FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Gordon, A Fiellin, D Friedmann, P Gourevitch, M Kraemer, K Arnsten, J Saitz, R AF Gordon, Adam J. Fiellin, David A. Friedmann, Peter D. Gourevitch, Marc N. Kraemer, Kevin L. Arnsten, Julia H. Saitz, Richard CA Soc Gen Internal Med Subst Abuse TI Update in Addiction Medicine for the Primary Care Clinician SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE substance-related disorders; primary health care; review literature ID RANDOMIZED CONTROLLED-TRIAL; ALCOHOL-USE DISORDERS; SELF-HELP GROUPS; OUTCOMES; BUPRENORPHINE; TOPIRAMATE; DEPENDENCE; ADULTS; AUDIT; ABUSE C1 [Gordon, Adam J.] Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15206 USA. [Gordon, Adam J.] VA Pittsburgh Healthcare Syst, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. [Gordon, Adam J.; Kraemer, Kevin L.] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA USA. [Fiellin, David A.] Yale Univ, Sch Med, New Haven, CT USA. [Friedmann, Peter D.] Brown Univ, Alpert Med Sch, Rhode Isl Hosp,Div Gen Internal Med, Providence VA Med Ctr,Ctr Syst Outcomes & Qual Ch, Providence, RI 02912 USA. [Gourevitch, Marc N.] NYU, Sch Med, New York, NY USA. [Arnsten, Julia H.] Albert Einstein Coll Med, New York, NY USA. [Arnsten, Julia H.] Montefiore Med Ctr, New York, NY USA. [Saitz, Richard] Boston Med Ctr, Gen Internal Med Sect, CARE Unit, Boston, MA USA. [Saitz, Richard] Boston Univ, Sch Med, Boston, MA 02118 USA. [Saitz, Richard] Boston Univ, Sch Publ Hlth, Youth Alcohol Prevent Ctr, Boston, MA 02215 USA. [Saitz, Richard] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. RP Gordon, A (reprint author), Univ Pittsburgh, Sch Med, VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailcode 151-C-H,7180 Highland Dr 151 C-H, Pittsburgh, PA 15206 USA. EM adam.gordon@va.gov OI Fiellin, David/0000-0002-4006-010X; Gourevitch, Marc/0000-0001-6865-2126; /0000-0002-2535-1427 FU Society of General Internal Medicine's Substance Abuse Interest Group FX All authors are members of the Society of General Internal Medicine's Substance Abuse Interest Group to which we are deeply indebted for its support. The authors also wish to thank Margaret Krumm for her contributions of coordinating the review and editing this paper. NR 27 TC 8 Z9 8 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2008 VL 23 IS 12 BP 2112 EP 2116 DI 10.1007/s11606-008-0806-7 PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 379VJ UT WOS:000261424000026 PM 18830761 ER PT J AU Kadzielski, J Malhotra, LR Zurakowski, D Lee, SGP Jupiter, JB Ring, D AF Kadzielski, John Malhotra, Leah R. Zurakowski, David Lee, Sang-Gil P. Jupiter, Jesse B. Ring, David TI Evaluation of Preoperative Expectations and Patient Satisfaction After Carpal Tunnel Release SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Carpal tunnel syndrome; patient expectations; outcome ID TOTAL HIP-ARTHROPLASTY; IDIOPATHIC ARM PAIN; REPLACEMENT SURGERY; BREAST-CANCER; KNEE SURGERY; OUTCOMES; HEALTH; OPTIMISM; PREDICT; OSTEOARTHRITIS AB Purpose We tested the hypothesis that preoperative expectations affect postoperative satisfaction and arm-specific, self-reported health Status after elective carpal tunnel release. Methods Forty-nine patients having elective carpal tunnel release completed questionnaires evaluating self-rated upper extremity-specific disability using the Disabilities of the Arm Shoulder and Hand (DASH) questionnaire, expectations regarding surgery (Preop Expectations Score), personal importance of: upper-extremity function, measures of general optimism.. the Life Orientation Test (LOT), as well as health-specific optimism, and the Multidimensional Health Locus Of Control scale. Six months after surgery, patients completed a 10-point Likert scale to assess satisfaction, the DASH, and measures determining (1) fulfillment of expectations (Postop Met Expectations Score) and (2) relief of specific systems (Postop Help Score). Results The DASH scores decreased significantly from an average of 37 points before surgery to an average of 15 points 6 months after carpal tunnel release (p <.001), and patients rated their satisfaction (mean +/- standard deviation) as 8 +/- 3. Preoperative expectations did not correlate with patient satisfaction or postoperative DASH scores. Multivariable analyses determined that patient satisfaction was best predicted by fulfillment of expectations (Postop Help Score alone, accounting for 41% of the variance in scores) and postoperative DASH scores were predicted by a combination of Postop Met Expectations Score and the LOT score (accounting for 31% of the variance in scores). Conclusions As measured in this Study, the strongest predictor of satisfaction after carpal tunnel release was relief of symptoms, and the strongest predictors of postoperative disability were met expectations and optimism; however, the majority of the variance in postoperative satisfaction remains unexplained. (J Hand Surg 2008;33A:1783-1788. Copyright (c) 2008 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, 55 Fruit St,YAW 2, Boston, MA 02114 USA. EM dring@partners.org NR 44 TC 29 Z9 29 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2008 VL 33A IS 10 BP 1783 EP 1788 DI 10.1016/j.jhsa.2008.06.019 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388FT UT WOS:000262006400014 PM 19084178 ER PT J AU Watson, J Ring, D AF Watson, Jeffrey Ring, David TI Influence of Psychological Factors on Grip Strength SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Depression; grip strength; performance-based; psychological distress; upper extremity ID PAIN CATASTROPHIZING SCALE; IDIOPATHIC ARM PAIN; DEPRESSIVE SYMPTOMS; PHYSICAL FUNCTION; NORMATIVE DATA; OLDER PERSONS; HEALTH-STATUS; PERFORMANCE; HAND; MEN AB Purpose Grip strength is widely used to assess upper-extremity function. Although grip strength is a quantitative measure of function. gogrip strength is a reflection of both physical irnpaimient as well as subjective. psychological factors. We investigated the detern- nants of grip strength with the hypothesis that psychological factors are associated with diminished girp strength. Methods One hundred thirty-four patients with an isolated, discrete upper-extremity condition had grip strength measurements, and, as part of one of several prospective clinical studies, during the same visit they completed 2 or more of the following surveys: the Center for Epidemlologic C Studies-Depression (CES-D) scale, Pain Anxiety Symptoms Scale, and Pain Catastrophizing Scale. Univariate and multivariable statistical analysis sought determinants of absolute grip strength and grip strength as a percentage of the opposite, uninvolved limb. Results Determinants of absolute grip strength included gender and grip strength of the uninvolved limb. The association between CES-D score and absolute grip strength was near significant but very weak. Multivariable regression analysis produced a best-fit model that retained grip strength of the uninvolved limb and CES-D scores. When grip strength of the involved limb was evaluated as percentage of grip strength of the uninvolved limb, CES-D score was a weak but significant predictor, and patients recovering from a fracture of the distal radius had weaker grip strength than did patients with nontraumatic conditions. Conclusions Depression scores were minimally associated with diminished grip strength. Psychological factors appear to affect disability (patient-reported health status) more than they affect performance-based measures of function. (J Hand Surg 2008;33A:1791-1795. Copyright (c) 2008 by the American Society for Surgery of the Hand. All rights reserved.) C1 [Ring, David] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 33 TC 15 Z9 15 U1 3 U2 10 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2008 VL 33A IS 10 BP 1791 EP 1795 DI 10.1016/j.jhsa.2008.07.006 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388FT UT WOS:000262006400016 PM 19084180 ER PT J AU Kong, BS Kim, YJ Suh, YS Jawa, A Nazzal, A Lee, SG AF Kong, Byeong Seon Kim, Yong Jin Suh, Young Suk Jawa, Andrew Nazzal, Adam Lee, Sang Gil TI Finger Soft Tissue Reconstruction Using Arterialized Venous Free Flaps Having 2 Parallel Veins SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE Arterialized venous free flap; finger; two parallel veins ID SKIN DEFECTS; CLINICAL-APPLICATIONS; HAND AB Purpose Arterialized venous free flaps with a single straight venous axis may require redirection of either the efferent or affere vein for anastornosis to the digital vessels. To simplify these flaps, the authors propose use of an arterialized venous free flap having 2 parallel veins that does not require redirection of the veins. Methods The authors performed 44 arterialized venous free flaps having 2 parallel veins for the reconstruction of digital soft tissue defects. The mean area of coverage was 6.5 cm(2). The donor sites included the volar aspect of the distal forearm in 35 cases, the thenar area in 8 cases, and the dorsal aspect of the foot in 1 case. Results Thirty-nine of the 44 flaps survived. Complete flap necrosis occurred in 5 cases, and flap congestion was seen in 28 cases. Conclusions The authors had satisfactory results using arterialized venous free flaps having 2 parallel veins. By using these flaps, the authors were able to simplify the technique of arterialized venous flaps. (J Hand Surg 2008;33A: 1802-1806. (c) 2008 Published by Elsevier Inc. on behalf of the American Society for Surgery of the Hand.) C1 [Kong, Byeong Seon] Busan Centum Hosp, Dept Orthoped Surg, Hand & Microsurg Ctr, Pusan, South Korea. Massachusetts Gen Hosp, Dept Orthopaed Surg, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Kong, BS (reprint author), Busan Centum Hosp, Dept Orthoped Surg, Hand & Microsurg Ctr, 1077-1 Kwangan 3 Dong Suyoung Gu, Pusan, South Korea. EM gongja2000@yahoo.co.kr NR 17 TC 16 Z9 19 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD DEC PY 2008 VL 33A IS 10 BP 1802 EP 1806 DI 10.1016/j.jhsa.2008.08.001 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 388FT UT WOS:000262006400018 PM 19084182 ER PT J AU Souer, JS Mudgal, CS AF Souer, J. S. Mudgal, C. S. TI PLATE FIXATION IN CLOSED IPSILATERAL MULTIPLE METACARPAL FRACTURES SO JOURNAL OF HAND SURGERY-EUROPEAN VOLUME LA English DT Article DE closed; multiple; metacarpal fractures; plating ID PHALANGEAL FRACTURES; HAND; COMPLICATIONS; FINGERS; SCREWS; SHAFT AB Closed multiple metacarpal fractures are uncommon. They are usually associated with significant soft tissue swelling. Early stable fixation and functional rehabilitation optimises outcome. We present a review of 19 patients with 43 metacarpal fractures treated by early open reduction and internal fixation with 2 mm plates. Eighteen patients recovered a full range of motion, while one patient was lost to follow-up. Implant removal on account of extensor irritation was required in only two metacarpals in two patients. Plating of multiple closed metacarpal fractures is a safe, reliable and consistently reproducible treatment method. C1 [Mudgal, C. S.] Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Boston, MA 02114 USA. RP Mudgal, CS (reprint author), Massachusetts Gen Hosp, Orthopaed Hand & Upper Extrem Serv, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM cmudgal@partners.org NR 21 TC 10 Z9 11 U1 1 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1753-1934 J9 J HAND SURG-EUR VOL JI J. Hand Surg.-Eur. Vol. PD DEC PY 2008 VL 33E IS 6 BP 740 EP 744 DI 10.1177/1753193408090101 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 392VX UT WOS:000262331400007 PM 18694922 ER PT J AU Frakt, AB Pizer, SD Hendricks, AM AF Frakt, Austin B. Pizer, Steven D. Hendricks, Ann M. TI Controlling Prescription Drug Costs: Regulation and the Role of Interest Groups in Medicare and the Veterans Health Administration SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID PRESSURE GROUPS; POLITICS; BENEFIT; PRICES; CARE; ACT AB Medicare and the Veterans Health Administration (VA) both finance large outpatient prescription drug programs, though in very different ways. In the ongoing debate on how to control Medicare spending, some suggest that Medicare should negotiate directly with drug manufacturers, as the VA does. In this article we relate the role of interest groups to policy differences between Medicare and the VA and, in doing so, explain why such a large change to the Medicare drug program is unlikely. We argue that key policy differences are attributable to stable differences in interest group involvement. While this stability makes major changes in Medicare unlikely, it suggests the possibility of leveraging VA drug purchasing to achieve savings in Medicare. This could be done through a VA-administered drug-only benefit for Medicare-enrolled veterans. Such a partnership could incorporate key elements of both programs: capacity to accept large numbers of enrollees (like Medicare) and leverage to negotiate prescription drug prices (like the VA). Moreover, it could be implemented at no cost to the VA while achieving savings for Medicare and beneficiaries. C1 [Frakt, Austin B.; Pizer, Steven D.; Hendricks, Ann M.] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. [Frakt, Austin B.; Pizer, Steven D.; Hendricks, Ann M.] VA Boston Healthcare Syst, Boston, MA USA. RP Frakt, AB (reprint author), VA Boston Healthcare Syst, Boston, MA USA. FU Department of Veterans Affairs Health Services Research and Development Service [IIR 04-233-1] FX This research was supported by the Department of Veterans Affairs Health Services Research and Development Service Grant No. IIR 04-233-1. This is an investigator-initiated, peer-reviewed grant. Although the authors interviewed some current and former Medicare and Department of Veterans Affairs administrators as part of this research, this article was neither reviewed nor approved by Medicare or Department of Veterans Affairs administrators prior to submission for publication. The views expressed in this article are those of the authors and do not necessarily reflect the positions of the Department of Veterans Affairs or Boston University. We thank Dan Plafcan, Lynn Wolfsfeld, Julia Prentice, and two anonymous reviewers for their helpful comments on earlier versions of this article. NR 66 TC 2 Z9 2 U1 1 U2 3 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD DEC PY 2008 VL 33 IS 6 BP 1079 EP 1106 DI 10.1215/03616878-2008-032 PG 28 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 383AV UT WOS:000261647400005 PM 19038872 ER PT J AU Sussner, KM Lindsay, AC Greaney, ML Peterson, KE AF Sussner, Katarina M. Lindsay, Ana C. Greaney, Mary L. Peterson, Karen E. TI The Influence of Immigrant Status and Acculturation on the Development of Overweight in Latino Families: A Qualitative Study SO JOURNAL OF IMMIGRANT AND MINORITY HEALTH LA English DT Article DE Child obesity and overweight; Immigrants; Acculturation; Latino AB Exposure to obesogenic environments in the U. S. may foster development of overweight in immigrants with greater acculturation. Few studies document mechanisms of the acculturation process from immigrants' own perspectives or describe implications on the children of immigrants. Focus groups and in-depth interviews were conducted with immigrant Latina mothers (N = 51) examining mothers' beliefs, attitudes and practices related to early child feeding and weight. Focus group participants completing the Marin Acculturation Scale more closely identified with Latino culture, although the mean score (2.04, SD = 0.59) was close to "bicultural''. Analysis revealed seven themes when mothers compared lifestyles between their native countries and the U. S., related to changes in (1) diet, perceived food quality and availability, (2) food and eating practices, (3) breastfeeding practices, (4) beliefs about food, child feeding and weight status, (5) weight status of mothers and children, (6) physical activity and sedentary lifestyles, and (7) social isolation and support. C1 [Sussner, Katarina M.] Mt Sinai Sch Med, Dept Oncol Sci Canc Prevent & Control, New York, NY 10029 USA. [Lindsay, Ana C.; Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Greaney, Mary L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Peterson, Karen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Sussner, KM (reprint author), Mt Sinai Sch Med, Dept Oncol Sci Canc Prevent & Control, 1425 Madison Ave,Box 1130, New York, NY 10029 USA. EM katarina.sussner@mssm.edu FU NCI NIH HHS [R03 CA108347, R03 CA108347-01]; NICHD NIH HHS [R01 HD037368, R01 HD37368] NR 60 TC 58 Z9 59 U1 3 U2 21 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1557-1912 J9 J IMMIGR MINOR HEALT JI J. Immigr. Minor. Health PD DEC PY 2008 VL 10 IS 6 BP 497 EP 505 DI 10.1007/s10903-008-9137-3 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V13DX UT WOS:000207648600003 PM 18373200 ER PT J AU Fudaba, Y Onoe, T Chittenden, M Shimizu, A Shaffer, JM Bronson, R Sykes, M AF Fudaba, Yasuhiro Onoe, Takashi Chittenden, Meredith Shimizu, Akira Shaffer, Juanita M. Bronson, Roderick Sykes, Megan TI Abnormal Regulatory and Effector T Cell Function Predispose to Autoimmunity following Xenogeneic Thymic Transplantation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SKIN-GRAFT TOLERANCE; FETAL PIG THYMUS; NUDE-MICE; HOMEOSTATIC PROLIFERATION; NEGATIVE SELECTION; THYMECTOMIZED MICE; POSITIVE SELECTION; CUTTING EDGE; ATHYMIC MICE; PORCINE MHC AB Porcine thymus grafts support robust murine and human thymopoiesis, generating a diverse T cell repertoire that is deleted of donor and host-reactive cells, achieving specific xenograft tolerance. Positive selection is mediated exclusively by the xenogeneic thymic MHC. Although thymectomized, T cell-depleted normal mice usually remain healthy following xenogeneic thymic transplantation, thymus-grafted congenitally athymic mice frequently develop multiorgan autoimmunity. We investigated the etiology of this syndrome by adoptively transferring lymphocyte populations from fetal pig thymus-grafted BALB/c nude mice to secondary BALB/c nude recipients. Fetal pig thymus-grafted nude mice generated normal numbers of CD25(+)Foxp3(+)CD4 T cells, but these cells lacked the capacity to block autoimmunity. Moreover, thymocytes and peripheral CD4(+)CD25(-) cells from fetal pig thymus-grafted nude mice, but not those from normal mice, induced autoimmunity in nude recipients. Injection of thymic epithelial cells from normal BALB/c mice into fetal pig thymus grafts reduced autoimmunity and enhanced regulatory function of splenocytes. Our data implicate abnormalities in postthymic maturation, expansion, and/or survival of T cells positively selected by a xenogeneic MHC, as well as incomplete intrathymic deletion of thymocytes recognizing host tissue-specific Ags, in autoimmune pathogenesis. Regulatory cell function is enhanced and negative selection of host-specific thymocytes may potentially also be improved by coimplantation of recipient thymic epithelial cells in the thymus xenograft. The Journal of Immunology, 2008, 181: 7649-7659. C1 [Fudaba, Yasuhiro; Onoe, Takashi; Chittenden, Meredith; Shimizu, Akira; Shaffer, Juanita M.; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Boston, MA 02129 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Transplantat Biol Res Ctr, Massachusetts Gen Hosp E Bldg 149-5102,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU National Institutes of Health [P01 A1045897, P01 HL18646]; Juvenile Diabetes Research Foundation Basic Science [1-2007-723]; Japan Society for the Promotion of Science FX This work was supported by National Institutes of Health Grants P01 A1045897 and P01 HL18646, Juvenile Diabetes Research Foundation Basic Science Grant 1-2007-723, and Immerge BT. Y.F. was supported in part by the Uchara Memorial Foundation. T.O. was supported in part by a Postdoctoral Fellowship for Research of Abroad front the Japan Society for the Promotion of Science. NR 49 TC 8 Z9 8 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 7649 EP 7659 PG 11 WC Immunology SC Immunology GA 376YX UT WOS:000261220000026 PM 19017953 ER PT J AU Pazos, M Siccardi, D Mumy, KL Bien, JD Louie, S Shi, HN Gronert, K Mrsny, RJ McCormick, BA AF Pazos, Michael Siccardi, Dario Mumy, Karen L. Bien, Jeffrey D. Louie, Steve Shi, Hai Ning Gronert, Karsten Mrsny, Randall J. McCormick, Beth A. TI Multidrug Resistance-Associated Transporter 2 Regulates Mucosal Inflammation by Facilitating the Synthesis of Hepoxilin A(3) SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENTERICA SEROTYPE TYPHIMURIUM; ARACHIDONATE 12-LIPOXYGENASE; SALMONELLA-TYPHIMURIUM; INTESTINAL EPITHELIA; TRANSEPITHELIAL MIGRATION; NEUTROPHIL MIGRATION; IN-VITRO; T-CELLS; COLITIS; DRUG AB Neutrophil transmigration across mucosal surfaces contributes to dysfunction of epithelial barrier properties, a characteristic underlying many mucosal inflammatory diseases. Thus, insight into the directional movement of neutrophils across epithelial barriers will provide important information relating to the mechanisms of such inflammatory disorders. The eicosanoid hepoxilin A(3), an endogenous product of 12-lipoxygenase activity, is secreted from the apical surface of the epithelial barrier and establishes a chemotactic gradient to guide neutrophils from the submucosa across epithelia to the luminal site of an inflammatory stimulus, the final step in neutrophil recruitment. Currently, little is known regarding how hepoxilin A(3) is secreted from the intestinal epithelium during an inflammatory insult. In this study, we reveal that hepoxilin A(3) is a substrate for the apical efflux ATP-binding protein transporter multidrug resistance-associated protein 2 (MRP2). Moreover, using multiple in vitro and in vivo models, we show that induction of intestinal inflammation profoundly up-regulates apical expression of MRP2, and that interfering with hepoxilin A(3) synthesis and/or inhibition of MRP2 function results in a marked reduction in inflammation and severity of disease. Lastly, examination of inflamed intestinal epithelia in human biopsies revealed up-regulation of MRP2. Thus, blocking hepoxilin A(3) synthesis and/or inhibiting MRP2 may lead to the development of new therapeutic strategies for the treatment of epithelial-associated inflammatory conditions. The Journal of Immunology, 2008, 181: 8044-8052. C1 [Pazos, Michael; Siccardi, Dario; Mumy, Karen L.; Bien, Jeffrey D.; Louie, Steve; Shi, Hai Ning; McCormick, Beth A.] Massachusetts Gen Hosp, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. [Siccardi, Dario; Mumy, Karen L.; McCormick, Beth A.] Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. [Gronert, Karsten] Univ Calif Berkeley, Sch Optometry, Ctr Eye Dis & Dev, Berkeley, CA 94720 USA. [Mrsny, Randall J.] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Mrsny, Randall J.] Unity Pharmaceut, Menlo Pk, CA 94025 USA. RP McCormick, BA (reprint author), Massachusetts Gen Hosp, CNY 114 16th St 3503, Charlestown, MA 02129 USA. EM mccormic@helix.mgh.harvard.edu FU National Institutes of Health [DK 56754, DK 33506]; National Eye Institute [EY01613604]; Harvard Medical School; Department of Surgery at Massachusetts General Hospital; National Institutes of Health Minority Supplement Award FX This research was supported by National Institutes of Health Grants DK 56754 and DK 33506 (to B.A.M.), National Eye Institute Grant EY01613604 (to K.G.), and a T32 Training Grant sponsored by Harvard Medical School and the Department of Surgery at Massachusetts General Hospital (to K.L.M.). M.P. was supported by a National Institutes of Health Minority Supplement Award. NR 49 TC 19 Z9 19 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 8044 EP 8052 PG 9 WC Immunology SC Immunology GA 376YX UT WOS:000261220000070 PM 19017997 ER PT J AU Huang, SH Dunkley-Thompson, J Tang, YH Macklin, EA Steel-Duncan, J Singh-Minott, I Ryland, EG Smikle, M Walker, BD Christie, CDC Feeney, ME AF Huang, SiHong Dunkley-Thompson, Jacqueline Tang, YanHua Macklin, Eric A. Steel-Duncan, Julianne Singh-Minott, Indira Ryland, Elizabeth G. Smikle, Monica Walker, Bruce D. Christie, Celia D. C. Feeney, Margaret E. TI Deficiency of HIV-Gag-Specific T Cells in Early Childhood Correlates with Poor Viral Containment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED CHILDREN; DISEASE PROGRESSION; HIV-1-INFECTED INFANTS; LYMPHOCYTE RESPONSES; CD8-T-CELL MEMORY; IMMUNE-RESPONSES; TYPE-1 INFECTION; CD4-T-CELL HELP; 1ST YEAR AB Perinatal HIV infection is characterized by a sustained high-level viremia and a high risk of rapid progression to AIDS, indicating a failure of immunologic containment of the virus. We hypothesized that age-related differences in the specificity or function of HIV-specific T cells may influence HIV RNA levels and clinical outcome following perinatal infection. In this study, we defined the HIV epitopes targeted by 76 pediatric subjects (47 HIV infected and 29 HIV exposed, but uninfected), and assessed the ability of HIV-specific CD8 and CD4 T cells to degranulate and produce IFN-gamma, TNF-alpha, and IL-2. No responses were detected among HIV-uninfected infants, whereas responses among infected subjects increased in magnitude and breadth with age. Gag-specific responses were uncommon during early infancy, and their frequency was significantly lower among children younger than 24 mo old (p = 0.014). Importantly, Gag responders exhibited significantly lower HIV RNA levels than nonresponders (log viral load 5.8 vs 5.0; p = 0.005). Both the total and Gag-specific T cell frequency correlated inversely with viral load after correction for age, whereas no relationship with targeting of other viral proteins was observed. Functional assessment of HIV-specific T cells by multiparameter flow cytometry revealed that polyfunctional CD8 cells were less prevalent in children before 24 mo of age, and that HIV-specific CD4 cell responses were of universally low frequency among anti retroviral-naive children and absent in young infants. These cross-sectional data suggest that qualitative differences in the CD8 response, combined with a deficiency of HIV-specific CD4 cells, may contribute to the inability of young infants to limit replication of HIV. The Journal of Immunology, 2008, 181: 8103-8111. C1 [Huang, SiHong; Tang, YanHua; Ryland, Elizabeth G.; Walker, Bruce D.; Feeney, Margaret E.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. [Huang, SiHong; Tang, YanHua; Ryland, Elizabeth G.; Walker, Bruce D.; Feeney, Margaret E.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. [Huang, SiHong; Tang, YanHua; Ryland, Elizabeth G.; Walker, Bruce D.; Feeney, Margaret E.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Dunkley-Thompson, Jacqueline; Steel-Duncan, Julianne; Singh-Minott, Indira; Smikle, Monica; Christie, Celia D. C.] Univ W Indies, Kingston Perinatal AIDS Program, Kingston 7, Jamaica. [Dunkley-Thompson, Jacqueline; Steel-Duncan, Julianne; Singh-Minott, Indira; Smikle, Monica; Christie, Celia D. C.] Univ W Indies, Dept Obstet Gynecol & Pediat, Kingston 7, Jamaica. [Huang, SiHong; Feeney, Margaret E.] Childrens Hosp, Boston, MA 02115 USA. [Macklin, Eric A.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Macklin, Eric A.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Huang, SiHong] Pfizer & Merck, Beth Israel Deaconess Med Ctr, Harvard Massachusetts Inst Technol Hlth Sci & Tec, Clin Investigator Training Program, Boston, MA 02215 USA. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Feeney, ME (reprint author), Massachusetts Gen Hosp East, 5th Floor,149 13th St, Charlestown, MA 02129 USA. EM mfeency@partners.org RI Macklin, Eric/E-2955-2013 OI Macklin, Eric/0000-0003-1618-3502 FU Elizabeth Glaser Pediatric AIDS Foundation; Charles H. Hood Foundation; National Institutes of Health [R01-AI068497]; Children Elizabeth Glaser Scientist Award FX This work was supported by grants From the Elizabeth Glaser Pediatric AIDS Foundation (to M.E.F. and C.D.C.C.), Jewelers for Children, Charles H. Hood Foundation (to M.E.F.), and National Institutes of Health (R01-AI068497, to M.E.F.). S.H. is supported by the Clinical Investigator Training Program. B.D.W. is a Doris Duke Distinguished Clinical Scientist and a Howard Hughes Investigator. C.D.C.C. is a recipient of the International Leadership Award from the Elizabeth Glaser Pediatric AIDS Foundation. KEY. is a recipient of the 2006 Jewelers for Children Elizabeth Glaser Scientist Award. NR 58 TC 24 Z9 24 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2008 VL 181 IS 11 BP 8103 EP 8111 PG 9 WC Immunology SC Immunology GA 376YX UT WOS:000261220000076 PM 19018003 ER PT J AU Sun, BK Tsao, H AF Sun, Bryan K. Tsao, Hensin TI X-Chromosome Inactivation and Skin Disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Review ID INCONTINENTIA PIGMENTI; DNA METHYLATION; WILMS-TUMOR; XIST GENE; EXPRESSION; LINES; RNA; MUTATION; BLASCHKO; FEMALES AB X-chromosome inactivation (XCI) is the process in which females transcriptionally silence one of their two X chromosomes in early embryonic development, equalizing X chromosome gene expression between males and females. XCI depends on a gene called XIST, a functional RNA molecule that does not code for a protein. Recent studies indicate abundant intergenic transcription and nonprotein coding RNAs in the human genome, which are suspected to function in modulating gene expression. XCI may therefore serve as a useful model to learn and understand the potential function of these elements, as well as their effects on human disease. Here, we review the genetic and molecular basis of XCI and describe how the mechanistics of this process lead to the phenotypes of X-linked skin diseases, most notably in the pattern of lines, swirls, and whorls first noted by the dermatologist Alfred Blaschko. We suggest that XCI, and other epigenetic phenomena, will continue to impact our understanding of the genetic mechanisms of disease. C1 [Tsao, Hensin] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Tsao, Hensin] Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. RP Tsao, H (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Bartlett 622,50 Blossom St, Boston, MA 02114 USA. EM htsao@partners.org OI Sun, Bryan/0000-0002-0740-0125 NR 37 TC 24 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2008 VL 128 IS 12 BP 2753 EP 2759 DI 10.1038/jid.2008.145 PG 7 WC Dermatology SC Dermatology GA 374RX UT WOS:000261062500004 PM 18509358 ER PT J AU Dadras, SS Skrzypek, A Nguyen, L Shin, JW Schulz, MMP Arbiser, J Mihm, MC Detmar, M AF Dadras, Soheil S. Skrzypek, Adrienne Nguyen, Lynh Shin, Jay W. Schulz, Martin M. P. Arbiser, Jack Mihm, Martin C. Detmar, Michael TI Prox-1 Promotes Invasion of Kaposiform Hemangioendotheliomas SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID KASABACH-MERRITT PHENOMENON; ENDOTHELIAL-CELLS; DIFFERENTIATION; HERPESVIRUS; EXPRESSION; SARCOMA; SYSTEM; BLOOD; MODEL; GENE AB Kaposi's sarcoma (KS) is the most frequently occurring malignant tumor in patients infected with HIV. Recent studies have revealed that infection of vascular endothelial cells with KS-associated herpes virus in vitro results in a lymphatic reprogramming of these cells, with potent induction of the lymphatic marker genes podoplanin and vascular endothelial growth factor receptor-3, which is mediated by upregulation of the transcription factor Prox1. However, the potential effects of Prox1 expression on the biology of KS and, in particular, on the aggressive and invasive behavior of KS tumors in vivo have remained unknown. We stably expressed Prox1 cDNA in the two mouse hemangioendothelioma cell lines EOMA and Py-4-1, well-established murine models for kaposiform hemangioendothelioma. Surprisingly, we found that expression of Prox1 was sufficient to induce a more aggressive behavior of tumors growing in syngenic mice, leading to enhanced local invasion into the muscular layer and to cellular anaplasia in vivo, and increased migration rate in vitro. This enhanced malignant phenotype was associated with upregulation of several genes involved in proteolysis, cell adhesion, and migration. Together, these results indicate that Prox1 plays an important, previously unanticipated role in mediating the aggressive behavior of vascular neoplasms such as KS. C1 [Dadras, Soheil S.; Skrzypek, Adrienne; Nguyen, Lynh; Shin, Jay W.; Detmar, Michael] Cutaneous Biol Res Ctr, Dept Dermatol, Boston, MA USA. [Dadras, Soheil S.; Mihm, Martin C.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Dadras, Soheil S.; Mihm, Martin C.] Harvard Univ, Sch Med, Boston, MA USA. [Shin, Jay W.; Schulz, Martin M. P.; Detmar, Michael] ETH, Swiss Fed Inst Technol, Inst Pharmaceut Sci, Zurich, Switzerland. [Arbiser, Jack] Emory Univ, Dept Dermatol, Atlanta, GA 30322 USA. RP Dadras, SS (reprint author), Stanford Univ, Med Ctr, 300 Pasteur Dr, Stanford, CA 94305 USA. EM sdadras@stanford.edu FU NIH/NCI [CA69184, CA86410, CA92644]; Susan G. Komen Breast Cancer Foundation; American Cancer Society Program Project [9923901]; Swiss National Fund [3100A0-108207]; Austrian Science Foundation [S9408-B11]; Commission of the European Communities [LSHC-CT-2005-518178]; NIH Pathology Training Grant; Cutaneous Biology Research Center; Massachusetts General Hospital/Shiseido Co. Ltd. Agreement FX We thank L. Janes and J. Bertoncini for expert technical assistance, Dr S. I. Tomarev for providing the pcDNA3/hProx-1 cDNA, Dr D. G. Jackson for the mouse anti-LYVE-1 antibody, and Drs K. Alitalo and Y. Hong for the antiProx-1 antibodies. This work was supported by NIH/NCI grants CA69184, CA86410, and CA92644 (M. D.), the Susan G. Komen Breast Cancer Foundation (M. D.), American Cancer Society Program Project Grant 9923901 (M. D.), Swiss National Fund grant 3100A0-108207 (M. D.), Austrian Science Foundation grant S9408-B11 (M. D.), Commission of the European Communities grant LSHC-CT-2005-518178 (M. D.), an NIH Pathology Training Grant (S. S. D.), and by the Cutaneous Biology Research Center through the Massachusetts General Hospital/Shiseido Co. Ltd. Agreement (M. D.). NR 31 TC 23 Z9 25 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2008 VL 128 IS 12 BP 2798 EP 2806 DI 10.1038/jid.2008.176 PG 9 WC Dermatology SC Dermatology GA 374RX UT WOS:000261062500010 PM 18580962 ER PT J AU Jackonis, MJ Deyton, L Hess, WJ AF Jackonis, Michael J. Deyton, Lawrence Hess, William J. TI War, Its Aftermath, and US Health Policy: Toward a Comprehensive Health Program for America's Military Personnel, Veterans, and Their Families SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article AB This essay discusses the challenges faced by veterans returning to society in light of the current organization and structure of the military, veterans', and overall U.S. health care systems. It also addresses the need for an integrated health care financing and delivery system to ensure a continuum of care for service members, veterans, dependents, and other family members. The health care systems of both the Department of Defense and the Department of Veterans Affairs execute their responsibilities to active duty service members, while their families and retirees/veterans are under separate legal authorities. Although they perform their mandates with extraordinary commitment and demonstrably high quality, both systems need to explore improved communication, coordination, and sharing, as well as increased collaboration with the Department of Health and Human Services programs serving the same populations, far beyond current efforts. The health care-related missions and the locus of health care delivery of each agency are admittedly unique, but their distinctions must not be permitted to impede system integration and coordination of a continuum of care provided to the men and women who serve the nation, and their families. C1 [Deyton, Lawrence] US Dept Vet Affairs, Washington, DC USA. [Deyton, Lawrence] George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Sci, Washington, DC 20052 USA. [Hess, William J.] Natl Naval Med Ctr, Bethesda, MD USA. NR 39 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 2008 VL 36 IS 4 BP 677 EP 689 DI 10.1111/j.1748-720X.2008.00322.x PG 13 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 378ZR UT WOS:000261364300008 PM 19093991 ER PT J AU Goldstein, MM Blumenthal, D AF Goldstein, Melissa M. Blumenthal, David TI Building an Information Technology Infrastructure SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article ID ELECTRONIC HEALTH RECORDS; CARE AB The widespread adoption of health information technology (HIT) has been recognized as both a necessary element of health reform and a required building block of a modern, high performing health care system. C1 [Goldstein, Melissa M.] George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Washington, DC 20037 USA. [Goldstein, Melissa M.] George Washington Univ, Med Ctr, Dept Clin Management, Washington, DC 20037 USA. [Goldstein, Melissa M.] George Washington Univ, Med Ctr, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Blumenthal, David] Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy & Phys, Boston, MA 02114 USA. [Blumenthal, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Goldstein, MM (reprint author), George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv, Dept Hlth Policy, Washington, DC 20037 USA. NR 25 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 2008 VL 36 IS 4 BP 709 EP 715 DI 10.1111/j.1748-720X.2008.00326.x PG 7 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 378ZR UT WOS:000261364300012 PM 19093995 ER PT J AU Morone, JA Blumenthal, D AF Morone, James A. Blumenthal, David TI Nine Lessons for Health Reform: Or Will We Finally Learn from the Past ? SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article AB Health care reform sits, once again, in the eye of the political storm. This article, based on an analysis of past health care debates, offers nine historical lessons for contemporary reformers. We describe the most important political do's and don'ts. C1 [Morone, James A.] Brown Univ, Providence, RI 02912 USA. [Blumenthal, David] Massachusetts Gen Hosp, Partners Healthcare Syst, Inst Hlth Policy, Boston, MA 02114 USA. [Blumenthal, David] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Morone, JA (reprint author), Brown Univ, Providence, RI 02912 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD WIN PY 2008 VL 36 IS 4 BP 722 EP 724 DI 10.1111/j.1748-720X.2008.00328.x PG 3 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 378ZR UT WOS:000261364300014 PM 19093997 ER PT J AU Ascon, DB Ascon, M Satpute, S Lopez-Briones, S Racusen, L Colvin, RB Soloski, MJ Rabb, H AF Ascon, Dolores B. Ascon, Miguel Satpute, Shailesh Lopez-Briones, Sergio Racusen, Lorraine Colvin, Robert B. Soloski, Mark J. Rabb, Hamid TI Normal mouse kidneys contain activated and CD3(+)CD4(-)CD8(-) double-negative T lymphocytes with a distinct TCR repertoire SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE DN T cells; NK cells; cytokines; ischemia; rodents ID RENAL ISCHEMIA-REPERFUSION; CELL-ACTIVATION; INTERFERON-GAMMA; HUMAN LIVER; INJURY; MICE; ALPHA; POPULATIONS; CYTOKINES; MODEL AB Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3(int) T cells). Similar to liver and lung, a high percentage of unconventional CD3(+)CD4(-)CD8(-) double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4(+) and CD8(+) T lymphocytes in the kidney had a high proportion of activated CD69(+) and effector/memory CD44CD62L ligand phenotypes. Also, a small percentage of CD4(+)CD25(+) forkhead box p3(+) and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-gamma and TNF-alpha by CD4(+) and CD8(+) T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process. J. Leukoc. Biol. 84: 1400-1409; 2008. C1 [Ascon, Dolores B.; Ascon, Miguel; Satpute, Shailesh; Lopez-Briones, Sergio; Racusen, Lorraine; Soloski, Mark J.; Rabb, Hamid] Johns Hopkins Univ, Sch Med, Dept Pathol & Med, Baltimore, MD USA. [Colvin, Robert B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Ascon, DB (reprint author), BriJen Biotech, UMBC Technol Ctr, Baltimore, MD 21227 USA. EM dascon@brijenbiotech.com; hrabb1@jhmi.edu OI Lopez-Briones, Sergio/0000-0003-0273-0958 FU National Institutes of Health [R01 DK54770, 3R01DK054770-05S1, 3R01DK054770-06A1, HL073944, RO1 AI42287, R21 AI063133] FX This study was supported by National Institutes of Health grants R01 DK54770 (H. R.), 3R01DK054770-05S1 (D.B.A.), 3R01DK054770-06A1 (M.A.), SCCOR HL073944 (H.R.), RO1 AI42287 (M.J.S.), and R21 AI063133 (M.J.S.). We thank Dr. Abdel Hamad for advice with DN T cells. We also thank Dr. Hye Ryoun Jang for help in kidney surgery. NR 38 TC 31 Z9 32 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC 1 PY 2008 VL 84 IS 6 BP 1400 EP 1409 DI 10.1189/jlb.0907651 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 374GR UT WOS:000261032300007 PM 18765477 ER PT J AU McCaslin, SE Inslicht, SS Metzler, TJ Henn-Haase, C Maguen, S Neylan, TC Choucroun, G Marmar, CR AF McCaslin, Shannon E. Inslicht, Sabra S. Metzler, Thomas J. Henn-Haase, Clare Maguen, Shira Neylan, Thomas C. Choucroun, Gerard Marmar, Charles R. TI Trait Dissociation Predicts Posttraumatic Stress Disorder Symptoms in a Prospective Study of Urban Police Officers SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE Dissociation; traumatic stress; police officers ID EMERGENCY SERVICES PERSONNEL; CIVILIAN MISSISSIPPI SCALE; SEXUAL-ABUSE; PERITRAUMATIC DISSOCIATION; VIETNAM VETERANS; NEUROPEPTIDE-Y; PTSD SYMPTOMS; RISK-FACTORS; TRAUMA; RELIABILITY AB The current study prospectively examines the predictive relationship of trait dissociation, assessed during academy training, to PTSD symptoms assessed at 12 months of active police duty in relatively young and healthy police academy recruits (N = 180). The roles of pre-academy trauma exposure, exposure to life-threatening critical incidents during police duty, and peritraumatic dissociation at the time of the officer's worst critical incident were also examined. Utilizing path analytic techniques, greater trait dissociation, assessed during academy training, was predictive of both peritraumatic dissociation, and PTSD symptoms assessed at 12 months of police service. Moreover, after accounting for trait dissociation and peritraumatic dissociation, the relationship of previous trauma to later PTSD symptoms was no longer significant, demonstrating that the effect of previous trauma on later vulnerability to PTSD symptoms in this sample may be mediated by both trait and peritraumatic dissociation. C1 [McCaslin, Shannon E.; Inslicht, Sabra S.; Metzler, Thomas J.; Henn-Haase, Clare; Maguen, Shira; Neylan, Thomas C.; Marmar, Charles R.] San Francisco VA Med Ctr, Mental Hlth Serv, San Francisco, CA USA. [McCaslin, Shannon E.; Inslicht, Sabra S.; Metzler, Thomas J.; Henn-Haase, Clare; Maguen, Shira; Neylan, Thomas C.; Marmar, Charles R.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Choucroun, Gerard] No Calif Inst Res & Educ, San Francisco, CA USA. RP McCaslin, SE (reprint author), Vet Affairs Med Ctr, PTSD Res Program, 4150 Clement St 116P, San Francisco, CA 94121 USA. EM Shannon.McCaslin@ucsf.edu FU NIMH NIH HHS [R01 MH056350] NR 54 TC 22 Z9 22 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD DEC PY 2008 VL 196 IS 12 BP 912 EP 918 DI 10.1097/NMD.0b013e31818ec95d PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 383DE UT WOS:000261653500008 PM 19077859 ER PT J AU Kim, SP Simeral, JD Hochberg, LR Donoghue, JP Black, MJ AF Kim, Sung-Phil Simeral, John D. Hochberg, Leigh R. Donoghue, John P. Black, Michael J. TI Neural control of computer cursor velocity by decoding motor cortical spiking activity in humans with tetraplegia SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID PRIMATE PRIMARY MOTOR; FREE ARM MOVEMENTS; 3-DIMENSIONAL SPACE; INTERNAL-MODELS; VISUAL TARGETS; CELL DISCHARGE; KALMAN FILTER; CORTEX; POPULATION; DIRECTION AB Computer-mediated connections between human motor cortical neurons and assistive devices promise to improve or restore lost function in people with paralysis. Recently, a pilot clinical study of an intracortical neural interface system demonstrated that a tetraplegic human was able to obtain continuous two-dimensional control of a computer cursor using neural activity recorded from his motor cortex. This control, however, was not sufficiently accurate for reliable use in many common computer control tasks. Here, we studied several central design choices for such a system including the kinematic representation for cursor movement, the decoding method that translates neuronal ensemble spiking activity into a control signal and the cursor control task used during training for optimizing the parameters of the decoding method. In two tetraplegic participants, we found that controlling a cursor's velocity resulted in more accurate closed-loop control than controlling its position directly and that Cursor velocity control was achieved more rapidly than position control. Control quality was further improved over conventional linear filters by using a probabilistic method, the Kalman filter, to decode human motor cortical activity. Performance assessment based on standard metrics used for the evaluation of a wide range of pointing devices demonstrated significantly improved cursor control with velocity rather than position decoding. C1 [Kim, Sung-Phil; Black, Michael J.] Brown Univ, Dept Comp Sci, Providence, RI 02912 USA. [Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.] Ctr Restorat & Regenerat Med, Rehabil R&D Serv, Dept Vet Affairs, Providence, RI 02912 USA. [Simeral, John D.; Hochberg, Leigh R.; Donoghue, John P.] Brown Univ, Dept Neurosci, Providence, RI 02912 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. [Hochberg, Leigh R.] Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. [Donoghue, John P.] Cyberkinet Neurotechnol Syst Inc, Foxboro, MA 02035 USA. RP Kim, SP (reprint author), Brown Univ, Dept Comp Sci, Box 1910,115 Waterman St, Providence, RI 02912 USA. EM spkim@cs.brown.edu; black@cs.brown.edu OI Hochberg, Leigh/0000-0003-0261-2273 FU NIH-NINDS [R01 NS 50867-01, NS25074]; Katie Sarnson Foundation; Office of Naval Research [N0014-04-1-082, N0014-07-1-0803]; European Neurobotics Program [FP6-IST-001917]; Rehabilitation Research and Development Service, Department of Veterans Affairs FX This work is partially supported by NIH-NINDS R01 NS 50867-01 as part of the NSF/NIH Collaborative Research in Computational Neuroscience Program, NIH-NINDS NS25074, the Katie Sarnson Foundation, and by the Office of Naval Research (awards N0014-04-1-082 and N0014-07-1-0803). This material is based upon work supported in part by the Office of Research and Development, Rehabilitation R&D Service, Department of Veterans Affairs (JDS, LRH). We also thank the European Neurobotics Program FP6-IST-001917 and Rehabilitation Research and Development Service, Department of Veterans Affairs. The clinical trial from which these data are derived is sponsored by Cyberkinetics Neurotechnology Systems, Inc. We thank Gregory Shakhnarovich, Frank Wood and Wilson Truccolo for comments and assistance. We also thank Abe Caplan, Eric Peterson, Michael Fritz and Cyberkinetics Neurotechnology Systems. Inc. for running the recording sessions described here. NR 49 TC 155 Z9 157 U1 1 U2 17 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD DEC PY 2008 VL 5 IS 4 BP 455 EP 476 DI 10.1088/1741-2560/5/4/010 PG 22 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 388LD UT WOS:000262020400010 PM 19015583 ER PT J AU Liu, Y Dinkin, MJ Loewenstein, JI Rizzo, JF Cestari, DM AF Liu, Yao Dinkin, Marc J. Loewenstein, John I. Rizzo, Joseph F., III Cestari, Dean M. TI Multifocal Electroretinographic Abnormalities in Ethambutol-Induced Visual Loss SO JOURNAL OF NEURO-OPHTHALMOLOGY LA English DT Article ID TOXICITY AB Two patients who developed decreased visual acuity after several months of ethambutol treatment for Mycobacterium avium-intracellulare infection had bitemporal visual field defects that suggested optic chiasm damage. Multifocal electroretinography (mfERG) disclosed markedly low-amplitude responses at fixation and in the regions corresponding to the visual field defects. These results suggested that the visual dysfunction might be entirely attributable to retinal rather than optic nerve toxicity. These are the first reported patients to show mfERG abnormalities that correspond to bitemporal visual field defects and add to the growing evidence that ethambutol damages the retina. C1 [Cestari, Dean M.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Neuroophthalmol,Neuroophthalmol Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv DMP, Boston, MA 02114 USA. [Dinkin, Marc J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Cestari, DM (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Neuroophthalmol,Neuroophthalmol Serv, 243 Charles St,9th Floor Massachusetts Eye & Ear, Boston, MA 02114 USA. EM dean_cestari@meei.harvard.edu NR 8 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-8022 J9 J NEURO-OPHTHALMOL JI J. Neuro-Ophthal. PD DEC PY 2008 VL 28 IS 4 BP 278 EP 282 PG 5 WC Clinical Neurology; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 380BI UT WOS:000261440100003 PM 19145124 ER PT J AU Theodore, S Cao, S McLean, PJ Standaert, DG AF Theodore, Shaji Cao, Shuwen McLean, Pamela J. Standaert, David G. TI Targeted Overexpression of Human alpha-Synuclein Triggers Microglial Activation and an Adaptive Immune Response in a Mouse Model of Parkinson Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Adeno-associated virus; Dopamine; Glia; Immunoglobulin; Lymphocytes; Neurodegeneration; Neuroinflammation ID ADENOASSOCIATED VIRUS TYPE-2; MEDIATED GENE-TRANSFER; CENTRAL-NERVOUS-SYSTEM; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; ALTERNATIVE ACTIVATION; REACTIVE MICROGLIA; PROTEIN-KINASE; LEWY BODIES; CELL INJURY AB Microglial activation and adaptive immunity have been implicated in the neurodegenerative processes in Parkinson disease. It has been proposed that these responses may be triggered by modified forms of alpha-synuclein (alpha-SYN), particularly nitrated species, which are released as a consequence of dopaminergic neurodegeneration. To examine the relationship between alpha-SYN, microglial activation, Mouse model of Parkinson and adaptive immunity, We used a disease in which human alpha-SYN is overexpressed by a recombinant adeno-associated virus vector, serotype 2 (AAV2-SYN); this overexpression leads to slow degeneration of dopaminergic neurons. Microglial activation and components of the adaptive immune response were assessed using immunohistochemistry; quantitative polymerase chain reaction was used to examine cytokine expression. Four weeks after injection, there was a marked increase in CD68-positive microglia and greater infiltration of B and T lymphocytes in the substantia nigra pars compacta of the AAV2-SYN group than in controls. At 12 weeks, CD68 staining declined, but B- and T-cell infiltration persisted. Expression of proinflammatory cytokines was enhanced, whereas markets of alternative activation (i.e. arginase I and interleukins 4 and 13) were not altered. Increased immunoreactivity activity for mouse immunoglobulin was detected at all time points in the AAV2-SYN animals. These data show that overexpression of alpha-SYN alone, in the absence of overt neurodegeneration, is sulficient to trigger neuroinflammation with both microglial activation and stimulation of adaptive immunity. C1 [Theodore, Shaji; Cao, Shuwen; Standaert, David G.] Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, Birmingham, AL 35294 USA. [McLean, Pamela J.] Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. RP Standaert, DG (reprint author), Univ Alabama, Ctr Neurodegenerat & Expt Therapeut, 1719 6th Ave S,CIRC 516, Birmingham, AL 35294 USA. EM dstandaert@uab.edu RI Cao, Shuwen/E-1924-2016 FU National Institutes of Health [P50 NS38372, P30 NS057098]; American Parkinson's Disease Association FX This work was supported by the National Institutes of Health (Grant No. P50 NS38372 and P30 NS057098) and by the American Parkinson's Disease Association. NR 63 TC 93 Z9 98 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2008 VL 67 IS 12 BP 1149 EP 1158 DI 10.1097/NEN.0b013e31818e5e99 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 378VH UT WOS:000261352100004 PM 19018246 ER PT J AU Freeman, SH Kandel, R Cruz, L Rozkalne, A Newell, K Frosch, MP Hedley-Whyte, ET Locascio, JJ Lipsitz, LA Hyman, BT AF Freeman, Stefanie H. Kandel, Ruth Cruz, Luis Rozkalne, Anete Newell, Kathy Frosch, Matthew P. Hedley-Whyte, E. Tessa Locascio, Joseph J. Lipsitz, Lewis A. Hyman, Bradley T. TI Preservation of Neuronal Number Despite Age-Related Cortical Brain Atrophy in Elderly Subjects Without Alzheimer Disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Aging; Cerebral cortex; Neurons; Stereology ID HUMAN CEREBRAL-CORTEX; RHESUS-MONKEY; HUMAN NEOCORTEX; GRAY-MATTER; IN-VIVO; LAYER 1; DECLINE; MRI AB Cerebral volume loss has long been associated with normal aging, bill Whether this is due to aging itself or to age-related diseases, including incipient Alzheimer disease, is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathologic diagnosis of, Alzheimer disease or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. we used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age, but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant during a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons. underlies neocortical volume loss with increasing age in the absence of Alzheimer disease. C1 [Freeman, Stefanie H.; Frosch, Matthew P.; Hedley-Whyte, E. Tessa; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Pathol, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. [Freeman, Stefanie H.; Rozkalne, Anete; Frosch, Matthew P.; Locascio, Joseph J.; Hyman, Bradley T.] Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Alzheimer Res Unit, Boston, MA 02114 USA. [Kandel, Ruth; Lipsitz, Lewis A.] Harvard Univ, Sch Med, Hebrew Senior Life & Beth Israel Deaconess Med Ct, Boston, MA USA. [Cruz, Luis] Boston Univ, Ctr Polymer Studies, Dept Phys, Boston, MA 02215 USA. [Newell, Kathy] Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66103 USA. [Locascio, Joseph J.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Freeman, SH (reprint author), 200 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM freestefanie@gmail.com RI Cruz Cruz, Luis/B-2685-2013 FU Massachusetts Alzheimer Disease Research Center [AG05134, AG09487, AG004390, R01-AG021133, R21-AG023661, R03-AG024633] FX Supportcd by Grant Nos. AG05134. AG09487, AG004390. R01-AG021133, R21-AG023661, and R03-AG024633 from the Massachusetts Alzheimer Disease Research Center. NR 35 TC 68 Z9 70 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD DEC PY 2008 VL 67 IS 12 BP 1205 EP 1212 DI 10.1097/NEN.0b013e31818fc72f PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 378VH UT WOS:000261352100009 PM 19018241 ER PT J AU Vincent, JL Kahn, I Snyder, AZ Raichle, ME Buckner, RL AF Vincent, Justin L. Kahn, Itamar Snyder, Abraham Z. Raichle, Marcus E. Buckner, Randy L. TI Evidence for a Frontoparietal Control System Revealed by Intrinsic Functional Connectivity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID ANTERIOR CINGULATE CORTEX; DEFAULT-MODE NETWORK; BOLD SIGNAL FLUCTUATIONS; HUMAN PREFRONTAL CORTEX; RESTING-STATE NETWORKS; HUMAN CEREBRAL-CORTEX; COGNITIVE CONTROL; MEMORY RETRIEVAL; EPISODIC MEMORY; WORKING-MEMORY AB Vincent JL, Kahn I, Snyder AZ, Raichle ME, Buckner RL. Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J Neurophysiol 100: 3328-3342, 2008. First published September 17, 2008; doi: 10.1152/jn.90355.2008. Two functionally distinct, and potentially competing, brain networks have been recently identified that can be broadly distinguished by their contrasting roles in attention to the external world versus internally directed mentation involving long-term memory. At the core of these two networks are the dorsal attention system and the hippocampal-cortical memory system, a component of the brain's default network. Here spontaneous blood-oxygenation-level-dependent ( BOLD) signal correlations were used in three separate functional magnetic resonance imaging data sets ( n = 105) to define a third system, the frontoparietal control system, which is spatially interposed between these two previously defined systems. The frontoparietal control system includes many regions identified as supporting cognitive control and decision-making processes including lateral prefrontal cortex, anterior cingulate cortex, and inferior parietal lobule. Detailed analysis of frontal and parietal cortex, including use of high-resolution data, revealed clear evidence for contiguous but distinct regions: in general, the regions associated with the frontoparietal control system are situated between components of the dorsal attention and hippocampal-cortical memory systems. The frontoparietal control system is therefore anatomically positioned to integrate information from these two opposing brain systems. C1 [Vincent, Justin L.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Vincent, Justin L.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Vincent, Justin L.; Snyder, Abraham Z.; Raichle, Marcus E.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Snyder, Abraham Z.; Raichle, Marcus E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. [Raichle, Marcus E.] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. [Raichle, Marcus E.] Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO USA. [Vincent, Justin L.; Kahn, Itamar; Buckner, Randy L.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. [Kahn, Itamar; Buckner, Randy L.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Vincent, JL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,WJH 274, Cambridge, MA 02138 USA. EM vincent@nmr.mgh.harvard.edu FU National Institutes of Health [AG-021910, NS-06833]; Mallinckrodt Institute of Radiology; AAMCBR; McDonnell Foundation; Howard Hughes Medical Institute FX This work was supported by National Institutes of Health Grants AG-021910 and NS-06833, the Mallinckrodt Institute of Radiology, AAMCBR, the James S McDonnell Foundation, and the Howard Hughes Medical Institute. NR 97 TC 600 Z9 608 U1 18 U2 74 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD DEC PY 2008 VL 100 IS 6 BP 3328 EP 3342 DI 10.1152/jn.90355.2008 PG 15 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 380EQ UT WOS:000261449400030 PM 18799601 ER PT J AU McMurtray, AM Sultzer, DL Monserratt, L Yeo, T Mendez, MF AF McMurtray, Aaron M. Sultzer, David L. Monserratt, Lorena Yeo, Tuty Mendez, Mario F. TI Content-specific delusions from right caudate lacunar stroke: Association with prefrontal hypometabolism SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID NEURO-BEHAVIORAL CHANGES; BASAL GANGLIA; COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; LESIONS; INFARCTS; DEMENTIA; CIRCUITS; NUCLEUS; CORTEX AB Patients with caudate lesions can present with content-specific delusions, possibly due to disruption of frontosubcortical circuits connecting the frontal lobes with the basal ganglia. This study included eight patients who presented with content-specific delusions after right caudate stroke and an equal number of matched controls, without stroke or delusions. Compared to controls, patients with caudate lesions performed less well on tests of memory, abstract reasoning, and frontal executive functions, and had significantly reduced metabolism in the inferior prefrontal cortex. These patients suggest an etiological relationship between alterations in inferior prefrontal functions and the development of content-specific delusions. C1 [McMurtray, Aaron M.; Sultzer, David L.; Monserratt, Lorena; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Neurol Serv, Los Angeles, CA 90073 USA. [McMurtray, Aaron M.; Sultzer, David L.; Monserratt, Lorena; Mendez, Mario F.] VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Psychiat & Mental Hlth Serv, Los Angeles, CA 90073 USA. [McMurtray, Aaron M.; Sultzer, David L.; Monserratt, Lorena; Yeo, Tuty; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [McMurtray, Aaron M.; Sultzer, David L.; Monserratt, Lorena; Yeo, Tuty; Mendez, Mario F.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. RP Mendez, MF (reprint author), VA Greater Los Angeles Healthcare Syst, Neurobehav Unit 116AF, Neurol Serv, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmendez@ucla.edu FU PHS HHS [R01 56031] NR 31 TC 11 Z9 11 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD WIN PY 2008 VL 20 IS 1 BP 62 EP 67 DI 10.1176/appi.neuropsych.20.1.62 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 264SP UT WOS:000253311000006 PM 18305285 ER PT J AU McQueen, M MacCollin, M Gusella, J Plotkin, SR AF McQueen, Mary MacCollin, Mia Gusella, James Plotkin, Scott R. TI Patient and Physician Attitudes Regarding Clinical Trials in Neurofibromatosis 1 SO JOURNAL OF NEUROSCIENCE NURSING LA English DT Article AB Neurofibromatosis 1 (NF1) is a multisystem genetic disorder that primarily affects the skin (freckling and cafe-au-lait macules), nervous system (neurofibromas, optic gliomas, and learning disabilities), and skeletal system (pseudoarthroses). The interest in pharmacological intervention for patients with NF1 has grown in recent years. However, little is known about the attitudes and priorities of patients, families, and physicians regarding participation in clinical trials. We surveyed 74 adult patients or parents of patients with NF1 and 69 care providers participating in a neurofibromatosis clinic to assess their willingness to participate in clinical trials and their opinions about which conditions they thought were most important to treat. Both patients and care providers are willing to participate in clinical trials for NF1 and both groups rate malignant peripheral nerve sheath tumors as the most urgent for new treatments. There are concordant views among patients and physicians concerning clinical trials for NF1, and patients do not dismiss participation in placebo-controlled trials. Neuroscience nurses are poised to facilitate the research process from conception through implementation as they take the viewpoints of our study populations into consideration. C1 [MacCollin, Mia; Plotkin, Scott R.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [McQueen, Mary] Univ Colorado, Wardenburg Hlth Ctr, Boulder, CO 80309 USA. [Gusella, James] Harvard Univ, Sch Med, Ctr Neurofibromatosis & Allied Disorders, Boston, MA USA. [Gusella, James] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM splotkin@partners.org FU Neurofibromatosis Inc., New England; Alsam Foundation FX This work was supported by grants to James Gusella, PhD, from Neurofibromatosis Inc., New England, and from the Alsam Foundation. NR 10 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0888-0395 J9 J NEUROSCI NURS JI J. Neurosci. Nurs. PD DEC PY 2008 VL 40 IS 6 BP 341 EP 345 PG 5 WC Clinical Neurology; Nursing SC Neurosciences & Neurology; Nursing GA V13AM UT WOS:000207639700005 PM 19170300 ER PT J AU Ahmad, M Rose, ME Vagni, V Griffith, RP Dixon, CE Kochanek, PM Hickey, RW Graham, SH AF Ahmad, Muzamil Rose, Marie E. Vagni, Vincent Griffith, Raymond P. Dixon, C. Edward Kochanek, Patrick M. Hickey, Robert W. Graham, Steven H. TI Genetic Disruption of Cyclooxygenase-2 Does Not Improve Histological or Behavioral Outcome After Traumatic Brain Injury in Mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE cyclooxygenase; prostaglandin E(2); TUNEL staining; behavior; Morris water maze ID CELL-DEATH; INHIBITOR ROFECOXIB; COX-2 INHIBITORS; IN-SITU; RATS; EXPRESSION; CELECOXIB; INFLAMMATION; NEURONS; EDEMA AB Increasing evidence suggests a role for cyclooxygenase-2 (COX-2) in traumatic brain injury (TBI). In the present study, the role of COX-2 in TBI was investigated using COX-2 gene-disrupted (COX-2 null) mice and wild-type (WT) controls that were subjected to the controlled cortical impact (CCI) model of TBI. There was increased expression of COX-2 in ipsilateral hippocampus in WT mice subjected to CCI. CCI resulted in a significant increase in prostaglandin E(2) concentrations in WT compared with COX-2 null hippocampi. There was a significant increase in TUNEL staining of CA1 neurons 24 hr after CCI in WT, but not in COX-2 null mice, compared with sham-operated controls, which is consistent with a protective role for COX-2 in the early phase of injury after TBI. However, there was no difference in lesion volume 21 days after CCI in COX-2 null and WT mice. COX-2 gene disruption did not alter Morris water maze performance. Taken together, these results suggest only a minor role for COX-2 activity in determining outcome after TBI in mouse. (c) 2008 Wiley-Liss, Inc. C1 [Ahmad, Muzamil; Rose, Marie E.; Graham, Steven H.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15206 USA. [Ahmad, Muzamil; Rose, Marie E.; Graham, Steven H.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. [Vagni, Vincent; Kochanek, Patrick M.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA USA. [Griffith, Raymond P.; Dixon, C. Edward] Univ Pittsburgh, Sch Med, Dept Neurosurg, Pittsburgh, PA 15261 USA. [Kochanek, Patrick M.; Hickey, Robert W.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. RP Graham, SH (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 151-UH,7108 Highland Dr, Pittsburgh, PA 15206 USA. EM sgra@pitt.edu RI Kochanek, Patrick/D-2371-2015 OI Kochanek, Patrick/0000-0002-2627-913X FU Department of Veterans Affairs/Department of Defense; Traumatic Brain Injury Initiative Merit Review Program; NIH [R01 NS37459] FX Contract grant sponsor: Department of Veterans Affairs/Department of Defense, Traumatic Brain Injury Initiative Merit Review Program (to S.H.G.); Contract grant sponsor: NIH; Contract grant number: R01 NS37459 (to S.H.G.). NR 48 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC PY 2008 VL 86 IS 16 BP 3605 EP 3612 DI 10.1002/jnr.21809 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 383CO UT WOS:000261651900012 PM 18711748 ER PT J AU Susarla, SM Dodson, TB Kaban, LB AF Susarla, Srinivas M. Dodson, Thomas B. Kaban, Leonard B. TI Measurement and Interpretation of a Maxillary Occlusal Cant in the Frontal Plane SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID ASYMMETRY; EXPANSION AB Purpose: A cant of the maxillary intermolar (M1-M1) plane is a reflection of facial asymmetry and can be measured on an anterior-posterior cephalogram in degrees relative to the true horizontal or directly on the patient as the difference in millimeters between the right and left medial canthi to canine distances. The purpose of this study is to measure the correlation between the maxillary cant measured in degrees and measured in millimeters. Materials and Methods: We hypothesize that the number of degrees of maxillary cant equals the millimeter difference between the lengths of the 2 sides of the maxilla, based upon the trigonometric relationship between the degree of cant, vertical length, and M1-M1 distance. To confirm this hypothesis, we evaluated a range of M1-M1 distances and Computed the predicted vertical discrepancy between the 2 sides of the maxilla. Bivariate correlations were used to evaluate the association between the degree of cant and predicted vertical discrepancy. Results: In the range of M1-M1 distances (47.5-61.1 mm) evaluated, cants ranging from 3 to 10 degrees are highly correlated with the vertical difference in millimeters (r = 0.96 P < .01). The mean error between the degree of cant and vertical difference was 9%. Conclusion: The degrees Of occlusal cant relative to the true horizontal measured cephalometrically in the frontal plane is equal to the linear millimeter difference between the right and left medial canthi to the right and left canine tips. (C) 2008 American Association of Oral and Maxillofacial Surgeons C1 [Susarla, Srinivas M.; Kaban, Leonard B.] Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. [Dodson, Thomas B.] Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. [Dodson, Thomas B.] Massachusetts Gen Hosp, Ctr Appl Clin Invest, Boston, MA 02114 USA. RP Susarla, SM (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. EM smsusarla@gmail.com OI Susarla, Srinivas/0000-0003-0155-8260 FU Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation; Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund FX This study was made possible by Support from the Oral and Maxillofacial Surgery Foundation Fellowship in Clinical Investigation (S.M.S.) and the Massachusetts General Hospital Department of Oral and Maxillofacial Surgery Education and Research Fund (T.B.D., S.M.S.). NR 7 TC 7 Z9 7 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2008 VL 66 IS 12 BP 2498 EP 2502 DI 10.1016/j.joms.2008.06.072 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 378VB UT WOS:000261351400013 PM 19022130 ER PT J AU Peritz, DC Duncan, C Kurek, K Perez-Atayde, AR Lehmann, LE AF Peritz, David C. Duncan, Christine Kurek, Kyle Perez-Atayde, Antonio R. Lehmann, Leslie E. TI Visceral Varicella Zoster Virus (VZV) After Allogeneic Hematopoietic Stem Cell Transplant (HSCT) in Pediatric Patients With Chronic Graft-Versus-Host Disease (cGVHD) SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE hematopoietic stem cell transplant; reactivation of varicella zoster virus; allogeneic; chronic graft-versus-host disease; hyponatremia ID BONE-MARROW-TRANSPLANTATION; HERPES-ZOSTER; RISK-FACTORS; INFECTION; ACYCLOVIR; CHILDREN; INVOLVEMENT AB Reactivation of latent varicella zoster virus is one infectious complication associated with the extensive immuno-suppression necessary for hematopoietic stein cell transplant. Most cases are limited to skin and mortality is low. Isolated visceral zoster is rare, presenting with ileus/abdominal pain, hepatitis, and/or hyponatremia. We present 2 cases of visceral varicella zoster virus in adolescents with chronic graft-versus-host disease after hematopoietic stein cell transplant. Both presented with elevated liver enzymes, severe abdominal pain, and hyponatremia but lacked cutaneous involvement. Both received high-dose acyclovir and showed improvement, but eventually expired from hepatic failure. The diagnosis of visceral zoster can be difficult especially without cutaneous manifestations. Vigilance is necessary in patients with chronic graft-versus-host disease, abdominal pain, and/or hepatitis and antiviral therapy should be initiated promptly. C1 [Peritz, David C.; Duncan, Christine; Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kurek, Kyle; Perez-Atayde, Antonio R.] Childrens Hosp, Boston, MA 02115 USA. RP Peritz, DC (reprint author), 44 Binney St, Boston, MA 02115 USA. EM David_Peritz@dfci.harvard.edu NR 18 TC 10 Z9 10 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD DEC PY 2008 VL 30 IS 12 BP 931 EP 934 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 381DW UT WOS:000261516800016 PM 19131784 ER PT J AU Lovejoy, FH Nathan, DG Zuckerman, BS Pizzo, PA Fleisher, GR Vinci, RJ AF Lovejoy, Frederick H., Jr. Nathan, David G. Zuckerman, Barry S. Pizzo, Philip A. Fleisher, Gary R. Vinci, Robert J. TI The Merger of Two Pediatric Residency Programs: Lessons Learned SO JOURNAL OF PEDIATRICS LA English DT Editorial Material C1 [Lovejoy, Frederick H., Jr.; Pizzo, Philip A.; Fleisher, Gary R.] Childrens Hosp, Dept Med, Boston, MA 02115 USA. [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zuckerman, Barry S.; Vinci, Robert J.] Boston Med Ctr, Dept Pediat, Boston, MA USA. [Pizzo, Philip A.] Stanford Med Sch, Palo Alto, CA USA. RP Lovejoy, FH (reprint author), Childrens Hosp, Dept Med, 300 Longwood Ave,Hunnewell 2, Boston, MA 02115 USA. EM lovejoy@tch.harvard.edu OI Vinci, Robert/0000-0002-2616-1879; Zuckerman, Barry/0000-0002-0044-2592 NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR JI J. Pediatr. PD DEC PY 2008 VL 153 IS 6 BP 731 EP 732 DI 10.1016/j.jpeds.2008.07.036 PG 2 WC Pediatrics SC Pediatrics GA 383FK UT WOS:000261659300001 PM 19014810 ER PT J AU Cole, CM Sundararaj, KP Leite, RS Nareika, A Slate, EH Sanders, JJ Lopes-Virella, MF Huang, Y AF Cole, C. M. Sundararaj, K. P. Leite, R. S. Nareika, A. Slate, E. H. Sanders, J. J. Lopes-Virella, M. F. Huang, Y. TI A trend of increase in periodontal interleukin-6 expression across patients with neither diabetes nor periodontal disease, patients with periodontal disease alone, and patients with both diseases SO JOURNAL OF PERIODONTAL RESEARCH LA English DT Article DE periodontal diseases; diabetes mellitus; interleukin-6; gene expression ID INFLAMMATION; MEDIATOR AB Epidemiological studies have established that patients with diabetes have increased prevalence and severity of periodontal disease. However, the periodontal expression of inflammatory cytokines and matrix metalloproteinases (MMPs) in diabetic patients has not been well characterized. The objective of this study was to determine the difference in the periodontal expression of MMP-1, MMP-8, interleukin-6, tumor necrosis factor-alpha and interleukin-1 beta between diabetic and nondiabetic patients. Periodontal tissue specimens were collected from nine nondiabetic patients without periodontal disease (group 1), from 11 nondiabetic patients with periodontal disease (group 2) and from seven diabetic patients with periodontal disease (group 3). The expression of MMP-1, MMP-8, interleukin-6, tumor necrosis factor-alpha and interleukin-1 beta was quantified using real-time polymerase chain reaction. The nonparametric Kruskal-Wallis test showed that the difference in interleukin-6 expression among the groups was statistically significant (p = 0.04). Furthermore, the generalized Kruskal-Wallis nonparametric linear-by-linear association test showed a statistically significant trend of increase in the expression of interleukin-6 from group 1 to group 2 to group 3 (p = 0.02) and a suggestion of such a trend for MMP-1 (p = 0.05). No increase in MMP-8 expression was observed in patients in group 3 compared to patients in groups 1 and 2. Although the average expression levels of MMP-1, interleukin-1 beta and tumor necrosis factor-alpha were increased from group 1 to group 3, the differences were not statistically significant. A trend of increased interleukin-6 expression in periodontal tissues was observed across patients with neither diabetes nor periodontal disease, patients with periodontal disease alone, and patients with both diseases. C1 [Cole, C. M.; Leite, R. S.; Sanders, J. J.] Med Univ S Carolina, Div Periodont, Dept Stomatol, Coll Dent Med, Charleston, SC 29403 USA. [Sundararaj, K. P.; Nareika, A.; Lopes-Virella, M. F.; Huang, Y.] Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29403 USA. [Slate, E. H.] Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA. [Lopes-Virella, M. F.; Huang, Y.] Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Huang, Y (reprint author), Med Univ S Carolina, Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu FU NIH [DE16353]; NIH/NCRR COBRE [P20 RR017696] FX This work was supported by NIH grant DE16353 and a Merit Review Grant from the Department of Veterans Affairs (to YH). EHS, JJS, SDL and MFL-V additionally acknowledge partial support from the NIH/NCRR COBRE project P20 RR017696. NR 28 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3484 J9 J PERIODONTAL RES JI J. Periodont. Res. PD DEC PY 2008 VL 43 IS 6 BP 717 EP 722 DI 10.1111/j.1600-0765.2008.01082.x PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 374TZ UT WOS:000261067900016 PM 18627438 ER PT J AU Claude, O Picard, A O'Sullivan, N Baccache, S Momtchilova, M Enjolras, O Vazquez, MP Diner, PA AF Claude, O. Picard, A. O'Sullivan, N. Baccache, S. Momtchilova, M. Enjolras, O. Vazquez, M. P. Diner, P. A. TI Use of ultrasonic dissection in the early surgical management of periorbital haemangiomas SO JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY LA English DT Article DE Haemangioma; Periorbital; Ultrasonic scalpel; Dissectron (R); Amblyopia ID INTRALESIONAL CORTICOSTEROID INJECTION; CAPILLARY HEMANGIOMAS; VASCULAR MALFORMATIONS; CUTANEOUS HEMANGIOMAS; INFANTILE HEMANGIOMA; ADRENAL SUPPRESSION; ARTERY-OCCLUSION; LASER TREATMENT; THERAPY; INFANCY AB Purpose: To evaluate the efficacy and safety of the early surgical excision of periorbital haemangiomas with an ultrasonic scalpel in infants at risk of visual impairment. Study: A retrospective analysis of 67 infants diagnosed to be at risk of amblyopia from periorbital haemangiomas, treated consecutively with the Dissectron (R) between 1994 and 2005. Ophthalmic outcome parameters included the pre- and postoperative measurement of visual axis occlusion, strabismus, astigmatism, and degree of amblyopia. Results: Visual performance showed an overall improvement of 30% following treatment. Seventy-six patients were found to have abnormal ophthalmic examinations preoperatively, compared to 46 following surgery. After surgery, visual axis occlusion decreased from 73 to 6%; amblyopia decreased from 67 to 22%, strabismus decreased from 26 to 18% and astigmatism (>one dioptre) decreased from 66 to 31 %. Mean astigmatism values decreased from 3.5 to 1.9 dioptres. No new cases of astigmatism, strabismus or amblyopia were diagnosed postoperativeiy. Three minor complications resolved with conservative treatment. All patients were satisfied with the outcome of their surgery. Conclusion: Early surgical excision of periorbital haemangiomas using the Dissectron (R) in infants with an established risk of visual impairment is a safe and effective alternative to pharmacological therapy. The use of the Dissectron (R) is associated with reduced operative times and a shorter hospital stay. (C) 2007 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. C1 [Claude, O.; Picard, A.; Baccache, S.; Enjolras, O.; Vazquez, M. P.; Diner, P. A.] Univ Paris 06, Children Hosp Armand Trousseau, INSERM, U714,Dept Plast & Maxillofacial Surg, F-75012 Paris, France. [O'Sullivan, N.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Plast Surg Res Lab, Boston, MA 02114 USA. [Momtchilova, M.] Univ Paris 06, Children Hosp Armand Trousseau, Dept Ophthalmol, F-75012 Paris, France. RP Claude, O (reprint author), Univ Paris 06, Children Hosp Armand Trousseau, INSERM, U714,Dept Plast & Maxillofacial Surg, 26 Rue Docteur Arnold Netter, F-75012 Paris, France. EM olivier_claude@hotmail.com NR 35 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1748-6815 J9 J PLAST RECONSTR AES JI J. Plast. Reconstr. Aesthet. Surg. PD DEC PY 2008 VL 61 IS 12 BP 1479 EP 1485 DI 10.1016/j.bjps.2007.09.027 PG 7 WC Surgery SC Surgery GA 381EI UT WOS:000261518000009 PM 18037085 ER PT J AU Greer, JA Pirl, WF Park, ER Lynch, TJ Ternel, JS AF Greer, Joseph A. Pirl, William F. Park, Elyse R. Lynch, Thomas J. Ternel, Jennifer S. TI Behavioral and psychological predictors of chemotherapy adherence in patients with advanced non-small cell lung cancer SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Non-small cell lung cancer; Chemotherapy; Adherence ID QUALITY-OF-LIFE; DEPRESSION; SURVIVAL; DISTRESS; SMOKING; ANXIETY; SCALE AB Objective: Dose delays and reductions in chemotherapy due to hematologic toxicities are common among patients with advanced non-small cell lung cancer (NSCLC). However, limited data on behavioral or psychological predictors of chemotherapy adherence exist. The goal of this study was to explore the frequency and clinical predictors of infusion dose delays and reductions in this patient population. Methods: Fifty patients newly diagnosed with advanced NSCLC of high performance status (Eastern Cooperative Oncology Group Performance Status=0-1) completed baseline assessments on quality of life (Functional Assessment of Cancer Therapy - Lung) and mood (Hospital Anxiety and Depression Scale) within 8 weeks of diagnosis. Participants were followed prospectively for 6 months. Chemotherapy dosing data came from medical chart review. Results: All patients received chemotherapy during the course of the study, beginning with a platinum-based doublet (74%), an oral epidermal growth factor receptor-tyrosine kinase inhibitor (14%), or a parenteral single agent (12%). Forty percent (n=20) of patients had a dose delay (39%) and/or reduction (16%) in their scheduled infusions. Fisher's Exact Tests and regression analyses showed that patients who experienced neutropenia, smoked at the time of diagnosis, or reported heightened baseline anxiety were significantly more likely to experience dose delays or reductions. There were no associations between chemotherapy adherence and patient demographics, performance status, or quality of life. Conclusion: In this sample, more than one third of patients with advanced NSCLC experienced either a dose delay or reduction in prescribed chemotherapy regimens. Behavioral and psychological factors, such as tobacco use and anxiety symptoms, appear to play an important role in chemotherapy adherence, though further study is required to confirm these findings. (C) 2008 Elsevier Inc. All rights reserved. C1 [Greer, Joseph A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Greer, JA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. EM jgreer2@partners.org FU NIH/NCI [R03 CA129478, K23 CA115908]; Amgen (Temel) FX This work was supported by NIH/NCI R03 CA129478 (Greer), NIH/NCI K23 CA115908 (Pirl), and an investigator-initiated research grant from Amgen (Temel). NR 16 TC 41 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 2008 VL 65 IS 6 BP 549 EP 552 DI 10.1016/j.jpsychores.2008.03.005 PG 4 WC Psychiatry SC Psychiatry GA 382RK UT WOS:000261622900006 PM 19027443 ER PT J AU Huffman, JC Smith, FA Blais, MA Januzzi, JL Fricchione, GL AF Huffman, Jeff C. Smith, Felicia A. Blais, Mark A. Januzzi, James L. Fricchione, Gregory L. TI Anxiety, independent of depressive symptoms, is associated with in-hospital cardiac complications after acute myocardial infarction SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE Anxiety; Depression; Depressive disorder, major; Myocardial infarction ID CORONARY-ARTERY-DISEASE; PRIMARY-CARE PATIENTS; HEART-DISEASE; CARDIOVASCULAR-DISEASE; MAJOR DEPRESSION; CHEST-PAIN; TASK-FORCE; EVENTS; IMPACT; DISORDERS AB Objective: Post-myocardial infarction (MI) anxiety, independent of demographic and medical variables, has been linked to in-hospital cardiac complications in prior studies, but such studies have not included a concomitant assessment of depressive symptoms. The aim of this exploratory study was to determine whether post-MI anxiety was associated with in-hospital cardiac complications, independent of depressive symptoms. Methods: Subjects within 72 hours of acute MI (n=110) were prospectively assessed for anxiety [using the Beck Anxiety Inventory (BAI)] and depressive symptoms (using the Beck Depression Inventory-II and structured interview diagnoses of major depressive disorder). Individual in-hospital complications and pooled serious cardiac complications (defined as recurrent ischemia, reinfarction, congestive heart failure, and ventricular arrhythmia requiring intervention) were recorded via chart review. Results: On hierarchical multiple logistic regression analysis that accounted for demographic variables, cardiac illness, and depressive symptoms, post-MI anxiety was significantly associated with pooled serious in-hospital cardiac complications (P=.003). In addition, when the anxiety measure was limited to only the psychological symptoms of anxiety ("BAI-P"), post-MI anxiety remained an independent predictor of cardiac complications (P=.015). Conclusions: These findings suggest that the association of post-MI anxiety with in-hospital cardiac complications exists above and beyond the effects of depression. Larger studies are needed to confirm these findings, and treatment studies are needed to determine the impact of anxiety treatment on in-hospital cardiac outcomes. (C) 2008 Elsevier Inc. All rights reserved. C1 [Huffman, Jeff C.; Smith, Felicia A.; Blais, Mark A.; Fricchione, Gregory L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Januzzi, James L.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Huffman, Jeff C.; Smith, Felicia A.; Blais, Mark A.; Januzzi, James L.; Fricchione, Gregory L.] Harvard Univ, Sch Med, Boston, MA USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Warren 1220C, Boston, MA 02114 USA. EM jhuffman@partners.org FU Kaplen Fellowship Award; Livingston Fellowship Award; Harvard Medical School, Boston, MA, USA FX The authors would like to thank Sara Nadelman for her editorial assistance. This study was supported by the Kaplen Fellowship Award Grant and the Livingston Fellowship Award Grant, both through Harvard Medical School, Boston, MA, USA. NR 43 TC 37 Z9 42 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 2008 VL 65 IS 6 BP 557 EP 563 DI 10.1016/j.jpsychores.2008.08.001 PG 7 WC Psychiatry SC Psychiatry GA 382RK UT WOS:000261622900008 PM 19027445 ER PT J AU Maserejian, NN Tavares, MA Hayes, C Soncini, JA Trachtenberg, FL AF Maserejian, Nancy Nairi Tavares, Mary A. Hayes, Catherine Soncini, Jennifer A. Trachtenberg, Felicia L. TI Rural and urban disparities in caries prevalence in children with unmet dental needs: The New England Children's Amalgam Trial SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE dental caries; child; rural health; urban health; oral health; New England; zero-inflated models ID ZERO-INFLATED POISSON; ORAL-HEALTH-STATUS; EPIDEMIOLOGY; DETERMINANTS; CONSUMPTION; ADOLESCENTS; ADULTS AB Objectives: To compare the prevalence of caries between rural and urban children with unmet dental health needs who participated in the New England Children's Amalgam Trial. Methods: Baseline tooth and surface caries were clinically assessed in children from rural Maine (n = 243) and urban Boston (n = 291), who were aged 6 to 10 years, with two or more posterior carious teeth and no previous amalgam restorations. Statistical analyses used negative binomial models for primary dentition caries and zero-inflated models for permanent dentition caries. Results: Urban children had a higher mean number of carious primary surfaces (8.5 versus 7.4) and teeth (4.5 versus 3.9) than rural children. The difference remained statistically significant after adjusting for sociodemographic factors and toothbrushing frequency. In permanent dentition, urban children were approximately three times as likely to have any carious surfaces or teeth. However, rural/urban dwelling was not statistically significant in the linear analysis of caries prevalence among children with any permanent dentition caries. Covariates that were statistically significant in all models were age and number of teeth. Toothbrushing frequency was also important for permanent teeth. Conclusions: Within this population of New England children with unmet oral health needs, significant differences were apparent between rural and urban children in the extent of untreated dental decay. Results indicate that families who agree to participate in programs offering reduced cost or free dental care may present with varying amounts of dental need based on geographic location. C1 [Maserejian, Nancy Nairi; Trachtenberg, Felicia L.] New England Res Inst, Watertown, MA 02472 USA. [Tavares, Mary A.; Soncini, Jennifer A.] Forsyth Inst, Boston, MA USA. [Hayes, Catherine] Tufts Univ, Sch Med, Dept Publ Hlth, Boston, MA 02111 USA. [Hayes, Catherine] Tufts Univ, Sch Med, Community Serv, Boston, MA 02111 USA. [Soncini, Jennifer A.] Boston Univ, Sch Dent Med, Dept Pediat Dent, Boston, MA 02215 USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU NIDCR NIH HHS [U01 DE11886] NR 31 TC 8 Z9 8 U1 0 U2 3 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2008 VL 68 IS 1 BP 7 EP 13 DI 10.1111/j.1752-7325.2007.00057.x PG 7 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 275TR UT WOS:000254095000002 PM 18179469 ER PT J AU Maserejian, NN Trachtenberg, F Hayes, C Tavares, M AF Maserejian, Nancy Nairi Trachtenberg, Felicia Hayes, Catherine Tavares, Mary TI Oral health disparities in children of immigrants: Dental caries experience at enrollment and during follow-up in the New England Children's Amalgam Trial SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE immigrants; dental care for children; pediatric dentistry; health services delivery; public health dentistry; caries; incidence; disparities ID SWEDEN; ACCULTURATION; PREVALENCE; FAMILIES; SERVICE; AGE AB Objectives: Previous research shows increased dental decay among immigrants, but little is known about the oral health of the growing population of children of immigrants. We compared the children of immigrants to the children of US-born caregivers in their caries experience at enrollment and their new caries increments during the 5-year New England Children's Amalgam Trial (NECAT). Methods: NECAT recruited 283 Boston-area children aged 6 to 10 with untreated caries and offered free semiannual preventive and restorative dental care during the trial. Sociodemographic factors and caregiver immigrant status were assessed through interviews. Multivariate negative binomial models evaluated the association between caregiver immigrant status and clinically assessed carious surfaces. Results: Forty percent of these Boston-area children had immigrant caregivers. At baseline, the children of immigrants had more carious surfaces (11.5 versus 9.4, adjusted for race/ethnicity, age, gender, and caregiver smoking status). Caregiver language preference explained some of this association. Immigrant status and language preference were not associated with 5-year caries increments. Conclusions: Prevalent disparities in the unmet dental needs of the immigrants' children were quickly ameliorated during participation in NECAT. Dental initiatives that target neighborhoods and are sensitive to acculturation levels may help improve and maintain the oral health of immigrant families. C1 [Maserejian, Nancy Nairi; Trachtenberg, Felicia] New England Res Inst, Watertown, MA 02472 USA. [Hayes, Catherine] Tufts Univ, Sch Dent Med, Dept Publ Hlth, Boston, MA 02111 USA. [Hayes, Catherine] Tufts Univ, Sch Dent Med, Community Serv, Boston, MA 02111 USA. [Tavares, Mary] Forsyth Inst, Boston, MA USA. RP Maserejian, NN (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM nmaserejian@neriscience.com FU NIDCR NIH HHS [U01 DE11886] NR 25 TC 14 Z9 15 U1 0 U2 2 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD WIN PY 2008 VL 68 IS 1 BP 14 EP 21 DI 10.1111/j.1752-7325.2007.00060.x PG 8 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 275TR UT WOS:000254095000003 PM 18179466 ER PT J AU Pumbwe, L Curzon, M Wexler, HM AF Pumbwe, Lilian Curzon, Matthew Wexler, Hannah M. TI RAPID MULTIPLEX PCR ASSAY FOR SIMULTANEOUS DETECTION OF MAJOR ANTIBIOTIC RESISTANCE DETERMINANTS IN CLINICAL ISOLATES OF BACTEROIDES FRAGILIS SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article ID INDUCIBLE METRONIDAZOLE RESISTANCE; ANAEROBIC-BACTERIA; CONJUGATIVE TRANSPOSON; NIM GENES; SUSCEPTIBILITY; CLINDAMYCIN; PREVALENCE; SPP.; ERMF; CFIA AB This study developed a rapid and cost-effective multiplex polymerase chain reaction assay (M-PCR) for simultaneous detection of major clinically relevant antibiotic resistance genes in Bacteroides fragilis. The M-PCR optimized amplification conditions with primers designed for detection of five resistance genes: carbapenems (cfiA) and cephalosporins (cepA), clindamycin (ermF), metronidazole (nimA-F) and tetracycline (tetQ), plus a set of primers for the B. fragilis 16S rRNA gene (positive control). An initial single PCR was performed for each gene, followed by a gradient PCR to determine the optimal PCR conditions for each primer set. This was followed by several test M-PCRs using the Qiagen multiplex PCR kit (Valencia, CA) with 60 ng of a template DNA mastermix containing all genes of interest and 0.2 mu M of each primer set. Multiplex PCR products were detectable at annealing temperatures ranging from 53-57C for 30-35 cycles. The final optimized M-PCR was then used to evaluate 21 different B. fragilis isolates from various patients. Eleven different M-PCR genotypes were obtained, which correlated with phenotypic antibiograms and nitrocefin beta-lactamase production assays. This M-PCR provides an accurate, rapid, sensitive and cost-effective tool for detecting clinically relevant antibiotic resistance genes in B. fragilis, and owing to its high sensitivity, it could also be used to investigate the prevalence of such genetic determinants in mixed bacterial specimens. C1 [Pumbwe, Lilian; Wexler, Hannah M.