 ER PT J AU Ferreira, JC Bensenor, F Rocha, MJ Salge, JM Kacmarek, RM Carvalho, CCR AF Ferreira, J. C. Bensenor, F. Rocha, M. J. Salge, J. M. Kacmarek, R. M. Carvalho, C. C. R. TI Pressure-Volume Curves of Patients with Idiopathic Pulmonary Fibrosis (IPF): Evidence of Small Airway and Alveolar Collapse during Mechanical Ventilation. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ferreira, J. C.; Rocha, M. J.; Salge, J. M.; Carvalho, C. C. R.] Univ Sao Paulo Med Sch, Resp ICU, Div Pulm, Sao Paulo, Brazil. [Bensenor, F.] Univ Sao Paulo Med Sch, Hosp Clin, Div Anesthesia, Sao Paulo, Brazil. [Kacmarek, R. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM ju-ferreira@uol.com.br RI Salge, Joao/B-5157-2015 OI Salge, Joao/0000-0001-5121-0129 NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A2992 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102227 ER PT J AU Funke, M Shea, BS Groom, JR Brooks, SF Chun, J Tager, AM AF Funke, M. Shea, B. S. Groom, J. R. Brooks, S. F. Chun, J. Tager, A. M. TI Lysophosphatidic Acid Contributes to an Apoptosis Paradox in Lung Fibrosis. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Funke, M.; Shea, B. S.; Groom, J. R.; Brooks, S. F.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chun, J.] Scripps Res Inst, La Jolla, CA 92037 USA. EM mfunke@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1988 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101107 ER PT J AU Gong, MN Bajwa, EK Thompson, BT Christiani, DC AF Gong, M. N. Bajwa, E. K. Thompson, B. T. Christiani, D. C. TI Body Mass Index Is Associated with the Development of ARDS. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gong, M. N.] Mt Sinai Sch Med, New York, NY 10029 USA. [Bajwa, E. K.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM Michelle.Gong@mssm.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5851 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105442 ER PT J AU Gong, MN Bajwa, EK Thompson, BT Christiani, DC AF Gong, M. N. Bajwa, E. K. Thompson, B. T. Christiani, D. C. TI Use of ACE Inhibitors and Development and Outcome in ARDS SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Gong, M. N.] Mt Sinai Sch Med, New York, NY USA. [Bajwa, E. K.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. EM Michelle.Gong@mssm.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2009 VL 179 MA A5095 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104559 ER PT J AU Harris, RS Wongviriyawong, C Kone, M Winkler, T Musch, G Melo, MFV Venegas, JG AF Harris, R. S. Wongviriyawong, C. Kone, M. Winkler, T. Musch, G. Melo, M. F. Vidal Venegas, J. G. TI Paradoxical Dilatation of Central Airways after Methacholine (MCh) Challenge in Asthma. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Harris, R. S.; Wongviriyawong, C.; Kone, M.; Winkler, T.; Musch, G.; Melo, M. F. Vidal; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, R. S.; Wongviriyawong, C.; Kone, M.; Winkler, T.; Musch, G.; Melo, M. F. Vidal; Venegas, J. G.] Harvard Univ, Sch Med, Boston, MA USA. EM rharris@partners.org RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A2413 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101532 ER PT J AU Herrero, R Kajikawa, O Matute-Bello, G Fu, X Wong, VA Martin, TR AF Herrero, R. Kajikawa, O. Matute-Bello, G. Fu, X. Wong, V. A. Martin, T. R. TI The N-Terminal Sequence of Soluble FasL Determines Its Bioactivity SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Herrero, R.; Kajikawa, O.; Matute-Bello, G.; Wong, V. A.] VA Puget Sound, Seattle, WA USA. [Herrero, R.; Kajikawa, O.; Matute-Bello, G.; Fu, X.; Wong, V. A.] U Washington, Seattle, WA USA. EM rherrero@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2496 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101615 ER PT J AU Ho, G Mao, Y Chandrasena, A Lam, D Frank, JA AF Ho, G. Mao, Y. Chandrasena, A. Lam, D. Frank, J. A. TI The Contribution of Claudin 4 to In Vitro Alveolar Epithelial Barrier Repair SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ho, G.; Chandrasena, A.; Frank, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lam, D.; Frank, J. A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mao, Y.; Frank, J. A.] NCIRE VHRI, San Francisco, CA USA. EM gwendolyn.ho@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2395 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101514 ER PT J AU Kathuria, H Carretero, J Marquez, H Hinds, A Williams, MC Wong, KK AF Kathuria, H. Carretero, J. Marquez, H. Hinds, A. Williams, M. C. Wong, K. K. TI Increased Ets-1 Positively Correlates with Caveolin-1 Expression in Mouse Non-Small Cell Lung Cancer (NSCLC) Progression and Metastasis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kathuria, H.; Marquez, H.; Hinds, A.; Williams, M. C.] Boston Univ, Med Ctr, Boston, MA USA. [Carretero, J.; Wong, K. K.] Dana Farber Canc Inst, Boston, MA 02115 USA. EM hasmeena@bu.edu RI Carretero, Julian/N-5214-2014 OI Carretero, Julian/0000-0001-7269-8506 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2676 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101795 ER PT J AU Kling, DE Sollinger, CA Cavicchio, AJ Schnitzer, JJ Kinane, TB AF Kling, D. E. Sollinger, C. A. Cavicchio, A. J. Schnitzer, J. J. Kinane, T. B. TI Alveolar Septation Is Inhibited by Retinoic Acid Via an Epithelial-Specific Mechanism in Rat Fetal Lung Explants SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kling, D. E.; Sollinger, C. A.; Cavicchio, A. J.; Kinane, T. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schnitzer, J. J.] Boston Sci Corp, Natick, MA USA. EM dkling@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2645 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101764 ER PT J AU Koff, PB Min, S Freitag, TJ James, SS Keith, RL Kveton, C Carwin, S Stelzner, TJ Brand, DW Ritzwoller, DP Beck, AL Voelkel, NF Vandivier, RW AF Koff, P. B. Min, S. Freitag, T. J. James, S. S. Keith, R. L. Kveton, C. Carwin, S. Stelzner, T. J. Brand, D. W. Ritzwoller, D. P. Beck, A. L. Voelkel, N. F. Vandivier, R. W. TI Proactive Integrated Care Reduces Critical Care & Improves Quality-of-Life in COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Koff, P. B.; Freitag, T. J.; James, S. S.] Univ CO Hosp, Aurora, CO USA. [Min, S.; Keith, R. L.; Vandivier, R. W.] Univ CO Hlth Sci Ctr, Dept Med, Aurora, CO USA. [Keith, R. L.] Denver Vet Affairs Med Ctr, Dept Med, Denver, CO USA. [Kveton, C.; Carwin, S.; Stelzner, T. J.; Brand, D. W.; Ritzwoller, D. P.; Beck, A. L.] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. [Voelkel, N. F.] VA Commonwealth Univ, Dept Med, Richmond, VA USA. EM patricia.koff@uch.edu NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A3100 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102335 ER PT J AU Kradin, RL ODonnell, W Medoff, B Mark, EJ Nishino, M AF Kradin, R. L. ODonnell, W. Medoff, B. Mark, E. J. Nishino, M. TI Atypical Alveolar Lipoproteinosis: An Idiopathic Pathological Syndrome Reflecting Abnormal Intraalveolar Macrophage Disruption. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kradin, R. L.; ODonnell, W.; Medoff, B.; Mark, E. J.; Nishino, M.] Massachsusetts Gen Hosp, Boston, MA USA. EM rkradin@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3027 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102262 ER PT J AU Ku, CH Lin, CC Liu, IL Lin, JC Chang, FY Christiani, DC AF Ku, C. H. Lin, C. C. Liu, I. L. Lin, J. C. Chang, F. Y. Christiani, D. C. TI Effectiveness of Bacille Calmette-Guerin (BCG) Vaccination in Taiwan. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ku, C. H.; Lin, C. C.; Liu, I. L.] NDMC, Sch Publ Hlth, Taipei, Taiwan. [Lin, J. C.; Chang, F. Y.] NDMC, Dept Internal Med, Triserv Gen Hosp, Taipei, Taiwan. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, D. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM cku@ndmctsgh.edu.tw NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4783 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104247 ER PT J AU Ku, CH Liu, IL Lin, CC Lin, JC Chang, FY Christiani, DC AF Ku, C. H. Liu, I. L. Lin, C. C. Lin, J. C. Chang, F. Y. Christiani, D. C. TI A Cross-Sectional Study on TB Infection in Taiwan. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Ku, C. H.; Liu, I. L.; Lin, C. C.] NDMC, Sch Publ Hlth, Taipei, Taiwan. [Lin, J. C.; Chang, F. Y.] NDMC, Dept Internal Med, Triserv Gen Hosp, Taipei, Taiwan. [Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Christiani, D. C.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. [Christiani, D. C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. EM cku@ndmctsgh.edu.tw NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4782 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104246 ER PT J AU Kurahashi, K Kajikawa, O Matute-Bello, G Martin, TR AF Kurahashi, K. Kajikawa, O. Matute-Bello, G. Martin, T. R. TI FasL and LPS Have Synergistic Effects on Inflammation of Epithelial Cells. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Kurahashi, K.; Kajikawa, O.; Matute-Bello, G.; Martin, T. R.] VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA USA. [Kurahashi, K.; Kajikawa, O.; Matute-Bello, G.; Martin, T. R.] Univ Washington, Sch Med, Dept Med, Div Pulm & Crit Care Med, Seattle, WA 98195 USA. [Kurahashi, K.] Yokohama City Univ, Grad Sch Med, Dept Anesthesiol & Crit Care Med, Yokohama, Kanagawa 232, Japan. EM yasuk@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5642 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105233 ER PT J AU Leu, SW Shi, LY Zhao, GF Lien, E Sheidlin, A Zhao, H Hales, CA AF Leu, S. W. Shi, L. Y. Zhao, G. F. Lien, E. Sheidlin, A. Zhao, H. Hales, C. A. TI The p38 Mitogen-Activated Protein Kinase (MAPK) Dependent Signaling Is Essential for Acute Lung Injury Induced by Low Molecular Weight Hyaluronan. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Leu, S. W.; Shi, L. Y.; Zhao, G. F.; Zhao, H.; Hales, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Leu, S. W.] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan. [Lien, E.] Univ Massachusetts, Sch Med, Program Immunol, Worcester, MA USA. [Sheidlin, A.] Genzyme Corp, Framingham, MA 01701 USA. EM sleu@partners.org NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A5680 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105271 ER PT J AU Linas, BP Freedberg, KA Horsburgh, CR AF Linas, B. P. Freedberg, K. A. Horsburgh, C. R. TI Revisiting the Effectiveness of LTBI Screening in the US SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Linas, B. P.; Freedberg, K. A.] Mass Gen Hosp, Boston, MA USA. [Horsburgh, C. R.] Boston Univ, Sch Publ Hlth, Boston, MA USA. EM blinas@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A5283 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104747 ER PT J AU Lipke, AB Wong, VA Matute-Bello, G Martin, TR AF Lipke, A. B. Wong, V. A. Matute-Bello, G. Martin, T. R. TI Mechanisms of Enhanced Lung Injury in Febrile Hyperthermia: Role of Alveolar Epithelial Apoptosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Lipke, A. B.; Wong, V. A.; Martin, T. R.] VA Puget Sound, Seattle, WA USA. [Matute-Bello, G.] Ctr Lung Biol, Seattle, WA USA. EM ablipke@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3862 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103215 ER PT J AU Liu, F Shea, BS Mih, JD Tager, AM Tschumperlin, DJ AF Liu, F. Shea, B. S. Mih, J. D. Tager, A. M. Tschumperlin, D. J. TI Lung Parenchymal Tissue Stiffness in Fibrosis Measured by Atomic Force Microscopy Microindentation. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Liu, F.; Mih, J. D.; Tschumperlin, D. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Shea, B. S.; Tager, A. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM fliu@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 1 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. PY 2009 VL 179 MA A3438 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102673 ER PT J AU Liu, L Oh, WY Suter, MJ Gulati, A Bouma, BE Rowe, SM Tearney, GJ AF Liu, L. Oh, W. Y. Suter, M. J. Gulati, A. Bouma, B. E. Rowe, S. M. Tearney, G. J. TI Ultrahigh-Resolution 3D Optical Imaging of the Swine Pulmonary Airways SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Liu, L.; Oh, W. Y.; Suter, M. J.; Gulati, A.; Bouma, B. E.; Tearney, G. J.] Harvard Univ, Sch Med, Boston, MA USA. [Liu, L.; Oh, W. Y.; Suter, M. J.; Gulati, A.; Bouma, B. E.; Tearney, G. J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rowe, S. M.] Univ Alabama Birmingham, Birmingham, AL USA. EM tearney@helix.mgh.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1221 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100222 ER PT J AU Mao, Y Chandrasena, A Araujo, L Ho, G Frank, JA AF Mao, Y. Chandrasena, A. Araujo, L. Ho, G. Frank, J. A. TI Claudin 4 Is Induced in the Alveolar Epithelium by a JNK-Dependent Mechanism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Chandrasena, A.; Araujo, L.; Ho, G.; Frank, J. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Frank, J. A.] San Francisco VA Med Ctr, San Francisco, CA USA. [Mao, Y.; Frank, J. A.] NCIRE VHRI, San Francisco, CA USA. EM james.frank@ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5001 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104465 ER PT J AU Mauri, T Berra, L Kumwilaisak, K Pivi, S Ufberg, J Kueppers, F Pesenti, A Bigatello, LM AF Mauri, T. Berra, L. Kumwilaisak, K. Pivi, S. Ufberg, J. Kueppers, F. Pesenti, A. Bigatello, L. M. TI Could Lateral Horizontal Position Decrease Aspiration of Gastric Contents in Intubated Patients in a Surgical Intensive Care Unit? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mauri, T.; Pesenti, A.] Univ Milano Bicocca, Dept Expt Med, Monza, MI, Italy. [Berra, L.; Kumwilaisak, K.; Pivi, S.; Bigatello, L. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Berra, L.; Kumwilaisak, K.; Pivi, S.; Bigatello, L. M.] Harvard Univ, Sch Med, Boston, MA USA. [Ufberg, J.; Kueppers, F.] Temple Sch Med, Dept Med, Philadelphia, PA USA. EM tommymauri@gmail.com NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1569 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100569 ER PT J AU Mortensen, EM Copeland, LA Pugh, MJ de Molina, RM Restrepo, MI Anzueto, A AF Mortensen, E. M. Copeland, L. A. Pugh, M. J. de Molina, R. Malo Restrepo, M. I. Anzueto, A. TI Impact of Prior Statin and ACE Inhibitor Use on Mortality for Subjects Hospitalized with COPD Exacerbations. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mortensen, E. M.; Copeland, L. A.; Pugh, M. J.; de Molina, R. Malo; Restrepo, M. I.; Anzueto, A.] South Texas Vet Hlth Care Syst, San Antonio, TX USA. [Mortensen, E. M.; Copeland, L. A.; Pugh, M. J.; de Molina, R. Malo; Restrepo, M. I.; Anzueto, A.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. EM mortensene@uthscsa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5354 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104818 ER PT J AU Moy, ML Patel, S Mancinelli, C Matthess, K Healey, J Bonato, P AF Moy, M. L. Patel, S. Mancinelli, C. Matthess, K. Healey, J. Bonato, P. TI Accuracy of the Step Activity Monitor and Omron HJ-720ITC in Moderate-Severe COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moy, M. L.; Matthess, K.] VA Boston Healthcare Syst, Boston, MA USA. [Patel, S.; Mancinelli, C.; Bonato, P.] Spaulding Rehabil Hosp, Charlestown, MA USA. [Moy, M. L.; Matthess, K.; Bonato, P.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. EM marilyn.moy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3850 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103203 ER PT J AU Moy, ML Janney, AW Nguyen, HQ Cohen, M Richardson, CR AF Moy, M. L. Janney, A. W. Nguyen, H. Q. Cohen, M. Richardson, C. R. TI An Internet-Mediated Walking Program Promotes Free-Living Ambulation in COPD SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Moy, M. L.] VA Boston Healthcare Syst, Boston, MA USA. [Janney, A. W.] Univ Michigan, Ann Arbor, MI 48109 USA. [Nguyen, H. Q.] Univ Washington, Seattle, WA 98195 USA. [Cohen, M.] VA New York Harbor, New York, NY USA. [Richardson, C. R.] Ann Arbor VA Med Ctr, Ann Arbor, MI USA. EM marilyn.moy@va.gov NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3859 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103212 ER PT J AU Mrabat, HM Garg, HG Hales, CA AF Mrabat, H. M. Garg, H. G. Hales, C. A. TI Growth Inhibition of Pulmonary Artery Smooth Muscle Cells Following Long Term Heparin Treatment. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Mrabat, H. M.; Garg, H. G.; Hales, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM hmrabat@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1854 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100853 ER PT J AU Nuernberg, AM Zhai, R Thompson, BT Christiani, DC AF Nuernberg, A. M. Zhai, R. Thompson, B. T. Christiani, D. C. TI Genetic Polymorphisms in the Insulin Growth Factor Pathway and Outcomes in ARDS. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nuernberg, A. M.; Zhai, R.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Nuernberg, A. M.; Thompson, B. T.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM anuernberg@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3888 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103241 ER PT J AU Nyendak, M Swarbrick, G Null, M Cansler, M Frieder, M Mayanja-Kizza, H Mugerwa, RD Boom, WH Zalwango, S Rajaraman, V Sherman, D Mori, T McWeeney, S Park, B Lewinsohn, DA Lewinsohn, DM AF Nyendak, M. Swarbrick, G. Null, M. Cansler, M. Frieder, M. Mayanja-Kizza, H. Mugerwa, R. D. Boom, W. H. Zalwango, S. Rajaraman, V. Sherman, D. Mori, T. McWeeney, S. Park, B. Lewinsohn, D. A. Lewinsohn, D. M. TI The Diagnostic Potential of the CD8(+) T Cell Response: Identification of Immunodominant CD8(+) T Cell Antigens and the Potential To Differentiate Latent from Active Tuberculosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Nyendak, M.; Swarbrick, G.; Null, M.; Cansler, M.; Rajaraman, V.; Mori, T.; McWeeney, S.; Park, B.; Lewinsohn, D. A.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Swarbrick, G.; Null, M.; Cansler, M.; Frieder, M.; Lewinsohn, D. M.] Portland VA Med Ctr, Portland, OR USA. [Mayanja-Kizza, H.; Mugerwa, R. D.; Zalwango, S.] Makerere Univ, Kampala, Uganda. [Boom, W. H.] Case Western Reserve Univ, TB Res Unit, Cleveland, OH 44106 USA. [Sherman, D.] Univ Washington, Seattle, WA 98195 USA. EM nyendakm@ohsu.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1016 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100017 ER PT J AU Saboisky, JP Nandedkar, S Eckert, DJ Jordan, AS David, WS Ali, M White, DP Trinder, JA Nicholas, CL Malhotra, A AF Saboisky, J. P. Nandedkar, S. Eckert, D. J. Jordan, A. S. David, W. S. Ali, M. White, D. P. Trinder, J. A. Nicholas, C. L. Malhotra, A. TI The Selective Examination of Genioglossus (GG) Muscle Fiber Density (FD) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Saboisky, J. P.; Eckert, D. J.; Jordan, A. S.; White, D. P.; Malhotra, A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Saboisky, J. P.; Eckert, D. J.; Jordan, A. S.; White, D. P.; Malhotra, A.] Harvard Univ, Sch Med, Div Sleep Med, Boston, MA USA. [David, W. S.; Ali, M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Trinder, J. A.; Nicholas, C. L.] Univ Melbourne, Dept Psychol, Melbourne, Vic, Australia. [Nandedkar, S.] Cardinal Hlth, Hopewell Jct, NY USA. RI Saboisky, Julian/P-5782-2014 OI Saboisky, Julian/0000-0002-9450-6023 NR 2 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4214 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103567 ER PT J AU Sheu, CC Zhai, R Wang, Z Gong, MN Tejera, P Chen, F Su, L Thompson, BT Christiani, DC AF Sheu, C. C. Zhai, R. Wang, Z. Gong, M. N. Tejera, P. Chen, F. Su, L. Thompson, B. T. Christiani, D. C. TI Heme Oxygenase-1 Gene Polymorphisms Are Associated with the Development of Acute Respiratory Distress Syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sheu, C. C.; Zhai, R.; Wang, Z.; Tejera, P.; Chen, F.; Su, L.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Mt Sinai Sch Med, New York, NY USA. [Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM csheu@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4624 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104089 ER PT J AU Sheu, CC Gong, MN Zhai, R Bajwa, EK Gallagher, DC Chen, F Clardy, PF Thompson, BT Christiani, DC AF Sheu, C. C. Gong, M. N. Zhai, R. Bajwa, E. K. Gallagher, D. C. Chen, F. Clardy, P. F. Thompson, B. T. Christiani, D. C. TI Infection-Related Acute Respiratory Distress Syndrome: Epidemiology, Microbiology, Risk and Prognostic Factors. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Sheu, C. C.; Zhai, R.; Chen, F.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Mt Sinai Sch Med, New York, NY USA. [Bajwa, E. K.; Thompson, B. T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallagher, D. C.; Clardy, P. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM csheu@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A4637 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104102 ER PT J AU Shi, LY Leu, SW Sheidlin, A Zhao, H Hales, CA AF Shi, L. Y. Leu, S. W. Sheidlin, A. Zhao, H. Hales, C. A. TI TLR2 Modulates the Effects of the Low Molecular Weight Hyaluronan (LMW HA)-Induced Lung Inflammation. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Shi, L. Y.; Leu, S. W.; Zhao, H.; Hales, C. A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA USA. [Shi, L. Y.] Hangzhou Normal Univ, Dept Immunol, Hangzhou, Zhejiang, Peoples R China. [Leu, S. W.] Chang Gung Mem Hosp, Div Pulm & Crit Care Med, Chiayi, Taiwan. [Sheidlin, A.] Genzyme Corp, Cambridge, MA USA. EM LSHI3@PARTNERS.ORG NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A3993 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103346 ER PT J AU Slatore, CG Udris, EM Cecere, LM Moss, BR Bryson, CL Au, DH AF Slatore, C. G. Udris, E. M. Cecere, L. M. Moss, B. R. Bryson, C. L. Au, D. H. TI Provider Communication among Patients with Chronic Obstructive Pulmonary Disease: Association with Patient Reported Outcomes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Slatore, C. G.; Udris, E. M.; Cecere, L. M.; Moss, B. R.; Bryson, C. L.; Au, D. H.] Vet Affairs Puget Sound Healthcare Syst, Hlth Serv Res & Dev, Seattle, WA USA. EM cslatore@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5200 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104664 ER PT J AU Slatore, CG Au, DH Gould, MK AF Slatore, C. G. Au, D. H. Gould, M. K. TI Insurance Status and Disparities in Outcomes of Lung Cancer Care: A Systematic Review. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Slatore, C. G.; Au, D. H.] VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. [Gould, M. K.] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA. EM cslatore@u.washington.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3748 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103101 ER PT J AU Song, Y Baer, M Lima, J Zhuo, H Wiener-Kronish, JP Bebbington, C Lynch, SV AF Song, Y. Baer, M. Lima, J. Zhuo, H. Wiener-Kronish, J. P. Bebbington, C. Lynch, S. V. TI Antibody-Antibiotic Combination Therapy Significantly Reduces Lung Injury and Improves Survival in Mice Infected with P. aeruginosa SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Song, Y.; Lima, J.; Lynch, S. V.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Baer, M.; Bebbington, C.] KalaBios INC, San Francisco, CA USA. [Zhuo, H.] UCSF, CVRI, San Francisco, CA USA. [Wiener-Kronish, J. P.] Massachusetts Gen Hosp, Deaprtment Anesthesia & Crit Care, Boston, MA 02114 USA. EM songy@anesthesia.ucsf.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A5110 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104574 ER PT J AU Suter, MJ Riker, DR Bouma, BE Beamis, JF Tearney, GJ AF Suter, M. J. Riker, D. R. Bouma, B. E. Beamis, J. F. Tearney, G. J. TI Comprehensive Microscopy of the Swine and Human Pulmonary Airways In Vivo SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Suter, M. J.; Bouma, B. E.; Tearney, G. J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Riker, D. R.; Beamis, J. F.] Lahey Clin Med Ctr, Burlington, MA 01803 USA. EM msuter@partners.org NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3536 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102770 ER PT J AU Syrkina, OL Quinn, DA Chales, CA AF Syrkina, O. L. Quinn, D. A. Chales, C. A. TI TLR 4 and JNK I Link to Smoke Inhalation Lung Injury from Fire. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Syrkina, O. L.; Quinn, D. A.; Chales, C. A.] Massachusetts Genereal Hosp, Boston, MA USA. [Syrkina, O. L.; Quinn, D. A.; Chales, C. A.] Harvard Univ, Sch Med, Boston, MA USA. [Syrkina, O. L.] Shriners Burn Hosp, Boston, MA USA. EM osyrkina@partners.org NR 0 TC 0 Z9 0 U1 1 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. PY 2009 VL 179 MA A5570 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105161 ER PT J AU Troy, P Lewis, G Janocha, AJ Van Horn, T Erzurum, SC Waxman, AB Systrom, DM AF Troy, P. Lewis, G. Janocha, A. J. Van Horn, T. Erzurum, S. C. Waxman, A. B. Systrom, D. M. TI Abnormal Transpulmonary Metabolite Flux in Exercise Induced Pulmonary Arterial Hypertension. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Troy, P.; Lewis, G.; Van Horn, T.; Waxman, A. B.; Systrom, D. M.] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. [Janocha, A. J.; Erzurum, S. C.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. EM dsystrom@partners.org NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 2009 VL 179 MA A4131 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103484 ER PT J AU Vaporidi, K Bloch, KD Zapol, WM AF Vaporidi, K. Bloch, K. D. Zapol, W. M. TI Endothelial Nitric Oxide (NO) Synthase (NOS3) Contributes to Ventilator-Induced Lung Injury (VILI) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Vaporidi, K.; Bloch, K. D.; Zapol, W. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3830 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103183 ER PT J AU Wang, Z Chen, F Zhai, R Zhang, L Su, L Lin, X Thompson, TB Christiani, DC AF Wang, Z. Chen, F. Zhai, R. Zhang, L. Su, L. Lin, X. Thompson, T. B. Christiani, D. C. TI Plasma Neutrophil Elastase and Elafin Imbalance Is Associated with ARDS Development SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wang, Z.; Chen, F.; Zhai, R.; Zhang, L.; Su, L.; Lin, X.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Thompson, T. B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3867 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103220 ER PT J AU Waxman, AB Lawler, L AF Waxman, A. B. Lawler, L. TI Cicletanine Therapy Is Well Tolerated in Patients with Advanced Pulmonary Arterial Hypertension (PAH) SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Waxman, A. B.; Lawler, L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Waxman, A. B.] Harvard Univ, Sch Med, Boston, MA USA. EM abwaxman@partners.org NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A3353 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102588 ER PT J AU Wilker, EH Mordukhovich, I Suh, H Wright, RO Sparrow, D Vokonas, P Schwartz, J AF Wilker, E. H. Mordukhovich, I. Suh, H. Wright, R. O. Sparrow, D. Vokonas, P. Schwartz, J. TI Association between Black Carbon Exposure, Oxidative Stress Genes and Blood Pressure in the Normative Aging Study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wilker, E. H.; Suh, H.; Wright, R. O.; Schwartz, J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Mordukhovich, I.] Univ N Carolina, Chapel Hill, NC USA. [Sparrow, D.; Vokonas, P.] VA Boston Healthcare Syst, Boston, MA USA. EM ewilker@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A1173 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100174 ER PT J AU Winkler, T Venegas, JG AF Winkler, T. Venegas, J. G. TI Insufficient Volume of Deep Breath (DB) Can Explain Bronchoconstrictor Effect of DBs in Asthma. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Winkler, T.; Venegas, J. G.] Massachusetts Gen Hosp, Dept Anesthsia & Crit Care, Boston, MA 02114 USA. RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2424 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101543 ER PT J AU Wongviriyawong, C Winkler, T Venegas, JG AF Wongviriyawong, C. Winkler, T. Venegas, J. G. TI Modeling the Stability of Tidal Volume (VT) during Bronchoconstriction. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Wongviriyawong, C.] MIT, Cambridge, MA 02139 USA. [Winkler, T.; Venegas, J. G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Winkler, T.; Venegas, J. G.] Harvard Univ, Sch Med, Boston, MA USA. EM minto@mit.edu RI Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A6048 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733105639 ER PT J AU Yu, L Hales, CA AF Yu, L. Hales, C. A. TI Inhibition of CXCR4 Activity Attenuates Development of Pulmonary Hypertension and Vascular Remodeling Induced by Hypoxia in Rats. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Yu, L.; Hales, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Yu, L.; Hales, C. A.] Harvard Univ, Sch Med, Boston, MA USA. EM lyu3@partners.org NR 0 TC 0 Z9 0 U1 1 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. PY 2009 VL 179 MA A2359 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101478 ER PT J AU Zhai, R Chen, F Sheu, C Su, L Gong, MN Tejera, P Thompson, TB Christiani, DC AF Zhai, R. Chen, F. Sheu, C. Su, L. Gong, M. N. Tejera, P. Thompson, T. B. Christiani, D. C. TI High-Order Interactions among Genetic Variants in Angiogenesis Pathway Genes and ARDS Risk SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhai, R.; Chen, F.; Sheu, C.; Su, L.; Tejera, P.; Christiani, D. C.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Gong, M. N.] Mt Sinai Sch Medidine, New York, NY USA. [Thompson, T. B.; Christiani, D. C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM rzhai@hsph.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A2502 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733101621 ER PT J AU Zhao, G John, B Syrkina, O Kolliputi, N Zhao, H Shaik, R Hales, C AF Zhao, G. John, B. Syrkina, O. Kolliputi, N. Zhao, H. Shaik, R. Hales, C. TI Aorta to Main Pulmonary Shunt Induces Significantly More Intraacinar Arteriole Remodeling in the Left Lung Than Right Lung. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhao, G.; John, B.; Syrkina, O.; Kolliputi, N.; Zhao, H.; Shaik, R.; Hales, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kolliputi, Narasaiah/I-6050-2012 OI Kolliputi, Narasaiah/0000-0002-2654-1900 NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 2009 VL 179 MA A3398 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102633 ER PT J AU Zhao, H Leu, SW Shi, LY Dedaj, R Zhao, GF Shen, LJ Lien, E Fitzgerald, KA Sheidlin, A Quinn, DA Hales, CA AF Zhao, H. Leu, S. W. Shi, L. Y. Dedaj, R. Zhao, G. F. Shen, L. J. Lien, E. Fitzgerald, K. A. Sheidlin, A. Quinn, D. A. Hales, C. A. TI Toll like Receptor 4, a Negative Regulator in Low Molecular Weight Hyaluronan Induced Acute Lung Injury. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Zhao, H.; Leu, S. W.; Shi, L. Y.; Dedaj, R.; Zhao, G. F.; Quinn, D. A.; Hales, C. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shen, L. J.; Lien, E.; Fitzgerald, K. A.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Sheidlin, A.] Genzyme Corp, Framingham, MA 01701 USA. EM hzhao5@partners.org NR 0 TC 0 Z9 0 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. PY 2009 VL 179 MA A4247 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733103600 ER PT J AU Minowada, G Miller, YE AF Minowada, George Miller, York E. TI Overexpression of Sprouty 2 in Mouse Lung Epithelium Inhibits Urethane-Induced Tumorigenesis SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE Sprouty; lung cancer; mouse; chemoprevention; Ras ID K-RAS; MOLECULAR PATHOGENESIS; SIGNAL-TRANSDUCTION; A/J MICE; GROWTH; CANCER; PATHWAY; TUMORS; EXPRESSION; PULMONARY AB Members of the Sprouty family encode novel proteins that are thought to function primarily as intracellular antagonists of the Ras-signaling pathway. Increased Ras signaling is a critical characteristic of human lung adenocarcinoma, the most common type of non-small cell lung cancer. Sprouty 2 is expressed in the lung epithelium, the tissue layer from which lung cancers arise. We hypothesized that overexpression of Sprouty 2 in the distal lung epithelium would inhibit lung tumorigenesis. To test the hypothesis, the consequences of overexpressing Sprouty 2 in the distal lung epithelium on urethane-induced mouse lung tumorigenesis were determined. Urethane is a chemical carcinogen found in tobacco smoke that causes activating mutations in Kras and induces lung tumors in mice. Sprouty 2-overexpressor mice developed significantly fewer lung tumors compared with their littermate controls (113.2 +/- 1.1 versus 18.1 +/- 1.3, P = 0.006). Tumor diameter was also significantly smaller in Sprouty 2 overexpressors (0.85 mm +/- 0.03 versus 0.95 mm +/- 0.02, P = 0.005). Sprouty 2 overexpression did not alter Kras mutational frequencies in urethane-induced tumors, suggesting that the tumor-suppressing effect of Sprouty 2 overexpression acts at a stage after Kras mutation, perhaps by interfering with receptor tyrosine kinase-induced signaling. These results demonstrate that Sprouty 2 overexpression inhibited both tumor initiation and subsequent tumor growth. C1 [Miller, York E.] Univ Colorado, Ctr Canc, Denver Vet Affairs Med Ctr, Div Pulm Sci & Crit Care Med, Denver, CO 80220 USA. [Miller, York E.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. [Minowada, George] Louis Stokes Cleveland Vet Affairs Med Ctr, Cleveland, OH USA. [Minowada, George] Case Western Reserve Univ, Univ Hosp Cleveland, Div Pulm & Crit Care Med, Cleveland, OH 44106 USA. RP Miller, YE (reprint author), Univ Colorado, Ctr Canc, Denver Vet Affairs Med Ctr, Div Pulm Sci & Crit Care Med, Pulm 111A, Denver, CO 80220 USA. EM york.miller@uchsc.edu FU University of California, San Francisco; Skin Diseases Research Center FX The first author developed the conditional Spry2GOF transgenic line as a postdoctoral fellow in Gail Martin's laboratory at the University of California, San Francisco. The authors thank her for her support and encouragement. The authors thank the histopathology core facility in the Skin Diseases Research Center for processing, sectioning, and staining of tissue, and the sequencing core facility in the orthopedics department for sequencing. An early version of this work was presented at the 2003 Thomas L. Petty Aspen Lung Conference and reported in abstract form (31). NR 31 TC 19 Z9 19 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD JAN PY 2009 VL 40 IS 1 BP 31 EP 37 DI 10.1165/rcmb.2008-0147OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 388XW UT WOS:000262054700005 PM 18635814 ER PT J AU Lin, HW Bhattacharyya, N AF Lin, Harrison W. Bhattacharyya, Neil TI Diagnostic and staging accuracy of magnetic resonance imaging for the assessment of sinonasal disease SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article DE Chronic sinusitis; computed tomography; diagnosis; magnetic resonance imaging; radiation exposure; sinusitis; staging ID CHRONIC RHINOSINUSITIS; COMPUTED-TOMOGRAPHY; PARANASAL SINUSES; CT; SINUSITIS; MRI; RADIATION AB Background: Concerns over radiation exposure with paranasal sinus computed tomography (CT) have recently evolved. Magnetic resonance imaging (MRI) may be more advantageous in this regard, but the diagnostic assessment of MRI in chronic rhinosinusitis (CRS) has not been reported. The purpose of this study was to determine the correlation between CT- and MRI-based staging and diagnosis of CRS. Methods: Paired CT and MRI scans of 89 adult patients who were imaged by both modalities within a 3-month time period for evaluation of pituitary disease were scored for sinus disease using the Lund-Mackay system in a randomized and blinded fashion. The Lund scores were compared for similarity, correlation, and diagnostic classification between modalities. Results: The mean Lund scores were 2.3 +/- 0.6 (95% CI) for CT-based staging and 2.1 +/- 0.5 for MRI-based staging with a median time interval between scans of 3 days. The difference means was not statistically significant (p = 0.444, paired t-test). Correlation analysis revealed a significant association between CT- and MRI-based scores (Pearson's r = 0.837, p < 0.001). Disease classification agreement analysis using published Lund score cutoffs (3 versus 4) for the likelihood of true sinus disease revealed that CT- and MRI-based scoring agreed on 76 cases (85.4%). Disagreement occurred in 13 cases (kappa: 0.557, p < 0.001). Sensitivity, specificity, positive predictive value, and negative predictive value were 66.7, 90.1, 63.2, and 91.4%, respectively. Conclusion: Lund-Mackay staging of sinus disease by MRI is closely correlated to corresponding staging based on CT. MRI does not significantly overstage or overclassify patients with sinus disease. C1 [Bhattacharyya, Neil] Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, Boston, MA 02115 USA. [Lin, Harrison W.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Lin, Harrison W.; Bhattacharyya, Neil] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Bhattacharyya, N (reprint author), Brigham & Womens Hosp, Div Otolaryngol Head & Neck Surg, 45 Francis St, Boston, MA 02115 USA. EM neiloy@massmed.org NR 18 TC 15 Z9 15 U1 0 U2 3 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AMJ RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2009 VL 23 IS 1 BP 36 EP 39 DI 10.2500/ajra.2009.23.3260 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 430NN UT WOS:000264995900008 PM 19379610 ER PT J AU Chennupati, SK Chiu, AG Tamashiro, E Banks, CA Cohen, MB Bleier, BS Kofonow, JM Tam, E Cohen, NA AF Chennupati, Sri Kiran Chiu, Alexander G. Tamashiro, Edwin Banks, Caroline A. Cohen, Michael B. Bleier, Benjamin S. Kofonow, Jennifer M. Tam, Eric Cohen, Noam A. TI Effects of an LL-37-derived antimicrobial peptide in an animal model of biofilm Pseudomonas sinusitis SO AMERICAN JOURNAL OF RHINOLOGY & ALLERGY LA English DT Article DE Animal model; antimicrobial peptide; biofilm; cathelicidin; LL-37; Pseudomonas; sinusitis; topical therapies ID CHRONIC RHINOSINUSITIS; BACTERIAL BIOFILMS; IN-VITRO; STAPHYLOCOCCUS-AUREUS; TOPICAL TOBRAMYCIN; LL-37; MUCOSA; INFECTIONS; SPECIMENS; SURGERY AB Background: LL-37, all innate immunity protein expressed within sinonasal mucosa, has in vitro antibacterial and antifungal properties as Well as efficacy against preformed Pseudomonas aeruginosa biofilms. We hypothesize that a 24 amino acid peptide derivative of LL-37 will show efficacy against biofilm-forming P. aeruginosa in ail established animal model of sinusitis. Methods: Five groups of six New Zealand rabbits were each infected with P. aeruginosa (PAO-1) and fitted with irrigating catheters 7 days later. Each group was instilled with either one of three different concentrations of peptide, a positive control of topical tobramycin, or the carrier solution without the peptide once a day for 10 days. Nasal diluent was collected throughout the irrigation period to assess for persistence or resolution of infection by determining colony-forming units (CFU). At study end, sinus mucosa was harvested for histological assessment of inflammation and SEM evaluation for ciliary integrity and presence Of biofilms. Results: Topical tobramycin at 400X minimum inhibitory concentration and 2.5 mg/mL of peptide were effective in significantly lowering CFUs after 10 days of irrigation. Histological evaluation showed increased signs of inflammation in a dose-dependent manner within mucosa and bone of the groups receiving the peptide. SEM analysis showed ciliary loss in a dose-dependent manner. Biofilms were present ill all groups except for the highest concentration of peptide and tobramycin. Conclusion: High concentrations of LL-37-derived peptide showed in vivo ability to eradicate Pseudomonas biofilms and decrease bacterial counts. However, increasing concentrations of peptide showed proinflammatory and ciliotoxic effects oil sinus mucosa. C1 [Chennupati, Sri Kiran; Chiu, Alexander G.; Tamashiro, Edwin; Bleier, Benjamin S.; Cohen, Noam A.] Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. [Tamashiro, Edwin; Kofonow, Jennifer M.; Tam, Eric; Cohen, Noam A.] Philadelphia Vet Affairs Med Ctr, Div Otolaryngol, Philadelphia, PA USA. [Banks, Caroline A.; Cohen, Michael B.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Chiu, AG (reprint author), Univ Penn, Dept Otorhinolaryngol Head & Neck Surg, 5 Silverstein,3400 Spruce St, Philadelphia, PA 19104 USA. EM alexander.chiu@uphs.upenn.edu RI Chiu, Alexander/J-1230-2014; Tamashiro, Edwin/C-5062-2012; OI Chiu, Alexander/0000-0002-7592-6575; Tamashiro, Edwin/0000-0002-3153-6292; Cohen, Noam/0000-0002-9462-3932 NR 42 TC 38 Z9 38 U1 0 U2 6 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1945-8924 J9 AMJ RHINOL ALLERGY JI Am. J. Rhinol. Allergy PD JAN-FEB PY 2009 VL 23 IS 1 BP 46 EP 51 DI 10.2500/ajra.2009.23.3261 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 430NN UT WOS:000264995900010 PM 19379612 ER PT J AU Martin, KK Wigginton, JB Babikian, VL Pochay, VE Crittenden, MD Rudolph, JL AF Martin, Kristin K. Wigginton, Jeremy B. Babikian, Viken L. Pochay, Val E. Crittenden, Michael D. Rudolph, James L. TI Intraoperative cerebral high-intensity transient signals and postoperative cognitive function: a systematic review SO AMERICAN JOURNAL OF SURGERY LA English DT Review DE Embolism; Transcranial Doppler; Postoperative cognitive dysfunction; Surgery; Cardiac surgery; Carotid endarterectomy; Orthopedic surgery ID ARTERY-BYPASS-SURGERY; MULTIFREQUENCY TRANSCRANIAL DOPPLER; TOTAL KNEE ARTHROPLASTY; CAROTID-ENDARTERECTOMY; CARDIAC-SURGERY; OFF-PUMP; CARDIOPULMONARY BYPASS; ON-PUMP; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; NEUROCOGNITIVE FUNCTION AB BACKGROUND: Much attention in the literature has focused on the relationship between perioperative microemboli during cardiac and vascular surgery and postoperative cognitive decline. Transcranial Doppler ultrasonography (TCD) has been used to measure high-intensity transient signals (HITS), which represent microemboli during cardiac, vascular, and orthopedic surgery. The purpose of this study was to systematically examine the literature with respect to HITS and postoperative cognitive function. METHODS: Systematic PubMed searches identified articles related to the use of TCD and cognitive function in the surgical setting. RESULTS: The literature remains largely undecided on the role of HITS and cognitive impairment after Surgery, with most studies being underpowered to show a relationship. Although the cognitive effects of HITS may be difficult to detect, subclinical microemboli present potential harm, which may be modifiable. CONCLUSIONS: TCD represents a tool for intraoperative cerebral monitoring to reduce the number of HITS during surgery. (C) 2009 Published by Elsevier Inc. C1 [Rudolph, James L.] VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. [Martin, Kristin K.] Plaza Med Ctr, Ft Worth, TX USA. [Martin, Kristin K.] Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA. [Wigginton, Jeremy B.] Univ Mississippi, Sch Med, Jackson, MS 39216 USA. [Babikian, Viken L.; Pochay, Val E.] VA Boston Healthcare Syst, Dept Neurol, Boston, MA 02130 USA. [Crittenden, Michael D.] VA Boston Healthcare Syst, Div Cardiac Surg, Boston, MA 02130 USA. [Babikian, Viken L.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Rudolph, James L.] Harvard Univ, Sch Med, Boston, MA USA. RP Rudolph, JL (reprint author), VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, JP-182,150 S Huntington Ave, Boston, MA 02130 USA. EM jrudolph@partners.org FU American Foundation for Aging Research Medical Student Training in Aging Research Program; VA Rehabilitation Career Development; [AG026781] FX This work was supported by grant AG026781 (J.B.W., J.L.R.) and the American Foundation for Aging Research Medical Student Training in Aging Research Program (J.B.W., K.K.M., J.L.R.). J.L.R. is supported by a VA Rehabilitation Career Development Award. NR 66 TC 42 Z9 49 U1 1 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD JAN PY 2009 VL 197 IS 1 BP 55 EP 63 DI 10.1016/j.amjsurg.2007.12.060 PG 9 WC Surgery SC Surgery GA 392CR UT WOS:000262281000010 PM 18723157 ER PT J AU Kobel, M Kalloger, SE Carrick, J Huntsman, D Asad, H Oliva, E Ewanowich, CA Soslow, RA Gilks, CB AF Koebel, Martin Kalloger, Steve E. Carrick, Jon Huntsman, David Asad, Haider Oliva, Esther Ewanowich, Carol A. Soslow, Robert A. Gilks, C. Blake TI A Limited Panel of Immunomarkers Can Reliably Distinguish Between Clear Cell and High-grade Serous Carcinoma of the Ovary SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovary; clear cell carcinoma; serous carcinoma; WT1; ER; HNF-1 beta ID DISTINCT-HISTOLOGIC-TYPE; IMMUNOHISTOCHEMICAL DETECTION; CLINICAL IMPLICATIONS; POOR-PROGNOSIS; EXPRESSION; TUMOR; ADENOCARCINOMAS; REPRODUCIBILITY; ENDOMETRIUM; RESISTANCE AB The distinction of ovarian clear cell carcinomas (CCCs) from high-grade serous carcinomas (HG-SCs) is sometimes a diagnostic challenge. With the recognition that CCCs respond poorly to conventional chemotherapy there are efforts to initiate clinical trials for CCC, making accurate diagnosis critical. The purpose Of this Study was to test and validate a set of antibodies that could aid in the diagnosis Of CCC, using a series of cases from different centers in North America. Using a test set of 133 CCCs, we identified the following markers: Cyclin E, estrogen receptor, hepatocyte nuclear factor (HNF)-1 beta, Ki-67, p21, p53, and Wilms tumor (WT)1 that show significant discrimination from 200 HG-SCs. For validation, these markers were characterized on an independent set of 104 CCCs from 3 other centers. There were no significant differences in expression of these 7 markers between the independent test and validation sets of CCC. Combining all CCC cases (N = 237), HNF-1 beta showed the highest sensitivity (82.5%) and specificity (95.2%) for CCC, and WT1 for HG-SC (sensitivity: 79.9%, specificity: 97.4%). A diagnostic panel consisting of WT1. ER, and HNF-1 beta demonstrated nearly identical performance as a panel using all 7 markers in distinguishing CCCs from HG-SCs, correctly classifying 84% of cases. Three percent of cases were misclassified and 13% carried an uninformative triple negative immunophenotype. CCCs show a distinct, reproducible immunophenotype, compared with HG-SCs, and a panel of 3 immunomarkers can serve as a diagnostic aid in problematic cases. C1 [Koebel, Martin; Kalloger, Steve E.; Carrick, Jon; Huntsman, David; Gilks, C. Blake] Vancouver Gen Hosp, Dept Pathol, Genet Pathol Evaluat Ctr, Prostate Res Ctr, Vancouver, BC V5Z 1M9, Canada. [Koebel, Martin; Kalloger, Steve E.; Carrick, Jon; Huntsman, David; Gilks, C. Blake] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Ewanowich, Carol A.] Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. [Ewanowich, Carol A.] Royal Alexandra Hosp, Edmonton, AB, Canada. [Koebel, Martin] Charite Hosp, Inst Pathol, Berlin, Germany. [Asad, Haider; Soslow, Robert A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Oliva, Esther] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Gilks, CB (reprint author), Vancouver Gen Hosp, Dept Pathol, Genet Pathol Evaluat Ctr, Prostate Res Ctr, Room 1207,1st Floor JPPN,855 W 12th Ave, Vancouver, BC V5Z 1M9, Canada. EM Blake.Gilks@vch.ca RI Kalloger, Steve/B-3949-2010; Kobel, Martin/A-7373-2011; OI Kobel, Martin/0000-0002-6615-2037 FU National Career Institute of Canada [017051]; Michael Smith Foundation for Health Research Unit [INRUA006045]; Sanofi-Aventis; Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency; Eli Lilly Canada FX Funded by the National Career Institute of Canada (no. 017051), the Michael Smith Foundation for Health Research Unit Grant (no. INRUA006045) to C. Blake Gilks, and by an unrestricted educational grant from Sanofi-Aventis. Supported by the Cheryl Brown Ovarian Cancer Outcomes Unit of the British Columbia Cancer Agency. Martin Kobel received Fellowship Support from Eli Lilly Canada. NR 30 TC 100 Z9 108 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2009 VL 33 IS 1 BP 14 EP 21 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 392CO UT WOS:000262280700002 PM 18830127 ER PT J AU Westfall, DE Folpe, AL Paner, GP Oliva, E Goldstein, L Alsabeh, R Gown, AM Amin, MB AF Westfall, Danielle E. Folpe, Andrew L. Paner, Gladell P. Oliva, Esther Goldstein, Lynn Alsabeh, Randa Gown, Allen M. Amin, Mahul B. TI Utility of a Comprehensive Immunohistochemical Panel in the Differential Diagnosis of Spindle Cell Lesions of the Urinary Bladder SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 24-30, 2007 CL San Diego, CA SP US & Canadian Acad Pathol DE urinary bladder; spindle cell; pseudosarcomatous myofibroblastic proliferation; sarcomatoid carcinoma; leiomyosarcoma; p63; ALK; cytokeratin 5/6; smooth muscle actin; pankeratin ID INFLAMMATORY MYOFIBROBLASTIC TUMOR; OF-THE-LITERATURE; SARCOMATOID CARCINOMA; GENITOURINARY TRACT; EXPRESSION; PROLIFERATIONS; P63; LEIOMYOSARCOMA; CARCINOSARCOMA; PSEUDOTUMOR AB Spindle cell lesions of the urinary bladder are uncommon, but when encountered in clinical practice, pose a difficult diagnostic challenge as the differential diagnostic considerations ire Vast. Pseudosarcomatous processes significantly overlap with malignant tumors (sarcomatoid urothelial carcinoma and leiomyosarcoma) ill their morphology and published immunohistochemical profile [pancytokeratin pan (CK), smooth Muscle actin (SMA), and desmin]. p63 has been studied rarely and CK 5/6 and CK 34 beta E12 have not been analyzed in the bladder in this diagnostic context. In the current study, 45 typical examples of spindle cell lesions [10 pseudosarcomatous myofibroblastic proliferations (PMP), 22 sarcomatoid urothelial carcinomas, and 13 smooth Muscle tumors] of the urinary bladder were immunostained with a panel containing broad spectrum anticytokeratin antibodies (OSCAR or AE1/ AE3), as well as antibodies to CK 34 beta 3E12, CK 5/6, p63, SMA, and anaplastic lymphoma kinase (ALK). The immunoreactivity was as follows: PMP-CK (OSCAR) 7/10 (70%), CK (AE1/AE3) 7/9 (78%), CK 34 beta E12 0/10 MY.), CK 5/6 0/9 (0%), p63 0/9 (0%,,), SMA 10/10 (100%), ALK 2/10 (20%), sarcomatoid urothelial carcinoma-CK (OSCAR) 15/22 (68%), CK (AE1/AE3) 14/20 (70%) CK 34 beta E12 5/20 (25%), CK5/6 6/22 (27%), p63 11/22 (50%), SMA 16/22 (73%), ALK 0/22 (0%); and smooth muscle tumors-CK (OSCAR) 7/13 (54%), CK (AE1/AE3) 7/12 (58%, ), CK 34 beta E12 0/12 (0%,), CK 5/6 0/12 (0%), p63 3/13 (23%), SMA II/13 (85%), ALK 0/13 (0%,). Positivity for keratin was typically Focal to moderate ill smooth muscle tumors and more commonly moderate to diffuse ill sarcomatoid carcinomas and PMP. Our data indicate that there is significant immunohistochemistry I overlap between the different spindle cell lesions, each of which has unique clinicopathologic, prognostic, and therapeutic ramifications. Within the context of morphology, an immunohistochemical panel composed of broad-spectrum antibodies to cytokeratin as well as antibodies to SMA, ALK, p63, and CK 5/6 will be a useful diagnostic adjunct,: a combination of pankeratin, SMA, and ALK positivity favors PMP; expression of several cytokeratin and especially CK 34 beta E12 and CK 5/6 with p63 favors sarcomatoid carcinoma and SMA positivity with overall absence or other markers favors leiomyosarcoma. C1 [Westfall, Danielle E.; Paner, Gladell P.; Alsabeh, Randa; Amin, Mahul B.] Cedars Sinai Med Ctr, Dept Pathol & Lab Med, Los Angeles, CA 90048 USA. [Folpe, Andrew L.] Mayo Clin, Rochester, MN USA. [Oliva, Esther] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Goldstein, Lynn; Gown, Allen M.] PhenoPath Labs, Seattle, WA USA. RP Amin, MB (reprint author), Cedars Sinai Med Ctr, Dept Pathol & Lab Med, 8700 Beverly Blvd,Suite 8728, Los Angeles, CA 90048 USA. EM aminm@cshs.org NR 30 TC 29 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2009 VL 33 IS 1 BP 99 EP 105 