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Pumbwe, Lilian; Curzon, Matthew; Wexler, Hannah M.] Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Pumbwe, L (reprint author), Wadsworth Anaerobe Lab, Bldg 304,Room E3-226, Los Angeles, CA 90073 USA. EM lilskil@ucla.edu FU Department of Veterans Affairs FX This study was supported by Merit Review Funds from the Department of Veterans Affairs. NR 28 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1060-3999 J9 J RAPID METH AUT MIC JI J Rapid Methods Autom. Microbiol. PD DEC PY 2008 VL 16 IS 4 BP 381 EP 393 DI 10.1111/j.1745-4581.2008.00143.x PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 378ZZ UT WOS:000261365100010 ER PT J AU Petri, M Naqibuddin, M Carson, KA Wallace, DJ Weisman, MH Holliday, SL Sampedro, M Narayana, S Fox, PT Franklin, C Padilla, PA Brey, RL AF Petri, Michelle Naqibuddin, Mohammad Carson, Kathryn A. Wallace, Daniel J. Weisman, Michael H. Holliday, Stephen L. Sampedro, Margaret Narayana, Shalini Fox, Peter T. Franklin, Crystal Padilla, Patricia A. Brey, Robin L. TI Brain Magnetic Resonance Imaging in Newly Diagnosed Systemic Lupus Erythematosus SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE SYSTEMIC LUPUS ERYTHEMATOSUS; MAGNETIC RESONANCE IMAGING; CEREBRALATROPHY ID OVERT NEUROPSYCHIATRIC MANIFESTATIONS; MULTIPLE-SCLEROSIS; ANTIPHOSPHOLIPID ANTIBODIES; ANTICARDIOLIPIN ANTIBODIES; REVISED CRITERIA; CEREBRAL ATROPHY; DISEASE-ACTIVITY; RATING-SCALE; MRI; CLASSIFICATION AB Objective. We wished to determine the prevalence of cerebral atrophy and focal lesions in a cohort of patients with newly diagnosed systemic lupus erythematosus (SLE) and the association of these brain abnormalities with clinical characteristics. Methods. A total of 97 patients with SLE, within 9 months of diagnosis, with 4 or more American College of Rheumatology classification criteria, were enrolled. Brain magnetic resonance imaging was performed. Results. The patients were 97% female. mean age 38.1 (SD 12.2) years, education 15.1 (2.8) years; 59 Caucasian, I I African American, 19 Hispanic, 5 Asian, and 3 other ethnicity. Cerebral atrophy was prevalent in 18% (95% Cl 11%-27%): mild in 12%, moderate in 5%. Focal lesions were prevalent in 8% (95% Cl 4%-16%): mild in 2%, moderate in 5%. severe in 1%. Patients with cerebral atrophy were more likely to have anxiety disorder (p = 0.04). Patients with focal lesions were more likely to be African American (p = 0.045) and had higher Safety of Estrogens in Lupus Erythematosus National Assessment SLEDAI scores (p = 0.02) and anti-dsDNA (p = 0.05). Conclusion. In this population with newly diagnosed SLE, brain abnormalities were prevalent in 25% of patients. These findings suggest that the brain may be affected extremely early in the course of SLE, even before the clinical diagnosis of SLE is made. Followup of these patients is planned. to determine the reversibility or progression of these abnormalities and their association with and potential predictive value for subsequent neuropsychiatric SLE manifestations. (First Release Sept 15 2008 J Rheumatol 200835:2348-54: doi: 10.3899/jrheum.071010) C1 [Petri, Michelle; Naqibuddin, Mohammad; Sampedro, Margaret] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Carson, Kathryn A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Wallace, Daniel J.; Weisman, Michael H.] Univ Calif Los Angeles, David Geffen Sch Med, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Holliday, Stephen L.] S Texas Vet Hlth Care Syst, Psychol Serv, San Antonio, TX USA. [Narayana, Shalini; Fox, Peter T.; Franklin, Crystal] Univ Texas Hlth Sci Ctr San Antonio, Res Imaging Ctr, San Antonio, TX 78229 USA. [Narayana, Shalini] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Padilla, Patricia A.; Brey, Robin L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Neurol, San Antonio, TX 78229 USA. RP Petri, M (reprint author), Johns Hopkins Univ, 1830 E Monument St,Suite 7500, Baltimore, MD 21205 USA. EM mpetri@jhmi.edu RI Fox, Peter/B-4725-2010; Narayana, Shalini/F-3031-2010 OI Fox, Peter/0000-0002-0465-2028; FU NIH [RO1-AR049125, AR043727]; Johns Hopkins University General Clinical Research Center [M01-RR00052]; University of Texas Health Science Center at San Antonio Frederic C. Bartter General Clinical Research Center [MOI-RR01346] FX The Brain CONECTIONS study is supported by NIH RO1-AR049125. AR043727. and the Johns Hopkins University General Clinical Research Center (K. Carson is supported by M01-RR00052) and the University of Texas Health Science Center at San Antonio Frederic C. Bartter General Clinical Research Center (MOI-RR01346). NR 53 TC 33 Z9 35 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2008 VL 35 IS 12 BP 2348 EP 2354 DI 10.3899/jrehum.071010 PG 7 WC Rheumatology SC Rheumatology GA 379XA UT WOS:000261428400013 PM 18793003 ER PT J AU Christie, M Mckenna, JT Connolly, NP Bolortuya, Y Mccarley, RW Strecker, RE AF Christie, M. Mckenna, J. T. Connolly, N. P. Bolortuya, Y. Mccarley, R. W. Strecker, R. E. TI The rat-psychomotor vigilance task: sleep disruption and basal forebrain adenosine dialysis SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 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 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 67 EP 67 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300161 ER PT J AU Fuller, CA Fuller, PM Robinson, EL AF Fuller, C. A. Fuller, P. M. Robinson, E. L. TI Blue light affects timing of sleep in rhesus monkeys but not sleep homeostasis SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 [Fuller, C. A.; Robinson, E. L.] Univ Calif Davis, Sect NPB, Davis, CA 95616 USA. [Fuller, P. M.] Harvard Univ, Sch Med, Dept Neurol, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 79 EP 79 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300192 ER PT J AU Roth, T Mccall, W Wessel, T Amato, D Paska, W Fava, M AF Roth, T. Mccall, W. Wessel, T. Amato, D. Paska, W. Fava, M. TI Eszopiclone co-administered with fluoxetine for insomnia co-existing with major depressive disorder (MDD): a subgroup analysis SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 [Roth, T.] Henry Ford Sleep Disorders Ctr, Detroit, MI USA. [Mccall, W.] Wake Forest Univ Hlth Sci, Winston Salem, NC 27109 USA. [Wessel, T.; Amato, D.] Sepracor Inc, Marlborough, MA USA. [Paska, W.] GlaxoSmithKline Inc, Greenford, Middx, England. [Fava, M.] 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 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 191 EP 192 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300534 ER PT J AU Fava, M Schaefer, K Rockett, CB Amato, D Roth, T AF Fava, M. Schaefer, K. Rockett, C. B. Amato, D. Roth, T. TI Differential sleep effects of eszopiclone treatment and discontinuation in patients with primary insomnia and insomnia co-existing with major depressive disorder (MDD) or generalized anxiety disorder (GAD) SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 [Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Roth, T.] Henry Ford Sleep Disorders Ctr, Detroit, MI USA. [Schaefer, K.; Amato, D.] Sepracor Inc, Marlborough, MA USA. [Rockett, C. B.] GlaxoSmithKline Inc, Durham, NC 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 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 192 EP 192 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300536 ER PT J AU Partinen, M Leger, D Hirshkowitz, M Chokroverty, S Hedner, J AF Partinen, M. Leger, D. Hirshkowitz, M. Chokroverty, S. Hedner, J. TI Frequency of insomnia symptoms in PCPS patients: results of the EQUINOX international survey SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 [Leger, D.] Physiol Explorat Fonct Ctr Sommeil, Hotel Dieu, Paris, France. [Hirshkowitz, M.] VA Med Ctr, Sleep Disorders & Res Ctr, Houston, TX USA. [Chokroverty, S.] New Jersey Neurosci Inst, JFK Med Ctr, Edison, NJ USA. [Hedner, J.] Sahlgrens Univ Hosp, Sleep Lab Unit, Dept Resp Med & Allergol, Gothenburg, Sweden. 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 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 196 EP 197 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300550 ER PT J AU Gass, N Kalinchuk, A Stenberg, T AF Gass, N. Kalinchuk, A. Stenberg, T. TI Basal forebrain adenosine receptors and REM sleep recovery in rats SO JOURNAL OF SLEEP RESEARCH LA English DT Meeting Abstract CT 19th Congress of the European-Sleep-Research-Society CY SEP 09-13, 2008 CL Glasgow, SCOTLAND SP European Sleep Res Soc C1 [Gass, N.; Stenberg, T.] Univ Helsinki, Helsinki, Finland. [Kalinchuk, A.] Harvard Univ, Sch Med, Boston VA Healthcare Syst, 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 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 BP 202 EP 202 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 400EH UT WOS:000262850300566 ER PT J AU McKenna, JT Cordeira, JW Christie, MA Tartar, JL McCoy, JG Lee, E McCarley, RW Strecker, RE AF McKenna, James T. Cordeira, Joshua W. Christie, Michael A. Tartar, Jaime L. McCoy, John G. Lee, Eunho McCarley, Robert W. Strecker, Robert E. TI Assessing sleepiness in the rat: a multiple sleep latencies test compared to polysomnographic measures of sleepiness SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE electroencephalogram; non-rapid eye movement; rat; sleep; sleep latency ID LIGHT-DARK CYCLES; ANOVA DESIGNS; DEPRIVATION; EEG; INTENSITY; SPECTRA; VALUES; MEMORY; MICE AB Sleepiness following 6 h of sleep deprivation (SD) was evaluated with a rat multiple sleep latencies test (rMSLT), and the findings were compared to conventional polysomnographic measures of sleepiness. The 6 h of SD was produced by automated activity wheels, and was terminated at either the end of the light period or at the beginning of the dark period. The rMSLT consisted of 5 min wakefulness induced by sensory stimulation followed by 25 min of freedom to sleep. This procedure was repeated every 30 min for 3 h and was designed to minimize the amount of sleep lost due to the testing procedure. In separate rats, 6 h SD was followed by undisturbed recovery, allowing evaluation of conventional polysomnographic measures of sleepiness. Sleep onset latencies were reduced following SD, with recovery in the light (baseline = 8 min, 3 s versus post-SD = 1 min, 17 s) and dark period (baseline = 14 min, 17 s versus 7 min, 7 s). Sleep onset latencies were not altered by varying the duration criterion for the first sleep bout (i.e., sleep bout length criteria of 10, 20, 30, or 60 s were compared). Polysomnographic variables (non-rapid eye movement sleep episode duration, delta power, and number of awakenings) also provided reliable indirect measures of sleepiness, regardless of whether the recovery sleep occurred in the light or dark period. Evaluation of effect size indicated that the rMSLT was a strong measure of sleepiness, and was influenced by homeostatic, circadian, and illumination factors. The rMSLT provided a simple, objective, robust and direct measure of sleepiness that was as effective as conventional polysomnographic measures of sleepiness. C1 [McKenna, James T.; Cordeira, Joshua W.; Christie, Michael A.; Tartar, Jaime L.; McCoy, John G.; Lee, Eunho; McCarley, Robert W.; Strecker, Robert E.] Harvard Univ, Sch Med, Brockton, MA 02301 USA. [McKenna, James T.; Christie, Michael A.; McCarley, Robert W.; Strecker, Robert E.] VA Boston Healthcare Syst, Dept Psychiat, Brockton, MA 02301 USA. [Cordeira, Joshua W.] Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. [Tartar, Jaime L.] Nova SE Univ, Dept Social & Behav Sci, Ft Lauderdale, FL 33314 USA. [McCoy, John G.] Univ So Mississippi, Dept Psychol, Hattiesburg, MS 39406 USA. [Lee, Eunho] SK Holdings, Discovery Lab, Taejon, South Korea. RP McKenna, JT (reprint author), Harvard Univ, Sch Med, VAMC Res 151-C,940 Belmont St,Bldg 44,Rm 111, Brockton, MA 02301 USA. EM james_mckenna@hms.harvard.edu RI McCarley, Robert/N-5562-2014; OI McCarley, Robert/0000-0001-5705-7495; Tartar, Jaime/0000-0002-3452-0579 FU US Department of Veterans; Medical Research Awards; NIH [HL060292, MH039683, HL07901, MH070156] FX We thank Y. Bolortuya and B. Jeffrey for technical assistance, Margaret Niznikiewicz for statistical advice, and Ritchie Brown for editorial review. This research was supported by US Department of Veterans A. airs Medical Research Awards to RWM and RES, NIH HL060292, NIH MH039683, NIH HL07901 to JLT and JTM, and NIH MH070156 to JTM. NR 38 TC 6 Z9 6 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 IS 4 BP 365 EP 375 DI 10.1111/j.1365-2869.2008.00686.x PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 377PO UT WOS:000261263300002 PM 18823428 ER PT J AU Christie, MA McKenna, JT Connolly, NP McCarley, RW Strecker, RE AF Christie, Michael A. McKenna, James T. Connolly, Nina P. McCarley, Robert W. Strecker, Robert E. TI 24 hours of sleep deprivation in the rat increases sleepiness and decreases vigilance: introduction of the rat-psychomotor vigilance task SO JOURNAL OF SLEEP RESEARCH LA English DT Article DE mean sleep latency test; psychomotor vigilance task; rat; sleep; sleep deprivation; sleep latency; vigilance ID SUSTAINED ATTENTION PERFORMANCE; SLOW-WAVE ACTIVITY; LATENCY TEST; EXCESSIVE SLEEPINESS; DOSE-RESPONSE; TIME-COURSE; REM-SLEEP; RESTRICTION; EEG; HOMEOSTASIS AB A novel animal-analog of the human psychomotor vigilance task (PVT) was validated by subjecting rats to 24 h of sleep deprivation (SD) and examining the effect on performance in the rat-PVT (rPVT), and a rat multiple sleep latency test (rMSLT). During a three-phase (separate cohorts) crossover design, vigilance performance in the rPVT was compared with 24 h SD-induced changes in sleepiness assessed by polysomnographic evaluation and the rMSLT. Twenty-four hours of SD was produced by brief rotation of activity wheels at regular intervals in which the animals resided throughout the experiment. In the rPVT experiment, exercise controls (EC) experienced the same overall amount of locomotor activity as during SD, but allowed long periods of undisturbed sleep. After 24 h SD response latencies slowed, and lapses increased significantly during rPVT performance when compared with baseline and EC conditions. During the first 3 h of the recovery period following 24 h SD, polysomnographic measures indicated sleepiness. Latency to fall asleep after 24 h SD was assessed six times during the first 3 h after SD. Rats fell asleep significantly faster immediately after SD, than after non-SD baseline sessions. In conclusion, 24 h of SD in rats increased sleepiness, as indicated by polysomnography and the rMSLT, and impaired vigilance as measured by the rPVT. The rPVT closely resembles the human PVT test widely used in human sleep research and will assist investigation of the neurobiologic mechanisms that produce vigilance impairments after sleep disruption. C1 VA Boston Healthcare Syst, Brockton, MA USA. Harvard Univ, Sch Med, Brockton, MA 02401 USA. RP Strecker, RE (reprint author), 940 Belmont St,Res 151-C, Brockton, MA 02301 USA. EM michael_christie@hms.harvard.edu; robert_strecker@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs Medical Research Service Award; NHLBI [P50 HL060292, T32 HL07901]; NIMH [R37 MH039683, F32 MH070156] FX We thank Lauren Kane, Stephanie Cummings, Jeremy Beech, and Courtney Foster for technical assistance. This research was supported by the Department of Veterans Affairs Medical Research Service Award to RES, NHLBI - P50 HL060292 (RES & RWM), NIMH - R37 MH039683 (RWM), NHLBI T32 HL07901 (MAC & JTM), NIMH - F32 MH070156 (JTM). NR 37 TC 17 Z9 17 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0962-1105 J9 J SLEEP RES JI J. Sleep Res. PD DEC PY 2008 VL 17 IS 4 BP 376 EP 384 DI 10.1111/j.1365-2869.2008.00698.x PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 377PO UT WOS:000261263300003 PM 19021853 ER PT J AU Horn, JH Pratt, SR Durrant, JD AF Horn, Jennifer H. Pratt, Sheila R. Durrant, John D. TI Parameters to Maximize 2f2-f1 Distortion Product Otoacoustic Emission Levels SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE distortion product otoacoustic emissions (DPOAEs); parameters; 2f2-f1; input-output functions ID NORMALLY HEARING SUBJECTS; PRIMARY FREQUENCIES RATIO; HUMAN NEWBORNS; HUMAN EARS; AMPLITUDE; HUMANS; 2F1-F2; ADULTS; PHASE; INTERRELATIONS AB Purpose: Past research has established parameters for the 2f1-f2 distortion product otoacoustic emissions (DPOAEs) that enhance response levels ( e. g., L1-L2 = 10 dB; f2/f1 = 1.22; L1, L2 = 65, 55 dB SPL). These same parameters do not optimize 2f2-f1 DPOAEs. Therefore, this study was conducted to evaluate more completely those parameters that produce the most robust 2f2-f1 output. Method: Input-output functions of the 2f2-f1 component were obtained from 20 normal-hearing adults ( with f2 = 2000 Hz and 4000 Hz). Frequency ratios, level differences, and overall sound levels were manipulated with parameter combinations chosen to expand on information established in previous studies. The DPOAE signal-to-noise ratio (SNR), response presence, and output levels were measured. Results: In general, mean SNRs and 2f2-f1 levels were greater, and DPOAEs were present more often for 2000 than for 4000 Hz across all parameter combinations. No single parameter combination resulted in pronounced maxima for 2f2-f1, which is consistent with past studies but is in sharp contrast to results for the more familiar 2f1-f2. Conclusions: Overall, the results suggest that to maximize the 2f2-f1 level, lower test frequencies, low frequency ratio, essentially equal levels of primary tones, and moderate stimulus levels are best, and such parameters might be important for applying DPOAE measurement to assessment of normal and impaired auditory function. C1 [Horn, Jennifer H.] Univ Pittsburgh, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. [Horn, Jennifer H.; Pratt, Sheila R.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Horn, JH (reprint author), Univ Pittsburgh, Dept Commun Sci & Disorders, 4033 Forbes Tower, Pittsburgh, PA 15260 USA. EM jhhst15@pitt.edu RI Pratt, Sheila/H-7139-2013 NR 35 TC 3 Z9 4 U1 0 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC 1 PY 2008 VL 51 IS 6 BP 1620 EP 1629 DI 10.1044/1092-4388(2008/07-0179) PG 10 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 376PS UT WOS:000261196100019 PM 18664689 ER PT J AU Campbell, DA Henderson, WG Englesbe, MJ Hall, BL O'Reilly, M Bratzler, D Dellinger, EP Neumayer, L Bass, BL Hutter, MM Schwartz, J Ko, C Itani, K Steinberg, SM Siperstein, A Sawyer, RG Turner, DJ Khuri, SF AF Campbell, Darrell A., Jr. Henderson, William G. Englesbe, Michael J. Hall, Bruce L. O'Reilly, Michael Bratzler, Dale Dellinger, E. Patchen Neumayer, Leigh Bass, Barbara L. Hutter, Matthew M. Schwartz, James Ko, Clifford Itani, Kamal Steinberg, Steven M. Siperstein, Allan Sawyer, Robert G. Turner, Douglas J. Khuri, Shukri F. TI Surgical Site Infection Prevention: The Importance of Operative Duration and Blood Transfusion-Results of the First American College of Surgeons-National Surgical Quality Improvement Program Best Practices Initiative SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID RISK ADJUSTMENT; HOSPITALS; CARE; COMPLICATIONS; MORTALITY; INCREASE; NSQIP; TRIAL AB BACKGROUND: Surgical site infections (SSI) continue to be a significant problem in surgery. The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) Best Practices Initiative compared process and structural characteristics among 117 private sector hospitals in an effort to define best practices aimed at preventing SSI. STUDY DESIGN: Using standard NSQIP methodologies, we identified 20 low outlier and 13 high outlier hospitals for SSI using data from the ACS-NSQIP in 2006. Each hospital was administered a process of care survey, and site visits were conducted to five hospitals. Comparisons between the low and high outlier hospitals were made with regard to patient characteristics, operative variables, structural variables, and processes of care. RESULTS: Hospitals that were high outliers for SSI had higher trainee-to-bed ratios (0.61 versus 0.25, p < 0.0001), and the operations took significantly longer (128.3 +/- 104.3 minutes versus 102.7 +/- 83.9 minutes, p < 0.001). Patients operated on at low outlier hospitals were less likely to present to the operating room anemic (4.9% versus 9.7%, p = 0.007) or to receive a transfusion (5.1% versus 8.0%, p = 0.03). In general, perioperative policies and practices were very similar between the low and high outlier hospitals, although low outlier hospitals were readily identified by site visitors. Overall, low outlier hospitals were smaller, efficient in the delivery of care, and experienced little operative staff turnover. CONCLUSIONS: Our findings suggest that evidence-based SSI prevention practices do not easily distinguish well from poorly performing hospitals. But structural and process of care characteristics of hospitals were found to have a significant association with good results. (J Am Coll Surg 2008;207: 810-820. (C) 2008 by the American College of Surgeons) C1 [Campbell, Darrell A., Jr.; Englesbe, Michael J.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [O'Reilly, Michael] Univ Michigan, Dept Anesthesiol, Ann Arbor, MI 48109 USA. [Henderson, William G.] VA NSQIP, Aurora, CO USA. [Bratzler, Dale] Washington Univ, Oklahoma Fdn Med Qual, St Louis, MO USA. [Hall, Bruce L.] Washington Univ, Dept Surg, St Louis, MO USA. [Dellinger, E. Patchen] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Neumayer, Leigh] Univ Utah, Salt Lake City, UT USA. [Bass, Barbara L.] Methodist Hosp, Houston, TX 77030 USA. [Itani, Kamal; Khuri, Shukri F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Hutter, Matthew M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Steinberg, Steven M.] Ohio State Univ, Columbus, OH 43210 USA. [Siperstein, Allan] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Sawyer, Robert G.] Univ Virginia, Charlottesville, VA USA. [Turner, Douglas J.] Univ Maryland, Baltimore, MD 21201 USA. [Schwartz, James] Kaiser Sunnyside Med Ctr, Sunnyside, CA USA. [Ko, Clifford] Amer Coll Surg, Chicago, IL USA. RP Englesbe, MJ (reprint author), Univ Michigan, Dept Surg, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. RI Steinberg, Steven/E-4142-2011; OI Englesbe, Michael/0000-0001-8691-9111 NR 33 TC 109 Z9 109 U1 4 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD DEC PY 2008 VL 207 IS 6 BP 810 EP 820 DI 10.1016/j.jamcollsurg.2008.08.018 PG 11 WC Surgery SC Surgery GA 382GE UT WOS:000261592800003 PM 19183526 ER PT J AU Boyd, CM Landefeld, CS Counsell, SR Palmer, RM Fortinsky, RH Kresevic, D Burant, C Covinsky, KE AF Boyd, Cynthia M. Landefeld, C. Seth Counsell, Steven R. Palmer, Robert M. Fortinsky, Richard H. Kresevic, Denise Burant, Christopher Covinsky, Kenneth E. TI Recovery of Activities of Daily Living in Older Adults After Hospitalization for Acute Medical Illness SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE hospitalization; functional decline; recovery ID HOME HEALTH-CARE; PROSPECTIVE-PAYMENT SYSTEM; HIP FRACTURE PATIENTS; POST-ACUTE CARE; FUNCTIONAL OUTCOMES; THERAPY INTENSITY; REHABILITATION; DISABILITY; COMMUNITY; INDEPENDENCE AB To compare functional outcomes in the year after discharge for older adults discharged from the hospital after an acute medical illness with a new or additional disability in their basic self-care activities of daily living (ADL) (compared with preadmission baseline 2 weeks before admission) with those of older adults discharged with baseline ADL function and identify predictors of failure to recover to baseline function 1 year after discharge. Observational. Tertiary care hospital, community teaching hospital. Older (aged >= 70) patients nonelectively admitted to general medical services (1993-1998). Number of ADL disabilities at preadmission baseline and 1, 3, 6, and 12 months after discharge. Outcomes were death, sustained decline in ADL function, and recovery to baseline ADL function at each time point. By 12 months after discharge, of those discharged with new or additional ADL disability, 41.3% died, 28.6% were alive but had not recovered to baseline function, and 30.1% were at baseline function. Of those discharged at baseline function, 17.8% died, 15.2% were alive but with worse than baseline function, and 67% were at their baseline function (P <.001). Of those discharged with new or additional ADL disability, the presence or absence of recovery by 1 month was associated with long-term outcomes. Age, cardiovascular disease, dementia, cancer, low albumin, and greater number of dependencies in instrumental ADLs independently predicted failure to recover. For older adults discharged with new or additional disability in ADL after hospitalization for medical illness, prognosis for functional recovery is poor. Rehabilitation interventions of longer duration and timing than current reimbursement allows, caregiver support, and palliative care should be evaluated. C1 [Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. [Boyd, Cynthia M.] Johns Hopkins Univ, Sch Med, Dept Med, Ctr Aging & Hlth, Baltimore, MD 21224 USA. [Boyd, Cynthia M.] Johns Hopkins Univ, Dept Hlth Policy & Management, Ctr Aging & Hlth, Baltimore, MD 21224 USA. [Boyd, Cynthia M.] Johns Hopkins Univ, Roger C Lipitz Ctr Integrated Hlth Care, Bloomberg Sch Publ Hlth, Baltimore, MD 21224 USA. [Landefeld, C. Seth; Covinsky, Kenneth E.] Univ Calif San Francisco, Dept Med, Div Geriatr, San Francisco, CA USA. [Landefeld, C. Seth; Covinsky, Kenneth E.] San Francisco VA Med Ctr, Interdisciplinary Res Program Improve Care Older, San Francisco, CA USA. [Landefeld, C. Seth; Covinsky, Kenneth E.] San Francisco VA Med Ctr, Qual Scholars Program, San Francisco, CA USA. [Counsell, Steven R.] Indiana Univ, Ctr Aging Res, Indianapolis, IN 46204 USA. [Palmer, Robert M.] Univ Pittsburgh, Sch Med Ctr, Div Geriatr Med, Pittsburgh, PA USA. [Fortinsky, Richard H.] Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. [Fortinsky, Richard H.] Univ Connecticut, Ctr Hlth, Div Geriatr, Farmington, CT USA. [Kresevic, Denise] Case Western Reserve Univ, Sch Nursing, Dept Sociol & Bioeth,Univ Hosp Case Med Ctr, Louis Stokes Cleveland Vet Affairs Med Ctr,GRE, Cleveland, OH 44106 USA. RP Boyd, CM (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Mason F Lord Bldg,Ctr Tower,7th Floor,5200 Easter, Baltimore, MD 21224 USA. EM cboyd1@jhmi.edu FU National Institute on Aging [AG029233, AG00912, AG10418, K24AG029812]; Johns Hopkins University (CMB); Summa Health System Foundation to Akron City Hospital; John A. Hartford Foundation, Inc. [2003-0455] FX Conflict of Interest: Drs. Landefeld, Covinsky, Palmer, Counsell Fortinsky, Burant, and Kresevic have all received funding from the NIA. Dr Kresevic has received funding from the Department of Veterans Affairs. Drs. Landefeld and Boyd have received funding from the John A. Hartford Foundation. Dr. Boyd was a Pfizer/American Geriatrics Society Junior Faculty Scholar for Research on Health Outcomes during the conduct of this study. Dr. Boyd is a Johns Hopkins Bayview Scholar in the Center for Innovative Medicine. This work was supported by grants from the National Institute on Aging to the Claude Pepper Older Americans Independence Center at Case Western Reserve University and Johns Hopkins University (CMB), National Institute on Aging Grants AG029233, AG00912, AG10418, and K24AG029812. The Summa Health System Foundation to Akron City Hospital, and the John A. Hartford Foundation, Inc. 2003-0455 to the University of California, San Francisco.; Author Contributions: Dr. Boyd conceptualized the manuscript, obtained funding, developed the design of the analysis with Dr. Covinsky and wrote the manuscript. Dr. Landefeld and Dr. Counsell were responsible for collaborating in study design and implementation, obtaining funding, analysis and interpretation of data and critical revision of the manuscript for important intellectual content. Dr. Palmer was a co-investigator responsible for collaborating in design and implementation, interpretation of data, and critical revision of the manuscript for important intellectual content. Dr. Fortinsky was a co-investigator responsible for collaborating in the analysis and interpretation of data and critical revision of the manuscript for important intellectual content. Dr. Kresevic was a co-investigator responsible for collaborating in design and implementation, interpretation of data, and critical revision of the manuscript for important intellectual content. Dr. Covinsky was responsible for supervision of the entire project and manuscript and collaborated on the design and implementation and analysis and interpretation of data and undertook critical revision of this manuscript for important intellectual content.; Sponsors' Role: The funding sources had no role in the design and conduct of the study; collection, management, analysis or interpretation of the data; or the preparation, review, or approval of the manuscript. NR 50 TC 166 Z9 171 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 EI 1532-5415 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2008 VL 56 IS 12 BP 2171 EP 2179 DI 10.1111/j.1532-5415.2008.02023.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 378ZP UT WOS:000261364100001 PM 19093915 ER PT J AU Sarkisian, CA Gruenewald, TL Boscardin, WJ Seeman, TE AF Sarkisian, Catherine A. Gruenewald, Tara L. Boscardin, W. John Seeman, Teresa E. TI Preliminary Evidence for Subdimensions of Geriatric Frailty: The MacArthur Study of Successful Aging SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE frailty; disability; aged; comorbidity ID OLDER-ADULTS; FUNCTIONAL DECLINE; PHYSICAL-ACTIVITY; ELDERLY-PEOPLE; WOMENS HEALTH; DISABILITY; MORTALITY; COAGULATION; ACTIVATION; PHENOTYPE AB To identify frailty subdimensions. Longitudinal cohort (MacArthur Study). Three U.S. urban centers. One thousand one hundred eighteen high-functioning subjects aged 70 to 79 in 1988. Participants with three or more of five Cardiovascular Health Study (CHS) frailty criteria (weight loss, weak grip, exhaustion, slow gait, and low physical activity) in 1991 were classified as having the CHS frailty phenotype. To identify frailty subdimensions, factor analysis was conducted using the CHS variables and an expanded set including the CHS variables, cognitive impairment, interleukin-6 (IL-6), C-reactive protein (CRP), subjective weakness, and anorexia. Participants with four or more of 10 criteria were classified as having an expanded frailty phenotype. Predictive validity of each identified frailty subdimension was assessed using regression models for 4-year disability and 9-year mortality. Two subdimensions of the CHS phenotype and four subdimensions of the expanded frailty phenotype were identified. Cognitive function was consistently part of a subdimension including slower gait, weaker grip, and lower physical activity. The CHS subdimension of slower gait, weaker grip, and lower physical activity predicted disability (adjusted odds ratio (AOR)=1.7, 95% confidence interval (CI)=1.3-2.2) and mortality (AOR=1.5, 95% CI=1.3-1.8). Subdimensions of the expanded model with predictive validity were higher IL-6 and CRP (AOR=1.2 for mortality); slower gait, weaker grip, lower physical activity, and lower cognitive function (AOR=1.8 for disability; AOR=1.5 for mortality), and anorexia and weight loss (AOR=1.2 for disability). This study provides preliminary empirical support for subdimensions of geriatric frailty, suggesting that pathways to frailty differ and that subdimension-adapted care might enhance care of frail seniors. C1 [Sarkisian, Catherine A.] GRECC, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. [Sarkisian, Catherine A.; Gruenewald, Tara L.; Seeman, Teresa E.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90095 USA. [Boscardin, W. John] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Sarkisian, CA (reprint author), GRECC, VA Greater Los Angeles Healthcare Syst, Bldg 220,Room 315 11G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM csarkisian@mednet.ucla.edu FU Paul B. Beeson Career Development Award in Aging; National Institute on Aging [1K23AG0 24811-03, R21, 5 R21 AG025764-02, 5 P30 AG017265-08]; University of Southern California/University of California at Los Angeles Center for the Study of Biodemography and Population Health; MacArthur Research Network on Successful Aging; John D. and Catherine T. MacArthur Foundation FX The authors want to express their appreciation to Ms. Constance Gewa, Ms. Sungjin Kim, and Ms. Diana Liao for carefully carrying out the computer programming necessary for this manuscript.; Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this manuscript. This work was supported by a Paul B. Beeson Career Development Award in Aging, National Institute on Aging (1K23AG0 24811-03), an R21 from the National Institute on Aging (5 R21 AG025764-02), the University of Southern California/University of California at Los Angeles Center for the Study of Biodemography and Population Health, National Institute on Aging (5 P30 AG017265-08), and by the MacArthur Research Network on Successful Aging and the MacArthur Research Network on SES and Health through grants from the John D. and Catherine T. MacArthur Foundation.; Author Contributions: All four authors contributed to the study concept and design, analysis and interpretation of data, and preparation of the manuscript. Dr. Seeman also contributed to subject enrollment and data collection. Sponsor's Role: The funders had no role in this investigation's design, conduct, or reporting. NR 29 TC 48 Z9 49 U1 4 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2008 VL 56 IS 12 BP 2292 EP 2297 DI 10.1111/j.1532-5415.2008.02041.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 378ZP UT WOS:000261364100017 PM 19016933 ER PT J AU Shay, K Burris, JF AF Shay, Kenneth Burris, James F. CA State Art Planning Comm TI Setting the Stage for a New Strategic Plan for Geriatrics and Extended Care in the Veterans Health Administration: Summary of the 2008 VA State of the Art Conference, "The Changing Faces of Geriatrics and Extended Care: Meeting the Needs of Veterans in the Next Decade" SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INTEGRATED CARE; PRISM-E; DEPRESSION; OUTCOMES; PARTICIPATE; MANAGEMENT; PROGRAM; MODELS AB The Department of Veterans Affairs (VA) assumed an early leadership role in focusing on care of elderly adults. In 1998, the Federal Advisory Committee on the Future of VA Long-Term Care, appointed by the VA Undersecretary for Health, recommended redirection of VA's extended care programs toward noninstitutional forms. A decade later, VA's Office of Geriatrics and Extended Care (GEC) initiated a strategic planning process by convening experts in geriatrics and health care, policy, and finance in Virginia on March 25 to 27, 2008, to present to VA clinicians and clinical managers the "State of the Art" of VA GEC. Recurring clinical themes included rising numbers and complexity of aging veterans, recent addition of younger veterans to VA's extended care mix, challenges that dementia and mental illness exert throughout GEC, and need for seamlessness in delivery of care across multiple venues. Ongoing research efforts quantifying demand and resources and validating models of care will remain indispensible for meeting clinical challenges. Serious undersupply of clinicians of all disciplines with general or specialty geriatrics knowledge persists. Much of VA's healthcare workforce and leadership are approaching retirement age, driving the need for new educational approaches, recruitment and retention strategies, and innovative delivery systems. Growing dependence on informal caregivers highlights the need for supporting these partners. VA's healthcare budget allocation illustrates how national policy dictates systemic, regional, and local clinical decisions. Rehabilitation of the newest veterans is resulting in systemwide efficiencies. Educating and empowering patients and families results in optimized utilization of health resources. C1 [Shay, Kenneth; Burris, James F.] US Dept Vet Affairs, Off Geriatr & Extended Care, Washington, DC USA. RP Shay, K (reprint author), VA Cent Off 114, 810 Vermont Ave NW, Washington, DC 20420 USA. EM Kenneth.shay@va.gov NR 20 TC 12 Z9 12 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2008 VL 56 IS 12 BP 2330 EP 2339 DI 10.1111/j.1532-5415.2008.02079.x PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 378ZP UT WOS:000261364100023 PM 19093933 ER PT J AU Luks, AM Johnson, RJ Swenson, ER AF Luks, Andrew M. Johnson, Richard J. Swenson, Erik R. TI Chronic Kidney Disease at High Altitude SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; MODERATELY HIGH-ALTITUDE; RIGHT PULMONARY-ARTERY; STAGE RENAL-DISEASE; CHRONIC HYPOXIA; RAT-KIDNEY; SEA-LEVEL; TUBULOINTERSTITIAL INJURY; RESPIRATORY ALKALOSIS; IMPAIRED ANGIOGENESIS AB With a prevalence of 10 to 11% in the general population, it is likely that many patients with chronic kidney disease will visit or reside in mountainous areas. Little is known, however, about whether short- or long-duration, high-altitude exposure poses a risk in this patient population. Given that many areas of the kidney are marginally oxygenated even at sea level and that kidney disease may result in further renal hypoxia and hypoxia-associated renal injury, there is concern that high altitude may accelerate the progression of chronic kidney disease. In this review, we address how chronic kidney disease and its management is affected at high altitude. We postulate that arterial hypoxemia at high altitude poses a risk of faster disease progression in those with preexisting kidney disease. In addition, we consider the risks of developing acute altitude illness in patients with chronic kidney disease and the appropriate use of medications for the prevention and treatment of these problems. C1 [Swenson, Erik R.] Univ Washington, VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, Seattle, WA 98108 USA. [Johnson, Richard J.] Univ Colorado, Div Renal Dis & Hypertens, Denver, CO 80202 USA. RP Swenson, ER (reprint author), Univ Washington, VA Puget Sound Hlth Care Syst, Div Pulm & Crit Care Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM eswenson@u.washington.edu FU NHLBI NIH HHS [R01 HL068607, R01 HL068607-07A2]; NIDDK NIH HHS [R01 DK052121-12, R01 DK052121] NR 105 TC 21 Z9 22 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD DEC PY 2008 VL 19 IS 12 BP 2262 EP 2271 DI 10.1681/ASN.2007111199 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 381MC UT WOS:000261539300007 PM 18842990 ER PT J AU Stelfox, HT Goverman, J AF Stelfox, Henry Thomas Goverman, Jeremy TI The Number, Content, and Quality of Randomized Controlled Trials in the Prevention and Care of Injuries SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE Injury; Trauma; Randomized controlled trial; Systematic review; Research design ID GLOBAL BURDEN; METHODOLOGIC QUALITY; CLINICAL-TRIALS; DISEASE; DISABILITY; MORTALITY; JOURNALS AB Background: Injuries represent an important and growing global burden of disease. The availability of evidence-based injury control interventions is unknown. We aimed to assess trends with respect to the number, content, and methodologic quality of reports of randomized controlled trials (RCTs) in the prevention and care of injuries. Methods: We searched MEDLINE and the Cochrane Central Register of Controlled Trials for reports of RCTs of interventions in the prevention and care of injuries published between January 1, 1966 and January 1, 2006. Ten percent of reports, stratified by year, were randomly sampled. Studies were abstracted using a standardized form for nature of intervention, sample size, patients studied, and methodologic quality. Results: The rate of publication of injury-related RCTs increased from 1.2 to 5.3 articles per 100 RCTs published in MEDLINE (p < 0.001) during the study period. A total of 308 reports were included in the analysis of content and methodologic quality. Poisonings (31 [10%]) were the single most common isolated mechanism of patient injury studied, whereas only 12 reports (4%) focused on road traffic injuries. The majority of interventions were hospital based (211 [68%]) and half (45%) were judged to be only available in high-income countries. Allocation concealment was deemed adequate in 73 articles (24%). One quarter of reports documented blinding of participants (77 [25%]), investigators (68 [22%]), and outcome assessors (83 [27%]). Only 44 articles (14%) reported intention-to-treat analyses. Conclusions: The number of RCTs specific to the prevention and care of injuries is small, but increasing. The reporting of injury-related RCTs has important deficiencies including inadequate allocation concealment; failure to blind patients, investigators, and assessors; and per protocol analyses. In addition, many interventions studied are not available in low-income countries where the majority of the world's population resides and injury rates are highest. C1 [Stelfox, Henry Thomas] Univ Calgary, Foothills Med Ctr, Dept Crit Care Med, Calgary, AB T2N 2T9, Canada. [Goverman, Jeremy] Massachusetts Gen Hosp, Dept Surg, Burns Serv, Boston, MA 02114 USA. RP Stelfox, HT (reprint author), Univ Calgary, Foothills Med Ctr, Dept Crit Care Med, EG23A,1403-29 St NW, Calgary, AB T2N 2T9, Canada. EM tom.stelfox@calgaryhealthregion.ca FU Canadian Institutes of Health Research FX H.T.S. was supported by a Postdoctoral Fellowship award from the Canadian Institutes of Health Research. NR 26 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD DEC PY 2008 VL 65 IS 6 BP 1488 EP 1493 DI 10.1097/TA.0b013e3181568cfc PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 383WV UT WOS:000261706000054 PM 19077647 ER PT J AU Litz, BT AF Litz, Brett T. TI Early Intervention for Trauma: Where Are We and Where Do We Need to Go? A Commentary SO JOURNAL OF TRAUMATIC STRESS LA English DT Article; Proceedings Paper CT 23rd Annual Conference of the International-Society-of-Traumatic-Studies CY NOV, 2007 CL Baltimore, MD SP Int Soc Traumat Studies ID POSTTRAUMATIC-STRESS-DISORDER; MANAGEMENT AB In this commentary, the author underscores the importance of early intervention for trauma and describes the challenges that lie ahead for researchers, decision makers, and care providers. The author also provides a review of where things stand, briefly reviews psychological first aid strategies, and underscores where we need to go from here. Although the field has advanced considerably in the last decade or so, and there are compelling trials underway, there is much work that needs to be done, especially in terms of effectiveness and the task of integrating early intervention into various work cultures, such as the military. C1 [Litz, Brett T.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Litz, Brett T.] Massachusetts Vet Epidemiol Res & Informat Ctr, Natl Ctr PTSD, VA Boston Healthcare Syst, Boston, MA 02130 USA. RP Litz, BT (reprint author), NCPTSD 116B4, 150 S Huntington Ave, Boston, MA 02130 USA. EM brett.litz@va.gov NR 9 TC 24 Z9 24 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD DEC PY 2008 VL 21 IS 6 BP 503 EP 506 DI 10.1002/jts.20373 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 391ZD UT WOS:000262271800002 PM 19107726 ER PT J AU Ricci, P Cantisani, V D'Onotrip, M Sahani, D Pagliara, E Calliada, F Mehmet, E Sanjeva, K Faccioli, N Pozzi-Mucelli, R D'Ambrosio, U Passariello, R AF Ricci, Paolo Cantisani, Vito D'Onotrip, Mirko Sahani, Dushyant Pagliara, Elisa Calliada, Fabrizio Mehmet, Erturk Sanjeva, Kalva Faccioli, Nicola Pozzi-Mucelli, Roberto D'Ambrosio, Ugo Passariello, Roberto TI Behavior of Hepatocellular Adenoma on Real-time Low-Mechanical Index Contrast-Enhanced Ultrasonography With a Second-Generation Contrast Agent SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE contrast-enhanced ultrasonography; hepatocellular adenoma; second-generation ultrasound contrast media; ultrasonography ID FOCAL NODULAR HYPERPLASIA; LIVER-SPECIFIC MICROBUBBLES; COLOR DOPPLER SONOGRAPHY; PROSPECTIVE MULTICENTER; HEPATIC ADENOMAS; LESIONS; DIFFERENTIATION; ULTRASOUND; BENIGN; TUMORS AB Objective. The purpose of this study was to describe the behavior of histologically proven hepatocellular adenoma (HCA) on low-mechanical index (MI) contrast-enhanced ultrasonography (CEUS). Methods. A review of the databases from 4 academic hospitals revealed 18 patients (15 female and 3 male; mean age, 40 years; range, 25-71 years) with 25 histologically proven HCA lesions who were studied with CEUS at a low MI (0.04-0.1). Results. Twenty-four of 25 lesions (96%; 95% confidence interval [CI], 80.5%-99.3%) showed high-intensity enhancement, scored as 3 on a scale of 0 to 3, whereas only 1 lesion (4%; 95% CI, 0.7%-19.5%) was scored as 2. The time of peak enhancement ranged between 10 and 19 seconds (average, 13 seconds). All but 1 of the 25 lesions (96%; 95% CI, 80.5%-99.3%) showed early homogeneous and centripetal enhancement during the hepatic arterial phase. No portal venous phase enhancement was observed in any lesion because all showed rapid wash-out (100%; 95% CI, 86.7%-100%). Twenty lesions (80%; 95% CI, 60.9%-91.1 %) were found to be isoechoic to slightly hypoechoic during the portal phase, and 19 (76%; 95% CI, 56.6%-88.5%) were isoechoic to mildly hypoechoic, whereas 7 (24%; 95% CI, 11.5%-43.4%) were hypoechoic during the late phase. Conclusions. Contrast-enhanced ultrasonography is an effective technique for identifying the microvascular and macrovascular characteristics of HCA. Typically, HCA shows early (10-19 seconds) and centripetal enhancement during the arterial phase and isoechogenicity or mild hypoechogenicity during the portal phase, remaining slightly hypoechoic or isoechoic during the late phase in most cases. C1 [Ricci, Paolo; Cantisani, Vito; Pagliara, Elisa; D'Ambrosio, Ugo; Passariello, Roberto] Univ Roma La Sapienza, Dept Radiol, Rome, Italy. [D'Onotrip, Mirko; Faccioli, Nicola; Pozzi-Mucelli, Roberto] Univ Verona, Dept Radiol, I-37100 Verona, Italy. [Sahani, Dushyant; Sanjeva, Kalva] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Calliada, Fabrizio] Univ Pavia, Dept Radiol, Policlin San Matteo, I-27100 Pavia, Italy. [Mehmet, Erturk] Sisli Etfal Training & Res Hosp, Dept Radiol, Istanbul, Turkey. RP Ricci, P (reprint author), Azienda Policlin Umberto 1, Dipartimento Sci Radiol, Viale Regina Elena 324, I-00161 Rome, Italy. EM paolo.ricci@uniroma1.it RI D'Onofrio, Mirko/S-6828-2016; OI D'Onofrio, Mirko/0000-0003-3229-9329; CANTISANI, VITO/0000-0003-1525-214X NR 20 TC 10 Z9 11 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2008 VL 27 IS 12 BP 1719 EP 1726 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 377WQ UT WOS:000261283200006 PM 19022997 ER PT J AU Spencer, JK Adler, RS AF Spencer, Jacqueline K. Adler, Ronald S. TI Utility of Portable Ultrasound in a Community in Ghana SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE developing countries; Ghana; portable ultrasound ID DEVELOPING-COUNTRIES; DEVELOPING-WORLD; ULTRASONOGRAPHY AB Objective. in many developing countries, access to medical imaging is limited by availability of resources. Portable ultrasound shows great promise to meet the needs in these countries because it is transportable and relatively inexpensive, and it has a wide range of applications. As part of the Ghana Health Mission, Sekondi-Takoradi, Ghana, we explored the utility of ultrasound in primary care and hospital settings during March 2004. Our objective was to evaluate the clinical utility of a portable ultrasound machine in a variety of physical conditions and multiple clinical scenarios. Methods. Ultrasound examinations were performed at 2 primary care sites and 2 hospitals using a portable ultrasound machine with linear and curved linear phased array transducers. Most ultrasound examinations were musculoskeletal, with the remainder being obstetric, pelvic, breast, vascular, abdominal, and genitourinary examinations. Results. In clinic settings, musculoskeletal ultrasound represented 46% (16) of the ultrasound examinations performed, and 29% (10) of the cases were a combination of abdominal, pelvic, and genitourinary examinations. In hospital settings, abdominal, pelvic, and genitourinary ultrasound examinations combined were 56% (18), and musculoskeletal was 41 % (13). Of the 67 ultrasound examinations performed, 81 % (54) showed abnormal findings, 81 % (54) were considered to add to the clinical diagnosis, and 40% (27) influenced medical care for the patients. Conclusions. This experience shows the usefulness of portable ultrasound examinations performed by a skilled radiologist in a clinical setting in Ghana; the challenge is to address how to best incorporate ultrasound into the current practice of medical professionals in developing countries. C1 [Adler, Ronald S.] Hosp Special Surg, Div Ultrasound & Body Imaging, Dept Radiol & Imaging, New York, NY 10021 USA. [Spencer, Jacqueline K.] VA Boston Healthcare Syst, Dept Primary & Ambulatory Care, Boston, MA USA. RP Adler, RS (reprint author), Hosp Special Surg, Div Ultrasound & Body Imaging, Dept Radiol & Imaging, 535 E 70th St, New York, NY 10021 USA. EM adlerr@hss.edu NR 13 TC 32 Z9 32 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD DEC PY 2008 VL 27 IS 12 BP 1735 EP 1743 PG 9 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 377WQ UT WOS:000261283200008 PM 19022999 ER PT J AU McDougal, WS AF McDougal, W. Scott TI Factors Predicting Renal Functional Outcome After Partial Nephrectomy COMMENT SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2008 VL 180 IS 6 BP 2368 EP 2368 DI 10.1016/j.juro.2008.08.112 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 373OT UT WOS:000260982200025 ER PT J AU Schanzer, A Mega, J Meadows, J Samson, RH Bandyk, DF Conte, MS AF Schanzer, Andres Mega, Jessica Meadows, Judith Samson, Russell H. Bandyk, Dennis F. Conte, Michael S. TI Risk stratification in critical limb ischemia: Derivation and validation of a model to predict amputation-free survival using multicenter surgical outcomes data SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 62nd Annual Meeting of the Society-for-Vascular-Surgery CY JUN 05-08, 2008 CL San Diego, CA SP Soc Vasc Surg ID PERIPHERAL-ARTERIAL-DISEASE; EXTREMITY BYPASS-SURGERY; C-REACTIVE PROTEIN; QUALITY-OF-LIFE; VEIN BYPASS; INFRAINGUINAL BYPASS; VASCULAR-DISEASE; CONTROLLED-TRIAL; HIGH PREVALENCE; MORTALITY AB Background: Patients with critical limb ischemia (CLI) are a heterogeneous population with respect to risk for mortality and limb loss, complicating clinical decision-making. Endovascular options, compared with bypass, offer a tradeoff between reduced procedural risk and inferior durability. Risk stratified data predictive of amputation-free survival (AFS) may improve clinical decision making and allow for better assessment of new technology in the CLI population. Methods. This was a retrospective analysis of prospectively collected data from patients who underwent infrainguinal vein by ass surgery for CLI. Two datasets were used: the PREVENT III randomized trial (n = 1404) and a multicenter. P registry (n = 716) from three distinct vascular centers (two academic, one community-based). The PREVENT III cohort was randomly assigned to a derivation set (n = 953) and to a validation set (11 = 451). The primary endpoint was AFS. Predictors of AFS identified on univariate screen (inclusion threshold, P < .20) were included in a stepwise selection Cox model. The resulting five significant predictors were assigned an integer score to stratify, patients into three risk groups. The prediction rule was internally validated in the PREVENT III validation set and externally validated in the multicenter cohort. Results: The estimated 1-year AFS in the derivation, internal validation, and external validation sets were 76.3%, 72.5%, and 77.0%, respectively. In the derivation set, dialysis (hazard ratio [HR] 2.81, P < .0001), tissue loss (HR 2.22, P = .0004), age 2:75 (HR 1.64, P = .001), hematocrit <= 30 (HR 1.61, P = .012), and advanced CAD (HR 1.41, P = .021) were significant predictors for ATS in the multivariable model. An integer score, derived from the 9 coefficients, was used to generate three risk categories (low <= 3 [44.4% of cohort], medium 4-7 [46.7% of cohort], high >= 8 [8.8% of cohort]). Stratification of the patients, in each dataset, according to risk category yielded three significantly different Kaplan-Meier estimates for 1-year AFS (86%, 73%, and 45% for low, medium, and high risk groups, respectively). For a given risk category, the ATS estimate was consistent between the derivation and validation sets. Conclusion: Among patients selected to undergo surgical bypass for infrainguinal disease, this parsimonious risk stratification model reliably identified a category of CLI patients with a >50% chance of death or major amputation at 1 year. Calculation of a "PIII risk score" may be useful for surgical decision making and for clinical trial designs in the CLI population. (J Vasc Surg 2008;48:1464-71.) C1 [Schanzer, Andres] Univ Massachusetts, Mem Med Ctr, Div Vasc & Endovasc Surg, Worcester, MA 01655 USA. [Mega, Jessica] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Meadows, Judith; Conte, Michael S.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Samson, Russell H.] Florida State Univ, Sarasota, FL USA. [Bandyk, Dennis F.] Univ S Florida, Tampa, FL USA. RP Schanzer, A (reprint author), Univ Massachusetts, Mem Med Ctr, Div Vasc & Endovasc Surg, 55 Lake Ave N, Worcester, MA 01655 USA. EM schanzea@ummhc.org FU NHLBI NIH HHS [T32 HL007575-17, T32 HL007575-23, T32 HL007575-20, T32 HL007575-22, T32 HL007575-16, T32 HL007575-19, T32 HL007575-24, T32 HL007575, T32 HL007575-21, T32 HL007575-18] NR 38 TC 110 Z9 111 U1 2 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD DEC PY 2008 VL 48 IS 6 BP 1464 EP 1471 DI 10.1016/j.jvs.2008.07.062 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 388FX UT WOS:000262006800017 PM 19118735 ER PT J AU Li, X Sodroski, J AF Li, Xing Sodroski, Joseph TI The TRIM5 alpha B-Box 2 Domain Promotes Cooperative Binding to the Retroviral Capsid by Mediating Higher-Order Self-Association SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROTEIN-PROTEIN INTERACTIONS; MURINE LEUKEMIA-VIRUS; RESTRICTION FACTOR; TRIPARTITE MOTIF; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; RHESUS TRIM5-ALPHA; CYCLOPHILIN-A; HIV-1 AB The retroviral restriction factor, TRIM5 alpha, blocks infection of a spectrum of retroviruses soon after virus entry into the cell. TRIM5 alpha consists of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. The B-box 2 domain is essential for retrovirus restriction by TRIM5 alpha, but its specific function is unknown. We show here that the B-box 2 domain mediates higher-order self-association of TRIM5 alpha rh oligomers. This self-association increases the efficiency of TRIM5 alpha binding to the retroviral capsid, thus potentiating restriction of retroviral infection. The contribution of the B-box 2 domain to cooperative TRIM5 alpha association with the retroviral capsid explains the conditional nature of the restriction phenotype exhibited by some B-box 2 TRIM5 alpha mutants; the potentiation of capsid binding that results from B-box 2-mediated self-association is essential for restriction when B30.2(SPRY) domain-mediated interactions with the retroviral capsid are weak. Thus, B-box 2-dependent higher-order self-association and B30.2(SPRY)-dependent capsid binding represent complementary mechanisms whereby sufficiently dense arrays of capsid-bound TRIM5 alpha proteins can be achieved. C1 [Li, Xing] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Div Aids,Med Sch, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Dept Immunol & Infect Dis, Sch Publ Hlth, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Div Aids,Med Sch, 44 Binney St JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009 FU National Institutes of Health [AI063987, AI076094, AI06354]; International AIDS Vaccine Initiative FX We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation.; This study was supported by the National Institutes of Health (grants AI063987 and AI076094 and a Center for AIDS Research Award AI06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. NR 49 TC 76 Z9 79 U1 0 U2 9 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 DEC PY 2008 VL 82 IS 23 BP 11495 EP 11502 DI 10.1128/JVI.01548-08 PG 8 WC Virology SC Virology GA 370UX UT WOS:000260789700002 PM 18799578 ER PT J AU Shun, MC Botbol, Y Li, X Di Nunzio, F Daigle, JE Yan, N Lieberman, J Lavigne, M Engelman, A AF Shun, Ming-Chieh Botbol, Yair Li, Xiang Di Nunzio, Francesca Daigle, Janet E. Yan, Nan Lieberman, Judy Lavigne, Marc Engelman, Alan TI Identification and Characterization of PWWP Domain Residues Critical for LEDGF/p75 Chromatin Binding and Human Immunodeficiency Virus Type 1 Infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID INTEGRASE INTERACTOR LEDGF/P75; NUCLEAR-LOCALIZATION SIGNAL; HIV-1 INTEGRASE; GROWTH-FACTOR; DNA INTEGRATION; IN-VITRO; COACTIVATOR P75; HUMAN GENOME; HUMAN-CELLS; PREINTEGRATION COMPLEXES AB Lens epithelium-derived growth factor (LEDGF)/p75 functions as a bimodal tether during lentiviral DNA integration: its C-terminal integrase-binding domain interacts with the viral preintegration complex, whereas the N-terminal PWWP domain can bind to cellular chromatin. The molecular basis for the integrase-LEDGF/p75 interaction is understood, while the mechanism of chromatin binding is unknown. The PWWP domain is homologous to other protein interaction modules that together comprise the Tudor clan. Based on primary amino acid sequence and three-dimensional structural similarities, 24 residues of the LEDGF/p75 PWWP domain were mutagenized to garner essential details of its function during human immunodeficiency virus type 1 (HIV-1) infection. Mutating either Trp-21 or Ala-51, which line the inner wall of a hydrophobic cavity that is common to Tudor clan members, disrupts chromatin binding and virus infectivity. Consistent with a role for chromatin-associated LEDGF/p75 in stimulating integrase activity during infection, recombinant W21A protein is preferentially defective for enhancing integration into chromatinized target DNA in vitro. The A51P mutation corresponds to the S270P change in DNA methyltransferase 3B that causes human immunodeficiency, centromeric instability, and facial anomaly syndrome, revealing a critical role for this amino acid position in the chromatin binding functions of varied PWWP domains. Our results furthermore highlight the requirement for a conserved Glu in the hydrophobic core that mediates interactions between other Tudor clan members and their substrates. This initial systematic mutagenesis of a PWWP domain identifies amino acid residues critical for chromatin binding function and the consequences of their changes on HIV-1 integration and infection. C1 [Shun, Ming-Chieh; Li, Xiang; Di Nunzio, Francesca; Daigle, Janet E.; Engelman, Alan] Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Shun, Ming-Chieh; Li, Xiang; Di Nunzio, Francesca; Daigle, Janet E.; Engelman, Alan] Harvard Univ, Div Aids, Sch Med, Boston, MA 02115 USA. [Botbol, Yair; Lavigne, Marc] Inst Pasteur, Dept Virol, Unit Struct Biol, F-75724 Paris, France. [Yan, Nan; Lieberman, Judy] Harvard Univ, Immune Dis Inst, Sch Med, Boston, MA 02115 USA. [Yan, Nan; Lieberman, Judy] Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. RP Engelman, A (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Sch Med, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu RI Li, Xiang/C-4588-2011; Lieberman, Judy/A-2717-2015; Di Nunzio, Francesca/A-6153-2014 OI Di Nunzio, Francesca/0000-0003-2879-3164 FU National Institutes of Health (NIH) [AI39394, AI70042, AI45587, AI60354, AI07245]; Agence Nationale de Recherche sur le SIDA; HMS CFAR Scholar Award FX HeLa TZM-b1 cells were obtained through the NIH AIDS Research and Reference Reagent Program from John Kappes, Xiaoyun Wu, and Tranzyme, Inc. We thank Manuel Llano for advice with the fractionation technique used for chromatin binding analyses, Peter Cherepanov and Lavanya Krishnan for their comments on the manuscript, and L. Krishnan for advice with figure preparation.; This study was supported by grants from the National Institutes of Health (NIH) (AI39394 and AI70042 [A.E.], AI45587 [J.L.], and AI60354 [Harvard Medical School Center for AIDS Research]) and the Agence Nationale de Recherche sur le SIDA (2005/004 and 2006/124 [M. L.]). N.Y. was supported by a HMS CFAR Scholar Award, and M.-C. S. was supported by NIH Training Grant AI07245. NR 71 TC 45 Z9 46 U1 1 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 DEC PY 2008 VL 82 IS 23 BP 11555 EP 11567 DI 10.1128/JVI.01561-08 PG 13 WC Virology SC Virology GA 370UX UT WOS:000260789700008 PM 18799576 ER PT J AU Zahn, RC Rett, MD Korioth-Schmitz, B Sun, Y Buzby, AP Goldstein, S Brown, CR Byrum, RA Freeman, GJ Letvin, NL Hirsch, VM Schmitz, JE AF Zahn, Roland C. Rett, Melisa D. Korioth-Schmitz, Birgit Sun, Yue Buzby, Adam P. Goldstein, Simoy Brown, Charles R. Byrum, Russell A. Freeman, Gordon J. Letvin, Norman L. Hirsch, Vanessa M. Schmitz, Joern E. TI Simian Immunodeficiency Virus (SIV)-Specific CD8(+) T-Cell Responses in Vervet African Green Monkeys Chronically Infected with SIVagm SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING ANTIBODY-RESPONSES; I-ASSOCIATED MYELOPATHY; HIV-1 INFECTION; NATURAL HOSTS; GRANZYME-B; VIRAL LOAD; PROLIFERATIVE CAPACITY; PROGRAMMED DEATH-1; IMMUNE-RESPONSES; TYPE-1 INFECTION AB African green monkeys (AGM) do not develop overt signs of disease following simian immunodeficiency virus (SIV) infection. While it is still unknown how natural hosts like AGM can cope with this lentivirus infection, a large number of investigations have shown that CD8(+) T-cell responses are critical for the containment of AIDS viruses in humans and Asian nonhuman primates. Here we have compared the phenotypes of T-cell subsets and magnitudes of SIV-specific CD8(+) T-cell responses in vervet AGM chronically infected with SIVagm and rhesus monkeys (RM) infected with SIVmac. In comparison to RM, vervet AGM exhibited weaker signs of immune activation and associated proliferation of CD8(+) T cells as detected by granzyme B, Ki-67, and programmed death 1 staining. By gamma interferon enzyme-linked immunospot assay and intracellular cytokine staining, SIV Gag- and Env-specific immune responses were detectable at variable but lower levels in vervet AGM than in RM. These observations demonstrate that natural hosts like SIV-infected vervet AGM develop SIV-specific T-cell responses, but the disease-free course of infection does not depend on the generation of robust CD8(+) T-cell responses. C1 [Zahn, Roland C.; Rett, Melisa D.; Korioth-Schmitz, Birgit; Sun, Yue; Buzby, Adam P.; Letvin, Norman L.; Schmitz, Joern E.] Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med,Ctr Life Sci, Boston, MA 02115 USA. [Goldstein, Simoy; Brown, Charles R.; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Byrum, Russell A.] Bioqual Inc, Rockville, MD 20852 USA. [Freeman, Gordon J.] Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Dept Med,Sch Med, Boston, MA 02115 USA. RP Schmitz, JE (reprint author), Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med,Ctr Life Sci, ECLS 1037,3 Blackfan Circle, Boston, MA 02115 USA. EM jschmitz@bidmc.harvard.edu RI Korioth-Schmitz, Birgit/M-7816-2015 OI Korioth-Schmitz, Birgit/0000-0002-5271-9223 FU NIH [AI065335, AI56299]; NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) [AI067854]; Harvard Medical School Center for AIDS Research (CFAR) [AI060354]; Foundation for the NIH through the Grand Challenges in Global Health initiative; Division of Intramural Research FX This work was supported by the NIH grants AI065335 (to J.E.S.) and AI56299 (to G.J.F.), NIAID Center for HIV/AIDS Vaccine Immunology (CHAVI) grant AI067854 (to N.L.L.), Harvard Medical School Center for AIDS Research (CFAR) grant AI060354, the Foundation for the NIH through the Grand Challenges in Global Health initiative (G.J.F.), and the Division of Intramural Research, NIAID, NIH (V. M. H., S. G., and C. R. B.). NR 76 TC 28 Z9 28 U1 0 U2 1 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 DEC PY 2008 VL 82 IS 23 BP 11577 EP 11588 DI 10.1128/JVI.01779-08 PG 12 WC Virology SC Virology GA 370UX UT WOS:000260789700010 PM 18829748 ER PT J AU Kar, AK Diaz-Griffero, F Li, Y Li, X Sodroski, J AF Kar, Alak Kanti Diaz-Griffero, Felipe Li, Yuan Li, Xing Sodroski, Joseph TI Biochemical and Biophysical Characterization of a Chimeric TRIM21-TRIM5 alpha Protein SO JOURNAL OF VIROLOGY LA English DT Article ID TRIM5-ALPHA RESTRICTION FACTOR; RETROVIRAL RESTRICTION; B30.2 DOMAIN; SIMIAN IMMUNODEFICIENCY; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; VIRUS RESTRICTION; UBIQUITIN LIGASE; HIV-1 INFECTION AB The tripartite motif (TRIM) protein, TRIM5 alpha, is an endogenous factor in primates that recognizes the capsids of certain retroviruses after virus entry into the host cell. TRIM5 alpha promotes premature uncoating of the capsid, thus blocking virus infection. Low levels of expression and tendencies to aggregate have hindered the biochemical, biophysical, and structural characterization of TRIM proteins. Here, a chimeric TRIM5 alpha protein (TRIM5Rh-21R) with a RING domain derived from TRIM21 was expressed in baculovirus-infected insect cells and purified. Although a fraction of the TRIM5Rh-21R protein formed large aggregates, soluble fractions of the protein formed oligomers (mainly dimers), exhibited a protease-resistant core, and contained a high percentage of helical secondary structure. Cross-linking followed by negative staining and electron microscopy suggested a globular structure. The purified TRIM5Rh-21R protein displayed E3-ligase activity in vitro and also self-ubiquitylated in the presence of ubiquitin-activating and -conjugating enzymes. The purified TRIM5Rh-21R protein specifically associated with human immunodeficiency virus type 1 capsid-like complexes; a deletion within the V1 variable region of the B30.2(SPRY) domain decreased capsid binding. Thus, the TRIM5Rh-21R restriction factor can directly recognize retroviral capsid-like complexes in the absence of other mammalian proteins. C1 [Kar, Alak Kanti; Diaz-Griffero, Felipe; Li, Yuan; Li, Xing; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst,Div AIDS, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst,Div AIDS, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Li, Yuan/B-4098-2013 FU National Institutes of Health [AI063987, AI076094]; Center for AIDS Research Award [AI06354]; International AIDS Vaccine Initiative FX We thank Charles Langelier and Wesley Sundquist for the plasmids expressing the OSF-FL and OSF-Delta V1 proteins and for helpful discussions. We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation.; This study was supported by grants from the National Institutes of Health (AI063987 and AI076094) and a Center for AIDS Research Award (AI06354), the International AIDS Vaccine Initiative, and the late William F. McCarty-Cooper. NR 52 TC 56 Z9 56 U1 1 U2 10 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 DEC PY 2008 VL 82 IS 23 BP 11669 EP 11681 DI 10.1128/JVI.01559-08 PG 13 WC Virology SC Virology GA 370UX UT WOS:000260789700018 PM 18799572 ER PT J AU Langelier, CR Sandrin, V Eckert, DM Christensen, DE Chandrasekaran, V Alam, SL Aiken, C Olsen, JC Kar, AK Sodroski, JG Sundquist, WI AF Langelier, Charles R. Sandrin, Virginie Eckert, Debra M. Christensen, Devin E. Chandrasekaran, Viswanathan Alam, Steven L. Aiken, Christopher Olsen, John C. Kar, Alak Kanti Sodroski, Joseph G. Sundquist, Wesley I. TI Biochemical Characterization of a Recombinant TRIM5 alpha Protein That Restricts Human Immunodeficiency Virus Type 1 Replication SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; E3 UBIQUITIN LIGASE; RETROVIRAL RESTRICTION; HIV-1 INFECTION; CYCLOPHILIN-A; B30.2(SPRY) DOMAIN; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; RHESUS TRIM5-ALPHA; STRUCTURAL BASIS AB The rhesus monkey intrinsic immunity factor TRIM5 alpha(rh) recognizes incoming capsids from a variety of retroviruses, including human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV), and inhibits the accumulation of viral reverse transcripts. However, direct interactions between restricting TRIM5 alpha proteins and retroviral capsids have not previously been demonstrated using pure recombinant proteins. To facilitate structural and mechanistic studies of retroviral restriction, we have developed methods for expressing and purifying an active chimeric TRIM5 alpha(rh) protein containing the RING domain from the related human TRIM21 protein. This recombinant TRIM5-21R protein was expressed in SF-21 insect cells and purified through three chromatographic steps. Two distinct TRIM5-21R species were purified and shown to correspond to monomers and dimers, as analyzed by analytical ultracentrifugation. Chemically cross-linked recombinant TRIM5-21R dimers and mammalian-expressed TRIM5-21R and TRIM5 alpha proteins exhibited similar sodium dodecyl sulfate-polyacrylamide gel electrophoresis mobilities,indicating that mammalian TRIM5 alpha proteins are predominantly dimeric. Purified TRIM5-21R had ubiquitin ligase activity and could autoubquitylate with different E2 ubiquitin conjugating enzymes in vitro. TRIM5-21R bound directly to synthetic capsids composed of recombinant HIV-1 CA-NC proteins and to authentic EIAV core particles. HIV-1 CA-NC assemblies bound dimeric TRIM5-21R better than either monomeric TRIM5-21R or TRIM5-21R constructs that lacked the SPRY domain or its V1 loop. Thus, our studies indicate that TRIM5 alpha proteins are dimeric ubiquitin E3 ligases that recognize retroviral capsids through direct interactions mediated by the SPRY domain and demonstrate that these activities can be recapitulated in vitro using pure recombinant proteins. C1 [Langelier, Charles R.; Sandrin, Virginie; Eckert, Debra M.; Christensen, Devin E.; Chandrasekaran, Viswanathan; Alam, Steven L.; Sundquist, Wesley I.] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA. [Aiken, Christopher] Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. [Olsen, John C.] Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Dept Med, Chapel Hill, NC 27599 USA. [Kar, Alak Kanti; Sodroski, Joseph G.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. RP Sundquist, WI (reprint author), Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA. EM wes@biochem.utah.edu FU National Institutes of Health [AI076121, AI063978, AI076094, AI045405, GM082545] FX We are grateful to Chad Nelson and the University of Utah Mass Spectrometry facility for ESI and LC mass spectral analyses, Rachel Klevit for the gift of expression vectors for E1 and E2 enzymes, and Chris Hill for critical review of the manuscript.; This research was supported by National Institutes of Health grants AI076121 (to C. A.), AI063978 and AI076094 (to J. G. S.), and AI045405 and GM082545 (to W. I. S.). NR 74 TC 93 Z9 94 U1 1 U2 5 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 DEC PY 2008 VL 82 IS 23 BP 11682 EP 11694 DI 10.1128/JVI.01562-08 PG 13 WC Virology SC Virology GA 370UX UT WOS:000260789700019 PM 18799573 ER PT J AU Salloum, S Oniangue-Ndza, C Neumann-Haefelin, C Hudson, L Giugliano, S Siepen, MAD Nattermann, J Spengler, U Lauer, GM Wiese, M Klenerman, P Bright, H Scherbaum, N Thimme, R Roggendorf, M Viazov, S Timm, J AF Salloum, Shadi Oniangue-Ndza, Cesar Neumann-Haefelin, Christoph Hudson, Laura Giugliano, Silvia Siepen, Marc Aus Dem Nattermann, Jacob Spengler, Ulrich Lauer, Georg M. Wiese, Manfred Klenerman, Paul Bright, Helen Scherbaum, Norbert Thimme, Robert Roggendorf, Michael Viazov, Sergei Timm, Joerg TI Escape from HLA-B*08-Restricted CD8 T Cells by Hepatitis C Virus Is Associated with Fitness Costs SO JOURNAL OF VIROLOGY LA English DT Article ID RNA HELICASE DOMAIN; LYMPHOCYTE RESPONSE; CHRONIC INFECTION; SOURCE OUTBREAK; SINGLE-SOURCE; IN-VIVO; TYPE-1; REPLICATION; PROTEASE; GAG AB The inherent sequence diversity of the hepatitis C virus (HCV) represents a major hurdle for the adaptive immune system to control viral replication. Mutational escape within targeted CD8 epitopes during acute HCV infection has been well documented and is one possible mechanism for T-cell failure. HLA-B*08 was recently identified as one HLA class I allele associated with spontaneous clearance of HCV replication. Selection of escape mutations in the immunodominant HLA-B*08-restricted epitope HSKKKCDEL(1395-1403) was observed during acute infection. However, little is known about the impact of escape mutations in this epitope on viral replication capacity. Their previously reported reversion back toward the consensus residue in patients who do not possess the B*08 allele suggests that the consensus sequence in this epitope is advantageous for viral replication in the absence of immune pressure. The aim of this study was to determine the impact of mutational escape from this immunodominant epitope on viral replication. We analyzed it with a patient cohort with chronic HCV genotype 1b infection and in a single-source outbreak (genotype 1b). Sequence changes in this highly conserved region are rare and selected almost exclusively in the presence of the HLA-B*08 allele. When tested in the subgenomic replicon (Con1), the observed mutations reduce viral replication compared with the prototype sequence. The results provide direct evidence that escape mutations in this epitope are associated with fitness costs and that the antiviral effect of HLA-B*08-restricted T cells is sufficiently strong to force the virus to adopt a relatively unfavorable sequence. C1 [Salloum, Shadi; Oniangue-Ndza, Cesar; Giugliano, Silvia; Siepen, Marc Aus Dem; Roggendorf, Michael; Viazov, Sergei; Timm, Joerg] Univ Essen Gesamthsch, Dept Virol, D-45147 Essen, Germany. [Neumann-Haefelin, Christoph; Thimme, Robert] Univ Freiburg, Dept Med 2, D-79106 Freiburg, Germany. [Hudson, Laura; Bright, Helen] GlaxoSmithKline Inc, Dept Virol, Stevenage SG1 2NY, Herts, England. [Nattermann, Jacob; Spengler, Ulrich] Univ Bonn, Dept Med 1, D-53105 Bonn, Germany. [Lauer, Georg M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02129 USA. [Wiese, Manfred] St Georg Hosp, Dept Med 2, D-04129 Leipzig, Germany. [Klenerman, Paul] John Radcliffe Hosp, Oxford Biomed Res Ctr, Oxford OX3 9DU, England. [Scherbaum, Norbert] Hosp Univ Duisburg Essen, Rhine State Hosp, Dept Psychiat & Psychotherapy, Addict Res Grp, D-45147 Essen, Germany. RP Timm, J (reprint author), Univ Essen Gesamthsch, Dept Virol, Virchowstr 179, D-45147 Essen, Germany. EM joerg.timm@uni-due.de RI Neumann-Haefelin, Christoph/E-5550-2011 FU Deutsche Forschungsgemeinschaft DFG [TI 323/3-1]; Wellcome Trust, James Martin School; NIHR Biomedical Research Centre Programme; Federal Ministry of Education and Research (German Hepatitis Network) FX We thank the East German Study Group e.V. for contributing samples of the East German Anti-D cohort.; J.T. was supported by the Deutsche Forschungsgemeinschaft DFG (TI 323/3-1). P. K. was supported by the Wellcome Trust, James Martin School for the 21st Century, and NIHR Biomedical Research Centre Programme. This work was supported by the Federal Ministry of Education and Research (German Hepatitis Network). NR 33 TC 34 Z9 34 U1 0 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 DEC PY 2008 VL 82 IS 23 BP 11803 EP 11812 DI 10.1128/JVI.00997-08 PG 10 WC Virology SC Virology GA 370UX UT WOS:000260789700032 PM 18815309 ER PT J AU Accortt, EE Freeman, MP Allen, JJB AF Accortt, Eynav Elgavish Freeman, Marlene P. Allen, John J. B. TI Women and Major Depressive Disorder: Clinical Perspectives on Causal Pathways SO JOURNAL OF WOMENS HEALTH LA English DT Review ID PREMENSTRUAL DYSPHORIC DISORDER; FRONTAL EEG ASYMMETRY; NATIONAL-COMORBIDITY-SURVEY; SEX-DIFFERENCES; POSTPARTUM DEPRESSION; LIFE STRESS; GENDER DIFFERENCES; MENSTRUAL-CYCLE; ELECTROENCEPHALOGRAPHIC ASYMMETRY; PSYCHIATRIC-DISORDERS AB Background and aims: Epidemiological data on the prevalence of mood disorders demonstrate that major depressive disorder (MDD) is approximately twice as common in women as in men and that its first onset peaks during the reproductive years. We aimed to review key social, psychological, and biological factors that seem strongly implicated in the etiology of major depression and to focus on sex-specific aspects of depression, such as the role of a woman's reproductive life cycle in depressive symptomatology. Methods: A review of the literature, from 1965 to present, was conducted. Results: An integrated etiological model best explains gender and sex differences in depression. Social, psychological, and biological variables must be simultaneously taken into account. These vulnerabilities include ( but are not limited to) gender-specific roles in society, life stress such as trauma, a tendency toward ruminative coping strategies, and the effects of sex hormones and genetic factors. Conclusions: To effectively treat MDD in women and to prevent the recurrence of illness in vulnerable women, clinicians must understand the sex-specific aspects of mood disorders over the longitudinal course of women's reproductive lives. A biopsychosocial approach should, therefore, be the main focus of future research and practice, to eventually result in an integrated etiological model of depression in women. Based on the prevalence of MDD in women, timely screening, diagnosis, and intervention should be public health priorities. C1 [Accortt, Eynav Elgavish; Allen, John J. B.] Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. [Freeman, Marlene P.] Massachusetts Gen Hosp, Dept Psychiat, Ctr Womens Mental Hlth, Boston, MA 02114 USA. RP Accortt, EE (reprint author), Univ Arizona, Dept Psychol, POB 210068, Tucson, AZ 85721 USA. EM eynav@email.arizona.edu FU National Institute for Mental Health; U. S. Food and Drug Administration; GlaxoSmithKline; Meadows Foundation; Chatham Institute (KV Pharmaceuticals), Lilly, Forest; National Institutes of Health; National Alliance for Research on Schizophrenia and Depression; Institute for Mental Health Research FX E. E. A. has nothing to disclose. M. P. F. received research support from the National Institute for Mental Health, U. S. Food and Drug Administration, GlaxoSmithKline, The Meadows Foundation, Honorarium from CME program from the Chatham Institute (KV Pharmaceuticals), Lilly, Forest. J.B.A. received funding from the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression, and the Institute for Mental Health Research. NR 122 TC 46 Z9 49 U1 6 U2 22 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2008 VL 17 IS 10 BP 1583 EP 1590 DI 10.1089/jwh.2007.0592 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OG UT WOS:000261331500008 PM 19049352 ER PT J AU Bartels, C Goetz, S Ward, E Carnes, M AF Bartels, Christie Goetz, Sarah Ward, Earlise Carnes, Molly TI Internal Medicine Residents' Perceived Ability to Direct Patient Care: Impact of Gender and Experience SO JOURNAL OF WOMENS HEALTH LA English DT Article ID SEX-ROLE INVENTORY; WOMEN; STEREOTYPES; LEADERSHIP; METAANALYSIS AB Background: Physicians are expected to effect patient care by giving orders to members of a healthcare team. Because women are socialized to be less directive than men, the assertive behavior required of new physicians may be experienced differently by male and female residents. We sought to explore the effects of gender and year of training on residents' experiences and perceived ability to direct patient care. Methods: This was a mixed-methods, cross-sectional, descriptive study employing a quantitative written survey and qualitative interviews among internal medicine residents at an academic health center. Measurements included questionnaires and interviews about stress, assertiveness, and personal factors that influence their effectiveness in directing patient care. Analyses examined differences by gender and year of training. Results: One hundred residents were invited to participate; 65 returned questionnaires, and 16 of these residents were interviewed. Compared with male residents, female residents selected less assertive behaviors for clinical scenarios ( p = 0.047) and were more likely to perceive gender as inhibiting their ability to influence patient care ( p = 0.01). Stress associated with being assertive varied more with experience than gender. Interviews corroborated these findings and supported the complexity of gender norms for behavior for female residents in a directive leadership position. Conclusions: When compared with male peers, female residents reported more gender issues in residency and chose less assertive behaviors in clinical scenarios. Experience mitigated some gender differences. Our findings suggest that discussion of the existing research on prescriptive gender norms for behavior and leadership may be warranted in resident orientation. C1 [Bartels, Christie; Carnes, Molly] Univ Wisconsin, Dept Med, Madison, WI 53715 USA. [Carnes, Molly] William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RP Carnes, M (reprint author), Univ Wisconsin, Dept Med Psychiat & Ind & Syst Engn, Ctr Womens Hlth Res, 700 Regent St,Suite 101, Madison, WI 53715 USA. EM mlcarnes@wisc.edu FU University of Wisconsin-Madison School of Medicine and Public Health; Jean Manchester Biddick-Bascom Endowed Professorship; Meriter Hospital FX This work was supported by a Shapiro Grant from the University of Wisconsin-Madison School of Medicine and Public Health, the Jean Manchester Biddick-Bascom Endowed Professorship, and Meriter Hospital. We thank Tim Hess for statistical support and Linda Baier for reviewing the manuscript. NR 27 TC 16 Z9 16 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2008 VL 17 IS 10 BP 1615 EP 1621 DI 10.1089/jwh.2008.0798 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 378OG UT WOS:000261331500012 PM 19049356 ER PT J AU Martin, JL Alam, T Harker, JO Josephson, KR Alessi, CA AF Martin, Jennifer L. Alam, Tarannum Harker, Judith O. Josephson, Karen R. Alessi, Cathy A. TI Sleep in Assisted Living Facility Residents Versus Home-Dwelling Older Adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article DE Sleep; Aging; Circadian rhythms; Assisted living ID ACTIVITY RHYTHMS; INDEX; WAKE AB Background. Sleep problems among assisted living facility (ALF) residents are not well understood, and sleep-related differences between ALF residents and home-dwelling older adults have not been examined. Methods. We compared sleep patterns in 19 ALF residents to sleep patterns in 19 matched home-dwelling older people (age >= 65 years). All were participating in the follow-up portion of a longitudinal study of sleep and functional outcomes following post-acute rehabilitation. Sleep was assessed with the Pittsburgh Sleep Quality Index and l week of wrist actigraphy. Results. By actigraphy, ALF residents awoke earlier in the morning and exhibited more nighttime awakenings compared to home-dwelling participants (06:50 hours +/- 1:29 hours vs 07:51 hours +/- 1:19 hours and 19.5 +/- 8.5 vs 12.9 +/- 11.4 awakenings, respectively). Conclusions. Larger studies are needed to confirm these initial findings that ALF residents have more disrupted sleep than do home-dwelling older persons, and to examine the functional and health consequences of poor sleep among ALF residents. C1 [Martin, Jennifer L.; Alam, Tarannum; Harker, Judith O.; Josephson, Karen R.; Alessi, Cathy A.] VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. [Martin, Jennifer L.; Alessi, Cathy A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Martin, JL (reprint author), VA Sepulveda GRECC 11E, 16111 Plummer St, North Hills, CA 91343 USA. EM jennifer.martin@va.gov FU National Institute on Aging (NIA) [K23AG028452]; VA Special Fellowship Program in Advanced Geriatrics; VA Health Services Research and Development Service [IIR01-053-1, AlA03-047]; UCLA Older Americans Independence Center (OAIC) [5-P60-AG010415]; VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center FX This work was supported by National Institute on Aging (NIA) grant K23AG028452, the VA Special Fellowship Program in Advanced Geriatrics, VA Health Services Research and Development Service grants IIR01-053-1 and AlA03-047. UCLA Older Americans Independence Center (OAIC) grant 5-P60-AG010415, and by the VA Greater Los Angeles Healthcare System Geriatric Research, Education and Clinical Center.; Portions of this article were presented at the 2005 American Geriatrics Society meeting, Orlando, Florida. NR 17 TC 6 Z9 6 U1 0 U2 1 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD DEC PY 2008 VL 63 IS 12 BP 1407 EP 1409 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 395PG UT WOS:000262535400018 PM 19126856 ER PT J AU Isshiki, K He, ZH Maeno, Y Ma, RC Yasuda, Y Kuroki, T White, GS Patti, ME Weir, GC King, GL AF Isshiki, Keiji He, Zhiheng Maeno, Yasuhiro Ma, Ronald C. Yasuda, Yutaka Kuroki, Tatsuya White, Gregory S. Patti, Mary E. Weir, Gordon C. King, George L. TI Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells SO KIDNEY INTERNATIONAL LA English DT Article DE diabetes; insulin; SOCS2; STAT; signaling; nephropathy ID GROWTH-FACTOR-I; DIABETIC-NEPHROPATHY; CYTOKINE SIGNALING-2; SKELETAL-MUSCLE; SUPPRESSOR; RECEPTOR; MICE; COMPLICATIONS; PROTEINS; MELLITUS AB Renal hypertrophy and deposition of extracellular matrix proteins are consistent findings in diabetic nephropathy and these processes can be halted or reversed by euglycemic control. Using DNA microarray analysis of glomerular RNA from control and diabetic rats we found that the expression levels of insulin-like growth factor 1 receptor (IGF-1R) were increased while those of suppressor of cytokine signaling 2 (SOCS2) and STAT5 were decreased. All of these changes were normalized by islet cell transplantation. Overexpression of SOCS2 in rat mesangial cells inhibited IGF-1-induced activation of extracellular signal-regulated kinase, which subsequently reduced type IV collagen and DNA synthesis, an effect due to interaction of SOCS2 with IGF-1R. Inhibition of SOCS2 overexpression by small interfering RNA suppressed IGF-1R-mediated actions by preventing phosphorylation of tyrosine 317 in the p66Shc adaptor protein; however, overexpression of either SOCS1 or SOCS3 did not affect IGF-1R signaling. Insulin directly increased STAT5 and SOCS2 expression in mesangial cells. This study shows that insulin can inhibit the mitogenic action of IGF-1 in mesangial cells by regulating STAT5/SOCS2 expression. Insulin deficiency may contribute to the mesangial expansion found in diabetes through reduced STAT5/SOCS2 expression. C1 [Isshiki, Keiji; He, Zhiheng; Maeno, Yasuhiro; Ma, Ronald C.; Yasuda, Yutaka; Kuroki, Tatsuya; White, Gregory S.; Patti, Mary E.; Weir, Gordon C.; King, George L.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU National Institute of Health [DK53105]; Joslin's Diabetes and Endocrinology Research Center [DK36836]; American Diabetes Association; Juvenile Diabetes Research Foundation FX This work is supported by a grant from National Institute of Health (DK53105) to GLK, and DK36836 (Joslin's Diabetes and Endocrinology Research Center Grant). KI and YY are recipients of American Diabetes Association mentor-based fellowship. ZH is a recipient of Juvenile Diabetes Research Foundation fellowship. NR 37 TC 8 Z9 9 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2008 VL 74 IS 11 BP 1434 EP 1443 DI 10.1038/ki.2008.403 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 372CQ UT WOS:000260879600011 PM 19008912 ER PT J AU Zalyapin, EA Bouley, R Hasler, U Vilardaga, JP Lin, HY Brown, D Ausiello, DA AF Zalyapin, Elena A. Bouley, Richard Hasler, Udo Vilardaga, Jean-Pierre Lin, Herbert Y. Brown, Dennis Ausiello, Dennis A. TI Effects of the renal medullary pH and ionic environment on vasopressin binding and signaling SO KIDNEY INTERNATIONAL LA English DT Article DE G-protein-coupled receptor signaling; vasopressin; hypertonicity ID THICK ASCENDING LIMB; DUCT PRINCIPAL CELLS; ARGININE-VASOPRESSIN; COLLECTING DUCT; MOLECULAR-CLONING; CAMP PRODUCTION; ANGIOTENSIN-II; WATER CHANNEL; V2 RECEPTOR; RAT-KIDNEY AB The kidney has a cortico-medullary interstitial gradient of decreasing pH and increasing concentrations of sodium chloride and urea, but the influence of these gradients on receptor signaling is largely unknown. Here, we measured G-protein coupled receptor function in LLC-PK1 cells acutely exposed to conditions mimicking different kidney regions. Signaling through the parathyroid hormone receptor, normally expressed in the cortex, was greatly reduced at an acidic pH similar to that of the inner medulla. Parathyroid hormone receptor, tagged with green fluorescent protein, showed no ligand-induced internalization. In contrast, under both acidic and hyperosmotic conditions, vasopressin increased intracellular cAMP, and upon binding to its type 2 receptor (V2R) was internalized and degraded. Dosedisplacement binding assays with selective vasopressin/oxytocin receptor ligands under inner medullary conditions indicated a shift in the V2R pharmacological profile. Oxytocin did not bind to the V2R, as it does under normal conditions and the vasopressin type 1 receptor (V1R) had reduced affinity for vasopressin compared to the V2R in low pH and high osmolality. We suggest that the cortico-medullary gradient causes a receptor-specific selectivity in ligand binding that is of functional significance to the kidney. While the gradient is important for urinary concentration, it may also play a substantial role in fine-tuning of the vasopressin response through the V2R. C1 [Bouley, Richard] Massachusetts Gen Hosp, Div Nephrol, MGH Ctr Syst Biol, Program Membrane Biol,Simches Res Ctr, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Vilardaga, Jean-Pierre] Harvard Univ, Sch Med, Boston, MA USA. RP Bouley, R (reprint author), Massachusetts Gen Hosp, Div Nephrol, MGH Ctr Syst Biol, Program Membrane Biol,Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM bouley.richard@mgh.harvard.edu FU NIH [PO1DK38452, DK071837]; National Kidney Foundation; Swiss FSBMB Fellowship; ECOR Fellowship; Boston Area Diabetes and Endocrinology Research Center [DK57521]; Study of Inflammatory Bowel Disease [DK43341] FX This work was supported by NIH grants PO1DK38452 (DB and DAA). H. Y. Lin was supported by an NIH RO1award (DK071837). R. Bouley received an investigator award from the National Kidney Foundation. U. Hasler is supported by a Swiss FSBMB Fellowship as well as an ECOR Fellowship awarded by MGH. The Microscopy Core facility of the MGH Program in Membrane Biology receives additional support from the Boston Area Diabetes and Endocrinology Research Center (DK57521) and the Center for the Study of Inflammatory Bowel Disease (DK43341). NR 78 TC 10 Z9 10 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2008 VL 74 IS 12 BP 1557 EP 1567 DI 10.1038/ki.2008.412 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 382TJ UT WOS:000261628000010 PM 18813286 ER PT J AU Fiorentino, M Zadra, G Palescandolo, E Fedele, G Bailey, D Fiore, C Nguyen, PL Migita, T Zamponi, R Di Vizio, D Priolo, C Sharma, C Xie, W Hemler, ME Mucci, L Giovannucci, E Finn, S Loda, M AF Fiorentino, Michelangelo Zadra, Giorgia Palescandolo, Emanuele Fedele, Giuseppe Bailey, Dyane Fiore, Christopher Nguyen, Paul L. Migita, Toshiro Zamponi, Raffaella Di Vizio, Dolores Priolo, Carmen Sharma, Chandan Xie, Wanling Hemler, Martin E. Mucci, Lorelei Giovannucci, Edward Finn, Stephen Loda, Massimo TI Overexpression of fatty acid synthase is associated with palmitoylation of Wnt1 and cytoplasmic stabilization of beta-catenin in prostate cancer SO LABORATORY INVESTIGATION LA English DT Article DE beta-catenin; fatty acid synthase; prostate cancer; immunohistochemistry; palmitoylation; Wnt1 ID EXPRESSION; CELLS; CARCINOMA; APOPTOSIS; GROWTH; ADENOCARCINOMA; LOCALIZATION; PREDICTOR; INHIBITOR; MORTALITY AB Fatty acid synthase (FASN), a key metabolic enzyme for liponeogenesis highly expressed in several human cancers, displays oncogenic properties such as resistance to apoptosis and induction of proliferation when overexpressed. To date, no mechanism has been identified to explain the oncogenicity of FASN in prostate cancer. We generated immortalized prostate epithelial cells (iPrECs) overexpressing FASN, and found that (14)C-acetate incorporation into palmitate synthesized de novo by FASN was significantly elevated in immunoprecipitated Wnt-1 when compared to isogenic cells not overexpressing FASN. Overexpression of FASN caused membranous and cytoplasmic beta-catenin protein accumulation and activation, whereas FASN knockdown by short-hairpin RNA resulted in a reduction in the extent of beta-catenin activation. Orthotopic transplantation of iPrECs overexpressing FASN in nude mice resulted in invasive tumors that overexpressed beta-catenin. A strong significant association between FASN and cytoplasmic ( stabilized) beta-catenin immunostaining was found in 862 cases of human prostate cancer after computerized subtraction of the membranous beta-catenin signal (P < 0.001, Spearman's rho = 0.33). We propose that cytoplasmic stabilization of beta-catenin through palmitoylation of Wnt-1 and subsequent activation of the pathway is a potential mechanism of FASN oncogenicity in prostate cancer. C1 [Fiorentino, Michelangelo; Zadra, Giorgia; Palescandolo, Emanuele; Fedele, Giuseppe; Bailey, Dyane; Fiore, Christopher; Nguyen, Paul L.; Migita, Toshiro; Zamponi, Raffaella; Priolo, Carmen; Finn, Stephen; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Dept Med Oncol, Boston, MA 02115 USA. [Di Vizio, Dolores; Hemler, Martin E.] Harvard Univ, Sch Med, Childrens Hosp, Dept Urol, Boston, MA USA. [Sharma, Chandan] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Xie, Wanling] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Mucci, Lorelei; Giovannucci, Edward] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Brigham & Womens Hosp,Channing Lab, Boston, MA 02115 USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, D1536,44 Binney St, Boston, MA 02115 USA. EM massimo_loda@dfci.harvard.edu FU National Cancer Institute [RO1CA131945, PO1CA89021, P50 CA90381, P50 CA55075]; Prostate Cancer Foundation, DFCI-Novartis Drug Development Program; Linda and Arthur Gelb Center for Translational Research; Jimmy Fund; Loda laboratory; Samuel Waxman Foundation [SPA P01-Waxman-CS01]; NIH [GM38903]; American-Italian Cancer Foundation FX This work (to ML) was supported from the National Cancer Institute (RO1CA131945, PO1CA89021, P50 CA90381 and CA55075), the Prostate Cancer Foundation, DFCI-Novartis Drug Development Program, the Linda and Arthur Gelb Center for Translational Research, a gift from Nuclea Biomarkers to the Jimmy Fund and the Loda laboratory, and the Samuel Waxman Foundation (SPA P01-Waxman-CS01). This study was also support to MEH from NIH grant GM38903. GZ and EP are supported by grants from the American-Italian Cancer Foundation. We are grateful to Dr William C Hahn for the engineering of the immortalized human prostate epithelial cell lines and to Dr Phillip Febbo and Dr Ramesh A Shivdasani for helpful suggestions. NR 43 TC 60 Z9 64 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD DEC PY 2008 VL 88 IS 12 BP 1340 EP 1348 DI 10.1038/labinvest.2008.97 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 375JD UT WOS:000261109100008 PM 18838960 ER PT J AU Norden, AD Drappatz, J Wen, PY AF Norden, Andrew D. Drappatz, Jan Wen, Patrick Y. TI Novel anti-angiogenic therapies for malignant gliomas SO LANCET NEUROLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; HIGH-GRADE GLIOMAS; NEWLY-DIAGNOSED GLIOBLASTOMA; TUMOR ANGIOGENESIS; IN-VIVO; ANAPLASTIC ASTROCYTOMA; METRONOMIC CHEMOTHERAPY; EUROPEAN ORGANIZATION; RADIATION-THERAPY AB Background Despite optimum treatment with surgery, radiation therapy, and chemotherapy, most patients with malignant glioma have a poor prognosis. Malignant gliomas are vascular tumours that produce vascular endothelial growth factor (VEGF), which is an important mediator of angiogenesis. Preclinical data indicate that angiogenesis is essential for the proliferation and survival of malignant glioma cells, which suggests that inhibition of angiogenesis might be an effective therapeutic strategy. Anti-angiogenic therapies that target VEGF and the VEGF receptor (VEGFR) are effective adjuncts to the treatment of solid tumours. Normalisation of dilated and leaky tumour vasculature might also enable anti-angiogenic therapy to increase the efficacy of radiation therapy and cytotoxic chemotherapy. Recent developments Several studies have investigated the use of bevacizumab-a humanised monoclonal antibody against VEGF-for patients with recurrent malignant glioma. Treatment with bevacizumab is commonly combined with cytotoxic chemotherapy and results in dramatic responses seen on radiographs, prolongation of progression-free survival, and less need for corticosteroids. Similar results have been shown with small-molecule inhibitors of VEGFR, such as cediranib. Anti-angiogenic treatment is generally well tolerated but common adverse effects include hypertension and proteinuria, whereas the potentially more serious adverse effects, such as thromboembolic disease and haemorrhage, occur infrequently. At least half of patients fail to respond to anti-angiogenic treatment and the response duration is variable. Resistance to anti-angiogenic therapy might implicate alternative pro-angiogenic factors, such as basic fibroblast growth factor, stromal-derived factor-la, the angiopoietin receptor Tie2, and placental growth factor. Anti-angiogenic therapy might also lead to mobilisation of circulating endothelial cells towards the turnout, which supports angiogenesis. Another possible mechanism of resistance of malignant glioma cells might be upregulation of pro-invasive molecules, which would result in increased infiltrative turnout growth along the blood vessels. Where next? Although anti-angiogenic therapies are promising, the duration of response with available regimens is modest. Continuing investigations will determine whether these drugs are best used for newly diagnosed or recurrent tumours and will establish the optimum combinations with radiation, cytotoxic chemotherapy, and other targeted molecular compounds. As yet, there are no effective treatments for patients on anti-angiogenic therapies whose tumours progress. Further understanding of the mechanisms of resistance to anti-angiogenic therapies and better selection of patients will be crucial to improve outcomes for patients with malignant glioma. C1 [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Brigham & Womens Hosp, Dept Neurol, Div Neurooncol, Boston, MA 02115 USA. [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Dept Med Oncol, Ctr Neurooncol, Boston, MA USA. [Norden, Andrew D.; Drappatz, Jan; Wen, Patrick Y.] Harvard Univ, Sch Med, Boston, MA USA. RP Norden, AD (reprint author), Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St, Boston, MA 02115 USA. EM anorden@partners.org FU Cure Brain Tumor research funds FX The authors thank the Amos E Wasgatt, Neil Harrington, Christopher S Elliott, and Par Fore The Cure Brain Tumor research funds for their financial support. NR 84 TC 126 Z9 135 U1 0 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD DEC PY 2008 VL 7 IS 12 BP 1152 EP 1160 DI 10.1016/S1474-4422(08)70260-6 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 379KV UT WOS:000261396000020 PM 19007739 ER PT J AU Platt, MP Cunnane, ME Curtin, HD Metson, R AF Platt, Michael P. Cunnane, Mary E. Curtin, Hugh D. Metson, Ralph TI Anatomical Changes of the Ethmoid Cavity After Endoscopic Sinus Surgery SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 111th Annual Meeting of the Triological-Society CY MAY 03-04, 2008 CL Orlando, FL SP Triol Soc DE Endoscopic sinus surgery; ethmoid sinus; sinusitis ID PARANASAL SINUSES; CYSTIC-FIBROSIS; FACIAL GROWTH; CT AB Objective: Alteration of the bony architecture of the sinus cavities has been observed in chronic sinusitis. Plasticity of the ethmoid sinus framework after endoscopic surgery, however, is a newly described entity. The objective of this study was to determine the incidence and extent of changes in ethmoid size after ethmoidectomy. Study Design: Retrospective review performed at an academic medical center. Methods: Computed tomography scans performed from 2006 through 2007 at the Massachusetts Eye and Ear Infirmary (n = 5,131) were reviewed to identify 100 consecutive patients who underwent sinus surgery and met inclusion criteria. Seven dimensions were measured for each pre- and postoperative scan (n = 200) using Voxar 3D software. Results: Computed tomography scans performed before and 2 to 37 months after ethmoidectomy demonstrated a decrease of 1.1 +/- 1.6 mm in mean ethmoid cavity width at the level of the cribriform plate and posterior globe after surgery (P < .0001). Twenty-five patients (25%) had > 1 mm decrease in mean ethmoid width, and six patients (6%) had a decrease of >2 mm (mean 3.1 +/- 0.9 mm). These findings seemed to be the result of postoperative bowing of the medial ethmoid walls with a corresponding increase in orbital volume. These volumetric changes resulted in a postoperative subclinical retrodisplacement (enophthalmos) of the globes (mean 0.2 +/- 0.8 mm, P = .008). The extent of surgery, including performance of frontal recess dissection (P = .007) and total ethmoidectomy (P = .021) were found to be independent predictors of the observed changes in sinus dimensions. Conclusions: Postsurgical plasticity of the ethmoid cavity is a new concept supported by observed changes in sinus dimensions after ethmoidectomy. These changes C1 [Platt, Michael P.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Cunnane, Mary E.] Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. [Curtin, Hugh D.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. EM Ralph_metson@meei.harvard.edu NR 10 TC 5 Z9 5 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2008 VL 118 IS 12 BP 2240 EP 2244 DI 10.1097/MLG.0b013e31818379cd PG 5 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 405CV UT WOS:000263200900029 PM 19029868 ER PT J AU Cavo, M Attal, M Gertz, MA Giralt, S Ludwig, H Morgan, GJ Anderson, KC AF Cavo, Michele Attal, Michel Gertz, Morie A. Giralt, Sergio Ludwig, Heinz Morgan, Gareth J. Anderson, Kenneth C. TI Proceedings of an educational symposium at the 34th Annual Meeting of the European Group for Blood and Marrow Transplantation 30 March 2008 Florence, Italy Lenalidomide in multiple myeloma: in pursuit of optimal treatment SO LEUKEMIA RESEARCH LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/24nd Meeting of the EBMT-Nurses-Group/7th Meeting of the EBMT-Data-Management-Group CY MAR 30-APR 02, 2008 CL Florence, ITALY SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data Management Grp ID NEWLY-DIAGNOSED MYELOMA; ELDERLY UNTREATED PATIENTS; BORTEZOMIB PLUS MELPHALAN; AUTOLOGOUS TRANSPLANTATION; COMBINATION THERAPY; RANDOMIZED-TRIAL; DEXAMETHASONE; THALIDOMIDE; CHEMOTHERAPY; PREDNISONE C1 [Cavo, Michele] Univ Bologna, Sch Med, Seragnoli Inst Hematol & Med Oncol, Bologna, Italy. [Attal, Michel] Univ Toulouse 3, Dept Haematol, F-31062 Toulouse, France. [Attal, Michel] Purpan Hosp, Dept Haematol, Toulouse, France. [Gertz, Morie A.] Mayo Clin, Dept Internal Med, Div Hematol, Rochester, MN USA. [Giralt, Sergio] Univ Texas Houston, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Ludwig, Heinz] Wilhelminenspital Stadt Wien, Ctr Oncol & Haematol, Dept Med 1, Vienna, Austria. [Morgan, Gareth J.] Inst Canc Res, Sutton, Surrey, England. [Morgan, Gareth J.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cavo, M (reprint author), Univ Bologna, Sch Med, Seragnoli Inst Hematol & Med Oncol, Bologna, Italy. OI CAVO, MICHELE/0000-0003-4514-3227 NR 69 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2008 VL 32 SU 1 BP S1 EP S24 DI 10.1016/S0145-2126(08)70002-X PG 24 WC Oncology; Hematology SC Oncology; Hematology GA 369UY UT WOS:000260720600001 PM 18954677 ER PT J AU Kozak, KR Hong, TS Sluss, PM Lewandrowski, EL Aleryani, SL MacDonald, SM Choi, NC Yock, TI AF Kozak, Kevin R. Hong, Theodore S. Sluss, Patrick M. Lewandrowski, Elizabeth L. Aleryani, Samir L. MacDonald, Shannon M. Choi, Noah C. Yock, Torunn I. TI Cardiac blood biomarkers in patients receiving thoracic (chemo)radiation SO LUNG CANCER LA English DT Article DE Cardiotoxicity; Troponin; CK-MB; BNP; Radiation; Lung cancer ID BREAST-CANCER; ADJUVANT RADIOTHERAPY; LUNG-CANCER; POSTOPERATIVE RADIOTHERAPY; HODGKINS-DISEASE; SURVIVORS; CHILDREN; SOCIETY; MARKERS; RISK AB Cardiotoxicity is a known consequence of thoracic irradiation and there are multiple overlapping risk factors for cardiac disease and thoracic malignancies. In this study, we quantified the impact of thoracic (chemo) radiation on cardiac troponin T (TnT), creatine kinase-myocardial. band (CK-MB) and aminoterminal. pro-brain natriuretic peptide (NT-proBNP). Thirty patients receiving radiation therapy to the thorax with or without concurrent chemotherapy were evaluated. Serum was collected at baseline, 2 weeks into treatment and at the completion of radiation therapy. TnT, CK-MB and NT-proBNP were quantified using commercially available immunoassays. Cardiac dosimetric parameters and clinical. risk factors were examined. In 29 of 30 patients, serum TnT remained undetectable (<0.01 ng/mL) throughout (chemo) radiation. In the one patient with detectable serum TnT, levels did not change significantly with treatment. Similarly, thoracic (chemo)radiation did not cause statistically significant elevations in serum CK-MB and NT-proBNP. Thus, contemporary thoracic (chemo) radiation does not commonly result in elevations of serum TnT, CK-MB or NT-proBNP. Elevations in these markers during treatment merit further evaluation. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Kozak, Kevin R.; Hong, Theodore S.; MacDonald, Shannon M.; Choi, Noah C.; Yock, Torunn I.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Kozak, Kevin R.] Massachusetts Gen Hosp, Harvard Radiat Oncol Program, Boston, MA 02114 USA. [Sluss, Patrick M.; Lewandrowski, Elizabeth L.; Aleryani, Samir L.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Kozak, KR (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM kkozak@partners.org NR 20 TC 17 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 0169-5002 J9 LUNG CANCER JI Lung Cancer PD DEC PY 2008 VL 62 IS 3 BP 351 EP 355 DI 10.1016/j.lungcan.2008.03.024 PG 5 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 391EX UT WOS:000262217700011 PM 18462828 ER PT J AU Setsompop, K Alagappan, V Gagoski, B Witzel, T Polimeni, J Potthast, A Hebrank, F Fontius, U Schmitt, F Wald, LL Adalsteinsson, E AF Setsompop, Kawin Alagappan, Vijayanand Gagoski, Borjan Witzel, Thomas Polimeni, Jonathan Potthast, Andreas Hebrank, Franz Fontius, Ulrich Schmitt, Franz Wald, Lawrence L. Adalsteinsson, Elfar TI Slice-Selective RF Pulses for In Vivo B(1)(+) Inhomogeneity Mitigation at 7 Tesla Using Parallel RF Excitation With a 16-Element Coil SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel excitation; slice-selective excitation; RF inhomogeneity mitigation; multidimensional RF pulse; RF coil array ID TRANSMIT SENSE; 8 CHANNELS; DESIGN; MRI AB Slice-selective RF waveforms that mitigate severe B dagger inhomogeneity at 7 Tesla using parallel excitation were designed and validated in a water phantom and human studies on six subjects using a 16-element degenerate stripline array coil driven with a butler matrix to utilize the eight most favorable birdcage modes. The parallel RF waveform design applied magnitude least-squares (MLS) criteria with an optimized k-space excitation trajectory to significantly improve profile uniformity compared to conventional least-squares (LS) designs. Parallel excitation RF pulses designed to excite a uniform in-plane flip angle (FA) with slice selection in the z-direction were demonstrated and compared with conventional sinc-pulse excitation and RF shimming. In all cases, the parallel RF excitation significantly mitigated the effects of inhomogeneous B dagger on the excitation FA. The optimized parallel RF pulses for human B dagger mitigation were only 67% longer than a conventional sinc-based excitation, but significantly outperformed RF shimming. For example the standard deviations (SDs) of the in-plane FA (averaged over six human studies) were 16.7% for conventional sinc excitation, 13.3% for RF shimming, and 7.6% for parallel excitation. This work demonstrates that excitations with parallel RF systems can provide slice selection with spatially uniform FAs at high field strengths with only a small pulse-duration penalty. Magn Reson Med 60:1422-1432, 2008. (C) 2008 Wiley-Liss, Inc. C1 [Setsompop, Kawin; Gagoski, Borjan; Adalsteinsson, Elfar] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Alagappan, Vijayanand; Witzel, Thomas; Polimeni, Jonathan; Wald, Lawrence L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Witzel, Thomas; Wald, Lawrence L.; Adalsteinsson, Elfar] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Potthast, Andreas; Hebrank, Franz] Siemens Med Solut, Charlestown, MA USA. [Fontius, Ulrich; Schmitt, Franz] Siemens Med Solut, Erlangen, Germany. RP Setsompop, K (reprint author), Room 776A,Bldg 36,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM kawin@mit.edu RI Adalsteinsson, Elfar/F-2477-2010; Setsompop, Kawin/P-1464-2014; Witzel, Thomas/P-1402-2014; Polimeni, Jonathan/P-1395-2014; Wald, Lawrence/D-4151-2009 OI Setsompop, Kawin/0000-0003-0455-7634; Polimeni, Jonathan/0000-0002-1348-1179; FU National Institute of Biomedical Imaging and Boengineering (NIBIB); National Institutes of Health (NIH) [R01EB006847, R01EB007942, R01EB000790]; National Center for Research Resources (NCRR), NIH [P41RR14075]; Siemens Medical Solutions; R.J. Shillman Career Development Award; MIND Institute FX Grant sponsor: National Institute of Biomedical Imaging and Boengineering (NIBIB), National Institutes of Health (NIH); Grant numbers: R01EB006847, R01EB007942, R01EB000790; National Center for Research Resources (NCRR), NIH; Grant number: P41RR14075; Grant sponsors: Siemens Medical Solutions; R.J. Shillman Career Development Award; MIND Institute. NR 30 TC 71 Z9 71 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2008 VL 60 IS 6 BP 1422 EP 1432 DI 10.1002/mrm.21739 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377AW UT WOS:000261225100018 PM 19025908 ER PT J AU Cao, HH Ackerman, JL Hrovat, MI Graham, L Glimcher, MJ Wu, YT AF Cao, Haihui Ackerman, Jerome L. Hrovat, Mirko I. Graham, Lila Glimcher, Melvin J. Wu, Yaotang TI Quantitative Bone Matrix Density Measurement by Water- and Fat-Suppressed Proton Projection MRI (WASPI) With Polymer Calibration Phantoms SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE bone; MRI; WASPI; LITE ultrashort T-2 imaging ID IN-VIVO; POLY(METHYL METHACRYLATE); CONTRAST AGENTS; PEO/PMMA BLENDS; DYNAMICS; OSTEOMALACIA; SEQUENCES; PEO AB The density of the organic matrix of bone substance is a critical parameter necessary to clinically evaluate and distinguish structural and metabolic pathological conditions such as osteornalacia in adults and rickets in growing children. Water- and fat-suppressed proton projection MRI (WASPI) was developed as a noninvasive means to obtain this information. In this study, a density calibration phantom was developed to convert WASPI intensity to true bone matrix density. The phantom contained a specifically designed poly(ethylene oxide)/poly(m ethyl methacrylate) (PEO/PMMA) blend, whose IVIRI properties (T-1, T-2, and resonance linewidth) were similar to those of solid bone matrix (collagen, tightly bound water, and other immobile molecules), minimizing the need to correct for differences in T-1 and/or T-2 relaxation between the phantom and the subject. Cortical and trabecular porcine bone specimens were imaged using WASPI with the calibration phantom in the field of view (FOV) as a stable intensity reference. Gravimetric and amino acid analyses were carried out on the same specimens after WASPI, and the chemical results were found to be highly correlated (r(2) = 0.98 and 0.95, respectively) to the WASPI intensity. By this procedure the WASPI intensity can be used to obtain the true bone matrix mass density Ing cm(-3). Magn Reson Med 60:1433-1443,2008. (C) 2008 Wiley-Liss, Inc. C1 [Cao, Haihui; Ackerman, Jerome L.; Graham, Lila; Glimcher, Melvin J.; Wu, Yaotang] Childrens Hosp, Dept Orthoped Surg, Lab Study Skeletal Disorders & Rehabil, Boston, MA 02115 USA. [Cao, Haihui; Ackerman, Jerome L.; Wu, Yaotang] Massachusetts Gen Hosp, Dept Radiol, Martinos Ctr, Biomat Lab, Charlestown, MA USA. [Ackerman, Jerome L.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Hrovat, Mirko I.] Mirtech Inc, Brockton, MA USA. [Ackerman, Jerome L.; Graham, Lila; Glimcher, Melvin J.; Wu, Yaotang] Harvard Univ, Sch Med, Boston, MA USA. RP Wu, YT (reprint author), Childrens Hosp, Dept Orthoped Surg, Lab Study Skeletal Disorders & Rehabil, 300 Longwood Ave, Boston, MA 02115 USA. EM yaotang.wu@childrens.harvard.edu RI Ackerman, Jerome/E-2646-2015 OI Ackerman, Jerome/0000-0001-5176-7496 FU National Institute of Biomedical Imaging and Bioengineering, NIH [R01-EB004012]; National Institute of Aging, NIH [R01-AG014701]; NIH Division of Research Resources [S10-RR16811, P41-RR14075]; Peabody Foundation; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging FX Grant sponsor: National Institute of Biomedical Imaging and Bioengineering, NIH; Grant number: R01-EB004012; Grant sponsor: National Institute of Aging, NIH; Grant number: R01-AG014701; NIH Division of Research Resources; Grant numbers: S10-RR16811, P41-RR14075; Grant sponsors: Peabody Foundation; MIND Institute; Athinoula A. Martinos Center for Biomedical Imaging. NR 26 TC 29 Z9 32 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0740-3194 EI 1522-2594 J9 MAGN RESON MED JI Magn. Reson. Med. PD DEC PY 2008 VL 60 IS 6 BP 1433 EP 1443 DI 10.1002/mrm.21771 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 377AW UT WOS:000261225100019 PM 19025909 ER PT J AU Makris, N Angelone, L Tulloch, S Sorg, S Kaiser, J Kennedy, D Bonmassar, G AF Makris, Nikos Angelone, Leonardo Tulloch, Seann Sorg, Scott Kaiser, Jonathan Kennedy, David Bonmassar, Giorgio TI MRI-based anatomical model of the human head for specific absorption rate mapping SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE Head; Morphometry; Segmentation; Volumetry; Specific absorption rate; Bioelectromagnetic computation ID DIGITAL BRAIN PHANTOM; DIELECTRIC-PROPERTIES; BIOLOGICAL TISSUES; SAR CALCULATIONS; FREQUENCY-RANGE; FIELD; RESONANCE; EXPOSURE; MHZ; VOLUME AB In this study, we present a magnetic resonance imaging (MRI)-based, high-resolution, numerical model of the head of a healthy human subject. In order to formulate the model, we performed quantitative volumetric segmentation on the human head, using T1-weighted MRI. The high spatial resolution used (1 x 1 x 1 mm3), allowed for the precise computation and visualization of a higher number of anatomical structures than provided by previous models. Furthermore, the high spatial resolution allowed us to study individual thin anatomical structures of clinical relevance not visible by the standard model currently adopted in computational bioelectromagnetics. When we computed the electromagnetic field and specific absorption rate (SAR) at 7 Tesla MRI using this high-resolution model, we were able to obtain a detailed visualization of such fine anatomical structures as the epidermis/dermis, bone structures, bone-marrow, white matter and nasal and eye structures. C1 [Makris, Nikos; Angelone, Leonardo; Kennedy, David; Bonmassar, Giorgio] Massachusetts Gen Hosp, HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Makris, Nikos; Tulloch, Seann; Sorg, Scott; Kaiser, Jonathan; Kennedy, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, HST Athinoula A Martinos Ctr,Ctr Morphomet Anal, Boston, MA 02129 USA. [Makris, Nikos; Tulloch, Seann; Sorg, Scott; Kaiser, Jonathan; Kennedy, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Neurol, HST Athinoula A Martinos Ctr,Ctr Morphomet Anal, Boston, MA 02129 USA. [Makris, Nikos; Tulloch, Seann; Sorg, Scott; Kaiser, Jonathan; Kennedy, David] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol Serv, HST Athinoula A Martinos Ctr,Ctr Morphomet Anal, Boston, MA 02129 USA. [Makris, Nikos] Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. [Angelone, Leonardo] Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. RP Bonmassar, G (reprint author), Massachusetts Gen Hosp, HST Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM giorgio@nmr.mgh.harvard.edu RI Kennedy, David/H-3627-2012; OI Angelone, Leonardo/0000-0002-1105-021X FU National Association for Research in Schizophrenia and Depression (NARSAD); National Institutes of Health National Center for Complementary and Alternative Medicine NCAM; Fairway Trust; NIH [NS34189, EB005149, R01 EB002459, P41 RR014075]; MIND institute FX Preparation of this article was supported in part by grants from: The National Association for Research in Schizophrenia and Depression (NARSAD) and the National Institutes of Health National Center for Complementary and Alternative Medicine NCAM (NM); the Fairway Trust and NIH grants NS34189 & EB005149 (DK); R01 EB002459 and P41 RR014075 (GB), and the MIND institute. The authors would like to thank the many people that kindly contributed to this project with discussions and useful insights, including Franz Schmitt, Franz Hebrank and Andreas Potthast (Siemens Medical Systems), CK Chou and Goga Bit Babik (Motorola Corporate EME), Chris Collins (Penn State), David Kaplan, Sergio Fantini, Peter Wong, and Mark Cronin- Golomb (Tufts University). We would like also to thank the colleagues at the A. Martinos Center, including Martjin Cloos, Graham Wiggins, Mary Foley, and Larry Wald for their help with the MRI images, and Mr. George Papadimitriou and Mr. James Howard and for their contributions to this study. NR 63 TC 25 Z9 26 U1 1 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0140-0118 EI 1741-0444 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD DEC PY 2008 VL 46 IS 12 BP 1239 EP 1251 DI 10.1007/s11517-008-0414-z PG 13 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 376JY UT WOS:000261181100008 PM 18985401 ER PT J AU Bailey, FA AF Bailey, F. Amos TI "I Am Not Afraid of Dying. I Just Don't Want To Be There When it Happens" SO MEDICAL CARE LA English DT Editorial Material ID PHYSICIAN-ASSISTED SUICIDE; OF-LIFE DECISIONS; PALLIATIVE CARE; MEDICAL-PRACTICE; END; EUTHANASIA; OUTCOMES; CANCER; DEATH C1 Birmingham VAMC, Birmingham, AL 35233 USA. RP Bailey, FA (reprint author), Birmingham VAMC, 700 S 19th St, Birmingham, AL 35233 USA. EM amos-bailey@va.gov NR 23 TC 0 Z9 0 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2008 VL 46 IS 12 BP 1195 EP 1197 DI 10.1097/MLR.0b013e3181904fd8 PG 3 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 379UC UT WOS:000261420700001 PM 19300307 ER PT J AU Keyhani, S Hebert, PL Ross, JS Federman, A Zhu, CW Siu, AL AF Keyhani, Salomeh Hebert, Paul L. Ross, Joseph S. Federman, Alex Zhu, Carolyn W. Siu, Albert L. TI Electronic Health Record Components and the Quality of Care SO MEDICAL CARE LA English DT Article DE quality of health care; personal health record; hypertension; ambulatory care ID RANDOMIZED CONTROLLED-TRIAL; CLINICAL REMINDERS; MEDICAL-RECORD; UNITED-STATES; ORDER ENTRY; ERRORS; SYSTEM; IMPACT; TRANSFORMATION; PRESCRIPTION AB Background: Electronic health records (EHRs) have been promoted as an important tool to improve quality of care. We examined the association between EHR components, a complete EHR, and the quality of care. Methods: Using data from the 2005 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey, we conducted a cross-sectional analysis of all visits with an established primary care provider and examined the association between presence of EHR components and: (1) blood pressure control; and (2) receipt of appropriate therapy for chronic conditions. We examined similar associations for complete EHRs which we defined as one that includes physician and nursing notes, electronic reminder system, computerized prescription order entry, test results, and computerized test order entry. We constructed multivariate models to examine the association between EHR components and each outcome controlling for patient sociodemographic, health, physician practice, and geographic factors. Results: We found no association between electronic physician notes and blood pressure control or receipt of appropriate therapies, with the exception of inhaled steroids among asthmatics (adjusted odds ratio 2.86; 95% confidence interval, 1.12-7.32). We found no association between electronic reminder systems and blood pressure control or receipt of appropriate therapies, with the exception of angiotensin converting enzyme inhibitors or angiotensin receptor blockers in patients with diabetes with hypertension (odds ratio 2.58; 95% confidence interval, 1.22-5.42). We found no association between electronic physician notes and any measure of quality. We found no relationship between having a complete EHR and any of the quality measures investigated. Conclusions: We found no consistent association between blood pressure control, management of chronic conditions, and specific EHR components. Future research focusing on how an EHR is implemented and used and how care is integrated through an EHR will improve our understanding of the impact of EHRs on the quality of care. C1 [Keyhani, Salomeh; Hebert, Paul L.] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. [Keyhani, Salomeh; Ross, Joseph S.; Zhu, Carolyn W.; Siu, Albert L.] James J Peters Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Bronx, NY USA. [Ross, Joseph S.; Zhu, Carolyn W.; Siu, Albert L.] Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY 10029 USA. [Federman, Alex] Mt Sinai Sch Med, Dept Gen Internal Med, New York, NY 10029 USA. RP Keyhani, S (reprint author), Mt Sinai Sch Med, Dept Hlth Policy, Box 1077,1 Gustave L Levy Pl, New York, NY 10029 USA. EM salomeh.keyhani@mountsinai.org FU Department of Veterans Affairs Health Services Research and Development Service [TRP-02-149]; Hartford Foundation; Robert Wood Johnson Foundation FX Supported by Department of Veterans Affairs Health Services Research and Development Service project #TRP-02-149 (to S.K., J.S.R., and A.L.S.); the Hartford Foundation (to J.S.R.); and the Robert Wood Johnson Foundation (to A.R). NR 33 TC 50 Z9 51 U1 4 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2008 VL 46 IS 12 BP 1267 EP 1272 DI 10.1097/MLR.0b013e31817e18ae PG 6 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 379UC UT WOS:000261420700011 PM 19300317 ER PT J AU Cannon, CP Kumar, A AF Cannon, Christopher P. Kumar, Amit TI Management of hypertension in the presence of other cardiometabolic risk factors SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID RENIN-ANGIOTENSIN SYSTEM; CARDIAC OUTCOMES TRIAL; PRESSURE LOWERING ARM; NORMAL BLOOD-PRESSURE; METABOLIC SYNDROME; INSULIN-RESISTANCE; OVERWEIGHT/OBESE PATIENTS; DIABETES-MELLITUS; FACTOR CLUSTERS; UNITED-STATES C1 [Cannon, Christopher P.] Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp, Boston, MA 02115 USA. [Kumar, Amit] Univ Massachusetts, Sch Med, Dept Hosp Med, Worcester, MA USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, TIMI Study Grp, Div Cardiovasc,Brigham & Womens Hosp, Boston, MA 02115 USA. NR 54 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD DEC PY 2008 VL 92 BP 49 EP 57 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 402SX UT WOS:000263034500005 ER PT J AU Cooper, RA Dicianno, BE Brewer, B LoPresti, E Ding, D Simpson, R Grindle, G Wang, HW AF Cooper, Rory A. Dicianno, Brad E. Brewer, Bambi LoPresti, Edmund Ding, Dan Simpson, Richard Grindle, Garrett Wang, Hongwu TI A perspective on intelligent devices and environments in medical rehabilitation SO MEDICAL ENGINEERING & PHYSICS LA English DT Review DE Rehabilitation; Intelligent systems; Machine learning; Physical impairment; Wheelchairs; Cognitive impairment ID INDUCED MOVEMENT THERAPY; TRAUMATIC BRAIN-INJURY; UPPER-LIMB FUNCTION; OF-THE-ART; UPPER EXTREMITY; STROKE REHABILITATION; RANDOMIZED CROSSOVER; ASSISTIVE-TECHNOLOGY; INTERFACE PRESSURE; CARE COORDINATION AB Globally, the number of people older than 65 years is anticipated to double between 1997 and 2025, while at the same time the number of people with disabilities is growing at it similar rate, which makes technical advances and social policies critical to attain, prolong, and preserve quality of life. Recent advancements in technology, including computation, robotics, machine learning, communication, and miniaturization of sensors have been used primarily in manufacturing, military, space exploration, and entertainment. However, few efforts have been made to utilize these technologies to enhance the quality of life of people with disabilities. This article offers a perspective of future development in seven emerging areas: translation of research into clinical practice, pervasive assistive technology, cognitive assistive technologies, rehabilitation monitoring and coaching technologies, robotic assisted therapy, and personal mobility and manipulation technology. Published by Elsevier Ltd on behalf of IPEM C1 [Cooper, Rory A.; Dicianno, Brad E.; Brewer, Bambi; Ding, Dan; Simpson, Richard; Grindle, Garrett; Wang, Hongwu] VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Rehabil Res & Dev Serv, Pittsburgh, PA 15206 USA. [Cooper, Rory A.; Dicianno, Brad E.; Brewer, Bambi; LoPresti, Edmund; Ding, Dan; Simpson, Richard; Grindle, Garrett; Wang, Hongwu] Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. [Cooper, Rory A.; Dicianno, Brad E.; Brewer, Bambi; LoPresti, Edmund; Ding, Dan; Simpson, Richard; Grindle, Garrett; Wang, Hongwu] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. [Cooper, Rory A.; Dicianno, Brad E.; Brewer, Bambi; LoPresti, Edmund; Ding, Dan; Simpson, Richard; Grindle, Garrett; Wang, Hongwu] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. [Dicianno, Brad E.; Simpson, Richard] Univ Pittsburgh, Med Ctr, Ctr Assist Technol, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Dept Vet Affairs, Rehabil Res & Dev Serv, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. EM rcooper@pitt.edu RI Wang, Hongwu/J-6133-2013; Simpson, Richard/G-5683-2015; OI Wang, Hongwu/0000-0002-6567-9144; Simpson, Richard/0000-0002-6306-9393; Dicianno, Brad/0000-0003-0738-0192 FU National Science Foundation [EEC-0540865]; Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs [B3142C] FX This material is based upon work supported by the National Science Foundation under Cooperative Agreement EEC-0540865. This material is also based upon work supported by the Office of Research and Development, Rehabilitation Research & Development Service, Department of Veterans Affairs, Grant# B3142C. NR 122 TC 21 Z9 21 U1 1 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD DEC PY 2008 VL 30 IS 10 BP 1387 EP 1398 DI 10.1016/j.medengphy.2008.09.003 PG 12 WC Engineering, Biomedical SC Engineering GA 386WX UT WOS:000261914400014 PM 18993108 ER PT J AU Xu, QY Hamilton, RJ Schowengerdt, RA Alexander, B Jiang, SB AF Xu, Qianyi Hamilton, Russell J. Schowengerdt, Robert A. Alexander, Brian Jiang, Steve B. TI Lung tumor tracking in fluoroscopic video based on optical flow SO MEDICAL PHYSICS LA English DT Article DE biomedical optical imaging; collimators; diagnostic radiography; image sequences; lung; medical image processing; pneumodynamics; tumours ID DYNAMIC MULTILEAF COLLIMATORS; MODULATED RADIATION-THERAPY; RESPIRATION-GATED RADIOTHERAPY; IMPLANTED FIDUCIAL MARKERS; INSPIRATION BREATH-HOLD; DMLC TECHNIQUE; TARGET VOLUME; ORGAN MOTION; DELIVERY; FEASIBILITY AB Respiratory gating and tumor tracking for dynamic multileaf collimator delivery require accurate and real-time localization of the lung tumor position during treatment. Deriving tumor position from external surrogates such as abdominal surface motion may have large uncertainties due to the intra- and interfraction variations of the correlation between the external surrogates and internal tumor motion. Implanted fiducial markers can be used to track tumors fluoroscopically in real time with sufficient accuracy. However, it may not be a practical procedure when implanting fiducials bronchoscopically. In this work, a method is presented to track the lung tumor mass or relevant anatomic features projected in fluoroscopic images without implanted fiducial markers based on an optical flow algorithm. The algorithm generates the centroid position of the tracked target and ignores shape changes of the tumor mass shadow. The tracking starts with a segmented tumor projection in an initial image frame. Then, the optical flow between this and all incoming frames acquired during treatment delivery is computed as initial estimations of tumor centroid displacements. The tumor contour in the initial frame is transferred to the incoming frames based on the average of the motion vectors, and its positions in the incoming frames are determined by fine-tuning the contour positions using a template matching algorithm with a small search range. The tracking results were validated by comparing with clinician determined contours on each frame. The position difference in 95% of the frames was found to be less than 1.4 pixels (similar to 0.7 mm) in the best case and 2.8 pixels (similar to 1.4 mm) in the worst case for the five patients studied. C1 [Xu, Qianyi] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. [Xu, Qianyi; Schowengerdt, Robert A.] Univ Arizona, Dept Elect & Comp Engn, Tucson, AZ 85721 USA. [Hamilton, Russell J.] Univ Arizona, Dept Radiat Oncol, Tucson, AZ 85721 USA. [Alexander, Brian] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Alexander, Brian] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Jiang, Steve B.] Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. RP Xu, QY (reprint author), Fox Chase Canc Ctr, Dept Radiat Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. FU NIH [1 R21 CA110177-01A1]; Varian Medical Systems, Inc. FX This work was partially supported by research grants from NIH (1 R21 CA110177-01A1) and Varian Medical Systems, Inc. NR 61 TC 36 Z9 36 U1 2 U2 5 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2008 VL 35 IS 12 BP 5351 EP 5359 DI 10.1118/1.3002323 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 376VB UT WOS:000261210000016 PM 19175094 ER PT J AU Pfeiffer, D Sutlief, S Feng, WZ Pierce, HM Kofler, J AF Pfeiffer, Douglas Sutlief, Steven Feng, Wenzheng Pierce, Heather M. Kofler, Jim TI AAPM Task Group 128: Quality assurance tests for prostate brachytherapy ultrasound systems SO MEDICAL PHYSICS LA English DT Article DE biological organs; biomedical ultrasonics; brachytherapy; cancer; dosimetry; image resolution; quality assurance; tumours ID CANCER; SPEED; SOUND AB While ultrasound guided prostate brachytherapy has gained wide acceptance as a primary treatment tool for prostate cancer, quality assurance of the ultrasound guidance system has received very little attention. Task Group 128 of the American Association of Physicists in Medicine was created to address quality assurance requirements specific to transrectal ultrasound used for guidance of prostate brachytherapy. Accurate imaging guidance and dosimetry calculation depend upon the quality and accuracy of the ultrasound image. Therefore, a robust quality assurance program for the ultrasound system is essential. A brief review of prostate brachytherapy and ultrasound physics is provided, followed by a recommendation for elements to be included in a comprehensive test phantom. Specific test recommendations are presented, covering grayscale visibility, depth of penetration, axial and lateral resolution, distance measurement, area measurement, volume measurement, needle template/electronic grid alignment, and geometric consistency with the treatment planning computer. C1 [Pfeiffer, Douglas] Boulder Community Foothills Hosp, Dept Imaging, Boulder, CO 80301 USA. [Sutlief, Steven] VA Puget Sound Hlth Care Syst, VA Med Ctr, Seattle, WA 98108 USA. [Feng, Wenzheng] William Beaumont Hosp, Royal Oak, MI 48073 USA. [Pierce, Heather M.] CIRS Inc, Norfolk, VA 23513 USA. [Kofler, Jim] Mayo Clin, Rochester, MN 55905 USA. RP Pfeiffer, D (reprint author), Boulder Community Foothills Hosp, Dept Imaging, Boulder, CO 80301 USA. EM dpfeiffer@bch.org NR 19 TC 19 Z9 20 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD DEC PY 2008 VL 35 IS 12 BP 5471 EP 5489 DI 10.1118/1.3006337 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 376VB UT WOS:000261210000029 PM 19175107 ER PT J AU Anderson, KL Casey, MB Thompson, WL Burrage, MS Pezaris, E Kosslyn, SM AF Anderson, Karen L. Casey, M. Beth Thompson, William L. Burrage, Marie S. Pezaris, Elizabeth Kosslyn, Stephen M. TI Performance on Middle School Geometry Problems With Geometry Clues Matched to Three Different Cognitive Styles SO MIND BRAIN AND EDUCATION LA English DT Article AB This study investigated the relationship between 3 ability-based cognitive styles (verbal deductive, spatial imagery, and object imagery) and performance on geometry problems that provided different types of clues. The purpose was to determine whether students with a specific cognitive style outperformed other students, when the geometry problems provided clues compatible with their cognitive style. Students were identified as having a particular cognitive style when they scored equal to or above the median on the measure assessing this ability. A geometry test was developed in which each problem could be solved on the basis of verbal reasoning clues (matching verbal deductive cognitive style), mental rotation clues (matching spatial imagery cognitive style), or shape memory clues (matching object imagery cognitive style). Straightforward cognitive style-clue-compatibility relationships were not supported. Instead, for the geometry problems with either mental rotation or shape memory clues, students with a combination of both verbal and spatial cognitive styles tended to do the best. For the problems with verbal reasoning clues, students with either a verbal or a spatial cognitive style did well, with each cognitive style contributing separately to success. Thus, both spatial imagery and verbal deductive cognitive styles were important for solving geometry problems, whereas object imagery was not. For girls, a spatial imagery cognitive style was advantageous for geometry problem solving, regardless of type of clues provided. C1 [Casey, M. Beth] Boston Coll, Lynch Sch Educ, Program Appl Dev & Educ Psychol, Chestnut Hill, MA 02492 USA. [Anderson, Karen L.] Stonehill Coll, Dept Educ Studies, Easton, MA USA. [Thompson, William L.; Burrage, Marie S.; Kosslyn, Stephen M.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Pezaris, Elizabeth] Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA USA. [Kosslyn, Stephen M.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Casey, MB (reprint author), Boston Coll, Lynch Sch Educ, Program Appl Dev & Educ Psychol, 201 Campion Hall, Chestnut Hill, MA 02492 USA. EM caseyb@bc.edu NR 48 TC 7 Z9 7 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1751-2271 J9 MIND BRAIN EDUC JI Mind Brain Educ. PD DEC PY 2008 VL 2 IS 4 BP 188 EP 197 DI 10.1111/j.1751-228X.2008.00053.x PG 10 WC Education & Educational Research; Psychology, Developmental SC Education & Educational Research; Psychology GA V15NW UT WOS:000207809700006 ER PT J AU Chen, G Jingbo, A Wang, M Farley, S Lee, LY Lee, LC Sawicki, MP AF Chen, Gao Jingbo, A. Wang, Min Farley, Steven Lee, Lung-Yi Lee, Lung-Ching Sawicki, Mark P. TI Menin Promotes the Wnt Signaling Pathway in Pancreatic Endocrine Cells SO MOLECULAR CANCER RESEARCH LA English DT Article ID HISTONE METHYLTRANSFERASE COMPLEX; TUMOR-SUPPRESSOR PROTEIN; BETA-CATENIN; NEOPLASIA TYPE-1; WNT/BETA-CATENIN; GENE-EXPRESSION; STEM-CELLS; TRANSCRIPTION; OSTEOBLAST; GROWTH AB Menin is a tumor suppressor protein mutated in patients with multiple endocrine neoplasia type 1. We show that menin is essential for canonical Wnt/beta-catenin signaling in cultured rodent islet tumor cells. In these cells, overexpression of menin significantly enhances TCF gene assay reporter activity in response to beta-catenin activation. Contrastingly, inhibition of menin expression with Men1 siRNA decreases TCF reporter gene activity. Likewise, multiple endocrine neoplasia type 1 disease associated missense mutations of menin abrogate the ability to increase TCF reporter gene activity. We show that menin physically interacts with proteins involved in the canonical Wnt signaling pathway, including beta-catenin, TCF3 (TCFL1), and weakly with TCF4 (TCFL2). Menin overexpression increases expression of the Wnt/beta-catenin downstream target gene Axing, which is associated with increased H3K4 trimethylation of the Axing gene promoter. Moreover, inhibition of menin expression by siRNA abrogates H3K4 trimethylation and Axing gene expression. Based on these studies, we hypothesized that Wnt signaling could inhibit islet cell proliferation because loss of menin function is thought to increase endocrine tumor cell proliferation. TGP61 rodent islet tumor cells treated with a glycogen synthase kinase 3 beta inhibitor that increases Writ pathway signaling had decreased cell proliferation compared with vehicle-treated cells. Collectively, these data suggest that menin has an essential role in Wnt/beta-catenin signaling through a mechanism that eventually affects histone trimethylation of the downstream target gene Axing, and activation of Wnt/beta-catenin signaling inhibits islet tumor cell proliferation. (Mol Cancer Res 2008;6(12):1894-907) C1 [Sawicki, Mark P.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Sawicki, MP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CHS 72-215, Los Angeles, CA 90095 USA. EM msawicki@ucla.edu FU NIH [R01CA095148]; VA Merit FX Grant support: NIH grant R01CA095148 and VA Merit grants (M.P. Sawicki). 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 49 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2008 VL 6 IS 12 BP 1894 EP 1907 DI 10.1158/1541-7786.MCR-07-2206 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 385OZ UT WOS:000261824800010 PM 19074834 ER PT J AU Gao, BB Stuart, L Feener, EP AF Gao, Ben-Bo Stuart, Lisa Feener, Edward P. TI Label-free Quantitative Analysis of One-dimensional PAGE LC/MS/MS Proteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID SMOOTH-MUSCLE-CELLS; DIFFERENTIAL MASS-SPECTROMETRY; COMPLEX PEPTIDE MIXTURES; RESOLUTION LC-MS; ANGIOTENSIN-II; LIQUID-CHROMATOGRAPHY; IN-VIVO; SHOTGUN PROTEOMICS; EXPRESSION; PROTEINS AB A widely used method for protein identification couples prefractionation of protein samples by one-dimensional (1D) PAGE with LC/MS/MS. We developed a new label-free quantitative algorithm by combining measurements of spectral counting, ion intensity, and peak area on 1D PAGE-based proteomics. This algorithm has several improvements over other label-free quantitative algorithms: (i) Errors in peak detection are reduced because the retention time is based on each LC/MS/MS run and actual precursor m/z. (ii) Detection sensitivity is increased because protein quantification is based on the combination of peptide count, ion intensity, and peak area. (iii) Peak intensity and peak area are calculated in each LC/MS/MS run for all slices from 1D PAGE for every single identified protein and visualized as a Western blot image. The sensitivity and accuracy of this algorithm were demonstrated by using standard curves (17.4 fmol to 8.7 pmol), complex protein mixtures (30 fmol to 1.16 pmol) of known composition, and spiked protein (34.8 fmol to 17.4 pmol) in complex proteins. We studied the feasibility of this approach using the secretome of angiotensin II (Ang II)-stimulated vascular smooth muscle cells (VSMCs). From the VSMC-conditioned medium, 629 proteins were identified including 212 putative secreted proteins. 26 proteins were differently expressed in control and Ang II-stimulated VSMCs, including 18 proteins not previously reported. Proteins related to cell growth (CYR61, protein NOV, and clusterin) were increased, whereas growth arrest-specific 6 (GAS6) and growth/differentiation factor 6 were decreased by Ang II stimulation. Ang II-stimulated changes of plasminogen activator inhibitor-1, GAS6, cathepsin B, and periostin were validated by Western blot. In conclusion, a novel label-free quantitative analysis of 1D PAGELC/MS/MS-based proteomics has been successfully applied to the identification of new potential mediators of Ang II action and may provide an alternative to traditional protein staining methods. Molecular & Cellular Proteomics 7:2399-2409,2008. C1 [Gao, Ben-Bo; Stuart, Lisa; Feener, Edward P.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Gao, BB (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM benbo.gao@joslin.harvard.edu FU National Institutes of Health [DK60165, DK36836]; Adler Foundation FX This work was supported, in whole or in part, by National Institutes of Health Grants DK60165 and DK36836. This work was also supported by the Adler Foundation. 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 43 TC 55 Z9 57 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD DEC PY 2008 VL 7 IS 12 BP 2399 EP 2409 DI 10.1074/mcp.M800104-MCP200 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 378NK UT WOS:000261328200009 PM 18676994 ER PT J AU Parra, LA Baust, T El Mestikawy, S Quiroz, M Hoffman, B Haflett, JM Yao, JK Torres, GE AF Parra, Leonardo A. Baust, Tracy El Mestikawy, Salah Quiroz, Marisol Hoffman, Beth Haflett, Jack M. Yao, Jeffrey K. Torres, Gonzalo E. TI The Orphan Transporter Rxt1/NTT4 (SLC6A17) Functions as a Synaptic Vesicle Amino Acid Transporter Selective for Proline, Glycine, Leucine, and Alanine SO MOLECULAR PHARMACOLOGY LA English DT Article ID VESICULAR GLUTAMATE TRANSPORTER; CENTRAL-NERVOUS-SYSTEM; INORGANIC-PHOSPHATE COTRANSPORTER; NEUROTRANSMITTER TRANSPORTER; MOLECULAR-CLONING; NMDA RECEPTOR; RAT-BRAIN; ACETYLCHOLINE TRANSPORTER; DEPENDENT TRANSPORTER; EXPRESSION PATTERN AB Rxt1/NTT4 (SLC6A17) belongs to a gene family of "orphan transporters" whose substrates and consequently functions remain unidentified. Although Rxt1/NTT4 was previously thought to function as a sodium-dependent plasma membrane transporter, recent studies localized the protein to synaptic vesicles of glutamatergic and GABAergic neurons. Here, we provide evidence indicating that Rxt1/NTT4 functions as a vesicular transporter selective for proline, glycine, leucine, and alanine. Using Western blot, immunoprecipitation, immunocytochemistry, and polymerase chain reaction approaches, we demonstrate that PC12 cells express the Rxt1/NTT4 gene and protein. Small interfering RNA (siRNA)- mediated knockdown of Rxt1/NTT4 in PC12 cells resulted in selective reductions in uptake levels for proline, glycine, leucine, and alanine. Likewise, gas chromatography analysis of amino acid content in an enriched synaptic vesicle fraction from wild-type and siRNA-Rxt1/NTT4 PC12 cells revealed that proline, glycine, leucine, and alanine levels were decreased in siRNA-treated cells compared with wild-type cells. Furthermore, Rxt1/NTT4-transfected Chinese hamster ovary (CHO) cells exhibited significant uptake increases of these amino acids compared with mock-transfected CHO cells. Finally, proline uptake in both PC12 cells and Rxt1/NTT4-transfected CHO cells was dependent on the electrochemical gradient maintained by the vacuolar-type H+-ATPase. These data indicate that the orphan Rxt1/NTT4 protein functions as a vesicular transporter for proline, glycine, leucine, and alanine, further suggesting its important role in synaptic transmission. C1 [Parra, Leonardo A.; Baust, Tracy; Quiroz, Marisol; Torres, Gonzalo E.] Univ Pittsburgh, Sch Med, Dept Neurobiol, Pittsburgh, PA 15261 USA. [Parra, Leonardo A.; Baust, Tracy; Quiroz, Marisol; Torres, Gonzalo E.] Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. [El Mestikawy, Salah] Univ Paris 06, INSERM, U513, Paris, France. [El Mestikawy, Salah] McGill Univ, Dept Psychiat, Douglas Hosp, Res Ctr, Montreal, PQ, Canada. [Hoffman, Beth] Amgen Inc, Dept Neurosci, Thousand Oaks, CA 91320 USA. [Haflett, Jack M.; Yao, Jeffrey K.] VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15261 USA. [Yao, Jeffrey K.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. RP Torres, GE (reprint author), Univ Pittsburgh, Sch Med, Dept Neurobiol, Room 6061,BST3,3501 5th Ave, Pittsburgh, PA 15261 USA. EM gtorres@pitt.edu FU Amgen research [200620123] FX This work was funded in part by Amgen research agreement 200620123. NR 66 TC 18 Z9 19 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2008 VL 74 IS 6 BP 1521 EP 1532 DI 10.1124/mol.108.050005 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 373WG UT WOS:000261003600004 PM 18768736 ER PT J AU Stewart, D Desai, R Cheng, Q Liu, AP Forman, SA AF Stewart, Deirdre Desai, Rooma Cheng, Qi Liu, Aiping Forman, Stuart A. TI Tryptophan Mutations at Azi-Etomidate Photo-Incorporation Sites on alpha(1) or beta(2) Subunits Enhance GABA(A) Receptor Gating and Reduce Etomidate Modulation SO MOLECULAR PHARMACOLOGY LA English DT Article ID GENERAL ANESTHETIC ETOMIDATE; A-RECEPTOR; DIRECT ACTIVATION; BETA-3 SUBUNIT; BINDING CAVITY; PROPOFOL; BENZODIAZEPINES; DESENSITIZATION; INCREASES; RESIDUES AB The potent general anesthetic etomidate produces its effects by enhancing GABA(A) receptor activation. Its photolabel analog [H-3]azi-etomidate labels residues within transmembrane domains on alpha and beta subunits: alpha Met236 and beta Met286. We hypothesized that these methionines contribute to etomidate sites formed at alpha-beta subunit interfaces and that increasing side-chain bulk and hydrophobicity at either locus would mimic etomidate binding and block etomidate effects. Channel activity was electrophysiologically quantified in alpha(1)beta(2)gamma(2L) receptors with alpha(1)M236W or beta(2)M286W mutations, in both the absence and the presence of etomidate. Measurements included spontaneous activation, GABA EC50, etomidate agonist potentiation, etomidate direct activation, and rapid macrocurrent kinetics. Both alpha(1)M236W and beta(2)M286W mutations induced spontaneous channel opening, lowered GABA EC50, increased maximal GABA efficacy, and slowed current deactivation, mimicking effects of etomidate on alpha(1)beta(2)gamma(2L) channels. These changes were larger with alpha(1)M236W than with beta(2)M286W. Etomidate (3.2 mu M) reduced GABA EC50 much less in alpha(1)M236W beta(2)gamma(2L) receptors (2-fold) than in wild type (23-fold). However, etomidate was more potent and efficacious in directly activating alpha(1)M236W beta(2)gamma(2L) compared with wild type. In alpha(1)beta(2)M286W gamma(2L) receptors, etomidate induced neither agonist-potentiation nor direct channel activation. These results support the hypothesis that alpha(1)Met236 and beta(2)Met286 are within etomidate sites that allosterically link to channel gating. Although alpha(1)M236W produced the larger impact on channel gating, beta(2)M286W produced more profound changes in etomidate sensitivity, suggesting a dominant role in drug binding. Furthermore, quantitative mechanistic analysis demonstrated that wild-type and mutant results are consistent with the presence of only one class of etomidate sites mediating both agonist potentiation and direct activation. C1 [Stewart, Deirdre; Desai, Rooma; Cheng, Qi; Liu, Aiping; Forman, Stuart A.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Beecher Mallincrodt Labs, Boston, MA 02114 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Beecher Mallincrodt Labs, Gray Jackson 4,55 Fruit St, Boston, MA 02114 USA. EM saforman@partners.org FU National Institutes of General Medical Sciences [R01-GM66724, P01-GM58448] FX This research was supported by grants from the National Institutes of General Medical Sciences (R01-GM66724 and P01-GM58448). NR 33 TC 44 Z9 44 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD DEC PY 2008 VL 74 IS 6 BP 1687 EP 1695 DI 10.1124/mol.108.050500 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 373WG UT WOS:000261003600020 PM 18805938 ER PT J AU Ergenc, AF Li, MW Toner, M Biggers, JD Lloyd, KCK Olgac, N AF Ergenc, Ali Fuat Li, Ming-Wen Toner, Mehmet Biggers, John D. Lloyd, K. C. Kent Olgac, Nejat TI Rotationally Oscillating Drill (Ros-Drill (c)) for Mouse ICSI Without Using Mercury SO MOLECULAR REPRODUCTION AND DEVELOPMENT LA English DT Article DE ICSI; microinjection; assisted reproduction; micromanipulation ID INTRACYTOPLASMIC SPERM INJECTION; PIEZO-DRIVEN PIPETTES; SPERMATOZOA; OOCYTES; MICRODYNAMICS; FERTILIZATION; TERM; MICE AB Intracytoplasmic sperm injection (ICSI) is an important assisted reproductive technology (ART). Due to deployment difficulties and low efficiency of the earlier (conventional) version of ICSI, especially in the mouse, a piezo-assisted ICSI technique had evolved as a popular ART methodology in recent years. An important and remaining problem with this technique, however, is that it requires small amounts of mercury to stabilize the pipette tip when piezoelectric force pulses are applied. To eliminate this problem we developed and tested a completely different and mercury-free technology, called the "Ros-Drill (c)" (rotationally oscillating drill). The technique uses microprocessor-control led rotational oscillations on a spiked micropipette without mercury or piezo. Preliminary experimental results show that this new microinjection technology gives high survival rate (> 70% of the injected oocytes) and fertilization rate (> 80% of the survived oocytes), and blastocyst formation rates in early trials (similar to 50% of the survived oocytes). Blastocysts created by Ros-Drill (c) ICSI were transferred into the uteruses of pseudopregnant surrogate mothers and healthy pups were born and weaned. The Ros-Drill (c) ICSI technique is automated and therefore; it requires a very short preliminary training for the specialists, as evidenced in many successful biological trials. These advantages of Ros-Drill (c) ICSI over conventional and piezo-assisted ICSI are clearly demonstrated and it appears to have resolved an important problem in reproductive biology. Mol. Reprod. Dev. 75: 1744-1751, 2008. (c) 2008 Wiley-Liss, Inc. C1 [Ergenc, Ali Fuat; Olgac, Nejat] Univ Connecticut, Dept Mech Engn, Storrs, CT 06269 USA. [Li, Ming-Wen; Lloyd, K. C. Kent] Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. [Toner, Mehmet; Biggers, John D.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. [Toner, Mehmet; Biggers, John D.] Shriners Hosp Children, Boston, MA USA. [Biggers, John D.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Ergenc, AF (reprint author), Univ Connecticut, Dept Mech Engn, 191 Auditorium Rd,EII Build Unit 3139, Storrs, CT 06269 USA. EM ergenc@engr.uconn.edu FU NIH [R24RR018934-01]; UC Davis Mouse Biology Program FX NIH; Grant number: R24RR018934-01; Grant sponsor: UC Davis Mouse Biology Program. NR 17 TC 8 Z9 8 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1040-452X J9 MOL REPROD DEV JI Mol. Reprod. Dev. PD DEC PY 2008 VL 75 IS 12 BP 1744 EP 1751 DI 10.1002/mrd.20919 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology SC Biochemistry & Molecular Biology; Cell Biology; Developmental Biology; Reproductive Biology GA 372AG UT WOS:000260873200007 PM 18437690 ER PT J AU Skog, J Wurdinger, T van Rijn, S Meijer, DH Gainche, L Sena-Esteves, M Curry, WT Carter, BS Krichevsky, AM Breakefield, XO AF Skog, Johan Wuerdinger, Tom van Rijn, Sjoerd Meijer, Dimphna H. Gainche, Laura Sena-Esteves, Miguel Curry, William T., Jr. Carter, Bob S. Krichevsky, Anna M. Breakefield, Xandra O. TI Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers SO NATURE CELL BIOLOGY LA English DT Article ID GENE-EXPRESSION; MESSENGER-RNA; CELLS; EXOSOMES; CANCER; ANGIOGENESIS; RECEPTOR; MEMBRANE; DETERMINANTS; SUPPRESSION AB Glioblastoma tumour cells release microvesicles (exosomes) containing mRNA, miRNA and angiogenic proteins. These microvesicles are taken up by normal host cells, such as brain microvascular endothelial cells. By incorporating an mRNA for a reporter protein into these microvesicles, we demonstrate that messages delivered by microvesicles are translated by recipient cells. These microvesicles are also enriched in angiogenic proteins and stimulate tubule formation by endothelial cells. Tumour-derived microvesicles therefore serve as a means of delivering genetic information and proteins to recipient cells in the tumour environment. Glioblastoma microvesicles also stimulated proliferation of a human glioma cell line, indicating a self-promoting aspect. Messenger RNA mutant/variants and miRNAs characteristic of gliomas could be detected in serum microvesicles of glioblastoma patients. The tumour-specific EGFRvIII was detected in serum microvesicles from 7 out of 25 glioblastoma patients. Thus, tumour-derived microvesicles may provide diagnostic information and aid in therapeutic decisions for cancer patients through a blood test. C1 [Skog, Johan; Wuerdinger, Tom; van Rijn, Sjoerd; Meijer, Dimphna H.; Gainche, Laura; Sena-Esteves, Miguel; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. [Skog, Johan; Wuerdinger, Tom; van Rijn, Sjoerd; Meijer, Dimphna H.; Gainche, Laura; Sena-Esteves, Miguel; Breakefield, Xandra O.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. [Skog, Johan; Wuerdinger, Tom; van Rijn, Sjoerd; Meijer, Dimphna H.; Gainche, Laura; Sena-Esteves, Miguel; Breakefield, Xandra O.] Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA. [Wuerdinger, Tom] VU Med Ctr, Dept Neurosurg, Neurooncol Res Grp, Canc Ctr Amsterdam, NL-1007 MB Amsterdam, Netherlands. [Curry, William T., Jr.; Carter, Bob S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Krichevsky, Anna M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Breakefield, XO (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, 149 13th St, Charlestown, MA 02129 USA. EM breakefield@hms.harvard.edu RI leng, xianwei/F-9073-2011 FU Wenner-Gren Foundation [NCI CA86355, NCI CA69246]; Goldhirs Foundation; Brain Tumor Society; American Brain Tumor Association FX We wish to express our gratitude to B. Tannous for supplying the Gluc lentivirus construct, C. Maguire, M. Broekman, K. Miranda, L. Russo and O. Saydam for fruitful discussions. We also would like to thank Applied Biosystems for supplying the miRNA qRT-PCR primers and S. Idema (Neuro-oncology Research Group, Cancer Center Amsterdam) for supplying some of the serum/biopsy samples. This work was supported by the Wenner-Gren Foundation (J.S.) Stiftelsen Olle Engkvist Byggmastare (J.S.), NCI CA86355 (X. O. B. and M. S. E.), NCI CA69246 (X. O. B., M. S. E. and B. S. C.), The Goldhirs Foundation (B. S. C.) the Brain Tumor Society (A. M. K.) and the American Brain Tumor Association (T. W.). NR 37 TC 1486 Z9 1571 U1 44 U2 209 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD DEC PY 2008 VL 10 IS 12 BP 1470 EP U209 DI 10.1038/ncb1800 PG 12 WC Cell Biology SC Cell Biology GA 377OZ UT WOS:000261261800019 PM 19011622 ER PT J AU Gadhoum, SZ Sackstein, R AF Gadhoum, Samah Zeineb Sackstein, Robert TI CD15 expression in human myeloid cell differentiation is regulated by sialidase activity SO NATURE CHEMICAL BIOLOGY LA English DT Article ID HUMAN HEMATOPOIETIC PROGENITORS; ANTI-CD44 MONOCLONAL-ANTIBODIES; HUMAN T-CELLS; E-SELECTIN; ADHESION MOLECULES; LYMPHOCYTE MIGRATION; PLASMA-MEMBRANE; DENDRITIC CELLS; LEUKEMIA CELLS; BONE-MARROW AB The glycan determinant CD15 (also known as Lewis x, or Le(x)) is a distinguishing marker for human myeloid cells and mediates neutrophil adhesion to dendritic cells. Despite broad interest in this structure, the mechanisms underlying CD15 expression remain relatively uncharacterized. Accordingly, we investigated the molecular basis of increasing CD15 expression associated with human myeloid cell differentiation. Flow cytometric analysis of differentiating cells together with biochemical studies using inhibitors of glycan synthesis and of sialidases showed that increased CD15 expression is not due to de novo biosynthesis of CD15, but results predominantly from induction of alpha(2- 3)-sialidase activity, which yields CD15 from cell-surface sialyl-CD15 (also known as sialyl-Lewis x, sLe(x) or CD15s). This differentiation-associated conversion of surface CD15s to CD15 occurs mainly on glycoproteins. Until now, modulation of post-translational glycan modifications has been attributed solely to dynamic variations in glycosyltransferase expression. Our results unveil a new paradigm by demonstrating a critical role for post-Golgi membrane glycosidase activity in the 'biosynthesis' of a key glycan determinant. C1 [Gadhoum, Samah Zeineb; Sackstein, Robert] Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. [Gadhoum, Samah Zeineb; Sackstein, Robert] Harvard Univ, Sch Med, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. [Sackstein, Robert] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Sackstein, Robert] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sackstein, R (reprint author), Brigham & Womens Hosp, Dept Dermatol, 75 Francis St, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU US National Heart, Lung, and Blood Institute [RO1 HL60528]; US National Institute of Diabetes and Digestive and Kidney Diseases [R21 DK075012]; Team Jobie Leukemia Research fund FX We are grateful to D. Floyd, S. Hamdan, C. Silvescu and C. Knoblauch for technical support, to J. Merzaban, N. Stamatos, C. Dimitroff and M. Burdick for helpful discussions of the manuscript, and to I. Galinsky, R. Stone, D. DeAngelo, M. Wadleigh and A. Sirulnik for assistance in procuring leukemia samples. This work was supported by US National Heart, Lung, and Blood Institute grant RO1 HL60528 (R.S.), US National Institute of Diabetes and Digestive and Kidney Diseases grant R21 DK075012 (R.S.) and the Team Jobie Leukemia Research fund (R.S.). NR 44 TC 40 Z9 43 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD DEC PY 2008 VL 4 IS 12 BP 751 EP 757 DI 10.1038/nchembio.116 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 373FH UT WOS:000260955900011 PM 18953356 ER PT J AU Burnett-Bowie, SAM AF Burnett-Bowie, Sherri-Ann M. TI Is twice-yearly denosumab beneficial in postmenopausal women with osteopenia but no history of fracture? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE BMD; bone turnover marker; denosumab; osteoporosis; women ID OSTEOPOROSIS; RECEPTOR AB This Practice Point commentary discusses the findings and limitations of the first randomized, placebo-controlled trial of twice-yearly denosumab to be performed in postmenopausal women with low BMD but no previous fracture. Bone et al. found that treatment with denosumab significantly increased BMD at all sites measured and reduced the levels of bone turnover markers when compared with placebo. Despite these beneficial effects, denosumab was associated with increased rates of sore throat, rash and infections requiring hospitalization. Furthermore, the study was limited by lack of information on antifracture efficacy, although such information will presumably be forthcoming in the near future. Here, I highlight how denosumab therapy differs from other antiresorptive agents with respect to mechanism of action and effects on BMD. The findings of Bone et al. suggest that denosumab might represent a novel anti-osteoporosis agent. Nonetheless, further investigations of efficacy and long-term safety are needed before denosumab can be adopted into routine clinical practice. C1 [Burnett-Bowie, Sherri-Ann M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Burnett-Bowie, Sherri-Ann M.] Harvard Univ, Sch Med, Boston, MA USA. RP Burnett-Bowie, SAM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Thier 1051,50 Blossom St, Boston, MA 02114 USA. EM sburnett-bowie@partners.org OI Burnett-Bowie, Sherri-Ann/0000-0002-0064-096X NR 7 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD DEC PY 2008 VL 4 IS 12 BP 660 EP 661 DI 10.1038/ncpendmet0981 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375JB UT WOS:000261108900007 PM 18981994 ER PT J AU Jain, SH Sadow, PM Nose, V Dluhy, RG AF Jain, Shilpa H. Sadow, Peter M. Nose, Vania Dluhy, Robert G. TI A patient with ectopic cortisol production derived from malignant testicular masses SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Article DE adrenal rest cells; adrenocortical carcinoma; Cushing syndrome; Leydig cell tumor ID CUSHINGS-SYNDROME; ADRENOGENITAL SYNDROME; TUMORS AB Background A 65-year-old man presented to an oncology clinic with bilateral testicular masses, lower extremity edema, and cushingoid appearance. Investigations Measurements of serum cortisol and adrenocorticotropic hormone levels, testicular ultrasound and abdominal CT scans, and review of histopathology to identify the cellular origin of the ectopic cortisol production. Diagnosis Cushing syndrome was diagnosed on the basis of a markedly elevated 24-hour urine free cortisol level and classic cushingoid features. The etiology of Cushing syndrome was determined to be an adrenocortical carcinoma arising from testicular adrenal rest cells. Nevertheless, the possibility of a malignant Leydig cell tumor with ectopic cortisol production could not be excluded. Management Mitotane and metyrapone were used to decrease cortisol production. Excess mineralocorticoid activity was blocked with spironolactone; sodium retention was also managed with sodium restriction and diuretics. Despite initial success with this regimen, the patient died as a result of tumor progression and complications of poorly controlled hypercortisolism. C1 [Dluhy, Robert G.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. [Sadow, Peter M.; Dluhy, Robert G.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Nose, Vania] Harvard Univ, Sch Med, Boston, MA USA. [Sadow, Peter M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. EM shjain@partners.org NR 12 TC 6 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD DEC PY 2008 VL 4 IS 12 BP 695 EP 700 DI 10.1038/ncpendmet0985 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 375JB UT WOS:000261108900013 PM 18941436 ER PT J AU Brugge, WR AF Brugge, William R. TI Contrast-enhanced endoscopic ultrasound for diagnosis of pancreatic malignancy-a visual aid or a distraction? SO NATURE CLINICAL PRACTICE GASTROENTEROLOGY & HEPATOLOGY LA English DT Editorial Material DE contrast-enhanced EUS; diagnosis; EUS; pancreatic adenocarcinoma; pancreatic lesions ID EUS-GUIDED FNA; FOCAL PANCREATITIS; TUMORS; ULTRASONOGRAPHY; DISEASES; CANCER AB Endoscopic ultrasound with fine-needle aspiration (EUS-FNA) is the gold standard for diagnosis of pancreatic malignancy. This commentary discusses the findings and limitations of a study by Dietrich and colleagues that examined the operative characteristics of contrast-enhanced EUS (CE-EUS) in patients with a solitary, solid, pancreatic mass of less than 4 cm in diameter. The authors compared the vascularity of adenocarcinomas with that of neuroendocrine tumors and other lesions of the pancreas. The finding of decreased vascularity on CE-EUS had a sensitivity of 92% and a specificity of 100% for the differentiation of adenocarcinomas from neuroendocrine tumors. It seems unlikely that CE-EUS will replace EUS-FNA for the diagnosis of pancreatic malignancy, but CE-EUS might have a role in differentiating adenocarcinomas from neuroendocrine tumors. It might be possible to use CE-EUS to assist in confirming the diagnosis of neuroendocrine tumors and perhaps in directing EUS-FNA. C1 [Brugge, William R.] Massachusetts Gen Hosp, GI Unit, GI Endoscopy, Boston, MA 02114 USA. [Brugge, William R.] Harvard Univ, Sch Med, Boston, MA USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit, GI Endoscopy, Blake 452C, Boston, MA 02114 USA. EM wbrugge@partners.org NR 13 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4378 J9 NAT CLIN PRACT GASTR JI Nat. Clin. Pract. Gastroenterol. Hepatol. PD DEC PY 2008 VL 5 IS 12 BP 662 EP 663 DI 10.1038/ncpgasthep1285 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 376PY UT WOS:000261196700002 PM 18852727 ER PT J AU Hodi, FS Fisher, DE AF Hodi, F. Stephen Fisher, David E. TI Adoptive transfer of antigen-specific CD4(+) T cells in the treatment of metastatic melanoma SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE antigen-specific; CD4+T cells; cancer; metastatic melanoma ID CANCER; THERAPY; IMMUNOTHERAPY AB Clinical investigations of adoptive therapy in solid tumors have primarily focused on CD8(+) cells. A study by Hunder et al. is the first to demonstrate the significance of antigen-specific CD4(+) T cells. An in vitro method was used to treat a patient with metastatic melanoma using autologous CD4(+) cells against NY-ESO-1 (cancer and/or testis antigen 1). The successful adoptive transfer of antigen-specific CD4(+) cells to a patient with metastatic melanoma is not only an important technical accomplishment but also provides increased understanding of tumor immunity. This report demonstrates an impressive persistence of adoptively transferred cells together with durability of clinical response. CD4(+) T cells that target a particular antigen can augment T-cell responses to other tumor-associated targets. These observations underline the importance of ongoing research for effective, non-toxic immune therapies for cancer. C1 [Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Melanoma Program, Boston, MA 02114 USA. [Fisher, David E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Hodi, F. Stephen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Melanoma Program, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Melanoma Program, 55 Fruit St, Boston, MA 02114 USA. EM dfisher3@partners.org NR 7 TC 9 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD DEC PY 2008 VL 5 IS 12 BP 696 EP 697 DI 10.1038/ncponc1259 PG 2 WC Oncology SC Oncology GA 376QE UT WOS:000261197300006 PM 18852719 ER PT J AU Rosenberg, JE Oh, WK AF Rosenberg, Jonathan E. Oh, William K. TI What is the current status of second-line chemotherapy for castration-resistant prostate cancer? SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material DE chemotherapy; chemotherapy resistance; mitoxantrone; prostate cancer; salvage treatment ID MITOXANTRONE; DOCETAXEL; PREDNISONE; SURVIVAL; TAX-327; PHASE-2 AB Patients with castration-resistant prostate cancer (CRPC) who show progression of disease after first-line chemotherapy with docetaxel have few proven treatment options. Mitoxantrone plus prednisone is frequently used in this setting. The retrospective analysis by Berthold et al. of mitoxantrone after first-line docetaxel in patients with CRPC suggests that mitoxantrone has a modest level of activity in this setting, with a second-line PSA response rate of 15% and a median time to PSA progression of 3.2 months. Patients with CRPC treated with docetaxel after progression on first-line mitoxantrone had a PSA response rate of 28% and a median time to PSA progression of 5.9 months. In this analysis, median survival of patients was 10 months and did not differ according to choice of first-line agent. Mitoxantrone therapy can be considered in select patients after failure of first-line docetaxel, and vice versa. Other cytotoxic agents such as carboplatin might have a limited role in this patient population. In general, patients with CRPC should be directed towards clinical trials, when available. C1 [Rosenberg, Jonathan E.; Oh, William K.] Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02446 USA. [Rosenberg, Jonathan E.; Oh, William K.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Rosenberg, JE (reprint author), Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, 44 Binney St,D1230, Boston, MA 02446 USA. EM jonathan_rosenberg@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 8 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD DEC PY 2008 VL 5 IS 12 BP 650 EP 651 DI 10.1038/ncpuro1232 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 379GF UT WOS:000261384000006 PM 18936787 ER PT J AU Cooper, JD Smyth, DJ Smiles, AM Plagnol, V Walker, NM Allen, JE Downes, K Barrett, JC Healy, BC Mychaleckyj, JC Warram, JH Todd, JA AF Cooper, Jason D. Smyth, Deborah J. Smiles, Adam M. Plagnol, Vincent Walker, Neil M. Allen, James E. Downes, Kate Barrett, Jeffrey C. Healy, Barry C. Mychaleckyj, Josyf C. Warram, James H. Todd, John A. TI Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci SO NATURE GENETICS LA English DT Article ID LARGE-SCALE; PKC-THETA; DISEASES; REGION; BACH2 AB We carried out a meta-analysis of data from three genome-wide association (GWA) studies of type 1 diabetes (T1D), testing 305,090 SNPs in 3,561 T1D cases and 4,646 controls of European ancestry. We obtained further support for 4q27 (IL2-IL21, P = 1.9 x 10(-8)) and, after genotyping an additional 6,225 cases, 6,946 controls and 2,828 families, convincing evidence for four previously unknown and distinct risk loci in chromosome regions 6q15 (BACH2, P = 4.7 x 10(-12)), 10p15 (PRKCQ, P = 3.7 x 10(-9)), 15q24 (CTSH, P = 3.2 x 10(-15)) and 22q13 (C1QTNF6, P = 2.0 x 10(-8)). C1 [Cooper, Jason D.; Smyth, Deborah J.; Plagnol, Vincent; Walker, Neil M.; Allen, James E.; Downes, Kate; Barrett, Jeffrey C.; Healy, Barry C.; Todd, John A.] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0XY, England. [Smiles, Adam M.; Warram, James H.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Mychaleckyj, Josyf C.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA. RP Cooper, JD (reprint author), Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0XY, England. EM jason.cooper@cimr.cam.ac.uk RI Allen, James/B-2457-2009; Plagnol, Vincent/A-5667-2011; Todd, John/A-3542-2010; OI Allen, James/0000-0002-3894-4854; Walker, Neil/0000-0001-9796-7688; smyth, deborah/0000-0002-6330-2669; Plagnol, Vincent/0000-0002-5597-9215 FU Juvenile Diabetes Research Foundation International; Wellcome Trust; National Institute for Health Research Cambridge Biomedical Centre; Wellcome Trust Strategic Award [079895]; Wellcome Trust [076113] FX This work was funded by the Juvenile Diabetes Research Foundation International, the Wellcome Trust and the National Institute for Health Research Cambridge Biomedical Centre. The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (079895). We thank all study participants and family members. We gratefully acknowledge D. Clayton for methodology advice and comments on the manuscript. We acknowledge use of DNA from the British 1958 Birth Cohort collection, funded by the Medical Research Council and the Wellcome Trust. We thank The Avon Longitudinal Study of Parents and Children laboratory in Bristol and the British 1958 Birth Cohort team, including S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton, for preparing and providing the control DNA samples. We also thank H. Stevens, P. Clarke, G. Coleman, S. Duley, D. Harrison, S. Hawkins, M. Maisuria, T. Mistry and N. Taylor for preparation of DNA samples. We acknowledge use of DNA from the Human Biological Data Interchange and Diabetes UK for the USA and UK multiplex families, respectively; the Norwegian Study Group for Childhood Diabetes (D. Undlien and K. Ronningen) for the Norwegian families; D. Savage, C. Patterson, D. Carson and P. Maxwell for the Northern Irish families; the Genetics of Type 1 Diabetes in Finland (GET1FIN); J. Tuomilehto, L. Kinnunen, E. Tuomilehto-Wolf, V. Harjutsalo and T. Valle for the Finnish families; and C. Guja and C. Ionescu-Tirgoviste for the Romanian families. WTCCC: This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data are available from http://www.wtccc.org.uk/. Funding for the project was provided by the Wellcome Trust under award 076113 (see ref. 1). NIMH: We gratefully acknowledge the National Institute of Mental Health for generously allowing the use of their control CEL and genotype data. Control subjects from the National Institute of Mental Health Schizophrenia Genetics Initiative (NIMH-GI), data and biomaterials are being collected by the "Molecular Genetics of Schizophrenia II'' (MGS-2) collaboration. The investigators and co-investigators are as follows: P.V. Gejman (Collaboration coordinator) and A. R. Sanders (ENH/Northwestern University, MH059571); F. Amin (Emory University School of Medicine, MH59587); N. Buccola (Louisiana State University Health Sciences Center, MH067257); W. Byerley (University of California-Irvine, MH60870); C. R. Cloninger (Washington University, St. Louis, U01, MH060879); R. Crowe (PI) and D. Black (University of Iowa, MH59566); R. Freedman (University of Colorado, MH059565); D. Levinson (University of Pennsylvania, MH061675); B. Mowry (University of Queensland, MH059588); and J. Silverman (Mt. Sinai School of Medicine, MH59586). The samples were collected by V.L. Nimgaonkar's group at the University of Pittsburgh as part of a multi-institutional collaborative research project with J. Smoller and P. Sklar (Massachusetts General Hospital) (grant MH 63420). GoKinD: We acknowledge the National Institutes of Health for allowing the use of their control allele signal intensity and genotype data. The dataset(s) used for the analyses described in this manuscript were obtained from the GAIN Database, controlled through dbGaP accession number phs000018.v1.p1. NR 15 TC 261 Z9 265 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2008 VL 40 IS 12 BP 1399 EP 1401 DI 10.1038/ng.249 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 376XI UT WOS:000261215900012 PM 18978792 ER PT J AU Dengler, HS Baracho, GV Omori, SA Bruckner, S Arden, KC Castrillon, DH DePinho, RA Rickert, RC AF Dengler, Hart S. Baracho, Gisele V. Omori, Sidne A. Bruckner, Shane Arden, Karen C. Castrillon, Diego H. DePinho, Ronald A. Rickert, Robert C. TI Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation SO NATURE IMMUNOLOGY LA English DT Article ID CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN GENE REARRANGEMENTS; INTERLEUKIN-7 RECEPTOR; REGULATORY FACTOR-4; IMMUNE-SYSTEM; MICE LACKING; EXPRESSION; ACTIVATION; LINEAGE; PROLIFERATION AB The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation. Early deletion of Foxo1 caused a substantial block at the pro-B cell stage due to a failure to express interleukin 7 receptor-alpha. Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to lower expression of the recombination-activating genes Rag1 and Rag2. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to lower expression of L-selectin and failed class-switch recombination due to impaired upregulation of the gene encoding activation-induced cytidine deaminase. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function. C1 [Dengler, Hart S.; Baracho, Gisele V.; Omori, Sidne A.; Bruckner, Shane; Rickert, Robert C.] Burnham Inst Med Res, Program Inflammatory Dis Res, La Jolla, CA 92037 USA. [Arden, Karen C.] Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. [Castrillon, Diego H.] Univ Texas SW Med Ctr Dallas, Dept Pathol, Dallas, TX 75390 USA. [DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Rickert, RC (reprint author), Burnham Inst Med Res, Program Inflammatory Dis Res, La Jolla, CA 92037 USA. EM robert@burnham.org FU US National Institutes of Health [AI059447]; American Cancer Society; Robert A. and Renee E. Befler Foundation Institute for Innovative Cancer Science FX We thank K. Rajewsky (Harvard University) and M. Reth (Max-Planck Institute) for Cd21Cre and mb1Cre mice, respectively; B. Finlay (Burnham Institute for Medical Research) and K. Mowen (The Scripps Research Institute) for retroviruses expressing Bcl-xL and Cre, respectively; and S. Hedrick and members of the Rickert laboratory for discussions and reading of the manuscript. Supported by the US National Institutes of Health (AI059447 to R. C. R.), the American Cancer Society (R. A. D.) and the Robert A. and Renee E. Befler Foundation Institute for Innovative Cancer Science (R. A. D.). NR 50 TC 145 Z9 148 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2008 VL 9 IS 12 BP 1388 EP 1398 DI 10.1038/ni.1667 PG 11 WC Immunology SC Immunology GA 372FY UT WOS:000260888700014 PM 18978794 ER PT J AU Engelman, JA Chen, L Tan, XH Crosby, K Guimaraes, AR Upadhyay, R Maira, M McNamara, K Perera, SA Song, YC Chirieac, LR Kaur, R Lightbown, A Simendinger, J Li, T Padera, RF Garcia-Echeverria, C Weissleder, R Mahmood, U Cantley, LC Wong, KK AF Engelman, Jeffrey A. Chen, Liang Tan, Xiaohong Crosby, Katherine Guimaraes, Alexander R. Upadhyay, Rabi Maira, Michel McNamara, Kate Perera, Samanthi A. Song, Youngchul Chirieac, Lucian R. Kaur, Ramneet Lightbown, Angela Simendinger, Jessica Li, Timothy Padera, Robert F. Garcia-Echeverria, Carlos Weissleder, Ralph Mahmood, Umar Cantley, Lewis C. Wong, Kwok-Kin TI Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers SO NATURE MEDICINE LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; MICE; MUTATIONS; RAS; TUMORIGENESIS; SENSITIVITY; EXPRESSION; P110-ALPHA AB Somatic mutations that activate phosphoinositide 3-kinase (PI3K) have been identified in the p110-alpha catalytic subunit (encoded by PIK3CA)(1). They are most frequently observed in two hotspots: the helical domain (E545K and E542K) and the kinase domain (H1047R). Although the p110-alpha mutants are transforming in vitro, their oncogenic potential has not been assessed in genetically engineered mouse models. Furthermore, clinical trials with PI3K inhibitors have recently been initiated, and it is unknown if their efficacy will be restricted to specific, genetically defined malignancies. In this study, we engineered a mouse model of lung adenocarcinomas initiated and maintained by expression of p110-alpha H1047R. Treatment of these tumors with NVP-BEZ235, a dual pan-PI3K and mammalian target of rapamycin (mTOR) inhibitor in clinical development, led to marked tumor regression as shown by positron emission tomography-computed tomography, magnetic resonance imaging and microscopic examination. In contrast, mouse lung cancers driven by mutant Kras did not substantially respond to single-agent NVP-BEZ235. However, when NVP-BEZ235 was combined with a mitogen-activated protein kinase kinase (MEK) inhibitor, ARRY-142886, there was marked synergy in shrinking these Kras-mutant cancers. These in vivo studies suggest that inhibitors of the PI3K-mTOR pathway may be active in cancers with PIK3CA mutations and, when combined with MEK inhibitors, may effectively treat KRAS mutated lung cancers. C1 Beth Israel Hosp, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Engelman, Jeffrey A.; Song, Youngchul; Kaur, Ramneet] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Engelman, Jeffrey A.; Kaur, Ramneet; Cantley, Lewis C.; Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Chen, Liang; Tan, Xiaohong; McNamara, Kate; Perera, Samanthi A.; Wong, Kwok-Kin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Chen, Liang; Tan, Xiaohong; McNamara, Kate; Perera, Samanthi A.; Wong, Kwok-Kin] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. [Crosby, Katherine; Lightbown, Angela; Simendinger, Jessica] Cell Signaling Technol, Danvers, MA 01923 USA. [Guimaraes, Alexander R.; Upadhyay, Rabi; Weissleder, Ralph; Mahmood, Umar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Guimaraes, Alexander R.; Upadhyay, Rabi; Weissleder, Ralph; Mahmood, Umar] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Maira, Michel; Garcia-Echeverria, Carlos] Novartis Inst Biomed Res, Oncol Dis Area, CH-4057 Basel, Switzerland. [Chirieac, Lucian R.; Padera, Robert F.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Weissleder, Ralph; Cantley, Lewis C.] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Hosp, Beth Israel Deaconess Med Ctr, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu; KWONG1@PARTNERS.ORG RI Cantley, Lewis/D-1800-2014; OI Cantley, Lewis/0000-0002-1298-7653; wong, kwok kin/0000-0001-6323-235X FU US National Institutes of Health (NIH) [CA120060-01]; American Association for Cancer Research; International Association for the Study of Lung Cancer; NIH [CA089021, P01 CA117969, R01 GM41890, K08 AG024004, R01 CA122794, R01 AG2400401]; Dana-Farber-Harvard Cancer Center Lung Cancer Specialized Program of Research Excellence (SPORE) [P50 CA090578]; Dana-Farber-Harvard Cancer Center Gastrointestinal Cancer SPORE [P50 CA127003, U24-CA092782]; Joan Scarangello Foundation to Conquer Lung Cancer; Cecily and Robert Harris Foundation; Flight Attendant Medical Research Institute FX CCSP-rtTA mice were generously provided by J. Whitsett at the University of Cincinnati. Tet-op-Kras mice were generously provided by H. Varmus (Memorial Sloan-Kettering Cancer Center). LSL-Kras G12D mice were kindly provided by T. Jacks (Massachusetts Institute of Technology). This work was supported by US National Institutes of Health (NIH) K08 grant CA120060-01 (J. A. E.), the American Association for Cancer Research (J. A. E.), the International Association for the Study of Lung Cancer (J. A. E.), NIH prostate cancer grant P01 CA089021 (L. C. C.), NIH pancreatic cancer grant P01 CA117969 (L. C. C.), NIH grant R01 GM41890 (L. C. C.), a Dana-Farber-Harvard Cancer Center Lung Cancer Specialized Program of Research Excellence (SPORE) grant P50 CA090578 (J. A. E. and K.-K.W.) and Dana-Farber-Harvard Cancer Center Gastrointestinal Cancer SPORE grants P50 CA127003 (J. A. E., R. W., U. M. and L. C. C.) and U24-CA092782 (R. W., U. M., A. R. G.). K.-K.W. was supported by NIH grants K08 AG024004, R01 CA122794 and R01 AG2400401; the Joan Scarangello Foundation to Conquer Lung Cancer; the Cecily and Robert Harris Foundation; and the Flight Attendant Medical Research Institute. NR 21 TC 754 Z9 776 U1 3 U2 38 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 DEC PY 2008 VL 14 IS 12 BP 1351 EP 1356 DI 10.1038/nm.1890 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 379JX UT WOS:000261393600019 PM 19029981 ER PT J AU Yu, PB Deng, DY Lai, CS Hong, CC Cuny, GD Bouxsein, ML Hong, DW McManus, PM Katagiri, T Sachidanandan, C Kamiya, N Fukuda, T Mishina, Y Peterson, RT Bloch, KD AF Yu, Paul B. Deng, Donna Y. Lai, Carol S. Hong, Charles C. Cuny, Gregory D. Bouxsein, Mary L. Hong, Deborah W. McManus, Patrick M. Katagiri, Takenobu Sachidanandan, Chetana Kamiya, Nobuhiro Fukuda, Tomokazu Mishina, Yuji Peterson, Randall T. Bloch, Kenneth D. TI BMP type I receptor inhibition reduces heterotopic ossification SO NATURE MEDICINE LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROGRESSIVA FOP; BONE-FORMATION; SMAD PROTEINS; DIFFERENTIATION; MOUSE; ACVR1; ALK2; MUTATION; ARREST AB Fibrodysplasia ossificans progressiva (FOP) is a congenital disorder of progressive and widespread postnatal ossification of soft tissues(1-4) and is without known effective treatments. Affected individuals harbor conserved mutations in the ACVR1 gene that are thought to cause constitutive activation of the bone morphogenetic protein (BMP) type I receptor, activin receptor-like kinase-2 (ALK2)(5). Here we show that intramuscular expression in the mouse of an inducible transgene encoding constitutively active ALK2 (caALK2), resulting from a glutamine to aspartic acid change at amino acid position 207, leads to ectopic endochondral bone formation, joint fusion and functional impairment, thus phenocopying key aspects of human FOP. A selective inhibitor of BMP type I receptor kinases, LDN-193189 (ref. 6), inhibits activation of the BMP signaling effectors SMAD1, SMAD5 and SMAD8 in tissues expressing caALK2 induced by adenovirus specifying Cre (Ad. Cre). This treatment resulted in a reduction in ectopic ossification and functional impairment. In contrast to localized induction of caALK2 by Ad. Cre (which entails inflammation), global postnatal expression of caALK2 (induced without the use of Ad. Cre and thus without inflammation) does not lead to ectopic ossification. However, if in this context an inflammatory stimulus was provided with a control adenovirus, ectopic bone formation was induced. Like LDN-193189, corticosteroid treatment inhibits ossification in Ad.Cre-injected mutant mice, suggesting caALK2 expression and an inflammatory milieu are both required for the development of ectopic ossification in this model. These results support the role of dysregulated ALK2 kinase activity in the pathogenesis of FOP and suggest that small molecule inhibition of BMP type I receptor activity may be useful in treating FOP and heterotopic ossification syndromes associated with excessive BMP signaling. C1 [Yu, Paul B.; Deng, Donna Y.; Lai, Carol S.; Hong, Deborah W.; McManus, Patrick M.; Sachidanandan, Chetana; Peterson, Randall T.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. [Yu, Paul B.; Bloch, Kenneth D.] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. [Yu, Paul B.; Bloch, Kenneth D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Div Cardiovasc Med, Nashville, TN 37232 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. [Cuny, Gregory D.] Brigham & Womens Hosp, Lab Drug Discovery Neurodegenerat, Harvard NeuroDiscovery Ctr, Cambridge, MA 02139 USA. [Cuny, Gregory D.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02215 USA. [Bouxsein, Mary L.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Katagiri, Takenobu] Saitama Med Univ, Div Pathophysiol, Res Ctr Genom Med, Hidaka, Saitama 3501241, Japan. [Kamiya, Nobuhiro; Fukuda, Tomokazu; Mishina, Yuji] NIEHS, Mol Dev Biol Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Yu, PB (reprint author), Massachusetts Gen Hosp, Div Cardiol, Dept Med, Thier 505,50 Blossom St, Boston, MA 02114 USA. EM pbyu@partners.org RI Hong, Charles/C-9989-2010 FU US National Institutes of Health [HL079943, HL074352]; US National Institute of Environmental Health Sciences Intramural Research Program [ES071003-10]; Howard Hughes Medical Institute Early Career Award; GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease; Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders at the University of Pennsylvania FX We thank P. ten Dijke (Leiden University Medical Center) for providing BRE-Luc and CAGA-Luc and K. Miyazono (University of Tokyo) for providing caALK2, caALK3, caALK4, caALK5, caALK6 and caALK7. We are grateful to H. Beppu, E. Schipani, H. Kronenberg, A. Wagers, J. Groppe, W. Zapol and F. Kaplan for insightful discussions and technical expertise, A. Graveline and D. Panus for technical assistance and E. Buys for technical expertise. This work was supported by US National Institutes of Health grants HL079943 (P.B.Y.) and HL074352 (K. D. B.), the US National Institute of Environmental Health Sciences Intramural Research Program grant ES071003-10 (Y.M.) and Partners Healthcare. This work was also supported by a Howard Hughes Medical Institute Early Career Award (P.B.Y.), a Pulmonary Hypertension Association Mentored Clinical Scientist Award (P.B.Y.), a grant from the GlaxoSmithKline Research & Education Foundation for Cardiovascular Disease (P.B.Y.) and a Developmental Grant from the Center for Research in Fibrodysplasia Ossificans Progressiva and Related Disorders at the University of Pennsylvania (C. C. H.). NR 33 TC 269 Z9 279 U1 5 U2 28 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 DEC PY 2008 VL 14 IS 12 BP 1363 EP 1369 DI 10.1038/nm.1888 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 379JX UT WOS:000261393600021 PM 19029982 ER PT J AU Hartley, JL Salehi-Ashtiani, K Hill, DE AF Hartley, James L. Salehi-Ashtiani, Kourosh Hill, David E. TI Proteome expression moves in vitro: resources and tools for harnessing the human proteome SO NATURE METHODS LA English DT Editorial Material ID OPEN READING FRAMES; ORFEOME VERSION 1.1; COLLECTION; GENOME AB Comprehensive sets of clones and improved high-throughput methods for production of functional proteins now allow proteome-scale in vitro experiments on nearly 15,000 human genes. C1 [Hartley, James L.] NCI, SAIC Frederick, Frederick, MD 21702 USA. [Salehi-Ashtiani, Kourosh; Hill, David E.] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Salehi-Ashtiani, Kourosh; Hill, David E.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Hartley, JL (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov; kourosh_salehi-ashtiani@dfci.harvard.edu; david_hill@dfci.harvard.edu RI Hill, David/B-6617-2011; OI Salehi-Ashtiani, Kourosh/0000-0002-6521-5243 NR 12 TC 3 Z9 3 U1 0 U2 3 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 DEC PY 2008 VL 5 IS 12 BP 1001 EP 1002 DI 10.1038/nmeth1208-1001 PG 2 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 376WC UT WOS:000261212700009 PM 19034266 ER PT J AU Fernandez-Suarez, M Ting, AY AF Fernandez-Suarez, Marta Ting, Alice Y. TI Fluorescent probes for super-resolution imaging in living cells SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID PHOTOACTIVATED LOCALIZATION MICROSCOPY; OPTICAL RECONSTRUCTION MICROSCOPY; DIFFRACTION RESOLUTION BARRIER; SMALL-MOLECULE PROBES; LIVE CELLS; STIMULATED-EMISSION; QUANTUM DOTS; IN-VIVO; STED MICROSCOPY; NEAR-FIELD AB In 1873, Ernst Abbe discovered that features closer than similar to 200 nm cannot be resolved by lens-based light microscopy. In recent years, however, several new far-field super-resolution imaging techniques have broken this diffraction limit, producing, for example, video-rate movies of synaptic vesicles in living neurons with 62 nm spatial resolution. Current research is focused on further improving spatial resolution in an effort to reach the goal of video-rate imaging of live cells with molecular (1-5 nm) resolution. Here, we describe the contributions of fluorescent probes to far-field super-resolution imaging, focusing on fluorescent proteins and organic small-molecule fluorophores. We describe the features of existing super-resolution fluorophores and highlight areas of importance for future research and development. C1 [Fernandez-Suarez, Marta; Ting, Alice Y.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Fernandez-Suarez, Marta] Massachusetts Gen Hosp, Ctr Engn Med, Charlestown, MA 02129 USA. RP Fernandez-Suarez, M (reprint author), MIT, Dept Chem, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM martafs@alum.mit.edu; ating@mit.edu NR 120 TC 601 Z9 614 U1 64 U2 441 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD DEC PY 2008 VL 9 IS 12 BP 929 EP 943 DI 10.1038/nrm2531 PG 15 WC Cell Biology SC Cell Biology GA 375PW UT WOS:000261126800013 PM 19002208 ER PT J AU Dresemann, G Sorenson, G Reardon, DA Hosius, C Parker, R Nikolova, Z AF Dresemann, G. Sorenson, G. Reardon, D. A. Hosius, C. Parker, R. Nikolova, Z. TI QUANTIFYING ASSESSMENTS FOR GLIOBLASTOMA MULTIFORME (GBM) FOR CLINICAL TRIALS - AN ALTERNATIVE APPROACH SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 8th Congress of the European-Association-for-Neuro-Oncology (EANO) CY SEP 12-14, 2008 CL Barcelona, SPAIN SP European Assoc Neuro Oncol C1 [Dresemann, G.] CTC Standort Franz Hosp, Dulmen, Germany. [Sorenson, G.] Massachusetts Gen Hosp, Charlestown, MA USA. [Reardon, D. A.] Duke Univ, Med Ctr, Durham, NC USA. [Hosius, C.] Novartis Pharma Oncol, Nurnberg, Germany. [Parker, R.; Nikolova, Z.] Novartis Pharma Oncol, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD DEC PY 2008 VL 10 IS 6 BP 1139 EP 1139 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 383TG UT WOS:000261695800318 ER PT J AU Helt, M Kelley, E Kinsbourne, M Pandey, J Boorstein, H Herbert, M Fein, D AF Helt, Molly Kelley, Elizabeth Kinsbourne, Marcel Pandey, Juhi Boorstein, Hilary Herbert, Martha Fein, Deborah TI Can Children with Autism Recover? If So, How? SO NEUROPSYCHOLOGY REVIEW LA English DT Review DE Autism spectrum disorders; Language development; Recovery; Stereotyped motor behavior ID PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE BEHAVIORAL INTERVENTION; FUSIFORM FACE AREA; FOLLOW-UP; SPECTRUM DISORDERS; YOUNG-CHILDREN; REPETITIVE BEHAVIORS; JOINT ATTENTION; 1ST YEAR; COMMUNICATION INTERVENTION AB Although Autism Spectrum Disorders (ASD) are generally assumed to be lifelong, we review evidence that between 3% and 25% of children reportedly lose their ASD diagnosis and enter the normal range of cognitive, adaptive and social skills. Predictors of recovery include relatively high intelligence, receptive language, verbal and motor imitation, and motor development, but not overall symptom severity. Earlier age of diagnosis and treatment, and a diagnosis of Pervasive Developmental Disorder-Not Otherwise Specified are also favorable signs. The presence of seizures, mental retardation and genetic syndromes are unfavorable signs, whereas head growth does not predict outcome. Controlled studies that report the most recovery came about after the use of behavioral techniques. Residual vulnerabilities affect higher-order communication and attention. Tics, depression and phobias are frequent residual co-morbidities after recovery. Possible mechanisms of recovery include: normalizing input by forcing attention outward or enriching the environment; promoting the reinforcement value of social stimuli; preventing interfering behaviors; mass practice of weak skills; reducing stress and stabilizing arousal. Improving nutrition and sleep quality is non-specifically beneficial. C1 [Helt, Molly; Boorstein, Hilary; Fein, Deborah] Univ Connecticut, Dept Psychol, Storrs, CT 06268 USA. [Kelley, Elizabeth] Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. [Kinsbourne, Marcel] New Sch, Dept Psychol, New York, NY USA. [Pandey, Juhi] Childrens Hosp Philadelphia, Ctr Autism Res, Philadelphia, PA 19104 USA. [Herbert, Martha] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Herbert, Martha] Massachusetts Gen Hosp, TRANSCEND Res Program, Charlestown, MA USA. RP Helt, M (reprint author), Univ Connecticut, Dept Psychol, Storrs, CT 06268 USA. EM molly.helt@uconn.edu NR 180 TC 110 Z9 113 U1 10 U2 42 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1040-7308 EI 1573-6660 J9 NEUROPSYCHOL REV JI Neuropsychol. Rev. PD DEC PY 2008 VL 18 IS 4 BP 339 EP 366 DI 10.1007/s11065-008-9075-9 PG 28 WC Psychology, Clinical; Neurosciences SC Psychology; Neurosciences & Neurology GA 400HJ UT WOS:000262858300007 PM 19009353 ER PT J AU Owens, MJ Krulewicz, S Simon, JS Sheehan, DV Thase, ME Carpenter, DJ Plott, SJ Nemeroff, CB AF Owens, Michael J. Krulewicz, Stan Simon, Jeffrey S. Sheehan, David V. Thase, Michael E. Carpenter, David J. Plott, Susan J. Nemeroff, Charles B. TI Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE antidepressant; transporters; reuptake; occupancy; depression; SSRI ID REUPTAKE INHIBITORS; CEREBROSPINAL-FLUID; DOUBLE-BLIND; RESISTANT DEPRESSION; CLINICAL-RESPONSE; MAJOR DEPRESSION; BINDING PROFILE; PLASMA-LEVELS; ANTIDEPRESSANTS; METABOLITES AB Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter ( NET) antagonists. However, the relative magnitude of effect at each of these sites during treatment is unknown. Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition. Outpatient subjects (N = 86) meeting criteria for major depression were enrolled in a multicenter, 8 week, randomized, double-blind, parallel group, antidepressant treatment study. Subjects were treated by forced-titration of paroxetine CR (12.5-75 mg/day) or venlafaxine XR (75-375 mg/day) over 8 weeks. Blood samples were collected weekly to estimate transporter inhibition. Both medications produced dose-dependent inhibition of the SERT and NET. Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90% (SD 7) and 85% ( SD 10), respectively. Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36% ( SD 19) and 60% ( SD 13), respectively. The adjusted mean change from baseline ( mean 28.6) at week 8 LOCF in MADRS total score was -16.7 ( SE 8.59) and -17.3 ( SE 8.99) for the paroxetine and venlafaxine-treated patients, respectively. The magnitudes of the antidepressant effects were not significantly different from each other (95% CI - 3.42, 4.54, p = 0.784). The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo. NET antagonism has been posited to contribute to the antidepressant effects of these compounds. The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present. C1 [Owens, Michael J.; Plott, Susan J.; Nemeroff, Charles B.] Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Lab Neuropsychopharmacol, Atlanta, GA 30322 USA. [Krulewicz, Stan; Carpenter, David J.] GlaxoSmithKline Inc, Neurosci Med Dev Ctr, Clin Psychiat N Amer, King Of Prussia, PA USA. [Simon, Jeffrey S.] Northbrooke Res Ctr, Brown Deer, WI USA. [Sheehan, David V.] Univ S Florida, Dept Psychiat, Tampa, FL USA. [Thase, Michael E.] Univ Penn, Philadelphia Vet Affairs Med Ctr, Dept Psychiat, Philadelphia, PA 19104 USA. RP Owens, MJ (reprint author), Emory Univ, Dept Psychiat & Behav Sci, Sch Med, Lab Neuropsychopharmacol, 101 Woodruff Circle,Suite 4000, Atlanta, GA 30322 USA. EM mowens@emory.edu RI Owens, Michael/G-5191-2012 FU GlaxoSmithKline; NIH [MH-77083, MH-69056, MH-58922, MH-42088, MH-39415, MH-68036] FX We thank Drs Raj Rajani, Murray Rosenthal, and Nicholas Vatakis for their contribution to this study. We also acknowledge Peter Gething, B. S. at INC Research and Mary Kelley, Ph. D ( Departments of Psychiatry and Behavioral Sciences and Biostatistics, Emory University) for performing the statistical analyses and Kathy Sheehan, Ph. D. ( Department of Psychiatry, University of South Florida) for the post hoc MADRS response and remission analyses. This work was supported by a collaborative research grant to MJO from GlaxoSmithKline. The authors are also supported by NIH MH-77083, MH-69056, MH-58922, MH-42088, MH-39415, and MH-68036. NR 43 TC 32 Z9 33 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD DEC PY 2008 VL 33 IS 13 BP 3201 EP 3212 DI 10.1038/npp.2008.47 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 370GP UT WOS:000260751000021 PM 18418363 ER PT J AU Forghani, R Farb, RI AF Forghani, R. Farb, R. I. TI Diagnosis and temporal evolution of signs of intracranial hypotension on MRI of the brain SO NEURORADIOLOGY LA English DT Article DE Intracranial hypotension; Intracranial hypovolemia; MRI; FLAIR ID CEREBROSPINAL-FLUID LEAKS; CERVICAL EPIDURAL VEINS; THUNDERCLAP HEADACHE; POSTURAL HEADACHE; MANAGEMENT; PRESSURE; HYPOVOLEMIA; FEATURES AB Introduction A comprehensive evaluation of cranial magnetic resonance imagings (MRIs) of 23 patients with intracranial hypotension (IH) was performed, and the evolution of the abnormalities on follow-up MRIs was correlated with the clinical outcome. Materials and methods The MRI report database at the University Health Network in Toronto was searched, and 23 cases of IH were identified between 2001 and 2007. A retrospective review of the MRIs of the brain and the electronic patient chart was performed. A control group of 40 subjects was also selected to complement the analysis of the pituitary gland. Results A positive venous distention sign (VDS) was observed in 23 out of 23 patients and was the first sign to disappear on early follow-up scans following successful treatment. Pachymeningeal enhancement was seen in 23 out of 23 patients, and pachymeningeal thickening was detectable on unenhanced fluid attenuation inversion recovery (FLAIR) sequences in 17 out of 23 patients (74%). An increase in pituitary size in IH was also demonstrated based on the measured pituitary height and was qualitatively detectable in 12 out of 21 (57%) patients as the protrusion of the pituitary gland above the sella turica (two postpartum patients were excluded from this analysis). Overall, there was good correlation between the imaging findings and clinical outcome following treatment. Conclusion Accurate diagnosis and follow-up of IH should be possible is some patients on unenhanced MRI of the brain by combining the signs on FLAIR and sagittal T1W images, enabling timely diagnosis in unsuspected cases and avoiding unnecessary administration of gadolinium compounds. In addition, VDS might be useful for early assessment of response to treatment. C1 [Forghani, R.] McGill Univ, Ctr Hlth, Dept Radiol, Montreal, PQ, Canada. [Farb, R. I.] Univ Toronto, Toronto Western Hosp, Dept Med Imaging, Div Neuroradiol, Toronto, ON M5T 2S8, Canada. RP Forghani, R (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Gray 273A-55 Fruit St, Boston, MA 02114 USA. EM rforghani@partners.org NR 34 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0028-3940 J9 NEURORADIOLOGY JI Neuroradiology PD DEC PY 2008 VL 50 IS 12 BP 1025 EP 1034 DI 10.1007/s00234-008-0445-z PG 10 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 385CS UT WOS:000261791300005 PM 18795275 ER PT J AU McInerney, PA Ncama, BP Wantland, D Bhengu, BR McGibbon, C Davis, SM Corless, IB Nicholas, PK AF McInerney, Patricia A. Ncama, Busisiwe P. Wantland, Dean Bhengu, Busisiwe R. McGibbon, Chris Davis, Sheila M. Corless, Inge B. Nicholas, Patrice K. TI Quality of life and physical functioning in HIV-infected individuals receiving antiretroviral therapy in KwaZulu-Natal, South Africa SO NURSING & HEALTH SCIENCES LA English DT Article DE adherence; HIV; AIDS; quality of life ID HEALTH SURVEY SF-36; SUB-SAHARAN AFRICA; MEDICATION ADHERENCE; DRUG-RESISTANCE; TUBERCULOSIS; METAANALYSIS; OUTCOMES; PROGRAM AB KwaZulu-Natal province, South Africa, accounts for 28.7% of the HIV infection total and one-third of infections among youth and children in South Africa. The purpose of this study was to examine the variables of HIV/AIDS symptoms, social support, influence of comorbid medical problems, length of time adhering to antiretroviral therapy medications, quality of life, adherence to antiretroviral medications, and physical functioning in HIV-infected individuals. Based on our model, the combination of these variables was found to determine physical functioning outcomes and adherence to HIV medications. Significant relationships were observed between physical functioning and the dependent variables of length of time on medications, comorbid health problems, and social support. A linear regression model was built to determine the degree to which these variables predicted physical functioning. In total, these predictor variables explained 29% of the variance in physical functioning. These results indicate that those individuals who reported a greater length of time on medications, fewer comorbid health problems, and greater social support had better physical functioning. C1 [McInerney, Patricia A.; Ncama, Busisiwe P.; Bhengu, Busisiwe R.] Univ KwaZulu Natal, Sch Nursing, Durban, South Africa. [Wantland, Dean] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Davis, Sheila M.] Massachusetts Gen Hosp, MGH Inst Hlth Profess, Dept Infect Dis, Boston, MA 02114 USA. [Corless, Inge B.; Nicholas, Patrice K.] Massachusetts Gen Hosp, MGH Inst Hlth Profess, Grad Program Nursing, Boston, MA 02114 USA. [Nicholas, Patrice K.] Brigham & Womens Hosp, Ctr Nursing Excellence, Div Social Med & Hlth Inequal, Boston, MA 02115 USA. [McGibbon, Chris] Univ New Brunswick, Dept Kinesiol, Fredericton, NB, Canada. RP Nicholas, PK (reprint author), 1 Brigham Circle,4th Floor,Suite 6, Boston, MA USA. EM pnicholas@partners.org OI Corless, Inge/0000-0003-0438-2037 NR 23 TC 12 Z9 12 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1441-0745 J9 NURS HEALTH SCI JI Nurs. Health Sci. PD DEC PY 2008 VL 10 IS 4 BP 266 EP 272 DI 10.1111/j.1442-2018.2008.00410.x PG 7 WC Nursing SC Nursing GA 369CW UT WOS:000260672100007 PM 19128302 ER PT J AU Aguirre, V Stylopoulos, N Grinbaum, R Kaplan, LM AF Aguirre, Vincent Stylopoulos, Nicholas Grinbaum, Ronit Kaplan, Lee M. TI An Endoluminal Sleeve Induces Substantial Weight Loss and Normalizes Glucose Homeostasis in Rats with Diet-Induced Obesity SO OBESITY LA English DT Article ID JEJUNAL BYPASS SLEEVE; BETA-CELL FUNCTION; Y GASTRIC BYPASS; FOOD-INTAKE; BARIATRIC SURGERY; BODY-WEIGHT; ILEAL TRANSPOSITION; PORCINE MODEL; ELECTRICAL-STIMULATION; ENERGY-BALANCE AB To investigate the contributions of two surgical gut manipulations-exclusion of the proximal intestine from alimentary flow and exposure of the jejunum to partially digested nutrients-to body weight regulation and metabolism, we have developed a rat model of an investigational device, the endoluminal sleeve (ELS). The ELS is a 10 cm, nutrient-impermeable, flexible tube designed for endoluminal implantation. ELS devices were surgically implanted in the duodenal bulb of rats with diet-induced obesity. Body weight, food intake, stool caloric content, and glucose homeostasis were subsequently evaluated. ELS-implanted rats demonstrated a 20% reduction of body weight compared to sham-operated (SO) controls. ELS-treated animals consumed an average of 27% fewer kcal/day than SO, and there was no evidence of malabsorption. ELS treatment improved fasting glycemia and glucose tolerance after oral and intraperitoneal (IP) administration. ELS treatment enhanced insulin sensitivity, as demonstrated by decreased fasting and glucose-stimulated insulin levels and confirmed by calculation of homeostasis model assessment of insulin resistance (IR). These data suggest that selective bypass of the proximal intestine by ELS, with enhanced delivery of partially digested nutrients to the jejunum, mimics many of the effects of Roux-en-Y gastric bypass (RYGB) on body weight and glucose metabolism. Thus, ELS implantation may be an effective treatment for obesity and diabetes. Since the ELS device is amenable to endoscopic placement, it may offer a valuable alternative to more invasive surgical approaches in selected patients with obesity and its metabolic complications. C1 [Aguirre, Vincent; Stylopoulos, Nicholas; Grinbaum, Ronit; Kaplan, Lee M.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Aguirre, Vincent; Stylopoulos, Nicholas; Grinbaum, Ronit; Kaplan, Lee M.] Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. [Aguirre, Vincent; Stylopoulos, Nicholas; Grinbaum, Ronit; Kaplan, Lee M.] Harvard Univ, Sch Med, Boston, MA USA. RP Kaplan, LM (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. EM lmkaplan@partners.org FU National Institutes of Health [DK057478, DK046200, DK043351]; GI Dynamics (Watertown, MA); [DK007191]; [HD052961] FX We thank Andy Levine for invaluable help in the development of the rat ELS model and Philip Davis and Lynn Wartschaw for excellent technical assistance. We also thank Morris White and Daniel Podolsky for their helpful review of the manuscript. These studies were supported by National Institutes of Health grants DK057478, DK046200, DK043351 (to L.M.K.); training awards DK007191 (to V.A.) and HD052961 (to N.S.); and a research grant from GI Dynamics (Watertown, MA). NR 39 TC 56 Z9 60 U1 1 U2 4 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 DEC PY 2008 VL 16 IS 12 BP 2585 EP 2592 DI 10.1038/oby.2008.502 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 379OJ UT WOS:000261405800004 PM 19279655 ER PT J AU Lara-Castro, C Doud, EC Tapia, PC Munoz, AJ Fernandez, JR Hunter, GR Gower, BA Garvey, WT AF Lara-Castro, Cristina Doud, Erin C. Tapia, Patrick C. Munoz, Andres J. Fernandez, Jose R. Hunter, Gary R. Gower, Barbara A. Garvey, W. Timothy TI Adiponectin Multimers and Metabolic Syndrome Traits: Relative Adiponectin Resistance in African Americans SO OBESITY LA English DT Article ID HIGH-MOLECULAR-WEIGHT; INSULIN SENSITIVITY; GENETIC ADMIXTURE; WAIST CIRCUMFERENCE; SERUM ADIPONECTIN; FAT DISTRIBUTION; RISK-FACTORS; PLASMA; PIOGLITAZONE; ASSOCIATIONS AB African Americans (AAs) tend to have lower total adiponectin levels compared to European Americans (EA); however, it is not known whether race affects adiponectin multimer distribution and their relationships to metabolic traits. We measured total adiponectin, high molecular weight (HMW), low molecular weight (LMW) (i.e., hexamer), and trimer adiponectin in 132 normoglycemic premenopausal women (75 AAs, 57 EAs), together with measures of total and abdominal fat, plasma lipids, insulin sensitivity (S(i)), and genetic admixture estimates. We found that lower total adiponectin in AAs was explained by reduced LMW, and trimer forms because levels of HMW did not differ between races. In EAs, HMW was highly correlated with multiple metabolic syndrome traits. In contrast, the LMW and trimer forms were most highly correlated with metabolic traits in AAs, including abdominal adiposity, lipids, and S(i). At similar levels of visceral adiposity, AAs exhibited significantly lower LMW adiponectin than EAs. Similarly, at comparable levels of HMW and LMW adiponectin, AAs were more insulin resistant than their EA counterparts. In conclusion, (i) serum adiponectin is lower in AAs predominantly as a result of reduced concentrations of LMW and trimers multimeric forms; (ii) LMW and trimer, not HMW, are most broadly correlated with metabolic traits in AAs. Thus, HMW adiponectin may exert less bioactivity in explaining the metabolic syndrome trait cluster in populations of predominant African genetic background. C1 [Lara-Castro, Cristina; Doud, Erin C.; Tapia, Patrick C.; Munoz, Andres J.; Fernandez, Jose R.; Hunter, Gary R.; Gower, Barbara A.; Garvey, W. Timothy] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Garvey, W. Timothy] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Lara-Castro, C (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. EM larac@uab.edu FU NIH [DK 49779, DK51684, DK-38764, PO1 HL-55782]; UAB GCRC [M01-RR00032]; CNRU [P30-DK56336]; T32 grant [HL-007457]; Merit Review program of the Department of Veterans Affairs; Nestle Food Co FX We thank our sources of support: the NIH grants DK 49779, DK51684, DK-38764, and PO1 HL-55782, the UAB GCRC M01-RR00032, the CNRU (P30-DK56336), the T32 grant (HL-007457) (PI: S. Oparil), and the Merit Review program of the Department of Veterans Affairs. We also acknowledge support from Nestle Food Co. for providing Stouffer's Lean Cuisine entrees. NR 44 TC 23 Z9 24 U1 0 U2 0 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 DEC PY 2008 VL 16 IS 12 BP 2616 EP 2623 DI 10.1038/oby.2008.411 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 379OJ UT WOS:000261405800008 PM 18820653 ER PT J AU Chonghaile, TN Letai, A AF Chonghaile, T. Ni Letai, A. TI Mimicking the BH3 domain to kill cancer cells SO ONCOGENE LA English DT Review DE BH3 mimetic; Bcl-2; apoptosis; cancer; drug resistance and ABT-737 ID OUTER MITOCHONDRIAL-MEMBRANE; CHRONIC LYMPHOCYTIC-LEUKEMIA; SMALL-MOLECULE INHIBITOR; BCL-2 FAMILY PROTEINS; SURVIVAL-PROMOTING PROTEINS; MIMETIC ABT-737; CYTOCHROME-C; X-L; PROAPOPTOTIC ACTIVITY; ANTIAPOPTOTIC BCL-2 AB Cancer cells show deviant behavior that induces apoptotic signaling. To survive, cancer cells typically acquire changes enabling evasion of death signals. One way they do this is by increasing the expression of anti- apoptotic BCL-2 proteins. Anti-apoptotic BCL-2 family proteins antagonize death signaling by forming heterodimers with pro-death proteins. Heterodimer formation occurs through binding of the pro-apoptotic protein's BH3 domain into the hydrophobic cleft of anti- apoptotic proteins. The BH3 mimetics are small molecule antagonists of the anti- apoptotic BCL-2 members that function as competitive inhibitors by binding to the hydrophobic cleft. Under certain conditions, antagonism of antiapoptotic BCL-2 family proteins can unleash pro-death molecules in cancer cells. Thus, the BH3 mimetics are a new class of cancer drugs that specifically target a mechanism of cancer cell survival to selectively kill cancer cells. Oncogene (2009) 27, S149-S157; doi: 10.1038/onc.2009.52 C1 [Chonghaile, T. Ni; Letai, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530B,44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu RI Ni Chonghaile, Triona/L-9418-2015 OI Ni Chonghaile, Triona/0000-0002-3041-4031 NR 93 TC 105 Z9 105 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD DEC PY 2008 VL 27 SU 1 BP S149 EP S157 DI 10.1038/onc.2009.52 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 478DA UT WOS:000268566800013 ER PT J AU Danial, NN AF Danial, N. N. TI BAD: undertaker by night, candyman by day SO ONCOGENE LA English DT Review DE BAD; apoptosis; metabolism; survival signaling ID BCL-X-L; DEPENDENT PROTEIN-KINASE; CULTURED HIPPOCAMPAL-NEURONS; HUMAN PANCREATIC-ISLETS; PROMOTES CELL-SURVIVAL; CYTOCHROME-C RELEASE; DNA-DAMAGE RESPONSE; DEATH AGONIST BAD; GROWTH-FACTOR-II; BETA-CELLS AB The BH3-only pro-apoptotic proteins are upstream sensors of cellular damage that selectively respond to specific, proximal death and survival signals. Genetic models and biochemical studies indicate that these molecules are latent killers until activated through transcriptional or post-translational mechanisms in a tissue-restricted and signal-specific manner. The large number of BH3-only proteins, their unique subcellular localization, protein-interaction network and diverse modes of activation suggest specialization of their damage-sensing function, ensuring that the core apoptotic machinery is poised to receive input from a wide range of cellular stress signals. The apoptotic response initiated by the activation of BH3-only proteins ultimately culminates in allosteric activation of pro-apoptotic BAX and BAK, the gateway proteins to the mitochondrial pathway of apoptosis. From activation of BH3-only proteins to oligomerization of BAX and BAK and mitochondrial outer membrane permeabilization, an intricate network of interactions between the pro-and anti-apoptotic members of the BCL-2 family orchestrates the decision to undergo apoptosis. Beyond regulation of apoptosis, multiple BCL-2 proteins have recently emerged as active components of select homeostatic pathways carrying other cellular functions. This review focuses on BAD, which was the first BH3-only protein linked to proximal survival signals through phosphorylation by survival kinases. In addition to findings that delineated the physiological role of BAD in apoptosis and its dynamic regulation by phosphorylation, studies pointing to new roles for this protein in other physiological pathways, such as glucose metabolism, are highlighted. By executing its 'day' and 'night' jobs in metabolism and apoptosis, respectively, BAD helps coordinate mitochondrial fuel metabolism and the apoptotic machinery. Oncogene (2009) 27, S53-S70; doi: 10.1038/onc.2009.44 C1 [Danial, N. N.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Danial, N. N.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Danial, NN (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 3 Blackfan Circle,CLSB 11-143, Boston, MA 02115 USA. EM nika_danial@dfci.harvard.edu FU National Cancer Institute (NCI, Rockville, MD, USA) [5 K01 CA106596-02]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, Bethesda, MD, USA) [R01 DK078081-01]; Iacocca Foundation ( Boston, MA, USA); Juvenile Diabetes Research Foundation (JDRF, London, UK); Novartis (Basel, Switzerland); DFCI/Novartis Drug Discovery Program FX NN Danial iscurrent ly receiving grant support from the National Cancer Institute (NCI, Rockville, MD, USA) (5 K01 CA106596-02), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, Bethesda, MD, USA) (R01 DK078081-01), the Iacocca Foundation ( Boston, MA, USA) and the Juvenile Diabetes Research Foundation (JDRF, London, UK). The author is also in receipt of a grant from Novartis ( Basel, Switzerland) as part of the DFCI/Novartis Drug Discovery Program and has a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund (Durham, NC, USA). NN Danial is a consultant/an advisor for the Novartis Institute for Biomedical Research (NIBR, Cambridge, MA, USA). NR 176 TC 119 Z9 120 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC PY 2008 VL 27 BP S53 EP S70 DI 10.1038/onc.2009.44 PG 18 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 478DA UT WOS:000268566800005 PM 19641507 ER PT J AU Stipp, RN Goncalves, RB Hofling, JF Smith, DJ Mattos-Graner, RO AF Stipp, R. N. Goncalves, R. B. Hofling, J. F. Smith, D. J. Mattos-Graner, R. O. TI Transcriptional analysis of gtfB, gtfC, and gbpB and their putative response regulators in several isolates of Streptococcus mutans SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE gene expression; genetic diversity; glucan-binding protein; glucosyltransferase; Streptococcus mutans; two-component system ID GLUCAN-BINDING PROTEINS; BIOFILM FORMATION; COMPETENCE DEVELOPMENT; GENETIC COMPETENCE; GLUCOSYLTRANSFERASE; EXPRESSION; DIVERSITY; STRAINS; SYSTEM; GROWTH AB Background: Streptococcus mutans, a major dental caries pathogen, expresses several virulence genes that mediate its growth, accumulation on tooth surfaces, and acid-mediated tooth demineralization. GtfB and GtfC catalyze the extracellular synthesis of water-insoluble glucan matrix from sucrose, and are essential for accumulation of bacteria in the dental biofilm. GbpB, an essential protein of S. mutans, might also mediate cell-surface interaction with glucan. Methods: In this study, we determined the transcription levels of gtfB, gtfC, and gbpB, and several putative transcriptional response regulators (rr) at different phases of planktonic growth in 11 S. mutans strains. Aim/Methods: Activities of gtfB and gtfC were growth-phase dependent and assumed divergent patterns in several strains during specific phases of growth, while gbpB activities appeared to be under modest influence of the growth phase. Transcription patterns of the rr vicR, covR, comE, ciaR, and rr1 were growth-phase dependent and some of these genes were expressed in a highly coordinated way. Each rr, except comE, was expressed by all the strains. Patterns of virulence and regulatory genes were, however, strain-specific. Conclusions: The findings suggest that mechanisms controlling virulence gene expression are variable among genotypes, providing the notion that the genetic diversity of S. mutans may have important implications for understanding mechanisms that regulate the expression of virulence genes in this species. C1 [Stipp, R. N.; Goncalves, R. B.; Hofling, J. F.; Mattos-Graner, R. O.] Univ Estadual Campinas, Dept Microbiol & Immunol, Piracicaba Dent Sch, Campinas, SP, Brazil. [Smith, D. J.] Forsyth Inst, Dept Immunol, Boston, MA USA. RP Mattos-Graner, RO (reprint author), Univ Estadual Campinas, Dept Microbiol & Imunol, Fac Odontol Piracicaba, Av Limeira 901, BR-13414018 Piracicaba, SP, Brazil. EM rmgraner@fop.unicamp.br RI Mattos-Graner, Renata/C-9410-2012 OI Mattos-Graner, Renata/0000-0001-8309-8135 FU Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [02/07156-1, 03/01836-3, 04/03242-6]; NIH-Fogarty [TW-06324] FX This study was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP, grant 02/07156-1). R.O.M-G is supported by FAPESP (proc. 03/01836-3). R.N.S. was supported by FAPESP (proc. 04/03242-6) and NIH-Fogarty TW-06324. We thank Drs Edgard Graner and Michelle Agostini (FOP-UNI-CAMP, SP, Brazil) for assistance with the semi-quantitative RT-PCR analysis, and Dr Siu Mui Tsai (CENA/ESALQ-USP, SP, Brazil) for assistance with the sequence analysis. NR 38 TC 18 Z9 19 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD DEC PY 2008 VL 23 IS 6 BP 466 EP 473 DI 10.1111/j.1399-302X.2008.00451.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 360JI UT WOS:000260053400005 PM 18954352 ER PT J AU Isenbarger, TA Carr, CE Johnson, SS Finney, M Church, GM Gilbert, W Zuber, MT Ruvkun, G AF Isenbarger, Thomas A. Carr, Christopher E. Johnson, Sarah Stewart Finney, Michael Church, George M. Gilbert, Walter Zuber, Maria T. Ruvkun, Gary TI The Most Conserved Genome Segments for Life Detection on Earth and Other Planets SO ORIGINS OF LIFE AND EVOLUTION OF BIOSPHERES LA English DT Article DE Polymerase chain reaction; DNA; RNA; Ribosome; Panspermia; Mars ID WATER RESERVOIRS; COMMON ANCESTOR; MARS; METEORITE; PCR; SEQUENCES; EVOLUTION; TRANSPORTER; DIVERSITY; PHYLOGENY AB On Earth, very simple but powerful methods to detect and classify broad taxa of life by the polymerase chain reaction (PCR) are now standard practice. Using DNA primers corresponding to the 16S ribosomal RNA gene, one can survey a sample from any environment for its microbial inhabitants. Due to massive meteoritic exchange between Earth and Mars (as well as other planets), a reasonable case can be made for life on Mars or other planets to be related to life on Earth. In this case, the supremely sensitive technologies used to study life on Earth, including in extreme environments, can be applied to the search for life on other planets. Though the 16S gene has become the standard for life detection on Earth, no genome comparisons have established that the ribosomal genes are, in fact, the most conserved DNA segments across the kingdoms of life. We present here a computational comparison of full genomes from 13 diverse organisms from the Archaea, Bacteria, and Eucarya to identify genetic sequences conserved across the widest divisions of life. Our results identify file 16S and 23S ribosomal RNA genes as well as other universally conserved nucleotide sequences in genes encoding particular classes of transfer RNAs and within the nucleotide binding domains of ABC transporters as the most conserved DNA sequence segments across phylogeny. This set of sequences defines a core set of DNA regions that have changed the least over billions of years of evolution and provides a means to identify and classify divergent life, including ancestrally related life on other planets. C1 [Isenbarger, Thomas A.; Finney, Michael; Ruvkun, Gary] Massachusetts Gen Hosp, Dept Mol Biol, Cambridge, MA USA. [Isenbarger, Thomas A.; Finney, Michael; Ruvkun, Gary] Harvard Univ, Microbial Sci Initiat, Cambridge, MA 02138 USA. [Carr, Christopher E.; Johnson, Sarah Stewart; Zuber, Maria T.] MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA USA. [Church, George M.] Harvard Univ, Sch Med, Dept Genet, Cambridge, MA 02138 USA. [Gilbert, Walter] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Cambridge, MA USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU National Aeronautics and Space Administration [NNG05GK27G] FX TAI thanks Professor Jo Handelsman for support during the preparation of this manuscript, Ilya Ruvinsky and members of the Ruvkun laboratory for helpful comments and review of the manuscript, Lance Davidow for assistance with computing resources, and Qinghu Ren at TIGR for helpful discussions regarding ABC transporters. This work was funded by National Aeronautics and Space Administration grant NNG05GK27G. NR 55 TC 22 Z9 22 U1 4 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0169-6149 J9 ORIGINS LIFE EVOL B JI Orig. Life Evol. Biosph. PD DEC PY 2008 VL 38 IS 6 BP 517 EP 533 DI 10.1007/s11084-008-9148-z PG 17 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 403FD UT WOS:000263067600005 PM 18853276 ER PT J AU Price, DL Wong, RJ Randolph, GW AF Price, Daniel L. Wong, Richard J. Randolph, Gregory W. TI Invasive Thyroid Cancer: Management of the Trachea and Esophagus SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article ID RECURRENT LARYNGEAL NERVE; EXTERNAL-BEAM RADIOTHERAPY; PAPILLARY CARCINOMA; AIRWAY INVASION; DIFFERENTIATED CARCINOMA; LARYNGOTRACHEAL INVASION; RESECTIONAL MANAGEMENT; SURGICAL-MANAGEMENT; RISK; ULTRASONOGRAPHY AB Well-differentiated thyroid cancer most commonly presents as an intrathyroidal tumor; however, extrathyroidal extension occurs in approximately 6% to 13% of patients and carries a significant negative impact on survival. Extrathyroidal disease may involve critical structures in the central neck, including the recurrent laryngeal nerves, trachea, esophagus, and larynx, requiring surgery extending significantly beyond the thyroid gland. Appropriate surgical management is of great importance and can normalize survival curves, whereas gross residual disease postoperatively may lead to recurrence and decreased survival. Adjuvant postoperative therapies for thyroid cancers with extrathyroidal extension include thyroid hormone suppression, radioactive iodine therapy, and external beam radiotherapy. This summary reviews approaches to the management of invasive thyroid cancers involving the aerodigestive tract. C1 [Price, Daniel L.; Wong, Richard J.] Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, New York, NY 10065 USA. [Randolph, Gregory W.] Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Endocrine Surg Serv, Thyroid & Parathyroid Surg Div, Boston, MA 02114 USA. [Randolph, Gregory W.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Price, DL (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, Head & Neck Serv, 1275 York Ave, New York, NY 10065 USA. EM Priced12@mskcc.org OI Price, Daniel/0000-0003-3398-0562 FU NCI NIH HHS [T32 CA009685, T32 CA009685-17] NR 64 TC 17 Z9 20 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD DEC PY 2008 VL 41 IS 6 BP 1155 EP + DI 10.1016/j.otc.2008.08.002 PG 16 WC Otorhinolaryngology SC Otorhinolaryngology GA 390PV UT WOS:000262177100010 PM 19040976 ER PT J AU Nadol, JB Eddington, DK Burgess, BJ AF Nadol, Joseph B., Jr. Eddington, Donald K. Burgess, Barbara J. TI Foreign Body or Hypersensitivity Granuloma of the inner Ear After Cochlear Implantation: One Possible Cause of a Soft Failure? SO OTOLOGY & NEUROTOLOGY LA English DT Article DE Cochlear implant; Granuloma; Histopathology of ear; Soft failure ID SILICONE ALLERGY; MALFUNCTION AB Hypothesis: A tissue response in the form of foreign body or a hypersensitivity reaction to cochlear implantation is common and may be one possible cause of a soft failure of cochlear implantation. Background: After a successful cochlear implantation, delayed failure may occur. The causes of a "soft" failure, that is, one in which device malfunction cannot be proven, are unknown. Methods: The histopathology of the temporal bones of a patient who, in life, had experienced a soft failure after cochlear implantation was described. In addition, the temporal bones of 8 other subjects who, in life, had undergone cochlear implantation were studied for evidence of a foreign body or hypersensitivity reaction. Results: In the case report, a necrotizing granulomatous giant cell reaction surrounded the cochlear implant electrode track through the mastoid and the middle ear and into the cochlea in both ears. There was osteolysis of the cribrose area, otic capsule, and bone between the facial nerve and the cochlea and destruction of the organ of Corti and spiral ganglion. In the additional 8 cases studied, a similar, although less pronounced, foreign body or hypersensitivity reaction was seen in 6 (75%) of the cases. Conclusion: A foreign body or hypersensitivity reaction in the form of giant cells and lymphocytic cell infiltration is common after cochlear implantation and may be one possible cause of soft failure. C1 [Nadol, Joseph B., Jr.; Eddington, Donald K.; Burgess, Barbara J.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. EM joseph_nadol@meei.harvard.edu FU National Institutes of Health/National Institute on Deafness and Other Communication [R01 DC000152] FX This study was supported by Grant R01 DC000152 from the National Institutes of Health/National Institute on Deafness and Other Communication Disorders. NR 26 TC 16 Z9 17 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1531-7129 J9 OTOL NEUROTOL JI Otol. Neurotol. PD DEC PY 2008 VL 29 IS 8 BP 1076 EP 1084 DI 10.1097/MAO.0b013e31818c33cf PG 9 WC Clinical Neurology; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 379LH UT WOS:000261397200005 PM 18997635 ER PT J AU Yang, LL Wang, SX Lim, G Sung, B Zeng, Q Mao, JR AF Yang, Liling Wang, Shuxing Lim, Grewo Sung, Backil Zeng, Qing Mao, Jianren TI Inhibition of the ubiquitin-proteasome activity prevents glutamate transporter degradation and morphine tolerance SO PAIN LA English DT Article DE Glutamate transporter; EAAC1; GLAST; GLT-1; Morphine tolerance; MG-132 ID ABNORMAL PAIN SENSITIVITY; SPINAL-CORD; RECEPTOR ANTAGONIST; NEUROPATHIC PAIN; CELL-DEATH; RATS; EXPRESSION; SYSTEM; HYPERALGESIA; DEPENDENCE AB Glutamate transporters play a Crucial role in physiological glutamate homeostasis and neurotoxicity. Recently, we have shown that downregulation of glutamate transporters after chronic morphine exposure contributed to the development of morphine tolerance. In the present study, we examined whether regulation of the glutamate transporter expression with the proposed proteasome inhibitor MG-132 would contribute to the development of tolerance to repeated intrathecal (twice daily x 7 days) morphine administration in rats. The results showed that MG-132 (5 nmol) given intrathecally blocked morphine-induced glutamate transporter downregulation and the decrease in glutamate uptake activity within the spinal cord dorsal horn. Co-administration of morphine (15 nmol) with MG-132 (vehicle = 1 < 2.5 < 5 = 10 nmol) also dose-dependently prevented the development of morphine tolerance in rats. These findings suggest that prevention of spinal glutamate transporter downregulation may regulate the glutamatergic function that has been implicated in the development of morphine tolerance. The possible relationship between MG-132-mediated regulation of glutamate transporters, ubiquitin-proteasome system, and the cellular Mechanisms of morphine tolerance is discussed in light of these findings. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Yang, Liling; Wang, Shuxing; Lim, Grewo; Sung, Backil; Zeng, Qing; Mao, Jianren] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,MGH Ctr Translat Pain, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU US PHS RO1 [DE 18214, DE18538, NS45681] FX This work was supported by US PHS RO1 Grants DE 18214, DE18538, and NS45681. NR 31 TC 15 Z9 16 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2008 VL 140 IS 3 BP 472 EP 478 DI 10.1016/j.pain.2008.09.028 PG 7 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 388BK UT WOS:000261995100013 PM 18986766 ER PT J AU Sepucha, KR Levin, CA Uzogara, EE Barry, MJ O'Connor, AM Mulley, AG AF Sepucha, Karen R. Levin, Carrie A. Uzogara, Ekeorna E. Barry, Michael J. O'Connor, Annette M. Mulley, Albert G. TI Developing instruments to measure the quality of decisions: Early results for a set of symptom-driven decisions SO PATIENT EDUCATION AND COUNSELING LA English DT Article DE Quality; Decisions; Decision making; Decision quality; Measurement ID PATIENT; CARE; OSTEOARTHRITIS; PROGRAM; SYSTEMS; KNOWLEDGE AB Objective: To identify a set of critical facts and key goals and concerns for five common medical conditions, benign prostate disease, hip and knee osteoarthritis, herniated disc and spinal stenosis and examine the validity of the method for identifying these items. Methods: Investigators identified facts and goals through literature reviews and qualitative work with patients and providers. A cross-sectional survey of patients and providers was conducted to examine the accuracy, importance and completeness of the identified items. Results: 42 facts (6-16 per condition) and 31 goals and concerns (4-13 per condition) were identified. 182 responses were obtained from patients (76.5% response rate) and 113 responses from providers (78% response rate). Overall, the facts were accurate, important and complete across all conditions. For one condition (hip osteoarthritis), the goals did not meet the criteria for completeness. There was more disagreement between patients and providers around the ranking of goals than of facts. Conclusions: Overall, respondents found the identified facts and goals accurate, important and complete. Significant differences between patients' and providers' rankings highlight the importance of including both perspectives. Practice implications: Instruments to measure whether or not patients are informed and the extent to which treatments reflect patients' goals must balance patients' and providers' perspectives when selecting items to include. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Sepucha, Karen R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hlth Decis Res Unit, Boston, MA 02114 USA. [O'Connor, Annette M.] Univ Ottawa, Ottawa, CA USA. RP Sepucha, KR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hlth Decis Res Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM ksepucha@partners.org RI Agaliotis, Maria/G-5334-2012 FU Foundation for Informed Medical Decision Making (FIMDM) FX Role of the funding source: The study was funded by the Foundation for Informed Medical Decision Making (FIMDM), a not for-profit organization. Dr. Levin is employed by FIMDM and collaborated on the Study design, collection of data and interpretation of the data. NR 23 TC 30 Z9 31 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD DEC PY 2008 VL 73 IS 3 BP 504 EP 510 DI 10.1016/j.pec.2008.07.009 PG 7 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 382UL UT WOS:000261630800017 PM 18718734 ER PT J AU Voronov, P Tobin, MJ Billings, K Cote, CJ Iyer, A Suresh, S AF Voronov, Polina Tobin, Michael J. Billings, Kathleen Cote, Charles J. Iyer, Aditya Suresh, Santhanam TI Postoperative pain relief in infants undergoing myringotomy and tube placement: comparison of a novel regional anesthetic block to intranasal fentanyl - a pilot analysis SO PEDIATRIC ANESTHESIA LA English DT Article DE myringotomy tube; postoperative analgesia; nerve of Arnold block; intranasal fentanyl ID SEVOFLURANE ANESTHESIA; CHILDREN; ACETAMINOPHEN AB Aim: The aim of this study was to investigate the use of a novel regional anesthetic technique for the management of pain in the postoperative period in infants and children undergoing myringotomy and tube placement. Methods: After institutional review board (IRB) approval was obtained, 200 children were randomized in this double blind, prospective, randomized controlled trial to receive either a nerve block of the auricular branch of the Vagus (Nerve of Arnold) with 0.2 ml of 0.25% bupivacaine or receive intranasal fentanyl 2 mcg.kg(-1) after induction of general anesthesia. Patients were monitored in the recovery room for analgesia, need for additional analgesia, incidence of nausea and vomiting, and time to discharge from the hospital. Additional analgesics administered in the PACU, surgical short-stay unit as well as at home were also recorded. Results: There was no difference in the pain scores between groups (P = 0.53); there was no difference in the amount of rescue medications between groups (P = 0.86); there was no difference in the incidence of nausea and vomiting between groups (P = 0.34); there was no difference in the time to discharge between groups (P = 0.5). Conclusions: This pilot study demonstrates the efficacy of a peripheral nerve block for management of postoperative pain in infants and children undergoing myringotomy and tube placement. This may be a viable alternative for postoperative pain control in this population. Future multi-center, randomized controlled trials may be necessary to validate the efficacy of this block in infants and children. C1 [Voronov, Polina; Suresh, Santhanam] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Chicago, IL 60611 USA. [Tobin, Michael J.] Shriners Hosp Children, Oak Pk, IL USA. [Billings, Kathleen] Northwestern Univ, Childrens Mem Hosp, Div Pediat Otolaryngol, Feinberg Sch Med, Chicago, IL 60611 USA. [Cote, Charles J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Iyer, Aditya] Northwestern Univ, Childrens Mem Hosp, Feinberg Sch Med, Chicago, IL 60611 USA. RP Suresh, S (reprint author), 2300 Childrens Plaza, Chicago, IL 60614 USA. EM ssuresh@childrensmemorial.org NR 7 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD DEC PY 2008 VL 18 IS 12 BP 1196 EP 1201 DI 10.1111/j.1460-9592.2008.02789.x PG 6 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 367GM UT WOS:000260540500008 PM 19076574 ER PT J AU Zhang, XP Cote, CJ AF Zhang, Xiaopeng Cote, Charles J. TI Raynaud's phenomenon in a child presenting as oxygen desaturation during transfusion with cold blood SO PEDIATRIC ANESTHESIA LA English DT Article DE transfusion; Raynaud's; blood; monitoring; pulse oximetry ID ENDOTHELIN-1 AB We report a case of Raynaud's phenomenon (RP) triggered by transfusion of cold blood to a pediatric burn patient under general anesthesia. The child was febrile so a decision was made to not use a blood warmer. When the blood was rapidly administered the child suddenly developed 'desaturation'. The child was placed on 100% oxygen, adequate ventilation assured, and the color of his oral mucosa assessed as 'pink'. Placement of the oximeter on the opposite hand revealed 100% saturation. To our knowledge, this is the first case of apparent RP reported in a pediatric patient triggered by transfusion of cold blood. C1 [Zhang, Xiaopeng; Cote, Charles J.] Harvard Univ, Sch Med, Div Pediat Anesthesia,Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Mass Gen Hosp Childre, Boston, MA 02115 USA. RP Cote, CJ (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM cjcote@partners.org NR 8 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1155-5645 J9 PEDIATR ANESTH JI Pediatr. Anesth. PD DEC PY 2008 VL 18 IS 12 BP 1208 EP 1210 DI 10.1111/j.1460-9592.2008.02782.x PG 3 WC Anesthesiology; Pediatrics SC Anesthesiology; Pediatrics GA 367GM UT WOS:000260540500010 PM 19076576 ER PT J AU Inhoff, T Monnikes, H Noetzel, S Stengel, A Goebel, M Dinh, QT Riedl, A Bannert, N Wisser, AS Wiedenmann, B Klapp, BF Tache, Y Kobelt, P AF Inhoff, Tobias Moennikes, Hubert Noetzel, Steffen Stengel, Andreas Goebel, Miriam Dinh, Q. Thai Riedl, Andrea Bannert, Norbert Wisser, Anna-Sophia Wiedenmann, Bertram Klapp, Burghard F. Tache, Yvette Kobelt, Peter TI Desacyl ghrelin inhibits the orexigenic effect of peripherally injected ghrelin in rats SO PEPTIDES LA English DT Article DE Rat; Desacyl ghrelin; Ghrelin; Food intake; c-Fos; ARC ID DES-ACYL GHRELIN; HYPOTHALAMIC ARCUATE NUCLEUS; STIMULATES FOOD-INTAKE; FOS EXPRESSION; PARAVENTRICULAR NUCLEUS; CONSCIOUS RATS; PEPTIDE; BRAIN; STOMACH; NEURONS AB Studies showed that the metabolic unlike the neuroendocrine effects of ghrelin could be abrogated by co-administered unacylated ghrelin. The aim was to investigate the interaction between ghrelin and desacyl ghrelin administered intraperitoneally on food intake and neuronal activity (c-Fos) in the arcuate nucleus in non-fasted rats. Ghrelin (13 mu g/kg) significantly increased food intake within the first 30 min post-injection. Desacyl ghrelin at 64 and 127 mu g/kg injected simultaneously with ghrelin abolished the stimulatory effect of ghrelin on food intake. Desacyl ghrelin alone at both doses did not alter food intake. Both doses of desacyl ghrelin injected separately in the light phase had no effects on food intake when rats were fasted for 12 h. Ghrelin and desacyl ghrelin (64 mu g/kg) injected alone increased the number of Fos positive neurons in the arcuate nucleus compared to vehicle. The effect on neuronal activity induced by ghrelin was significantly reduced when injected simultaneously with desacyl ghrelin. Double labeling revealed that nesfatin-1 immunoreactive neurons in the arcuate nucleus are activated by simultaneous injection of ghrelin and desacyl ghrelin. These results suggest that desacyl ghrelin suppresses ghrelin-induced food intake by curbing ghrelin-induced increased neuronal activity in the arcuate nucleus and recruiting nesfatin-1 immunopositive neurons. (c) 2008 Elsevier Inc. All rights reserved. C1 [Dinh, Q. Thai; Riedl, Andrea; Klapp, Burghard F.; Kobelt, Peter] Charite, Div Psychosomat Med & Psychotherapy, Dept Med, D-10117 Berlin, Germany. [Inhoff, Tobias; Noetzel, Steffen; Wisser, Anna-Sophia; Wiedenmann, Bertram; Kobelt, Peter] Charite, Div Hepatol Gastroenterol & Endocrinol, Dept Med, D-10117 Berlin, Germany. [Stengel, Andreas; Goebel, Miriam] Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Ctr Neurobiol Stress,Digest Dis Div, Los Angeles, CA 90024 USA. [Stengel, Andreas; Goebel, Miriam; Tache, Yvette] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Moennikes, Hubert] Martin Luther Hosp, Dept Med, Berlin, Germany. [Moennikes, Hubert] Martin Luther Hosp, Inst Neurogastroenterol, Berlin, Germany. [Bannert, Norbert] Robert Koch Inst, D-1000 Berlin, Germany. RP Kobelt, P (reprint author), Charite, Div Psychosomat Med & Psychotherapy, Dept Med, Campus Mitte,Luisenstr 13A, D-10117 Berlin, Germany. EM peter.kobelt@charite.de FU Charite Universitatsmedizin Berlin [UFF 2008-251]; Research Career Scientist Award; Department of Veterans Affairs; NIHDK [R01 33061] FX This work was supported by grants from the Charite Universitatsmedizin Berlin (UFF 2008-251), and grants to Y.T. (Research Career Scientist Award, Department of Veterans Affairs and NIHDK R01 33061). NR 38 TC 102 Z9 108 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD DEC PY 2008 VL 29 IS 12 BP 2159 EP 2168 DI 10.1016/j.peptides.2008.09.014 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 384BG UT WOS:000261718000010 PM 18938204 ER PT J AU Abdolmaleky, HM Zhou, JR Thiagalingam, S Smith, CL AF Abdolmaleky, Hamid Mostafavi Zhou, Jing-Rong Thiagalingam, Sam Smith, Cassandra L. TI Epigenetic and pharmacoepigenomic studies of major psychoses and potentials for therapeutics SO PHARMACOGENOMICS LA English DT Review DE bipolar disorder; brain; chromatin; DNA methylation; epigenetics; nutrition; pharmacoepigenomics; pharmacogenomics; psychiatry; schizophrenia ID FRAGILE-X-SYNDROME; ADULT-MOUSE BRAIN; DNA-METHYLATION; METHYLENETETRAHYDROFOLATE REDUCTASE; SCHIZOPHRENIC-PATIENTS; BIPOLAR DISORDER; DOWN-REGULATION; HISTONE MODIFICATIONS; PLASMA HOMOCYSTEINE; PREFRONTAL CORTEX AB Individuals with neuropsychiatric diseases have epigenetic programming disturbances, both in the brain, which is the primary affected organ, and in secondary tissues. Epigenetic modulations are molecular modifications made to DNA, RNA and proteins that fine-tune genotype into phenotype and do not include DNA base changes. For instance, gene-expression modulation is linked to epigenetic codes in chromatin that consist of post-replication DNA methylation and histone protein modifications (e.g., methylation, acetylation and so on), particularly in gene-promoter regions. Epigenetic coding is modulated globally, and in a gene-specific manner by environmental exposures that include nutrition, toxins, drugs and so on. Analysis of epigenetic aberrations in diseases helps to identify dysfunctional genes and pathways, establish more robust cause-effect relationships than genetic studies alone, and identify new pharmaceutical targets and drugs, including nucleic acid reagents such as inhibitory RNAs. The emerging science of pharmacoepigenomics can impact the treatment of psychiatric and other complex diseases. In fact, some therapeutics now in use target epigenetic programming. In the near future, epigenetic interventions should help stabilize affected individuals and lead to prevention strategies. C1 [Abdolmaleky, Hamid Mostafavi; Zhou, Jing-Rong] Harvard Univ, Sch Med, Lab Nutr & Metab, BIDMC, Boston, MA 02115 USA. [Abdolmaleky, Hamid Mostafavi; Smith, Cassandra L.] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Abdolmaleky, Hamid Mostafavi; Thiagalingam, Sam] Boston Univ, Sch Med, Dept Med Genet & Genom, Boston, MA 02215 USA. [Abdolmaleky, Hamid Mostafavi] Iran Univ Med Sci, Dept Psychiat, Tehran, Iran. [Abdolmaleky, Hamid Mostafavi] Iran Univ Med Sci, Tehran Psychiat Inst, Tehran, Iran. RP Abdolmaleky, HM (reprint author), Harvard Univ, Sch Med, Lab Nutr & Metab, BIDMC, Boston, MA 02115 USA. EM sabdolma@bidmc.harvard.edu OI Thiagalingam, Sam/0000-0001-5211-266X; Smith, Cassandra/0000-0002-0346-8907 NR 154 TC 22 Z9 24 U1 0 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD DEC PY 2008 VL 9 IS 12 BP 1809 EP 1823 DI 10.2217/14622416.9.12.1809 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399EK UT WOS:000262783000012 PM 19072640 ER PT J AU Heitjan, DF Asch, DA Ray, R Rukstalis, M Patterson, F Lerman, C AF Heitjan, D. F. Asch, D. A. Ray, Riju Rukstalis, Margaret Patterson, Freda Lerman, C. TI Cost-effectiveness of pharmacogenetic testing to tailor smoking-cessation treatment SO PHARMACOGENOMICS JOURNAL LA English DT Article DE addiction; genetic testing; Monte Carlo simulation; tobacco dependence ID NICOTINE REPLACEMENT THERAPY; RECEPTOR PARTIAL AGONIST; SHORT-TERM RESPONSE; TOBACCO DEPENDENCE; TRANSDERMAL NICOTINE; CIGARETTE-SMOKING; SUSTAINED-RELEASE; CONTROLLED-TRIAL; FOLLOW-UP; BUPROPION AB We evaluated the cost-effectiveness of a range of smoking cessation drug treatments, including varenicline, transdermal nicotine (TN), bupropion and the use of a genetic test to choose between TN and bupropion. We performed Monte Carlo simulation with sensitivity analysis, informing analyses with published estimates of model parameters and current prices for genetic testing and smoking-cessation therapy. The primary outcomes were discounted life-years (LY) and lifetime tobacco-cessation treatment costs. In the base case, varenicline treatment was optimal with an ICER, compared to bupropion, of $2985/LY saved. In sensitivity analyses, varenicline was in all cases (and bupropion in most cases) admissible; only under favorable assumptions was the genetically tailored approach competitive. Our data suggest that an untailored approach of treatment with either bupropion or varenicline is a cost-effective form of tobacco dependence treatment, but a tailored approach for selecting between TN and bupropion can be cost-effective under plausible assumptions. C1 [Heitjan, D. F.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Heitjan, D. F.; Asch, D. A.; Lerman, C.] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Heitjan, D. F.; Asch, D. A.; Ray, Riju; Rukstalis, Margaret; Patterson, Freda; Lerman, C.] Philadelphia Vet Adm Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. [Asch, D. A.; Lerman, C.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Asch, D. A.] Univ Penn, Transdisciplinary Tobacco Use Res Ctr, Philadelphia, PA 19104 USA. [Ray, Riju] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Rukstalis, Margaret; Patterson, Freda; Lerman, C.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. RP Heitjan, DF (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, 622 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM dheitjan@mail.med.upenn.edu RI Ray, Riju/D-1113-2009; Heitjan, Daniel/D-1116-2009; OI Asch, David/0000-0002-7970-286X FU National Cancer Institute [P50 CA084718, R01 CA063562]; National Institutes on Drug Abuse FX We acknowledge the contributions of the following investigators to the pharmacogenetic studies on which this analysis was based: Wade H Berrettini, Susan Crystal-Mansour, Leonard Epstein, Larry Hawk, Vyga Kaufmann, David Main, Ray Niaura, Angela Pinto, Peter Shields, Susan Ware and E Paul Wileyto. We also thank Steven Siegel for helpful comments on an earlier draft.; Sources of funding: This study was supported by Grants P50 CA084718 from the National Cancer Institute and National Institutes on Drug Abuse and R01 CA063562 from the National Cancer Institute, which had no role in its design, conduct or reporting. NR 62 TC 21 Z9 23 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD DEC PY 2008 VL 8 IS 6 BP 391 EP 399 DI 10.1038/sj.tpj.6500492 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 372CC UT WOS:000260878100004 PM 18347612 ER PT J AU Troemel, ER Felix, MA Whiteman, NK Barriere, A Ausubel, FM AF Troemel, Emily R. Felix, Marie-Anne Whiteman, Noah K. Barriere, Antoine Ausubel, Frederick M. TI Microsporidia Are Natural Intracellular Parasites of the Nematode Caenorhabditis elegans SO PLOS BIOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; INNATE IMMUNITY; BACTERIAL PATHOGENS; OLIGONUCLEOTIDE PROBES; LISTERIA-MONOCYTOGENES; MAXIMUM-LIKELIHOOD; BIOLOGICAL-CONTROL; MODEL; POPULATIONS; INFECTION AB For decades the soil nematode Caenorhabditis elegans has been an important model system for biology, but little is known about its natural ecology. Recently, C. elegans has become the focus of studies of innate immunity and several pathogens have been shown to cause lethal intestinal infections in C. elegans. However none of these pathogens has been shown to invade nematode intestinal cells, and no pathogen has been isolated from wild-caught C. elegans. Here we describe an intracellular pathogen isolated from wild-caught C. elegans that we show is a new species of microsporidia. Microsporidia comprise a large class of eukaryotic intracellular parasites that are medically and agriculturally important, but poorly understood. We show that microsporidian infection of the C. elegans intestine proceeds through distinct stages and is transmitted horizontally. Disruption of a conserved cytoskeletal structure in the intestine called the terminal web correlates with the release of microsporidian spores from infected cells, and appears to be part of a novel mechanism by which intracellular pathogens exit from infected cells. Unlike in bacterial intestinal infections, the p38 MAPK and insulin/insulin-like growth factor (IGF) signaling pathways do not appear to play substantial roles in resistance to microsporidian infection in C. elegans. We found microsporidia in multiple wild-caught isolates of Caenorhabditis nematodes from diverse geographic locations. These results indicate that microsporidia are common parasites of C. elegans in the wild. In addition, the interaction between C. elegans and its natural microsporidian parasites provides a system in which to dissect intracellular intestinal infection in vivo and insight into the diversity of pathogenic mechanisms used by intracellular microbes. C1 [Troemel, Emily R.; Ausubel, Frederick M.] Harvard Univ, Sch Med, Dept Genet, Dept Mol Biol, Boston, MA USA. [Troemel, Emily R.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Felix, Marie-Anne; Barriere, Antoine] Univ Paris 06, CNRS, Inst Jacques Monod, Paris, France. [Felix, Marie-Anne; Barriere, Antoine] Univ Paris 07, Inst Jacques Monod, CNRS, F-75251 Paris, France. [Whiteman, Noah K.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA. RP Troemel, ER (reprint author), Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. EM etroemel@ucsd.edu FU Leukemia/Lymphoma Society; Kirschstein National Research Service Award (NRSA); National Institutes of Allergy and Infectious Diseases [F32AI069732]; National Institutes of Health (NIH) [R01 AI064332, R01 AI072508, P01 AI044220]; French Research Ministry; Centre National de la Recherche Scientifique; Inflammatory Bowel Disease [DK43351]; Boston Area Diabetes and Endocrinology Research Center [DK57521] FX This work was supported by a Leukemia/Lymphoma Society Fellowship to ERT, a Kirschstein National Research Service Award (NRSA) fellowship to NKW from the National Institutes of Allergy and Infectious Diseases (F32AI069732), National Institutes of Health (NIH) grants R01 AI064332, R01 AI072508, and P01 AI044220 awarded to FMA. AB and M-AF were supported by the French Research Ministry and the Centre National de la Recherche Scientifique. Electron microscopy was performed in the Microscopy Core of the Center for Systems Biology, which is supported by an Inflammatory Bowel Disease Grant DK43351 and a Boston Area Diabetes and Endocrinology Research Center Award DK57521. NR 68 TC 95 Z9 101 U1 4 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2008 VL 6 IS 12 BP 2736 EP 2752 DI 10.1371/journal.pbio.0060309 PG 17 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 386WQ UT WOS:000261913700015 PM 19071962 ER PT J AU Nishikawa, T Gulbahce, N Motter, AE AF Nishikawa, Takashi Gulbahce, Natali Motter, Adilson E. TI Spontaneous Reaction Silencing in Metabolic Optimization SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID ESCHERICHIA-COLI METABOLISM; LIMITED CONTINUOUS-CULTURE; IN-SILICO MODELS; FLUX ANALYSIS; SACCHAROMYCES-CEREVISIAE; OBJECTIVE FUNCTIONS; GENETIC ROBUSTNESS; GROWTH PHENOTYPES; CELL BIOLOGY; NETWORKS AB Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this behavior remain very poorly understood. Here we predict computationally and analytically that any organism evolving to maximize growth rate, ATP production, or any other linear function of metabolic fluxes tends to significantly reduce the number of active metabolic reactions compared to typical nonoptimal states. The reduced number appears to be constant across the microbial species studied and just slightly larger than the minimum number required for the organism to grow at all. We show that this massive spontaneous reaction silencing is triggered by the irreversibility of a large fraction of the metabolic reactions and propagates through the network as a cascade of inactivity. Our results help explain existing experimental data on intracellular flux measurements and the usage of latent pathways, shedding new light on microbial evolution, robustness, and versatility for the execution of specific biochemical tasks. In particular, the identification of optimal reaction activity provides rigorous ground for an intriguing knockout-based method recently proposed for the synthetic recovery of metabolic function. C1 [Nishikawa, Takashi; Motter, Adilson E.] Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA. [Nishikawa, Takashi; Motter, Adilson E.] Northwestern Univ, NW Inst Complex Syst, Evanston, IL USA. [Nishikawa, Takashi] Clarkson Univ, Div Math & Comp Sci, New York, NY USA. [Gulbahce, Natali] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Gulbahce, Natali] Northwestern Univ, Ctr Complex Network Res, Evanston, IL USA. [Gulbahce, Natali] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Motter, AE (reprint author), Northwestern Univ, Dept Phys & Astron, Evanston, IL 60208 USA. EM motter@northwestern.edu RI Nishikawa, Takashi/B-3752-2010 OI Nishikawa, Takashi/0000-0002-2147-0242 FU National Science Foundation (NSF) [DMR-0520513]; Materials Research Center of Northwestern University (AEM); Department of Energy [DE-AC52-06NA25396]; NSF [DMS-0709212] FX This work was supported by the National Science Foundation (NSF) Materials Research Science and Engineering Center program (Grant No. DMR-0520513) at the Materials Research Center of Northwestern University (AEM), Department of Energy under contract DE-AC52-06NA25396 (NG), and NSF under Grant No. DMS-0709212 (TN and AEM). NR 79 TC 27 Z9 27 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD DEC PY 2008 VL 4 IS 12 AR e1000236 DI 10.1371/journal.pcbi.1000236 PG 12 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 415HB UT WOS:000263923800016 PM 19057639 ER PT J AU Hill, AS Nishino, A Nakajo, K Zhang, GX Fineman, JR Selzer, ME Okamura, Y Cooper, EC AF Hill, Alexis S. Nishino, Atsuo Nakajo, Koichi Zhang, Giuxin Fineman, Jaime R. Selzer, Michael E. Okamura, Yasushi Cooper, Edward C. TI Ion Channel Clustering at the Axon Initial Segment and Node of Ranvier Evolved Sequentially in Early Chordates SO PLOS GENETICS LA English DT Article ID KCNQ POTASSIUM CHANNELS; K+ CHANNEL; ANKYRIN-G; NEURAL CREST; ANTICONVULSANT RETIGABINE; MOLECULAR EVOLUTION; ANTIEPILEPTIC DRUGS; SPIKE INITIATION; VOLTAGE SENSOR; MOTOR-NEURON AB In many mammalian neurons, dense clusters of ion channels at the axonal initial segment and nodes of Ranvier underlie action potential generation and rapid conduction. Axonal clustering of mammalian voltage-gated sodium and KCNQ (Kv7) potassium channels is based on linkage to the actin-spectrin cytoskeleton, which is mediated by the adaptor protein ankyrin-G. We identified key steps in the evolution of this axonal channel clustering. The anchor motif for sodium channel clustering evolved early in the chordate lineage before the divergence of the wormlike cephalochordate, amphioxus. Axons of the lamprey, a very primitive vertebrate, exhibited some invertebrate features ( lack of myelin, use of giant diameter to hasten conduction), but possessed narrow initial segments bearing sodium channel clusters like in more recently evolved vertebrates. The KCNQ potassium channel anchor motif evolved after the divergence of lampreys from other vertebrates, in a common ancestor of shark and humans. Thus, clustering of voltage-gated sodium channels was a pivotal early innovation of the chordates. Sodium channel clusters at the axon initial segment serving the generation of action potentials evolved long before the node of Ranvier. KCNQ channels acquired anchors allowing their integration into pre-existing sodium channel complexes at about the same time that ancient vertebrates acquired myelin, saltatory conduction, and hinged jaws. The early chordate refinements in action potential mechanisms we have elucidated appear essential to the complex neural signaling, active behavior, and evolutionary success of vertebrates. C1 [Hill, Alexis S.; Zhang, Giuxin; Fineman, Jaime R.; Selzer, Michael E.; Cooper, Edward C.] Univ Penn, Dept Neurol, Penn Epilepsy Ctr, Philadelphia, PA 19104 USA. [Hill, Alexis S.; Zhang, Giuxin; Fineman, Jaime R.; Selzer, Michael E.; Cooper, Edward C.] David Mahoney Inst Neurol Sci, Philadelphia, PA 19104 USA. [Nishino, Atsuo] Osaka Univ, Grad Sch Sci, Dept Biol, Dev Biol Lab, Osaka, Japan. [Nakajo, Koichi] Natl Inst Physiol Sci, Okazaki, Aichi 444, Japan. [Selzer, Michael E.] US Dept Vet Affairs, Off Res & Dev, Washington, DC USA. [Okamura, Yasushi] Osaka Univ, Grad Sch Med, Dept Integrat Physiol, Osaka, Japan. RP Cooper, EC (reprint author), Univ Penn, Dept Neurol, Penn Epilepsy Ctr, Philadelphia, PA 19104 USA. EM edc@mail.med.upenn.edu RI Nakajo, Koichi/H-4104-2011; Nishino, Atsuo/F-5393-2013 FU NIH [R01-NS14837, R01NS38537, R24-HD050838]; US-Japan Brain Research Cooperative Program [R01 NS49119] FX This work was supported by the Roy and Diana Vagelos Scholars Program in the Molecular Life Sciences ( AH), NIH Grants R01-NS14837( MES), R01NS38537 ( MES), R24-HD050838 ( MES), the Craig H. Neilsen Foundation ( MES), a Japan- U. S. Brain Research Cooperative Program Grant ( YO), a Human Frontiers Science Program Short Term Fellowship ( ECC), a US-Japan Brain Research Cooperative Program Supplement ( R01 NS49119, ECC), and the Miles Family Fund ( ECC). The funders had no role in study design, conduct, data interpretation, or manuscript preparation. NR 107 TC 62 Z9 64 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2008 VL 4 IS 12 AR e1000317 DI 10.1371/journal.pgen.1000317 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 411RO UT WOS:000263667900032 PM 19112491 ER PT J AU Pare, G Chasman, DI Parker, AN Nathan, DM Miletich, JP Zee, RY Ridker, PM AF Pare, Guillaume Chasman, Daniel I. Parker, Alexander N. Nathan, David M. Miletich, Joseph P. Zee, Robert Y. Ridker, Paul M. TI Novel Association of HK1 with Glycated Hemoglobin in a Non-Diabetic Population: A Genome-Wide Evaluation of 14,618 Participants in the Women's Genome Health Study SO PLOS GENETICS LA English DT Article ID RED-BLOOD-CELL; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; ZINC TRANSPORTER; GLUCOKINASE GENE; FASTING GLUCOSE; BIRTH-WEIGHT; RISK LOCI; TYPE-2; HAPLOTYPE AB Type 2 diabetes is a leading cause of morbidity and mortality. While genetic variants have been found to influence the risk of type 2 diabetes mellitus, relatively few studies have focused on genes associated with glycated hemoglobin, an index of the mean blood glucose concentration of the preceding 8-12 weeks. Epidemiologic studies and randomized clinical trials have documented the relationship between glycated hemoglobin levels and the development of long-term complications in diabetes; moreover, higher glycated hemoglobin levels in the subdiabetic range have been shown to predict type 2 diabetes risk and cardiovascular disease. To examine the common genetic determinants of glycated hemoglobin levels, we performed a genome-wide association study that evaluated 337,343 SNPs in 14,618 apparently healthy Caucasian women. The results show that glycated hemoglobin levels are associated with genetic variation at the GCK ( rs730497; P = 2.8x10(-12)), SLC30A8 ( rs13266634; P = 9.8x10(-8)), G6PC2 ( rs1402837; P = 6.8x10-(10)), and HK1 ( rs7072268; P = 6.4x10(-9)) loci. While associations at the GCK, SLC30A8, and G6PC2 loci are confirmatory, the findings at HK1 are novel. We were able to replicate this novel association in an independent validation sample of 455 additional non-diabetic men and women. HK1 encodes the enzyme hexokinase, the first step in glycolysis and a likely candidate for the control of glucose metabolism. This observed genetic association between glycated hemoglobin levels and HK1 polymorphisms paves the way for further studies of the role of HK1 in hemoglobin glycation, glucose metabolism, and diabetes. C1 [Pare, Guillaume; Chasman, Daniel I.; Zee, Robert Y.; Ridker, Paul M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. [Pare, Guillaume; Chasman, Daniel I.; Zee, Robert Y.; Ridker, Paul M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA USA. [Parker, Alexander N.; Miletich, Joseph P.] Amgen Inc, Cambridge, MA USA. [Nathan, David M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA USA. RP Pare, G (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. EM gpare@rics.bwh.harvard.edu FU NCI NIH HHS [CA047988, R01 CA047988]; NHLBI NIH HHS [HL080467, R01 HL043851, R01 HL080467] NR 47 TC 50 Z9 51 U1 3 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD DEC PY 2008 VL 4 IS 12 AR e1000312 DI 10.1371/journal.pgen.1000312 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 411RO UT WOS:000263667900027 PM 19096518 ER PT J AU Schormann, N Senkovich, O Walker, K Wright, DL Anderson, AC Rosowsky, A Ananthan, S Shinkre, B Velu, S Chattopadhyay, D AF Schormann, N. Senkovich, O. Walker, K. Wright, D. L. Anderson, A. C. Rosowsky, A. Ananthan, S. Shinkre, B. Velu, S. Chattopadhyay, D. TI Structure-based approach to pharmacophore identification, in silico screening, and three-dimensional quantitative structure-activity relationship studies for inhibitors of Trypanosoma cruzi dihydrofolate reductase function SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE Chagas' disease; antifolate; DHFR; structure-activity relationship; HASL; eHiTS ID SELECTIVE INHIBITORS; CHAGAS-DISEASE; PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII; CHEMOTHERAPY; DESIGN; DERIVATIVES; ANALOGS; POTENT; OPTIMIZATION AB We have employed a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) approach to predict the biochemical activity for inhibitors of T. cruzi dihydrofolate reductase-thymidylate synthase (DHFR-TS). Crystal structures of complexes of the enzyme with eight different inhibitors of the DHFR activity together with the structure in the substrate-free state (DHFR domain) were used to validate and refine docking poses of ligands that constitute likely active conformations. Structural information from these complexes formed the basis for the structure-based alignment used as input for the QSAR study. Contrary to indirect ligand-based approaches the strategy described here employs a direct receptor-based approach. The goal is to generate a library of selective ea inhibitors for further development as antiparasitic agents. 3D-QSAR models were obtained for T cruzi DHFR-TS (30 inhibitors in learning set) and human DHFR (36 inhibitors in learning set) that show a very good agreement between experimental and predicted enzyme inhibition data. For crossvalidation of the QSAR model(s), we have used the 10% leave-one-out method. The derived 3D-QSAR models were tested against a few selected compounds (a small test set of six inhibitors for each enzyme) with known activity, which were not part of the learning set, and the quality of prediction of the initial 3D-QSAR models demonstrated that such studies are feasible. Further refinement of the models through integration of additional activity data and optimization of reliable docking poses is expected to lead to an improved predictive ability. C1 [Schormann, N.; Senkovich, O.; Walker, K.; Shinkre, B.; Velu, S.; Chattopadhyay, D.] Univ Alabama, Dept Pharmaceut Sci, Birmingham, AL 35294 USA. [Wright, D. L.; Anderson, A. C.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Rosowsky, A.] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. [Ananthan, S.] So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. RP Chattopadhyay, D (reprint author), Univ Alabama, Dept Pharmaceut Sci, Birmingham, AL 35294 USA. EM debasish@uab.edu NR 36 TC 22 Z9 24 U1 1 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD DEC PY 2008 VL 73 IS 4 BP 889 EP 901 DI 10.1002/prot.22115 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 375QV UT WOS:000261129300009 PM 18536013 ER PT J AU Wolf, EJ Miller, MW Orazem, RJ Weiefich, MR Castillo, DT Milford, J Kaloupek, DG Keane, TM AF Wolf, Erika J. Miller, Mark W. Orazem, Robert J. Weiefich, Mariann R. Castillo, Diane T. Milford, Jaime Kaloupek, Danny G. Keane, Terence M. TI The MMPI-2 Restructured Clinical Scales in the Assessment of Posttraumatic Stress Disorder and Comorbid Disorders SO PSYCHOLOGICAL ASSESSMENT LA English DT Article DE Minnesota Multiphasic Personality Inventory-2; Restructured Clinical Scales; posttraumatic stress disorder; internalizing; externalizing ID DSM-IV ANXIETY; RC SCALES; MENTAL-DISORDERS; STRUCTURAL RELATIONSHIPS; INTERNALIZING SUBTYPES; MOOD DISORDERS; PTSD SCALE; VETERANS; PERSONALITY; VALIDITY AB This study examined the psychometric properties of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) Restructured Clinical Scales (RCSs) in individuals with posttraumatic stress disorder (PTSD) receiving clinical services at Department of Veterans Affairs medical centers. Study 1 included 1,098 men who completed the MMPI-2 and were assessed for a range of psychological disorders via structured clinical interview. Study 2 included 136 women who completed the MMPI-2 and were interviewed with the Clinician Administered Scale for PTSD. The utility of the RCSs was compared with that of the Clinical Scales (CSs) and the Keane PTSD (PK) scale. The RCSs demonstrated good psychometric properties and patterns of associations with other measures of psychopathology that corresponded to current theory regarding the structure of comorbidity. A notable advantage of the RCSs compared with the MMPI-2 CSs was their enhanced construct validity and clinical utility in the assessment of comorbid internalizing and externalizing psychopathology. The PK scale demonstrated incremental validity in the prediction of PTSD beyond that of the RCSs or CSs. C1 [Wolf, Erika J.; Miller, Mark W.; Orazem, Robert J.; Weiefich, Mariann R.; Kaloupek, Danny G.; Keane, Terence M.] VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. [Wolf, Erika J.; Orazem, Robert J.] Boston Univ, Dept Psychol, Boston, MA 02215 USA. [Castillo, Diane T.; Milford, Jaime] VA New Mexico Healthcare Syst, Mexico City, DF, Mexico. [Miller, Mark W.; Kaloupek, Danny G.; Keane, Terence M.] Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. EM mark.miller5@va.gov OI Miller, Mark/0000-0001-6393-8563; Wolf, Erika/0000-0003-2666-2435 FU NIMH NIH HHS [5F31MH074267-3, F31 MH074267, F31 MH074267-01A2, F31 MH074267-02, F31 MH074267-03] NR 55 TC 26 Z9 27 U1 8 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2008 VL 20 IS 4 BP 327 EP 340 DI 10.1037/a0012948 PG 14 WC Psychology, Clinical SC Psychology GA 383HD UT WOS:000261663800002 PM 19086756 ER PT J AU Nieuwland, MS Kuperberg, GR AF Nieuwland, Mante S. Kuperberg, Gina R. TI When the Truth Is Not Too Hard to Handle: An Event-Related Potential Study on the Pragmatics of Negation SO PSYCHOLOGICAL SCIENCE LA English DT Article ID BRAIN POTENTIALS; LANGUAGE COMPREHENSION; SENTENCE VERIFICATION AB Our brains rapidly map incoming language onto what we hold to be true. Yet there are claims that such integration and verification processes are delayed in sentences containing negation words like not. However, studies have often confounded whether a statement is true and whether it is a natural thing to say during normal communication. In an event-related potential (ERP) experiment, we aimed to disentangle effects of truth value and pragmatic licensing on the comprehension of affirmative and negated real-world statements. As in affirmative sentences, false words elicited a larger N400 ERP than did true words in pragmatically licensed negated sentences (e.g., "In moderation, drinking red wine isn't bad/good..."), whereas true and false words elicited similar responses in unlicensed negated sentences (e.g., "A baby bunny's fur isn't very hard/soft..."). These results suggest that negation poses no principled obstacle for readers to immediately relate incoming words to what they hold to be true. C1 [Nieuwland, Mante S.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Nieuwland, Mante S.; Kuperberg, Gina R.] Harvard Univ, Sch Med, MIT, Massachusetts Gen Hosp,Athinoula A Martinos Ctr B, Cambridge, MA 02138 USA. RP Nieuwland, MS (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM mante@nmr.mgh.harvard.edu FU NIMH NIH HHS [R01 MH071635, R01 MH071635-05, R01-MH071635] NR 30 TC 70 Z9 71 U1 2 U2 15 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD DEC PY 2008 VL 19 IS 12 BP 1213 EP 1218 DI 10.1111/j.1467-9280.2008.02226.x PG 6 WC Psychology, Multidisciplinary SC Psychology GA 384BH UT WOS:000261718100003 PM 19121125 ER PT J AU Gray, KM LaRowe, SD Upadhyaya, HP AF Gray, Kevin M. LaRowe, Steven D. Upadhyaya, Himanshu P. TI Cue Reactivity in Young Marijuana Smokers: A Preliminary Investigation SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article DE marijuana; cannabis; craving; cue reactivity; adolescent ID ADOLESCENT CIGARETTE SMOKERS; CRAVING QUESTIONNAIRE; CANNABIS WITHDRAWAL; SMOKING CUES; IN-VIVO; ALCOHOL; DEPENDENCE; USERS AB To develop and evaluate the feasibility of a cue reactivity paradigm for young marijuana smokers, the authors set up a laboratory procedure involving neutral and marijuana-related imagery, video, and in vivo cues. Fifteen adolescents and young adults with cannabis use disorders completed the procedure, which included continuous measurement of skin conductance and heart rate. Participants also completed questionnaires regarding marijuana craving before, during, and after cue presentations. Higher levels of craving and skin conductance were observed during marijuana cue presentations. The procedure appears to elicit cue reactivity among adolescents and young adults with cannabis use disorders and should be further evaluated and refined with a larger sample. Implications for future studies are discussed. C1 [Gray, Kevin M.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Youth Div, Charleston, SC 29425 USA. [LaRowe, Steven D.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA. [LaRowe, Steven D.] Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Subst Abuse Treatment Ctr, Charleston, SC USA. [Upadhyaya, Himanshu P.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Div Clin Neurosci, Charleston, SC 29425 USA. RP Gray, KM (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, Youth Div, 67 President St,POB 250861, Charleston, SC 29425 USA. EM graykm@musc.edu FU NCRR NIH HHS [M01 RR001070-29, M01 RR001070, M01 RR 01070]; NIDA NIH HHS [K12 DA000357-07, K12 DA000357, 5K12 DA 000357] NR 28 TC 26 Z9 26 U1 3 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD DEC PY 2008 VL 22 IS 4 BP 582 EP 586 DI 10.1037/a0012985 PG 5 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 380JO UT WOS:000261462200015 PM 19071985 ER PT J AU Zhang, XY Cao, LY Song, C Wu, GY Chen, DC Qi, LY Wang, F Xiu, MH Chen, S Zhang, YY Lu, L Kosten, TA Kosten, TR AF Zhang, Xiang Yang Cao, Lian Yuan Song, Cai Wu, Gui Ying Chen, Da Chun Qi, Ling Yan Wang, Fan Xiu, Mei Hong Chen, Song Zhang, Yingyang Lu, Lin Kosten, Therese A. Kosten, Thomas R. TI Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia on long-term treatment with antipsychotics SO PSYCHOPHARMACOLOGY LA English DT Article DE Schizophrenia; Smoking; Nicotine; Cytokine; Immune ID NICOTINE DEPENDENCE; CIGARETTE-SMOKING; NEUROLEPTIC TREATMENT; INTERLEUKIN-2; PSYCHOPATHOLOGY; ASSOCIATION; RECEPTORS; IL-2; RESISTANT; CELLS AB Schizophrenia is associated with various abnormalities in the immune system. Suppression of inflammatory cytokines by cigarette smoke is well-established. The purpose of this study was to determine any differences in cytokine profiles in smokers and nonsmokers with schizophrenia and whether there were any relationships among altered cytokine profiles and psychopathological symptoms. Serum interleukin (IL)-2, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha levels were measured in 96 male inpatients with DSM-IV schizophrenia: 66 smokers and 30 nonsmokers. Symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The positive PANSS symptoms were lower in smokers than nonsmokers, while the negative symptoms were lower in those who smoked more cigarettes. Cytokine levels were positively correlated: IL-2 level with IL-6 and IL-6 with both IL-8 and TNF-alpha. Both IL-2 and IL-6, but not IL-8 or TNF-alpha, were significantly lower in smokers than nonsmokers (p < 0.002; p < 0.01). Lower IL-2 levels correlated with fewer negative symptoms and with smoking more cigarettes. The fewer positive symptoms in smokers and fewer negative symptoms in those who smoked more cigarettes may be associated with nicotine-induced suppression of some inflammatory cytokines. C1 [Zhang, Xiang Yang; Wu, Gui Ying; Zhang, Yingyang; Kosten, Therese A.; Kosten, Thomas R.] Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. [Zhang, Xiang Yang; Cao, Lian Yuan; Chen, Da Chun; Qi, Ling Yan; Wang, Fan; Xiu, Mei Hong; Chen, Song; Zhang, Yingyang] Beijing Hui Long Guan Hosp, Ctr Biol Psychiat, Beijing, Peoples R China. [Song, Cai] Univ Prince Edward Isl, Atlantic Vet Coll, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada. [Song, Cai] NRC Inst Nutrisci & Hlth, Charlottetown, PE, Canada. [Lu, Lin] Peking Univ, Natl Inst Drug Dependence, Beijing 100871, Peoples R China. RP Kosten, TR (reprint author), Baylor Coll Med, VA Med Ctr, Menninger Dept Psychiat & Behav Sci, Res Bldg 110,2002 Holcombe Blvd, Houston, TX 77030 USA. EM xyzhang@bcm.edu; kosten@bcm.edu FU NIDA NIH HHS [K05-DA0454, P50-DA18827] NR 51 TC 19 Z9 19 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2008 VL 201 IS 3 BP 383 EP 389 DI 10.1007/s00213-008-1295-4 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 374IP UT WOS:000261037300007 PM 18719893 ER PT J AU Sarna, L Bialous, SA Cooley, ME Jun, HJ Feskanich, D AF Sarna, Linda Bialous, Stella A. Cooley, Mary E. Jun, Hee-Jin Feskanich, Diane TI Impact of smoking and smoking cessation on health-related quality of life in women in the Nurses' Health Study SO QUALITY OF LIFE RESEARCH LA English DT Article DE Smoking; Smoking cessation; Health-related quality of life; Quality of life; Women; Tobacco ID UNITED-STATES; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; EX-SMOKERS; QUESTIONNAIRE; OBESITY; ADULTS AB To examine the relationship between smoking and health-related quality of life (HRQOL) and the impact of quitting smoking on changes in HRQOL among women in the two Nurses' Health Study (NHS) cohorts (n = 158,736) who were 29 to 71 years of age in 1992/1993 when they reported data on smoking status and completed the Short Form-36 version 1 (SF-36). At baseline, the SF-36 physical component scores (SF-PCS) and mental component scores (SF-MCS) were examined by smoking status (never, 56%, former, 32%, and current, 13%) within 10-year age groups. Smoking characteristics were analyzed as correlates of SF-36. Changes in smoking status and SF-PCS and SF-MCS, adjusted for comorbid disease and other covariates, were reassessed at 4-year intervals among current smokers in 1992/1993 and those who either continued smoking after 4 and 8 years or reported not smoking at both intervals. Smokers had lower HRQOL (SF-PCS and SF-MCS) as compared to never and former smokers. Current smoking, cigarettes per day and time since quitting were associated with significantly lower SF-PCS and SF-MCS. Continuing smokers and those who quit had significant declines in SF-PCS over time and significant improvements in SF-MCS at 8 years. There was minimal difference between groups, with some greater improvements in SF-MCS among those reporting non-smoking at 8 years. These findings support the lower ratings of HRQOL by smokers, but quitting alone, after an average of 21 years of smoking, did not improve HRQOL. Further study focused on the HRQOL impact of quitting smoking is needed. C1 [Sarna, Linda] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bialous, Stella A.] Tobacco Policy Int, San Francisco, CA USA. [Cooley, Mary E.] Dana Farber Canc Inst, Phyllis E Cantor Ctr, Boston, MA 02115 USA. [Jun, Hee-Jin; Feskanich, Diane] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Jun, Hee-Jin; Feskanich, Diane] Harvard Univ, Sch Med, Boston, MA USA. RP Sarna, L (reprint author), Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. EM lsarna@sonnet.ucla.edu FU NCI NIH HHS [CA87979, CA50385, K07 CA095118, K07 CA92696-02, R01 CA050385] NR 34 TC 37 Z9 39 U1 0 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0962-9343 J9 QUAL LIFE RES JI Qual. Life Res. PD DEC PY 2008 VL 17 IS 10 BP 1217 EP 1227 DI 10.1007/s11136-008-9404-8 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 378SO UT WOS:000261344400002 PM 18931942 ER PT J AU Rubenstein, LV Hempel, S Farmer, MM Asch, SM Yano, EM Dougherty, D Shekelle, PW AF Rubenstein, L. V. Hempel, S. Farmer, M. M. Asch, S. M. Yano, E. M. Dougherty, D. Shekelle, P. W. TI Finding order in heterogeneity: types of quality-improvement intervention publications SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID PATIENT-OUTCOMES-RESEARCH; RANDOMIZED CLINICAL-TRIALS; HEALTH-CARE; ORGANIZATIONAL-CHANGE; TRANSLATING RESEARCH; SYSTEMATIC REVIEWS; ASTHMA-CARE; DESIGN; IMPLEMENTATION; POLICY AB Background: Stakeholders in quality improvement agree on the need for augmenting and synthesising the scientific literature supporting it. The diversity of perspectives, approaches, and contexts critical to advancing quality improvement science, however, creates challenges. The paper explores the heterogeneity in clinical quality improvement intervention (QII) publications. Methods: A preliminary classification framework was developed for QII articles, aiming for categories homogeneous enough to support coherent scientific discussion on QII reporting standards and facilitate systematic review. QII experts were asked to identify articles important to QII science. The framework was tested and revised by applying it to the article set. The final framework screened articles into (1) empirical literature on development and testing of QIIs; (2) QII stories, theories, and frameworks; (3) QII literature syntheses and meta-analyses; or (4) development and testing of QII-related tools. To achieve homogeneity, category (1) required division into (1a) development of QIIs; 1(b) history, documentation, or description of QIIs; or (1c) success, effectiveness or impact of QIIs. Results: By discussing unique issues and established standards relevant to each category, QII stakeholders can advance QII practice and science, including the scope and conduct of systematic literature reviews. C1 [Rubenstein, L. V.; Farmer, M. M.; Asch, S. M.; Yano, E. M.; Shekelle, P. W.] Vet Affairs Greater Los Angeles Healthcare Syst S, North Hills, CA 91343 USA. [Rubenstein, L. V.; Hempel, S.; Asch, S. M.; Shekelle, P. W.] RAND Corp, Santa Monica, CA USA. [Rubenstein, L. V.; Yano, E. M.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Rubenstein, L. V.; Asch, S. M.; Shekelle, P. W.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Dougherty, D.] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Rubenstein, LV (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst S, 16111 Plummer St 152, North Hills, CA 91343 USA. EM lisa_rubenstein@rand.org FU Agency for Healthcare Research and Quality (AHRQ) [HHSP233200400717P]; Centers for Disease Control and Prevention FX Agency for Healthcare Research and Quality (AHRQ) under a contract to LVR ( contract no HHSP233200400717P) funded by an Interagency Agreement between AHRQ and the Centers for Disease Control and Prevention. NR 98 TC 31 Z9 31 U1 0 U2 1 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 DEC PY 2008 VL 17 IS 6 BP 403 EP 408 DI 10.1136/qshc.2008.028423 PG 6 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 380YK UT WOS:000261501800004 PM 19064654 ER PT J AU Boland, GWL Blake, MA Hahn, PF Mayo-Smith, WW AF Boland, Giles W. L. Blake, Michael A. Hahn, Peter F. Mayo-Smith, William W. TI Incidental Adrenal Lesions: Principles, Techniques, and Algorithms for Imaging Characterization SO RADIOLOGY LA English DT Review ID CHEMICAL-SHIFT MR; CONTRAST-ENHANCED CT; POSITRON-EMISSION-TOMOGRAPHY; GUIDED RADIOFREQUENCY ABLATION; NON-HODGKIN LYMPHOMA; HISTOGRAM ANALYSIS; ADRENOCORTICAL CARCINOMA; PATHOLOGICAL CORRELATION; F-18-FDG PET/CT; UNENHANCED CT AB Incidental adrenal lesions are commonly detected at computed tomography, and lesion characterization is critical, particularly in the oncologic patient. Imaging tests have been developed that can accurately differentiate these lesions by using a variety of principles and techniques, and each is discussed in turn. An imaging algorithm is provided to guide radiologists toward the appropriate test to make the correct diagnosis. (C) RSNA, 2008 C1 [Boland, Giles W. L.; Blake, Michael A.; Hahn, Peter F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02111 USA. [Mayo-Smith, William W.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Dept Radiol, Providence, RI 02903 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, White Bldg 270C,55 Fruit St, Boston, MA 02111 USA. EM gboland@partners.org NR 116 TC 138 Z9 147 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2008 VL 249 IS 3 BP 756 EP 775 DI 10.1148/radiol.2493070976 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 375UP UT WOS:000261139300006 PM 19011181 ER PT J AU Kopans, DB Rusby, JE AF Kopans, Daniel B. Rusby, Jennifer E. TI Cutaneous Caves and Subcutaneous Adipose Columns in the Breast: Radiologic-Pathologic Correlation SO RADIOLOGY LA English DT Article ID SKIN THICKNESS AB Purpose: To investigate the histologic correlations of the innumerable 2-3-mm radiolucencies that project over the breast, as seen on mammograms. Materials and Methods: With institutional review board approval and HIPAA compliance, this work involved detailed x-ray imaging of discarded tissue from two mastectomy specimens, together with histologic examination of the skin and subcutaneous fat and evaluation of the skin during reduction mammoplasty surgery in two patients. Results: Comparison of the histologic findings with the findings on x-ray images demonstrated that the lucencies seen by using mammography are cutaneous caves in the underside of the dermis into which insert columns of fat projecting up from the subcutaneous adipose tissue. This finding was confirmed with evaluation of the skin during reduction surgery. Conclusion: As far as is known, this is the first description of a complex of anatomic structures that explain radiolucencies evident by using mammography. (C) RSNA, 2008 C1 [Kopans, Daniel B.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Dept Radiol,Breast Imaging Div, Boston, MA 02114 USA. [Rusby, Jennifer E.] Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Div Surg Oncol, Boston, MA 02114 USA. RP Kopans, DB (reprint author), Massachusetts Gen Hosp, Avon Comprehens Breast Evaluat Ctr, Wang Ambulatory Care Ctr, Dept Radiol,Breast Imaging Div, 15 Parkman St,Suite 240, Boston, MA 02114 USA. EM dkopans@partners.org NR 7 TC 7 Z9 7 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2008 VL 249 IS 3 BP 779 EP 784 DI 10.1148/radiol.2493080112 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 375UP UT WOS:000261139300007 PM 18849506 ER PT J AU Bredella, MA Misra, M Miller, KK Madisch, I Sarwar, A Cheung, A Klibanski, A Gupta, R AF Bredella, Miriam A. Misra, Madhusmita Miller, Karen K. Madisch, Ijad Sarwar, Ammar Cheung, Arnold Klibanski, Anne Gupta, Rajiv TI Distal Radius in Adolescent Girls with Anorexia Nervosa: Trabecular Structure Analysis with High-Resolution Flat-Panel Volume CT SO RADIOLOGY LA English DT Article ID X-RAY ABSORPTIOMETRY; BONE-STRUCTURE; COMPUTED-TOMOGRAPHY; TEMPORAL BONE; MICRO-CT; OSTEOPOROSIS; DENSITY; WOMEN; FRACTURES; CALCANEUS AB Purpose: To examine trabecular microarchitecture with high-resolution flat-panel volume computed tomography (CT) and bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) in adolescent girls with anorexia nervosa (AN) and to compare these results with those in normal-weight control subjects. Materials and Methods: The study was approved by the institutional review board and complied with HIPAA guidelines. Informed consent was obtained. Twenty adolescent girls, 10 with mild AN (mean age, 15.9 years; range, 13-18 years) and 10 age- and sex-matched normal-weight control subjects (mean age, 15.9 years; range, 12-18 years) underwent flat-panel volume CT of distal radius to determine apparent trabecular bone volume fraction (BV/TV), apparent trabecular number (TbN), apparent trabecular thickness (TbTh), and apparent trabecular separation (TbSp). All subjects underwent DXA of spine, hip, and whole body to determine BMD and body composition. The means and standard deviations (SDs) of structure parameters were calculated for AN and control groups. Groups were compared (Student t test). Linear regression analysis was performed. Results: AN subjects compared with control subjects, respectively, showed significantly lower mean values for BV/TV (0.37% +/- 0.05 [SD] vs 0.46% +/- 0.03, P = .0002) and TbTh (0.31 mm +/- 0.03 vs 0.39 mm +/- 0.03, P < .0001) and higher mean values for TbSp (0.54 mm +/- 0.13 vs 0.44 mm +/- 0.04, P = .02). TbN was lower in AN subjects than in control subjects, but the difference was not significant (1.17 mm(-3) +/- 0.15 vs 1.22 mm(-3) +/- 0.07, P = .43). There was no significant difference in BMD between AN and control subjects. BMD parameters showed positive correlation with BV/TV and TbTh in the control group (r = 0.55-0.84, P = .05-.01) but not in AN patients. Conclusion: Flat-panel volume CT is effective in evaluation of trabecular structure in adolescent girls with AN and demonstrates that bone structure is abnormal in these patients compared with that in normal-weight control subjects despite normal BMD. (c) RSNA, 2008 C1 [Bredella, Miriam A.; Madisch, Ijad; Sarwar, Ammar; Cheung, Arnold; Gupta, Rajiv] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Misra, Madhusmita; Miller, Karen K.; Klibanski, Anne] Massachusetts Gen Hosp, Dept Med, Neuroendocrine Unit, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. RP Bredella, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Yawkey 6E, Boston, MA 02114 USA. EM mbredella@partners.org FU National Institutes of Health [R01 DK062249, K23 RR018851, M01 RR01066] FX Supported by National Institutes of Health grants R01 DK062249, K23 RR018851, and M01 RR01066. NR 45 TC 51 Z9 51 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2008 VL 249 IS 3 BP 938 EP 946 DI 10.1148/radiol.2492080173 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 375UP UT WOS:000261139300026 PM 19011190 ER PT J AU Cantwell, CP Pena, CS Gervais, DA Hahn, PF Dawson, SL Mueller, PR AF Cantwell, Colin P. Pena, Constantino S. Gervais, Debra A. Hahn, Peter F. Dawson, Steven L. Mueller, Peter R. TI Thirty Years' Experience with Balloon Dilation of Benign Postoperative Biliary Strictures: Long-term Outcomes SO RADIOLOGY LA English DT Article ID ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; FOLLOW-UP; CLINICAL-TRIAL; DILATATION; MANAGEMENT; HEPATICOJEJUNOSTOMY; SUCCESS AB Purpose: To determine the effectiveness of percutaneous balloon dilation of benign postoperative biliary strictures. Materials and Methods: We received approval from our institutional review board to undertake this retrospective HIPAA-compliant study, and informed consent was waived. From April 1, 1977, to April 1, 2007, percutaneous biliary balloon dilation (PBBD) was performed in 85 patients with benign biliary strictures. In the 75 patients with follow-up (31 male, 44 female; mean age, 56 years; mean follow-up, 8 years), 205 PBBD procedures were performed during 112 treatments of 84 biliary strictures. PBBD of the stricture was performed with a noncompliant balloon (8-12-mm diameter). PBBD procedures were repeated at 2- to 14-day intervals until cholangiography demonstrated free drainage of contrast material to the bowel and no residual stenosis. An internal-external biliary drain was left in situ for a mean of 14-22 days and removed after a clinical trial of catheter clamping and a normal cholangiogram. Results: All procedures were technically successful, and 52, 11, 10, and two patients underwent a total of one, two, three, and four PBBD treatments, respectively. Four of 205 procedures (2%) led to major complications: two subphrenic abscesses, one hepatic arterial pseudoaneurysm, and one case of hematobilia treated with transfusion. Six patients died from unrelated causes and three from hepatitis C-related liver failure. The probability of a patient not developing clinically significant restenosis at 5, 10, 15, 20, and 25 years was 0.52, 0.49, 0.49, 0.41, and 0.41, respectively, after the first PBBD treatment and 0.43, 0.30, 0.20, 0.20, and 0.20, respectively, after the second PBBD treatment. No significant difference was found in the rate of clinically significant restenosis after the first PBBD between strictures at anastomotic and nonanastomotic sites (P = .75). During the follow-up period, 56 of 75 patients (75%) had successful management with PBBD. Conclusion: PBBD of benign strictures demonstrates long-term effectiveness. No significant difference was found in the rate of clinically significant restenosis after PBBD of biliary strictures at anastomotic and nonanastomotic sites. (c) RSNA, 2008 C1 Massachusetts Gen Hosp, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cantwell, CP (reprint author), St Vincents Hosp, Elm Pk, Dublin 4, Ireland. EM ccanty@gofree.indigo.ie NR 17 TC 18 Z9 21 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2008 VL 249 IS 3 BP 1050 EP 1057 DI 10.1148/radiol.2491080050 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 375UP UT WOS:000261139300039 PM 18812559 ER PT J AU Roedl, JB Colen, RR Holalkere, NS Fischman, AJ Choi, NC Blake, MA AF Roedl, Johannes B. Colen, Rivka R. Holalkere, Nagaraj S. Fischman, Alan J. Choi, Noah C. Blake, Michael A. TI Adenocarcinomas of the esophagus: Response to chemoradiotherapy is associated with decrease of metabolic tumor volume as measured on PET-CT. Comparison to histopathologic and clinical response evaluation SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Esophageal cancer; PET-CT; Tumor volume; Chemoradiotherapy; Response ID POSITRON-EMISSION-TOMOGRAPHY; CELL LUNG-CANCER; NEOADJUVANT CHEMORADIOTHERAPY; FDG-PET; ESOPHAGOGASTRIC JUNCTION; ENDOSCOPIC ULTRASOUND; CARCINOMA; THERAPY; CHEMOTHERAPY; SURVIVAL AB Purpose: We determined whether evaluation of treatment response is feasible by measuring metabolic tumor volume parameters on 18F-FDG (Fluorodeoxyglucose) PET-CT (Positron emission tomography-Computed tomography). We compared the response evaluation based on metabolic tumor volume parameters to a histopathologic and clinical response evaluation (clinical response criteria: RECIST criteria = Response evaluation criteria in solid tumors, and WHO criteria = World health organization). Patients and methods: A total of 51 study subjects with adenocarcinomas (Type I due to Siewert classification) of the esophagus underwent PET-CT scans before and after neoadjuvant chemoradiotherapy. Tumor volume, maximum and mean standardized uptake values (SUV) were assessed before and after chemoradiotherapy. Furthermore, the total lesion glycolysis (TLG) was calculated by multiplying the tumor volume by the mean SUV of the volume. Clinical response evaluation was performed with endoscopic ultrasound and CT using RECIST and WHO criteria. The reference standard for treatment response was the postsurgical histopathology. Results: The decrease of tumor volume between the pre- and post-treatment PET-CT scans was a better predictor of histopathologic response and survival than the decrease of the SUV and of the clinical response evaluation based on RECIST and WHO criteria. The highest accuracy, however, was achieved when using the TLG for the identification of treatment responders. A decrease of the TLG by >78% between pre- and post-therapy scans predicted histopathologic response with a sensitivity and specificity of 91% and 93%, respectively. Conclusions: Tumor volume and TLG can be used to assess treatment response and survival in patients with esophageal adenocarcinoma. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 89 (2008) 278-286. C1 [Roedl, Johannes B.; Colen, Rivka R.; Holalkere, Nagaraj S.; Fischman, Alan J.; Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Choi, Noah C.] Massachusetts Gen Hosp, Div Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Roedl, JB (reprint author), Massachusetts Gen Hosp, Dept Radiol, Fruit St 55, Boston, MA 02114 USA. EM johannes.roedl@gmail.com OI Holalkere, Nagaraj/0000-0001-6324-7682 NR 33 TC 62 Z9 67 U1 1 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 2008 VL 89 IS 3 BP 278 EP 286 DI 10.1016/j.radonc.2008.06.014 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 388WL UT WOS:000262050600005 PM 18701180 ER PT J AU Pawlicki, T Yoo, S Court, LE McMillan, SK Rice, RK Russell, JD Pacyniak, JM Woo, MK Basran, PS Shoales, J Boyer, AL AF Pawlicki, Todd Yoo, Sua Court, Laurence E. McMillan, Sharon K. Rice, Roger K. Russell, J. Donald Pacyniak, John M. Woo, Milton K. Basran, Parminder S. Shoales, Jason Boyer, Arthur L. TI Moving from IMRT QA measurements toward independent computer calculations using control charts SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE Statistical Process Control; Control charts; IMRT QA; Independent computer calculation ID INTENSITY-MODULATED RADIOTHERAPY; QUALITY-ASSURANCE; VERIFICATION AB Background and purpose: In this study, we investigated IMRT QA using Statistical Process Control for the purpose of comparing the processes of patient-specific measurements and the corresponding independent computer calculations. Materials and methods: Point dose data from the treatment planning system (TPS), independent computer calculations, and physical measurements for prostate and head and neck cases were studied. Control charts were used to analyze the IMRT QA processes from several institutions in the academic and community setting. Control charts are a method to describe the performance of a process. The width of the control chart limits (or action limits) describes the process' ability to meet clinical specifications of +/- 5%. In all, 24 process comparisons were made (112 measurement QA and 12 independent computer calculation QA). Results: For head and neck IMRT QA, the average process ability for the measurement QA was +/- 6.9% compared to +/- 7.2% for the independent computer calculation QA. For prostate IMRT QA, the average process ability was 4.4% for both measurement QA and independent computer calculation QA. It was found that 11 of the 24 processes were in control. At none of the institutions were the processes of measurements and independent computer calculations both in control and performing within clinical specifications. Conclusion: There is room to improve the processes of IMRT QA measurements and independent computer calculations. In situations where the improvement of the processes is such that each is in control and well within clinical specifications, it may be appropriate to suspend patient-specific IMRT QA measurements for every patient in the place of independent computer calculations. (C) 2008 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 89 (2008) 330-337. C1 [Pawlicki, Todd; Rice, Roger K.] Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. [Yoo, Sua] Duke Univ, Dept Radiat Oncol, Durham, NC 27706 USA. [Court, Laurence E.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [McMillan, Sharon K.] Decatur Mem Hosp, Dept Radiat Oncol, Decatur, IL USA. RP Pawlicki, T (reprint author), Univ Calif San Diego, Dept Radiat Oncol, 3855 Hlth Sci Dr 0843, La Jolla, CA 92093 USA. EM tpaw@ucsd.edu NR 12 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD DEC PY 2008 VL 89 IS 3 BP 330 EP 337 DI 10.1016/j.radonc.2008.07.002 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 388WL UT WOS:000262050600011 PM 18701175 ER PT J AU Hardin, CC Harris, RS AF Hardin, C. Corey Harris, R. Scott TI Mid-Frequency Ventilation in Acute Respiratory Distress Syndrome: The New Wave ... length? SO RESPIRATORY CARE LA English DT Editorial Material ID ACUTE LUNG INJURY; TIDAL-VOLUME VENTILATION; PRESSURE; MODEL C1 [Harris, R. Scott] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Harris, RS (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Bulfinch 148,55 Fruit St, Boston, MA 02114 USA. EM rharris@partners.org NR 15 TC 1 Z9 1 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 DEC PY 2008 VL 53 IS 12 BP 1655 EP 1656 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 381BZ UT WOS:000261511100002 PM 19025696 ER PT J AU Kasinath, BS Mariappan, MM Sataranatarajan, K Lee, MJ Choudhury, GG Feliers, D AF Kasinath, B. S. Mariappan, M. M. Sataranatarajan, K. Lee, M. J. Choudhury, G. Ghosh Feliers, D. TI Novel mechanisms of protein synthesis in diabetic nephropathy-role of mRNA translation SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE Protein synthesis; MicroRNA; Signaling reactions; Insulin; Glucose; Angiotensin II; Vascular endothelial growth factor ID RENAL EPITHELIAL-CELLS; GLYCOGEN-SYNTHASE KINASE-3; ANGIOTENSIN-II; INITIATION-FACTOR; SIGNALING PATHWAYS; MAMMALIAN TARGET; GENE-EXPRESSION; LET-7 MICRORNA; HIGH GLUCOSE; HNRNP-K AB Ambient protein levels are affected by both synthesis and degradation. Synthesis of a protein is regulated by transcription and messenger RNA (mRNA) translation. Translation has emerged as an important site of regulation of protein expression during development and disease. It is under the control of distinct factors that regulate initiation, elongation and termination phases. Regulation of translation occurs via signaling reactions, guanosine diphosphate-guanosine triphosphate binding and by participation of non-coding RNA species such as microRNA. Recent work has revealed an important role for translation in hypertrophy, matrix protein synthesis, elaboration of growth factors in in vivo and in vitro models of diabetic nephropathy. Studies of translation dysregulation in diabetic nephropathy have enabled identification of novel therapeutic targets. Translation of mRNA is a fertile field for exploration in investigation of kidney disease. C1 [Kasinath, B. S.; Mariappan, M. M.; Sataranatarajan, K.; Lee, M. J.; Choudhury, G. Ghosh; Feliers, D.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, OBrien Kidney Res Ctr, San Antonio, TX 78229 USA. [Kasinath, B. S.; Mariappan, M. M.; Sataranatarajan, K.; Lee, M. J.; Choudhury, G. Ghosh; Feliers, D.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Kasinath, BS (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, OBrien Kidney Res Ctr, MC 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM kasinath@uthscsa.edu FU O'Brien Kidney Research Center, BSK, JLB [NIH-DK061597]; BSK [NIH-DK077295]; American Diabetes Association [7-05-RA-60]; VA Research Service; Juvenile Diabetes Research Foundation [3-2007-245]; American Heart Association [SDG 0630283N]; VA Research Career Scientist Award; [NIH-DK050190] FX Studies were supported by grants from the NIH-DK061597 (O'Brien Kidney Research Center, BSK, JLB), NIH-DK077295 (BSK), American Diabetes Association-7-05-RA-60 (BSK), VA Research Service (BSK, GGC, JLB), Juvenile Diabetes Research Foundation-3-2007-245 (MMM/BSK), NIH-DK050190 (GGC), American Heart Association SDG 0630283N (DF). GGC is a recipient of the VA Research Career Scientist Award. NR 83 TC 7 Z9 8 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2008 VL 9 IS 4 BP 255 EP 266 DI 10.1007/s11154-008-9091-3 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 365BB UT WOS:000260379800002 PM 18654857 ER PT J AU Byne, W Tatusov, A Yiannoulos, G Vong, GS Marcus, S AF Byne, William Tatusov, Alex Yiannoulos, Georgia Vong, Ghe S. Marcus, Sue TI Effects of mental illness and aging in two thalamic nuclei SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Bipolar disorder; Psychosis; Aging; Oligodendrocyte; Myelin ID ANTERIOR CINGULATE CORTEX; MAJOR DEPRESSIVE DISORDER; EFFERENT CONNECTIONS; NEURON NUMBER; OLIGODENDROCYTE DYSFUNCTION; NEUROPATHOLOGY CONSORTIUM; HIPPOCAMPAL-FORMATION; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; BIPOLAR DISORDER AB We previously reported a schizophrenia associated reduction of neuronal and oligodendrocyte number in the anterior principal thalamic nucleus (APN) in a cohort of severely impaired elderly subjects with schizophrenia (SZ) relative to age matched nonpsychiatric controls (NCs). The present study was undertaken to determine 1) if those findings could be replicated in an independent sample of less chronically impaired subjects with SZ and NCs stratified across a broader age range; 2) if the findings are specific to SZ or are also seen in unipolar major depressive (MDD) or bipolar disorder (BPD); and 3) if the findings are specific to the APN or also seen in another thalamic nucleus. Computer assisted stereological methods were employed to determine the number of neurons and oligodendrocytes in the APN and centromedian nucleus (CMN) of the Nissl-stained thalamic sections maintained by the Stanley Foundation Brain Bank. This collection includes specimens from NCs and age matched subjects with diagnoses of SZ, MDD, or BPD who died between the ages of 25 and 68. Data were analyzed by mixed-effects linear regressions adjusting for demographic variables and known history of exposure to psychotropic medications. Oligodendrocyte number was decreased in both nuclei relative to NCs in subjects with SZ and in that subset of subjects with BPD who had experienced psychotic episodes. Compared to NCs both of these patient groups also exhibited an attenuation of an age-related increase in the number of oligodendrocytes. Contrary to our previous report, we did not detect a SZ-associated deficit in neuronal number in the APN. A history of exposure to neuroleptics, however, was associated with a decrease in neuronal number in both nuclei, but this decrease did not vary in relation to cumulative lifetime neuroleptic exposure in fluphenazine equivalents. Among subjects with psychiatric diagnoses, exposure to lithium was associated with an increase in the number of oligodendrocytes. No effects were detected for exposure to anticonvulsants or for abuse of alcohol or other substances. Published by Elsevier B.V. C1 [Byne, William; Tatusov, Alex; Yiannoulos, Georgia; Vong, Ghe S.] Bronx Vet Affairs Med Ctr, Div Basic & Lab Res, Bronx, NY 10468 USA. [Byne, William; Tatusov, Alex; Vong, Ghe S.; Marcus, Sue] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Byne, W (reprint author), Bronx Vet Affairs Med Ctr, Div Basic & Lab Res, Res Bldg Rm 2F37,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM william.byne@mssm.edu FU NIH [MH66998, MH45212]; Veterans Merit Review Award FX Supported by the Veterans Integrated Services Network-3 Mental Illness Research, Education and Clinical Center, NIH grants MH66998, MH45212 and a Veterans Merit Review Award. NR 57 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2008 VL 106 IS 2-3 BP 172 EP 181 DI 10.1016/j.schres.2008.08.023 PG 10 WC Psychiatry SC Psychiatry GA 385YU UT WOS:000261850300010 PM 18835520 ER PT J AU Escamilla, M Lee, BD Ontiveros, A Raventos, H Nicolini, H Mendoza, R Jerez, A Munoz, R Medina, R Figueroa, A Walss-Bass, C Armas, R Contreras, S Ramirez, ME Dassori, A AF Escamilla, Michael Lee, Byung Dae Ontiveros, Alfonso Raventos, Henriette Nicolini, Humberto Mendoza, Ricardo Jerez, Alvaro Munoz, Rodrigo Medina, Rolando Figueroa, Andres Walss-Bass, Consuelo Armas, Regina Contreras, Salvador Ramirez, Mercedes E. Dassori, Albana TI The epsin 4 gene is associated with psychotic disorders in families of Latin American origin SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Epsin 4 gene; Schizophrenia; Phenotype; Biobehavioral Science; Single nucleotide polymorphisms (SNPs) ID LINKAGE DISEQUILIBRIUM; SCHIZOPHRENIA; SUSCEPTIBILITY; CLATHRIN; ENTHOPROTIN; SUPPORT; LOCUS AB This study attempted to replicate evidence for association of the Epsin 4 gene (which encodes enthoprotin, a protein involved in vesicular transport) to schizophrenia in a new sample of families segregating schizophrenia drawn from the Latin American population. 1423 subjects (767 with a history of psychosis) from 337 Latino families were genotyped using three single nucleotide polymorphisms (SNPs) spanning the Epsin 4 gene. A family based association test was utilized to test for association of these SNPs to the phenotypes of psychosis and schizophrenia. Haplotypes defined by these three SNPs showed significant association to the phenotype of psychosis in this sample (global p value=0.014, bi-allelic p value=0.047). Variation in the Epsin 4 gene is significantly associated with psychotic disorder in this Latino population. This provides additional support for the involvement of enthoprotin in the pathogenesis of schizophrenia and other psychotic disorders. (C) 2008 Elsevier B.V. All rights reserved. C1 [Escamilla, Michael; Lee, Byung Dae; Medina, Rolando; Walss-Bass, Consuelo; Contreras, Salvador; Ramirez, Mercedes E.; Dassori, Albana] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Psychiat Genet Res Center, San Antonio, TX 78229 USA. [Ontiveros, Alfonso] Inst Informac & Invest Salud Mental, Monterrey, Mexico. [Raventos, Henriette] Univ Costa Rica, Ctr Invest Biol & Mol, San Jose, Costa Rica. [Medina, Rolando; Dassori, Albana] S Texas Vet Hlth Syst, Dept Psychiat, San Antonio, TX USA. [Nicolini, Humberto] Gep Estudios Med & Familiares Carracci SC, Mexico City, DF, Mexico. [Mendoza, Ricardo] Univ Calif Los Angeles, Harbor Med Ctr, Dept Psychiat & Biobehav Sci, Torrance, CA 90509 USA. [Jerez, Alvaro] Ctr Invest Biomed, Guatemala City, Guatemala. [Munoz, Rodrigo] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. [Escamilla, Michael; Figueroa, Andres] Univ Texas Hlth Sci Ctr San Antonio, Reg Acad Hlth Ctr, S Texas Med Genet Res Group, Edinburg, TX USA. [Armas, Regina] Univ Calif San Francisco, Langley Porter Psychiat Inst, San Francisco, CA 94143 USA. [Figueroa, Andres] Univ Texas Pan Amer, Dept Comp Sci, Edinburg, TX 78541 USA. RP Escamilla, M (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Psychiat Genet Res Center, 7703 Floyd Curl Dr MC 7789, San Antonio, TX 78229 USA. EM escamillam@uthscsa.edu OI Nicolini, Humberto/0000-0003-2494-0067; Raventos, Henriette/0000-0001-9423-8308; Jerez Magana, Alvaro Antonio/0000-0002-1208-3769 FU International Neuro-Genetics Association of Spanish America and the United States (INGASU); NIMH; University of Texas Health Science Center at San Antonio [MH60881]; University of California at Los Angeles-Harbor [MH60875] FX Additional principal investigators who participated in these grants were Dr. Henriette Raventos (University of Costa Rica, San Jose, Costa Rica), Dr. Alfonso Ontiveros (Instituto de Informacion de Investigacion en Salud Mental. Monterrey, Mexico), Dr. Humberto Nicolini (Medical and Family Research Group. Carracci S.C., Mexico City. Mexico). Dr. Rodrigo Munoz (Family Health Centers of San Diego, California), and Dr. Alvaro Jerez (Centro Internacional de Trastornos Afectivos y de la Conducta Adictiva-CITACA, Guatemala). Additional investigators from the University ofTexas Health Science Center at San Antonio included Dr. Albana Dassori and Dr. Rolando Medina. NR 19 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2008 VL 106 IS 2-3 BP 253 EP 257 DI 10.1016/j.schres.2008.09.005 PG 5 WC Psychiatry SC Psychiatry GA 385YU UT WOS:000261850300020 PM 18929466 ER PT J AU Morrow, EM Kane, A Goff, DC Walsh, CA AF Morrow, Eric M. Kane, Anna Goff, Donald C. Walsh, Christopher A. TI Sequence analysis of P21-activated kinase 3 (PAK3) in chronic schizophrenia with cognitive impairment SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Mental retardation; Pfropfschizophrenie; P21-activated kinase PAK3; Cognitive development ID LINKED MENTAL-RETARDATION; DISORDERS; MUTATION AB The P27-activated kinase PAK3 is critical for cognitive development and truncating mutations cause non-syndromic mental retardation (MR). Missense mutations are also associated with psychotic disorders, most commonly with schizophrenia involving premorbid MR, namely "pfropfschizophrenie". We set out to measure the frequency of sequence variants in PAK3 in schizophrenia without premorbid MR. We conducted complete gene reseqeuncing of all coding exons and exon-intron boundaries in patients with schizophrenia with cognitive impairment but without premorbid MR. Deleterious variants in schizophrenia alone were rare (<1/ 159 or 0.6%). Thereby, while PAK3 remains a strong biological candidate in psychosis, evidence from human genetics provides strongest support for a link to pfropfschizophrenie and not to schizophrenia without premorbid intellectual disability. (C) 2008 Elsevier B.V. All rights reserved. C1 [Morrow, Eric M.; Kane, Anna; Walsh, Christopher A.] Harvard Univ, Childrens Hosp Boston, Sch Med, Div Genet, Boston, MA 02115 USA. [Morrow, Eric M.; Kane, Anna; Walsh, Christopher A.] Howard Hughes Med Inst, Div Neurogenet, Chevy Chase, MD USA. [Morrow, Eric M.; Kane, Anna; Walsh, Christopher A.] Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA USA. [Morrow, Eric M.; Goff, Donald C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Schizophrenia Res Program, Boston, MA 02114 USA. RP Walsh, CA (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Div Genet, New Res Bldg 266,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM cwalsh@bidmc.harvard.edu RI Morrow, Eric/J-2767-2013 FU NIMH [1 K23MH080954-01, K24 MH002025-06]; Burroughs Wellcome Fund; Rappaport Research Scholarship FX We are grateful to the patients who participated in this study. We are grateful for support from the NIMH (1 K23MH080954-01 to E.M.M). E.M.M. holds a Career Award for Medical Scientists from the Burroughs Wellcome Fund and is also grateful for support from the Rappaport Research Scholarship in Neuroscience at MGH. This work was supported by a NARSADYoung Investigator award to E.M.M. who is the Sidney R. Baer. Jr. Foundation Investigator. D.C.G. is supported by a mid-career development award from the NIMH (K24 MH002025-06). CAW. is an Investigator of the Howard Hughes Medical Institute. NR 15 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2008 VL 106 IS 2-3 BP 265 EP 267 DI 10.1016/j.schres.2008.08.021 PG 3 WC Psychiatry SC Psychiatry GA 385YU UT WOS:000261850300022 PM 18805672 ER PT J AU Goff, DC Cather, C Gottlieb, JD Evins, AE Walsh, J Raeke, L Otto, MW Schoenfeld, D Green, MF AF Goff, Donald C. Cather, Corinne Gottlieb, Jennifer D. Evins, A. Eden Walsh, Jared Raeke, Lisa Otto, Michael W. Schoenfeld, David Green, Michael F. TI Once-weekly D-cycloserine effects on negative symptoms and cognition in schizophrenia: An exploratory study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; D-cycloserine; Negative symptoms; Cognition; Memory consolidation ID AGONIST D-CYCLOSERINE; PLACEBO-CONTROLLED TRIAL; D-ASPARTATE RECEPTORS; CONVENTIONAL NEUROLEPTICS; GLYCINE RECEPTOR; D-SERINE; EXTINCTION; MEMORY; ANTIPSYCHOTICS; EFFICACY AB Background: Daily dosing with D-cycloserine has inconsistently improved negative symptoms in schizophrenia patients, whereas intermittent dosing significantly facilitated exposure-based therapy in two studies of patients with phobic anxiety. In animal models. single-dose administration enhances memory consolidation, but tachyphylaxis develops with repeated dosing. The objective of this exploratory study was to assess whether once-weekly dosing with D-cycloserine will produce persistent improvements in negative symptoms and cognition. Methods: Fifty stable adult schizophrenia outpatients treated with any antipsychotic except clozapine were enrolled and 38 were randomized, double-blind, in a parallel-group, eight-week add-on trial of D-cycloserine 50 mg or placebo administered once-weekly. Symptom rating scales and a cognitive battery were administered at baseline and week 8 before the dose of study drug. As an exploratory analysis of memory consolidation, the Logical Memory Test, modified to measure recall after 7 days, was administered at baseline and after the first weekly dose of D-cycloserine. The primary outcome measures were change from baseline to week 8 on the SANS total score and on a composite cognitive score. Results: Thirty-three subjects (87%) completed the trial. D-cycloserine significantly improved SANS total scores compared to placebo at week 8. Cognitive performance did not improve with D-cycloserine at 8 weeks. Delayed thematic recall on the Logical Memory Test was significantly improved with the first dose of D-cycloserine compared to placebo. Performance on immediate thematic recall and item recall on the Logical Memory Test did not differ between treatments. Conclusions: Once-weekly dosing with D-cycloserine for 8 weeks produced persistent improvement of negative symptoms compared to placebo, although statistical significance was, in part, the result of worsening of negative symptoms with placebo. Consistent with animal models, a single dose of D-cycloserine facilitated memory consolidation tested after 7 days on a test of thematic recall. These results must be considered preliminary since a number of outcomes were examined without correction for multiple tests. These findings suggest that once-weekly dosing with D-cycloserine for the treatment of negative symptoms merits further study, as do D-cycloserine effects on memory consolidation. (C) 2008 Elsevier B.V. All rights reserved. C1 [Goff, Donald C.; Cather, Corinne; Gottlieb, Jennifer D.; Evins, A. Eden; Walsh, Jared; Raeke, Lisa] Massachusetts Gen Hosp, Dept Psychiat, Freedom Trail Clin, Boston, MA 02114 USA. [Goff, Donald C.; Cather, Corinne; Gottlieb, Jennifer D.; Evins, A. Eden; Schoenfeld, David] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Schoenfeld, David] MGH Biostat Ctr, Boston, MA 02114 USA. [Otto, Michael W.] Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. [Green, Michael F.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Green, Michael F.] Univ Calif Los Angeles, VA Greater Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Goff, DC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Freedom Trail Clin, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM golf@psych.mgh.harvard.edu; ccather@partners.org; jgottlieb2@partners.org; a_eden_evins@hms.harvard.edu; jpwalsh@partners.org; lraeke@partners.org; mwotto@bu.edu; dschoenfeld@partners.org; mgreen@ucla.edu FU NIMH [2 K24 MH002025-06, 2 P50 MH0060450-08A1] FX This study was funded by NIMH 2 K24 MH002025-06 (D. Goff) and NIMH 2 P50 MH0060450-08A1 (J. Coyle). Dr. Goff had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. NR 42 TC 66 Z9 66 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD DEC PY 2008 VL 106 IS 2-3 BP 320 EP 327 DI 10.1016/j.schres.2008.08.012 PG 8 WC Psychiatry SC Psychiatry GA 385YU UT WOS:000261850300031 PM 18799288 ER PT J AU Zlotoff, DA Schwarz, BA Bhandoola, A AF Zlotoff, Daniel A. Schwarz, Benjamin A. Bhandoola, Avinash TI The long road to the thymus: the generation, mobilization, and circulation of T-cell progenitors in mouse and man SO SEMINARS IN IMMUNOPATHOLOGY LA English DT Review DE Hematopoietic stem cells; Hematopoietic progenitors; Mobilization; Thymic settling; Early thymic progenitors ID HEMATOPOIETIC STEM-CELLS; COLONY-STIMULATING FACTOR; COMMON LYMPHOID PROGENITORS; CHEMOKINE RECEPTOR CXCR4; UMBILICAL-CORD BLOOD; MURINE FETAL LIVER; BONE-MARROW-CELLS; SELF-RENEWAL; PERIPHERAL-BLOOD; LINEAGE COMMITMENT AB The majority of T cells develop in the thymus. T-cell progenitors in the thymus do not self-renew and so progenitor cells must be continuously imported from the blood into the thymus to maintain T-cell production. Recent work has shed light on both the identity of the cells that home to the thymus and the molecular mechanisms involved. This review will discuss the cells in the bone marrow and blood that are involved in early thymopoiesis in mouse and man. Understanding the pre-thymic steps in T-cell development may translate into new therapeutics, especially in the field of hematopoietic stem cell transplantation. C1 [Zlotoff, Daniel A.; Bhandoola, Avinash] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Schwarz, Benjamin A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Bhandoola, A (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 264 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM bhandooa@mail.med.upenn.edu FU National Institutes of Health; Scholar of the Leukemia and Lymphoma Society FX We thank Taku Kambayashi, Jeremiah Bell, and Jennifer Burg for their comments. This work was supported by grants from the National Institutes of Health. A. B. is a Scholar of the Leukemia and Lymphoma Society. NR 142 TC 20 Z9 20 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1863-2297 J9 SEMIN IMMUNOPATHOL JI Semin. Immunopathol. PD DEC PY 2008 VL 30 IS 4 BP 371 EP 382 DI 10.1007/s00281-008-0133-4 PG 12 WC Immunology; Pathology SC Immunology; Pathology GA 379QX UT WOS:000261412400002 PM 18925398 ER PT J AU Nuernberg, AM Christiani, DC AF Nuernberg, Amy M. Christiani, David C. TI The Future of Occupationally Related Diffuse Lung Disease SO SEMINARS IN RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE Occupational lung disease; toxicogenomics; biomarkers; environmental health; gene-environment interactions ID GENE-ENVIRONMENT INTERACTIONS; WORKERS; SUSCEPTIBILITY; POLYMORPHISMS; ASSOCIATION; BIOMARKER AB In the last 10 years alone, several new occupational lung diseases have been described. Progress in improving measurements of exposures and risk factors for exposure-related diseases has turned to molecular epidemiology and genomics methods in recent years. There has been a dramatic increase in the number of studies investigating genetic associations and biomarkers in occupationally related diffuse lung diseases. Specifically, identifying common variant genetic polymorphisms that may have low penetrance (modest relative risk), but Impart a high population-attributable risk of disease when exposure Occurs, has been a recent research focus. Candidate gene methodology is currently the Most Popular approach, but genome-wide association studies are now more feasible for studying gene-environment interactions. The results of these studies will better define populations at particularly high risk of disease after exposure, but it is important to realize that the mainstay of prevention for occupationally related diffuse lung disease remains prevention and control of airborne exposures. C1 [Nuernberg, Amy M.; Christiani, David C.] Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA. [Nuernberg, Amy M.; Christiani, David C.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. [Nuernberg, Amy M.; Christiani, David C.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Massachusetts Gen Hosp, Div Pulm & Crit Care Med, 665 Huntington Ave,SPH I-1407, Boston, MA 02115 USA. EM dchris@hsph.harvard.edu NR 28 TC 1 Z9 1 U1 0 U2 0 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 DEC PY 2008 VL 29 IS 6 BP 680 EP 684 DI 10.1055/s-0028-1101278 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 380EG UT WOS:000261448400011 PM 19221966 ER PT J AU Hough, S AF Hough, Sigmund TI From the Editor SO SEXUALITY AND DISABILITY LA English DT Editorial Material C1 VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, S (reprint author), VA Boston Healthcare Syst, Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM Sigmund_Hough@hms.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD DEC PY 2008 VL 26 IS 4 BP 187 EP 187 DI 10.1007/s11195-008-9095-7 PG 1 WC Rehabilitation SC Rehabilitation GA 373JF UT WOS:000260967200001 ER PT J AU Burns, S Mahalik, J Hough, S Greenwell, A AF Burns, Shaun Michael Mahalik, James R. Hough, Sigmund Greenwell, Ashley N. TI Adjustment to Changes in Sexual Functioning Following Spinal Cord Injury: The Contribution of Men's Adherence to Scripts for Sexual Potency SO SEXUALITY AND DISABILITY LA English DT Article DE Adjustment; Gender scripts; Masculinity; Spinal cord injury; Sexual functioning; Treatment interventions ID QUALITY-OF-LIFE; ERECTILE DYSFUNCTION; HELP-SEEKING; SATISFACTION; MASCULINITY; POPULATION; GENDER; HEALTH; IMPACT; PREDICTORS AB Recent epidemiological statistics suggest approximately 250,000 people in the United States live with a spinal cord injury. Men constitute roughly 82% of these individuals. Following spinal cord injury, men frequently experience significant changes in their sexual functioning. As a result, men with spinal cord injuries are at an increased risk for experiencing adjustment difficulties. Unfortunately, relatively little is known about factors that promote or impede men's adjustment to these changes. In the present article, the authors highlight how men's adherence to gender scripts for sexual potency may contribute to their adjustment following a spinal cord injury. To organize the discussion, the authors review related literature and, through case examples, illustrate how men's adherence to this gender norm may influence their post-injury mental health. Directions for gender-sensitive interventions and future clinical research are provided. C1 [Burns, Shaun Michael; Hough, Sigmund; Greenwell, Ashley N.] Boston Univ, Harvard Med Sch, Spinal Cord Injury Serv, VA Boston Healthcare Syst, Boston, MA 02215 USA. [Mahalik, James R.] Boston Coll, Dept Counseling Dev & Educ Psychol, Chestnut Hill, MA 02167 USA. RP Burns, S (reprint author), Boston Univ, Harvard Med Sch, Spinal Cord Injury Serv, VA Boston Healthcare Syst, Boston, MA 02215 USA. NR 64 TC 4 Z9 4 U1 4 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD DEC PY 2008 VL 26 IS 4 BP 197 EP 205 DI 10.1007/s11195-008-9091-y PG 9 WC Rehabilitation SC Rehabilitation GA 373JF UT WOS:000260967200003 ER PT J AU Hough, B AF Hough, Brian H. TI Shriver M.: What's Wrong with Timmy? SO SEXUALITY AND DISABILITY LA English DT Book Review C1 VA Boston Healthcare Syst, Volunteer Serv Spinal Cord Injury Serv SCI 128, W Roxbury, MA 02132 USA. RP Hough, B (reprint author), VA Boston Healthcare Syst, Volunteer Serv Spinal Cord Injury Serv SCI 128, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM author6698@yahoo.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0146-1044 J9 SEX DISABIL JI Sex. Disabil. PD DEC PY 2008 VL 26 IS 4 BP 241 EP 242 DI 10.1007/s11195-008-9102-z PG 2 WC Rehabilitation SC Rehabilitation GA 373JF UT WOS:000260967200007 ER PT J AU Reichardt, B Sarwar, A Bartling, SH Cheung, A Grasruck, M Leidecker, C Bredella, MA Brady, TJ Gupta, R AF Reichardt, Benjamin Sarwar, Ammar Bartling, Soenke H. Cheung, Arnold Grasruck, Michael Leidecker, Christianne Bredella, Miriam A. Brady, Thomas J. Gupta, Rajiv TI Musculoskeletal applications of flat-panel volume CT SO SKELETAL RADIOLOGY LA English DT Review DE Musculoskeletal applications; Flat-panel volume computed tomography; High-resolution imaging; Trabecular imaging ID HIGH-RESOLUTION MRI; COMPUTED-TOMOGRAPHY; STEM-CELLS; FUNDAMENTAL PRINCIPLES; SCAPHOID FRACTURE; SPIRAL CT; BONE; RADIOGRAPHY; DETECTORS; SCAFFOLDS AB Flat-panel volume computed tomography (fpVCT) is a recent development in imaging. We discuss some of the musculoskeletal applications of a high-resolution flat-panel CT scanner. FpVCT has four main advantages over conventional multidetector computed tomography (MDCT): high-resolution imaging; volumetric coverage; dynamic imaging; omni-scanning. The overall effective dose of fpVCT is comparable to that of MDCT scanning. Although current fpVCT technology has higher spatial resolution, its contrast resolution is slightly lower than that of MDCT (5-10HU vs. 1-3HU respectively). We discuss the efficacy and potential utility of fpVCT in various applications related to musculoskeletal radiology and review some novel applications for pediatric bones, soft tissues, tumor perfusion, and imaging of tissue-engineered bone growth. We further discuss high-resolution CT and omni-scanning (combines fluoroscopic and tomographic imaging). C1 [Reichardt, Benjamin; Sarwar, Ammar; Cheung, Arnold; Bredella, Miriam A.; Brady, Thomas J.; Gupta, Rajiv] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. [Bartling, Soenke H.] DKFZ, Dept Med Phys Radiol, Heidelberg, Germany. [Grasruck, Michael; Leidecker, Christianne] Siemens Med Solut, Forchheim, Germany. RP Gupta, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St,FND-216, Boston, MA 02114 USA. EM rgupta1@partners.org NR 23 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD DEC PY 2008 VL 37 IS 12 BP 1069 EP 1076 DI 10.1007/s00256-008-0473-0 PG 8 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 365BC UT WOS:000260379900002 PM 18443787 ER PT J AU Burgess, DJ Crowley-Matoka, M Phelan, S Dovidio, JF Kerns, R Roth, C Saha, S van Ryn, M AF Burgess, Diana Jill Crowley-Matoka, Megan Phelan, Sean Dovidio, John F. Kerns, Robert Roth, Craig Saha, Somnath van Ryn, Michelle TI Patient race and physicians' decisions to prescribe opioids for chronic low back pain SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE USA; Health disparities; Chronic pain; Medical decision-making; Race; Men; Prescribing ID PRIMARY-CARE PHYSICIANS; CORONARY-HEART-DISEASE; CHRONIC NONCANCER PAIN; PROVIDERS CONTRIBUTE; ETHNIC DISPARITIES; RACIAL-DIFFERENCES; RACE/ETHNICITY; GENDER; HEALTH; COMMUNICATION AB Nonwhite patients are less likely than white patients to have their pain adequately treated. This study examined the influence of patient race and patient verbal and nonverbal behavior on primary care physicians' treatment decisions for chronic low back pain in men. We randomly assigned physicians to receive a paper-based, clinical vignette of a chronic pain patient that differed in terms of patient race (white vs. black), verbal behavior ("challenging" vs. "non-challenging"), and nonverbal behavior (confident vs. dejected vs. angry). We employed a between-subjects factorial design and surveyed primary care physicians (N = 382), randomly selected from the American Medical Association Physician Masterfile. The primary dependent measure was the physician's decision as to whether (s)he would switch the patient to a higher dose or stronger type of opioid. Logistic regression was used to determine the effects of patient characteristics on physicians' prescribing decisions. There was a significant interaction between patient verbal behavior and patient race on physicians' decisions to prescribe opioids. Among black patients, physicians were significantly more likely to state that they would switch to a higher dose or stronger opioid for patients exhibiting "challenging" behaviors (e.g., demanding a specific narcotic, exhibiting anger) compared to those exhibiting "non-challenging" behaviors (55.1%). For white patients there was an opposite pattern of results in which physicians were slightly more likely to escalate treatment for patients exhibiting "non-challenging" (64.3%) vs. "challenging" (54.5%) verbal behaviors. Results point to the need for better understanding of the way a complex interplay of non-clinical characteristics affects physician behavior in order to improve quality of pain management and other clinical decision-making. Published by Elsevier Ltd. C1 [Burgess, Diana Jill] VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55419 USA. [Burgess, Diana Jill; Roth, Craig] Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. [Crowley-Matoka, Megan] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Crowley-Matoka, Megan] Pittsburgh Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Crowley-Matoka, Megan] Univ Pittsburgh, Dept Anthropol, Pittsburgh, PA 15260 USA. [Phelan, Sean] Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. [Dovidio, John F.] Yale Univ, Dept Psychol, New Haven, CT 06520 USA. [Kerns, Robert; Saha, Somnath] Yale Univ, Dept Psychiat, VA Connecticut Healthcare Syst, New Haven, CT 06520 USA. [Kerns, Robert; Saha, Somnath] Yale Univ, Dept Neurol, VA Connecticut Healthcare Syst, New Haven, CT 06520 USA. [Kerns, Robert; Saha, Somnath] Yale Univ, Dept Psychol, VA Connecticut Healthcare Syst, New Haven, CT 06520 USA. [Roth, Craig] Univ Minnesota, Minneapolis Vet Affairs Med Ctr, Minneapolis, MN 55455 USA. [van Ryn, Michelle] Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. [van Ryn, Michelle] Univ Minnesota, Dept Family Med & Community Hlth, Minneapolis, MN 55455 USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. [Saha, Somnath] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. RP Burgess, DJ (reprint author), VA Med Ctr, Ctr Chron Dis Outcomes Res, 1 Vet Dr, Minneapolis, MN 55419 USA. EM diana.burgess@med.va.gov; mcm29@imap.pitt.edu; phel0085@umn.edu; john.dovidio@yale.edu; robert.kerns@va.gov; craig.roth@va.gov; sahas@ohsu.edu; vanry001@umn.edu RI VAN RYN, MICHELLE/B-1664-2010; Burgess, Diana/A-1946-2016 NR 62 TC 40 Z9 40 U1 3 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2008 VL 67 IS 11 BP 1852 EP 1860 DI 10.1016/j.socscimed.2008.09.009 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 383EZ UT WOS:000261658200025 PM 18926612 ER PT J AU Krieger, N Chen, JT Waterman, PD Hartman, C Stoddard, AM Quinn, MM Sorensen, G Barbeau, EM AF Krieger, Nancy Chen, Jarvis T. Waterman, Pamela D. Hartman, Cathy Stoddard, Anne M. Quinn, Margaret M. Sorensen, Glorian Barbeau, Elizabeth M. TI The inverse hazard law: Blood pressure, sexual harassment, racial discrimination, workplace abuse and occupational exposures in US low-income black, white and Latino workers SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE Blood pressure; Health inequities; Occupational health; Racial discrimination; Sexual harassment; Workplace abuse; USA ID UNITED-STATES; AFRICAN-AMERICANS; SOCIAL HAZARDS; PUBLIC-HEALTH; RISK-FACTORS; SELF-REPORT; HYPERTENSION; POPULATION; PREVALENCE; ADULTS AB Research on societal determinants of health suggests the existence of an "inverse hazard law." which we define as: "The accumulation of health hazards tends to vary inversely with the power and resources of the populations affected." Yet, little empirical research has systematically investigated this topic, including in relation to workplace exposures. We accordingly designed the United for Health study (Greater Boston Area, Massachusetts, 2003-2004) to investigate the joint distribution and health implications of workplace occupational hazards (dust, fumes, chemical, noise, ergonomic strain) and social hazards (racial discrimination, sexual harassment, workplace abuse). Focusing on blood pressure as our health outcome, we found that among the 1202 low-income multi-racial/ethnic working class participants in our cohort - of whom 40% lived below the US poverty line 79% reported exposure to at least one social hazard and 82% to at least one high-exposure occupational hazard. Only sexual harassment, the least common social hazard, was associated with elevated systolic blood pressure (SBP) among the women workers. By contrast, no statistically significant associations were detectable between the other additional highly prevalent social and occupational hazards and SBP: we did, however, find suggestive evidence of an association between SBP and response to unfair treatment, implying that in a context of high exposure, differential susceptibility to the exposure matters. These results interestingly contrast to our prior findings for this same cohort, in which we found associations between self-reported experiences of racial discrimination and two other health outcomes: psychological distress and cigarette smoking. Likely explanations for these contrasting findings include: (a) the differential etiologic periods and pathways involving somatic health, mental health, and health behaviors, and (b) the high prevalence of adverse exposures, limiting the ability to detect significant associations. As clarified by the "inverse hazard law," to understand health inequities, research is needed that contrasts exposures and health status population-wide, not just among those most inequitably exposed. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Krieger, Nancy; Chen, Jarvis T.; Waterman, Pamela D.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Hartman, Cathy; Barbeau, Elizabeth M.] Hlth Dialog, Boston, MA 02109 USA. [Stoddard, Anne M.] New England Res Inst, Watertown, MA 02472 USA. [Quinn, Margaret M.] Univ Massachusetts, Dept Work Environm, Lowell, MA USA. [Sorensen, Glorian] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. RP Krieger, N (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Kresge 717,677 Huntington Ave, Boston, MA 02115 USA. EM nkrieger@hsph.harvard.edu FU PHS HHS [R01 OHO7366-01, R01 OHO7366-01S] NR 50 TC 48 Z9 48 U1 3 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD DEC PY 2008 VL 67 IS 12 BP 1970 EP 1981 DI 10.1016/j.socscimed.2008.09.039 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 388AY UT WOS:000261993900005 PM 18950922 ER PT J AU Singh, S Khosla, S Gupta, V AF Singh, Sarabjeet Khosla, Sandeep Gupta, Vishal TI The Role of Drug-Eluting Stents in Treating Cardiac Transplant Vasculopathy SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID CORONARY-ARTERY-DISEASE; ALLOGRAFT VASCULOPATHY; RECIPIENTS; MULTICENTER; ANGIOPLASTY; PREVENTION; REJECTION; OUTCOMES C1 Chicago Med Sch & Affiliated Hosp, Dept Med, Cardiol Sect, Chicago, IL USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Intervent Cardiol, Boston, MA USA. RP Singh, S (reprint author), Mt Sinai Hosp, Dept Cardiol, Chicago, IL 60608 USA. EM sarabjeetsingh_2000@yahoo.com NR 11 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD DEC PY 2008 VL 101 IS 12 BP 1198 EP 1199 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 384XR UT WOS:000261778000005 PM 19005449 ER PT J AU Hansson, T Hansson, E Malchau, H AF Hansson, Tommy Hansson, Elisabeth Malchau, Henrik TI Utility of Spine Surgery A Comparison of Common Elective Orthopaedic Surgical Procedures SO SPINE LA English DT Article DE quality of life; utility; spine surgery; elective surgery; spinal stenosis ID LOW-BACK-PAIN; TRIAL; FUSION; EUROQOL; EQ-5D; STATE; DISC AB Study Design. A 1-year prospective observational cohort study. Objective. To compare the utility before and 1 year after elective spine surgery with some other common orthopaedic surgical procedures. Summary of Background Data. By using global measures like EQ-5D and SF-36 for the determination of the utility, the changes in quality of life, quality of life (QoL) after an intervention different diagnoses, and treatments can be compared. Total hip replacement (THR) has become almost golden standard in this respect. Methods. Seven hundred seventy-seven subjects with different common orthopaedic diagnoses scheduled for elective surgery were just before surgery and 1 year after surgery answering both EQ-5D and SF-36. Four groups with different spine diagnoses and procedures were formed and compared with 8 other diagnoses and treatment groups. Results. Before surgery, subjects with spine diagnoses reported the lowest QoL of all diagnoses compared. Surgery for spinal stenosis, spondylolisthesis, and instability meant the largest improvement of all surgical interventions. Surgery for NHP gave a moderately good improvement, whereas surgery for CLBP only marginally improved those operated. Particularly THR but also TKR more or less completely normalized QoL but made it from a relatively high preoperative level. The greatest improvements after spine surgery, other surgical procedures, and different diagnoses were in the pain/discomfort domain. Conclusion. Spinal surgery in spinal stenosis, spondylolisthesis, and instability had in comparison to other types of elective orthopaedic surgery an outstanding better ability to improve the operated subject's health-related quality of life than other types of elective orthopaedic surgery. The utility of HNP surgery was somewhat lower and was rather marginal for those operated for nonspecific CLBP. C1 [Hansson, Tommy] SU Sahlgrenska Acad, Dept Orthopaed, S-41345 Gothenburg, Sweden. [Malchau, Henrik] Massachusetts Gen Hosp, Dept Orthopaed, Boston, MA 02114 USA. RP Hansson, T (reprint author), SU Sahlgrenska Acad, Dept Orthopaed, Bruna Straket 11, S-41345 Gothenburg, Sweden. EM tommy.hansson@orthop.gu.se FU FAS, Goteborg University; AFA FX Supported in part by the grants from FAS, Goteborg University, and AFA. NR 26 TC 28 Z9 28 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD DEC 1 PY 2008 VL 33 IS 25 BP 2819 EP 2830 DI 10.1097/BRS.0b013e31818e2914 PG 12 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 378SY UT WOS:000261345400017 PM 19050588 ER PT J AU Eckman, MH Wong, LKS Soo, YOY Lam, W Yang, SR Greenberg, SM Rosand, J AF Eckman, Mark H. Wong, Lawrence K. S. Soo, Yannie O. Y. Lam, Wynnie Yang, Song Ran Greenberg, Steven M. Rosand, Jonathan TI Patient-Specific Decision-Making for Warfarin Therapy in Nonvalvular Atrial Fibrillation How Will Screening With Genetics and Imaging Help? SO STROKE LA English DT Article DE atrial fibrillation; cerebral hemorrhage; decision support techniques; genetics; magnetic resonance imaging ID CEREBRAL AMYLOID ANGIOPATHY; SPONTANEOUS INTRACEREBRAL HEMORRHAGE; MATTER HYPERINTENSITY VOLUME; RANDOMIZED CONTROLLED-TRIALS; APOLIPOPROTEIN-E EPSILON-4; GRADIENT-ECHO MRI; QUALITY-OF-LIFE; RISK-FACTORS; INTRACRANIAL HEMORRHAGE; ANTITHROMBOTIC THERAPY AB Background and Purpose-Intracerebral hemorrhage (ICH) accounts for a majority of long-term morbidity and mortality associated with bleeding while on warfarin. Both ICH and warfarin-related ICH appear to have a genetic component. Furthermore, advanced neuroimaging using MRI can now identify individuals at increased risk of ICH. We explore whether screening strategies that include genetic profiling and neuroimaging might improve the safety of chronic anticoagulation for atrial fibrillation by identifying individuals from whom warfarin should be withheld. Methods-We used a Markov state transition decision model. Effectiveness was measured in quality-adjusted life-years. Data sources included the English language literature using MEDLINE searches and bibliographies from selected articles along with empirical data from our institutions. The base case was a 69-year-old man with newly diagnosed nonvalvular atrial fibrillation. Results-For patients at average risk for thromboembolic events and known to possess a hypothetical genetic profile increasing risk for warfarin ICH, anticoagulation remains the preferred strategy until the relative hazard of ICH exceeds 23.8. Genetic profiling would be favored for patients at low risk of thromboembolism (1.5% per year) if the hypothetical gene variant(s) conferred a relative risk of ICH > 4.1. Screening strategies in which patients underwent genotyping and MRI before anticoagulation did not improve aggregate patient outcomes unless the predictive power of MRI exceeded current best guess estimates and patients were at low to moderate risk of thromboembolism. Conclusion-Currently identified genetic markers of bleeding risk do not confer a risk of ICH sufficiently high to warrant routine genetic testing for patients at average risk of thromboembolism. Even if patients undergo screening with MRI as well as genotyping, currently available data on the role of MRI on risk of ICH and warfarin ICH do not support use of these tests for withholding anticoagulation in patients with atrial fibrillation. (Stroke. 2008; 39: 3308-3315.) C1 [Eckman, Mark H.] Univ Cincinnati, Med Ctr, Div Gen Internal Med, Cincinnati, OH 45267 USA. [Eckman, Mark H.] Univ Cincinnati, Med Ctr, Ctr Clin Effectiveness, Cincinnati, OH 45267 USA. [Wong, Lawrence K. S.; Soo, Yannie O. Y.; Lam, Wynnie] Chinese Univ Hong Kong, Dept Neurol, Hong Kong, Hong Kong, Peoples R China. Prince Wales Hosp, Acute Stroke Unit, Hong Kong, Hong Kong, Peoples R China. [Yang, Song Ran] Sun Yat Sen Univ, Dept Neurol, Guangzhou 510275, Guangdong, Peoples R China. [Greenberg, Steven M.; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Hemorrhag Stroke Res Grp, Boston, MA 02114 USA. [Rosand, Jonathan] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Eckman, MH (reprint author), Univ Cincinnati, Med Ctr, Div Gen Internal Med, POB 670535, Cincinnati, OH 45267 USA. EM mark.eckman@uc.edu RI Wong, Ka Sing Lawrence/N-3434-2015 OI Wong, Ka Sing Lawrence/0000-0002-2031-9866 FU National Institute of Diabetes and Digestive and Kidney Diseases [K23 DK075599]; National Heart, Lung, and Blood Institute [K30 HL078581-01]; Foundation for Informed Medical Decision Making; National Institutes of Neurological Disorders and Stroke [K23 NS42695-01, R01 NS04217]; Deane Institute for Integrative Study of Atrial Fibrillation and Stroke FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K23 DK075599, to M. H. E.), National Heart, Lung, and Blood Institute (K30 HL078581-01, to M. H. E.), and Foundation for Informed Medical Decision Making (to M. H. E.); by the National Institutes of Neurological Disorders and Stroke (K23 NS42695-01, to J. R., and R01 NS04217, to J. R. and S. M. G.), and the Deane Institute for Integrative Study of Atrial Fibrillation and Stroke (to J. R.). NR 68 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2008 VL 39 IS 12 BP 3308 EP 3315 DI 10.1161/STROKEAHA.108.523159 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 377AT UT WOS:000261224800027 PM 18845797 ER PT J AU Murata, Y Rosell, A Scannevin, RH Rhodes, KJ Wang, XY Lo, EH AF Murata, Yoshihiro Rosell, Anna Scannevin, Robert H. Rhodes, Kenneth J. Wang, Xiaoying Lo, Eng H. TI Extension of the Thrombolytic Time Window With Minocycline in Experimental Stroke SO STROKE LA English DT Article DE cerebral ischemia; hemorrhagic transformation; edema; tPA; neuroprotection ID TISSUE-PLASMINOGEN-ACTIVATOR; FOCAL CEREBRAL-ISCHEMIA; SPINAL-CORD-INJURY; AMYOTROPHIC-LATERAL-SCLEROSIS; TRAUMATIC BRAIN-INJURY; CYTOCHROME-C RELEASE; HEMORRHAGIC TRANSFORMATION; MATRIX-METALLOPROTEINASE; INTRACEREBRAL HEMORRHAGE; NEUTROPHIL INFILTRATION AB Background and Purpose-Thrombolysis with tPA is the only FDA-approved therapy for acute ischemic stroke. But its widespread application remains limited by narrow treatment time windows and the related risks of cerebral hemorrhage. In this study, we ask whether minocycline can prevent tPA-associated cerebral hemorrhage and extend the reperfusion window in an experimental stroke model in rats. Methods-Spontaneously hypertensive rats were subjected to embolic focal ischemia using homologous clots and treated with: saline at 1 hour; early tPA at 1 hour, delayed tPA at 6 hours; minocycline at 4 hours; combined minocycline at 4 hours plus tPA at 6 hours. Infarct volumes and hemorrhagic transformation were quantified at 24 hours. Gelatin zymography was used to measure blood levels of circulating matrix metalloproteinase-9 (MMP-9). Results-Early 1-hour thrombolysis restored perfusion and reduced infarction. Late 6-hour tPA did not decrease infarction but instead worsened hemorrhagic conversion. Combining minocycline with delayed 6-hour tPA decreased plasma MMP-9 levels, reduced infarction, and ameliorated brain hemorrhage. Blood levels of MMP-9 were also significantly correlated with volumes of infarction and hemorrhage. Conclusion-Combination therapy with minocycline may extend tPA treatment time windows in ischemic stroke. (Stroke. 2008; 39: 3372-3377.) C1 [Murata, Yoshihiro; Rosell, Anna; Wang, Xiaoying; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab,Dept Neurol, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. [Scannevin, Robert H.; Rhodes, Kenneth J.] Biogen IDEC, Cambridge, MA USA. RP Lo, EH (reprint author), Neuroprotect Res Lab, MGH E 149-2401, Charlestown, MA 02129 USA. EM Lo@helilx.mgh.harvard.edu FU NIH [R01-NS37074, R01-NS48422, R01-NS56548, P50-NS10828]; American Heart Association; Ministerio de Educacion y Ciencia [EXT2006/766] FX This work was supported in part by NIH grants R01-NS37074, R01-NS48422, R01-NS56548, P50-NS10828, and a Bugher award from the American Heart Association. Anna Rosell is the recipient of a postdoctoral grant from Ministerio de Educacion y Ciencia (EXT2006/766). NR 39 TC 98 Z9 102 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 DEC PY 2008 VL 39 IS 12 BP 3372 EP 3377 DI 10.1161/STROKEAHA.108.514026 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 377AT UT WOS:000261224800036 PM 18927459 ER PT J AU Foerch, C Arai, K Jin, G Park, KP Pallast, S van Leyen, K Lo, EH AF Foerch, Christian Arai, Ken Jin, Guang Park, Kyung-Pil Pallast, Stefanie van Leyen, Klaus Lo, Eng H. TI Experimental Model of Warfarin-Associated Intracerebral Hemorrhage SO STROKE LA English DT Article DE cerebral hemorrhage; warfarin; mice ID ORAL ANTICOAGULANT-THERAPY; ATRIAL-FIBRILLATION; HEMATOMA; STROKE; MICE; MANAGEMENT AB Background and Purpose-Future demographic changes predict an increase in the number of patients with atrial fibrillation. As long-term anticoagulation for the prevention of ischemic strokes becomes more prevalent, the burden of warfarin-associated intracerebral hemorrhage (W-ICH) is likely to grow. However, little is known about the clinical aspects and pathophysiologic mechanisms of W-ICH. This study describes the development of a mouse model of W-ICH in which hematoma growth and outcomes can be correlated with anticoagulation parameters. Methods-CD-1 mice were treated with warfarin (2 mg/kg per 24 hours) added to drinking water. ICH was induced by stereotactic injection of collagenase type VII (0.075 U) into the right striatum. Hemorrhagic blood volume was quantified by means of a photometric hemoglobin assay 2 and 24 hours after hemorrhage induction. Neurologic outcomes were assessed on a 5-point scale. Results-The international normalized ratio in nonanticoagulated mice was 0.8 +/- 0.1. After 24 (W-24) and 30 (W-30) hours of warfarin pretreatment, international normalized ratio values increased to 3.5 +/- 0.9 and 7.2 +/- 3.4, respectively. Compared with nonanticoagulated mice, mean hemorrhagic blood volume determined 24 hours after hemorrhage induction was found to be 2.5-fold larger in W-24 mice (P=0.019) and 3.1-fold larger in W-30 mice (P < 0.001, n=10 per group). Mortality at 24 hours after hemorrhage induction was 0% in nonanticoagulated mice, 10% in W-24 mice, and 30% in W-30 mice. Hematoma enlargement between 2 and 24 hours after hemorrhage induction was -1.4% for nonanticoagulated mice, 22.9% for W-24 mice, and 62.2% for W-30 mice. Conclusions-This study characterizes the first experimental model of W-ICH. It may be helpful in gaining further insights into the pathophysiology of W-ICH and may be used for testing the efficacy of treatment strategies, such as hemostatic therapy, in this severe subtype of stroke. (Stroke. 2008; 39: 3397-3404.) C1 [Foerch, Christian; Arai, Ken; Jin, Guang; Park, Kyung-Pil; Pallast, Stefanie; van Leyen, Klaus; Lo, Eng H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Charlestown, MA 02129 USA. RP Foerch, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroprotect Res Lab, Room 2414,149 13th St, Charlestown, MA 02129 USA. EM foerch@em.uni-frankfurt.de RI van Leyen, Klaus/C-9126-2013; OI Park, Kyung-Pil/0000-0003-4952-3796 FU Deutsche Forschungsgemeinschaft; National Institutes of Health [R01-NS37074, R01-NS48422, R01-NS53560, R01-NS56458] FX This study was supported in part by a grant from the Deutsche Forschungsgemeinschaft and by National Institutes of Health grants R01-NS37074, R01-NS48422, R01-NS53560, and R01-NS56458. NR 25 TC 57 Z9 57 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD DEC PY 2008 VL 39 IS 12 BP 3397 EP 3404 DI 10.1161/STROKEAHA.108.517482 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 377AT UT WOS:000261224800039 PM 18772448 ER PT J AU Veillette, G Fernandez-del Castillo, C AF Veillette, Gregory Fernandez-del Castillo, Carlos TI Distal Biliary Malignancy SO SURGICAL CLINICS OF NORTH AMERICA LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; EXTRAHEPATIC BILE-DUCTS; PROGNOSTIC-FACTORS; PANCREATIC FISTULAS; CHOLANGIOCARCINOMA; PANCREATICODUODENECTOMY; MANAGEMENT; CANCER; EXPERIENCE; CARCINOMA AB Distal cholangiocarcinoma (malignancy in the common bile duct from the cystic duct to the ampulla) remains a rare diagnosis. Most of these lesions are adenocarcinomas, and typically present with painless jaundice. If suspected, a high-quality CT scan and endoscopic retrograde cholangiopancreatography are required for diagnosis and staging. In addition, identification of risk factors, use of tumor markers, and advanced molecular testing may enhance diagnostic and prognostic capabilities. The treatment of choice for resectable disease is pancreaticoduodenectomy and the overall 5-year survival for resected distal cholangiocarcinoma remains 20% to 30%. C1 [Veillette, Gregory; Fernandez-del Castillo, Carlos] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Veillette, G (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,Wang Ambulatory Care Ctr Suite 460, Boston, MA 02114 USA. EM gveillette@partners.org NR 68 TC 14 Z9 14 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0039-6109 J9 SURG CLIN N AM JI Surg. Clin.-North Am. PD DEC PY 2008 VL 88 IS 6 BP 1429 EP + DI 10.1016/j.suc.2008.07.003 PG 20 WC Surgery SC Surgery GA 383SP UT WOS:000261694000017 PM 18992603 ER PT J AU Lancaster, RT Hutter, MM AF Lancaster, Robert T. Hutter, Matthew M. TI Bands and bypasses: 30-day morbidity and mortality of bariatric surgical procedures as assessed by prospective, multi-center, risk-adjusted ACS-NSQIP data SO SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-American-Gastrointestinal-and-Endoscopic-Surgeons CY APR 09-12, 2008 CL Philadelphia, PA SP Soc Amer Gastrointestinal & Endoscop Surg DE Bariatric surgery; Adjustable gastric band; Gastric bypass; NSQIP; Laparoscopic; Open ID ROUX-EN-Y; LAPAROSCOPIC GASTRIC BYPASS; POSTOPERATIVE MORTALITY; RANDOMIZED-TRIAL; NATIONAL TRENDS; SEVERE OBESITY; UNITED-STATES; US ADULTS; FOLLOW-UP; SURGERY AB Background Previous multi-institution comparisons of open and laparoscopic Roux-en-Y gastric bypass (ORYGB and LRYGB), and laparoscopic adjustable gastric banding (LAGB) have been limited by the lack of unique current procedural terminology (CPT) codes. Specific codes have been available for LRYGB and LAGB since 2005 and 2006, respectively. We compare the short-term safety of these procedures, using risk-adjusted clinical data from a multi-institutional quality improvement program. Methods The America College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) Participant Use File (PUF) was used to compare patients undergoing LRYGB with those undergoing ORYGB or LAGB. Results ORYGB versus LRYGB: The 2-year study period (2005-2006) included 5,777 patients (ORYGB = 1,146, LRYGB = 4,631). Patients undergoing ORYGB experienced a higher 30-day incidence of mortality (0.79% vs. 0.17%; p = 0.002), major complications rate (7.42% vs. 3.37%; p < 0.0001), any complication rate (13.18% vs. 6.69%; p < 0.0001), return visits to the OR (4.97% vs. 3.56%; p = 0.032), and longer postoperative length of stay (LOS) (median 3 vs. 2 days; p < 0.0001). After risk adjustment, ORYGB continued to demonstrate higher odds of major complication (OR = 2.04; [1.54, 2.69]). LAGB versus LRYGB: Analysis of 1 year of data from 2006 included 4,756 patients (LRYGB = 3,580, LAGB = 1,176). Those treated with LAGB experienced an equivalent 30-day mortality (0.09% vs. 0.14%; p = 1.0), and a lower rate of major complications (1.0% vs. 3.3%; p < 0.0001), any complication (2.6% vs. 6.7%; p < 0.0001), return visits to the OR (0.94% vs. 3.6%; p < 0.0001), and shorter postoperative LOS (median 1 vs. 2 days; p < 0.0001). Risk adjustment showed that LAGB was associated with a lower major complication odds (OR = 0.29; [0.16, 0.53]). Conclusions Compared with LRYGB, ORYGB is associated with higher 30-day mortality and higher risk-adjusted major complication rate. While ORYGB may sometimes be indicated, a laparoscopic approach may be safer for RYGB when feasible. LAGB, compared with LRYGB, has a similarly low mortality rate and a small but statistically significant decrease in risk-adjusted 30-day complications. Clinical efficacy and long-term outcomes will need to be evaluated to determine superiority between these procedures. C1 [Lancaster, Robert T.; Hutter, Matthew M.] Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, Codman Ctr Clin Effectiveness Surg, 15 Parkman St Wang ACC 335, Boston, MA 02114 USA. EM rtlancaster@partners.org; mhutter@partners.org NR 42 TC 69 Z9 69 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0930-2794 J9 SURG ENDOSC JI Surg. Endosc. PD DEC PY 2008 VL 22 IS 12 BP 2554 EP 2563 DI 10.1007/s00464-008-0074-y PG 10 WC Surgery SC Surgery GA 389JR UT WOS:000262089200003 PM 18806945 ER PT J AU Rusby, JE Smith, BL AF Rusby, Jennifer E. Smith, Barbara L. TI Unanswered questions in nipple-sparing mastectomy SO SURGICAL ONCOLOGY-OXFORD LA English DT Editorial Material ID TRANSPLANTED NIPPLE; BREAST-CANCER; CARCINOMA C1 [Rusby, Jennifer E.; Smith, Barbara L.] Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 9A,55 Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0960-7404 J9 SURG ONCOL JI Surg. Oncol.-Oxf. PD DEC PY 2008 VL 17 IS 4 BP 259 EP 260 DI 10.1016/j.suronc.2008.05.006 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 370IF UT WOS:000260755200001 PM 18602258 ER PT J AU Riboldi, M Chen, GTY Baroni, G Paganetti, H Seco, J AF Riboldi, M. Chen, G. T. Y. Baroni, G. Paganetti, H. Seco, J. TI Design and Testing of a Simulation Framework for Dosimetric Motion Studies Integrating an Anthropomorphic Computational Phantom into Four-dimensional Monte Carlo SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Monte Carlo; 4D dosimetry; Computational phantom; Organ motion ID ORGAN MOTION; COMPUTED-TOMOGRAPHY; ELECTRON-TRANSPORT; TISSUE PARAMETERS; DOSE CALCULATIONS; IMRT TREATMENTS; HUMAN ANATOMY; LUNG-CANCER; CT NUMBERS; RADIOTHERAPY AB We have designed a simulation framework for motion studies in radiation therapy by integrating the anthropomorphic NCAT phantom into a 4D Monte Carlo dose calculation engine based on DPM. Representing an artifact-free environment, the system can be used to identify class solutions as a function of geometric and dosimetric parameters. A pilot dynamic conformal study for three lesions (similar to 2.0 cm) in the right lung was performed (70 Gy prescription dose). Tumor motion changed as a function of tumor location, according to the anthropomorphic deformable motion model. Conformal plans were simulated with 0 to 2 cm margin for the aperture, with additional 0.5 cm for beam penumbra. The dosimetric effects of intensity modulated radiotherapy (IMRT) vs. conformal treatments were compared in a static case. Results show that the Monte Carlo simulation framework can model tumor tracking in deformable anatomy with high accuracy, providing absolute doses for IMRT and conformal radiation therapy. A target underdosage of up to 3.67 Gy (lower lung) was highlighted in the composite dose distribution mapped at exhale. Such effects depend on tumor location and treatment margin and are affected by lung deformation and ribcage motion. In summary, the complexity in the irradiation of moving targets has been reduced to a controlled simulation environment, where several treatment options can be accurately modeled and quantified The implemented tools will be utilized for extensive motion study in lung/liver irradiation. C1 [Riboldi, M.; Baroni, G.] Univ Milan, Dept Bioengn Politecn, TBMLab, I-20133 Milan, Italy. [Chen, G. T. Y.; Paganetti, H.; Seco, J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Chen, G. T. Y.; Paganetti, H.; Seco, J.