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 392CO UT WOS:000262280700012 PM 18941404 ER PT J AU Ellis, C Egede, LE AF Ellis, Charles Egede, Leonard E. TI Stroke Recognition Among Individuals With Stroke Risk Factors SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE stroke; cardiovascular disease; hypertension; diabetes; smoking; survey research ID AMERICAN-HEART-ASSOCIATION; EMERGENCY-DEPARTMENT; WARNING SIGNS; HEALTH-CARE; KNOWLEDGE; AWARENESS; DELAY; SYMPTOMS; TIME; EPIDEMIOLOGY AB Background: This study examined recognition of all 5 early warning signs/symptoms of stroke and appropriate first action to call 9-1-1 across stroke risk groups, Methods: Data from 264,684 adults from the 2003 Behavioral Risk Factor Surveillance System were examined. Recognition of the 5 warning signs/symptoms of stroke and appropriate first action to call 9-1-1 was compared among 3 stroke risk groups no stroke risk factors, stroke risk factors, and prior stroke, using multiple logistic regression controlling for covariates. Results: Recognition of the 5 individual warning signs of stroke ranged from 82% to 98%. Cumulative recognition of all 5 warning signs of stroke ranged from 30.8% in individuals with prior stroke to 12.6% in those with no stroke risk factors,. Cumulative recognition of all 5 warning signs of stroke and taking appropriate action to call 9-1-1 ranged from 26.1% in individuals with prior stroke to 11.2% in those with no stroke risk factors. Adjusted odds ratios for recognition of all 5 symptoms was 3.35 for individuals with previous stroke and 1.15 for individuals with stroke risk factors, compared with the reference group (individuals without stroke risk factors). Adjusted odds ratios for recognition of all 5 symptoms and taking appropriate action to call 9-1-1 was 3.06 for individuals with previous stroke and 1.14 for individuals with stroke risk factors, Conclusions: Recognition of individual stroke warning symptoms is high in general. Cumulative recognition of stroke warning signs and taking appropriate action is very low, although higher in those with prior stroke. C1 [Egede, Leonard E.] Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. [Ellis, Charles] Med Univ S Carolina, Dept Rehabil Sci, Charleston, SC 29425 USA. [Egede, Leonard E.] Ralph H Johnson VA Med Ctr, Charleston VA TREP, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, Dept Med, Charleston, SC 29425 USA. EM egedel@musc.edu NR 32 TC 15 Z9 19 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2009 VL 337 IS 1 BP 5 EP 10 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 400MQ UT WOS:000262872700002 PM 19057378 ER PT J AU Webb, R Jeffries, M Sawalha, AH AF Webb, Ryan Jeffries, Matlock Sawalha, Amr H. TI Uric Acid Directly Promotes Human T-Cell Activation SO AMERICAN JOURNAL OF THE MEDICAL SCIENCES LA English DT Article DE Uric acid; T cells; Gout; Autoimmunity ID ENDOGENOUS ADJUVANTS; IMMUNE-SYSTEM; PATHOGENESIS AB Background: Abnormally high serum uric acid levels have been associated with several disease conditions including gout and kidney stone disease. More recently, it was shown that uric acid crystals stimulate dendritic cell maturation, activate the NALP3 inflamasome, and enhance antigen-specific immune responses. We hypothesize that uric acid can also stimulate T cells directly and in the absence of antigen presentation. Methods: Purified primary human T cells were incubated with and without uric acid at concentrations of 50, 100, 150, and 200 mu g/mL. The expression of T-cell activation markers CD25 and CD70 was assessed by flow cytometry. In other experiments, Jurkat T cells were used and the expression of the costimulatory molecule CD70 was determined at the mRNA level. Result: Uric acid directly activates primary human T cells in tire absence of antigen presentation. Furthermore, primary human T cells and Jurkat T cells treated with uric acid overexpress the costimulatory molecule CD70, which plays an important role in T cell-B cell interaction and antibody production. Conclusions: The finding that uric acid directly promotes T-cell activation in ail antigen-independent system is novel and might play a mechanistic role in the inflammatory response observed in gouty arthritis and other immune-mediated diseases. C1 [Webb, Ryan; Jeffries, Matlock; Sawalha, Amr H.] Oklahoma Med Res Fdn, Arthritis & Immunol Program, Oklahoma City, OK 73104 USA. [Jeffries, Matlock; Sawalha, Amr H.] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. [Sawalha, Amr H.] US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Sawalha, AH (reprint author), 825 NE 13th St,MS 24, Oklahoma City, OK 73104 USA. EM amr-sawalha@omrf.ouhsc.edu OI Jeffries, Matlock/0000-0001-9516-4312 FU National Center for Research Resources [P20-RR015577]; University of Oklahoma College of Medicine FX This study was supported by NIH Grant number P20-RR015577 from the National Center for Research Resources and by funding from the University of Oklahoma College of Medicine. NR 14 TC 21 Z9 31 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-9629 J9 AM J MED SCI JI Am. J. Med. Sci. PD JAN PY 2009 VL 337 IS 1 BP 23 EP 27 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 400MQ UT WOS:000262872700005 PM 19057377 ER PT J AU Wharton, W Gleason, CE Lorenze, KR Markgraf, TS Ries, ML Carlsson, CM Asthana, S AF Wharton, Whitney Gleason, Carey E. Lorenze, Katelin R. Markgraf, Tamara S. Ries, Michele L. Carlsson, Cynthia M. Asthana, Sanjay TI Potential role of estrogen in the pathobiology and prevention of Alzheimer's disease SO AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH LA English DT Review DE Estrogen; estrogen therapy; hormone therapy; cognition; Alzheimer's disease; postmenopausal cognition; women's health initiative AB Over a decade of converging findings from clinical, observational and basic science research indicate that estrogen administration during the menopausal transition exerts beneficial effects on cognition and decreases a woman's risk of developing Alzheimer's disease (AD) later in life. This review article stresses the research focus of AD prevention, and introduces hormone therapy (HT) as a probable catalyst that may achieve this goal. Furthermore, this article outlines 3 mechanisms proposed to mediate estrogen's beneficial effects, discusses the controversy surrounding HT administration, and presents the most promising estrogen related research in AD prevention and treatment. Although controversial, cumulative evidence suggests that the potential of estrogen initiated during perimenopause to prevent AD needs to be systematically evaluated. C1 [Wharton, Whitney; Gleason, Carey E.; Lorenze, Katelin R.; Markgraf, Tamara S.; Ries, Michele L.; Carlsson, Cynthia M.; Asthana, Sanjay] Univ Wisconsin, Dept Med, Madison, WI 53705 USA. [Wharton, Whitney; Gleason, Carey E.; Lorenze, Katelin R.; Markgraf, Tamara S.; Ries, Michele L.; Carlsson, Cynthia M.; Asthana, Sanjay] William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI USA. RP Wharton, W (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, William S Middleton VA Hosp, 2500 Overlook Terrace,GRECC 11G, Madison, WI 53705 USA. EM wlwharto@medicine.wisc.edu FU NIH [AG029624, K07AG021582, K23AG024302, K23AG026752] FX This research was conducted with the help of the Section of Geriatrics and Gerontology, Department of Medicine at the University of Wisconsin, Madison and the Geriatric Research, Education and Clinical Center (GRECC), William S. Middleton Memorial Veterans Hospital. This research was supported by NIH grants AG029624, K07AG021582, K23AG024302 and K23AG026752. VA manuscript number 2008-31. NR 172 TC 7 Z9 7 U1 2 U2 4 PU E-CENTURY PUBLISHING CORP PI MADISON PA 40 WHITE OAKS LN, MADISON, WI 53711 USA SN 1943-8141 J9 AM J TRANSL RES JI Am. J. Transl. Res. PY 2009 VL 1 IS 2 BP 131 EP 147 PG 17 WC Oncology; Medicine, Research & Experimental SC Oncology; Research & Experimental Medicine GA V28PW UT WOS:000208693700004 PM 19956426 ER PT J AU Cook, CH Bickerstaff, AA Wang, JJ Zimmerman, PD Forster, MR Nadasdy, T Colvin, RB Hadley, GA Orosz, CG AF Cook, C. H. Bickerstaff, A. A. Wang, J-J. Zimmerman, P. D. Forster, M. R. Nadasdy, T. Colvin, R. B. Hadley, G. A. Orosz, C. G. TI Disruption of Murine Cardiac Allograft Acceptance by Latent Cytomegalovirus SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; DELAYED-TYPE HYPERSENSITIVITY; ANTI-CD4 MONOCLONAL-ANTIBODY; PLASMACYTOID DENDRITIC CELLS; RENAL-TRANSPLANT RECIPIENTS; CD8(+) T-CELLS; VIRAL-INFECTION; IN-VIVO; INTERFERON-ALPHA; NATURAL-KILLER AB Cytomegalovirus (CMV) reactivation is a well-described complication of solid organ transplantation. These studies were performed to (1) determine if cardiac allograft transplantation of latently infected recipients results in reactivation of CMV and (2) determine what impact CMV might have on development of graft acceptance/tolerance. BALB/c cardiac allografts were transplanted into C57BL/6 mice with/without latent murine CMV (MCMV). Recipients were treated with gallium nitrate induction and monitored for graft survival, viral immunity and donor reactive DTH responses. Latently infected allograft recipients had similar to 80% graft loss by 100 days after transplant, compared with similar to 8% graft loss in naive recipients. PCR evaluation demonstrated that MCMV was transmitted to cardiac grafts in all latently infected recipients, and 4/8 allografts had active viral transcription compared to 0/6 isografts. Latently infected allograft recipients showed intragraft IFN-alpha expression consistent with MCMV reactivation, but MCMV did not appear to negatively influence regulatory gene expression. Infected allograft recipients had disruption of splenocyte DTH regulation, but recipient splenocytes remained unresponsive to donor antigen even after allograft losses. These data suggest that transplantation in an environment of latent CMV infection may reactivate virus, and that intragraft responses disrupt development of allograft acceptance. C1 [Cook, C. H.; Bickerstaff, A. A.; Wang, J-J.; Zimmerman, P. D.; Forster, M. R.; Hadley, G. A.; Orosz, C. G.] Ohio State Univ, Dept Surg, Columbus, OH 43210 USA. [Nadasdy, T.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Cook, C. H.] Ohio State Univ, Dept Anesthesiol, Columbus, OH 43210 USA. [Colvin, R. B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Cook, CH (reprint author), Ohio State Univ, Dept Surg, Columbus, OH 43210 USA. EM charles.cook@osumc.edu RI Cook, Charles/D-5574-2009 OI Cook, Charles/0000-0003-4446-3616 FU Roche Organ Transplant Foundation (RBC) [NIH RO1 AI053094] FX The authors would like to thank Kelly Nye, Christina Sass, Jonathan Campbell and Bree Heestand for their technical assistance with these studies. We also thank Patricia Della Pelle for her assistance with the immunohistochemistry. This work was supported by NIH RO1 AI053094 (CHC) and a grant from the Roche Organ Transplant Foundation (RBC). NR 76 TC 23 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2009 VL 9 IS 1 BP 42 EP 53 DI 10.1111/j.1600-6143.2008.02457.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 386LT UT WOS:000261885400011 PM 18976295 ER PT J AU Weiss, MJ Guenther, DA Mezrich, JD Sahara, H Ng, CY Meltzer, AJ Sayre, JK Cochrane, ME Pujara, AC Houser, SL Sachs, DH Rosengard, BR Allan, JS Benichou, G Madsen, JC AF Weiss, M. J. Guenther, D. A. Mezrich, J. D. Sahara, H. Ng, C. Y. Meltzer, A. J. Sayre, J. K. Cochrane, M. E. Pujara, A. C. Houser, S. L. Sachs, D. H. Rosengard, B. R. Allan, J. S. Benichou, G. Madsen, J. C. TI The Indirect Alloresponse Impairs the Induction but Not Maintenance of Tolerance to MHC Class I-Disparate Allografts SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Heart transplantation; indirect allorecognition; kidney transplantation; rejection; tolerance ID MAJOR HISTOCOMPATIBILITY COMPLEX; REGULATORY T-CELLS; HLA-DR PEPTIDES; INDIRECT RECOGNITION; MINIATURE SWINE; GRAFT-REJECTION; CARDIAC ALLOGRAFTS; TRANSPLANTATION TOLERANCE; INDIRECT ALLORECOGNITION; HEART-TRANSPLANTATION AB We studied the effects of indirect allorecognition on the induction and maintenance phases of tolerance in miniature swine cotransplanted with heart and kidney allografts. MHC class I-mismatched heart and kidney grafts were cotransplanted in recipients receiving CyA for 12 days. Recipients were unimmunized or immunized with a set of donor-derived or control third-party MHC class I peptides either 21 days prior to transplantation or over 100 days after transplantation. T-cell proliferation, delayed type hypersensitivity reaction (DTH) and antibody production were assessed. All animals injected with donor MHC class I peptides developed potent indirect alloresponses specific to the immunizing peptides. While untreated recipients developed stable tolerance, all animals preimmunized with donor allopeptides rejected kidney-heart transplants acutely. In contrast, when peptide immunization was delayed until over 100 days after kidney-heart transplantation, no effects were observed on graft function or in vitro measures of alloimmunity. Donor peptide immunization prevented tolerance when administered to recipients pre transplantation but did not abrogate tolerance when administered to long-term survivors post transplantation. This suggests that the presence of T cells activated via indirect allorecognition represent a barrier to the induction but not the maintenance of tolerance. C1 [Weiss, M. J.; Guenther, D. A.; Mezrich, J. D.; Sahara, H.; Ng, C. Y.; Meltzer, A. J.; Sayre, J. K.; Cochrane, M. E.; Pujara, A. C.; Houser, S. L.; Sachs, D. H.; Rosengard, B. R.; Allan, J. S.; Madsen, J. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. [Rosengard, B. R.; Madsen, J. C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. [Allan, J. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Thorac Surg, Boston, MA USA. [Benichou, G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Abdominal Transplantat,Dept Surg, Boston, MA USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02115 USA. EM jcmadsen@partners.org FU National Heart Lung and Blood Institute [RO1HL54211, PO1HL18646]; American College of Surgeons Resident Research Award FX We thank Drs. Timothy M. Millington and Gregory R. Veillette for critical review of the article. We also thank Novartis for their gift of cyclosporine. This work was supported in part by the National Heart Lung and Blood Institute (RO1HL54211, PO1HL18646) of the National Institutes of Health and by an American College of Surgeons Resident Research Award to MJW. NR 51 TC 4 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 EI 1600-6143 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2009 VL 9 IS 1 BP 105 EP 113 DI 10.1111/j.1600-6143.2008.02494.x PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 386LT UT WOS:000261885400017 PM 19145702 ER PT J AU Porcheray, F DeVito, J Saidman, SL Yeap, BY Girouard, T Paine, R Xue, L Dargon, I Colvin, RB Wong, WC Zorn, E AF Porcheray, Fabrice DeVito, Julie Saidman, Susan L. Yeap, Beow Y. Girouard, Tim Paine, Rosemary Xue, Lijuan Dargon, Ian Colvin, Robert B. Wong, Waichi Zorn, Emmanuel TI Broad Autoantibody Responses in Chronic Humoral Rejection of Human Kidney Allografts. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Porcheray, Fabrice; DeVito, Julie; Saidman, Susan L.; Yeap, Beow Y.; Girouard, Tim; Paine, Rosemary; Xue, Lijuan; Dargon, Ian; Colvin, Robert B.; Wong, Waichi; Zorn, Emmanuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 225 EP 226 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800120 ER PT J AU Dib, MJ Kennealey, PT Farrell, ML Mandelbrot, D Curry, M Hertl, M Ko, DSC Cosimi, AB Tsoulfas, G Saidi, R Elias, N Johnson, SR Hanto, DW Markmann, JF Karp, SJ AF Dib, Martin J. Kennealey, Peter T. Farrell, Mary Lin Mandelbrot, Didier Curry, Michael Hertl, Martin Ko, Dicken S. C. Cosimi, A. Benedict Tsoulfas, Georgios Saidi, Reza Elias, Nahel Johnson, Scott R. Hanto, Douglas W. Markmann, James F. Karp, Seth J. TI Risk Factors for Chronic Kidney Disease (CDK) after Liver Transplantation: Implications for Performing Combined Liver and Kidney Transplantation (CLKT). SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Dib, Martin J.; Mandelbrot, Didier; Curry, Michael; Johnson, Scott R.; Hanto, Douglas W.; Karp, Seth J.] Beth Israel Deaconess Med Ctr, Div Transplantat, Boston, MA 02215 USA. [Dib, Martin J.; Kennealey, Peter T.; Farrell, Mary Lin; Hertl, Martin; Ko, Dicken S. C.; Cosimi, A. Benedict; Tsoulfas, Georgios; Saidi, Reza; Elias, Nahel; Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. RI Tsoulfas, Georgios/K-4801-2012 OI Tsoulfas, Georgios/0000-0001-5043-7962 NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 262 EP 262 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800248 ER PT J AU Kim, JI Sonawane, SB Lee, MK Moore, D Duff, PE Lian, MM Deng, S Lee, SH Choi, YW Caton, A Yeh, H Markmann, JF AF Kim, James I. Sonawane, S. B. Lee, M. K. Moore, D. Duff, P. E. Lian, M. M. Deng, S. Lee, S. H. Choi, Y. W. Caton, A. Yeh, H. Markmann, James F. TI Disruption of the GITR-GITRL Interaction Promotes T-reg Mediated Transplantation Tolerance by Reversal of Inflammation Induced Counter-Regulation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kim, James I.; Duff, P. E.; Lian, M. M.; Deng, S.; Yeh, H.; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sonawane, S. B.; Lee, M. K.; Moore, D.; Lee, S. H.; Choi, Y. W.] Univ Penn, Surg & Abramson Family Canc Ctr, Philadelphia, PA 19104 USA. [Caton, A.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 266 EP 266 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800262 ER PT J AU Porcheray, F Wong, W Saidman, SL DeVito, J Girouard, TC Chittenden, M Shaffer, J Tolkoff-Rubin, N Dey, BR Spitzer, TR Colvin, RB Cosimi, AB Kawai, T Sachs, DH Sykes, M Zorn, E AF Porcheray, Fabrice Wong, Waichi Saidman, Susan L. DeVito, Julie Girouard, Timothy C. Chittenden, Meredith Shaffer, Juanita Tolkoff-Rubin, Nina Dey, Bimalangshu R. Spitzer, Thomas R. Colvin, Robert B. Cosimi, A. Benedict Kawai, Tatsuo Sachs, David H. Sykes, Megan Zorn, Emmanuel TI B Cell Immunity in the Context of T Cell Tolerance after Combined Kidney and Bone-Marrow-Transplantation in Humans. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Porcheray, Fabrice; Wong, Waichi; Saidman, Susan L.; DeVito, Julie; Girouard, Timothy C.; Chittenden, Meredith; Shaffer, Juanita; Tolkoff-Rubin, Nina; Dey, Bimalangshu R.; Spitzer, Thomas R.; Colvin, Robert B.; Cosimi, A. Benedict; Kawai, Tatsuo; Sachs, David H.; Sykes, Megan; Zorn, Emmanuel] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI porcheray, fabrice/B-9505-2012 NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 280 EP 281 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800308 ER PT J AU Saidi, RF Bradley, J Greer, D Luskin, R O'Connor, K Delmonico, F Kennealey, P Elias, N Hertl, M Markmann, J AF Saidi, Reza F. Bradley, James Greer, David Luskin, Richard O'Connor, Kevin Delmonico, Francis Kennealey, Peter Elias, Nahel Hertl, Martin Markmann, James TI Changing Patterns of Organ Donation at a Single Center; Are Potential Brain Dead Donors Being Lost to Donation after Cardiac Death? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Reza F.; Greer, David; Kennealey, Peter; Elias, Nahel; Hertl, Martin; Markmann, James] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bradley, James; Luskin, Richard; O'Connor, Kevin; Delmonico, Francis] New England Organ Bank Inc, Newton, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 291 EP 291 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800348 ER PT J AU Sheehy, E O'Connor, K Luskin, R Selck, F Howard, R Cornell, D Finn, J Mone, T Delmonico, F AF Sheehy, Ellen O'Connor, Kevin Luskin, Richard Selck, Frederick Howard, Richard Cornell, Danielle Finn, Jan Mone, Thomas Delmonico, Francis TI Regional Differences in Mortality Significantly Impact Organ Availability. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [O'Connor, Kevin; Luskin, Richard] New England Organ Bank Inc, Newton, MA USA. [Howard, Richard] Univ Florida, Dept Surg, Gainesville, FL USA. [Cornell, Danielle] LifeQuest Organ Recovery Serv, Gainesville, FL USA. [Finn, Jan] Midwest Transplant Network, Westwood, KS USA. [Mone, Thomas] OneLegacy, Los Angeles, CA USA. [Delmonico, Francis] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 293 EP 293 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800353 ER PT J AU Millington, TM Ng, C Strom, TB Koulmanda, M Madsen, JC AF Millington, Timothy M. Ng, Choo Strom, Terry B. Koulmanda, Maria Madsen, Joren C. TI Treatment of Non-Human Primate Cardiac Allograft Recipients with IL-2/Fc, mIL-15/Fc and Sirolimus Prolongs Graft Survival. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Millington, Timothy M.; Ng, Choo; Madsen, Joren C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Strom, Terry B.; Koulmanda, Maria] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 300 EP 300 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800377 ER PT J AU Alejandro, R Pattou, F Markmann, JF Barton, FB Cagliero, E Wease, S Naji, A Hering, BJ AF Alejandro, Rodolfo Pattou, Francois Markmann, James F. Barton, Franca B. Cagliero, Enrico Wease, Stephen Naji, Ali Hering, Bernhard J. TI Islet after Kidney Transplantation from the Collaborative Islet Transplant Registry: 1999-2007. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Alejandro, Rodolfo] Univ Miami, Diabet Res Inst, Miami, FL USA. [Pattou, Francois] Lille Univ Hosp, Lab Therapie, Lille, France. [Markmann, James F.] Massachusetts Gen Hosp, Div Transplantat, Boston, MA 02114 USA. [Barton, Franca B.; Wease, Stephen] EMMES Corp, CITR, Rockville, MD USA. [Cagliero, Enrico] Harvard Univ, Sch Med, Ctr Islet Transplantat, MGH Diabet Ctr, Boston, MA USA. [Hering, Bernhard J.] Univ Minnesota, Diabetes Inst Immunol & Transplantat, Minneapolis, MN USA. [Naji, Ali] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 323 EP 323 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800457 ER PT J AU Saidi, R Hertl, M Ko, DSC Kennealey, P Kawai, T Markmann, J Bhan, AK Chung, R Cosimi, AB Elias, N AF Saidi, Reza Hertl, M. Ko, D. S. C. Kennealey, P. Kawai, T. Markmann, J. Bhan, A. K. Chung, R. Cosimi, A. B. Elias, N. TI Induction with Rabbit Antithymocyte Globulin Delays Recurrent Disease Following Orthotopic Liver Transplantation for Hepatitis C Virus. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Reza; Hertl, M.; Ko, D. S. C.; Kennealey, P.; Kawai, T.; Markmann, J.; Bhan, A. K.; Chung, R.; Cosimi, A. B.; Elias, N.] Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 326 EP 326 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800466 ER PT J AU Borges, C Sykes, M Kurtz, J AF Borges, Christopher Sykes, Megan Kurtz, Josef TI Expression of Intact Donor MHC Molecules by Recipient APC for the Tolerization of Alloreactive T Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Borges, Christopher; Sykes, Megan; Kurtz, Josef] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Borges, Christopher; Kurtz, Josef] Univ Cambridge Emmanuel Coll, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 358 EP 358 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800577 ER PT J AU LoCascio, S Sykes, M Kang, SM Kurtz, J AF LoCascio, Samuel Sykes, Megan Kang, Sang-Mo Kurtz, Josef TI Rapid Deletion of Peripheral Directly and Indirectly Alloreactive CD4 T Cells Following BMT with Costimulatory Blockade. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [LoCascio, Samuel; Sykes, Megan; Kurtz, Josef] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. [Kang, Sang-Mo] Univ Calif San Francisco, San Francisco, CA 94143 USA. [LoCascio, Samuel; Kurtz, Josef] Univ Cambridge Emmanuel Coll, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 358 EP 358 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800578 ER PT J AU Ueno, T Popoola, J Yeung, M Azuma, M Freeman, GJ Sayegh, MH Najafian, N AF Ueno, Takuya Popoola, Joyce Yeung, Melissa Azuma, Miyuki Freeman, Gordon J. Sayegh, Mohamed H. Najafian, Nader TI New Insights into the Interaction between Regulatory B7-H3 Molecule and Costimulatory CD28-B7 Pathway in Determining the Outcome of the Alloimmune Responses In Vivo. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Ueno, Takuya; Popoola, Joyce; Yeung, Melissa; Sayegh, Mohamed H.; Najafian, Nader] Brigham & Womens Hosp, Div Renal, Transplantat Res Ctr, Boston, MA 02115 USA. [Azuma, Miyuki] Tokyo Med & Dent Univ, Dept Mol Immunol, Tokyo, Japan. [Freeman, Gordon J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 359 EP 360 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800584 ER PT J AU Westermann-Clark, EV Hanto, R Donelan, K McMahon, PM Weinstein, MC Gazelle, S Rodrigue, JR AF Westermann-Clark, Emma V. Hanto, Ruthanne Donelan, Karen McMahon, Pamela M. Weinstein, Milton C. Gazelle, Scott Rodrigue, James R. TI Three Kidney Transplant Controversies: Results of a National Survey of Transplant Center Directors SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Westermann-Clark, Emma V.] Harvard Univ, Cambridge, MA 02138 USA. [Westermann-Clark, Emma V.; Hanto, Ruthanne] New England Program Kidney Exchange, Newton, MA USA. [Donelan, Karen] MGH, Inst Hlth Policy, Boston, MA USA. [Donelan, Karen; McMahon, Pamela M.; Weinstein, Milton C.; Gazelle, Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Rodrigue, James R.] Beth Israel Deaconess Med Ctr, Transplant Ctr, Boston, MA 02215 USA. [Gazelle, Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 387 EP 388 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800678 ER PT J AU Demirci, G Kilpatrick, L Kroemer, A Exley, M Li, XC AF Demirci, Gulcin Kilpatrick, Liz Kroemer, Alexander Exley, Mark Li, Xian C. TI NKT Cells Are Neither Necessary for Rejection nor Needed for Induction of Transplant Tolerance SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Demirci, Gulcin; Kilpatrick, Liz; Kroemer, Alexander; Exley, Mark; Li, Xian C.] Harvard Univ, Beth Israel Deac Med Ctr, Sch Med, Transplant Inst, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 395 EP 396 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800708 ER PT J AU Westermann-Clark, EV Hanto, R Donelan, K Halpern, EF McMahon, PM Weinstein, MC Gazelle, GS Rodrigue, JR AF Westermann-Clark, Emma V. Hanto, Ruthanne Donelan, Karen Halpern, Elkan F. McMahon, Pamela M. Weinstein, Milton C. Gazelle, G. Scott Rodrigue, James R. TI Survey of US Transplant Centers on Barriers to Implementation of Kidney Paired Donation, List Paired Donation, and Desensitization Protocols. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Westermann-Clark, Emma V.] Harvard Univ, Cambridge, MA 02138 USA. [Hanto, Ruthanne] New England Program Kidney Exchange, Newton, MA USA. [Donelan, Karen] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Westermann-Clark, Emma V.; Donelan, Karen; Halpern, Elkan F.; McMahon, Pamela M.; Gazelle, G. Scott] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Weinstein, Milton C.; Gazelle, G. Scott] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Rodrigue, James R.] Beth Israel Deaconess Med Ctr, Transplant Ctr, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 434 EP 434 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800850 ER PT J AU Cacciarelli, TV Wagener, M Karuman, P Wannstedt, C Akoad, M AF Cacciarelli, Thomas V. Wagener, Marilyn Karuman, Philip Wannstedt, Cheryl Akoad, Mohamed TI The Fate of "Refused" Imported and Locally Procurred Cadaver Donor Liver Allografts and Impact on Survival SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Cacciarelli, Thomas V.; Karuman, Philip; Wannstedt, Cheryl] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Wagener, Marilyn] Univ Pittsburgh, Pittsburgh, PA USA. [Akoad, Mohamed] Lahey Clin Fdn, Burlington, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 451 EP 451 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800914 ER PT J AU Ahmad, J Wagner, M Francis, FF Karuman, P Cacciarelli, TV AF Ahmad, Jawad Wagner, Marilyn Francis, Fadi F. Karuman, Phillip Cacciarelli, Thomas V. TI Impact of the MELD System on Long-Term Outcome after Liver Transplantation in United States Veterans SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Ahmad, Jawad; Wagner, Marilyn; Francis, Fadi F.; Karuman, Phillip] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Ahmad, Jawad] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 455 EP 455 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800927 ER PT J AU Weiner, J Yamada, K Ishikawa, Y Moran, S Etter, J Shimizu, A Sachs, D AF Weiner, Joshua Yamada, Kazuhiko Ishikawa, Yoshinori Moran, Shannon Etter, Justin Shimizu, Akira Sachs, David TI Prolonged Survival of GalT-KO Swine Skin on a Baboon Treated with Cyclosporine. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Weiner, Joshua; Yamada, Kazuhiko; Ishikawa, Yoshinori; Moran, Shannon; Etter, Justin; Shimizu, Akira; Sachs, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 470 EP 470 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800986 ER PT J AU Tocco, G Kim, P Kant, CD Wynn, H Lin, CP Yun, SH Benichou, G AF Tocco, Georges Kim, Pilhan Kant, Cavit D. Wynn, Henri Lin, Charles P. Yun, Seok-Hyun Benichou, Gilles TI The ins and outs of Cellular Migration in Transplantation Revisited through In Vivo Microscopy. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Tocco, Georges; Kant, Cavit D.; Wynn, Henri; Benichou, Gilles] Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02114 USA. [Kim, Pilhan; Lin, Charles P.; Yun, Seok-Hyun] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 476 EP 476 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801012 ER PT J AU Kim, KM Veillette, GR Meltzer, AJ Millington, TM Aoyama, A Cochrane, ME Sachs, DH Madsen, JC Allan, JS Rosengard, BR AF Kim, Karen M. Veillette, Gregory R. Meltzer, Andrew J. Millington, Timothy M. Aoyama, Akihiro Cochrane, Meghan E. Sachs, David H. Madsen, Joren C. Allan, James S. Rosengard, Bruce R. TI Donor Brain Death Fails To Abrogate Tolerance Induction in a Large-Animal Model of Kidney Transplantation. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kim, Karen M.; Veillette, Gregory R.; Meltzer, Andrew J.; Millington, Timothy M.; Aoyama, Akihiro; Cochrane, Meghan E.; Sachs, David H.; Madsen, Joren C.; Allan, James S.; Rosengard, Bruce R.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 482 EP 483 PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801037 ER PT J AU Da Silva, CG Skroch, M Studer, P Damrauer, SM Siracuse, JJ Maccariello, E Kaczmarek, E Ferran, C AF Da Silva, Cleide G. Skroch, Marco Studer, Peter Damrauer, Scott M. Siracuse, Jeffrey J. Maccariello, Elizabeth Kaczmarek, Elzbieta Ferran, Christiane TI The Pro-Proliferative Effects of A20 Map to the 7-Zinc Finger Domain: A Means To Define Small Peptides with Therapeutic Potential SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Da Silva, Cleide G.; Skroch, Marco; Studer, Peter; Damrauer, Scott M.; Siracuse, Jeffrey J.; Maccariello, Elizabeth; Kaczmarek, Elzbieta; Ferran, Christiane] Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 493 EP 493 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801079 ER PT J AU Meier, M Bode, W Nitschke, M Wong, WC Kramer, J Lehnert, H Steinhoff, J Fricke, L AF Meier, Markus Bode, Wibke Nitschke, Martin Wong, Waichi Kramer, Jan Lehnert, Hendrik Steinhoff, Juergen Fricke, Lutz TI Low Dose Tacrolimus Versus Mycophenolate-Mofetil in "Old for Old" Kidney Transplantation: A One Year Prospective Multicenter Randomized Controlled Trial SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Meier, Markus; Bode, Wibke; Nitschke, Martin; Kramer, Jan; Lehnert, Hendrik; Steinhoff, Juergen; Fricke, Lutz] Med Univ Lubeck, Transplant Ctr, D-23538 Lubeck, Germany. [Wong, Waichi] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 498 EP 498 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801097 ER PT J AU Schroppel, B Kruger, B Harris, S Breggia, A Yeung, M Garrison, K Himmelfarb, J Zhang, PL Colvin, RB Vella, J AF Schroppel, Bernd Krueger, Bernd Harris, Shay Breggia, Ann Yeung, Melissa Garrison, Krista Himmelfarb, Jonathan Zhang, Ping L. Colvin, Robert B. Vella, John TI Kidney Injury Molecule-1 (KIM-1) Expression in Deceased Donor Kidneys as a Diagnostic Biomarker of Tubular Injury SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Schroppel, Bernd; Krueger, Bernd] Mt Sinai Sch Med, Div Nephrol, New York, NY USA. [Schroppel, Bernd] Mt Sinai Sch Med, Transplant Inst, New York, NY USA. [Krueger, Bernd] Klinikum Ruhr Univ Bochum, Marienhosp Herne, Med Klin 1, Herne, Germany. [Harris, Shay; Breggia, Ann; Yeung, Melissa; Garrison, Krista; Himmelfarb, Jonathan; Vella, John] Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA. [Zhang, Ping L.] William Beaumont Hosp, Dept Anat Pathol, Royal Oak, MI 48073 USA. [Colvin, Robert B.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 519 EP 519 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801174 ER PT J AU Saidi, R Kennealey, P Elias, N Kawai, T Hertl, M Markmann, J Cosimi, AB Ko, DSC AF Saidi, Reza Kennealey, P. Elias, N. Kawai, T. Hertl, M. Markmann, J. Cosimi, A. B. Ko, D. S. C. TI Pyeloureterostomy or Ureteroneocystostomy in Kidney Transplantation: Is There a Difference? SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Saidi, Reza; Kennealey, P.; Elias, N.; Kawai, T.; Hertl, M.; Markmann, J.; Cosimi, A. B.; Ko, D. S. C.] Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 521 EP 521 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801180 ER PT J AU Kim, JI Duff, PE Deng, SP O'Connor, MR Yeh, HD Caton, A Markmann, JF AF Kim, James I. Duff, Patrick E. Deng, Shaoping O'Connor, Matthew R. Yeh, Heidi Caton, Andrew Markmann, James F. TI Foxp3 Upregulation in Peripheral CD4+CD25 Negative T Lymphocytes in Response to Alloantigen In Vivo. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Kim, James I.; Duff, Patrick E.; Deng, Shaoping; O'Connor, Matthew R.; Yeh, Heidi; Markmann, James F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Caton, Andrew] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 538 EP 538 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801245 ER PT J AU Chen, T Mylvaganam, GH Maker, M Thompson, ZP Xu, XL Jaafar, F Sarkar, A Coleman, DV Sachs, DH Berthiaume, F Poznansky, MC AF Chen, Tao Mylvaganam, Geetha H. Maker, Michael Thompson, Zachary P. Xu, Xiaolu Jaafar, Fatimah Sarkar, Aparajita Coleman, Dulcie V. Sachs, David H. Berthiaume, Francois Poznansky, Mark C. TI Coating of Skin Allografts or Integra with CXCL12 Significantly Delays Rejection as a Result of Recipient T Cell Chemorepulsion. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Chen, Tao; Mylvaganam, Geetha H.; Maker, Michael; Thompson, Zachary P.; Xu, Xiaolu; Poznansky, Mark C.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Jaafar, Fatimah; Coleman, Dulcie V.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Pathol, London, England. [Sachs, David H.] Massachusetts Gen Hosp, Res Ctr, Boston, MA 02114 USA. [Sarkar, Aparajita] Shriners Hosp Children, Dept Surg, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 557 EP 557 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801319 ER PT J AU Porcheray, F DeVito, J Xue, LJ Helou, Y Gigante, M Dargon, I Wong, WC Zorn, E AF Porcheray, Fabrice DeVito, Julie Xue, Lijuan Helou, Ynes Gigante, Marc Dargon, Ian Wong, Waichi Zorn, Emmanuel TI Characterization of Kidney Infiltrating B Cells during Acute Rejection in Humans. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Porcheray, Fabrice; DeVito, Julie; Xue, Lijuan; Helou, Ynes; Gigante, Marc; Dargon, Ian; Wong, Waichi; Zorn, Emmanuel] Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 624 EP 624 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801571 ER PT J AU Daniel, S Kaczmarek, E Choi, LY Fisher, MD Siracuse, JJ Csizmadia, E Damrauer, SM Studer, P Da Silva, CG Ferran, C AF Daniel, Soizic Kaczmarek, Elzbieta Choi, Lynn Y. Fisher, Mark D. Siracuse, Jeffrey J. Csizmadia, Eva Damrauer, Scott M. Studer, Peter Da Silva, Cleide G. Ferran, Christiane TI A20 Increases the Expression of Endothelial and Inducible Nitric Oxide Synthases in Endothelial and Smooth Muscle Cells To Protect from Transplant Arteriosclerosis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Harvard Univ, Sch Med, Div Vasc Surg, BIDMC, Boston, MA USA. Harvard Univ, Sch Med, Transplant Ctr, BIDMC, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 633 EP 633 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801607 ER PT J AU Sun, HY Cacciarelli, TV Wagener, MM Singh, N AF Sun, Hsin-Yun Cacciarelli, Thomas V. Wagener, Marilyn M. Singh, Nina TI Impact of Pre-Transplant Infections on Clinical Outcomes in Liver Transplant Recipients. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Sun, Hsin-Yun; Cacciarelli, Thomas V.; Singh, Nina] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Sun, Hsin-Yun] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Cacciarelli, Thomas V.; Wagener, Marilyn M.; Singh, Nina] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 637 EP 637 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801623 ER PT J AU Murray, DR Osaki, S Jewel-Ripp, P Johnson, MR Lozonschi, L Edwards, NM Kohmoto, T AF Murray, David R. Osaki, Satoru Jewel-Ripp, Polly Johnson, Maryl R. Lozonschi, Lucian Edwards, Niloo M. Kohmoto, Takushi TI Ventricular Assist Device Therapy in United States Veterans: A Single Center 5-Year Experience. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Murray, David R.; Osaki, Satoru; Jewel-Ripp, Polly; Lozonschi, Lucian; Edwards, Niloo M.; Kohmoto, Takushi] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. [Osaki, Satoru; Lozonschi, Lucian; Edwards, Niloo M.; Kohmoto, Takushi] Univ Wisconsin, Sch Med & Publ Hlth, Div Cardiothorac Surg, Madison, WI USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 655 EP 655 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801688 ER PT J AU Aoyama, A Millington, TM Boskovic, S Veillette, G Wain, JC Madsen, JC Kawai, T Allan, JS AF Aoyama, Akihiro Millington, Timothy M. Boskovic, Svjetlan Veillette, Gregory Wain, John C. Madsen, Joren C. Kawai, Tatsuo Allan, James S. TI Non-Human Primate Lung Transplantation Carries a High Incidence of Acute Rejection and Alloantibody Development. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 Massachusetts Gen Hosp, Div Thorac, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 662 EP 662 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801716 ER PT J AU Emamaullee, J Merani, S Toso, C Kin, T Pawlick, R Davis, J Edgar, R Locke, J Bonner-Weir, S Knudsen, LB Shapiro, J AF Emamaullee, Juliet Merani, Shaheed Toso, Christian Kin, Tatsuya Pawlick, Rena Davis, Joy Edgar, Ryan Locke, Jennifer Bonner-Weir, Susan Knudsen, Lotte B. Shapiro, James TI Porcine Marginal Mass Islet Autografts Resist Metabolic Failure over Time and Are Enhanced by Early Treatment with Liraglutide. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Emamaullee, Juliet; Merani, Shaheed; Toso, Christian; Kin, Tatsuya; Pawlick, Rena; Davis, Joy; Edgar, Ryan; Shapiro, James] Univ Alberta, Edmonton, AB, Canada. [Locke, Jennifer; Bonner-Weir, Susan] Joslin Diabet Ctr, Boston, MA 02215 USA. RI Kin, Tatsuya /A-3776-2012 OI Kin, Tatsuya /0000-0002-5179-6067 NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 671 EP 671 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801750 ER PT J AU Schuetz, C Lee, KM Machaidze, Z Smith, RN Deng, SP Markmann, JF AF Schuetz, Christian Lee, Kang Mi Machaidze, Zurab Smith, Rex Neal Deng, Shaoping Markmann, James F. TI Anti-Proliferative Effect of Immunosuppressive Drugs on Pancreatic beta-Cells. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Schuetz, Christian; Lee, Kang Mi; Machaidze, Zurab; Deng, Shaoping; Markmann, James F.] Massachusetts Gen Hosp, Transplant Surg Ctr, Boston, MA 02114 USA. [Smith, Rex Neal] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 673 EP 673 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801756 ER PT J AU Murakami, T Boskovic, S Nadazdin, O Ochiai, T Benichou, G Putheti, P Smith, RN Colvin, RB Strom, TB Sachs, DH Cosimi, AB Kawai, T AF Murakami, Toru Boskovic, Svjetlan Nadazdin, Ognjenka Ochiai, Takanori Benichou, Gilles Putheti, Prabhakar Smith, Rex-Neal Colvin, Robert B. Strom, Terry B. Sachs, David H. Cosimi, A. Benedict Kawai, Tatsuo TI Deletion of CD8 Memory T Cells and Antiviral Immunity in "Delayed Tolerance" Induction. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Murakami, Toru; Boskovic, Svjetlan; Nadazdin, Ognjenka; Ochiai, Takanori; Benichou, Gilles; Smith, Rex-Neal; Colvin, Robert B.; Cosimi, A. Benedict; Kawai, Tatsuo] Massachusetts Gen Hosp, Transplant Ctr, Boston, MA 02114 USA. [Putheti, Prabhakar; Strom, Terry B.] Beth Israel Deaconess Med Ctr, Transplant Ctr, Boston, MA 02215 USA. [Sachs, David H.] Massachusetts Gen Hosp, Tansplantat Biol Res Ctr, Charlestown, MA USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 721 EP 721 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801933 ER PT J AU Lee, KM Zhao, GP Schuetz, C Kim, J Lian, MM Markmann, J Deng, SP AF Lee, Kang Mi Zhao, Gaoping Schuetz, Christian Kim, James Lian, Moh-Moh Markmann, James Deng, Shaoping TI B Lymphocytes Down-Regulate Anti-CD45RB-Induced Tolerance in Islet Transplant Model. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Lee, Kang Mi; Zhao, Gaoping; Schuetz, Christian; Kim, James; Lian, Moh-Moh; Markmann, James; Deng, Shaoping] Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Schuetz, Christian/K-5234-2013 OI Schuetz, Christian/0000-0002-6828-4543 NR 0 TC 0 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 723 EP 723 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801942 ER PT J AU Graham, JA Fray, MA de Haseth, S Colvin, RB Madsen, JC Cosimi, BA Benichou, G Alessandrini, A AF Graham, Jay A. Fray, Michael A. de Haseth, Stephanie Colvin, Robert B. Madsen, Joren C. Cosimi, Benedict A. Benichou, Gilles Alessandrini, Alessandro TI Inhibition of the Kinase, GSK-3beta, Potentiates the Suppressive Function of Regulatory T Cells by Decreasing Cellular Death. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Graham, Jay A.; Fray, Michael A.; de Haseth, Stephanie; Colvin, Robert B.; Madsen, Joren C.; Cosimi, Benedict A.; Benichou, Gilles; Alessandrini, Alessandro] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 726 EP 726 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801952 ER PT J AU Hirohashi, T Chase, CM DellaPelle, PA Madsen, JC Russell, PS Colvin, RB AF Hirohashi, Tsutomu Chase, Catharine M. DellaPelle, Patricia A. Madsen, Joren C. Russell, Paul S. Colvin, Robert B. TI Role of NK Cells in Antibody Mediated Chronic Transplant Arteriopathy in Mice. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Hirohashi, Tsutomu; Chase, Catharine M.; Madsen, Joren C.; Russell, Paul S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [DellaPelle, Patricia A.; Colvin, Robert B.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 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 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 728 EP 728 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068801961 ER PT J AU Becker, WC Meghani, SH Barth, KS Wiedemer, N Gallagher, RM AF Becker, William C. Meghani, Salimah H. Barth, Kelly S. Wiedemer, Nancy Gallagher, Rollin M. TI Characteristics and Outcomes of Patients Discharged from the Opioid Renewal Clinic at the Philadelphia VA Medical Center SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID CHRONIC PAIN PATIENTS; PRIMARY-CARE; SUBSTANCE-ABUSE; THERAPY; MANAGEMENT AB The Opioid Renewal Clinic (ORC) is a pharmacist-run program that assists primary care providers in the management of chronic pain patients with aberrant behavior or high risk of prescription opioid abuse. In this study, charts of all discharged patients over a 22-month span (n = 86) were reviewed for outcomes for two years after discharge. The most frequent reason for discharge from the program was recurrent positive urine drug screens for illicit substances (n = 40; 47%). Only 15 (17%) were seen for addiction treatment in the two-year follow-up period. Forty-one percent of patients (n = 35) were prescribed opioids within two years of discharge. There was a positive correlation between length of time in the ORC and receipt of opioids post discharge. These outcomes reveal areas of need in the management of this complex population. C1 [Becker, William C.; Wiedemer, Nancy; Gallagher, Rollin M.] Philadelphia Vet Affairs Med Ctr, VISN4 MIRECC, Philadelphia, PA USA. Univ Penn, Sch Nursing, NewCourtland Ctr Transit & Hlth, Philadelphia, PA 19104 USA. [Barth, Kelly S.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Becker, WC (reprint author), VAMC 3900 Woodland Ave, Philadelphia, PA 19104 USA. EM William.Becker4@va.gov OI Becker, William/0000-0002-0788-1467 NR 13 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 2 BP 135 EP 139 AR PII 909499370 DI 10.1080/10550490902772496 PG 5 WC Substance Abuse SC Substance Abuse GA 418GX UT WOS:000264137800006 PM 19283565 ER PT J AU Newton, TF La Garza, R Kalechstein, AD Tziortzis, D Jacobsen, CA AF Newton, Thomas F. De La Garza, Richard, II Kalechstein, Ari D. Tziortzis, Desey Jacobsen, Caitlin A. TI Theories of Addiction: Methamphetamine Users' Explanations for Continuing Drug Use and Relapse SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; COCAINE-DEPENDENT PATIENTS; DSM-IV; IMPULSIVITY; REWARD; ABUSE; WITHDRAWAL; BEHAVIOR; BRAIN; DYSREGULATION AB A variety of preclinical models have been constructed to emphasize unique aspects of addiction-like behavior. These include Negative Reinforcement (Pain Avoidance), Positive Reinforcement (Pleasure Seeking), Incentive Salience (Craving), Stimulus Response Learning (Habits), and Inhibitory Control Dysfunction (Impulsivity). We used a survey to better understand why methamphetamine-dependent research volunteers (N = 73) continue to use methamphetamine, or relapse to methamphetamine use after a period of cessation of use. All participants met DSM-IV criteria for methamphetamine abuse or dependence, and did not meet criteria for other current Axis I psychiatric disorders or dependence on other drugs of abuse, other than nicotine. The questionnaire consisted of a series of face-valid questions regarding drug use, which in this case referred to methamphetamine use. Examples of questions include: Do you use drugs mostly to make bad feelings like boredom, loneliness, or apathy go away?, Do you use drugs mostly because you want to get high?, Do you use drugs mostly because of cravings?, Do you find yourself getting ready to take drugs without thinking about it?, and Do you impulsively take drugs?. The scale was anchored at 1 (not at all) and 7 (very much). For each question, the numbers of participants rating each question negatively (1 or 2), neither negatively or affirmatively (3-5), and affirmatively (6 or 7) were tabulated. The greatest number of respondents (56%) affirmed that they used drugs due to pleasure seeking. The next highest categories selected were impulsivity (27%) and habits(25%). Surprisingly, many participants reported that pain avoidance (30%) and craving (30%) were not important for their drug use. Results from this study support the contention that methamphetamine users (and probably other drug users as well) are more heterogeneous than is often appreciated, and imply that treatment development might be more successful if treatments targeted subtypes of patients, though a range of limitations to the approach used are acknowledged. C1 [Newton, Thomas F.; De La Garza, Richard, II] Baylor Coll Med, Menninger Dept Psychiatry& Behav Sci, Houston, TX 77030 USA. [Newton, Thomas F.; De La Garza, Richard, II] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Kalechstein, Ari D.; Tziortzis, Desey; Jacobsen, Caitlin A.] Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Newton, TF (reprint author), Baylor Coll Med, Menninger Dept Psychiatry& Behav Sci, 1 Baylor Plaza,BCM350, Houston, TX 77030 USA. EM tnewton@bcm.edu RI De La Garza, Richard/B-2489-2014; OI De La Garza, Richard/0000-0003-1943-4469; newton, thomas/0000-0002-3198-5901 FU NIDA NIH HHS [K24 DA017754, R01 DA023468, R21 DA017182] NR 51 TC 23 Z9 23 U1 2 U2 15 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 4 BP 294 EP 300 AR PII 911211983 DI 10.1080/10550490902925920 PG 7 WC Substance Abuse SC Substance Abuse GA 446FJ UT WOS:000266105800005 PM 19444733 ER PT J AU Wilens, T Adler, L Zhang, S Durell, T Walker, D Schuh, L Trzepacz, P AF Wilens, Timothy Adler, L. Zhang, S. Durell, T. Walker, D. Schuh, L. Trzepacz, P. TI Safety of Atomoxetine in ADHD Patients with or without Comorbid Alcohol Abuse and Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Meeting Abstract C1 [Wilens, Timothy] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 4 MA 29 BP 329 EP 329 PG 1 WC Substance Abuse SC Substance Abuse GA 446FJ UT WOS:000266105800032 ER PT J AU Adler, L Wilens, T Zhang, SY Durell, T Walker, D Schuh, L Jin, L Feldman, P Trzepacz, P AF Adler, Lenard Wilens, Timothy Zhang, Shuyu Durell, Todd Walker, Daniel Schuh, Leslie Jin, Ling Feldman, Peter Trzepacz, Paula TI Retrospective Safety Analysis of Atomoxetine in Adult ADHD Patients with or without Comorbid Alcohol Abuse and Dependence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; PSYCHIATRIC COMORBIDITY; ETHANOL; NEURONS; METHYLPHENIDATE; PREVALENCE; BRAIN AB This post hoc analysis compared the safety of atomoxetine treatment of ADHD in adults with or without comorbid alcohol abuse/dependence. Study completion rates in patients receiving atomoxetine were comparable between heavy drinkers (60.9%) and patients with no alcohol-use disorder (71.0%) but lower in nonheavy drinkers (35.7%); however, there was no significant difference in discontinuation rates due to adverse events or lack of efficacy among these groups. Alcohol-use disorder patients, especially heavy drinkers, generally experienced the greatest frequency of treatment-emergent adverse events in both the atomoxetine and placebo groups. Vital signs and measures of hepatic function were not significantly different among the 3 drinking status groups taking atomoxetine. ( Am J Addict 2009; 18: 393-401) C1 [Adler, Lenard] NYU, Langone Sch Med, Dept Psychiat & Child & Adolescent Psychiat, New York, NY 10016 USA. [Wilens, Timothy] Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. [Wilens, Timothy] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Zhang, Shuyu; Walker, Daniel; Schuh, Leslie; Jin, Ling; Feldman, Peter; Trzepacz, Paula] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Durell, Todd] Lilly USA LLC, Indianapolis, IN USA. RP Adler, L (reprint author), NYU, Sch Med, 530 1st Ave,7D, New York, NY 10016 USA. EM lenard.adler@med.nyu.edu NR 41 TC 17 Z9 17 U1 3 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2009 VL 18 IS 5 BP 393 EP 401 DI 10.1080/10550490903077663 PG 9 WC Substance Abuse SC Substance Abuse GA 539QX UT WOS:000273273500009 PM 19874159 ER PT J AU Zahajszky, J Rosenbaum, JF Tollefson, GD AF Zahajszky, Janos Rosenbaum, Jerrold F. Tollefson, Gary D. BE Schatzberg, AF Nemeroff, CB TI Fluoxetine SO AMERICAN PSYCHIATRIC PUBLISHING TEXTBOOK OF PSYCHOPHARMACOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID OBSESSIVE-COMPULSIVE DISORDER; SEROTONIN REUPTAKE INHIBITORS; PLACEBO-CONTROLLED TRIAL; BORDERLINE PERSONALITY-DISORDER; POSTTRAUMATIC-STRESS-DISORDER; MONOAMINE-OXIDASE INHIBITOR; MAJOR DEPRESSIVE DISORDER; RANDOMIZED CLINICAL-TRIAL; NORADRENALINE RE-UPTAKE; RECEPTOR-BINDING SITES C1 [Zahajszky, Janos] Calif Pacific Med Ctr, San Francisco, CA 94115 USA. [Rosenbaum, Jerrold F.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rosenbaum, Jerrold F.] Harvard Univ, Sch Med, Boston, MA USA. [Tollefson, Gary D.] Orexigen Therapeut, La Jolla, CA USA. RP Zahajszky, J (reprint author), Calif Pacific Med Ctr, San Francisco, CA 94115 USA. NR 195 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-1-58562-309-9 PY 2009 BP 289 EP 306 PG 18 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA BCF29 UT WOS:000310050700014 ER EF