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Riboldi, M (reprint author), Univ Milan, Dept Bioengn Politecn, TBMLab, P Za Leonardo Da Vinci 32, I-20133 Milan, Italy. EM marco.riboldi@polimi.it RI Baroni, Guido/D-3012-2011; Riboldi, Marco/I-2980-2014 OI Riboldi, Marco/0000-0002-2431-4966 FU NCI/NIH [R01-CA 111590]; Progetto Rocca foundation FX The work is partly supported by NCI/NIH R01-CA 111590. We also acknowledge the Progetto Rocca foundation for the support. NR 35 TC 1 Z9 1 U1 0 U2 4 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2008 VL 7 IS 6 BP 449 EP 456 PG 8 WC Oncology SC Oncology GA 388PR UT WOS:000262032200006 PM 19044324 ER PT J AU Allen, AM Wolfsberger, L Tishler, RB Court, LE AF Allen, Aaron M. Wolfsberger, Luciant Tishler, Roy B. Court, Laurence E. TI Options for Combining Altered Fractionation with IMRT SO TECHNOLOGY IN CANCER RESEARCH & TREATMENT LA English DT Article DE Altered fractionation; IMRT; Head and Neck ID INTENSITY-MODULATED RADIOTHERAPY; QUALITY-OF-LIFE; NECK-CANCER; RADIATION-THERAPY; ACCELERATED FRACTIONATION; CONVENTIONAL FRACTIONATION; OROPHARYNGEAL CARCINOMA; RANDOMIZED TRIAL; ADVANCED HEAD; 2ND CANCERS AB We set out to investigate IMRT-based concomitant boost. Eight patients with stage III/IV squamous cell carcinoma of the head and neck treated with once daily with chemoradiotherapy at the Dana-Farber/Brigham and Women's Hospital had their treatment plans reviewed with IRB approval. Each case was replanned for treatment with a a concomitant boost regimen. Plans delivered 1.9 Gy in 30 fractions to 57 Gy with a boost of 1.5 Gy in 10 fractions for a total dose of 72 Gy. The boost was planned with both IMRT and 3-D conformal, to compare the two techniques. For each patient, both plans (IMRT-IMRT and IMRT-3DCRT) were evaluated for target and avoidance coverage, monitor units and integral dose. Finally, we evaluated the plans for time to completion. The IMRT-IMRT and IMRT-3-DCRT techniques were equivalent for target coverage. 100% coverage of the GTV and PTV was achieved with 97% of the prescription dose. Hot spots were seen 104% to 108% with IMRT-IMRT plan and from 102-111% with the IMRT-3DCRT plans. The IMRT-IMRT boost had double the monitor units as the 3-DCRT boosts. When the total monitor units from both the initial and boost portions of the plans were e combined there was not a significant differnce. There was a slight increase in integral dose with the IMRT-IMRT plans of mean 3.8%. Planning time was increased for the 3-DCRT boost as opposed to the IMRT boost (mean 3.5 hours vs. 1.5 hours). More time was needed for quality assurance of the IMRT-IMRT plans (3.0 hours vs. 1.5 hours for IMRT-3-DCRT). We found that both IMRT-based concomitant-boost strategies are achievable and produce good dosimetric results. C1 [Allen, Aaron M.; Wolfsberger, Luciant; Tishler, Roy B.; Court, Laurence E.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02215 USA. RP Allen, AM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02215 USA. EM aallen@lroc.harvard.edu NR 19 TC 1 Z9 1 U1 0 U2 0 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 1533-0346 J9 TECHNOL CANCER RES T JI Technol. Cancer Res. Treat. PD DEC PY 2008 VL 7 IS 6 BP 457 EP 461 PG 5 WC Oncology SC Oncology GA 388PR UT WOS:000262032200007 PM 19044325 ER PT J AU Bryce, CL Zickmund, S Hess, R McTigue, KM Olshansky, E Fitzgerald, K Fischer, G AF Bryce, Cindy L. Zickmund, Susan Hess, Rachel McTigue, Kathleen M. Olshansky, Ellen Fitzgerald, Katharine Fischer, Gary TI Value Versus User Fees: Perspectives of Patients Before and After Using a Web-Based Portal for Management of Diabetes SO TELEMEDICINE JOURNAL AND E-HEALTH LA English DT Article DE diabetes; user fee; access fee; patient portal; quantitative and qualitative methods ID SELF-MANAGEMENT; HEALTH RECORDS; COMMUNICATION; IMPLEMENTATION; INFORMATION AB The objective of this work was to rate the potential or actual usefulness of 15 features of a Web-based portal for diabetes management and assess whether patients would be willing to pay user fees for portal access. We used a combination of qualitative methods (focus group discussions) and quantitative methods (survey responses) to examine patients' perspectives. We enrolled 21 patients before the diabetes-specific portal was released ("preportal" group) and 18 patients after it was released ("portal-users" group). The two groups were similar except that 67% of preportal patients and 100% of portal users were Internet users. Overall, portal features that were rated most favorably were the online calculator to estimate blood glucose control (characterized as "very useful" by 74% of patients), appointment reminder systems (74%), e-mail access to health team (74%), personal tracking logs (69%), and online scheduling (69%). More patients from the preportal group than the portal-users group favored personal logs (86% versus 50%; p = 0.015) and opportunities to form interest groups (62% versus 28%; p = 0.034). Of the 30 patients who assigned a dollar amount for 1 month of portal access, 20 assigned zero dollars. Discussions about payment focused on equity and access. Because fees are expected to discourage portal usage, many patients believed that the potential benefits associated with self-management would not be realized. Others felt that the health system would benefit financially from a portal and should therefore absorb the costs. Even if portals are valued, patients may be resistant to paying for them. This opposition stems from concerns about fairness and from the recognition that health systems may experience cost savings if patients manage their diabetes successfully. C1 [Bryce, Cindy L.; Zickmund, Susan; Hess, Rachel; McTigue, Kathleen M.; Fitzgerald, Katharine; Fischer, Gary] Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. [Bryce, Cindy L.; Zickmund, Susan; Hess, Rachel; McTigue, Kathleen M.; Olshansky, Ellen; Fitzgerald, Katharine; Fischer, Gary] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. [Bryce, Cindy L.] Univ Pittsburgh, Sect Decis Sci & Clin Syst Modeling, Pittsburgh, PA 15213 USA. [Bryce, Cindy L.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15213 USA. [Zickmund, Susan] VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. [Olshansky, Ellen] Univ Calif Irvine, Coll Hlth Sci, Program Nursing Sci, Irvine, CA USA. RP Bryce, CL (reprint author), Univ Pittsburgh, Ctr Res Hlth Care, 200 Meyran Ave,Suite 200, Pittsburgh, PA 15213 USA. EM brycecl@upmc.edu OI Bryce, Cindy/0000-0001-6356-6675 FU United States Air Force [W81XWH-04-2-003]; VA Health Services Research and Development Merit Review FX Portions of this research were sponsored by funding from the United States Air Force, administered by the U. S. Army Medical Research Acquisition Activity, Fort Detrick, Maryland, Award Number W81XWH-04-2-003. Review of material does not imply Department of the Air Force endorsement of factual accuracy or opinion. Dr. Zickmund is supported by a VA Health Services Research and Development Merit Review Grant. NR 17 TC 12 Z9 12 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1530-5627 J9 TELEMED J E-HEALTH JI Telemed. J. e-Health PD DEC PY 2008 VL 14 IS 10 BP 1035 EP 1043 DI 10.1089/tmj.2008.0005 PG 9 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 394UD UT WOS:000262473600004 PM 19119825 ER PT J AU Calfee, CS Ware, LB Eisner, MD Parsons, PE Thompson, BT Wickersham, N Matthay, MA AF Calfee, C. S. Ware, L. B. Eisner, M. D. Parsons, P. E. Thompson, B. T. Wickersham, N. Matthay, M. A. CA NHLBI Ards Network TI Plasma receptor for advanced glycation end products and clinical outcomes in acute lung injury SO THORAX LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; RANDOMIZED CONTROLLED-TRIAL; TIDAL VOLUME VENTILATION; SOLUBLE RECEPTOR; I CELLS; MECHANICAL VENTILATION; TRANSPORT PROTEINS; FLUID TRANSPORT; ALVEOLAR; RAGE AB Objectives: To determine whether baseline plasma levels of the receptor for advanced glycation end products (RAGE), a novel marker of alveolar type I cell injury, are associated with the severity and outcomes of acute lung injury, and whether plasma RAGE levels are affected by lower tidal volume ventilation. Design, setting and participants: Measurement of plasma RAGE levels from 676 subjects enrolled in a large randomised controlled trial of lower tidal volume ventilation in acute lung injury. Measurements and main results: Higher baseline plasma RAGE was associated with increased severity of lung injury. In addition, higher baseline RAGE was associated with increased mortality (OR for death 1.38 (95% CI 1.13 to 1.68) per 1 log increment in RAGE; p = 0.002) and fewer ventilator free and organ failure free days in patients randomised to higher tidal volumes. These associations persisted in multivariable models that adjusted for age, gender, severity of illness and the presence of sepsis or trauma. Plasma RAGE was not associated with outcomes in the lower tidal volume group (p = 0.09 for interaction in unadjusted analysis). In both tidal volume groups, plasma RAGE levels declined over the first 3 days; however, the decline was 15% greater in the lower tidal volume group (p = 0.02; 95% CI 2.4% to 25.0%). Conclusions: Baseline plasma RAGE levels are strongly associated with clinical outcomes in patients with acute lung injury ventilated with higher tidal volumes. Lower tidal volume ventilation may be beneficial in part by decreasing injury to the alveolar epithelium. C1 [Calfee, C. S.; Eisner, M. D.; Matthay, M. A.] Univ Calif San Francisco, Div Pulm & Crit Care Med, Dept Med, San Francisco, CA 94143 USA. [Calfee, C. S.; Matthay, M. A.] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Ware, L. B.; Wickersham, N.] Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN USA. [Eisner, M. D.; Matthay, M. A.] Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. [Parsons, P. E.] Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. [Thompson, B. T.] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. [Thompson, B. T.] Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. RP Calfee, CS (reprint author), Univ Calif San Francisco, Div Pulm & Crit Care, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM carolyn.calfee@ucsf.edu FU National Heart, Lung, and Blood Institute (NHLBI) [N01-HR 46054, 46055, 46056, 46057, 46058, 46059, 46060, 46061, 46062, 46063, 46064, HL 51856, HL081332]; National Center for Research Resources [KL2RR024130]; Flight Attendant Medical Research Institute FX This work was supported by contracts (N01-HR 46054, 46055, 46056, 46057, 46058, 46059, 46060, 46061, 46062, 46063, and 46064) from the National Heart, Lung, and Blood Institute (NHLBI). MAM was supported by NHLBI Grant HL 51856. CSC was supported by KL2RR024130 from the National Center for Research Resources, a component of the NIH, and by the Flight Attendant Medical Research Institute. LBW was supported by NHLBI Grant HL081332. NR 40 TC 143 Z9 152 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0040-6376 J9 THORAX JI Thorax PD DEC PY 2008 VL 63 IS 12 BP 1083 EP 1089 DI 10.1136/thx.2008.095588 PG 7 WC Respiratory System SC Respiratory System GA 374HG UT WOS:000261033800013 PM 18566109 ER PT J AU Yeiung, A Kam, R AF Yeiung, Albert Kam, Raymond TI Ethical and Cultural Considerations in Delivering Psychiatric Diagnosis: Reconciling the Gap Using MDD Diagnosis Delivery in Less-Acculturated Chinese Patients SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE discussing psychiatric diagnoses; depression; illness beliefs; cultural sensitivity; Chinese ID NEURASTHENIA; DEPRESSION; TRANSFORMATION; PSYCHOTHERAPY; PERSPECTIVE; COMPETENCE; AMERICANS; ATTITUDES; AUTONOMY; CONTEXT AB Talking to patients from diverse cultural backgrounds about their psychiatric disorders requires knowledge of one's own culture, the patients' cultures, and the ways in which they might interact, both in positive and unexpectedly negative ways. In this paper, we discuss the issues raised by discussing psychiatric diagnoses with Chinese-Americans who hold traditional illness beliefs and are not familiar with Western conceptions of psychiatric disorders. We explore how cultural values influence this aspect of medical practice, and suggest practical approaches to communicating the diagnosis of major depressive disorder in a culturally sensitive manner. Our clinical approach is to develop co-constructed illness narratives with patients, and to aid this process by refraining different elements of the clinical process into more culturally resonant forms. The following steps are suggested: 1) elicit patient's illness beliefs; 2) understand and acknowledge multiple explanatory models; 3) contextualize depressive symptoms into patient's physical health and social system; 4) introduce Western psychiatric theories in ways that reflect assumptions shared by Traditional Chinese Medicine (TCM); 5) involve patients' families whenever possible; and 6) use terminology that avoids unintended stigma. C1 [Yeiung, Albert] Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. [Yeiung, Albert; Kam, Raymond] S Cove Community Hlth Ctr, Boston, MA USA. [Kam, Raymond] Childrens Hosp, Boston, MA 02115 USA. [Yeiung, Albert; Kam, Raymond] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Yeiung, A (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. NR 49 TC 0 Z9 0 U1 2 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 EI 1461-7471 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD DEC PY 2008 VL 45 IS 4 BP 531 EP 552 DI 10.1177/1363461508100781 PG 22 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA 393BR UT WOS:000262346400001 ER PT J AU Powers, A Stowell, CP Dzik, WH Saidman, SL Lee, H Makar, RS AF Powers, Amy Stowell, Christopher P. Dzik, Walter H. Saidman, Susan L. Lee, Hang Makar, Robert S. TI Testing only donors with a prior history of pregnancy or transfusion is a logical and cost-effective transfusion-related acute lung injury prevention strategy SO TRANSFUSION LA English DT Article ID BLOOD-DONORS; TRALI; ANTIBODIES; PLASMA; IMPACT; SENSITIZATION; ANTIGEN AB Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatality reported to the Food and Drug Administration. Donor screening may reduce TRALI risk. This study sought to compare the efficacy and safety of different TRALI risk-reduction strategies at a hospital-based donor center. Samples from 1053 donors who answered questions regarding pregnancy and transfusion history were tested for HLA Class I and II antibodies using a flow cytometry-based screening assay. Donor history was compared with the presence of HLA alloantibodies. These data were used to model several TRALI risk-reduction strategies. The medical records of patients transfused fresh-frozen plasma (FFP) from highly alloimmunized donors were retrospectively reviewed for TRALI. HLA alloimmunization was observed among 25.4 percent (256/1009) of all female donors and among 12.0 percent (3/25) of those male donors who gave a history of prior transfusion. Prior pregnancy, reported by 52.6 percent (531/1009) of females, correlated significantly with HLA alloimmunization (p < 0.0001). The rate of HLA alloimmunization increased with parity. A positive pregnancy history was a sensitive (87.9%) screen for HLA alloimmunization with a negative predictive value of 93.5 percent (95% confidence interval, 91.3%-95.7%). Although 5.9 percent (27/459) of nulliparous, untransfused females demonstrated a positive screening test, only 1 percent (7/459) had a confirmed HLA alloantibody. Transfusion of FFP from donors found retrospectively to be highly alloimmunized led to reactions suggestive of TRALI in 2 of 26 recipients. Donor history is a reliable predictor of HLA alloimmunization. Testing only donors with a prior history of pregnancy or transfusion is a logical and cost-effective TRALI prevention strategy. C1 [Makar, Robert S.] Massachusetts Gen Hosp, Blood Transfus Serv, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Histocompatibil Lab, Dept Pathol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Lab & Transfus Med, Boston, MA 02215 USA. RP Makar, RS (reprint author), Massachusetts Gen Hosp, Blood Transfus Serv, Dept Pathol, 55 Fruit St,GRJ 206C, Boston, MA 02114 USA. EM rmakar@partners.org FU Evelyn and Robert Luick Memorial Fund FX This work was supported by the Evelyn and Robert Luick Memorial Fund. The authors have no conflicts of interest to disclose. NR 34 TC 45 Z9 47 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD DEC PY 2008 VL 48 IS 12 BP 2549 EP 2558 DI 10.1111/j.1537-2995.2008.01902.x PG 10 WC Hematology SC Hematology GA 380BG UT WOS:000261439900012 PM 18717778 ER PT J AU Fehr, T Sykes, M AF Fehr, Thomas Sykes, Megan TI Clinical experience with mixed chimerism to induce transplantation tolerance SO TRANSPLANT INTERNATIONAL LA English DT Review DE bone marrow transplantation; clinical trial; mixed chimerism; myeloma; tolerance ID BONE-MARROW-TRANSPLANTATION; TOTAL LYMPHOID IRRADIATION; STEM-CELL TRANSPLANTATION; RENAL-ALLOGRAFT RECIPIENTS; ANTIGEN-SPECIFIC HYPOREACTIVITY; DONOR LIVER-TRANSPLANTATION; IDENTICAL LITTERMATE DOGS; HUMANIZED ANTI-CD2 MAB; VERSUS-HOST-DISEASE; HEMATOPOIETIC CHIMERISM AB Lymphohematopoietic chimerism was first shown to be associated with donor-specific allograft tolerance more than 60 years ago. However, early clinical experience with bone marrow transplantation soon revealed that conventional, myeloablative approaches were far too toxic and the risk of graft-versus-host disease too great to justify using this technology for the purpose of organ allograft tolerance induction in the absence of malignant disease. In this review, we discuss a step-wise approach that has been applied by several centers to establish less toxic approaches to using hematopoietic cell transplantation (HCT) for tolerance induction. These steps include (i) feasibility and efficacy data for tolerance induction in large animal models; (ii) safety data in clinical trials for patients with hematologic malignancies; and (iii) pilot trials of combined HCT and kidney transplantation for tolerance induction. Thus far, only one published trial conducted at the Massachusetts General Hospital in Boston has achieved long-term acceptance of human leukocyte antigen-mismatched kidney allografts without chronic immunosuppressive therapy. Alternative protocols have been successful in large animals, but long-term organ allograft tolerance has not been reported in patients. Thus, proof-of-principle that nonmyeloablative induction of mixed chimerism can be used intentionally to induce organ allograft tolerance has now been achieved. Directions for further research to make this approach applicable for a broader patient population are discussed. C1 [Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, Boston, MA 02129 USA. [Fehr, Thomas] Univ Zurich Hosp, Sch Med, Dept Internal Med, Clin Nephrol, CH-8091 Zurich, Switzerland. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplanta, MGH E CNY 149,13th St, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu FU NIH; NCI; NHLBI; NIAID; Juvenile Diabetes Research Foundation; Multiple Myeloma Research Foundation; Swiss Foundation for Medical and Biological; Novartis Switzerland; Walter and Gertrud Siegenthaler Foundation; University of Zurich, Switzerland FX We thank Dr Yong-Guang and Dr Toshiki Saito for critical review of this manuscript and Ms Kelly Walsh for expert assistance with the manuscript. Megan Sykes was supported by NIH grants from the NCI, NHLBI and NIAID and by grants from the Juvenile Diabetes Research Foundation and Multiple Myeloma Research Foundation. Thomas Fehr was supported by a research fellowship of the Swiss Foundation for Medical and Biological Grants (with support from Novartis Switzerland) and a research fellowship of the Walter and Gertrud Siegenthaler Foundation (Medical Faculty, University of Zurich, Switzerland). NR 95 TC 49 Z9 54 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD DEC PY 2008 VL 21 IS 12 BP 1118 EP 1135 DI 10.1111/j.1432-2277.2008.00783.x PG 18 WC Surgery; Transplantation SC Surgery; Transplantation GA 369WF UT WOS:000260723900002 PM 18954364 ER PT J AU Saidi, RF Kennealey, PT Elias, N Kawai, T Hertl, M Farrell, M Goes, N Hartono, C Tolkoff-Rubin, N Cosimi, AB Ko, DSC AF Saidi, R. F. Kennealey, P. T. Elias, N. Kawai, T. Hertl, M. Farrell, M. Goes, N. Hartono, C. Tolkoff-Rubin, N. Cosimi, A. B. Ko, D. S. C. TI Deceased Donor Kidney Transplantation in Elderly Patients: Is There a Difference in Outcomes? SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID CADAVERIC RENAL-TRANSPLANTATION; REPLACEMENT THERAPIES; AGE; OLDER; RECIPIENTS; EXPERIENCE; DIALYSIS; HEMODIALYSIS; SURVIVAL; REGISTRY AB Introduction. There is a paucity of data on long-term outcomes of older kidney recipients. Our aim was to compare the early and long-term outcomes of deceased donor kidney transplantation in patients aged >= 60 years with outcomes in younger recipients. Materials and Methods. From 1998 to 2005, we performed 271 deceased donor kidney transplants. There were 76 recepients (28.1%) >60 years old. Older candidates were carefully selected based on their physiologic, cardiac, and performance status. Demographic data, including clinical characteristics, early complications, mortality, and patient and graft survival rates, were collected and analyzed. Results. Older patients had comparable perioperative mortality and morbidity, incidence of delayed graft function (DGF), length of stay, and readmissions compared with younger patients. The rates of acute rejection and major infections were also comparable between the 2 study groups. Among older recipients, 25/76 (32.1%) patients received extended criteria donor kidneys compared with only 35/195 (17.9%) of younger patients (P <.001). Nevertheless, equivalent 1-, 3-, and 5-year allograft survival rates were observed in elderly and young patients; 91.5% versus, 92.5%, 78.5% versus 81.9%, and 75.6% versus 78.5%, respectively. Overall patient survival was also comparable in both groups. Conclusion. Kidney transplantation in appropriately selected elderly recipients provides equivalent outcomes compared with those observed in younger patients. These observations support the notion that older recipients should not lose access to deceased donor kidney transplantation in the effort to achieve a perceived gain in social utility. C1 [Saidi, R. F.; Kennealey, P. T.; Elias, N.; Kawai, T.; Hertl, M.; Farrell, M.; Cosimi, A. B.; Ko, D. S. C.] Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. [Goes, N.; Hartono, C.; Tolkoff-Rubin, N.] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. RP Ko, DSC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Blake 655,55 Fruit St, Boston, MA 02114 USA. EM dko@partners.org NR 25 TC 3 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD DEC PY 2008 VL 40 IS 10 BP 3413 EP 3417 DI 10.1016/j.transproceed.2008.08.127 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 389ZE UT WOS:000262133300029 PM 19100401 ER PT J AU Welters, HJ Kulkarni, RN AF Welters, Hannah J. Kulkarni, Rohit N. TI Wnt signaling: relevance to beta-cell biology and diabetes SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 GENE; INSULIN-SECRETION; PROTEIN INTERACTIONS; PANCREATIC-ISLETS; CATENIN PATHWAY; GROWTH; PROLIFERATION; MICE; GLUCOSE; EXPRESSION AB Interest in the importance of Wnt signaling in diabetes has risen after identification of the transcription factor TCF7L2, a component of this pathway, as a strong risk factor for type 2 diabetes. Here, we review emerging new evidence that Wnt signaling influences endocrine pancreas development and modulates mature beta-cell functions including insulin secretion, survival and proliferation. Alterations in Wnt signaling might also impact other metabolic tissues involved in the pathogenesis of diabetes, with TCF7L2 proposed to modulate adipogenesis and regulate GLP-1 production. Together, these studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, highlighting the importance of further investigation of this pathway to develop new therapies for this disease. C1 [Welters, Hannah J.] Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Welters, HJ (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM hannah.welters@joslin.harvard.edu FU NIH [RO1 DK 67536, RO1 DK 68721]; Astra Zeneca FX Funding from NIH RO1 DK 67536, NIH RO1 DK 68721 and Astra Zeneca. NR 72 TC 78 Z9 81 U1 2 U2 11 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD DEC PY 2008 VL 19 IS 10 BP 349 EP 355 DI 10.1016/j.tem.2008.08.004 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 380PM UT WOS:000261477600001 PM 18926717 ER PT J AU El Khoury, J Luster, AD AF El Khoury, Joseph Luster, Andrew D. TI Mechanisms of microglia accumulation in Alzheimer's disease: therapeutic implications SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; BETA-AMYLOID FIBRILS; BONE-MARROW; HEMATOPOIETIC-CELLS; REACTIVE MICROGLIA; SCAVENGER RECEPTOR; BLOOD MONOCYTES; MOUSE MODEL; MICE; BRAIN AB In Alzheimer's disease (AD), and other conditions affecting integrity of the blood-brain barrier, microglia can originate in the bone marrow, migrate into the blood and enter the brain in a chemokine-dependent manner. CCR2, a chemokine receptor that controls mononuclear phagocyte infiltration into the brain in multiple sclerosis, bacterial meningitis and neuropathic pain, also regulates microglia accumulation in mouse models of AD. CCR2 deficiency leads to lower microglia accumulation and higher brain beta-amyloid (A beta) levels, indicating that early microglial accumulation promotes A beta clearance. In support of this protective role, enhancing microglia accumulation delays progression of AD. AD mice that constitutively express interieukin-1 in the brain, or that are deficient in peripheral mononuclear phagocyte transforming growth factor-beta signaling, have increased microglia accumulation around beta-amyloid plaques and reduced AD-like pathology. Regulating microglia recruitment into the brain is a novel therapeutic strategy to delay or stop progression of AD. Here, we review the role of microglia in AD and the mechanisms of their accumulation and discuss implications for AD therapy. C1 [El Khoury, Joseph; Luster, Andrew D.] Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, Charlestown, MA 02129 USA. [El Khoury, Joseph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. RP El Khoury, J (reprint author), Harvard Univ, Sch Med, Ctr Immunol & Inflammatory Dis, Massachusetts Gen Hosp,Div Rheumatol Allergy & Im, 149 13th St, Charlestown, MA 02129 USA. EM jelkhoury@partners.org FU National Institute of Neurological Disorders and Stroke [NS059005, NS044973]; Dana Foundation FX This work was supported by grants NS059005 (J.E.K.) and NS044973 (A.D.L.) from the National Institute of Neurological Disorders and Stroke (www.ninds.nih.gov) and a grant from the Dana Foundation (www.dana.org) Neuro-Immunology program (J.E.K.). NR 64 TC 91 Z9 92 U1 2 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD DEC PY 2008 VL 29 IS 12 BP 626 EP 632 DI 10.1016/j.tips.2008.08.004 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 384AD UT WOS:000261714800005 PM 18835047 ER PT J AU Sartor, AO Hricak, H Wheeler, TM Coleman, J Penson, DF Carroll, PR Rubin, MA Scardino, PT AF Sartor, A. Oliver Hricak, Hedvig Wheeler, Thomas M. Coleman, Jonathan Penson, David F. Carroll, Peter R. Rubin, Mark A. Scardino, Peter T. TI Evaluating Localized Prostate Cancer and Identifying Candidates for Focal Therapy SO UROLOGY LA English DT Review ID PREDICT PATHOLOGICAL STAGE; BEAM RADIATION-THERAPY; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY; TMPRSS2-ERG FUSION TRANSCRIPTS; GUIDED TEMPLATE BIOPSY; MR-IMAGING FINDINGS; RADICAL PROSTATECTOMY; PREOPERATIVE NOMOGRAM; NEEDLE-BIOPSY; PRETREATMENT NOMOGRAM AB Can focal therapy successfully control prostate cancer? Also, if so, which patients should be considered eligible? With limited data available from relatively few patients, these questions are difficult to answer. At this writing, the most likely candidates for focal therapy are patients with low-risk, small-volume tumors, located in 1 region or sector of the prostate, who would benefit from early intervention. The difficulty lies in reliably identifying these men. The larger number of cores obtained in each needle biopsy session has increased both the detection of prostate cancer and the potential risk of overtreating many patients whose cancers pose very little risk to life or health. Urologists typically perform at least a 12-core template biopsy. Although the debate continues about the optimal template, laterally and peripherally directed biopsies have been shown to improve the diagnostic yield. However, as many as 25% of tumors arise anteriorly and can be missed with peripherally directed techniques. Prostate cancer tends to be multifocal, even in its earliest stages. However, the secondary cancers are usually smaller and less aggressive than the index cancer. They appear similar to the incidental cancers found in cystoprostatectomy specimens and appear to have little effect on prognosis in surgical series. When a single focus of cancer is found in I core, physicians rightly suspect that more foci of cancer are present in the prostate. Assessing the risk in these patients is challenging when determined by the biopsy data alone. To predict the presence of a very low-risk or "indolent" cancer, nomograms have been developed to incorporate clinical stage, Gleason grade, prostate-specific antigen levels, and prostate volume, along with the quantitative analysis of the biopsy results. Transperineal "mapping" or "saturation" biopsies have been advocated to detect cancers missed or underestimated by previous transrectal biopsies. This approach could provide the accurate staging, grading, and tumor localization needed for a focal therapy program. Nevertheless, for men with minimal cancer who are amenable to active surveillance or focal therapy, consensus about the most accurate biopsy strategy has not yet been reached. Imaging, particularly magnetic resonance imaging and magnetic resonance spectroscopic imaging, has been used to assess men with early-stage prostate cancer. Large-volume cancers can be seen reasonably well, but small lesions have been difficult to detect reliably or measure accurately. Factors such as voxel resolution, organ movement, biopsy artifact, and benign changes have limited the consistent estimation of the quantitative tumor volume. Nevertheless, magnetic resonance imaging and magnetic resonance spectroscopic imaging can aid in evaluating patients with prostate cancer being considered for focal therapy by providing additional evidence that the patient does not harbor an otherwise undetected high-risk, aggressive cancer. In some cases, imaging can usefully identify the location of even a limited-sized index cancer. When imaging findings are substantiated by mapping biopsy results, confidence in the accurate characterization of the cancer is enhanced. Correlating the imaging results with tissue changes during and after treatment can be of use in monitoring the ablative effects in the prostate and in assessing for tumor recurrence. More work is necessary before staging studies can uniformly characterize a prostate cancer before therapy, much less reliably identify and locate small-volume cancer within the prostate. However, exploring the role of focal ablation as a therapeutic option for selected men with low-risk, clinically localized, prostate cancer need not await the emergence of perfectly accurate staging studies, any more than the application of radical surgery or radiotherapy have. Modern biopsy strategies, combined with optimal imaging and nomograms to estimate the pathologic stage and risk, taken together, provide a sound basis for the selection of appropriate patients for entry into prospective clinical trials of focal therapy. UROLOGY 72 (Suppl 6A): 12-24, 2008. (C) 2008 Published by Elsevier Inc. C1 [Sartor, A. Oliver] Harvard Univ, Sch Med, Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol,Dept Med, Boston, MA 02115 USA. [Hricak, Hedvig; Scardino, Peter T.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wheeler, Thomas M.] Baylor Coll Med, Houston, TX 77030 USA. [Penson, David F.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Carroll, Peter R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Rubin, Mark A.] Weill Cornell Med Ctr, New York, NY USA. RP Sartor, AO (reprint author), Tulane Canc Ctr, Dept Med, New Orleans, LA 70115 USA. EM osartor@tulane.edu OI Hricak, Hedvig/0000-0003-2240-9694; Rubin, Mark/0000-0002-8321-9950; Coleman, Jonathan/0000-0002-6428-7835 FU Steba Biotech FX The members of the International Task Force on Prostate Cancer and the Focal Lesion Paradigm are particularly indebted to the following people for their guidance and support: Pierre Dussault, Aurelie Hubert, Stephanie Adam, and Karyn Wagner from the task force scientific support team in Montreal, Canada. We are grateful to the following people for their scientific contributions: Fernando J. Bianco, MD, of The George Washington University Cancer Institute, Washington, DC, USA; Mark Einberton, MD, of University College London, London, United Kingdom; Avigdor Scherz, PhD, of the Weizmann Institute of Science, Rehovot, Israel; and John Trachtenberg, MD, of Princess Margaret Hospital, University Health Network, Toronto, Canada. We would also like to thank the medical editors from Memorial Sloan-Kettering Cancer Center, New York, NY, USA, for bibliographic, editorial, and writing assistance: Susan Aiello, DVM, ELS; Melissa Bogen, ELS; Barbara Kristaponis; Hope J. Lafferty, ELS; Michael McGregor, MA; Peggy McPartland; and Jennifer Swartz-Turfle. The task force was made possible in part with financial support from Steba Biotech. NR 109 TC 60 Z9 67 U1 0 U2 4 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 DEC PY 2008 VL 72 IS 6A BP 12 EP 24 DI 10.1016/j.urology.2008.10.004 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 389VE UT WOS:000262121800003 PM 19095124 ER PT J AU Hu, JC Kwan, L Krupski, TL Anger, JT Maliski, SL Connor, S Litwin, MS AF Hu, Jim C. Kwan, Lorna Krupski, Tracey L. Anger, Jennifer T. Maliski, Sally L. Connor, Sarah Litwin, Mark S. TI Determinants of Treatment Regret in Low-Income, Uninsured Men With Prostate Cancer SO UROLOGY LA English DT Article ID QUALITY-OF-LIFE; MEMORIAL ANXIETY SCALE; RADICAL PROSTATECTOMY; TREATMENT DECISIONS; MAX-PC; VALIDITY; RELIABILITY; UNCERTAINTY; RECURRENCE; CAPSURE AB OBJECTIVES The regret of a prostate cancer treatment choice, a significant dimension of health-related quality of life, has not been well-characterized. Little is known about its association with the fear of cancer recurrence or spirituality. METHODS We drew subjects from a men's health study composed of a clinically heterogeneous sample of subjects enrolled from a statewide, publicly funded assistance program that provided free prostate cancer treatment for uninsured, low-income men in California. We included men who completed a telephone interviews and self-administered questionnaires at Study enrollment and at 6 months of follow-up. Using validated instruments, we measured regret, health-related quality of life, fear of cancer recurrence, and spirituality through telephone interviews and self-administered questionnaires. RESULTS Of the 195 men, 90 underwent radical prostatectomy (46%), 50 underwent external beam radiotherapy (28%), and 51 underwent hormonal therapy (26%). Of these 195 men, 36 (18%) regretted their treatment choice. Multivariate analyses revealed that nonwhite men were more likely than white men to experience decisional regret (odds ratio [OR] range 7.27 to 12.26). Conversely, men confident of cancer cure (OR 0.19, 95% confident interval 0.04 to 0.86), rnen with greater spirituality (OR 0.91, 95% confidence interval 0.87 to 0.96), and men with acute treatment effects (OR 0.34, 95% confidence interval 0.12 to 0.93) were less likely to regret their treatment decisions. CONCLUSIONS In Our study, a fear of cancer recurrence, less spirituality, a longer interval since treatment, and nonwhite race were associated with treatment regret in low-income, underserved men with prostate cancer. Attempts to decrease anxiety and enhance spirituality in men treated for prostate cancer might diminish treatment regret. Additional Studies in racially diverse cohorts are needed to examine the association of regret with race. UROLOGY 72: 1274-1279, 2008. (C) 2008 Elsevier Inc. C1 [Hu, Jim C.] Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Urol, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, Boston, MA 02115 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Duke Univ, Sch Med, Div Urol, Durham, NC USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Hu, JC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Div Urol, Dana Farber Canc Inst,Lank Ctr Genitourinary Onco, 45 Francis St,ASBII-3, Boston, MA 02115 USA. EM jhu2@partners.org FU California Department of Health Services Cancer Detection Section FX This study was supported by an award from the California Department of Health Services Cancer Detection Section. NR 25 TC 21 Z9 21 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 DEC PY 2008 VL 72 IS 6 BP 1274 EP 1279 DI 10.1016/j.urology.2007.11.066 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 389VB UT WOS:000262121500020 PM 18313115 ER PT J AU Armstrong, D Lipsky, B Boulton, A AF Armstrong, David Lipsky, Benjamin Boulton, Andrew TI A Closer Look At The Prevalence Of MRSA And Its Impact On Empiric Therapy SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article C1 [Armstrong, David] Univ Arizona, Coll Med, SALSA, Tucson, AZ 85721 USA. [Boulton, Andrew] Univ Manchester, Manchester M13 9PL, Lancs, England. Coatesville Vet Affairs Med Ctr, Coatesville, PA USA. Roxborough Mem Hosp, Philadelphia, PA USA. [Lipsky, Benjamin] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Lipsky, Benjamin] Gen Internal Med Clin, Seattle, WA USA. [Lipsky, Benjamin] Vet Affairs Puget Sound Hlth Care Syst, Antibiot Res Clin, Seattle, WA USA. RP Armstrong, D (reprint author), Univ Arizona, Coll Med, SALSA, Tucson, AZ 85721 USA. RI Lipsky, Benjamin/B-4645-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD DEC PY 2008 BP 5 EP 10 PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 393EI UT WOS:000262353300001 ER PT J AU Armstrong Boulton Rogers Lipsky AF Dr Armstrong Dr Boulton Dr Rogers Dr Lipsky TI A Guide To Current MRSA Treatment Options SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Article C1 [Dr Armstrong] Univ Arizona, Coll Med, SALSA, Tucson, AZ 85721 USA. [Dr Boulton] Univ Manchester, Manchester M13 9PL, Lancs, England. Roxborough Mem Hosp, Philadelphia, PA USA. Coatesville Vet Affairs Med Ctr, Coatesville, PA USA. [Dr Lipsky] Univ Washington, Sch Med, Seattle, WA 98195 USA. [Dr Lipsky] Gen Internal Med Clin, Seattle, WA USA. [Dr Lipsky] Vet Affairs Puget Sound Hlth Care Syst, Antibiot Res Clin, Seattle, WA USA. [Dr Rogers] Broadlawns Med Ctr, Amputat Prevent Ctr, Des Moines, IA USA. RP Armstrong (reprint author), Univ Arizona, Coll Med, SALSA, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD DEC PY 2008 BP 11 EP 17 PG 7 WC Dermatology; Surgery SC Dermatology; Surgery GA 393EI UT WOS:000262353300002 ER PT J AU Ceol, CJ Houvras, Y White, RM Zon, LI AF Ceol, Craig J. Houvras, Yariv White, Richard M. Zon, Leonard I. TI Melanoma Biology and the Promise of Zebrafish SO ZEBRAFISH LA English DT Review ID ENDOTHELIN-B RECEPTOR; C-KIT PROTOONCOGENE; NEURAL-CREST; TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; WAARDENBURG-SYNDROME; CUTANEOUS MELANOMA; IN-VIVO; METASTATIC MELANOMA; GENE-EXPRESSION AB Advantageous organismal and technical attributes of the zebrafish are being increasingly applied to study cancer biology. Along with other tumor models, zebrafish that develop melanomas have been generated. In both genetics and phenotype, zebrafish melanomas are strikingly similar to their human counterparts. For this reason, studies in the zebrafish are poised to make significant contributions to melanoma biology. In this review, we summarize important features of human melanoma and discuss how the zebrafish can be used to address many questions that remain unanswered about this devastating disease. C1 [Zon, Leonard I.] Childrens Hosp, Karp Res Labs, Stem Cell Program, Boston, MA 02115 USA. [Ceol, Craig J.; Houvras, Yariv; White, Richard M.; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Ceol, Craig J.; Houvras, Yariv; White, Richard M.; Zon, Leonard I.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst,Howard Hughes Med Inst, Boston, MA 02115 USA. [Houvras, Yariv] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Zon, LI (reprint author), Childrens Hosp, Karp Res Labs, Stem Cell Program, 300 Longwood Ave,7th Floor, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU Charles A. King Trust Postdoctoral Fellowship; Bank of America; National Institutes of Health [K08-DK075432, R01-DK53298-08]; American Society for Clinical Oncology Young Investigator Award; Aid for Cancer Research Fellowship FX We are grateful to members of the Zon laboratory, especially Michael Dovey, for helpful discussions. C.J.C. is supported by a Charles A. King Trust Postdoctoral Fellowship, Bank of America, Co-Trustee; Y.H. by a National Institutes of Health K08 award (K08-DK075432); and R.M.W. by an American Society for Clinical Oncology Young Investigator Award and an Aid for Cancer Research Fellowship. Melanoma research by L.I.Z. is funded by NIH Grant R01-DK53298-08. NR 101 TC 17 Z9 20 U1 0 U2 8 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 EI 1557-8542 J9 ZEBRAFISH JI Zebrafish PD DEC PY 2008 VL 5 IS 4 BP 247 EP 255 DI 10.1089/zeb.2008.0544 PG 9 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA 396QE UT WOS:000262605400004 PM 19133823 ER PT J AU Sessa, AK White, R Houvras, Y Burke, C Pugach, E Baker, B Gilbert, R Look, AT Zon, LI AF Sessa, Anna K. White, Richard Houvras, Yariv Burke, Christopher Pugach, Emily Baker, Barry Gilbert, Rharaka Look, A. Thomas Zon, Leonard I. TI The Effect of a Depth Gradient on the Mating Behavior, Oviposition Site Preference, and Embryo Production in the Zebrafish, Danio rerio SO Zebrafish LA English DT Article ID REPRODUCTION AB Captive zebrafish (Danio rerio) exhibit a limited repertoire of mating behaviors, likely due to the somewhat unnatural environment of aquaria. Observations in their natural habitat led us to believe that a depth gradient within the mating setup would positively affect fish mating. By tilting the tank to produce a depth gradient, we observed novel behaviors along with a preference for oviposition in the shallow area. Although we did not see an increase in the likelihood of a pair of fish to mate, we did see an increase in the embryo output in both adults and juveniles. In the adults, tilting led to a significant increase in embryo production (436 +/- 35 tilted vs. 362 +/- 34 untilted; p < 0.05). A similar effect was seen in juvenile fish as they progressed through sexual maturity. These results suggest that tilting of mating cages in the laboratory setting will lead to demonstrable improvements in embryo production for zebrafish researchers, and highlights the possibility of other manipulations to increase fecundity. C1 [Sessa, Anna K.; White, Richard; Houvras, Yariv; Burke, Christopher; Pugach, Emily; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [White, Richard; Baker, Barry; Gilbert, Rharaka; Look, A. Thomas; Zon, Leonard I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [White, Richard; Zon, Leonard I.] Harvard Univ, Sch Med, Boston, MA USA. [Houvras, Yariv] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Zon, LI (reprint author), Karp Family Res Labs, 300 Longwood Ave,Room 7211, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NIDDK NIH HHS [P30 DK049216-139002, P30 DK049216] NR 17 TC 12 Z9 12 U1 1 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PD DEC PY 2008 VL 5 IS 4 BP 335 EP 339 DI 10.1089/zeb.2008.0535 PG 5 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA 396QE UT WOS:000262605400013 PM 19133832 ER PT J AU Weiner, DK Perera, S Rudy, TE Glick, RM Shenoy, S Delitto, A AF Weiner, Debra K. Perera, Subashan Rudy, Thomas E. Glick, Ronald M. Shenoy, Sonali Delitto, Anthony TI Efficacy of percutaneous electrical nerve stimulation and therapeutic exercise for older adults with chronic low back pain: A randomized controlled trial SO PAIN LA English DT Article DE Chronic low back pain; Older adults; Percutaneous electrical nerve stimulation; Exercise ID SELF-RATED HEALTH; LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; FOLLOW-UP; NEUROPSYCHOLOGICAL PERFORMANCE; SUBSEQUENT DISABILITY; BODY-COMPOSITION; FITNESS PROGRAM; ACUPUNCTURE; SCALE AB Chronic low back pain (CLBP) in older adults may be disabling and therapeutically challenging, largely because of the inefficacy and/or morbidity associated with traditional pain treatment. We conducted a randomized controlled trial in 200 men and women >= age 65 with CLBP to evaluate the efficacy of percutaneous electrical nerve stimulation (PENS) with and without general conditioning and aerobic exercise (GCAE), for reducing pain and improving physical function. Participants were randomized to receive (1) PENS, (2) control-PENS (brief electrical stimulation to control for treatment expectancy), (3) PENS + GCAE, or (4) control-PENS + GCAE, twice a week for 6 weeks. All (Our groups experienced significantly reduced pain (range -2.3 to -4.1 on the McGill Pain Questionnaire short form), improved self-reported disability (range -2.1 to -3.0 on Roland scale) and improved gait velocity (0.04-0.07 m/s), Sustained at 6 months. The GCAE groups experienced significantly fewer fear avoidance beliefs immediately post-intervention and at 6 months than non-GCAE groups. There were no significant side effects. Since brief electrical stimulation (i.e., control-PENS) facilitated comparably reduced pain and improved function at 6 months as compared with PENS, the exact dose of electrical stimulation required for analgesia cannot be determined. GCAE was more effective than PENS alone in reducing fear avoidance beliefs, but not in reducing pain or in improving physical function. Published by Elsevier B.V. on behalf of International Association For the Study of Pain. C1 [Weiner, Debra K.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15213 USA. [Weiner, Debra K.; Perera, Subashan] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Weiner, Debra K.; Rudy, Thomas E.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA 15260 USA. [Weiner, Debra K.; Rudy, Thomas E.; Glick, Ronald M.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. [Perera, Subashan; Rudy, Thomas E.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. [Glick, Ronald M.] Univ Pittsburgh, Ctr Integrat Med, Pittsburgh, PA 15260 USA. [Shenoy, Sonali; Delitto, Anthony] Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA 15260 USA. RP Weiner, DK (reprint author), VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM dweiner@pitt.edu RI Perera, Subashan/D-7603-2014 FU National Center [R01 AT000985]; National Institute on Aging; National Institutes of Health; Older Americans Independence Center [NIA P30 AG-024827] FX This work was supported in by Grant R01 AT000985 from the National Center for Complementary and Alternative Medicine and the National Institute on Aging, National Institutes of Health. Dr. Percra was also supported by the Pittsburgh Claude D. Pepper Older Americans Independence Center (NIA P30 AG-024827). NR 71 TC 16 Z9 20 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD NOV 30 PY 2008 VL 140 IS 2 BP 344 EP 357 DI 10.1016/j.pain.2008.09.005 PG 14 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 381QT UT WOS:000261551700011 PM 18930352 ER PT J AU Wynn, JK Green, MF Engel, S Korb, A Lee, J Glahn, D Nuechterlein, KH Cohen, MS AF Wynn, Jonathan K. Green, Michael F. Engel, Stephen Korb, Alex Lee, Junghee Glahn, David Nuechterlein, Keith H. Cohen, Mark S. TI Increased extent of object-selective cortex in schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE Schizophrenia; visual processing; functional MRI; object processing ID HUMAN VISUAL-CORTEX; BRAIN; RECOGNITION; AREAS; FMRI; REGISTRATION; DYSFUNCTION; ACTIVATION; RELATIVES; ACCURATE AB Schizophrenia patients exhibit deficits in various stages of visual information processing. Despite recent informative efforts to examine visual processing in schizophrenia with functional magnetic resonance imaging (fMRI), much remains unknown about the basic function, structure, and organization of key early visual processing areas in schizophrenia. This study examined magnitude and topography of regional brain activity in three early visual processing areas: early retinotopically organized areas (V1-V4), motion-sensitive areas (human area MT, hMT+), and object-recognition areas (lateral occipital complex, LO). Using visual stimuli that are known to preferentially activate each respective region, we compared responses in these areas in 22 schizophrenia patients and 19 normal controls. Activity in all three regions was of similar amplitude in schizophrenia patients and normal controls. Activity in retinotopically organized areas and hMT+ showed good spatial overlap between groups. However, activation of LO was more widely distributed in patients compared with normal controls. The findings of abnormal spatial organization of LO in schizophrenia patients may converge with behavioral evidence of deficits in schizophrenia patients for object-recognition tasks that are believed to be mediated by LO activity. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Wynn, Jonathan K.; Green, Michael F.; Lee, Junghee] VA Greater Los Angeles Healthcare Syst, MIRECC, Los Angeles, CA 90073 USA. [Wynn, Jonathan K.; Green, Michael F.; Korb, Alex; Lee, Junghee; Nuechterlein, Keith H.; Cohen, Mark S.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Engel, Stephen; Nuechterlein, Keith H.; Cohen, Mark S.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. [Glahn, David] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. RP Wynn, JK (reprint author), VA Greater Los Angeles Healthcare Syst, MIRECC, Bldg 210,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jkwynn@ucla.edu RI Wynn, Jonathan/H-3749-2014; Cohen, Mark/C-6610-2011; Lee, Junghee/C-5226-2014 OI Wynn, Jonathan/0000-0002-1763-8540; Cohen, Mark/0000-0001-6731-4053; Lee, Junghee/0000-0001-9567-8700 FU NIMH [MH43292, MH065707]; Brain Mapping Medical Research Organization; Brain Mapping Support Foundation; Pierson-Lovelace Foundation; Ahmanson Foundation; William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation; Tamkin Foundation; Jennifer Jones-Simon Foundation; Capital Group Companies Charitable Foundation; Robson Family; Northstar Fund FX Support for this study came from NIMH Grant MH43292 (PI: Michael F. Green, Ph.D) and NIMH Grant MH065707 (PI: Michael F. Green, Ph.D.). For generous support, we also thank the Brain Mapping Medical Research Organization, Brain Mapping Support Foundation, Pierson-Lovelace Foundation, The Ahmanson Foundation, William M. and Linda R. Dietel Philanthropic Fund at the Northern Piedmont Community Foundation, Tamkin Foundation, Jennifer Jones-Simon Foundation, Capital Group Companies Charitable Foundation, Robson Family, and Northstar Fund. The authors thank Poorang Nori and Alisa Malin for assistance in data collection. NR 39 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD NOV 30 PY 2008 VL 164 IS 2 BP 97 EP 105 DI 10.1016/j.pscychresns.2008.01.005 PG 9 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 381QS UT WOS:000261551600001 PM 18938066 ER PT J AU Ruan, PK Gray, RJ AF Ruan, Ping K. Gray, Robert J. TI Analyses of cumulative incidence functions via non-parametric multiple imputation SO STATISTICS IN MEDICINE LA English DT Article DE censoring complete data; competing risks; missing data; multiple imputation; partial likelihood estimation; penalized spline ID PROPORTIONAL HAZARDS MODEL; CENSORED REGRESSION DATA; SURVIVAL ANALYSIS; COMPETING RISK; AUXILIARY VARIABLES; SUBDISTRIBUTION; SPLINES; TESTS AB We describe a non-parametric multiple imputation method that recovers the missing potential censoring information from competing risks failure times for the analysis of cumulative incidence functions. The method can be applied in the settings of stratified analyses, time-varying covariates, weighted analysis of case-cohort samples and clustered survival data analysis, where no current available methods can be readily implemented. The method uses a Kaplan-Meier imputation method for the censoring times to form an imputed data set, SO Cumulative incidence can be analyzed using techniques and software developed for ordinary right censored survival data. We discuss the methodology and show from both simulations and real data examples that the method yields valid estimates and performs well. The method can be easily implemented via available software with a minor programming requirement (for the imputation step). It provides a practical, alternative analysis tool for otherwise complicated analyses of cumulative incidence of competing risks data. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Ruan, Ping K.] Harvard Univ, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Ruan, Ping K.] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Gray, Robert J.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Ruan, PK (reprint author), Harvard Univ, Ctr Biostat AIDS Res, 655 Huntington Ave, Boston, MA 02115 USA. EM pkruan@sdac.harvard.edu NR 26 TC 29 Z9 29 U1 0 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 29 PY 2008 VL 27 IS 27 BP 5709 EP 5724 DI 10.1002/sim.3402 PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 372MP UT WOS:000260906000010 PM 18712779 ER PT J AU Casas, A Di Venosa, G Vanzulli, S Perotti, C Mamome, L Rodriguez, L Simian, M Juarranz, A Pontiggia, O Hasan, T Batlle, A AF Casas, Adriana Di Venosa, Gabriela Vanzulli, Silvia Perotti, Christian Mamome, Leandro Rodriguez, Lorena Simian, Marina Juarranz, Angeles Pontiggia, Osvaldo Hasan, Tayyaba Batlle, Alcira TI Decreased metastatic phenotype in cells resistant to aminolevulinic acid-photodynamic therapy SO CANCER LETTERS LA English DT Article DE Photodynamic therapy; Aminolevulinic acid; Metastasis; Invasion; Adhesion ID MAMMARY ADENOCARCINOMA CELLS; 5-AMINOLEVULINIC ACID; PROSTATE-CANCER; EXTRACELLULAR-MATRIX; GLIOMA-CELLS; IN-VITRO; TUMOR; ADHESION; MODEL; FLUORESCENCE AB Photodynamic therapy (PDT) is a novel cancer treatment utilising a photosensitiser, visible light and oxygen. PDT often leaves a significant number of surviving tumour cells. In a previous work, we isolated and studied two PDT resistant clones derived from the mammary adenocarcinoma LM3 line (Int. J. Oncol. 29 (2006) 397-405). The isolated Clon 4 and Clon 8 exhibited a more fibroblastic, dendritic pattern and were larger than the parentals. In the present work we studied the metastatic potential of the two clones in comparison with LM3. We found that 100% of LM3 invaded Matrigel, whereas only 19 +/- 6% and 24 +/- 7% of Clon 4 and Clon 8 cells invaded. In addition, 100% of LM3 cells migrated towards a chemotactic stimulus whereas 38 +/- 8% and 73 +/- 10% of Clones 4 and 8, respectively, were able to migrate. In vivo, 100% of the LM3 injected mice developed spontaneous lung metastasis, whereas none of the Clon 8 did, and only one of the mice injected with Clon 4 did. No differences were found in the proteolytic enzyme profiles among the cells. Anchorage-dependent adhesion was also impaired in vivo in the resistant clones, evidenced by the lower tumour take, latency time and growth rates, although both clones showed in vitro higher binding to collagen I without overexpression of beta 1 integrin. This is the first work where the metastatic potential of cells surviving to PDT has been studied. PDT strongly affects the invasive phenotype of these cells, probably related to a higher binding to collagen. These findings may be crucial for the outcome of ALA-PDT of metastatic tumours, although further studies are needed to extrapolate the results to the clinic employing another photosensitisers and cell types. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Casas, Adriana; Di Venosa, Gabriela; Perotti, Christian; Mamome, Leandro; Rodriguez, Lorena; Batlle, Alcira] Univ Buenos Aires, CONICET, CIPYP, Buenos Aires, DF, Argentina. [Casas, Adriana; Di Venosa, Gabriela; Perotti, Christian; Mamome, Leandro; Rodriguez, Lorena; Batlle, Alcira] Univ Buenos Aires, Hosp Clin Jose de San Martin, Buenos Aires, DF, Argentina. [Vanzulli, Silvia] Acad Nacl Med Buenos Aires, Inst Estudios Oncol, RA-3092 Buenos Aires, DF, Argentina. [Simian, Marina; Pontiggia, Osvaldo] Inst Angel H Roffo, RA-5481 Buenos Aires, DF, Argentina. [Juarranz, Angeles] Univ Autonoma Madrid, Fac Ciencias, Dept Biol, E-28049 Madrid, Spain. [Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed WEL 224, Boston, MA 02114 USA. RP Casas, A (reprint author), Univ Buenos Aires, CONICET, CIPYP, Viamonte 1881,10 A,1056 Ciudad Buenos Aires,Cordo, Buenos Aires, DF, Argentina. EM adriana@qb.fcen.uba.ar RI Juarranz, Angeles/L-2446-2013 OI Juarranz, Angeles/0000-0002-6574-2887 FU National Cancer Center [PO1 CA84203]; National Institutes for Health [RO1 AR040352, PO1 CA084203]; Department of Defense [FA 9550-04-1-0079]; Argentine National Research Council; CONICET [PIP 4108/96, 5263/05, 105508/99-00]; Bunge y Born Foundation and Jorge Oster Argentina FX This research was funded by grants from the National Cancer Center PO1 CA84203, the National Institutes for Health RO1 AR040352, the Department of Defense FA 9550-04-1-0079, and the Argentine National Research Council (CONICET) (PIP 4108/96, 5263/05 and 105508/99-00). During the writing of this article, support to the authors was provided by National Institute of Health Grants PO1 CA084203 and RO1 AR040352. A.C. thanks Bunge y Born Foundation and Jorge Oster Argentina for financial support. NR 66 TC 19 Z9 19 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 28 PY 2008 VL 271 IS 2 BP 342 EP 351 DI 10.1016/j.canlet.2008.06.023 PG 10 WC Oncology SC Oncology GA 373YV UT WOS:000261010300017 PM 18662847 ER PT J AU Oberdoerffer, P Michan, S Mcvay, M Mostoslavsky, R Vann, J Park, SK Hartlerode, A Stegmuller, J Hafner, A Loerch, P Wright, SM Mills, KD Bonni, A Yankner, BA Scully, R Prolla, TA Alt, FW Sinclair, DA AF Oberdoerffer, Philipp Michan, Shaday Mcvay, Michael Mostoslavsky, Raul Vann, James Park, Sang-Kyu Hartlerode, Andrea Stegmuller, Judith Hafner, Angela Loerch, Patrick Wright, Sarah M. Mills, Kevin D. Bonni, Azad Yankner, Bruce A. Scully, Ralph Prolla, Tomas A. Alt, Frederick W. Sinclair, David A. TI SIRT1 Redistribution on Chromatin Promotes Genomic Stability but Alters Gene Expression during Aging SO CELL LA English DT Article ID DOUBLE-STRAND BREAKS; EMBRYONIC STEM-CELLS; SACCHAROMYCES-CEREVISIAE; LIFE-SPAN; DNA-DAMAGE; HISTONE H2AX; HETEROCHROMATIN FORMATION; CELLULAR SENESCENCE; GENOTOXIC STRESS; MATING-TYPE AB Genomic instability and alterations in gene expression are hallmarks of eukaryotic aging. The yeast histone deacetylase Sir2 silences transcription and stabilizes repetitive DNA, but during aging or in response to a DNA break, the Sir complex relocalizes to sites of genomic instability, resulting in the desilencing of genes that cause sterility, a characteristic of yeast aging. Using embryonic stem cells, we show that mammalian Sir2, SIRT1, represses repetitive DNA and a functionally diverse set of genes across the mouse genome. In response to DNA damage, SIRT1 dissociates from these loci and relocalizes to DNA breaks to promote repair, resulting in transcriptional changes that parallel those in the aging mouse brain. Increased SIRT1 expression promotes survival in a mouse model of genomic instability and suppresses age-dependent transcriptional changes. Thus, DNA damage-induced redistribution of SIRT1 and other chromatin-modifying proteins may be a conserved mechanism of aging in eukaryotes. C1 [Oberdoerffer, Philipp; Michan, Shaday; Mcvay, Michael; Stegmuller, Judith; Hafner, Angela; Loerch, Patrick; Bonni, Azad; Yankner, Bruce A.; Sinclair, David A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Oberdoerffer, Philipp; Michan, Shaday; Mcvay, Michael; Stegmuller, Judith; Hafner, Angela; Loerch, Patrick; Bonni, Azad; Yankner, Bruce A.; Sinclair, David A.] Harvard Univ, Sch Med, Glenn Labs Aging Res, Boston, MA 02115 USA. [Mostoslavsky, Raul] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Vann, James; Park, Sang-Kyu; Prolla, Tomas A.] Univ Wisconsin, Dept Genet & Med Genet, Madison, WI 53706 USA. [Hartlerode, Andrea; Scully, Ralph] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Hartlerode, Andrea; Scully, Ralph] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Wright, Sarah M.; Mills, Kevin D.] Jackson Lab, Bar Harbor, ME 04609 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Childrens Hosp,Immune Dis Inst, Boston, MA 02115 USA. [Alt, Frederick W.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM david_sinclair@hms.harvard.edu RI Scully, Ralph/F-5008-2013; OI Sinclair, David/0000-0002-9936-436X FU National Space Biomedical Research Institute [PF00903]; National Institutes of Health [NIH] [RO1GM068072, R01AG19719, NS047188, GM 073894, R01AG 020681]; Glenn Foundation for Medical Research FX D. A. S. wishes to thank B. Stillman and C. Westphal for advice and scientific discussions. We are also grateful to K. Rajewsky, D. Reinberg, D. Lamming, L. Guarente, A. Vaquero, and M. Jasin for advice and reagents. We thank E. Vollmann, J. Campbell, and D. Zimmerman for technical assistance and R. Bronson for mouse necropsy. We are especially grateful to P. Glenn, M. Collins, and L. Ellison for their support of aging research. P. O. was supported by a fellowship from the National Space Biomedical Research Institute (grant PF00903), the Sinclair Lab by grants RO1GM068072 and R01AG19719 (National Institutes of Health [NIH]), and the Glenn Foundation for Medical Research. D. A. S. and F. W. A. are Ellison Medical Foundation Senior Scholars. R. M. is a V and Kimmel Foundation Scholar. A. B. supported by NIH grant NS047188; R. S. by GM 073894; and J. V., S. P., and T. A. P. by R01AG 020681. F. W. A. is an Investigator of the Howard Hughes Medical Institute. D. A. S. is a consultant to Shaklee, Genocea, and Sirtris (a GSK company developing sirtuin-based drugs) and an inventor on Harvard patents licensed to GSK. NR 70 TC 389 Z9 403 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 28 PY 2008 VL 135 IS 5 BP 907 EP 918 DI 10.1016/j.cell.2008.10.025 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 376LA UT WOS:000261183900021 PM 19041753 ER PT J AU Araujo, P Nguyen, TT Froyland, L Wang, JD Kang, JX AF Araujo, Pedro Nguyen, Thu-Thao Froyland, Livar Wang, Jingdong Kang, Jing X. TI Evaluation of a rapid method for the quantitative analysis of fatty acids in various matrices SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Methylation; Methylation models; Gas chromatography; High performance thin layer chromatography ID METHYLATION; CHOLESTEROL; LIVER AB A simplified method for quantitative analysis of fatty acids in various matrices by gas chromatography is proposed as an alternative to the conventional method and the variables of the protocol examined to optimize the processing conditions. The modified method involves direct methylation of fatty acids in homogenized samples with boron trihalide (BF(3) or BCl(3) in methanol) followed by extraction with hexane. The addition of hexane to the reaction mixture after the methylation process can enhance the efficiency of fatty acid methylation and is critical for those samples that contain high levels of triglycerides. A mechanism underlying this effect is proposed. (C) 2008 Elsevier B.V. All rights reserved. C1 [Araujo, Pedro; Nguyen, Thu-Thao; Froyland, Livar] Natl Inst Nutr & Seafood Res NIFES, N-5817 Bergen, Norway. [Wang, Jingdong; Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Wang, Jingdong; Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Araujo, P (reprint author), Natl Inst Nutr & Seafood Res NIFES, POB 2029 Nordnes, N-5817 Bergen, Norway. EM pedro.araujo@nifes.no FU NIH [R01CA113605] FX This study was partially Supported by the NIH grant (R01CA113605) (J.X.K.). NR 17 TC 40 Z9 42 U1 1 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 28 PY 2008 VL 1212 IS 1-2 BP 106 EP 113 DI 10.1016/j.chroma.2008.10.006 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 377TF UT WOS:000261272800015 PM 18937951 ER PT J AU Smith, ER Loeffler, J Misra, M Pomerantz, SR Stemmer-Rachamimov, A Post, MD Harris, NL McKenna, M AF Smith, Edward R. Loeffler, Jay Misra, Madhusmita Pomerantz, Stuart R. Stemmer-Rachamimov, Anat Post, Miriam D. Harris, Nancy Lee McKenna, Michael TI A Boy with a Pituitary Tumor and Skull Abnormalities Pituitary adenoma, prolactin secreting, with atypical features and a high proliferation fraction. Osteoblastoma of the skull SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VALVULAR HEART-DISEASE; TRICUSPID REGURGITATION; MEDICAL THERAPY; CABERGOLINE; ADOLESCENTS; CHILDREN; HEADACHE; LESIONS; BROMOCRIPTINE; AMENORRHEA C1 [Smith, Edward R.] Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Loeffler, Jay] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Misra, Madhusmita] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stemmer-Rachamimov, Anat; Post, Miriam D.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Smith, Edward R.] Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. [Loeffler, Jay] Harvard Univ, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. [Misra, Madhusmita] Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. [Pomerantz, Stuart R.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Stemmer-Rachamimov, Anat; Post, Miriam D.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Smith, ER (reprint author), Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. FU Tercica; Ortho-McNeil Pharmaceutical; GE HealthCare FX Dr. Loeffler reports receiving consulting fees or being on the paid advisory boards of TransMolecular and Procore and having equity ownership in Procore; Dr. Misra, receiving grant support from Tercica and Ortho-McNeil Pharmaceutical, and Dr. Pomerantz, receiving lecture fees and grant support from GE HealthCare. No other potential conflict of interest relevant to this article was reported. NR 30 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 2008 VL 359 IS 22 BP 2367 EP 2377 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 377SG UT WOS:000261270300010 PM 19038883 ER PT J AU Blumenthal, D Morone, J AF Blumenthal, David Morone, James TI The Lessons of Success - Revisiting the Medicare Story SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Blumenthal, David] Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. [Morone, James] Brown Univ, Dept Polit Sci, Providence, RI 02912 USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 27 PY 2008 VL 359 IS 22 BP 2384 EP 2389 DI 10.1056/NEJMhpr0806879 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 377SG UT WOS:000261270300013 PM 19038885 ER PT J AU Doria, A Wojcik, J Xu, R Gervino, EV Hauser, TH Johnstone, MT Nolan, D Hu, FB Warram, JH AF Doria, Alessandro Wojcik, Joanna Xu, Rui Gervino, Ernest V. Hauser, Thomas H. Johnstone, Michael T. Nolan, David Hu, Frank B. Warram, James H. TI Interaction Between Poor Glycemic Control and 9p21 Locus on Risk of Coronary Artery Disease in Type 2 Diabetes SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; ADIPONECTIN GENE; META-ANALYSIS; INSULIN; EPIDEMIOLOGY; POLYMORPHISM; MELLITUS; SUSCEPTIBILITY AB Context A common allele on chromosome 9p21 has been repeatedly associated with increased risk of coronary artery disease ( CAD) in the general population. However, the magnitude of this effect in the population with diabetes has not been well characterized. Objective To examine the association of the 9p21 variant with CAD in individuals with type 2 diabetes and evaluate its interaction with poor glycemic control. Design, Setting, and Participants ( 1) Case- control study of 734 type 2 diabetes patients ( 322 with angiographically diagnosed CAD and 412 with no evidence of CAD) who were recruited between 2001 and 2006 at the Joslin Clinic, Beth Israel Deaconess Medical Center; and ( 2) independent cohort study of 475 type 2 diabetes patients from the Joslin Clinic whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004. Participants for both studies were genotyped for a representative single- nucleotide polymorphism at 9p21 ( rs2383206) and characterized for their long- term glycemic control by averaging multiple hemoglobin A(1c) ( HbA(1c)) measurements taken in the years before study entry. Main Outcome Measures For the case- control study, association between single-nucleotide polymorphism rs2383206 and CAD defined as angiographically documented stenosis greater than 50% in a major coronary artery or a main branch thereof was assessed and for the cohort study, cumulative 10- year mortality was documented. Results Individuals who were homozygous for the risk allele were significantly more frequent among case than control participants ( 42.3% vs 28.9P=. 0002). This association was unaffected by adjustment for cardiovascular risk factors, but the effect of the risk genotype was significantly magnified ( adjusted P for interaction=. 048) in the presence of poor glycemic control ( worst tertile of the distribution of HbA(1c) at examination). Relative to the CAD risk for patients with neither a 9p21 risk allele nor poor glycemic control, the CAD odds for participants having 2 risk alleles but not poor glycemic control were increased 2- fold ( odds ratio [ OR], 1.99; 95% confidence interval [ CI], 1.17- 3.41), whereas the odds for study participants with the same genotype and with poor glycemic control were increased 4- fold ( OR, 4.27; 95% CI, 2.26- 8.01). The interaction was stronger ( adjusted P=. 005) when a measure of long- term glycemic control ( 7- year average rather than most recent HbA(1c)) was used with ORs of 7.83 ( 95% CI, 3.49- 17.6) for participants having 2 risk alleles and a history of poor glycemia and 1.54 ( 95% CI, 0.72- 3.30) for participants with the same genotype but without this exposure. A similar interaction between 9p21 variant and poor glycemic control was observed with respect to cumulative 10- year mortality in the cohort study ( 43.6% in patients with 2 risk alleles and poor glycemic control, 23.1% in individuals with only the 2 risk alleles, 30.0% in individuals with only poor glycemic control, and 31.6% in individuals with neither factor, P for interaction, =. 036). Conclusion In this study population, the CAD risk associated with the 9p21 variant was increased in the presence of poor glycemic control in type 2 diabetes. C1 [Doria, Alessandro; Wojcik, Joanna; Xu, Rui; Nolan, David; Warram, James H.] Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. [Doria, Alessandro; Wojcik, Joanna; Xu, Rui; Gervino, Ernest V.; Hauser, Thomas H.; Hu, Frank B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Gervino, Ernest V.; Hauser, Thomas H.] Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. [Johnstone, Michael T.] Caritas St Elizabeth Med Ctr, Boston, MA USA. [Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Doria, Alessandro; Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM alessandro.doria@joslin.harvard.edu FU National Institutes of Health [HL73168, HL71981]; Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center [DK36836]; Donald W. Reynolds Foundation FX This study was supported by National Institutes of Health grants HL73168, HL71981, and DK36836 (Genetics Core of the Diabetes and Endocrinology Research Center at the Joslin Diabetes Center), and a grant from the Donald W. Reynolds Foundation. Role of the Sponsors: None of the funding agencies had any role in the design and conduct of the study, in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript. NR 40 TC 68 Z9 71 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 26 PY 2008 VL 300 IS 20 BP 2389 EP 2397 DI 10.1001/jama.2008.649 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 375YX UT WOS:000261150800021 PM 19033589 ER PT J AU Lyamin, OI Kosenko, PO Lapierre, JL Mukhametov, LM Siegel, JM AF Lyamin, Oleg I. Kosenko, Peter O. Lapierre, Jennifer L. Mukhametov, Lev M. Siegel, Jerome M. TI Fur Seals Display a Strong Drive for Bilateral Slow-Wave Sleep While on Land SO JOURNAL OF NEUROSCIENCE LA English DT Article DE EEG asymmetry; bilateral slow-wave sleep; slow-wave activity; sleep deprivation; sleep-wake cycle; Callorhinus ursinus ID UNIHEMISPHERIC SLEEP; SPECTRAL POWER; DEPRIVATION; EEG; ASYMMETRY; STIMULATION; DOLPHINS; RAT AB Fur seals (pinnipeds of the family Otariidae) display two fundamentally different patterns of sleep: bilaterally symmetrical slow-wave sleep (BSWS) as seen in terrestrial mammals and slow-wave sleep (SWS) with a striking interhemispheric EEG asymmetry (asymmetrical SWS or ASWS) as observed in cetaceans. We examined the effect of preventing fur seals from sleeping in BSWS on their pattern of sleep. Four northern fur seals (Callorhinus ursinus) kept on land were sleep deprived (SD) of BSWS for 3 consecutive days, followed by 1 recovery day. EEG asymmetry was evaluated both visually and by EEG spectral analysis. SD significantly reduced the percentage of high-voltage BSWS (on average to 14% of baseline) and REM sleep (to 60% of baseline) whereas the percentage of low-voltage BSWS was not affected. During the SD period, all seals repeatedly tried to enter BSWS (109-411 attempts per day). SD significantly increased the amount of ASWS in each seal when scored visually (to 116-235% of baseline) and the difference in the EEG slow-wave activity (spectral power in the range of 1.2-4.0 Hz) between the two hemispheres (117-197%) as measured by the asymmetry index. High-voltage BSWS and the amount of SWS in each hemisphere were significantly elevated during the first 4 h of recovery. These data indicate that fur seals display a homeostatic response to the loss of SWS and that alternating SWS in the two hemispheres does not adequately compensate for the absence of BSWS. C1 [Lyamin, Oleg I.; Lapierre, Jennifer L.; Siegel, Jerome M.] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, North Hills, CA 91343 USA. [Lyamin, Oleg I.; Lapierre, Jennifer L.; Siegel, Jerome M.] Univ Calif Los Angeles, Dept Psychiat, Sch Med, North Hills, CA 91343 USA. [Lyamin, Oleg I.; Kosenko, Peter O.; Mukhametov, Lev M.] Utrish Dolphinarium Ltd, Moscow 119071, Russia. RP Lyamin, OI (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Neurobiol Res 151A3, 16111 Plummer St, North Hills, CA 91343 USA. EM olyamin@ucla.edu FU National Science Foundation [0234687]; Defense Advanced Research Projects Agency [BAA0412F8034]; Department of Veterans Affairs; Utrish Dolphinarium, Ltd FX This work was supported by the National Science Foundation (Grant 0234687), the Defense Advanced Research Projects Agency (Grant BAA0412F8034), the Medical Research Service of the Department of Veterans Affairs, and the Utrish Dolphinarium, Ltd. We thank E. Belyaev, A. Kibalnikov, E. Nazarenko, J. Pryaslova, and O. Shpak for their assistance during the experiments. NR 28 TC 11 Z9 11 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 26 PY 2008 VL 28 IS 48 BP 12614 EP 12621 DI 10.1523/JNEUROSCI.2306-08.2008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 376OA UT WOS:000261191700003 PM 19036955 ER PT J AU Weissman, JR Kelley, RI Bauman, ML Cohen, BH Murray, KF Mitchell, RL Kern, RL Natowicz, MR AF Weissman, Jacqueline R. Kelley, Richard I. Bauman, Margaret L. Cohen, Bruce H. Murray, Katherine F. Mitchell, Rebecca L. Kern, Rebecca L. Natowicz, Marvin R. TI Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis SO PLOS ONE LA English DT Article ID RESPIRATORY-CHAIN DISORDERS; MTDNA MUTATIONS; GASTROINTESTINAL SYMPTOMS; DEVELOPMENTAL REGRESSION; DIAGNOSTIC-CRITERIA; LACTIC-ACIDOSIS; DNA MUTATIONS; COMPLEX-I; CHILDREN; DYSFUNCTION AB Background: Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder. Methodology/Principal Findings: We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity. Conclusions/Significance: Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism. C1 [Weissman, Jacqueline R.; Natowicz, Marvin R.] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. [Kelley, Richard I.; Kern, Rebecca L.] Kennedy Krieger Inst, Division of Metabolism, Baltimore, MD USA. [Kelley, Richard I.; Kern, Rebecca L.] Johns Hopkins Univ, Med Ctr, Dept Pediat, Baltimore, MD 21218 USA. [Bauman, Margaret L.; Murray, Katherine F.] Massachusetts Gen Hosp, LADDERS, Dept Pediat, Boston, MA 02114 USA. [Cohen, Bruce H.; Natowicz, Marvin R.] Cleveland Clin, Pediatrics Inst, Neurol Inst, Cleveland, OH USA. [Mitchell, Rebecca L.; Natowicz, Marvin R.] Cleveland Clin, Genom Med Inst, Cleveland, OH USA. [Natowicz, Marvin R.] Cleveland Clin, Lab Med Inst, Cleveland, OH USA. RP Weissman, JR (reprint author), Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. EM natowim@ccf.org FU Solving the Mystery of Autism Foundation, Inc; Green Foundation FX This work was supported in part by a grant from the Solving the Mystery of Autism Foundation, Inc. and from the Green Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 63 TC 93 Z9 97 U1 0 U2 10 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 NOV 26 PY 2008 VL 3 IS 11 AR e3815 DI 10.1371/journal.pone.0003815 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YG UT WOS:000265451400007 PM 19043581 ER PT J AU Van den Stock, J Grezes, J de Gelder, B AF Van den Stock, Jan Grezes, Julie de Gelder, Beatrice TI Human and animal sounds influence recognition of body language SO BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 8th International Multisensory Research Forum CY JUL, 2007 CL Univ Sydney, Sydney, AUSTRALIA HO Univ Sydney DE Multisensory; Body perception; Emotion ID COMBINED PERCEPTION; VOICE; FACE; EXPRESSIONS; EMOTION; INTEGRATION; RESPONSES; AMYGDALA; BINDING; FEAR AB In naturalistic settings emotional events have multiple correlates and are simultaneously perceived by several sensory systems. Recent studies have shown that recognition of facial expressions is biased towards the emotion expressed by a simultaneously presented emotional expression in the voice even if attention is directed to the face only. So far, no study examined whether this phenomenon also applies to whole body expressions, although there is no obvious reason why this crossmodal influence would be specific for faces. Here we investigated whether perception of emotions expressed in whole body movements is influenced by affective information provided by human and by animal vocalizations. Participants were instructed to attend to the action displayed by the body and to categorize the expressed emotion. The results indicate that recognition of body language is biased towards the emotion expressed by the simultaneously presented auditory information, whether it consist of human or of animal sounds. Our results show that a crossmodal influence from auditory to visual emotional information obtains for whole body video images with the facial expression blanked and includes human as well as animal sounds. (c) 2008 Elsevier B.V. All rights reserved. C1 [de Gelder, Beatrice] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [de Gelder, Beatrice] Harvard Univ, Sch Med, Charlestown, MA USA. [Van den Stock, Jan; de Gelder, Beatrice] Tilburg Univ, Cognit & Affect Neurosci Lab, Tilburg, Netherlands. [Van den Stock, Jan] Univ Hosp Leuven, Dept Old Age Psychiat, Louvain, Belgium. [Grezes, Julie] Ecole Normale Super, Cognit Neurosci Lab, INSERM, U742 & DEC, Paris, France. RP de Gelder, 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; Grezes, Julie/E-5060-2016 OI Van den Stock, Jan/0000-0001-5756-3195; NR 26 TC 33 Z9 33 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 25 PY 2008 VL 1242 BP 185 EP 190 DI 10.1016/j.brainres.2008.05.040 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 386EQ UT WOS:000261865500019 PM 18617158 ER PT J AU Ridker, PM Paynter, NP Rifai, N Gaziano, JM Cook, NR AF Ridker, Paul M. Paynter, Nina P. Rifai, Nader Gaziano, J. Michael Cook, Nancy R. TI C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction The Reynolds Risk Score for Men SO CIRCULATION LA English DT Article DE epidemiology; prevention; inflammation; genetics; risk factors ID TREATMENT PANEL-III; ROC CURVE; DISEASE; MODELS; PREVENTION; CHOLESTEROL; RECLASSIFICATION; RECOMMENDATIONS; VALIDATION; ABILITY AB Background-High-sensitivity C-reactive protein and family history are independently associated with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women); however, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men. Methods and Results-Among 10 724 initially healthy American nondiabetic men who were followed up prospectively over a median period of 10.8 years, we compared the test characteristics of global model fit, discrimination, calibration, and reclassification in 2 prediction models for incident cardiovascular events, one based on age, blood pressure, smoking status, total cholesterol, and high-density lipoprotein cholesterol (traditional model) and the other based on these risk factors plus high-sensitivity C-reactive protein and parental history of myocardial infarction before age 60 years (Reynolds Risk Score for men). A total of 1294 cardiovascular events accrued during study follow-up. Compared with the traditional model, the Reynolds Risk Score had better global fit (likelihood ratio test P<0.001), a superior (lower) Bayes information criterion, and a larger C-index (P<0.001). For the end point of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8% (1904/10 724) of the study population (and 20.2% [1392/6884] of those at 5% to 20% 10-year risk) into higher-or lower-risk categories, with markedly improved accuracy among those reclassified. For this model comparison, the net reclassification index was 5.3%, and the clinical net reclassification index was 14.2% (both P<0.001). In models based on the Adult Treatment Panel III preferred end point of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7% of the study population (and 20.1% of those at 5% to 20% 10-year risk) were reclassified to higher- or lower-risk groups, again with significantly improved global fit, larger C-index (P<0.001), and markedly improved accuracy among those reclassified. For this model, the net reclassification index was 8.4% and the clinical net reclassification index was 15.8% (both P<0.001). Conclusions-As previously shown in women, a prediction model in men that incorporates high-sensitivity C-reactive protein and parental history significantly improves global cardiovascular risk prediction. (Circulation. 2008; 118: 2243-2251.) C1 [Ridker, Paul M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent,Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent,Div Cardiovasc Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Donald W Reynolds Ctr Cardiovasc Res, Boston, MA 02215 USA. VA Boston Hlth Care Syst, MAVERIC, Boston, MA USA. RP Ridker, PM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent,Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM pridker@partners.org FU National Heart, Lung, and Blood Institute (Bethesda, Md); Donald W. Reynolds Foundation (Las Vegas, Nev); National Heart, Lung, and Blood Institute FX These analyses were funded by grants from the National Heart, Lung, and Blood Institute (Bethesda, Md) and the Donald W. Reynolds Foundation (Las Vegas, Nev). The Physicians Health Study is supported by grants from the National Heart, Lung, and Blood Institute. The funding agencies had no involvement in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the drafting of the manuscript. NR 23 TC 402 Z9 423 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 25 PY 2008 VL 118 IS 22 BP 2243 EP 4 DI 10.1161/CIRCULATIONAHA.108.814251 PG 13 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300005 PM 18997194 ER PT J AU Velagaleti, RS Gona, P Levy, D Aragam, J Larson, MG Tofler, GH Lieb, W Wang, TJ Benjamin, EJ Vasan, RS AF Velagaleti, Raghava S. Gona, Philimon Levy, Daniel Aragam, Jayashri Larson, Martin G. Tofler, Geoffrey H. Lieb, Wolfgang Wang, Thomas J. Benjamin, Emelia J. Vasan, Ramachandran S. TI Relations of Biomarkers Representing Distinct Biological Pathways to Left Ventricular Geometry SO CIRCULATION LA English DT Article DE aldosterone; biological markers; echocardiography; hypertrophy; remodeling; renin ID C-REACTIVE PROTEIN; ANGIOTENSIN-ALDOSTERONE SYSTEM; CONVERTING ENZYME-INHIBITOR; CORONARY HEART-DISEASE; TARGET ORGAN DAMAGE; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; METABOLIC SYNDROME; SERUM ALDOSTERONE; RISK-FACTORS AB Background-Several biological pathways are activated concomitantly during left ventricular (LV) remodeling. However, the relative contribution of circulating biomarkers representing these distinct pathways to LV geometry is unclear. Methods and Results-We evaluated 2119 Framingham Offspring Study participants (mean age, 57 years; 57% women) who underwent measurements of biomarkers of inflammation (C-reactive protein), hemostasis (fibrinogen and plasminogen activator inhibitor-1), neurohormonal activation (B-type natriuretic peptide), and renin-angiotensin-aldosterone system (aldosterone and renin modeled as a ratio [ARR]) and echocardiography at a routine examination. LV geometry was defined on the basis of sex-specific distributions of LV mass (LVM) and relative wall thickness (RWT): normal (LVM and RWT <80th percentile), concentric remodeling (LVM <80th percentile but RWT >= 80th percentile), eccentric hypertrophy (LVM >= 80th percentile but RWT <80th percentile), and concentric hypertrophy (LVM and RWT >80th percentile). We related the biomarker panel to LV geometry using polytomous logistic regression adjusting for clinical covariates and used backwards elimination to identify a parsimonious set of biomarkers associated with LV geometry. Modeled individually, C-reactive protein, fibrinogen, plasminogen activator inhibitor-1, and ARR were related to LV geometry (P<0.01). In multivariable analyses, the biomarker panel was significantly related to altered LV geometry (P<0.0001). On backwards elimination, logARR alone was significantly and positively associated with eccentric (odds ratio per SD increment, 1.20; 95% confidence interval, 1.05 to 1.37) and concentric LV hypertrophy (odds ratio per SD increment, 1.29; 95% confidence interval, 1.06 to 1.58). Conclusions-Our cross-sectional observations on a large community-based sample identified ARR as a key correlate of concentric and eccentric LV hypertrophy, consistent with a major role for the renin-angiotensin-aldosterone system in LV remodeling. (Circulation. 2008; 118: 2252-2258.) C1 [Velagaleti, Raghava S.; Gona, Philimon; Levy, Daniel; Larson, Martin G.; Lieb, Wolfgang; Wang, Thomas J.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Newark, NJ 07102 USA. [Aragam, Jayashri] Vet Adm Hosp, W Roxbury, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, W Roxbury, MA USA. [Gona, Philimon; Larson, Martin G.] Dept Math & Stat, W Roxbury, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Dept Sch Publ Hlth, Sch Med & Epidemiol, Prevent Med Sect, Boston, MA 02215 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Dept Sch Publ Hlth, Sch Med & Epidemiol, Cardiol Sect, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Newark, NJ 07102 USA. EM vasan@bu.edu RI Lieb, Wolfgang/C-1990-2012; OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institutes of Health [RO1-HL086875, RO1 HL67288, IIL080124, K24-HL04334] FX This work was supported by the National Heart, Lung, and Blood Institute (contract N01-HC-25195) and National Institutes of Health grants RO1-HL086875 (Dr Wang), RO1 HL67288, IIL080124, and K24-HL04334 (Dr Vasan). NR 48 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 25 PY 2008 VL 118 IS 22 BP 2252 EP U161 DI 10.1161/CIRCULATIONAHA.108.817411 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300006 ER PT J AU Davis, BR Kostis, JB Simpson, LM Black, HR Cushman, WC Einhorn, PT Farber, MA Ford, CE Levy, D Massie, BM Nawaz, S AF Davis, Barry R. Kostis, John B. Simpson, Lara M. Black, Henry R. Cushman, William C. Einhorn, Paula T. Farber, Michael A. Ford, Charles E. Levy, Daniel Massie, Barry M. Nawaz, Shah CA ALLHAT Collaborative Res Grp TI Heart Failure With Preserved and Reduced Left Ventricular Ejection Fraction in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial SO CIRCULATION LA English DT Article DE angiotensin-converting enzyme inhibitors; antihypertensive agents; calcium channel blockers; diuretics; heart failure; hypertension; ventricular ejection fraction ID SYSTOLIC FUNCTION; DIASTOLIC DYSFUNCTION; CARDIOVASCULAR HEALTH; OLMSTED COUNTY; PREVALENCE; COMMUNITY; POPULATION; PROGNOSIS; ALLHAT; MECHANISMS AB Background-Heart failure (HF) developing in hypertensive patients may occur with preserved or reduced left ventricular ejection fraction (PEF [>= 50%] or REF [<50%]). In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), 42 418 high-risk hypertensive patients were randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin, providing an opportunity to compare these treatments with regard to occurrence of hospitalized HFPEF or HFREF. Methods and Results-HF diagnostic criteria were prespecified in the ALLHAT protocol. EF estimated by contrast ventriculography, echocardiography, or radionuclide study was available in 910 of 1367 patients (66.6%) with hospitalized events meeting ALLHAT criteria. Cox regression models adjusted for baseline characteristics were used to examine treatment differences for HF (overall and by PEF and REF). HF case fatality rates were examined. Of those with EF data, 44.4% had HFPEF and 55.6% had HFREF. Chlorthalidone reduced the risk of HFPEF compared with amlodipine, lisinopril, or doxazosin; the hazard ratios were 0.69 (95% confidence interval [CI], 0.53 to 0.91; P=0.009), 0.74 (95% CI, 0.56 to 0.97; P=0.032), and 0.53 (95% CI, 0.38 to 0.73; P<0.001), respectively. Chlorthalidone reduced the risk of HFREF compared with amlodipine or doxazosin; the hazard ratios were 0.74 (95% CI, 0.59 to 0.94; P=0.013) and 0.61 (95% CI, 0.47 to 0.79; P<0.001), respectively. Chlorthalidone was similar to lisinopril with regard to incidence of HFREF (hazard ratio, 1.07; 95% CI, 0.82 to 1.40; P=0.596). After HF onset, death occurred in 29.2% of participants (chlorthalidone/amlodipine/lisinopril) with new-onset HFPEF versus 41.9% in those with HFREF (P<0.001; median follow-up, 1.74 years); and in the chlorthalidone/doxazosin comparison that was terminated early, 20.0% of HFPEF and 26.0% of HFREF patients died (P=0.185; median follow-up, 1.55 years). Conclusions-In ALLHAT, with adjudicated outcomes, chlorthalidone significantly reduced the occurrence of new-onset hospitalized HFPEF and HFREF compared with amlodipine and doxazosin. Chlorthalidone also reduced the incidence of new-onset HFPEF compared with lisinopril. Among high-risk hypertensive men and women, HFPEF has a better prognosis than HFREF. (Circulation. 2008; 118: 2259-2267.) C1 [Davis, Barry R.; Simpson, Lara M.; Ford, Charles E.] Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, Houston, TX 77030 USA. [Kostis, John B.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. [Black, Henry R.] NYU, Sch Med, New York, NY USA. [Cushman, William C.] Memphis Vet Affairs Med Ctr, Memphis, TN USA. [Einhorn, Paula T.] NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. [Farber, Michael A.] Crozer Keystone Hlth Network, Upland, PA USA. [Levy, Daniel] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massie, Barry M.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Davis, BR (reprint author), Univ Texas Houston, Hlth Sci Ctr, Sch Publ Hlth, 1200 Herman Pressler,Suite E801, Houston, TX 77030 USA. EM barry.r.davis@uth.tmc.edu FU National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services Bethesda, Md [N01-HC-35130] FX This research was supported by Health and Human Services contract N01-HC-35130 from the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, Bethesda, Md. The ALLHAT investigators acknowledge contributions of study medications supplied by Pfizer Inc (amlodipine and doxazosin), AstraZeneca (atenolol and lisinopril), and Bristol-Myers Squibb (pravastatin) and financial support provided by Pfizer Inc. NR 45 TC 73 Z9 77 U1 2 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD NOV 25 PY 2008 VL 118 IS 22 BP 2259 EP 2267 DI 10.1161/CIRCULATIONAHA.107.762229 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300007 PM 19001024 ER PT J AU Gupta, V Truong, QA Okada, DR Kiernan, TJ Yan, BP Cubeddu, RJ Roberts, DJ Abbara, S MacGillivray, TE Palacios, IF AF Gupta, Vishal Truong, Quynh A. Okada, David R. Kiernan, Thomas J. Yan, Bryan P. Cubeddu, Roberto J. Roberts, David J. Abbara, Suhny MacGillivray, Thomas E. Palacios, Igor F. TI Giant Left Circumflex Coronary Artery Aneurysm With Arteriovenous Fistula to the Coronary Sinus SO CIRCULATION LA English DT Editorial Material C1 [Gupta, Vishal; Kiernan, Thomas J.; Yan, Bryan P.; Cubeddu, Roberto J.; Palacios, Igor F.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Truong, Quynh A.; Okada, David R.; Abbara, Suhny] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Dept Cardiac Surg, Boston, MA 02114 USA. [Roberts, David J.] N Shore Med Ctr, Div Cardiol, Salem, MA USA. RP Gupta, V (reprint author), Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. EM vishalgupta@yahoo.com RI Yan, Bryan/C-3390-2008; Yan, Bryan/P-5928-2015 FU NHLBI NIH HHS [T32HL076136] NR 4 TC 8 Z9 8 U1 1 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 NOV 25 PY 2008 VL 118 IS 22 BP 2304 EP 2307 DI 10.1161/CIRCULATIONAHA.108.781617 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 377AO UT WOS:000261224300012 PM 19029479 ER PT J AU Gutierrez, GM Kong, E Sabbagh, Y Brown, NE Lee, JS Demay, MB Thomas, DM Hind, PW AF Gutierrez, Gabriel M. Kong, Elizabeth Sabbagh, Yves Brown, Nelson E. Lee, Jong-Seo Demay, Marie B. Thomas, David M. Hind, Philip W. TI Impaired bone development and increased mesenchymal progenitor cells in calvaria of RB1(-/-) mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE differentiation; retinoblastoma protein; osteoprogenitors ID RETINOBLASTOMA PROTEIN; TARGETED DISRUPTION; ADIPOCYTE DIFFERENTIATION; OSTEOBLAST LINEAGE; MAMMARY-GLAND; MUSCLE-CELLS; IN-VITRO; RB; GENE; INACTIVATION AB We have previously shown that the retinoblastoma protein (pRb) can activate expression of Runx2-dependent, bone-specific genes in cultured cells. We now show that pRb also plays a role early in osteogenesis, and that in primary RB1(-/-) calvarial cells there is an increased osteoprogenitor pool. To understand pRb's function in vivo, we generated a conditional RB1-KO mouse in which pRb expression is efficiently extinguished in osteoblasts. These animals display an apparent developmental defect in bones, most strikingly in the calvaria. Cultured RB1(-/-) calvarial osteoblasts fail to cease proliferation upon reaching confluence or following differentiation. Re-plating assays of primary RB1(-/-) calvarial cells after differentiation showed a clear adipogenic ability with increased multipotency. RB1(-/-) osteoblasts display a severe reduction in levels of mRNAs expressed late in differentiation. In this study, we present strong evidence that pRb has multiple regulatory roles in osteogenesis. Furthermore, in the absence of RB1(-/-) there is a larger pool of multipotent cells compared with the WT counterpart. This increased pool of osteoprogenitor cells may be susceptible to additional transforming events leading to osteosarcoma, and is therefore key to understanding RB1 as a target in malignancy. C1 [Gutierrez, Gabriel M.; Kong, Elizabeth; Brown, Nelson E.; Hind, Philip W.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Sabbagh, Yves; Demay, Marie B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. [Lee, Jong-Seo] Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. [Thomas, David M.] Peter MacCallum Canc Ctr, Sir Donald & Lady Trescowthick Labs, Melbourne, Vic 3002, Australia. [Thomas, David M.] Peter MacCallum Canc Ctr, Sir Donald & Lady Trescowthick Labs, Melbourne, Vic 3002, Australia. [Thomas, David M.] Ian Potter Fdn, Ctr Canc Genom & Predict Med, Melbourne, Vic 3002, Australia. RP Hind, PW (reprint author), Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM phinds@tuftsmedicalcenter.org OI Sabbagh, Yves/0000-0001-5339-6705; Gutierrez, Gabriel/0000-0001-8487-0414 FU National Institutes of Health [AG020208] FX The authors thank C. Kuperwasser and P. Yelick for helpful comments. This work was supported by National Institutes of Health Grant AG020208 (to P.W.H.). NR 43 TC 38 Z9 39 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2008 VL 105 IS 47 BP 18402 EP 18407 DI 10.1073/pnas.0805925105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300066 PM 19020086 ER PT J AU Breckwoldt, MO Chen, JW Stangenberg, L Aikawa, E Rodriguez, E Qiu, SM Moskowitz, MA Weissleder, R AF Breckwoldt, Michael O. Chen, John W. Stangenberg, Lars Aikawa, Elena Rodriguez, Elisenda Qiu, Shumei Moskowitz, Michael A. Weissleder, Ralph TI Tracking the inflammatory response in stroke in vivo by sensing the enzyme myeloperoxidase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE inflammation; ischemia; molecular imaging; MRI; brain ID ISCHEMIC-STROKE; ENHANCED MRI; CEREBRAL-ISCHEMIA; FOCAL ISCHEMIA; BRAIN ISCHEMIA; INJURY; NEUTROPHILS; INFARCTION; TRANSIENT; DISEASE AB Inflammation can extend ischemic brain injury and adversely affect outcome in experimental animal models. A key difficulty in translating animal studies to humans is the lack of a definitive method to confirm and track inflammation in the brain in vivo. Myeloper-oxidase (MPO), a key inflammatory enzyme secreted by activated neutrophils and macrophages/microglia, can generate highly reactive oxygen species to cause additional damage in cerebral ischemia. We report here that a functional, enzyme-activatable MRI agent can accurately track the oxidative activity of MPO noninvasively in stroke in living animals. We found that MPO is widely distributed in ischemic tissues, correlates positively with infarct size, and is detected even 3 weeks postinfarction. The peak level of MPO activity, determined by activation of the MPO-sensing agent in vivo and confirmed by MPO activity and quantitative RT-PCR assays, occurred on day 3 after ischemia. Both neutrophils and macrophages/microglia contribute to secrete MPO in the ischemic brain, although neutrophils peak earlier (days 1-3) whereas macrophages/microglia are most abundant later (days 3-7). In contrast to the conventional MRI agent diethylenetriamine-pentatacetate gadolinium, which reports blood-brain barrier disruption, MPO imaging is able to additionally track MPO activity and confirm inflammation on the molecular level in vivo, information that was previously only possible to obtain on ex vivo brain sections and impossible to assess in living human patients. Our findings could allow efficient noninvasive serial screening of therapies targeting inflammation and the use of MPO imaging as an imaging biomarker to risk-stratify patients. C1 [Breckwoldt, Michael O.; Chen, John W.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Charlestown, MA 02129 USA. [Breckwoldt, Michael O.; Chen, John W.; Stangenberg, Lars; Aikawa, Elena; Rodriguez, Elisenda; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. [Qiu, Shumei; Moskowitz, Michael A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. [Chen, John W.; Moskowitz, Michael A.; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. RP Chen, JW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, CNY 149,13th St, Charlestown, MA 02129 USA. EM chenjo@helix.mgh.harvard.edu FU German National Academic Foundation; Boehringer Ingelheim Fonds; German Research Foundation; Marie Curie Fellowship; National Institutes of Health [5K08HL081170, P50-NS10828-32, R24-CA92782, R01-HL078641] FX We thank Carlos Rangel, Claire Kaufman, Anne Yu, Jenny Chan, Vincent Lok, Todd Sponholtz, Yoshiko Iwamoto, and Ying Wei for experimental assistance and Peter Panizzi for helpful discussions. We acknowledge early contributions by Alexei Bogdanov and Manel Querol in developing MPO-Gd. M.O..B. was supported by the German National Academic Foundation and Boehringer Ingelheim Fonds. L.S. received support from the German Research Foundation. E.R. was supported by the Marie Curie Fellowship. This work was supported in part by National Institutes of Health Grants 5K08HL081170 (to J.W.C.), P50-NS10828-32 (to M.M.), and R24-CA92782 and R01-HL078641 (to R.W.). NR 35 TC 133 Z9 137 U1 2 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 25 PY 2008 VL 105 IS 47 BP 18584 EP 18589 DI 10.1073/pnas.0803945105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 380TY UT WOS:000261489300097 PM 19011099 ER PT J AU Ongusaha, PP Qi, HH Raj, L Kim, YB Aaronson, SA Davis, RJ Shi, Y Liao, JK Lee, SW AF Ongusaha, Pat P. Qi, Hank H. Raj, Lakshmi Kim, Young-Bum Aaronson, Stuart A. Davis, Roger J. Shi, Yang Liao, James K. Lee, Sam W. TI Identification of ROCK1 as an Upstream Activator of the JIP-3 to JNK Signaling Axis in Response to UVB Damage SO SCIENCE SIGNALING LA English DT Article AB Although apoptosis triggered by ultraviolet B (UVB)-mediated activation of the c-Jun N-terminal kinase (JNK) pathway is mediated by both intrinsic and extrinsic pathways, the mechanism of initiation of JNK activation remains obscure. Here, we report the characterization of the JNK-interacting protein 3 (JIP-3) scaffolding protein as an interacting partner of Rho-associated kinase 1 (ROCK1), as determined by tandem affinity protein purification. Upon UVB-induced stress in keratinocytes, ROCK1 was activated, bound to JIP-3, and activated the JNK pathway. Moreover, phosphorylation of JIP-3 by ROCK1 was crucial for the recruitment of JNK. Inhibition of the activity of ROCK1 in keratinocytes resulted in decreased activation of the JNK pathway and thus a reduction in apoptosis. ROCK1(+/-) mice exhibited decreased UVB-mediated activation of JNK and apoptosis relative to wild-type mice. Our findings present a new molecular mechanism by which ROCK1 functions as a UVB sensor that regulates apoptosis, an important event in the prevention of skin cancer. C1 [Ongusaha, Pat P.; Raj, Lakshmi; Lee, Sam W.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. [Ongusaha, Pat P.; Raj, Lakshmi; Lee, Sam W.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Qi, Hank H.; Shi, Yang] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Kim, Young-Bum] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. [Kim, Young-Bum] Harvard Univ, Sch Med, Boston, MA 02215 USA. [Aaronson, Stuart A.] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Howard Hughes Med Inst, Worcester, MA 01605 USA. [Davis, Roger J.] Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. [Liao, James K.] Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA 02139 USA. [Liao, James K.] Harvard Univ, Sch Med, Cambridge, MA 02139 USA. RP Lee, SW (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 13th St,Bldg 149, Charlestown, MA 02129 USA. EM swlee@partners.org FU NCI NIH HHS [R01 CA127247, R01 CA085214, P01 CA080058, R01 CA085681]; NHLBI NIH HHS [R01 HL070274, R01 HL052233-12, R01 HL052233, R01 HL080187-03, R01 HL070274-05, R01 HL080187]; NIDDK NIH HHS [R01 DK062729-05, R01 DK062729]; NINDS NIH HHS [P01 NS010828-330036, P01 NS010828] NR 52 TC 24 Z9 28 U1 2 U2 6 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 NOV 25 PY 2008 VL 1 IS 47 AR ra14 DI 10.1126/scisignal.1161938 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V10XU UT WOS:000207497500004 PM 19036714 ER PT J AU Li, XY Gounari, F Protopopov, A Khazaie, K von Boehmer, H AF Li, Xiaoyu Gounari, Fotini Protopopov, Alexei Khazaie, Khashayarsha von Boehmer, Harald TI Oncogenesis of T-ALL and nonmalignant consequences of overexpressing intracellular NOTCH1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; C-MYC; CELL-RECEPTOR; GENE-EXPRESSION; LYMPHOCYTE DEVELOPMENT; TUMOR-SUPPRESSOR; TRANSGENIC MICE; DOWN-REGULATION; ALPHA-BETA; PT-ALPHA AB Mutations resulting in overexpression of intracellular Notch1 (ICN1) are frequently observed in human T cell acute lymphoblastic leukemia (T-ALL). We have determined the consequences of ICN1 overexpression from retroviral vectors introduced into bone marrow cells. Early consequences are the generation of polyclonal nontumorigenic CD4(+)8(+) T cell receptor (TCR)-alpha beta(+) cells that do not qualify as tumor precursors despite the observation that they overexpress Notch 1 and c-Myc and degrade the tumor suppressor E2A by post-translational modification. The first tumorigenic cells are detected among more immature CD4(-)8(+)TCR-alpha beta(-) cells that give rise to monoclonal tumors with a single, unique TCR-beta chain and diverse TCR-alpha chains, pinpointing malignant transformation to a stage after pre-TCR signaling and before completion of TCR-alpha rearrangement. In T-ALL, E2A deficiency is accompanied by further transcriptional up-regulation of c-Myc and concomitant dysregulation of the c-Myc-p53 axis at the transcriptional level. Even though the tumors consist of phenotypically heterogeneous cells, no evidence for tumor stem cells was found. As judged by array-based comparative genomic hybridization (array CGH) and spectral karyotype (SKY) analysis, none of the tumors arise because of genomic instability. C1 [Li, Xiaoyu; Gounari, Fotini; Protopopov, Alexei; Khazaie, Khashayarsha; von Boehmer, Harald] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Gounari, Fotini] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Khazaie, Khashayarsha] Northwestern Univ, Dept Microbiol Immunol, Chicago, IL 60611 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 FU National Institutes of Health (NIH) [P01 CA109901, R01 AI45846, T32-CA70083]; Lymphoma Research Foundation FX This work was supported by National Institutes of Health (NIH) grants P01 CA109901 and R01 AI45846. X. Li is supported by the Lymphoma Research Foundation, Lee Fellowship, and NIH training grant T32-CA70083. NR 40 TC 57 Z9 58 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 24 PY 2008 VL 205 IS 12 BP 2851 EP U72 DI 10.1084/jem.20081561 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 378BE UT WOS:000261295300018 PM 18981238 ER PT J AU Hezel, AF Bardeesy, N AF Hezel, A. F. Bardeesy, N. TI LKB1; linking cell structure and tumor suppression SO ONCOGENE LA English DT Review DE polarity; mouse models; Peutz-Jeghers; cancer; hamartoma; STK11 ID PEUTZ-JEGHERS-SYNDROME; ACTIVATED PROTEIN-KINASE; LUNG-CANCER CELLS; SOMATIC MUTATIONS; METABOLIC CHECKPOINT; GLUCOSE-HOMEOSTASIS; ENDOTHELIAL-CELLS; LKB1-AMPK PATHWAY; CYCLE PROGRESSION; ENERGETIC STRESS AB Germ line mutations in the LKB1 tumor suppressor gene are associated with the Peutz-Jeghers polyposis and cancer syndrome. Somatic mutations in Lkb1 are observed in sporadic pulmonary, pancreatic and biliary cancers and melanomas. The LKB1 serine-threonine kinase functionally and biochemically links control of cellular structure and energy utilization through activation of the AMPK family of kinases. Lkb1 regulates cell polarity through downstream kinases including AMPKs, MARKs and BRSKs, and nutrient utilization and cellular metabolism through the AMPK-mTOR pathway. LKB1 has been shown to affect normal chromosomal segregation, TGF-beta signaling in the mesenchyme and WNT and p53 activity. Although each of the LKB1-dependent processes and downstream pathways have been individually delineated through work across a range of experimental systems, how they relate to Lkb1's role as a tumor suppressor remains to be fully explored and elucidated. The recent development of mouse cancer models harboring engineered mutations in Lkb1 have offered insights into how LKB1 may be functioning to restrain tumorigenesis and how its role as a master regulator of polarity and metabolism could contribute to its tumor suppressor function. C1 [Hezel, A. F.; Bardeesy, N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med, Boston, MA 02114 USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc,Dept Med, Boston, MA 02114 USA. EM Bardeesy.Nabeel@MGH.Harvard.edu NR 127 TC 112 Z9 118 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 24 PY 2008 VL 27 IS 55 BP 6908 EP 6919 DI 10.1038/onc.2008.342 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 375IU UT WOS:000261108200004 PM 19029933 ER PT J AU Sharma, U Chang, EW Yun, SH AF Sharma, Utkarsh Chang, Ernest W. Yun, Seok H. TI Long-wavelength optical coherence tomography at 1.7 mu m for enhanced imaging depth SO OPTICS EXPRESS LA English DT Article ID MULTIPLE-SCATTERING; IN-VIVO; SPECTRAL RANGE; DENSE TISSUE; MONTE-CARLO; NM; ATTENUATION; MICROSCOPY; CONTRAST; SIGNAL AB Multiple scattering in a sample presents a significant limitation to achieve meaningful structural information at deeper penetration depths in optical coherence tomography (OCT). Previous studies suggest that the spectral region around 1.7 mu m may exhibit reduced scattering coefficients in biological tissues compared to the widely used wavelengths around 1.3 mu m. To investigate this long-wavelength region, we developed a wavelength-swept laser at 1.7 mu m wavelength and conducted OCT or optical frequency domain imaging (OFDI) for the first time in this spectral range. The constructed laser is capable of providing a wide tuning range from 1.59 to 1.75 mu m over 160 nm. When the laser was operated with a reduced tuning range over 95 nm at a repetition rate of 10.9 kHz and an average output power of 12.3 mW, the OFDI imaging system exhibited a sensitivity of about 100 dB and axial and lateral resolution of 24 mu m and 14 mu m, respectively. We imaged several phantom and biological samples using 1.3 mu m and 1.7 mu m OFDI systems and found that the depth-dependent signal decay rate is substantially lower at 1.7 mu m wavelength in most, if not all samples. Our results suggest that this imaging window may offer an advantage over shorter wavelengths by increasing the penetration depths as well as enhancing image contrast at deeper penetration depths where otherwise multiple scattered photons dominate over ballistic photons. (c) 2008 Optical Society of America C1 [Yun, Seok H.] Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM syun@hms.harvard.edu FU National Institute Health [R33CA110130]; National Science Foundation [ECCS-0801412] FX This work was supported in part by National Institute Health (Grant R33CA110130) and National Science Foundation (Grant ECCS-0801412). Authors are grateful to M. Suter, B. Vakoc, G. Tearney, and B. Bouma for access to the 1.3-mu m system and P. Heim for helpful discussion. NR 27 TC 62 Z9 63 U1 0 U2 4 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 NOV 24 PY 2008 VL 16 IS 24 BP 19712 EP 19723 DI 10.1364/OE.16.019712 PG 12 WC Optics SC Optics GA 381UR UT WOS:000261561900031 PM 19030057 ER PT J AU Lietha, D Eck, MJ AF Lietha, Daniel Eck, Michael J. TI Crystal Structures of the FAK Kinase in Complex with TAE226 and Related Bis-Anilino Pyrimidine Inhibitors Reveal a Helical DFG Conformation SO PLOS ONE LA English DT Article AB Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase required for cell migration, proliferation and survival. FAK overexpression has been documented in diverse human cancers and is associated with a poor clinical outcome. Recently, a novel bis-anilino pyrimidine inhibitor, TAE226, was reported to efficiently inhibit FAK signaling, arrest tumor growth and invasion and prolong the life of mice with glioma or ovarian tumor implants. Here we describe the crystal structures of the FAK kinase bound to TAE226 and three related bis-anilino pyrimidine compounds. TAE226 induces a conformation of the N-terminal portion of the kinase activation loop that is only observed in FAK, but is distinct from the conformation in both the active and inactive states of the kinase. This conformation appears to require a glycine immediately N-terminal to the "DFG motif", which adopts a helical conformation stabilized by interactions with TAE226. The presence of a glycine residue in this position contributes to the specificity of TAE226 and related compounds for FAK. Our work highlights the fact that kinases can access conformational space that is not necessarily utilized for their native catalytic regulation, and that such conformations can explain and be exploited for inhibitor specificity. C1 [Lietha, Daniel; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Lietha, Daniel; Eck, Michael J.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. RP Lietha, D (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM eck@red.dfci.harvard.edu RI Lietha, Daniel/L-8041-2014 OI Lietha, Daniel/0000-0002-6133-6486 FU NIH [HL048675, CA080942]; Leukemia and Lymphoma Society; NCI [5T32CA09361] FX The research was supported in part by NIH grants HL048675 and CA080942 (MJE). MJE is the recipient of a Scholar Award from the Leukemia and Lymphoma Society. DL was supported by an institutional training grant from the NCI (5T32CA09361). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 27 Z9 28 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 NOV 24 PY 2008 VL 3 IS 11 AR e3800 DI 10.1371/journal.pone.0003800 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YA UT WOS:000265450800010 PM 19030106 ER PT J AU Moulton, EA Burstein, R Tully, S Hargreaves, R Becerra, L Borsook, D AF Moulton, Eric A. Burstein, Rami Tully, Shannon Hargreaves, Richard Becerra, Lino Borsook, David TI Interictal Dysfunction of a Brainstem Descending Modulatory Center in Migraine Patients SO PLOS ONE LA English DT Article AB Background: The brainstem contains descending circuitry that can modulate nociceptive processing (neural signals associated with pain) in the dorsal horn of the spinal cord and the medullary dorsal horn. In migraineurs, abnormal brainstem function during attacks suggest that dysfunction of descending modulation may facilitate migraine attacks, either by reducing descending inhibition or increasing facilitation. To determine whether a brainstem dysfunction could play a role in facilitating migraine attacks, we measured brainstem function in migraineurs when they were not having an attack (i.e. the interictal phase). Methods and Findings: Using fMRI (functional magnetic resonance imaging), we mapped brainstem activity to heat stimuli in 12 episodic migraine patients during the interictal phase. Separate scans were collected to measure responses to 41 degrees C and noxious heat (pain threshold+1 degrees C). Stimuli were either applied to the forehead on the affected side (as reported during an attack) or the dorsum of the hand. This was repeated in 12 age-gender-matched control subjects, and the side tested corresponded to that in the matched migraine patients. Nucleus cuneiformis (NCF), a component of brainstem pain modulatory circuits, appears to be hypofunctional in migraineurs. 3 out of the 4 thermal stimulus conditions showed significantly greater NCF activation in control subjects than the migraine patients. Conclusions: Altered descending modulation has been postulated to contribute to migraine, leading to loss of inhibition or enhanced facilitation resulting in hyperexcitability of trigeminovascular neurons. NCF function could potentially serve as a diagnostic measure in migraine patients, even when not experiencing an attack. This has important implications for the evaluation of therapies for migraine. C1 [Moulton, Eric A.; Tully, Shannon; Becerra, Lino; Borsook, David] Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, Belmont, MA 02178 USA. [Moulton, Eric A.; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. [Burstein, Rami] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hargreaves, Richard] Merck & Co Inc, West Point, PA USA. [Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula Martinos Ctr Bioengn, Dept Radiol, Charlestown, MA USA. RP Moulton, EA (reprint author), Harvard Univ, McLean Hosp, Sch Med, PAIN Grp,Brain Imaging Ctr, Belmont, MA 02178 USA. EM dborsook@partners.org FU NIH/NINDS [R01NS056195-02, R01NS051484-04]; Merck and Co FX This study was financially supported by NIH/NINDS grants to David Borsook (R01NS056195-02) and Rami Burstein (R01NS051484-04), and by an unrestricted grant from Merck and Co. These financial sponsors did not have a direct role in this study, and did not participate in the preparation of this manuscript. NR 46 TC 94 Z9 94 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 24 PY 2008 VL 3 IS 11 AR e3799 DI 10.1371/journal.pone.0003799 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 436YA UT WOS:000265450800009 PM 19030105 ER PT J AU Ono, K Condron, MM Ho, L Wang, J Zhao, W Pasinetti, GM Teplow, DB AF Ono, Kenjiro Condron, Margaret M. Ho, Lap Wang, Jun Zhao, Wei Pasinetti, Giulio M. Teplow, David B. TI Effects of Grape Seed-derived Polyphenols on Amyloid beta-Protein Self-assembly and Cytotoxicity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FIBRILS IN-VITRO; ALZHEIMERS-DISEASE; CROSS-LINKING; SYNAPTIC PLASTICITY; WINE CONSUMPTION; APOLIPOPROTEIN-E; TRANSGENIC MICE; ALPHA-SYNUCLEIN; FRENCH PARADOX; MOUSE MODEL AB Epidemiological evidence suggests that moderate consumption of red wine reduces the incidence of Alzheimer disease (AD). To study the protective effects of red wine, experiments recently were executed in the Tg2576 mouse model of AD. These studies showed that a commercially available grape seed polyphenolic extract, MegaNatural-AZ (MN), significantly attenuated AD-type cognitive deterioration and reduced cerebral amyloid deposition (Wang, J., Ho, L., Zhao, W., Ono, K., Rosensweig, C., Chen, L., Humala, N., Teplow, D. B., and Pasinetti, G. M. (2008) J. Neurosci. 28, 6388-6392). To elucidate the mechanistic bases for these observations, here we used CD spectroscopy, photo-induced cross-linking of unmodified proteins, thioflavin T fluorescence, size exclusion chromatography, and electron microscopy to examine the effects of MN on the assembly of the two predominant disease-related amyloid beta-protein alloforms, A beta 40 and A beta 42. We also examined the effects of MN on A beta-induced cytotoxicity by assaying 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide metabolism and lactate dehydrogenase activity in A beta-treated, differentiated pheochromocytoma (PC12) cells. Initial studies revealed that MN blocked A beta fibril formation. Subsequent evaluation of the assembly stage specificity of the effect showed thatMNwas able to inhibit protofibril formation, pre-protofibrillar oligomerization, and initial coil -> alpha-helix/beta-sheet secondary structure transitions. Importantly, MN had protective effects in assays of cytotoxicity in which MN was mixed with A beta prior to peptide assembly or following assembly and just prior to peptide addition to cells. These data suggest that MN is worthy of consideration as a therapeutic agent for AD. C1 [Ho, Lap; Wang, Jun; Zhao, Wei; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ono, Kenjiro; Condron, Margaret M.; Teplow, David B.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Ono, Kenjiro; Condron, Margaret M.; Teplow, David B.] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Ono, Kenjiro; Condron, Margaret M.; Teplow, David B.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA. [Ono, Kenjiro] Kanazawa Univ, Grad Sch Med Sci, Dept Neurol & Neurobiol, Kanazawa, Ishikawa 9208640, Japan. [Ho, Lap; Wang, Jun; Zhao, Wei; Pasinetti, Giulio M.] Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. [Ho, Lap; Pasinetti, Giulio M.] Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Pasinetti, GM (reprint author), Mt Sinai Sch Med, Dept Psychiat, 1468 Madison Ave,Rm 14-94C, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu; dteplow@ucla.edu RI Zhao, Wei/B-3220-2010; Zhao, Wei/A-2206-2010 FU National Institutes of Health [PO1 AT004511]; NCCAM; Department of Veterans Affairs Merit Review; James J. Peters Veterans Affairs Medical Center Geriatric Research Education Clinical Center Program, and Polyphenolics; Japan Human Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research; Alzheimer's Association; Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA; [AG027818] FX This work was supported, in whole or in part, by National Institutes of Health Grant PO1 AT004511 through the NCCAM (to L. H., G. M. P., and D. B. T.) and Grant AG027818(to (D. B. T.). This work also was supported by the Department of Veterans Affairs Merit Review grant and a grant from the James J. Peters Veterans Affairs Medical Center Geriatric Research Education Clinical Center Program, and Polyphenolics (to G. M. P.); grants from the Japan Human Science Foundation and the Mochida Memorial Foundation for Medical and Pharmaceutical Research (to K. O.); and grants from the Alzheimer's Association, and the Jim Easton Consortium for Alzheimer's Drug Discovery and Biomarkers at UCLA (to D. B. T.). 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 53 TC 103 Z9 109 U1 2 U2 27 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 NOV 21 PY 2008 VL 283 IS 47 BP 32176 EP 32187 DI 10.1074/jbc.M806154200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700004 PM 18815129 ER PT J AU Stamler, R Keutmann, HT Sidis, Y Kattamuri, C Schneyer, A Thompson, TB AF Stamler, Robin Keutmann, Henry T. Sidis, Yisrael Kattamuri, Chandramohan Schneyer, Alan Thompson, Thomas B. TI The Structure of FSTL3.Activin A Complex DIFFERENTIAL BINDING OF N-TERMINAL DOMAINS INFLUENCES FOLLISTATIN-TYPE ANTAGONIST SPECIFICITY SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BONE-MORPHOGENETIC PROTEIN; TGF-BETA SUPERFAMILY; ACTIVIN-BINDING; RECEPTOR-BINDING; FAMILY; GENE; CELL; MECHANISMS; MYOSTATIN; RECOGNITION AB Transforming growth factor beta family ligands are neutralized by a number of structurally divergent antagonists. Follistatin-type antagonists, which include splice variants of follistatin (FS288 and FS315) and follistatin-like 3 (FSTL3), have high affinity for activin A but differ in their affinity for other ligands, particularly bone morphogenetic proteins. To understand the structural basis for ligand specificity within FS-type antagonists, we determined the x-ray structure of activin A in complex with FSTL3 to a resolution of 2.5 angstrom. Similar to the previously resolved FS.activin A structures, the ligand is encircled by two antagonist molecules blocking all ligand receptor-binding sites. Recently, the significance of the FS N-terminal domain interaction at the ligand type I receptor site has been questioned; however, our data show that for FSTL3, the N-terminal domain forms a more intimate contact with activin A, implying that this interaction is stronger than that for FS. Furthermore, binding studies revealed that replacing the FSTL3 N-terminal domain with the corresponding FS domain considerably lowers activin A affinity. Therefore, both structural and biochemical evidence support a significant interaction of the N-terminal domain of FSTL3 with activin A. In addition, structural comparisons with bone morphogenetic proteins suggest that the interface where the N-terminal domain binds may be the key site for determining FS-type antagonist specificity. C1 [Stamler, Robin; Kattamuri, Chandramohan; Thompson, Thomas B.] Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Keutmann, Henry T.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Sidis, Yisrael] Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. [Schneyer, Alan] Baystate Med Ctr, Pioneer Valley Life Sci Inst, Springfield, MA 01107 USA. RP Thompson, TB (reprint author), Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Med Sci Bldg,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM tom.thompson@ucmail.uc.edu FU National Institutes of Health [GM084186, DK053828] FX This work was supported, in whole or in part, by National Institutes of Health Grants GM084186 ( to T. B. T.) and DK053828 ( to H. T. K.). NR 50 TC 32 Z9 35 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 NOV 21 PY 2008 VL 283 IS 47 BP 32831 EP 32838 DI 10.1074/jbc.M801266200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 372HW UT WOS:000260893700072 PM 18768470 ER PT J AU Shen, XH Liu, YC Hsu, YJ Fujiwara, Y Kim, J Mao, XH Yuan, GC Orkin, SH AF Shen, Xiaohua Liu, Yingchun Hsu, Yu-Jung Fujiwara, Yuko Kim, Jonghwan Mao, Xiaohong Yuan, Guo-Cheng Orkin, Stuart H. TI EZH1 Mediates Methylation on Histone H3 Lysine 27 and Complements EZH2 in Maintaining Stem Cell Identity and Executing Pluripotency SO MOLECULAR CELL LA English DT Article ID POLYCOMB GROUP PROTEINS; METHYLTRANSFERASE ACTIVITY; MOUSE DEVELOPMENT; DEVELOPMENTAL REGULATORS; DROSOPHILA ESC; DIFFERENTIATION; ENHANCER; EED; COMPLEXES; MESODERM AB Trimethylation on H3K27 (H3K27me3) mediated by Polycomb repressive complex 2 (PRC2) has been linked to embryonic stem cell (ESC) identity and pluripotency. EZH2, the catalytic subunit of PRC2, has been reported as the sole histone methyltransferase that methylates H3K27 and mediates transcriptional silencing. Analysis of Ezh2(-/-) ESCs suggests existence of an additional enzyme(s) catalyzing H3K27 methylation. We have identified EZH1, a homolog of EZH2 that is physically present in a noncanonical PRC2 complex, as an H3K27 methyltransferase in vivo and in vitro. EZH1 colocalizes with the H3K27me3 mark on chromatin and preferentially preserves this mark on development-related genes in Ezh2(-/-) ESCs. Depletion of Ezh1 in cells lacking Ezh2 abolishes residual methylation on H3K27 and derepresses H3K27me3 target genes, demonstrating a role of EZH1 in safeguarding ESC identity. Ezh1 partially complements Ezh2 in executing pluripotency during ESC differentiation, suggesting that cell-fate transitions require epigenetic specificity. C1 [Shen, Xiaohua; Hsu, Yu-Jung; Fujiwara, Yuko; Kim, Jonghwan; Orkin, Stuart H.] Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shen, Xiaohua; Hsu, Yu-Jung; Fujiwara, Yuko; Kim, Jonghwan; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Liu, Yingchun; Yuan, Guo-Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Kim, Jonghwan; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Mao, Xiaohong] Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA. [Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU Claudia Adams Barr Program in Cancer Research FX We are grateful to T. Magnuson for Eed-/- ESCs, G. Keller for T-GFP ESCs, A. Glaser, S., Schaft, J., Lubitz, S., Vintersten, K., van der Hoeven, F., Tufteland, Smith for 46C cells, and K. Helin for EED antibody. We thank R. Tomaino for K.R., Aasland, R., Anastassiadis, K., Ang, S.L., and Stewart, A.F. (2006). performing LC-MS/MS, DFCI Microarray Core for processing microarray sam- Multiple epigenetic maintenance factors implicated by the loss of M112 in ples, and W. Li, T. Liu, and X.S. Liu for assistance with MAT. We thank B. Wil- mouse development. Development 133, 1423-1432. son, C. Roberts, D. Levasseur, and X. Xia for criticism, and members of the Johnson, W.E., Li, W., Meyer, C.A., Gottardo, R., Carroll, J.S., Brown, M., and Orkin lab for their assistance. G.-C.Y. is supported by the Claudia Adams Barr Program in Cancer Research. S.H.O. is an Investigator of the HHMI. NR 47 TC 397 Z9 406 U1 0 U2 19 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 NOV 21 PY 2008 VL 32 IS 4 BP 491 EP 502 DI 10.1016/j.molcel.2008.10.016 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 377ZD UT WOS:000261290000007 PM 19026780 ER PT J AU Yang, G Li, YT Nishimura, EK Xin, H Zhou, AY Guo, YS Dong, L Denning, MF Nickoloff, BJ Cui, RT AF Yang, Guang Li, Yitang Nishimura, Emi K. Xin, Hong Zhou, Anyu Guo, Yinshi Dong, Liang Denning, Mitchell F. Nickoloff, Brian J. Cui, Rutao TI Inhibition of PAX3 by TGF-beta Modulates Melanocyte Viability SO MOLECULAR CELL LA English DT Article ID GROWTH-FACTOR-BETA; MICROPHTHALMIA GENE-PRODUCT; WAARDENBURG-SYNDROME; TRANSCRIPTION FACTOR; HUMAN SKIN; HUMAN MELANOMAS; CELL SURVIVAL; ULTRAVIOLET-B; IN-VIVO; EXPRESSION AB The protein encoded by paired-box homeotic gene 3 (PAX3) is a key regulator of the microphthalmia-associated transcription factor (Mito in the melanocyte lineage. Here, we show that PAX3 expression in skin is directly inhibited by TGF-beta/Smads. UV irradiation represses TGF-beta in keratinocytes, and the repression of TGF-beta/Smads upregulates PAX3 in melanocytes, which is associated with a UV-induced melanogenic response and consequent pigmentation. Furthermore, the TGF-beta-PAX3 signaling pathway interacts with the p53-POMC/MSH-MC1R signaling pathway, and both are crucial in melanogenesis. The activation of p53-POMC/MSH-MC1R signaling is required for the UV-induced melanogenic response because PAX3 functions in synergy with SOX10 in a cAMP-response element (CRE)-dependent manner to regulate the transcription of Mitf. This study will provide a rich foundation for further research on skin cancer prevention by enabling us to identify targeted small molecules in the signaling pathways of the UV-induced melanogenic response that are highly likely to induce naturally protective pigmentation. C1 [Xin, Hong; Guo, Yinshi; Dong, Liang; Denning, Mitchell F.; Nickoloff, Brian J.; Cui, Rutao] Loyola Univ Chicago, Dept Pathol, Inst Oncol, Cardinal Bernardin Canc Ctr,Stritch Sch Med, Maywood, IL 60153 USA. [Yang, Guang; Li, Yitang; Zhou, Anyu] Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst,Childrens Hosp Boston, Boston, MA 02115 USA. [Nishimura, Emi K.] Kanazawa Univ, Dept Stem Cell Med, Canc Res Inst, Kanazawa, Ishikawa 9200934, Japan. RP Cui, RT (reprint author), Loyola Univ Chicago, Dept Pathol, Inst Oncol, Cardinal Bernardin Canc Ctr,Stritch Sch Med, 2160 S 1st Ave, Maywood, IL 60153 USA. EM rcui@lumc.edu FU American Cancer Society [RSG-09022-01-CNE]; American Cancer Society-Illinois Division [08-026]; Elsa U. Pardee Foundation FX We thank Dr. Michel Goossens for the PAX3 construct. We also thank Dr. David E. Fisher, Dr. Scott R. Granter, Dr. Hans R Widlund, Dr. Jinyan Du, Dr. Xiansi Zhao, Dr. Jiwang Zhang, Dr. Guo Wei, Dr. Wei Li, and Dr. Hai Li for helpful comments. This work was supported by American Cancer Society (RSG-09022-01-CNE), American Cancer Society-Illinois Division (08-026), and Elsa U. Pardee Foundation (R.C.). No potential conflicts of interest were disclosed. NR 61 TC 47 Z9 49 U1 0 U2 10 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 NOV 21 PY 2008 VL 32 IS 4 BP 554 EP 563 DI 10.1016/j.molcel.2008.11.002 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 377ZD UT WOS:000261290000012 PM 19026785 ER PT J AU Swanson, KD Tang, Y Ceccarelli, DF Poy, F Sliwa, JP Neel, BG Eck, MJ AF Swanson, Kenneth D. Tang, Yong Ceccarelli, Derek F. Poy, Florence Sliwa, Jan P. Neel, Benjamin G. Eck, Michael J. TI The Skap-hom Dimerization and PH Domains Comprise a 3 '-Phosphoinositide-Gated Molecular Switch SO MOLECULAR CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; MEDIATED INTEGRIN ACTIVATION; T-CELL; CRYSTAL-STRUCTURE; ACTIN CYTOSKELETON; SIGNALING MODULE; STRUCTURAL BASIS; TYROSINE KINASE; PROTEIN; ADAPTER AB PH domains, by binding to phosphoinositides, often serve as membrane-targeting modules. Using crystallographic, biochemical, and cell biological approaches, we have uncovered a mechanism that the integrin-signaling adaptor Skap-hom uses to mediate cytoskeletal interactions. Skap-hom is a homodimer containing an N-terminal four-helix bundle dimerization domain, against which its two PH domains pack in a conformation incompatible with phosphoinositide binding. The isolated PH domains bind PI[3,4,5]P(3), and mutations targeting the dimerization domain or the PH domain's PI[3,4,5]P(3)-binding pocket prevent Skap-hom localization to ruffles. Targeting is retained when the PH domain is deleted or by combined mutation of the PI[3,4,5]P(3)-binding pocket and the PH/dimerization domain interface. Thus, the dimerization and PH domain form a PI[3,4,5]P(3)-responsive molecular switch that controls Skap-hom function. C1 [Swanson, Kenneth D.; Neel, Benjamin G.] Beth Israel Deaconess Med Ctr, Canc Biol Program, Div Hematol Oncol, Dept Med, Boston, MA 02115 USA. [Tang, Yong; Ceccarelli, Derek F.; Poy, Florence; Sliwa, Jan P.; Eck, Michael J.] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Tang, Yong; Ceccarelli, Derek F.; Poy, Florence; Eck, Michael J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Neel, BG (reprint author), Univ Toronto, Ontario Canc Inst, Dept Med Biophys, Toronto, ON M5G 1L7, Canada. EM bneel@uhnresearch.ca; eck@red.dfci.harvard.edu FU National Institutes of Health (NIH) [R01CA080942, P01HL048675, R37CA 41952, R01CA114945, 2T32 HL07623-23]; Canadian Institute of Health Research; Canadian-Strategic Training in Health Research fellowship FX We thank Q. Hao at MacCHESS beamline Al, T. Boggon and Y. Xu for assistance with data collection, R. Marmorstein for critical reading of the manuscript, F. Sicheri for help with FP, and L.C. Cantley for his support. This work was supported by National Institutes of Health (NIH) grants R01CA080942 and P01HL048675 to M.J.E., R37CA 41952 and R01CA114945 to B.G.N., and 2T32 HL07623-23 to K.D.S. and by the Canadian Institute of Health Research, the Canadian-Strategic Training in Health Research fellowship, to D.F.C. pEBHA-Fyb and mCherry-tagged actin were gifts from Chris Rudd (University of Cambridge) and Max Krummel (University of California, San Francisco), respectively. The authors declare that they have no competing financial interests. NR 48 TC 19 Z9 21 U1 0 U2 1 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 NOV 21 PY 2008 VL 32 IS 4 BP 564 EP 575 DI 10.1016/j.molcel.2008.09.022 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 377ZD UT WOS:000261290000013 PM 19026786 ER PT J AU Roberts, DA Hansen, VN Niven, AC Thompson, MG Seco, J Evans, PM AF Roberts, D. A. Hansen, V. N. Niven, A. C. Thompson, M. G. Seco, J. Evans, P. M. TI A low Z linac and flat panel imager: comparison with the conventional imaging approach SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; MONTE-CARLO-SIMULATION; BREMSSTRAHLUNG BEAMS; RADIATION-THERAPY; VERIFICATION; FEASIBILITY; ACCELERATOR; IRRADIATION; PROSTATE; POSITION AB Experimental and Monte Carlo simulations were conducted for an Elekta Ltd Precise Treatment System linac fitted with a low Z insert of sufficient thickness to remove all primary electrons. A variety of amorphous silicon based panels employing different scintillators were modelled to determine their response to a variety of x-ray spectra and produce an optimized portal imaging system. This study has shown that in a low Z configuration the vast majority of x-rays are produced in the nickel electron window, and with a combination of a carbon insert and caesium iodide based XVI-panel, significant improvement in the object contrast was achieved. For thin, head and neck-type geometries, contrast is 4.62 times greater for 1.6 cm bone in 5.8 cm water than the standard 6MV/iViewGT system. For thicker, pelvis-type geometries contrast increases by a factor of 1.3 for 1.6 cm of bone in 25.8 cm water. To obtain images with the same signal-to-noise ratio as the 6 MV/iViewGT system, dose reductions of a factor of 15 and 4.2 are possible for 5.8 cm and 25.8 cm phantoms respectively. This design has the advantage of being easily implemented on a standard linac and provides a portal image directly from the therapy beam aperture. C1 [Roberts, D. A.; Hansen, V. N.; Evans, P. M.] Inst Canc Res, Joint Dept Phys, Sutton, Surrey, England. [Roberts, D. A.; Hansen, V. N.; Evans, P. M.] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Niven, A. C.; Thompson, M. G.] Elekta Ltd, Crawley, W Sussex, England. [Seco, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roberts, DA (reprint author), Inst Canc Res, Joint Dept Phys, Downs Rd, Sutton, Surrey, England. RI Evans, Philip/A-6257-2009; Seco, Joao/J-4451-2012 FU Elekta Ltd; The Institute of Cancer Research; Cancer Research UK [C46/A3970] FX This work is supported by Elekta Ltd and The Institute of Cancer Research. Work of the radiotherapy physics group is partially supported by Cancer Research UK under programme grant C46/A3970. We are grateful for information provided by Elekta Ltd and Perkin Elmer for the purposes of modelling the linac and detectors. We are extremely grateful to Andrew Lake for helping with the experiments and to Alan Hitchings for advice on the target holder design. Also to Nick Smith, Clive Long and Craig Cummings for manufacturing and modifying the target insert and to Mike Partridge for useful discussions relating to detectors. We would also like to thank all the ICR/RMH physics staff who have contributed with comments or help with this work. NR 22 TC 26 Z9 26 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 21 PY 2008 VL 53 IS 22 BP 6305 EP 6319 DI 10.1088/0031-9155/53/22/003 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 370JL UT WOS:000260758400003 PM 18936518 ER PT J AU Stenman, JM Rajagopal, J Carroll, TJ Ishibashi, M McMahon, J McMahon, AP AF Stenman, Jan M. Rajagopal, Jay Carroll, Thomas J. Ishibashi, Makoto McMahon, Jill McMahon, Andrew P. TI Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature SO SCIENCE LA English DT Article ID BETA-CATENIN GENE; ENDOTHELIAL-CELLS; MOUSE DEVELOPMENT; RECEPTOR GENE; EXPRESSION; PROLIFERATION; ANGIOGENESIS; INACTIVATION; DISRUPTION; PATHWAY AB Every organ depends on blood vessels for oxygen and nutrients, but the vasculature associated with individual organs can be structurally and molecularly diverse. The central nervous system (CNS) vasculature consists of a tightly sealed endothelium that forms the blood- brain barrier, whereas blood vessels of other organs are more porous. Wnt7a and Wnt7b encode two Wnt ligands produced by the neuroepithelium of the developing CNS coincident with vascular invasion. Using genetic mouse models, we found that these ligands directly target the vascular endothelium and that the CNS uses the canonical Wnt signaling pathway to promote formation and CNS- specific differentiation of the organ's vasculature. C1 [Stenman, Jan M.; Rajagopal, Jay; Carroll, Thomas J.; Ishibashi, Makoto; McMahon, Jill; McMahon, Andrew P.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Rajagopal, Jay] Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. [McMahon, Andrew P.] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP McMahon, AP (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM mcmahon@mcb.harvard.edu FU Wenner-Gren Foundations (Sweden); National Heart, Lung, and Blood Institute [HL076393]; NIH [DK054364] FX We thank P. D'Amore for helpful discussions. Supported by a Wenner-Gren Foundations (Sweden) postdoctoral fellowship (J.M.S.), National Heart, Lung, and Blood Institute grant HL076393 (J.R.), and NIH grant DK054364 (A.P.M.). The authors have a patent pending on the basis of the results reported in this paper. A.P.M. has been a paid consultant for Merck, Genentech, and Wythe in the past 3 years. NR 27 TC 211 Z9 215 U1 3 U2 15 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 NOV 21 PY 2008 VL 322 IS 5905 BP 1247 EP 1250 DI 10.1126/science.1164594 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374HC UT WOS:000261033400042 PM 19023080 ER PT J AU Heinrich, MC Maki, RG Corless, CL Antonescu, CR Harlow, A Griffith, D Town, A McKinley, A Ou, WB Fletcher, JA Fletcher, CDM Huang, X Cohen, DP Baum, CM Demetri, GD AF Heinrich, Michael C. Maki, Robert G. Corless, Christopher L. Antonescu, Cristina R. Harlow, Amy Griffith, Diana Town, Ajia McKinley, Arin Ou, Wen-Bin Fletcher, Jonathan A. Fletcher, Christopher D. M. Huang, Xin Cohen, Darrel P. Baum, Charles M. Demetri, George D. TI Primary and Secondary Kinase Genotypes Correlate With the Biological and Clinical Activity of Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development CY SEP 12-15, 2006 CL Chicago, IL SP Amer Assoc Canc Res ID ACQUIRED-RESISTANCE; KIT MUTATIONS; INHIBITOR SU11248; MISSENSE MUTATION; SARCOMA-GROUP; GROWTH-FACTOR; IN-VITRO; MESYLATE; CANCER; EFFICACY AB Purpose Most gastrointestinal stromal tumors (GISTs) harbor mutant KIT or platelet-derived growth factor receptor alpha (PDGFRA) kinases, which are imatinib targets. Sunitinib, which targets KIT, PDGFRs, and several other kinases, has demonstrated efficacy in patients with GIST after they experience imatinib failure. We evaluated the impact of primary and secondary kinase genotype on sunitinib activity. Patients and Methods Tumor responses were assessed radiologically in a phase I/II trial of sunitinib in 97 patients with metastatic, imatinib-resistant/intolerant GIST. KIT/PDGFRA mutational status was determined for 78 patients by using tumor specimens obtained before and after prior imatinib therapy. Kinase mutants were biochemically profiled for sunitinib and imatinib sensitivity. Results Clinical benefit (partial response or stable disease for >= 6 months) with sunitinib was observed for the three most common primary GIST genotypes: KIT exon 9 (58%), KIT exon 11 (34%), and wild-type KIT/PDGFRA (56%). Progression-free survival (PFS) was significantly longer for patients with primary KIT exon 9 mutations (P = .0005) or with a wild-type genotype (P = .0356) than for those with KIT exon 11 mutations. The same pattern was observed for overall survival (OS). PFS and OS were longer for patients with secondary KIT exon 13 or 14 mutations (which involve the KIT-adenosine triphosphate binding pocket) than for those with exon 17 or 18 mutations (which involve the KIT activation loop). Biochemical profiling studies confirmed the clinical results. Conclusion The clinical activity of sunitinib after imatinib failure is significantly influenced by both primary and secondary mutations in the predominant pathogenic kinases, which has implications for optimization of the treatment of patients with GIST. C1 [Heinrich, Michael C.] Portland VA Med Ctr, Dept Med, Div Hematol Oncol, Portland, OR 97239 USA. Portland VA Med Ctr, Dept Cell & Dev Biol, Div Hematol Oncol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97239 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Pfizer Global Res & Dev, La Jolla, CA USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, Dept Med, Div Hematol Oncol, R&D 19,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM Heinrich@ohsu.edu FU NCI NIH HHS [1P50 CA127003-01, CA 47179] NR 39 TC 309 Z9 344 U1 3 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 NOV 20 PY 2008 VL 26 IS 33 BP 5352 EP 5359 DI 10.1200/JCO.2007.15.7461 PG 8 WC Oncology SC Oncology GA 376RA UT WOS:000261199500009 PM 18955458 ER PT J AU Heinrich, MC Owzar, K Corless, CL Hollis, D Borden, EC Fletcher, CDM Ryan, CW von Mehren, M Blanke, CD Rankin, C Benjamin, RS Bramwell, VH Demetri, GD Bertagnolli, MM Fletcher, JA AF Heinrich, Michael C. Owzar, Kouros Corless, Christopher L. Hollis, Donna Borden, Ernest C. Fletcher, Christopher D. M. Ryan, Christopher W. von Mehren, Margaret Blanke, Charles D. Rankin, Cathryn Benjamin, Robert S. Bramwell, Vivien H. Demetri, George D. Bertagnolli, Monica M. Fletcher, Jonathan A. TI Correlation of Kinase Genotype and Clinical Outcome in the North American Intergroup Phase III Trial of Imatinib Mesylate for Treatment of Advanced Gastrointestinal Stromal Tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RECEPTOR TYROSINE KINASE; OF-FUNCTION MUTATIONS; TERM-FOLLOW-UP; C-KIT; DOSE IMATINIB; SARCOMA-GROUP; GENE; INHIBITOR; EFFICACY; SAFETY AB Purpose Imatinib mesylate is standard treatment for patients who have advanced gastrointestinal stromal tumor (GIST), but not all patients benefit equally. In previous studies, GIST genotype correlated with treatment outcome and optimal imatinib dosing. Patients and Methods We examined the relationship between kinase genotype and treatment outcome for 428 patients enrolled on the North American phase III study SWOG S0033/CALGB 150105 and treated with either 400 mg or 800 mg daily doses of imatinib. Results The presence of KIT exon 11-mutant genotype (n = 283) correlated with improved treatment outcome when compared with KIT exon 9-mutant (n = 32) and wild-type (WT; n = 67) genotypes for objective response (complete response [CR]/ partial response [PR], 71.7% v 44.4% [P = .007]; and 44.6% [P = .0002], respectively); time to tumor progression (TTP; median 24.7 months v 16.7 and 12.8 months, respectively); and overall survival (OS; median 60.0 months v 38.4 and 49.0 months, respectively). The survival outcomes for patients with exon 9-mutant, exon 11-mutant or WT GIST were not affected by imatinib dose. However, there was evidence of improved response rates for patients with exon 9-mutant tumors treated with imatinib 800 mg versus 400 mg (CR/PR, 67% v 17%; P = .02). Patients who had CD117-negative GIST had similar TTP but inferior OS compared with patients who had CD117-positive disease, which suggests that patients who have CD117-negative GIST may benefit from imatinib treatment. In addition, we identified novel but rare mutations of the KIT extracellular domain (exons 8 and 9). Conclusion We confirmed the favorable impact of KIT exon 11 genotype when compared with KIT exon 9 and wild-type genotype for patients with advanced GIST who are treated with imatinib. C1 [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Div Hematol Oncol, Portland, OR 97239 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Tom Baker Canc Clin, Calgary, AB, Canada. RP Heinrich, MC (reprint author), Portland VA Med Ctr, 3710 SW US Vet Hosp Rd,R&D 19, Portland, OR 97239 USA. EM heinrich@ohsu.edu FU National Cancer Institute (NCI) [CA33601, CA04919, CA32291, CA27525, CA31946, CA32102, CA77202, U01-CA70172-01, N01-CM-17003]; Veterans Affairs Merit Review; Novartis Pharmaceuticals FX Supported in part by Grants No. CA33601, CA04919, CA32291, CA27525, CA31946, CA32102, and CA77202 from the National Cancer Institute (NCI); by Grants No. U01-CA70172-01 and N01-CM-17003 from the NCI; by a Veterans Affairs Merit Review Grant (M. H.); and by research funding from Novartis Pharmaceuticals. NR 28 TC 274 Z9 297 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 NOV 20 PY 2008 VL 26 IS 33 BP 5360 EP 5367 DI 10.1200/JCO.2008.17.4284 PG 8 WC Oncology SC Oncology GA 376RA UT WOS:000261199500010 PM 18955451 ER PT J AU Heymach, JV Paz-Ares, L De Braud, F Sebastian, M Stewart, DJ Eberhardt, WEE Ranade, AA Cohen, G Trigo, JM Sandler, AB Bonomi, PD Herbst, RS Krebs, AD Vasselli, J Johnson, BE AF Heymach, John V. Paz-Ares, Luis De Braud, Filippo Sebastian, Martin Stewart, David J. Eberhardt, Wilfried E. E. Ranade, Anantbhushan A. Cohen, Graham Trigo, Jose Manuel Sandler, Alan B. Bonomi, Philip D. Herbst, Roy S. Krebs, Annetta D. Vasselli, James Johnson, Bruce E. TI Randomized Phase II Study of Vandetanib Alone or With Paclitaxel and Carboplatin as First-Line Treatment for Advanced Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 12th World Conference on Lung Cancer CY SEP 02-06, 2007 CL Seoul, SOUTH KOREA ID RECEPTOR TYROSINE KINASE; PREVIOUSLY TREATED PATIENTS; ENDOTHELIAL GROWTH-FACTOR; CLINICAL-EVALUATION; MALIGNANT-TUMORS; TRIAL; ZD6474; GEFITINIB; COMBINATION; INHIBITOR AB Purpose Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). Patients and Methods All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P < .2) and to demonstrate noninferiority for vandetanib versus PC. Overall survival was a secondary assessment. Results The risk of progression was reduced for patients receiving VPC (n = 56) versus PC (n = 52; hazard ratio = 0.76, one-sided P = .098); median PFS was 24 weeks (VPC) and 23 weeks (PC). The vandetanib monotherapy arm (n = 73) was discontinued after a planned interim PFS analysis met the criterion for discontinuation (hazard ratio > 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. Conclusion VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had C1 [Johnson, Bruce E.] Dana Farber Canc Inst, Boston, MA 02115 USA. Doce Octubre Univ Hosp, Madrid, Spain. Hosp Clin Virgen Victoria, Malaga, Spain. European Inst Oncol, Milan, Italy. Johannes Gutenberg Univ Mainz, Med Klin 3, Mainz, Germany. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Duisburg Essen, Univ Klinikum Essen, Essen, Germany. Deenanath Mangeshkar Hosp & Res Ctr, Pune, Maharashtra, India. Mary Potter Oncol Ctr, Pretoria, South Africa. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Astra Zeneca, Wilmington, DE USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM bruce_johnson@dfci.harvard.edu RI IBIS, NUEVAS TERAPIA/P-3415-2015; de Braud, Filippo/B-9997-2017 OI de Braud, Filippo/0000-0003-0103-730X NR 32 TC 150 Z9 153 U1 1 U2 14 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 NOV 20 PY 2008 VL 26 IS 33 BP 5407 EP 5415 DI 10.1200/JCO.2008.17.3138 PG 9 WC Oncology SC Oncology GA 376RA UT WOS:000261199500017 PM 18936474 ER PT J AU Meigs, JB Shrader, P Sullivan, LM McAteer, JB Fox, CS Dupuis, J Manning, AK Florez, JC Wilson, PWF D'Agostino, RB Cupples, LA AF Meigs, James B. Shrader, Peter Sullivan, Lisa M. McAteer, Jarred B. Fox, Caroline S. Dupuis, Josee Manning, Alisa K. Florez, Jose C. Wilson, Peter W. F. D'Agostino, Ralph B., Sr. Cupples, L. Adrienne TI Genotype Score in Addition to Common Risk Factors for Prediction of Type 2 Diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; GLUCOSE-TOLERANCE; LIFE-STYLE; LOCI; POLYMORPHISMS; MELLITUS; DISEASE; METAANALYSIS; REPLICATION; POPULATION AB Background: Multiple genetic loci have been convincingly associated with the risk of type 2 diabetes mellitus. We tested the hypothesis that knowledge of these loci allows better prediction of risk than knowledge of common phenotypic risk factors alone. Methods: We genotyped single-nucleotide polymorphisms (SNPs) at 18 loci associated with diabetes in 2377 participants of the Framingham Offspring Study. We created a genotype score from the number of risk alleles and used logistic regression to generate C statistics indicating the extent to which the genotype score can discriminate the risk of diabetes when used alone and in addition to clinical risk factors. Results: There were 255 new cases of diabetes during 28 years of follow-up. The mean (+/-SD) genotype score was 17.7+/-2.7 among subjects in whom diabetes developed and 17.1+/-2.6 among those in whom diabetes did not develop (P<0.001). The sex-adjusted odds ratio for diabetes was 1.12 per risk allele (95% confidence interval, 1.07 to 1.17). The C statistic was 0.534 without the genotype score and 0.581 with the score (P=>0.01). In a model adjusted for sex and self-reported family history of diabetes, the C statistic was 0.595 without the genotype score and 0.615 with the score (P=0.11). In a model adjusted for age, sex, family history, body-mass index, fasting glucose level, systolic blood pressure, high-density lipoprotein cholesterol level, and triglyceride level, the C statistic was 0.900 without the genotype score and 0.901 with the score (P=0.49). The genotype score resulted in the appropriate risk reclassification of, at most, 4% of the subjects. Conclusions: A genotype score based on 18 risk alleles predicted new cases of diabetes in the community but provided only a slightly better prediction of risk than knowledge of common risk factors alone. C1 [Meigs, James B.; Shrader, Peter] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.; Shrader, Peter; Florez, Jose C.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [McAteer, Jarred B.; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Unit, Dept Med, Boston, MA 02114 USA. [Sullivan, Lisa M.; Dupuis, Josee; Manning, Alisa K.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [McAteer, Jarred B.; Florez, Jose C.] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Wilson, Peter W. F.] Emory Univ, Sch Med, Emory Program Cardiovasc Outcomes Res & Epidemiol, Atlanta, GA USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM jmeigs@partners.org OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603; Sullivan, Lisa/0000-0003-0726-7149 FU National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institute for Diabetes and Digestive and Kidney Diseases [R01 DK078616, K24 DK080140, K23 DK65978]; Boston University Linux Cluster for Genetic Analysis; National Institutes of Health National Center for Research Resources Shared Instrumentation [1S10RR163736-01A1]; Sanofi-Aventis; GlaxoSmithKline; Merck; Publicis Healthcare Communications Group FX Supported by a contract from the National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195), grants from the National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) (R01 DK078616 and K24 DK080140, to Dr. Meigs), an NIDDK Research Career Award (K23 DK65978, to Dr. Florez), and the Boston University Linux Cluster for Genetic Analysis, funded by a grant from the National Institutes of Health National Center for Research Resources Shared Instrumentation (1S10RR163736-01A1). Dr. Meigs reports serving on a consultancy board for Interleukin Genetics and receiving grants from Sanofi-Aventis and GlaxoSmithKline; and Dr. Florez, receiving consulting fees from Merck and Publicis Healthcare Communications Group, a global advertising agency engaged by Amylin Pharmaceuticals. No other potential conflict of interest relevant to this article was reported. NR 40 TC 392 Z9 405 U1 1 U2 14 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 NOV 20 PY 2008 VL 359 IS 21 BP 2208 EP 2219 DI 10.1056/NEJMoa0804742 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 373SW UT WOS:000260994000004 PM 19020323 ER PT J AU Lyssenko, V Jonsson, A Almgren, P Pulizzi, N Isomaa, B Tuomi, T Berglund, G Altshuler, D Nilsson, P Groop, L AF Lyssenko, Valeriya Jonsson, Anna Almgren, Peter Pulizzi, Nicolo Isomaa, Bo Tuomi, Tiinamaija Berglund, Goran Altshuler, David Nilsson, Peter Groop, Leif TI Clinical Risk Factors, DNA Variants, and the Development of Type 2 Diabetes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GENOME-WIDE ASSOCIATION; INSULIN SENSITIVITY; LOCI; PREDICTION; MELLITUS; REPLICATION; SECRETION; INDEXES; GENE AB Background: Type 2 diabetes mellitus is thought to develop from an interaction between environmental and genetic factors. We examined whether clinical or genetic factors or both could predict progression to diabetes in two prospective cohorts. Methods: We genotyped 16 single-nucleotide polymorphisms (SNPs) and examined clinical factors in 16,061 Swedish and 2770 Finnish subjects. Type 2 diabetes developed in 2201 (11.7%) of these subjects during a median follow-up period of 23.5 years. We also studied the effect of genetic variants on changes in insulin secretion and action over time. Results: Strong predictors of diabetes were a family history of the disease, an increased body-mass index, elevated liver-enzyme levels, current smoking status, and reduced measures of insulin secretion and action. Variants in 11 genes (TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1, IGF2BP2, SLC30A8, JAZF1, and HHEX) were significantly associated with the risk of type 2 diabetes independently of clinical risk factors; variants in 8 of these genes were associated with impaired beta-cell function. The addition of specific genetic information to clinical factors slightly improved the prediction of future diabetes, with a slight increase in the area under the receiver-operating-characteristic curve from 0.74 to 0.75; however, the magnitude of the increase was significant (P=1.0 x 10(-4)). The discriminative power of genetic risk factors improved with an increasing duration of follow-up, whereas that of clinical risk factors decreased. Conclusions: As compared with clinical risk factors alone, common genetic variants associated with the risk of diabetes had a small effect on the ability to predict the future development of type 2 diabetes. The value of genetic factors increased with an increasing duration of follow-up. C1 [Lyssenko, Valeriya; Jonsson, Anna; Almgren, Peter; Berglund, Goran; Nilsson, Peter; Groop, Leif] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Pulizzi, Nicolo] Univ Pisa, Pisa, Italy. [Isomaa, Bo; Tuomi, Tiinamaija] Folkhalsan Res Ctr, Helsinki, Finland. [Tuomi, Tiinamaija; Groop, Leif] Univ Helsinki, Cent Hosp, Helsinki, Finland. [Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lyssenko, V (reprint author), Lund Univ, Malmo Univ Hosp, Dept Clin Sci Diabet & Endocrinol, CRC, S-20502 Malmo, Sweden. EM valeri.lyssenko@med.lu.se RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 FU Swedish Research Council; Linne [31475113580]; Heart and Lung Foundation; Swedish Diabetes Research Society; Nordic Center of Excellence Grant in Disease Genetics; Diabetes Program at the Lund University; Finnish Diabetes Research Society; Sigrid Juselius Foundation; Pahlsson Foundation; Crafoord Foundation; Folkhalsan Research Foundation; Novo Nordisk Foundation; European Network of Genomic and Genetic Epidemiology; Wallenberg Foundation; European Foundation for the Study of Diabetes; Tethys; Merck; Eisai; MPM Capital; Novartis; Bristol-Myers Squibb Foundation; Eli Lilly; GlaxoSmithKline; Aventis; Sanofi FX Supported by grants from the Swedish Research Council (including Linne grant 31475113580), the Heart and Lung Foundation, the Swedish Diabetes Research Society, a Nordic Center of Excellence Grant in Disease Genetics, the Diabetes Program at the Lund University, the Finnish Diabetes Research Society, the Sigrid Juselius Foundation, the Pahlsson Foundation, the Crafoord Foundation, the Folkhalsan Research Foundation, the Novo Nordisk Foundation, the European Network of Genomic and Genetic Epidemiology, the Wallenberg Foundation, and the European Foundation for the Study of Diabetes. Dr. Lyssenko reports receiving consulting fees from Tethys; Dr. Altshuler, receiving consulting fees from Merck, Eisai, and MPM Capital and grant support from Novartis, receiving an unrestricted grant from the Bristol-Myers Squibb Foundation, and having an equity interest in MPM Capital; and Dr. Groop, receiving consulting fees from Tethys, Eli Lilly, GlaxoSmithKline, Aventis, and Sanofi, lecture fees from Aventis and Sanofi, and grant support from Novartis. No other potential conflict of interest relevant to this article was reported. We thank the patients for their participation and Anna Berglund, Margareta Svensson, and Malin Neptin for their excellent technical assistance. NR 30 TC 461 Z9 482 U1 4 U2 41 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 NOV 20 PY 2008 VL 359 IS 21 BP 2220 EP 2232 DI 10.1056/NEJMoa0801869 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 373SW UT WOS:000260994000005 PM 19020324 ER PT J AU Brass, SD Durand, ML Stone, JH Chen, JW Stone, JR Cohen, AB Harris, NL Friday, RP Utz, AL AF Brass, Steven D. Durand, Marlene L. Stone, John H. Chen, John W. Stone, James R. Cohen, Adam B. Harris, Nancy Lee Friday, Robert P. Utz, Andrea L. TI A Man with Chronic Daily Headache Giant-cell arteritis, involving the superficial temporal artery and small dural arteries SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SLEEP-APNEA SYNDROME; HYPERTROPHIC CRANIAL PACHYMENINGITIS; QUALITY STANDARDS SUBCOMMITTEE; NERVOUS-SYSTEM HISTOPLASMOSIS; CEREBROSPINAL-FLUID LEAKS; WEGENERS-GRANULOMATOSIS; INTRACRANIAL HYPOTENSION; PRACTICE PARAMETER; AMERICAN-ACADEMY; SARCOIDOSIS C1 [Brass, Steven D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Durand, Marlene L.; Stone, John H.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Chen, John W.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Stone, James R.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Brass, Steven D.] Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. [Stone, John H.] Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. [Chen, John W.] Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. [Stone, James R.] Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Brass, SD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. FU Teva Neuroscience; EMD Serono; Biogen; Bayer; Merck; Zymogenetics; Muscle Tech; GlaxoSmithKline; Proteon Therapeutics FX Dr. Brass reports receiving consulting fees from Teva Neuroscience, EMD Serono, Biogen, and Bayer; Dr. John Stone, consulting fees from Merck and Zymogenetics; and Dr. James Stone, consulting fees from Merck, Muscle Tech, GlaxoSmithKline, and Proteon Therapeutics. No other potential conflict of interest relevant to this article was reported. NR 59 TC 8 Z9 9 U1 0 U2 3 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 NOV 20 PY 2008 VL 359 IS 21 BP 2267 EP 2278 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 373SW UT WOS:000260994000012 PM 19020329 ER PT J AU Maggard, MA Yermilov, I Li, Z Maglione, M Newberry, S Suttorp, M Hilton, L Santry, HP Morton, JM Livingston, EH Shekelle, PG AF Maggard, Melinda A. Yermilov, Irina Li, Zhaoping Maglione, Margaret Newberry, Sydne Suttorp, Marika Hilton, Lara Santry, Heena P. Morton, John M. Livingston, Edward H. Shekelle, Paul G. TI Pregnancy and Fertility Following Bariatric Surgery A Systematic Review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID GASTRIC-BYPASS-SURGERY; VERTICAL-BANDED GASTROPLASTY; VITAMIN-A-DEFICIENCY; NEURAL-TUBE DEFECTS; MORBID-OBESITY; BILIOPANCREATIC DIVERSION; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; PHYSICAL-ACTIVITY AB Context Use of bariatric surgery has increased dramatically during the past 10 years, particularly among women of reproductive age. Objectives To estimate bariatric surgery rates among women aged 18 to 45 years and to assess the published literature on pregnancy outcomes and fertility after surgery. Evidence Acquisition Search of the Nationwide Inpatient Sample ( 1998- 2005) and multiple electronic databases ( Medline, EMBASE, Controlled Clinical Trials Register Database, and the Cochrane Database of Reviews of Effectiveness) to identify articles published between 1985 and February 2008 on bariatric surgery among women of reproductive age. Search terms included bariatric procedures, fertility, contraception, pregnancy, and nutritional deficiencies. Information was abstracted about study design, fertility, and nutritional, neonatal, and pregnancy outcomes after surgery. Evidence Synthesis Of 260 screened articles, 75 were included. Women aged 18 to 45 years accounted for 49% of all patients undergoing bariatric surgery ( > 50 000 cases annually for the 3 most recent years). Three matched cohort studies showed lower maternal complication rates after bariatric surgery than in obese women without bariatric surgery, or rates approaching those of nonobese controls. In 1 matched cohort study that compared maternal complication rates in women after laparoscopic adjustable gastric band surgery with obese women without surgery, rates of gestational diabetes ( 0% vs 22.1%, P <. 05) and preeclampsia ( 0% vs 3.1%, P <. 05) were lower in the bariatric surgery group. Findings were supported by 13 other bariatric cohort studies. Neonatal outcomes were similar or better after surgery compared with obese women without laparoscopic adjustable gastric band surgery ( 7.7% vs 7.1% for premature delivery; 7.7% vs 10.6% for low birth weight, P <. 05; 7.7% vs 14.6% for macrosomia, P <. 05). No differences in neonatal outcomes were found after gastric bypass compared with nonobese controls ( 26.3%- 26.9% vs 22.4%- 20.2% for premature delivery, P= not reported [ 1 study] and P=. 43 [ 1 study]; 7.7% vs 9.0% for low birth weight, P= not reported [ 1 study]; and 0% vs 2.6%- 4.3% for macrosomia, P= not reported [ 1 study and P=. 28 [ 1 study]). Findings were supported by 10 other studies. Studies regarding nutrition, fertility, cesarean delivery, and contraception were limited. Conclusion Rates of many adverse maternal and neonatal outcomes may be lower in women who become pregnant after having had bariatric surgery compared with rates in pregnant women who are obese; however, further data are needed from rigorously designed studies. C1 [Maggard, Melinda A.; Yermilov, Irina; Li, Zhaoping; Maglione, Margaret; Shekelle, Paul G.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Maggard, Melinda A.; Maglione, Margaret; Newberry, Sydne; Suttorp, Marika; Hilton, Lara; Shekelle, Paul G.] RAND Corp, Santa Monica, CA USA. [Yermilov, Irina; Li, Zhaoping; Shekelle, Paul G.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Santry, Heena P.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Morton, John M.] Stanford Univ, Sch Med, Dept Surg, Palo Alto, CA 94304 USA. [Livingston, Edward H.] Univ Texas Southwestern Sch Med, Dept Surg, Dallas, TX USA. RP Maggard, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, CHS 72-215,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mmaggard@mednet.ucla.edu FU Agency for Healthcare Research and Quality [290-02-0003]; US Department of Health and Human Services to the Southern California Evidence Based Practice Center; Robert Wood Johnson Physician Faculty Scholars program FX This project was funded under contract 290-02-0003 from the Agency for Healthcare Research and Quality, US Department of Health and Human Services to the Southern California Evidence Based Practice Center. Dr Maggard's time was supported in part by a grant from the Robert Wood Johnson Physician Faculty Scholars program. This work was requested by the American College of Obstetricians and Gynecologists. NR 84 TC 199 Z9 204 U1 2 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 19 PY 2008 VL 300 IS 19 BP 2286 EP 2296 DI 10.1001/jama.2008.641 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 373IO UT WOS:000260965500029 PM 19017915 ER PT J AU Stewart, AJ O'Farrell, DA Cormack, RA Hansen, JL Khan, AJ Mutyala, S Devlin, PM AF Stewart, Alexandra J. O'Farrell, Desmond A. Cormack, Robert A. Hansen, Jorgen L. Khan, Atif J. Mutyala, Subhakar Devlin, Philip M. TI Dose volume histogram analysis of normal structures associated with accelerated partial breast irradiation delivered by high dose rate brachytherapy and comparison with whole breast external beam radiotherapy fields SO RADIATION ONCOLOGY LA English DT Article ID INITIAL CLINICAL-EXPERIENCE; RADIATION-THERAPY; MAMMOSITE BRACHYTHERAPY; INTERSTITIAL BRACHYTHERAPY; BALLOON BRACHYTHERAPY; CONSERVING THERAPY; AMERICAN-SOCIETY; REGISTRY TRIAL; CANCER; TOXICITY AB Purpose: To assess the radiation dose delivered to the heart and ipsilateral lung during accelerated partial breast brachytherapy using a MammoSite (TM) applicator and compare to those produced by whole breast external beam radiotherapy (WBRT). Materials and methods: Dosimetric analysis was conducted on patients receiving MammoSite breast brachytherapy following conservative surgery for invasive ductal carcinoma. Cardiac dose was evaluated for patients with left breast tumors with a CT scan encompassing the entire heart. Lung dose was evaluated for patients in whom the entire lung was scanned. The prescription dose of 3400 cGy was 1 cm from the balloon surface. MammoSite dosimetry was compared to simulated WBRT fields with and without radiobiological correction for the effects of dose and fractionation. Dose parameters such as the volume of the structure receiving 10 Gy or more (V10) and the dose received by 20 cc of the structure (D20), were calculated as well as the maximum and mean doses received. Results: Fifteen patients were studied, five had complete lung data and six had left-sided tumors with complete cardiac data. Ipsilateral lung volumes ranged from 925-1380 cc. Cardiac volumes ranged from 337-551 cc. MammoSite resulted in a significantly lower percentage lung V30 and lung and cardiac V20 than the WBRT fields, with and without radiobiological correction. Conclusion: This study gives low values for incidental radiation received by the heart and ipsilateral lung using the MammoSite applicator. The volume of heart and lung irradiated to clinically significant levels was significantly lower with the MammoSite applicator than using simulated WBRT fields of the same CT data sets. Trial registration: Dana Farber Trial Registry number 03-179 C1 [O'Farrell, Desmond A.; Cormack, Robert A.; Hansen, Jorgen L.; Devlin, Philip M.] Harvard Univ, Sch Med, Dana Faber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Div Brachytherapy, Boston, MA 02115 USA. [Stewart, Alexandra J.] Royal Surrey Cty Hosp, St Lukes Canc Ctr, Surrey, England. [Mutyala, Subhakar] Montefiore Med Ctr, Dept Radiat Oncol, Bronx, NY 10467 USA. [Mutyala, Subhakar] Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Devlin, PM (reprint author), Harvard Univ, Sch Med, Dana Faber Brigham & Womens Canc Ctr, Dept Radiat Oncol,Div Brachytherapy, Boston, MA 02115 USA. EM ajsintheus@yahoo.co.uk; dofarrell@lroc.harvard.edu; rcormack@lroc.harvard.edu; jhansen@lroc.harvard.edu; atif.j.khan@gmail.com; smutyala@montefiore.org; pdevlin@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984; Khan, Atif/0000-0001-8640-8530 NR 39 TC 23 Z9 23 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND J9 RADIAT ONCOL JI Radiat. Oncol. PD NOV 19 PY 2008 VL 3 AR 39 DI 10.1186/1748-717X-3-39 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 394IY UT WOS:000262441600001 PM 19019216 ER PT J AU Wang, TY Xiao, L Alexander, KP Rao, SV Kosiborod, MN Rumsfeld, JS Spertus, JA Peterson, ED AF Wang, Tracy Y. Xiao, Lan Alexander, Karen P. Rao, Sunil V. Kosiborod, Mikhail N. Rumsfeld, John S. Spertus, John A. Peterson, Eric D. TI Antiplatelet Therapy Use After Discharge Among Acute Myocardial Infarction Patients With In-Hospital Bleeding SO CIRCULATION LA English DT Article DE anticoagulants; antiplatelet therapy; bleeding; myocardial infarction ID ACUTE CORONARY SYNDROMES; ST-SEGMENT ELEVATION; HIGH-RISK PATIENTS; CLINICAL-OUTCOMES; COLLABORATIVE METAANALYSIS; RANDOMIZED-TRIALS; BLOOD-TRANSFUSION; IMPACT; PREDICTORS; REGISTRY AB Background-Bleeding among patients with acute myocardial infarction (AMI) is associated with worse long-term outcomes. Although the mechanism underlying this association is unclear, a potential explanation is that withholding antiplatelet therapies long beyond resolution of the bleeding event may contribute to recurrent events. Methods and Results-We examined medication use at discharge, 1, 6, and 12 months after AMI among 2498 patients in the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) registry. Bleeding was defined as non-coronary artery bypass graft-related Thrombolysis of Myocardial Infarction major/minor bleeding or transfusion among patients with baseline hematocrit >= 28%. Logistic regression was used to evaluate the association between bleeding during the index AMI hospitalization and medication use. In-hospital bleeding occurred in 301 patients (12%) with AMI. Patients with in-hospital bleeding were less likely to be discharged on aspirin or thienopyridine (adjusted odds ratio = 0.45; 95% CI, 0.31 to 0.64; and odds ratio = 0.62; 95% CI, 0.42 to 0.91, respectively). At 1 month after discharge, although patients with in-hospital bleeding remained significantly less likely to receive aspirin (odds ratio = 0.68; 95% CI, 0.50 to 0.92), use of thienopyridines in the 2 groups started to become similar. By 1 year, antiplatelet therapy use was similar among patients with and without bleeding. Postdischarge cardiology follow-up was associated with greater antiplatelet therapy use than either primary care or no clinical follow-up. Conclusions-Patients whose index AMI is complicated by bleeding are less likely to be treated with antiplatelet therapies during the first 6 months after discharge. Early reassessment of antiplatelet eligibility may represent an opportunity to reduce the long-term risk of adverse outcomes associated with bleeding. (Circulation. 2008; 118: 2139-2145.) C1 [Wang, Tracy Y.; Alexander, Karen P.; Rao, Sunil V.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC 27705 USA. [Wang, Tracy Y.; Alexander, Karen P.; Rao, Sunil V.; Peterson, Eric D.] Duke Univ, Med Ctr, Durham, NC 27705 USA. [Xiao, Lan; Kosiborod, Mikhail N.; Spertus, John A.] Univ Missouri, Kansas City, MO 64110 USA. [Xiao, Lan; Kosiborod, Mikhail N.; Spertus, John A.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Rumsfeld, John S.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Wang, TY (reprint author), Duke Clin Res Inst, 2400 Pratt St,Room 0311,Terrace Level, Durham, NC 27705 USA. EM wang0085@mc.duke.edu FU Cardiovascular Outcomes, Inc; Cardiovascular Therapeutics, Inc, Palo Alto, Calif; Duke Clinical Research Institute, Durham, NC; CV Therapeutics, Inc, Palo Alto, Calif FX The PREMIER Quality Improvement Registry was organized by Cardiovascular Outcomes, Inc, a nonprofit 501( c)( 3) organization dedicated to the advancement of outcomes research and improvement of cardiovascular healthcare quality, and is funded by Cardiovascular Therapeutics, Inc, Palo Alto, Calif. More information on the PREMIER Quality Improvement Registry can be found at http://www.cvoutcomes.org. Funding and support for this publication were provided by the Duke Clinical Research Institute, Durham, NC. Funding for statistical analysis was provided by CV Therapeutics, Inc, Palo Alto, Calif. NR 27 TC 69 Z9 72 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 18 PY 2008 VL 118 IS 21 BP 2139 EP 2145 DI 10.1161/CIRCULATIONAHA.108.787143 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 373FB UT WOS:000260955300005 PM 18981304 ER PT J AU Tolle, JJ Waxman, AB Van Horn, TL Pappagianopoulos, PP Systrom, DM AF Tolle, James J. Waxman, Aaron B. Van Horn, Teresa L. Pappagianopoulos, Paul P. Systrom, David M. TI Exercise-Induced Pulmonary Arterial Hypertension SO CIRCULATION LA English DT Article DE circulation; exercise; hemodynamics; hypertension, pulmonary; physiology ID RIGHT ATRIAL PRESSURE; VASCULAR-RESISTANCE; ANAEROBIC THRESHOLD; DOPPLER-ECHOCARDIOGRAPHY; HEMODYNAMIC-RESPONSE; SYSTEMIC-SCLEROSIS; DIAGNOSIS; PATHOGENESIS; LIMIT AB Background-The clinical relevance of exercise-induced pulmonary arterial hypertension (PAH) is uncertain, and its existence has never been well studied by direct measurements of central hemodynamics. Using invasive cardiopulmonary exercise testing, we hypothesized that exercise-induced PAH represents a symptomatic stage of PAH, physiologically intermediate between resting pulmonary arterial hypertension and normal. Methods and Results-A total of 406 consecutive clinically indicated cardiopulmonary exercise tests with radial and pulmonary arterial catheters and radionuclide ventriculographic scanning were analyzed. The invasive hemodynamic phenotype of exercise-induced PAH (n = 78) was compared with resting PAH (n = 15) and normals (n = 16). Log-log plots of mean pulmonary artery pressure versus oxygen uptake ((V)over dotO(2)) were obtained, and a "join-point" for a least residual sum of squares for 2 straight-line segments (slopes m1, m2) was determined; m2m1 = "takeoff" pattern. At maximum exercise, (V) over dotO(2) (55.8 +/- 20.3% versus 66.5 +/- 16.3% versus 91.7 +/- 13.7% predicted) was lowest in resting PAH, intermediate in exercise-induced PAH, and highest in normals, whereas mean pulmonary artery pressure (48.4 +/- 11.1 versus 36.6 +/- 5.7 versus 27.4 + 3.7 mm Hg) and pulmonary vascular resistance (294 +/- 158 versus 161 +/- 60 versus 62 +/- 20 dyne . s . cm(-5), respectively; P<0.05) followed an opposite pattern. An exercise-induced PAH plateau (n = 32) was associated with lower (V) over dotO(2)max (60.6 +/- 15.1% versus 72.0 +/- 16.1% predicted) and maximum cardiac output (78.2 +/- 17.1% versus 87.8 +/- 18.3% predicted) and a higher resting pulmonary vascular resistance (247 +/- 101 versus 199 +/- 56 dyne . s . cm(-5); P<0.05) than takeoff (n = 40). The plateau pattern was most common in resting PAH, and the takeoff pattern was present in nearly all normals. Conclusions-Exercise-induced PAH is an early, mild, and clinically relevant phase of the PAH spectrum. (Circulation. 2008; 118: 2183-2189.) C1 [Tolle, James J.; Waxman, Aaron B.; Van Horn, Teresa L.; Pappagianopoulos, Paul P.; Systrom, David M.] Harvard Univ, Pulm & Crit Care Unit, Sch Med, Massachusetts Gen Hosp,Med Serv, Boston, MA 02114 USA. RP Tolle, JJ (reprint author), Harvard Univ, Pulm & Crit Care Unit, Sch Med, Massachusetts Gen Hosp,Med Serv, BUL 1-148,55 Fruit St, Boston, MA 02114 USA. EM jjtolle@yahoo.com OI Systrom, David/0000-0002-9610-6330 FU National Institutes of Health [K24HL04022-05] FX This work was supported by grant K24HL04022-05 from the National Institutes of Health. NR 46 TC 152 Z9 157 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 NOV 18 PY 2008 VL 118 IS 21 BP 2183 EP 2189 DI 10.1161/CIRCULATIONAHA.108.787101 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 373FB UT WOS:000260955300010 PM 18981305 ER PT J AU Chiu, IM Chen, A Zheng, Y Kosaras, B Tsiftsoglou, SA Vartanian, TK Brown, RH Carroll, MC AF Chiu, Isaac M. Chen, Adam Zheng, Yi Kosaras, Bela Tsiftsoglou, Stefanos A. Vartanian, Timothy K. Brown, Robert H., Jr. Carroll, Michael C. TI T lymphocytes potentiate endogenous neuroprotective inflammation in a mouse model of ALS SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyotrophic lateral sclerosis; microglia; neuroimmunology; neuroinflammation; T cells ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DEGENERATION; WILD-TYPE MICROGLIA; SPINAL-CORD; EXTEND SURVIVAL; NADPH OXIDASE; FAMILIAL ALS; MICE; CELLS; DISEASE AB Amyotrophic Lateral Sclerosis (ALS) is an adult-onset, progressive, motor neuron degenerative disease, in which the role of inflammation is not well established. Innate and adaptive immunity were investigated in the CNS of the Superoxide Dismutase 1 (SOD1)(G93A) transgenic mouse model of ALS. CD4(+) and CD8+ T cells infiltrated SOD1(G93A) spinal cords during disease progression. Cell-specific flow cytometry and gene expression profiling showed significant phenotypic changes in microglia, including dendritic cell receptor acquisition, and expression of genes linked to neuroprotection, cholesterol metabolism and tissue remodeling. Microglia dramatically up-regulated IGF-1 and down-regulated IL-6 expression. When mutant SOD1 mice were bred onto a TCR beta deficient background, disease progression was significantly accelerated at the symptomatic stage. In addition, microglia reactivity and IGF-1 levels were reduced in spinal cords of SOD1(G93A) (TCR beta(-/-)) mice. These results indicate that T cells play an endogenous neuroprotective role in ALS by modulating a beneficial inflammatory response to neuronal injury. C1 [Chiu, Isaac M.; Zheng, Yi; Tsiftsoglou, Stefanos A.; Carroll, Michael C.] Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA. [Chen, Adam; Brown, Robert H., Jr.] Massachusetts Gen Hosp, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. [Kosaras, Bela; Vartanian, Timothy K.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Chiu, IM (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Dept Pathol, Boston, MA 02115 USA. EM chiu@fas.haward.edu FU Amyotrophic Lateral Sclerosis Association; National Institutes of Health Training [Al 007306-23]; ALS Association; National Institute for Neurological Disease and Stroke; National Institute for Aging; ALS Research Foundation; Al-Athel Amyotrophic Lateral Sclerosis Foundation FX We thank Michael Haas, Vijay Kuchroo, and Tammy Hshieh for helpful, critical discussions; Eugene Ponomarev for CNS cell isolation and adult microglia culture advice; Laura Santambrogio, Jeng-Shin Lee, and Viraga Haridas for technical help; and Monica Carrasco for help with image analysis. This work was funded by the Amyotrophic Lateral Sclerosis Association (M.C.C., I.M.C.); National Institutes of Health Training Grant Al 007306-23 (to I.M.C.); and the ALS Association, National Institute for Neurological Disease and Stroke, National Institute for Aging, Angel Fund, Project ALS, Pierre L. de Bourgknect ALS Research Foundation, and Al-Athel Amyotrophic Lateral Sclerosis Foundation (R.B.). NR 36 TC 154 Z9 156 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 18 PY 2008 VL 105 IS 46 BP 17913 EP 17918 DI 10.1073/pnas.0804610105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 377BB UT WOS:000261225600063 PM 18997009 ER PT J AU Kahn, JM Asch, RJ Iwashyna, TJ Rubenfeld, GD Angus, DC Asch, DA AF Kahn, Jeremy M. Asch, Rebecca J. Iwashyna, Theodore J. Rubenfeld, Gordon D. Angus, Derek C. Asch, David A. TI Perceived barriers to the regionalization of adult critical care in the United States: a qualitative preliminary study SO BMC HEALTH SERVICES RESEARCH LA English DT Article ID HOSPITAL VOLUME; DELIVERY; ILL; ORGANIZATION; MORTALITY; MEDICINE; SERVICES; OUTCOMES; IMPACT AB Background: Regionalization of adult critical care services may improve outcomes for critically ill patients. We sought to develop a framework for understanding clinician attitudes toward regionalization and potential barriers to developing a tiered, regionalized system of care in the United States. Methods: We performed a qualitative study using semi-structured interviews of critical care stakeholders in the United States, including physicians, nurses and hospital administrators. Stakeholders were identified from a stratified-random sample of United States general medical and surgical hospitals. Key barriers and potential solutions were identified by performing content analysis of the interview transcriptions. Results: We interviewed 30 stakeholders from 24 different hospitals, representing a broad range of hospital locations and sizes. Key barriers to regionalization included personal and economic strain on families, loss of autonomy on the part of referring physicians and hospitals, loss of revenue on the part of referring physicians and hospitals, the potential to worsen outcomes at small hospitals by limiting services, and the potential to overwhelm large hospitals. Improving communication between destination and source hospitals, provider education, instituting voluntary objective criteria to become a designated referral center, and mechanisms to feed back patients and revenue to source hospitals were identified as potential solutions to some of these barriers. Conclusion: Regionalization efforts will be met with significant conceptual and structural barriers. These data provide a foundation for future research and can be used to inform policy decisions regarding the design and implementation of a regionalized system of critical care. C1 [Kahn, Jeremy M.; Asch, Rebecca J.] Univ Penn, Div Pulm Allergy & Crit Care, Sch Med, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. [Kahn, Jeremy M.] Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Iwashyna, Theodore J.] Univ Michigan, Div Pulm & Crit Care Med, Ann Arbor, MI 48109 USA. [Rubenfeld, Gordon D.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Program Trauma Emergency & Crit Care, Toronto, ON M4N 3M5, Canada. [Angus, Derek C.] Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA USA. [Asch, David A.] Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA 19104 USA. RP Kahn, JM (reprint author), Univ Penn, Div Pulm Allergy & Crit Care, Sch Med, 3400 Spruce St, Philadelphia, PA 19104 USA. EM jmkahn@mail.med.upenn.edu; aschrj@mail.med.upenn.edu; tiwashyn@umich.edu; gordon.rubenfeld@sunnybrook.ca; angusdc@ccm.upmc.edu; asch@wharton.upenn.edu RI Angus, Derek/E-9671-2012; OI Asch, David/0000-0002-7970-286X; Iwashyna, Theodore/0000-0002-4226-9310 FU United States National Institutes of Health [K23 HL082650] FX This work was supported by the University of Pennsylvania Leschly Fund. Dr. Kahn is supported by a career development award from the United States National Institutes of Health (K23 HL082650). The funding source had no role in the design, implementation, analysis or decision to publish this research. NR 28 TC 11 Z9 11 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 1472-6963 J9 BMC HEALTH SERV RES JI BMC Health Serv. Res. PD NOV 17 PY 2008 VL 8 AR 239 DI 10.1186/1472-6963-8-239 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 391LA UT WOS:000262233600002 PM 19014704 ER PT J AU Friedberg, JW Sharman, J Schaefer-Cutillo, J Johnston, PB De Vos, S LaCasce, A Leonard, JP Cripe, LD Sinha, R Gregory, SA Sweetenham, J Vose, JM Lowe, AM Levy, R Shipp, MA AF Friedberg, Jonatan W. Sharman, Jeff Schaefer-Cutillo, Julia Johnston, Patrick B. De Vos, Sven LaCasce, Ann Leonard, John P. Cripe, Larry D. Sinha, Rajni Gregory, Stephanie A. Sweetenham, John Vose, Julie M. Lowe, Ann M. Levy, R. Shipp, Margaret A. TI Fostamatinib Disodium (FosD), An Oral Inhibitor of Syk, Is Well-Tolerated and Has Significant Clinical Activity in Diffuse Large B Cell Lymphoma (DLBCL) and Chronic Lymphocytic Leukemia (SLL/CLL) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Friedberg, Jonatan W.; Schaefer-Cutillo, Julia] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. [Sharman, Jeff] Stanford Univ, Stanford, CA 94305 USA. [Johnston, Patrick B.] Mayo Clin, Grad Sch Med, Rochester, MN USA. [De Vos, Sven] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [LaCasce, Ann; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leonard, John P.] Weill Cornell Med Coll, Div Hem Onc, New York, NY USA. [Cripe, Larry D.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. [Sinha, Rajni] Emory Univ, Atlanta, GA 30322 USA. [Gregory, Stephanie A.] Rush Univ, Med Ctr, Sect Hematol & Stem Cell Transplantat, Chicago, IL 60612 USA. [Sweetenham, John] Taussig Canc Inst, Cleveland Clin, Cleveland, OH USA. [Vose, Julie M.] Univ NE Med Ctr, Omaha, NE USA. [Lowe, Ann M.] Rigel Pharmaceut, San Francisco, CA USA. [Levy, R.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 20 Z9 20 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 3 EP 4 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700004 ER PT J AU Kikushige, Y Miyamoto, T Lino, T Ishikawa, F Akashi, K AF Kikushige, Yoshikane Miyamoto, Toshihiro Lino, Tadafumi Ishikawa, Fumihiko Akashi, Koichi TI Hematopoictic Stem tells Are Primarily Involved in Pathogenesis of Chronic Lymphocytic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kikushige, Yoshikane; Miyamoto, Toshihiro] Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. [Lino, Tadafumi; Akashi, Koichi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ishikawa, Fumihiko] RIKEN Rsrch Ctr Allergy & Immunol, Rsrch Unit Human Dis Models, Yokohama, Kanagawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 17 EP 17 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700030 ER PT J AU Ramsay, AG Gorgun, G Holderried, TAW Zahrieh, D Liu, FL Quackenbush, J Croce, CM Gribben, JG AF Ramsay, Alan G. Gorgun, Gullu Holderried, Tobias A. W. Zahrieh, David Liu, Fenglong Quackenbush, John Croce, Carlo M. Gribben, John G. TI A Mouse Model for Immunotherapeutic Reversal of Leukemia-induced T Cell Dysfunction SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ramsay, Alan G.; Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, Inst Canc, Ctr Med Oncol, London, England. [Gorgun, Gullu; Holderried, Tobias A. W.; Zahrieh, David; Liu, Fenglong; Quackenbush, John] Dana Farber Canc Inst, Boston, MA 02115 USA. [Croce, Carlo M.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 17 EP 17 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700031 ER PT J AU Rowe, JM Sun, ZX Cassileth, PA Appelbaum, FR Wiernik, PH Lazarus, HM Blume, KG Fernandez, HF Litzow, MR Tallman, MS AF Rowe, Jacob M. Sun, Zhuoxin Cassileth, Peter A. Appelbaum, Frederick R. Wiernik, Peter H. Lazarus, Hillard M. Blume, Karl G. Fernandez, Hugo F. Litzow, Mark R. Tallman, Martin S. TI Treatment-Related Mortality and Relapse Rate from Time of Initiation of Post-Remission Therapy for Patients Receiving Allogeneic Transplantation, Autologous Transplantation or Intensive Chemotherapy: A Report from the Eastern Cooperative Oncology Group (ECOG) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rowe, Jacob M.] Technion Israel Inst Technol, Haifa, Israel. [Sun, Zhuoxin] Dana Farber Canc Inst, Boston, MA USA. [Cassileth, Peter A.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Appelbaum, Frederick R.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Seattle, WA 98195 USA. [Wiernik, Peter H.] New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Blume, Karl G.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Fernandez, Hugo F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Tallman, Martin S.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 25 EP 25 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700050 ER PT J AU Navarro, WH Agovi, MA Logan, B Bacigalupo, A Ballen, KK Bolwell, BJ Frangoul, H Gupta, V Hahn, T Juckett, M Lazarus, HM Litzow, MR Liesveld, J Moreb, J Marks, D McCarthy, PL Rizzo, JD AF Navarro, Willis H. Agovi, Manza-A Logan, Brent Bacigalupo, Andrea Ballen, Karen K. Bolwell, Brian J. Frangoul, Haydar Gupta, Vikas Hahn, Theresa Juckett, Mark Lazarus, Hillard M. Litzow, Mark R. Liesveld, Jane Moreb, Jan Marks, David McCarthy, Philip L. Rizzo, J. Douglas TI Obesity Does Not Preclude Safe and Effective Myeloablative Hematopoietic Cell Transplantation (HCT) for Acute Myeloid Leukemia (AML) in Adults SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Navarro, Willis H.] Natl Marrow Donor Program, Minneapolis, MN USA. [Agovi, Manza-A; Logan, Brent; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Bacigalupo, Andrea] San Martino Hosp, Genoa, Italy. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bolwell, Brian J.] Cleveland Clin, Cleveland, OH 44106 USA. [Frangoul, Haydar] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hahn, Theresa; Liesveld, Jane; McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Juckett, Mark] Univ WI Hosp & Clin, Madison, WI USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Moreb, Jan] Univ Florida, Shands Hosp, Gainesville, FL USA. [Marks, David] United Bristol Healthcare Trust, Bristol, Avon, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 26 EP 26 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700052 ER PT J AU Alousi, A Weisdorf, DJ Logan, BR Bolanos-Meade, J Goldstein, SC Ho, VT Hayes-Lattin, B Wingard, JR Horowitz, MM Levine, JE AF Alousi, Amin Weisdorf, Daniel J. Logan, Brent R. Bolanos-Meade, Javier Goldstein, Steven C. Ho, Vincent T. Hayes-Lattin, Brandon Wingard, John R. Horowitz, Mary M. Levine, John E. TI BMT CTN 0302: A Phase II Randomized Trial Evaluating Etanercept, Mycophenolate Mofetil (MMF), Denileukin Diftitox, and Pentostatin in Combination with Corticosteroids in 180 Patients (pts) with Newly Diagnosed Acute Graft Vs. Host Disease (aGVHD) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Alousi, Amin] Univ Texas MD Anderson Canc Ctr, Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. [Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA. [Bolanos-Meade, Javier] Johns Hopkins Univ, Baltimore, MD USA. [Goldstein, Steven C.] Univ Penn, Philadelphia, PA 19104 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wingard, John R.] Univ Florida, Shands Canc Ctr, Gainesville, FL USA. [Horowitz, Mary M.] Ctr Int Blood & Marrow Transplant Res, Ctr Clin Canc, Froedtert & Med Coll Wisconsin, Milwaukee, WI USA. [Levine, John E.] Univ Michigan, Blood & Marrow Transplantat Program, Ann Arbor, MI 48109 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 27 EP 28 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700056 ER PT J AU Kumar, S Flinn, IW Noga, SJ Hari, P Rifkin, RM Callander, NS Bhandari, M Wolf, JL Gasparetto, C Krishnan, A Grosman, DD Glass, J Sahovic, EA Shi, H Webb, IJ Richardson, P Rajkumar, SV AF Kumar, Shaji Flinn, Ian W. Noga, Stephen J. Hari, Parameswaran Rifkin, Robert M. Callander, Natalie Scott Bhandari, Manish Wolf, Jeffrey Lee Gasparetto, Cristina Krishnan, Amrita Grosman, Daren D. Glass, Jonathan Sahovic, Entezam Asim Shi, Hongliang Webb, Iain J. Richardson, Paul Rajkumar, S. Vincent TI Safety and Efficacy of Novel Combination Therapy with Bortezomib, Dexamethasone, Cyclophosphamide, and Lenalidomide in Newly Diagnosed Multiple Myeloma: Initial Results from the Phase I/II MultiCenter EVOLUTION Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rajkumar, S. Vincent] Mayo Clin, Coll Med, Rochester, MN USA. [Flinn, Ian W.] Sarah Cannon Res Inst, Nashville, TN USA. [Noga, Stephen J.] Alvin & Lois Lapidus Canc Inst, Baltimore, MD USA. [Hari, Parameswaran] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Rifkin, Robert M.] Rocky Mt Canc Ctr, Denver, CO USA. [Callander, Natalie Scott] Univ Washington, Madison, WI USA. [Bhandari, Manish] Christ Hosp, Cincinnati, OH 45219 USA. [Wolf, Jeffrey Lee] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Gasparetto, Cristina] Duke Univ, Med Ctr, Durham, NC USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Grosman, Daren D.] Mem Healthcare Canc Ctr, Hollywood, FL USA. [Glass, Jonathan] LSUHSC Shreveport, Feist Weiller Canc Ctr, Dept Med, Shreveport, LA USA. [Sahovic, Entezam Asim] Western Penn Hosp, Pittsburgh, PA 15224 USA. [Shi, Hongliang] Millennium Pharmaceut Takeda Oncol Co, Clin Biostat, Cambridge, MA USA. [Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 4 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 41 EP 42 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700094 ER PT J AU Richardson, P Lonial, S Jakubowiak, A Jagannath, S Raje, NS Avigan, D Ghobrial, IM Schlossman, RL Mazumder, A Munshi, NC Vesole, DH Joyce, R Doss, D Warren, DL Hayes, SW Kaster, S Delaney, C Lauria, M Mitsiades, C Hideshima, T Knight, RD Esseltine, DL Anderson, KC AF Richardson, Paul Lonial, Sagar Jakubowiak, Andrzej Jagannath, Sundar Raje, Noopur S. Avigan, David Ghobrial, Irene M. Schlossman, Robert L. Mazumder, Amitabha Munshi, Nikhil C. Vesole, David H. Joyce, Robin Doss, Deborah Warren, Diane L. Hayes, Stephen W. Kaster, Sarah Delaney, Carol Lauria, Marisa Mitsiades, Constantine Hideshima, Teru Knight, Robert D. Esseltine, Dixie-Lee Anderson, Kenneth C. TI Lenalidomide, Bortezomib, and Dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: Encouraging Efficacy in High Risk Groups with Updated Results of a Phase I/II Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul; Ghobrial, Irene M.; Schlossman, Robert L.; Munshi, Nikhil C.; Doss, Deborah; Warren, Diane L.; Hayes, Stephen W.; Mitsiades, Constantine; Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Jakubowiak, Andrzej] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Jagannath, Sundar; Mazumder, Amitabha; Vesole, David H.] St Vincents Comprehens Canc Ctr, New York, NY USA. [Raje, Noopur S.; Kaster, Sarah] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Avigan, David; Joyce, Robin; Delaney, Carol; Lauria, Marisa] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Knight, Robert D.] Celgene Corp, Summit, NJ 07901 USA. [Esseltine, Dixie-Lee] Millennium Pharmaceut Takeda Oncol Co, Cambridge, MA USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 41 EP 41 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700093 ER PT J AU Adamia, S AvetLoiseau, H Amin, SB Tai, YT Treon, SP Moreau, P Minvielle, S Li, C Anderson, KC Munshi, NC AF Adamia, Sophia AvetLoiseau, Herve Amin, Samirkumar B. Tai, Yu-Tzu Treon, Steven P. Moreau, Philippe Minvielle, Stephane Li, Cheng Anderson, Kenneth C. Munshi, Nikhil C. TI Microrna Expression Profile Identifies Distinct Clinically Relevant Sub-Groups in Multiple Myeloma: Novel Prognostic Markers and Potential Targets for Therapy SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Amin, Samirkumar B.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [AvetLoiseau, Herve; Moreau, Philippe; Minvielle, Stephane] Hop Nantes, Dept Hematol, F-44093 Nantes, France. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. RI Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 43 EP 43 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700097 ER PT J AU Pardanani, AD Gotlib, J Jamieson, C Cortes, J Talpaz, M Stone, RM Silverman, MH Shorr, J Gilliland, DG Tefferi, A AF Pardanani, Animesh D. Gotlib, Jason Jamieson, Catriona Cortes, Jorge Talpaz, Moshe Stone, Richard M. Silverman, Michael H. Shorr, Jolene Gilliland, D. Gary Tefferi, Ayalew TI A Phase I Study of TG101348, An Orally Bioavailable JAK2-Selective Inhibitor, in Patients with Myelofibrosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Pardanani, Animesh D.] Mayo Clin, Rochester, MN USA. [Gotlib, Jason] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Jamieson, Catriona] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. [Jamieson, Catriona] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA. [Cortes, Jorge] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Talpaz, Moshe] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Silverman, Michael H.] Biosirateg Consulting Ltd, Marblehead, MA USA. [Gilliland, D. Gary] Brigham & Womens Hosp, Boston, MA 02115 USA. [Shorr, Jolene] TargeGen Inc, San Diego, CA USA. [Tefferi, Ayalew] Mayo Clin Grad Sch Med, Div Hematol, Rochester, MN USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 43 EP 44 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700098 ER PT J AU Shah, NP Olszynski, P Sokol, L Verstovsek, S Hoffman, R List, AF Cortes, J Kantadian, HM Gilliland, DG Clary, DO Bui, LA Wadleigh, M AF Shah, Neil P. Olszynski, Patrycja Sokol, Lubomir Verstovsek, Srdan Hoffman, Ronald List, Alan F. Cortes, Jorge Kantadian, Hagop M. Gilliland, D. Gary Clary, Douglas O. Bui, Lynne A. Wadleigh, Martha TI A Phase I Study of XL019, a Selective JAK2 Inhibitor, in Patients with Primary Myelofibrosis, Post-Polycythemia Vera, or Post-Essential Thrombocythemia Myelofibrosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Shah, Neil P.; Olszynski, Patrycja] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Sokol, Lubomir; List, Alan F.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Verstovsek, Srdan; Cortes, Jorge] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hoffman, Ronald] Mt Sinai Sch Med, New York, NY USA. [List, Alan F.] Res Inst, Tampa, FL USA. [Kantadian, Hagop M.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gilliland, D. Gary] Brigham & Womens Hosp, Boston, MA 02115 USA. [Clary, Douglas O.; Bui, Lynne A.] Exelixis Inc, San Francisco, CA USA. [Wadleigh, Martha] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 44 EP 44 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700099 ER PT J AU Gyurkocza, B Storb, RF Storer, B Chauncey, T Niederwieser, D Shizuru, J Langston, A Pulsipher, M Bredeson, C Maziarz, RT Bruno, B Petersen, F Maris, M Agura, E Yeager, AM Bethge, WA Sahebi, F Vindelov, L McSweeney, PA Appelbaum, FR Maloney, DG Sandmaier, BM AF Gyurkocza, Boglarka Storb, Rainer F. Storer, Barry Chauncey, Thomas Niederwieser, Dietger Shizuru, Judith Langston, Amelia Pulsipher, Michael Bredeson, Christopher Maziarz, Richard T. Bruno, Benedetto Petersen, Finn Maris, Michael Agura, Edward Yeager, Andrew M. Bethge, Wolfgang A. Sahebi, Firoozeh Vindelov, Lars McSweeney, Peter A. Appelbaum, Frederick R. Maloney, David G. Sandmaier, Brenda M. TI Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients with De Novo and Secondary Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chauncey, Thomas] Univ Washington, Fred Hutchinson Canc Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Niederwieser, Dietger] Univ Leipzig, Leipzig, Germany. [Shizuru, Judith] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Langston, Amelia] Emory Univ, Atlanta, GA 30322 USA. [Pulsipher, Michael] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Bredeson, Christopher] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Petersen, Finn] LDS Hosp, Salt Lake City, UT USA. [Maris, Michael; McSweeney, Peter A.] Rocky Mt Canc Ctr, Denver, CO USA. [Agura, Edward] Baylor Univ, Med Ctr, Dallas, TX USA. [Yeager, Andrew M.] Univ Arizona, Tucson, AZ USA. [Bethge, Wolfgang A.] Univ Tubingen, Med Ctr, Tubingen, Germany. [Sahebi, Firoozeh] City Hope Natl Med Ctr, Duarte, CA USA. [Vindelov, Lars] Univ Copenhagen, Rigshosp, DK-2100 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 61 EP 61 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700150 ER PT J AU Roti, G Ross, KN Mecucci, C Ferrando, AA Aster, JC Stegmaier, K AF Roti, Giovanni Ross, Kenneth N. Mecucci, Cristina Ferrando, Adolfo A. Aster, Jon C. Stegmaier, Kimberly TI Chemical Genomic Screen Identifies Ionophores as Modulators of Notch1 in T-ALL SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Roti, Giovanni; Stegmaier, Kimberly] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ross, Kenneth N.] Harvard Univ, Broad Inst, Canc Program, Cambridge, MA 02138 USA. [Ross, Kenneth N.] MIT, Cambridge, MA 02139 USA. [Ferrando, Adolfo A.] Columbia Univ, Inst Canc Genet, New York, NY USA. [Aster, Jon C.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Stegmaier, Kimberly] Harvard Univ, Broad Inst, Boston, MA 02115 USA. [Stegmaier, Kimberly] MIT, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 81 EP 81 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700201 ER PT J AU Davies, J Yuk, D Nadler, L Guinan, E AF Davies, Jeff Yuk, Dongin Nadler, Lee Guinan, Eva TI Alloanergization of HILA-Mismatched Human Donor T Cells Results in the Generation of Allosuppressive CD4(+) T Regulatory Cells Both in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Davies, Jeff; Yuk, Dongin; Nadler, Lee; Guinan, Eva] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 83 EP 84 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700208 ER PT J AU Ooi, MG McMillin, DW Negri, JM Delmore, J Klippel, S Mitsiades, N Richardson, PG Anderson, KC Mitsiades, CS AF Ooi, Melissa G. McMillin, Douglas W. Negri, Joseph M. Delmore, Jake Klippel, Steffen Mitsiades, Nicholas Richardson, Paul G. Anderson, Kenneth C. Mitsiades, Constantine S. TI Compartment-Specific Bioluminescence Imaging (CS-BLI) High-Throughput Assays Provide Comparative Insights into the Impact of Osteoclasts Vs. Stromal Cells on Activity of Anti-Myeloma Therapeutics SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ooi, Melissa G.; McMillin, Douglas W.; Negri, Joseph M.; Delmore, Jake; Klippel, Steffen; Mitsiades, Nicholas; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 88 EP 88 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700220 ER PT J AU Freedman, AS Neelapu, S Nichols, CR Robertson, M Djulbegovic, B Winter, JN Gold, D Bender, J Stewart, M Ghalie, RG Hamlin, PA AF Freedman, Arnold S. Neelapu, Sattva Nichols, Craig R. Robertson, Michael Djulbegovic, Benjamin Winter, Jane N. Gold, Daniel Bender, John Stewart, Morgan Ghalie, Richard G. Hamlin, Paul A., Jr. TI A Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy with Mitumprotimut-T (ID-KLR) and GM-CSF Following Rituximab in Patients with CD20+Follicular Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Freedman, Arnold S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Neelapu, Sattva] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. [Nichols, Craig R.] Providence Canc Ctr, Portland, OR USA. [Robertson, Michael] Indiana Univ, Med Ctr, Indianapolis, IN USA. [Djulbegovic, Benjamin] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Winter, Jane N.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Gold, Daniel; Bender, John; Stewart, Morgan; Ghalie, Richard G.] Favrille Inc, San Diego, CA USA. [Hamlin, Paul A., Jr.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 94 EP 94 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700237 ER PT J AU Bianchi, G Oliva, L Cascio, P Pengo, N Orsi, A Fontana, F Pasqualetto, E Mezghrani, A Cerruti, F Calbi, V Palladini, G Giuliani, N Chauhan, D Anderson, KC Sitia, R Cenci, S AF Bianchi, Giada Oliva, Laura Cascio, Paolo Pengo, Niccolo Orsi, Andrea Fontana, Francesca Pasqualetto, Elena Mezghrani, Alexandre Cerruti, Fulvia Calbi, Valeria Palladini, Giovanni Giuliani, Nicola Chauhan, Dharminder Anderson, Kenneth C. Sitia, Roberto Cenci, Simone TI Proteasome Stress Causes Apoptotic Sensitivity of Multiple Myeloma Cells to Proteasome Inhibition SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bianchi, Giada; Chauhan, Dharminder; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Oliva, Laura; Pengo, Niccolo; Orsi, Andrea; Fontana, Francesca; Pasqualetto, Elena; Sitia, Roberto; Cenci, Simone] Ist Sci San Raffaele, DiBiT, Dept Biol & Technol, I-20132 Milan, Italy. [Cascio, Paolo; Cerruti, Fulvia] Univ Turin, Dept Vet Morphophysiol, Turin, Italy. [Mezghrani, Alexandre] CNRS, Inst Genet Humaine, Montpellier, France. [Calbi, Valeria] Ist Sci San Raffaele, Hematol & BMT Unit, I-20132 Milan, Italy. [Palladini, Giovanni] Univ Pavia, Dept Biochem, I-27100 Pavia, Italy. [Palladini, Giovanni] Univ Pavia, Ctr Amyloidosis, Fdn IRCCS Policlin San Matteo, I-27100 Pavia, Italy. [Giuliani, Nicola] Univ Parma, Hematol Unit, I-43100 Parma, Italy. [Giuliani, Nicola] Univ Parma, BMT, I-43100 Parma, Italy. RI Palladini, Giovanni/G-1763-2010 OI Palladini, Giovanni/0000-0001-5994-5138 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 98 EP 98 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700248 ER PT J AU Santo, L Vallet, S Hideshima, T Cirstea, D Pozzi, S Vaghela, N Ikeda, H Okawa, Y Gorgun, G Perrone, G Calabrese, E Squires, MS Ladetto, M Munshi, NC Boccadoro, M Anderson, KC Raje, N AF Santo, Loredana Vallet, Sonia Hideshima, Teru Cirstea, Diana Pozzi, Samantha Vaghela, Nileshwari Ikeda, Hiroshi Okawa, Yutaka Gorgun, Gullu Perrone, Giulia Calabrese, Elisabetta Squires, Matthew S. Ladetto, Marco Munshi, Nikhil C. Boccadoro, Mario Anderson, Kenneth C. Raje, Noopur TI AT7519, a Novel Small Molecule Multi-Cyclin Dependent Kinase Inhibitor, Induces Apoptosis in Multiple Myeloma VIA GSK3 beta SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Santo, Loredana; Hideshima, Teru; Cirstea, Diana; Pozzi, Samantha; Ikeda, Hiroshi; Okawa, Yutaka; Gorgun, Gullu; Perrone, Giulia; Calabrese, Elisabetta; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vallet, Sonia; Vaghela, Nileshwari] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Squires, Matthew S.] Astex Therapeut Ltd, Cambridge, England. [Ladetto, Marco; Boccadoro, Mario] Univ Turin, Div Hematol, Turin, Italy. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 2 Z9 2 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 99 EP 100 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700252 ER PT J AU Rickles, RJ Pierce, L Giordano, T Avery, W Farwell, M Crowe, D Tam, WF Chen, M Kansra, V McMillin, DW Anderson, KC Mitsiades, C Lee, MS AF Rickles, Richard J. Pierce, Laura Giordano, Thomas Avery, William Farwell, Melissa Crowe, David Tam, Winnie F. Chen, Mei Kansra, Vikram McMillin, Douglas W. Anderson, Kenneth C. Mitsiades, Constantine Lee, Margaret S. TI Preclinical Evaluation of CRx-501, a Potent Selective A2A Agonist as a Novel Drug Candidate for the Treatment of Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rickles, Richard J.; Pierce, Laura; Giordano, Thomas; Avery, William; Farwell, Melissa; Crowe, David; Tam, Winnie F.; Chen, Mei; Kansra, Vikram; Lee, Margaret S.] CombinatoRx Inc, Cambridge, MA USA. [McMillin, Douglas W.; Anderson, Kenneth C.; Mitsiades, Constantine] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 100 EP 100 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700253 ER PT J AU Zhao, BQ Chauhan, AK Patten, IS Dockal, M Scheiflinger, F Wagner, DD AF Zhao, Bing-Qiao Chauhan, Anil Kumar Patten, Ian S. Dockal, Michael Scheiflinger, Friedrich Wagner, Denisa D. TI VWF-Cleaving Protease ADAMTS13 Reduces Brain Injury Following Ischemic Stroke in Mice: Essential Role for VWF in Stroke SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhao, Bing-Qiao; Chauhan, Anil Kumar; Patten, Ian S.; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. [Dockal, Michael] Baxter Biosci, Prot Engn, Orth, Austria. [Scheiflinger, Friedrich] Baxter Innovat GmbH, Discovery Res, Vienna, Austria. NR 0 TC 0 Z9 0 U1 3 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 102 EP 102 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700260 ER PT J AU O'Connor, OA Pro, B Pinter-Brown, L Popplewell, L Barlett, N Shustov, A Lechowicz, MJ Savage, KJ Coiffier, B Jacobsen, E Zinzani, PL Goy, A Zain, J Wilroy, S Patterson, M Boyd, A Saunders, ME Cagnoni, P Horwitz, SM AF O'Connor, Owen A. Pro, Barbara Pinter-Brown, Lauren Popplewell, Leslie Barlett, Nancy Shustov, Andrei Lechowicz, Mary Jo Savage, Kerry J. Coiffier, Bertrand Jacobsen, Eric Zinzani, Pier Luigi Goy, Andre Zain, Jasmine Wilroy, Shannon Patterson, Molly Boyd, Adam Saunders, Michael E. Cagnoni, Pablo Horwitz, Steven M. TI PROPEL: A Multi-Center Phase 2 Open-Label Study of Pralatrexate (PDX) with Vitamin B-12 and Folic Acid Supplementation in Patients with Replapsed or Refractory Peripheral T-Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [O'Connor, Owen A.; Zain, Jasmine; Patterson, Molly] CUMC, New York, NY USA. [Pro, Barbara] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Pinter-Brown, Lauren] Univ Calif Los Angeles, Dept Internal Med, Div Oncol, Los Angeles, CA USA. [Popplewell, Leslie] City Hope Natl Med Ctr, Duarte, CA USA. [Barlett, Nancy] Washington Univ Med, Dept Internal Med, Div Oncol, St Louis, MO USA. [Shustov, Andrei] Univ Washington, Seattle, WA USA. [Lechowicz, Mary Jo] Emory Univ, Atlanta, GA 30322 USA. [Savage, Kerry J.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Coiffier, Bertrand] Ctr Hosp Lyon Sud, F-69310 Pierre Benite, France. [Jacobsen, Eric] Dana Farber, Boston, MA USA. [Zinzani, Pier Luigi] Univ Bologna, Dept Hematol Oncol, Bologna, Italy. [Goy, Andre] HUMC, Ctr Canc, Hackensack, NJ USA. [Wilroy, Shannon; Boyd, Adam; Saunders, Michael E.; Cagnoni, Pablo] Allos Therapeut Inc, Westminster, CO USA. [Horwitz, Steven M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Zinzani, Pier Luigi/J-9182-2016 OI Zinzani, Pier Luigi/0000-0002-2112-2651 NR 0 TC 2 Z9 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 103 EP 103 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700262 ER PT J AU Leonard, JP LaCasce, A Smith, MR Noy, A Yap, JT Van den Abbeele, AD Yu, JQ Chen-Kiang, S Ely, SA Vallabhajosula, S Chirieac, LR Larson, SM Shapiro, GI Schoder, H AF Leonard, John P. LaCasce, Ann Smith, Mitchell R. Noy, Ariela Yap, Jeffrey T. Van den Abbeele, Annick D. Yu, Jian Q. Chen-Kiang, Selina Ely, Scott A. Vallabhajosula, Shankar Chirieac, Lucian R. Larson, Steven M. Shapiro, Geoffrey I. Schoder, Heiko TI Cdk4/6 Inhibitor PD 0332991 Demonstrates Cell Cycle Inhibition Via FLT-PET Imaging and Tissue Analysis in Patients with Recurrent Mantle Cell Lymphoma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Leonard, John P.; Chen-Kiang, Selina; Ely, Scott A.] Weill Cornell Med Coll, Div Hem Onc, New York, NY USA. [LaCasce, Ann; Yap, Jeffrey T.; Van den Abbeele, Annick D.; Chirieac, Lucian R.; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Smith, Mitchell R.; Yu, Jian Q.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. [Noy, Ariela; Larson, Steven M.; Schoder, Heiko] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Vallabhajosula, Shankar] Weill Cornell Med Ctr, New York, NY USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 104 EP 104 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700265 ER PT J AU Rhodes, KE Gekas, C Gereige, L Helgadottir, H Ferrari, R Kurdistani, S Montecino-Rodriguez, E Basel-Duby, R Olson, E Orkin, SH Pellegrini, M Mikkola, H AF Rhodes, Katrin E. Gekas, Christos Gereige, Laurraine Helgadottir, Hildur Ferrari, Roberto Kurdistani, Siavash Montecino-Rodriguez, Encarnacion Basel-Duby, Rhonda Olson, Eric Orkin, Stuart H. Pellegrini, Matteo Mikkola, Hanna TI Mef2C Is a Lineage-Restricted Target Gene of Scl/Tal1 and Regulates Megakaryopoiesis and B-Cell Homeostasis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mikkola, Hanna] Univ Calif Los Angeles, ICSBM, MCDB, Los Angeles, CA USA. [Helgadottir, Hildur; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Basel-Duby, Rhonda; Olson, Eric] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 109 EP 109 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700279 ER PT J AU Gavathiotis, E Suzuki, M Davis, ML Pitter, K Bird, GH Katz, SG Tu, HC Kim, H Cheng, E Tjandra, N Walensky, LD AF Gavathiotis, Evripidis Suzuki, Motoshi Davis, Marguerite L. Pitter, Kenneth Bird, Gregory H. Katz, Samuel G. Tu, Ho-Chou Kim, Hyungjin Cheng, Emily Tjandra, Nico Walensky, Loren D. TI Structural Analysis of a BAX-BIM SAHB Complex Reveals a Novel BH3 Interaction Site on BAX for Therapeutic Activation of Apoptosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gavathiotis, Evripidis; Davis, Marguerite L.; Pitter, Kenneth; Bird, Gregory H.; Katz, Samuel G.; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston, Boston, MA 02115 USA. [Suzuki, Motoshi; Tjandra, Nico] NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. [Tu, Ho-Chou; Kim, Hyungjin; Cheng, Emily] Washington Univ, St Louis Sch Med, Div Mol Oncol, St Louis, MO USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 117 EP 117 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700301 ER PT J AU Bolli, N Payne, E Grabher, C Johnston, A Kanki, J Look, AT AF Bolli, Niccolo Payne, Elspeth Grabher, Clemens Johnston, Adam Kanki, John Look, A. Thomas TI Human Nucleophosmin (NPM1) Perturbs Myeloid Development in Zebrafish in Vivo SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bolli, Niccolo; Payne, Elspeth; Grabher, Clemens; Johnston, Adam; Kanki, John; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 120 EP 120 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700309 ER PT J AU Kuter, DJ Bussel, JB Newland, A de Wolf, JTM Guthrie, T Wasser, J Gehl, L Nie, K Berger, D AF Kuter, Davrt J. Bussel, James B. Newland, Adrian de Wolf, Joost T. M. Guthrie, Troy Wasser, Jeffrey Gehl, Lara Nie, Kun Berger, Dietmar TI Long-Term Treatment with Romiplostim in Patients with Chronic Immune Thrombocytopenic Purpura (ITP): 3-Year Update from An Open-Label SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol (ASH), Sanofi Aventis U.S. C1 [Kuter, Davrt J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bussel, James B.] New York Presbyterian Hosp, Dept Pediat & med, Div Hematol, New York, NY USA. [Newland, Adrian] Royal London Hosp, Dept Haematol, London E1 1BB, England. [de Wolf, Joost T. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Guthrie, Troy] Univ Florida, Baptist Canc Inst, Jacksonville, FL USA. [Wasser, Jeffrey] DeQuttro Community Canc Ctr, Manchester, CT USA. [Gehl, Lara; Nie, Kun; Berger, Dietmar] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 154 EP 154 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700403 ER PT J AU Parmar, K Kim, JM Shimamura, A Stuckert, A DeLoach, MK Zhu, K Mauch, PM Kutok, J Aster, J Akashi, K Gilliland, G D'Andrea, AD AF Parmar, Kalindi Kim, Jung Min Shimamura, Akiko Stuckert, Anna DeLoach, Mary K. Zhu, Kaya Mauch, Peter M. Kutok, Jeffery Aster, Jon Akashi, Koichi Gilliland, Gary D'Andrea, Alan D. TI Hematopoietic Stem Cell Defects in Novel Fanconi Anemia Mouse Models SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Parmar, Kalindi; Kim, Jung Min; Stuckert, Anna; DeLoach, Mary K.; Zhu, Kaya; Mauch, Peter M.; Akashi, Koichi; D'Andrea, Alan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Shimamura, Akiko] Univ Washington, Seattle, WA 98195 USA. [Kutok, Jeffery; Aster, Jon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Gilliland, Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 168 EP 168 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700441 ER PT J AU Baccarani, M Rosti, G Saglio, G Cortes, J Stone, R Niederwieser, DW Bleickardt, E Sinha, R Simonsson, B AF Baccarani, Michele Rosti, Gianantonio Saglio, Giuseppe Cortes, Jorge Stone, Richard Niederwieser, Dietger W. Bleickardt, Eric Sinha, Ritwik Simonsson, Bengt TI Dasatinib Time to and Durability of Major and Complete Cytogenetic Response (MCyR and CCyR) in Patients with Chronic Myeloid Leukemia in Chronic Phase (CML-CP) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Baccarani, Michele; Rosti, Gianantonio] Ist Ematol, Bologna, Italy. [Saglio, Giuseppe] Univ Turin, Dept Clin & Biol Sci, Turin, Italy. [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Stone, Richard] Dana Farber Canc Inst, Boston, MA 02115 USA. [Niederwieser, Dietger W.] Univ Leipzig, Hamatol Onkol Abt, Leipzig, Germany. [Bleickardt, Eric; Sinha, Ritwik] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Simonsson, Bengt] Univ Hosp, Dept Hematol, Uppsala, Sweden. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 172 EP 172 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700451 ER PT J AU Ofran, Y Brusic, V Kim, HT Soiffer, RJ Antin, JH Ritz, J AF Ofran, Yishay Brusic, Vladimir Kim, H. T. Soiffer, Robert J. Antin, J. H. Ritz, Jerome TI Diverse Patterns of T Cell Reactivity Directed against Multiple Y Chromosome-Derived, HLA a*0201 Restricted, Peptides in Patients with chronic Gvhd SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Brusic, Vladimir] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 177 EP 177 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700465 ER PT J AU Neuwirth, AK Campagna, DR Fleming, MD Bottomley, SS Neufeld, EJ AF Neuwirth, Anke K. Campagna, Dean R. Fleming, Mark D. Bottomley, Sylvia S. Neufeld, Ellis J. TI Systematic Analysis of Known Candidate Genes in 58 Probands with Previously Uncharacterized Congenital Sideroblastic Anemia: Evidence for Genetic Heterogeneity and Identification of Novel Mutations in ALAS2 and PUS1 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Fleming, Mark D.; Neufeld, Ellis J.] Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Bottomley, Sylvia S.] Univ Oklahoma, Hlth Sci Ctr, Hematol Oncol Sect, Oklahoma City, OK USA. RI Neufeld, Ellis/F-9331-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 184 EP 184 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700485 ER PT J AU Sankaran, VG Menne, TF Akie, TE Lettre, G Hirschhorn, JN Cantor, AB Orkin, SH AF Sankaran, Vijay G. Menne, Tobias F. Akie, Thomas E. Lettre, Guillaume Hirschhorn, Joel N. Cantor, Alan B. Orkin, Stuart H. TI Human Fetal Hemoglobin Expression Is Regulated by the Developmental Stage-Specific Repressor BCL11A SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Sankaran, Vijay G.; Menne, Tobias F.; Akie, Thomas E.; Lettre, Guillaume; Hirschhorn, Joel N.; Cantor, Alan B.] Childrens Hosp, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 185 EP 186 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700488 ER PT J AU Chapman, MA Brunet, JP Baker, A Keats, J Ahmann, G Schinzel, AC Moore, A Shanmugam, V Perkins, LM Auclair, D Hahn, WC Bergsagel, PL Fonseca, R Carpten, J Trent, J Golub, TR AF Chapman, Michael A. Brunet, Jean-Philippe Baker, Angela Keats, Jonathan Ahmann, Gregory Schinzel, Anna C. Moore, Anna Shanmugam, Vijayalakshmi Perkins, Louise M. Auclair, Daniel Hahn, William C. Bergsagel, P. Leif Fonseca, Rafael Carpten, John Trent, Jeffrey Golub, Todd R. TI Interim Analyses of the MMRC Reference Collection Identifies Recurrent Genomic-Level Events in Multiple Myeloma and Demonstrates That CDKN2C/p18 Deletion Is the Pre-Eminent Copy Number Alteration in Poor Prognosis Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chapman, Michael A.; Brunet, Jean-Philippe] Broad Inst, Cambridge, MA USA. [Baker, Angela; Moore, Anna; Shanmugam, Vijayalakshmi; Carpten, John] Translat Genom Res Inst, Integrated Canc Genom Div, Phoenix, AZ USA. [Keats, Jonathan; Ahmann, Gregory; Bergsagel, P. Leif; Fonseca, Rafael] Mayo Clin Arizona, Scottsdale, AZ USA. [Schinzel, Anna C.; Hahn, William C.; Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perkins, Louise M.; Auclair, Daniel] Multiple Myeloma Res Fdn, Norwalk, CT USA. [Trent, Jeffrey] Translat Genom Res Inst, Genet Basis Human Dis Div, Phoenix, AZ USA. RI Keats, Jonathan/B-2047-2009 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 188 EP 189 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700498 ER PT J AU Munshi, NC Li, C Minvielle, S Amin, SB Moreau, P Magrangeas, F Anderson, KC Avet-Loiseau, H AF Munshi, Nikhil C. Li, Cheng Minvielle, Stephane Amin, Samir B. Moreau, Philippe Magrangeas, Florence Anderson, Kenneth C. Avet-Loiseau, Herve TI Alternate Splicing Is a Frequent Event and Impacts Clinical Outcome in Myeloma: A High-Density Exon Array Analysis of Uniformly Treated Newly-Diagnosed Myeloma Patients SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Minvielle, Stephane; Moreau, Philippe; Magrangeas, Florence; Avet-Loiseau, Herve] Hop Nantes, Dept Hematol, Nantes, France. [Amin, Samir B.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 189 EP 189 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700499 ER PT J AU Payne, E Bolli, N Grabher, C Rhodes, J Kanki, J Galinsky, I Stone, R Cotter, FE Look, AT AF Payne, Elspeth Bolli, Niccolo Grabher, Clemens Rhodes, Jennifer Kanki, John Galinsky, Ilene Stone, Richard Cotter, Finbar E. Look, A. Thomas TI The Role of RNA Helicase Dead Box 18 in Zebrafish Hematopoiesis and Human MDS SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Payne, Elspeth] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Cotter, Finbar E.] Barts & London Queen Marys Sch Med & Dent, Ctr Haematol, London, England. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 189 EP 190 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700501 ER PT J AU Mercher, T Raffel, GD Moore, SA Cornejo, MG Baudry-Bluteau, D Cagnard, N Jesneck, J Pikman, Y Cullen, DE Williams, I Akashi, K Shigematsu, H Bourquin, JP Giovannini, M Vainchenker, W Levine, RL Lee, BH Bernard, O Gilliland, DG AF Mercher, Thomas Raffel, Glen D. Moore, Sandra A. Cornejo, Melanie G. Baudry-Bluteau, Dominique Cagnard, Nicolas Jesneck, Jonathan Pikman, Yana Cullen, Dana E. Williams, Ifor Akashi, Koichi Shigematsu, Hirokazu Bourquin, Jean-Pierre Giovannini, Marco Vainchenker, William Levine, Ross L. Lee, Benjamin H. Bernard, Olivier Gilliland, D. Gary TI OTT-MAL Activates the Notch Signaling Transcription Factor RBPJ and Cooperates with Mutant MPL to Induce Acute Megakaryoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cullen, Dana E.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Mercher, Thomas; Cagnard, Nicolas] Univ Paris 05, INSERM, EMI0210, Paris, France. [Raffel, Glen D.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Cornejo, Melanie G.; Cullen, Dana E.] Harvard Univ, Sch Med, Boston, MA USA. [Baudry-Bluteau, Dominique; Vainchenker, William] INSERM, U790, Villejuif, France. [Jesneck, Jonathan; Cullen, Dana E.; Akashi, Koichi; Shigematsu, Hirokazu] Dana Farber Canc Inst, Boston, MA 02115 USA. [Williams, Ifor] Emory Univ, Atlanta, GA 30322 USA. [Bourquin, Jean-Pierre] Univ Zurich, Zurich, Switzerland. [Giovannini, Marco] INSERM, U434, Paris, France. [Levine, Ross L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Bernard, Olivier] Hop Necker Enfants Malad, Hematol Lab, Paris, France. RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 192 EP 192 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700509 ER PT J AU Tian, M Campagna, DR Langer, N Choe, SK Paw, BH Justice, MJ Fleming, MD AF Tian, Meng Campagna, Dean R. Langer, Nathaniel Choe, Seong-Kyu Paw, Barry H. Justice, Monica J. Fleming, Mark D. TI Rsp1 Is Indispensable for mRNA Stability during Erythroid Terminal Differentiation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Campagna, Dean R.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Langer, Nathaniel; Choe, Seong-Kyu; Paw, Barry H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Hematol, Boston, MA 02115 USA. [Justice, Monica J.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Fleming, Mark D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 200 EP 200 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700533 ER PT J AU Arica, M Schrappe, M Hunger, S Carroll, WL Conter, V Di Lorenzo, P Manabe, A Saba, V Baruchel, A Vettenranta, K Tsuchida, M Benoit, Y Pieters, R Escherich, G Silverman, LB Pui, CH Valsecchi, MG AF Arica, Maurizio Schrappe, Martin Hunger, Stephen Carroll, William L. Conter, Valentino Di Lorenzo, Paola Manabe, Atsushi Saba, Vaskar Baruchel, Andre Vettenranta, Kim Tsuchida, Masahiro Benoit, Yves Pieters, Rob Escherich, Gabriele Silverman, Lewis B. Pui, Ching-Hon Valsecchi, Maria Grazia TI Clinical Outcome of 640 Children with Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Treated Between 1995 and 2005 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, SanofiAventis U.S. C1 [Arica, Maurizio] Azienda Osped Univ Meyer, Florence, Italy. [Schrappe, Martin] Univ Med Ctr, Kiel, Germany. [Hunger, Stephen] Univ Colorado, Coll Med, Pediat Heme Onc BMT, Aurora, CO USA. [Carroll, William L.] NYU, Sch Med, New York, NY USA. [Conter, Valentino] Univ Milano Bicocca, Osped S Gerardo, Dept Pediat, Monza, Italy. [Di Lorenzo, Paola] Univ Milano Bicocca, Dept Clin & Prevent Med, Monza, Italy. [Manabe, Atsushi] Tokyo Childrens Canc Study Grp, Tokyo, Japan. [Baruchel, Andre] Hop St Louis, Dept Pediat Hematol, Paris, France. [Vettenranta, Kim] Univ Helsinki, Childrens Hosp, Helsinki, Finland. [Tsuchida, Masahiro] Ibaraki Childrens Hosp, Dept Pediat, Mito, Ibaraki, Japan. [Pieters, Rob] Erasmus MC, Dept Pediat Hem Onc, Rotterdam, Netherlands. [Escherich, Gabriele] Univ Klinikum Hamburg Eppendorf, Hamburg, Germany. [Pui, Ching-Hon] St Jude Childrens Rsch Hosp, Dept Onc, Memphis, TN USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Valsecchi, Maria Grazia] Univ Milano Bicocca, Dept Clin & Prevent Med, Int Childhood Acute Lymphoblast Leukemia Study Gr, Monza, Italy. RI Schrappe, Martin/A-8109-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 213 EP 214 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700569 ER PT J AU Meems, H Meijer, AB Cullinan, D Mertens, K Gilbert, GE AF Meems, Henriet Meijer, Alexander B. Cullinan, Dave Mertens, Koen Gilbert, Gary E. TI Factor VIII C1 Domain Residues 2092-2093 Participate in Membrane Binding SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Meems, Henriet; Meijer, Alexander B.; Mertens, Koen] Sanquin Blood Supply Fdn, Dept Plasma Proteins, Amsterdam, Netherlands. [Cullinan, Dave; Gilbert, Gary E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 220 EP 220 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700588 ER PT J AU Xu, HM Geiger, H Szezur, K Deira, D Zheng, Y Settleman, J Srour, E Williams, DA Flippi, MD AF Xu, Haiming Geiger, Hartmut Szezur, Kathleen Deira, Deidra Zheng, Yi Settleman, Jeffrey Srour, Edward Williams, David A. Flippi, Marie-Dominique TI Absence of the Rho GTPase Activating Protein p190-B Enhances Long Term Hematopoietic Stem Cell Engraftment SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Xu, Haiming; Geiger, Hartmut; Szezur, Kathleen; Deira, Deidra; Flippi, Marie-Dominique] Cincinnati Childrens Res Fdn, Cincinnati, OH USA. [Settleman, Jeffrey] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Settleman, Jeffrey; Williams, David A.] Harvard Univ, Sch Med, Boston, MA USA. [Srour, Edward] Indiana Univ, Sch Med, Indianapolis, IN USA. [Williams, David A.] Childrens Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 229 EP 229 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700615 ER PT J AU Braggio, E Keats, JJ Lelcu, X Remstein, E Van Wier, S Jimenez-Zepeda, VH Valdez, R Schop, R Price-Troska, T Sacco, A Azab, F Greipp, PR Gertz, M Rajkumar, SV Chesi, M Stewart, K Dogan, A Bergsagel, PL Ghobrial, I Fonseca, R AF Braggio, Esteban Keats, J. Jonathan Lelcu, Xavier Remstein, Ellen Van Wier, Scott Jimenez-Zepeda, Victor H. Valdez, Riccardo Schop, Roelandt Price-Troska, Tammy Sacco, Antonio Azab, Feda Greipp, Philip R. Gertz, Moric Rajkumar, S. Vincent Chesi, Marta Stewart, Keith Dogan, Ahmet Bergsagel, Peter Leif Ghobrial, Irene Fonseca, Rafael TI TRAF3 and TNFAIP3, Two Negative Regulators of NF-Kb Signaling Pathways, Are Mutated in Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Braggio, Esteban; Keats, J. Jonathan; Jimenez-Zepeda, Victor H.; Price-Troska, Tammy; Chesi, Marta; Stewart, Keith; Bergsagel, Peter Leif] Mayo Clin, Scottsdale, AZ USA. [Lelcu, Xavier; Sacco, Antonio; Azab, Feda; Ghobrial, Irene] Dana Farber Canc Inst, Boston, MA 02115 USA. [Remstein, Ellen] Mayo Clin, Lab Med & Pathol, Rochester, MN USA. [Van Wier, Scott; Valdez, Riccardo; Schop, Roelandt] Mayo Clin Arizona, Scottsdale, AZ USA. [Rajkumar, S. Vincent] Mayo Clin, Coll Med, Rochester, MN USA. [Fonseca, Rafael] Mayo Clin Scottsdale, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 231 EP 231 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700620 ER PT J AU Braunstein, MJ Campagne, F Mukherjee, P Carrasco, DR Sukhdeo, K Protopopov, A Anderson, KC Batuman, O AF Braunstein, Marc J. Campagne, Fabien Mukherjee, Piali Carrasco, Daniel Ruben Sukhdeo, Kumar Protopopov, Alexei Anderson, Kenneth C. Batuman, Olcay TI Genome-Wide Profiling of Endothelial Progenitor Cells in Multiple Mycloma: Disease-Relevant Pathways and Overlaps with Common Cancer Biomarkers SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Braunstein, Marc J.; Batuman, Olcay] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Campagne, Fabien; Mukherjee, Piali] Cornell Univ, Inst Computat Biomed, Weill Med Coll, New York, NY 10021 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Campagne, Fabien/F-5158-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 233 EP 234 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700627 ER PT J AU Leleu, X Hong, FX Roccaro, AM Jia, X Sacco, A Moreau, AS Ngo, H Azab, AK Azab, F Melhem, M Anderson, KC Ghobrial, IM AF Leleu, Xaiaer Hong, Fangxin Roccaro, Aldo M. Jia, Xiaoying Sacco, Antonio Moreau, Anne-Sophie Ngo, Hai Azab, Abdel Kareem Azab, Feda Melhem, Molly Anderson, Kenneth C. Ghobrial, Irene M. TI Gene Transcriptional Activity Analysis in the 6q Region in Waldenstrom Macroglobulinemia (WM) Using ChIP-on-Chip Technology SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Leleu, Xaiaer; Moreau, Anne-Sophie] CHRU Lille, Hop Huriez, Serv Malad Sang, Lille, France. [Hong, Fangxin; Roccaro, Aldo M.; Jia, Xiaoying; Sacco, Antonio; Ngo, Hai; Azab, Abdel Kareem; Azab, Feda; Melhem, Molly; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 234 EP 234 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700629 ER PT J AU Loiseau, HA Li, C Magrangeas, F Guerin, C Gouraud, W Harousseau, JL Attal, M Marit, G Mathiot, C Facon, T Moreau, P Anderson, KC Campion, L Munshi, NC Minvielle, S AF Loiseau, Herve Avet Li, Cheng Magrangeas, Florence Guerin, Catherine Gouraud, Wilfried Harousseau, Jean-Luc Attal, Michel Marit, Gerald Mathiot, Claire Facon, Thierry Moreau, Philippe Anderson, Kenneth C. Campion, Loic Munshi, Nikhil C. Minvielle, Stephane TI In Myeloma, the Prognostic Impact of Hyperdiploidy Is Mainly Related to the Gain of Chromosome 5 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Loiseau, Herve Avet; Magrangeas, Florence; Guerin, Catherine; Gouraud, Wilfried; Harousseau, Jean-Luc; Moreau, Philippe; Minvielle, Stephane] Hop Nantes, Dept Hematol, Nantes, France. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Attal, Michel] Hop Purpan, Toulouse, France. [Marit, Gerald] CHU Bordeaux, Bordeaux, France. [Mathiot, Claire] Inst Curie, Dept Hematol, F-75231 Paris, France. [Facon, Thierry] CHRU Lille, Serv HA Matol, Lille, France. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Campion, Loic] Ctr Rene Gauducheau, St Herblain, France. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. RI FACON, THIERRY/M-9736-2014; Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 235 EP 235 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700633 ER PT J AU Roccaro, AM Sacco, A Chen, CZ Leleu, X Runnels, J Azab, F Azab, AK Jia, XY Ngo, HT Melhem, MR Burwick, N Quang, P Varticovski, L Novina, CD Rollins, BJ Anderson, KC Ghobrial, IM AF Roccaro, Aldo M. Sacco, Antonio Chen, Changzhong Leleu, Xavier Runnels, Judith Azab, Feda Azab, Abdel Kareem Jia, Xiaoying Ngo, Hai T. Melhem, Molly R. Burwick, Nicholas Quang, Phong Varticovski, Lyuba Novina, Carl D. Rollins, Barrett J. Anderson, Kenneth C. Ghobrial, Irene M. TI MicroRNA Signature in Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Roccaro, Aldo M.; Sacco, Antonio; Chen, Changzhong; Leleu, Xavier; Runnels, Judith; Azab, Feda; Azab, Abdel Kareem; Jia, Xiaoying; Ngo, Hai T.; Melhem, Molly R.; Burwick, Nicholas; Quang, Phong; Novina, Carl D.; Rollins, Barrett J.; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Varticovski, Lyuba] Natl Canc Ctr, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 235 EP 235 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700631 ER PT J AU Ngo, HT Hatjiharissi, E Leontovich, AA Chug, W Farag, M Leleu, X Jia, XY Runnels, J Roccaro, A Azab, AK Azab, F Sacco, A Burwick, N Melhem, MR Anderson, KC Fonseca, R Witzig, TE Ghobrial, IM AF Ngo, Hai T. Hatjiharissi, Evdoxia Leontovich, Alexey A. Chug, Wee Farag, Mena Leleu, Xavier Jia, Xiaoying Runnels, Judith Roccaro, Aldo Azab, Abdel Kareem Azab, Feda Sacco, Antonio Burwick, Nicholas Melhem, Molly R. Anderson, Kenneth C. Fonseca, Rafael Witzig, Thomas E. Ghobrial, Irene M. TI Proteomic Analysis of Multiple Myeloma Identifies Upregulation of CRIK Protein, a Novel Protein Regulating Migration and Adhesion SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ngo, Hai T.; Hatjiharissi, Evdoxia; Farag, Mena; Leleu, Xavier; Jia, Xiaoying; Runnels, Judith; Roccaro, Aldo; Azab, Abdel Kareem; Azab, Feda; Sacco, Antonio; Burwick, Nicholas; Melhem, Molly R.; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hatjiharissi, Evdoxia] Mayo Clin, Coll Med, Rochester, MN USA. [Fonseca, Rafael] Mayo Clin, Coll Med, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 239 EP 240 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700644 ER PT J AU Vallet, S Mukherjee, S Vaghela, N Pozzi, S Santo, L Cirstea, D Fulciniti, M Rahemtullah, A Attar, E Guimaraes, AR Xie, WL Patel, C Schoonmaker, J Weller, E Hideshima, T Munshi, NC Seehra, J Scadden, DT Anderson, KC Raje, N AF Vallet, Sonia Mukherjee, Siddhartha Vaghela, Nileshwari Pozzi, Samantha Santo, Loredana Cirstea, Diana Fulciniti, Mariateresa Rahemtullah, Aliyah Attar, Eyal Guimaraes, Alexander R. Xie, Wanling Patel, Chirayu Schoonmaker, Jesse Weller, Edie Hideshima, Teru Munshi, Nilchil C. Seehra, Jas Scadden, David T. Anderson, Kenneth C. Raje, Noopur TI Restoration of Bone Balance Via Activin a Inhibition Results in Anti-Myeloma Activity SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Vallet, Sonia; Vaghela, Nileshwari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Mukherjee, Siddhartha; Patel, Chirayu; Hideshima, Teru; Munshi, Nilchil C.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. [Pozzi, Samantha; Santo, Loredana; Attar, Eyal; Guimaraes, Alexander R.; Scadden, David T.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Mveloma Dis Ctr, Boston, MA 02115 USA. [Xie, Wanling] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. [Schoonmaker, Jesse] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. [Schoonmaker, Jesse] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA USA. [Weller, Edie; Seehra, Jas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Raje, Noopur] Acceleron Pharma Inc, Cambridge, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 240 EP 240 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700646 ER PT J AU Mani, M Dutta, J Zhang, Y Carrasco, DE Zhou, YM Gatt, M Baerlogie, B Shaughnessy, JD Anderson, KC Carrasco, DR AF Mani, Mala Dutta, Jui Zhang, Yunyu Carrasco, Daniel E. Zhou, Yiming Gatt, Moshe Baerlogie, Bart Shaughnessy, John D., Jr. Anderson, Kenneth C. Carrasco, Daniel Ruben TI The BCL9 Oncogene Promotes Tumor Progression by Conferring Enhanced Proliferative, Metastatic and Angiogenic Properties to Myeloma Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Zhou, Yiming; Baerlogie, Bart; Shaughnessy, John D., Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 241 EP 241 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700649 ER PT J AU Runnels, J Carlson, A Pitsillides, C Spencer, J Wu, J Azab, AK Roccaro, AM Moreau, AS Leleu, X Kung, A Rodig, SJ Anderson, KC Lin, CP Ghobrial, IM AF Runnels, Judith Carlson, Alicia Pitsillides, Costas Spencer, Joel Wu, Juwell Azab, Abdel Kareem Roccaro, Aldo M. Moreau, Anne-Sophie Leleu, Xavier Kung, Andrew Rodig, Scott J. Anderson, Kenneth C. Lin, Charles P. Ghobrial, Irene M. TI In Vivo Imaging Model of Multiple Myeloma and Its Cellular Interaction with the Bone Marrow Microenvironment SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Runnels, Judith; Azab, Abdel Kareem; Roccaro, Aldo M.; Moreau, Anne-Sophie; Leleu, Xavier; Kung, Andrew; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Carlson, Alicia; Pitsillides, Costas; Spencer, Joel; Wu, Juwell; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Ctr Syst Biol, Boston, MA 02114 USA. [Carlson, Alicia; Pitsillides, Costas; Spencer, Joel; Wu, Juwell; Lin, Charles P.] Massachusetts Gen Hosp, Adv Microscopy Program, Wellman Ctr Photomed, Boston, MA 02114 USA. [Rodig, Scott J.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 241 EP 241 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700648 ER PT J AU Miguel, JFS Schlag, R Khuageva, NK Dimopoulos, MA Shpilberg, O Kropff, MH Spicka, I Petrucci, MT Palumbo, A Samoilova, OS Dmoszynska, A Abdulkadyrov, KM Schots, R Jiang, B Mateos, MV Anderson, KC Esseltine, DL Liu, KV Cakana, A van de Velde, H Richardson, P AF Miguel, Jesus F. San Schlag, Rudolf Khuageva, Nuriet K. Dimopoulos, Meletios A. Shpilberg, Ofer Kropff, Martin H. Spicka, Ivan Petrucci, Maria Teresa Palumbo, Antonio Samoilova, Olga S. Dmoszynska, Anna Abdulkadyrov, Kudrat M. Schots, Rik Jiang, Bin Mateos, Maria-Victoria Anderson, Kenneth C. Esseltine, Dixie-Lee Liu, Kevin Cakana, Andrew van de Velde, Helgi Richardson, Paul TI Updated Follow-up and Results of Subsequent Therapy in the Phase III VISTA Trial: Bortezomib Plus Melphalan-Prednisone Versus Melphalan-Prednisone in Newly Diagnosed Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Miguel, Jesus F. San] USAL, CSIC, IBMCC, CIC,Hosp Univ Salamanca, Salamanca, Spain. [Schlag, Rudolf] Praxis Hematol & Oncol, Wurzburg, Germany. [Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Dept Hematol, Moscow, Russia. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, Martin H.] Univ Munster, Munster, Germany. [Spicka, Ivan] Charles Univ Praha, Dept Int Med 1, Prague, Czech Republic. [Petrucci, Maria Teresa] Univ Roma La Sapienza, Rome, Italy. [Palumbo, Antonio] Univ Turin, Div Ematol, AOU San Giovanni Battista, Turin, Italy. [Samoilova, Olga S.] Nizhnii Novgorod Reg Clin Hosp, Nizhnii Novgorod, Russia. [Dmoszynska, Anna] Med Univ Lublin, Lublin, Poland. [Abdulkadyrov, Kudrat M.] St Petersburg Clin Res Inst Hematol & Transfusiol, St Petersburg, Russia. [Schots, Rik] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Jiang, Bin] Peking Univ, Peoples Hosp, Beijing, Peoples R China. [Mateos, Maria-Victoria] Hosp Univ Salamanca, Salamanca, Spain. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Esseltine, Dixie-Lee] Takeda Oncol Co, Millennium Pharmaceut, Cambridge, MA USA. [Liu, Kevin] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Cakana, Andrew; van de Velde, Helgi] Johnson & Johnson Pharmaceut Res & Dev, Dept Clin R&D Oncol, Beerse, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 242 EP 242 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700651 ER PT J AU Patsoukis, N Lafuente, EM Meraner, P Li, LQ Dombkowski, D Rao, A Boussiotis, V AF Patsoukis, Nikolaos Lafuente, Esther M. Meraner, Paul Li, Lequn Dombkowski, David Rao, Anjana Boussiotis, Vassiliki TI RIAM Regulate Spatio-Temporal Distribution of PLC-gamma 1 and Calcium Mobilization during T Cell Activation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Patsoukis, Nikolaos; Lafuente, Esther M.; Li, Lequn; Boussiotis, Vassiliki] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA. [Meraner, Paul] Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. [Dombkowski, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rao, Anjana] Brigham & Womens Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 251 EP 252 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700674 ER PT J AU Matsuoka, K Cutler, C Koreth, J Antin, JH Soiffer, RJ Ritz, J AF Matsuoka, Ken-ichi Cutler, Corey Koreth, John Antin, Joseph H. Soiffer, Robert J. Ritz, Jerome TI Increased Proliferation of FoxP3 Regulatory T Cells after Allogeneic Hematopoietic Stem Cell Transplantation Is Counterbalanced by Increased Susceptibility to Apoptosis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Matsuoka, Ken-ichi; Cutler, Corey; Koreth, John; Antin, Joseph H.; Soiffer, Robert J.; Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 267 EP 268 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700721 ER PT J AU Lin, MI Zon, LI AF Lin, Michelle I. Zon, Leonard I. TI Genetic Analyses in Zebrafish Reveal That Angiopoietin-Like Proteins 1 and 2 Are Required for HSC Development during Embryogenesis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Lin, Michelle I.] Harvard Univ, Childrens Hosp, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 271 EP 271 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700730 ER PT J AU Toro, JJ Haile, DJ Chao, JH Jewell, PS Lee, S Freytes, CO AF Toro, Juan J. Haile, David J. Chao, Ju-Hsien Jewell, Pamela S. Lee, Shuko Freytes, Cesar O. TI The Department of Veterans Affairs Nutritional Status Classification Scheme Allows for Rapid Assessment of Nutritional Status Before Autologous Peripheral Blood Stem Cell Transplantation and Identifies Patients at High-Risk of Transplant-Related Complications SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Toro, Juan J.; Haile, David J.; Chao, Ju-Hsien; Jewell, Pamela S.; Lee, Shuko; Freytes, Cesar O.] Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 274 EP 274 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700740 ER PT J AU Wang, QF Dong, JF Mattison, R Prabhakar, S Arimura, FE Kaberlein, J Wang, CZ Wang, QB Nobrega, M Thirman, M AF Wang, Qianfei Dong, Jingfang Mattison, Ryan Prabhakar, Shyam Arimura, Fabio Eiji Kaberlein, Joseph Wang, Chong-zhi Wang, Qianben Nobrega, Marcelo Thirman, Michael TI Autoregulation of MEIS1 through a Distal Enhancer in Acute Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Qianfei; Dong, Jingfang; Mattison, Ryan; Arimura, Fabio Eiji; Kaberlein, Joseph; Wang, Chong-zhi; Nobrega, Marcelo; Thirman, Michael] Univ Chicago, Chicago, IL 60637 USA. [Prabhakar, Shyam] Genome Inst Singapore, Singapore, Singapore. [Wang, Qianben] Harvard Univ, Sch Med, Boston, MA USA. [Wang, Qianben] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 276 EP 277 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104700746 ER PT J AU Schriber, JR Agovi, MA Ballen, KK Bacigalupo, A Hale, GA Gupta, V Lazarus, HM Litzow, MR Marks, DI Giller, RH Maziarz, RT Bornhauser, M Isola, LM Bredeson, C Rizzo, JD AF Schriber, Jeffrey R. Agovi, Manza- A. Ballen, Karen K. Bacigalupo, Andrea Hale, Gregory A. Gupta, Vikas Lazarus, Hillard M. Litzow, Mark R. Marks, David I. Giller, Roger H. Maziarz, Richard T. Bornhauser, Martin Isola, Luis M. Bredeson, Christopher Rizzo, J. Douglas TI Second Unrelated Donor (URD) Transplant as a Rescue Strategy for 122 Patients with Primary Non Engraftment: Results from the CIBMTR SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Schriber, Jeffrey R.] Banner Good Samaritan Med Ctr, Phoenix, AZ USA. [Agovi, Manza- A.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ballen, Karen K.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bacigalupo, Andrea] Osped San Martino Genova, Genoa, Italy. [Hale, Gregory A.] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Marks, David I.] Bristol Royal Hosp Children, Bristol, Avon, England. [Giller, Roger H.] Childrens Hosp, Aurora, CO USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bornhauser, Martin] Univ Hosp Dresden, Dresden, Germany. [Isola, Luis M.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Bredeson, Christopher] Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 295 EP 295 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701018 ER PT J AU Levy, O Suter, EE Kalish, LA Gallington, LC Teghanemt, A Viriyakosol, S Soiffer, RJ Weiss, J Scannon, P Leung, HM Priebe, G Russell, J Walker, P Wessels, MR Guinan, E AF Levy, Ofer Suter, Eugenie E. Kalish, Leslie A. Gallington, Leighanne C. Teghanemt, Athmane Viriyakosol, Suganya Soiffer, Robert J. Weiss, Jerrold Scannon, Patrick Leung, Hoi M. Priebe, Gregory Russell, Janice Walker, Paul Wessels, Michael R. Guinan, Eva TI Myeloablative Hematopoietic Stem Cell Transplantation (HSCT) Is Accompanied by Endotoxemia, Activation of Endotoxin-Directed Innate Immunity, and Deficiency of Endogenous Proteins That Limit Endotoxin-Induced TNF Production SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Levy, Ofer; Suter, Eugenie E.; Gallington, Leighanne C.; Wessels, Michael R.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Kalish, Leslie A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Teghanemt, Athmane; Weiss, Jerrold] Univ Iowa, Dept Med, Iowa City, IA 52242 USA. [Viriyakosol, Suganya] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Soiffer, Robert J.; Russell, Janice] Dana Farber Canc Inst, Boston, MA 02115 USA. [Scannon, Patrick; Leung, Hoi M.] XOMA US LLC, Berkeley, CA USA. [Priebe, Gregory] Childrens Hosp, Div Crit Care Med, Boston, MA 02115 USA. [Walker, Paul] Spectral Diagnost, Toronto, ON, Canada. RI Gallington, Leighanne/G-9341-2011 OI Gallington, Leighanne/0000-0002-0383-7522 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 297 EP 298 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701024 ER PT J AU Juszczynski, P Chen, L Polo, JM Ranuncolo, SM Dalla-Favera, R Melnick, A Shipp, MA AF Juszczynski, Przemyslaw Chen, Linfeng Polo, Jose M. Ranuncolo, Stella M. Dalla-Favera, Riccardo Melnick, Ari Shipp, Margaret A. TI BCL6 Regulates Tonic BCR Signaling in Diffuse Large B-Cell Lymphomas by Repressing the SYK Phosphatase, PTPROt SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Juszczynski, Przemyslaw; Chen, Linfeng; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Polo, Jose M.; Ranuncolo, Stella M.; Melnick, Ari] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Dalla-Favera, Riccardo] Columbia Univ, Inst Canc Genet, Dept Pathol & Genet & Dev, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 298 EP 298 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701026 ER PT J AU Biernacki, MA Zhang, G Zhang, W Brusic, V Soiffer, RJ Neuberg, D Alyea, EP Tai, YT Munshi, NC Ritz, J Anderson, KC Wu, CJ AF Biernacki, Melinda A. Zhang, Guanglan Zhang, Wandi Brusic, Vladimir Soiffer, Robert J. Neuberg, Donna Alyea, Edwin P. Tai, Yu-Tzu Munshi, Nikhil C. Ritz, Jerome Anderson, Kenneth C. Wu, Catherine J. TI Novel Myeloma-Associated Antigens Revealed in the Context of Successful Syngeneic Hematopoietic Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Biernacki, Melinda A.] Univ Connecticut, Sch Med, Farmington, CT USA. [Zhang, Guanglan; Zhang, Wandi; Brusic, Vladimir] Canc Vaccine Ctr, Dana Farber Canc Inst, Boston, MA USA. [Soiffer, Robert J.; Alyea, Edwin P.; Tai, Yu-Tzu; Munshi, Nikhil C.; Ritz, Jerome; Anderson, Kenneth C.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 302 EP 303 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701039 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Wu, Z Bissonnette, A Somaiya, P MacNamara, C Uhl, L Avivi, I Katz, T Zarwan, C Joyce, R Levine, JD Boussiotis, V Tzachanis, D Lowe, K Dombagoda, D Giallombardo, N Mortellite, J Conway, K Fitzgerald, D Richardson, P Anderson, K Munshi, NC Tsumer, M Bisharat, L Rowe, J Kufe, D AF Avigan, David Rosenblatt, Jacalyn Vasir, Baldev Wu, Zekui Bissonnette, Adam Somaiya, Poorvi MacNamara, Claire Uhl, Lynne Avivi, Irit Katz, Tami Zarwan, Corrine Joyce, Robin Levine, James D. Boussiotis, Vassiliki Tzachanis, Dimitrios Lowe, Karen Dombagoda, Dilani Giallombardo, Nancy Mortellite, Jamie Conway, Katharine Fitzgerald, Donna Richardson, Paul Anderson, Kenneth Munshi, Nikhil C. Tsumer, Michal Bisharat, Lina Rowe, Jacob Kufe, Donald TI Fusion Cell Vaccination in Conjunction with Stem Cell Transplantation Is Well Tolerated, Induces Anti-Tumor Immunity and Is Associated with Responses in Patients with Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Avigan, David; Rosenblatt, Jacalyn; Somaiya, Poorvi; MacNamara, Claire; Uhl, Lynne; Zarwan, Corrine; Joyce, Robin; Levine, James D.; Boussiotis, Vassiliki; Tzachanis, Dimitrios; Lowe, Karen; Dombagoda, Dilani; Giallombardo, Nancy; Mortellite, Jamie; Conway, Katharine; Fitzgerald, Donna] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, Baldev; Wu, Zekui; Bissonnette, Adam; Richardson, Paul; Anderson, Kenneth; Munshi, Nikhil C.; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Avivi, Irit; Katz, Tami; Tsumer, Michal; Bisharat, Lina; Rowe, Jacob] Rambam Med Ctr, IL-31096 Haifa, Israel. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 306 EP 307 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701050 ER PT J AU Ho, V Dranoff, G Kim, H Vanneman, M Pasek, M Cutler, C Koreth, J Alyea, E Antin, JH Jerome, R Soiffer, RJ AF Ho, Vincent Dranoff, Glenn Kim, Haesook Vanneman, Matthew Pasek, Mildred Cutler, Corey Koreth, John Alyea, Edwin Antin, Joseph H. Jerome, Ritz Soiffer, Robert J. TI GM-CSF Secreting Leukemia Cell Vaccination after Allogeneic Reduced Intensity Hematopoietic Stem Cell Transplantation for Advanced Myeloid Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ho, Vincent; Dranoff, Glenn; Kim, Haesook; Vanneman, Matthew; Pasek, Mildred; Cutler, Corey; Koreth, John; Alyea, Edwin; Antin, Joseph H.; Jerome, Ritz; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 306 EP 306 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701049 ER PT J AU Ghobrial, IM Matous, J Padmanabhan, S Badros, A Schlossman, R Chuma, S Leduc, R Nelson, M O'Connor, K Sam, A Harris, B Soumerai, J Warren, D Birner, A Munshi, N Treon, SP Anderson, KC Richardson, P AF Ghobrial, Irene M. Matous, Jeffrey Padmanabhan, Swaminathan Badros, Ashraf Schlossman, Robert Chuma, Stacey Leduc, Renee Nelson, Marybeth O'Connor, Kelly Sam, Amy Harris, Brianna Soumerai, Jacob Warren, Diane Birner, Ann Munshi, Nikhil Treon, Steven P. Anderson, Kenneth C. Richardson, Paul TI Phase II Trial of Combination of Bortezomib and Rituximab in Relapsed and/or Refractory Waldenstrom Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.; Schlossman, Robert; Chuma, Stacey; Leduc, Renee; Nelson, Marybeth; O'Connor, Kelly; Sam, Amy; Harris, Brianna; Soumerai, Jacob; Warren, Diane; Birner, Ann; Munshi, Nikhil; Treon, Steven P.; Anderson, Kenneth C.; Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Padmanabhan, Swaminathan] Roswell Pk Canc Ctr, Buffalo, NY USA. [Badros, Ashraf] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 308 EP 309 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701056 ER PT J AU Tai, YT Soydan, E Fulciniti, M Song, WH Li, XF Burger, P Hong, FX Tonon, G Kim, K Rumizen, MJ Nahar, S Podar, K Chauhan, D Hideshima, T Carrasco, DR Munshi, NC Afar, D Anderson, KC AF Tai, Yu-Tzu Soydan, Ender Fulciniti, Mariateresa Song, Weihua Li, Xian-Feng Burger, Peter Hong, Fangxin Tonon, Giovanni Kim, Kihyun Rumizen, Mathew J. Nahar, Sabikun Podar, Klaus Chauhan, Dharminder Hideshima, Teru Carrasco, Daniel R. Munshi, Nikhil C. Afar, Daniel Anderson, Kenneth C. TI CS1 Promotes Multiple Myeloma Cell Adhesion, Clonogenic Growth, and Tumorigenicity Via C-Maf-Mediated Interactions with Bone Marrow Stromal Cells (BMSCs) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Tai, Yu-Tzu; Soydan, Ender; Fulciniti, Mariateresa; Song, Weihua; Li, Xian-Feng; Burger, Peter; Hong, Fangxin; Tonon, Giovanni; Kim, Kihyun; Rumizen, Mathew J.; Nahar, Sabikun; Podar, Klaus; Chauhan, Dharminder; Hideshima, Teru; Carrasco, Daniel R.; Munshi, Nikhil C.; Anderson, Kenneth C.] Dana Farber Canc Inst, Med Oncol, Boston, MA 02115 USA. [Afar, Daniel] PDL BioPharma Inc, Res, Redwood City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 311 EP 311 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701064 ER PT J AU Rickles, RJ Pierce, L Giordano, T Tam, WF McMillin, DW Anderson, KC Mitsiades, C Lee, MS AF Rickles, Richard J. Pierce, Laura Giordano, Thomas Tam, Winnie F. McMillin, Douglas W. Anderson, Kenneth C. Mitsiades, Constantine Lee, Margaret S. TI Adenosine A2A Receptor Agonism and PDE Inhibition: A Synergistic Multi-Target Mechanism Discovered through Systematic Combination Screening in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rickles, Richard J.; Pierce, Laura; Giordano, Thomas; Tam, Winnie F.; Lee, Margaret S.] CombinatoRx Inc, Cambridge, MA USA. [McMillin, Douglas W.; Anderson, Kenneth C.; Mitsiades, Constantine] Harvard Univ, Sch Med, Dana Farber Canc Inst,Dept Med, Jerome Lipper Multiple Myeloma Ctr,Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 313 EP 314 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701071 ER PT J AU LaBelle, JL Lawrence, CE Bird, GH Walensky, LD AF LaBelle, James L. Lawrence, Chelsea E. Bird, Gregory H. Walensky, Loren D. TI A Stapled BIM BH3 Helix Overcomes the MCL-1-Mediated Apoptotic Blockade of Refractory Hematologic Cancers SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [LaBelle, James L.; Lawrence, Chelsea E.; Bird, Gregory H.; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Program Canc Chem Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 319 EP 319 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701086 ER PT J AU Richardson, P Wolf, J Jakubowiak, A Zonder, J Lonial, S Irwin, DH Densmore, J Krishnan, A Raje, N Bar, MH Allerton, JP Schlossman, R Ghobrial, IM Munshi, NC Martin, T Laubach, J Colson, K Dean, S Tocco, D Steinfield, E Kendall, T O'Riley, K Hideshima, T Sportelli, P Gardner, L Anderson, KC AF Richardson, Paul Wolf, Jeffrey Jakubowiak, Andrzej Zonder, Jeffrey Lonial, Sagar Irwin, David H. Densmore, John Krishnan, Amrita Raje, Noopur Bar, Michael H. Allerton, Jeffrey P. Schlossman, Robert Ghobrial, Irene M. Munshi, Nikhil C. Martin, Thomas Laubach, Jacob Colson, Kathy Dean, Sarah Tocco, Deanna Steinfield, Elizabeth Kendall, Tara O'Riley, Kimberly Hideshima, Teru Sportelli, Peter Gardner, Lesa Anderson, Kenneth C. TI Phase I/II Results of a Multicenter Trial of Perifosine (KRX-0401) + Bortezomib in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma Who Were Previously Relapsed from or Refractory to Bortezomib SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul; Schlossman, Robert; Ghobrial, Irene M.; Munshi, Nikhil C.; Laubach, Jacob; Colson, Kathy; Dean, Sarah; Tocco, Deanna; Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Wolf, Jeffrey; Martin, Thomas; Steinfield, Elizabeth] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Jakubowiak, Andrzej; Kendall, Tara] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Zonder, Jeffrey; O'Riley, Kimberly] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Irwin, David H.] Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. [Densmore, John] Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. [Krishnan, Amrita] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Bar, Michael H.] Bennett Canc Ctr, Stamford, CT USA. [Allerton, Jeffrey P.] Guthrie Clin, Sayre, PA USA. [Sportelli, Peter; Gardner, Lesa] Keryx Biopharmaceut Inc, New York, NY USA. NR 0 TC 2 Z9 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 321 EP 322 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701094 ER PT J AU Weber, D Badros, AZ Jagannath, S Siegel, D Richon, V Rizvi, S Garcia-Vargas, J Reiser, D Anderson, KC AF Weber, Donna Badros, Ashraf Z. Jagannath, Sundar Siegel, David Richon, Victoria Rizvi, Syed Garcia-Vargas, Jose Reiser, David Anderson, Kenneth C. TI Vorinostat Plus Bortezomib for the Treatment of Relapsed/Refractory Multiple Myeloma: Early Clinical Experience SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Weber, Donna] Univ Texas MD Anderson Canc Ctr, Dept Lymphona & Myeloma, Houston, TX 77030 USA. [Badros, Ashraf Z.] Univ Maryland, Baltimore, MD 21201 USA. [Jagannath, Sundar] St Vincents Comp Canc Ctr, New York, NY USA. [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Richon, Victoria; Rizvi, Syed; Garcia-Vargas, Jose; Reiser, David] Merck & Co Inc, Upper Gwynedd, PA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Brookline, MA USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 322 EP 322 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701095 ER PT J AU Van Bennekom, CM Abel, G Anderson, T Stone, RM Kaufman, DW AF Van Bennekom, Carla M. Abel, Gregory Anderson, Theresa Stone, Richard M. Kaufman, David W. TI Patterns of Treatment among Patients with Recently-Diagnosed Myelodysplastic Syndromes in a National Registry, 2006-2008 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Van Bennekom, Carla M.; Anderson, Theresa; Kaufman, David W.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Abel, Gregory; Stone, Richard M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 324 EP 324 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701100 ER PT J AU Cortes, J Seiter, K Maziarz, RT Wetzler, M Craig, M Matous, J Luger, S Dey, B Schiller, GJ Pham, D Abboud, CN Krishnamurthy, M Brown, A Moore, JO AF Cortes, Jorge Seiter, Karen Maziarz, Richard Thomas Wetzler, Meir Craig, Michael Matous, Jeffrey Luger, Selina Dey, Bimalangshu Schiller, Gary J. Pham, Dat Abboud, Camille N. Krishnamurthy, Muthuswamy Brown, Archie, Jr. Moore, Joseph O. TI Superiority of Rasburicase Versus Allopurinol on Serum Uric Acid Control in Adult Patients with Hematological Malignancies at Risk of Developing Tumor Lysis Syndrome: Results of a Randomized Comparative Phase III Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cortes, Jorge] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Seiter, Karen] New York Med Coll, Valhalla, NY 10595 USA. [Maziarz, Richard Thomas] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Wetzler, Meir] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Craig, Michael] WVU, Morgantown, WV USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Luger, Selina] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Dey, Bimalangshu] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Schiller, Gary J.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Pham, Dat] UF Shands Jacksonville, Jacksonville, FL USA. [Abboud, Camille N.] Washington Univ, St Louis, MO USA. [Krishnamurthy, Muthuswamy] New York Methodist Hosp, Brooklyn, NY USA. [Brown, Archie, Jr.] Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. [Moore, Joseph O.] Duke Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 340 EP 341 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701143 ER PT J AU Ottmann, OG Spencer, A Prince, HM Bhalla, KN Fischer, T Liu, A Parker, K Jalaluddin, M Laird, G Woo, M Scott, JW DeAngelo, DJ AF Ottmann, Oliver G. Spencer, Andrew Prince, H. Miles Bhalla, Kapil N. Fischer, Thomas Liu, Angela Parker, Kathryn Jalaluddin, Muhammad Laird, Glen Woo, Margaret Scott, Jeffrey W. DeAngelo, Daniel J. TI Phase IA/II Study of Oral Panobinostat (LBH589), a Novel Pan-Deacetylase Inhibitor (DACi) Demonstrating Efficacy in Patients with Advanced Hematologic Malignancies. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ottmann, Oliver G.] Univ Frankfurt, Med Klin 2, Frankfurt, Germany. [Spencer, Andrew] Alfred Hosp, Clin Haematol & BMT, Melbourne, Vic, Australia. [Prince, H. Miles] Peter MacCallum Canc Ctr, Dept Haematol, Melbourne, Vic, Australia. [Bhalla, Kapil N.] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA. [Fischer, Thomas] Univ Magdeburg, Dept Hematol Oncol, D-39106 Magdeburg, Germany. [Liu, Angela; Parker, Kathryn; Laird, Glen; Woo, Margaret; Scott, Jeffrey W.] Novartis Oncol, Florham Pk, NJ USA. [Jalaluddin, Muhammad] Novartis Pharmaceut, Florham Pk, NJ USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 352 EP 353 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701182 ER PT J AU Brown, JR Stevenson, K Kim, HT Armand, P Cutler, C Fisher, DC Ho, V Koreth, J Ritz, J Antin, JH Soiffer, RJ Gribben, JG Alyea, E AF Brown, Jennifer R. Stevenson, Kristen Kim, Haesook T. Armand, Philippe Cutler, Corey Fisher, David C. Ho, Vincent Koreth, John Ritz, Jerome Antin, Joseph H. Soiffer, Robert J. Gribben, John G. Alyea, Edwin TI Comparative Outcome of Myeloablative and Reduced Intensity Allogeneic Stem Cell Transplantation for Chronic Lymphocytic Leukemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Jennifer R.; Stevenson, Kristen; Kim, Haesook T.; Armand, Philippe; Cutler, Corey; Fisher, David C.; Ho, Vincent; Koreth, John; Ritz, Jerome; Antin, Joseph H.; Soiffer, Robert J.; Alyea, Edwin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, Inst Canc, Ctr Med Oncol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 357 EP 358 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701196 ER PT J AU Canault, M Duerschmied, D Brill, A Patten, IS Bergmeier, W Wagner, DD AF Canault, Matthias Duerschmied, Daniel Brill, Alexander Patten, Ian Sean Bergmeier, Wolfgang Wagner, Denisa D. TI MAPK Inhibition Prevents TACE-Mediated Receptor Shedding and Improves the Hemostatic Function of Stored Platelets. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Canault, Matthias; Duerschmied, Daniel; Brill, Alexander; Patten, Ian Sean; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Bergmeier, Wolfgang] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. RI Canault, Matthias/H-5128-2013 OI Canault, Matthias/0000-0002-7880-5250 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 365 EP 365 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701214 ER PT J AU Friedberg, JW Younes, A Fisher, DC Gordon, LI Moore, JO Czuczman, MS Miller, TP Stiff, PJ Cheson, BD Forero-Torres, A McKinney, B Leonard, JP AF Friedberg, Jonathan W. Younes, Anas Fisher, David C. Gordon, Leo I. Moore, Joseph O. Czuczman, Myron S. Miller, Thomas P. Stiff, Patrick J. Cheson, Bruce D. Forero-Torres, Andres McKinney, Byron Leonard, John P. TI Durable Responses in Patients Treated with Galiximab (Anti-CD80) in Combination with Rituximab for Relapsed or Refractory Follicular Lymphoma: Long-Term Follow-up of a Phase II Clinical Trial. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Friedberg, Jonathan W.] Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY 77030 USA. [Younes, Anas] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 02115 USA. [Fisher, David C.] Dana Farber Canc Inst, Boston, MA 60611 USA. [Gordon, Leo I.] Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL USA. [Moore, Joseph O.] Duke Med Ctr, Durham, NC 14263 USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY USA. [Miller, Thomas P.] Univ Arizona, Arizona Canc Ctr, Tucson, AZ 60153 USA. [Stiff, Patrick J.] Loyola Univ, Med Ctr, Maywood, IL USA. [Cheson, Bruce D.] Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. [Forero-Torres, Andres] Univ Alabama, Birmingham, AL USA. [McKinney, Byron] Biogen Idec, San Diego, CA USA. [Leonard, John P.] Weill Cornell Med Coll, Div Hem Onc, New York, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 369 EP 370 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701228 ER PT J AU Ghobrial, IM Chuma, S Sam, A Leduc, R Nelson, M O'Connor, K Harris, B Soumerai, J Warren, D Jacobsen, E DeAngelo, D Anderson, KC Richardson, PG Witzig, TE Treon, SP AF Ghobrial, Irene M. Chuma, Stacey Sam, Amy Leduc, Renee Nelson, Marybeth O'Connor, Kelly Harris, Brianna Soumerai, Jacob Warren, Diane Jacobsen, Eric DeAngelo, Daniel Anderson, Kenneth C. Richardson, Paul G. Witzig, Thomas E. Treon, Steven P. TI Phase II Trial of the mTOR Inhibitor RAD001 in Relapsed and/or Refractory Waldenstrom Macroglobulinemia: The Dana Farber Cancer Institute Experience. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.; Chuma, Stacey; Sam, Amy; Leduc, Renee; Nelson, Marybeth; O'Connor, Kelly; Harris, Brianna; Soumerai, Jacob; Warren, Diane; Jacobsen, Eric; DeAngelo, Daniel; Anderson, Kenneth C.; Richardson, Paul G.; Treon, Steven P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Witzig, Thomas E.] Mayo Clin, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 372 EP 372 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701235 ER PT J AU Ghobrial, IM Leleu, X Rubin, N Xie, WL Hong, FX Chuma, S Leduc, R Nelson, M O'Connor, K Sam, A Harris, B Warren, D Sportelli, P Treon, SP Weller, E Anderson, KC Richardson, PG AF Ghobrial, Irene M. Leleu, Xavier Rubin, Nancy Xie, Wanling Hong, Fangxin Chuma, Stacey Leduc, Renee Nelson, Marybeth O'Connor, Kelly Sam, Amy Harris, Brianna Warren, Diane Sportelli, Peter Treon, Steven P. Weller, Edie Anderson, Kenneth C. Richardson, Paul G. TI Final Results of a Phase II Trial of the Novel Oral Akt Inhibitor Perifosine in Relapsed and/or Refractory Waldenstrom Macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.; Leleu, Xavier; Hong, Fangxin; Chuma, Stacey; Leduc, Renee; Nelson, Marybeth; O'Connor, Kelly; Sam, Amy; Harris, Brianna; Warren, Diane; Treon, Steven P.; Weller, Edie; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rubin, Nancy] Community Hosp Monterey Peninsula, Monterey, CA USA. [Xie, Wanling] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 372 EP 372 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701234 ER PT J AU Kay, NE Kim, HT Kempin, S Secreto, C Knox, T Tschumper, R Jelinek, DF Smoley, S Van Dyke, D Saltzman, J Rosen, ST Kahl, B Tallman, MS AF Kay, Neil E. Kim, Haesook T. Kempin, Sanford Secreto, Charla Knox, Traci Tschumper, Renee Jelinek, Diane F. Smoley, Stephanie Van Dyke, Daniel Saltzman, Joel Rosen, Steven T. Kahl, Brad Tallman, Martin S. TI Predictors of Clinical Outcome to Pentostatin, Cyclophosphamide and Rituximab (PCR) Followed by Campath for Relapsed/Refractory CLL - A Study of the Eastern Cooperative Oncology Group, E2903. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kay, Neil E.; Secreto, Charla; Knox, Traci; Tschumper, Renee; Jelinek, Diane F.; Smoley, Stephanie; Van Dyke, Daniel] Mayo Clin, Rochester, MN USA. [Kim, Haesook T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kempin, Sanford] St Vincents Hosp, Ctr Comprehens Canc, New York, NY USA. [Saltzman, Joel] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Rosen, Steven T.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Kahl, Brad] Univ Wisconsin, Madison, WI USA. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 387 EP 387 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701281 ER PT J AU Smoley, SA Van Dyke, DL Kay, NE Heerema, NA Dell'Aquila, ML Koduru, P Dal Cin, P Rassenti, L Byrd, JC Rai, KR Brown, JR Greaves, AW Kipps, TJ Dewald, GW AF Smoley, Stephanie A. Van Dyke, Daniel L. Kay, Neil E. Heerema, Nyla A. dell'Aquila, Marie L. Koduru, Prasad Dal Cin, Paola Rassenti, Laura Byrd, John C. Rai, Kanti R. Brown, Jennifer R. Greaves, Andrew W. Kipps, Thomas J. Dewald, Gordon W. TI Validation of CLL FISH Panel Scoring by Members of the Chronic Lymphocytic Leukemia Research Consortium. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kay, Neil E.] Mayo Clin, Div Hematol Oncol, Rochester, MN USA. [Heerema, Nyla A.; Byrd, John C.] Ohio State Univ, Columbus, OH 43210 USA. [dell'Aquila, Marie L.; Greaves, Andrew W.] Univ Calif San Diego, San Diego, CA 92103 USA. [Koduru, Prasad] Royal N Shore Hosp, Manhasset, NY USA. [Dal Cin, Paola] Brigham & Womens Hosp, Boston, MA 02115 USA. [Rassenti, Laura] Moores UCSD Canc Ctr, La Jolla, CA USA. [Rai, Kanti R.] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. [Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kipps, Thomas J.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 390 EP 391 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701291 ER PT J AU Davies, J De Lima, M Cooper, L Spitzer, T Kapoor, N Brennan, L Thall, P McMannis, J Champlin, R Nadler, L Guinan, E AF Davies, Jeff De Lima, Marcos Cooper, Laurence Spitzer, Thomas Kapoor, Neena Brennan, Lisa Thall, Peter McMannis, John Champlin, Richard Nadler, Lee Guinan, Eva TI Phase 1 Clinical Study of Adoptive Immunotherapy with Delayed Infusion of Alloanergized Donor T Cells to Improve Immune Reconstution after Haploidentical Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Davies, Jeff; Brennan, Lisa; Nadler, Lee; Guinan, Eva] Dana Farber Canc Inst, Boston, MA 02115 USA. [De Lima, Marcos; Cooper, Laurence; Thall, Peter; McMannis, John; Champlin, Richard] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Spitzer, Thomas] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kapoor, Neena] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 422 EP 423 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701378 ER PT J AU Koreth, J Stevenson, K Kim, HT Ho, VT Cutler, CS Armand, P Soiffer, RJ Antin, JH Alyea, EP AF Koreth, John Stevenson, Kristen Kim, Haesook T. Ho, Vincent T. Cutler, Corey S. Armand, Philippe Soiffer, Robert J. Antin, Joseph H. Alyea, Edwin P., III TI A Phase I/II Trial of Bortezomib, Tacrolimus and Methotrexate for Prophylaxis of Acute Graft Versus Host Disease after HLA Mismatched Reduced Intensity Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Koreth, John; Ho, Vincent T.; Cutler, Corey S.; Armand, Philippe; Soiffer, Robert J.; Antin, Joseph H.; Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 423 EP 423 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701380 ER PT J AU Brown, J McDonough, S Stevenson, K Reynolds, C Kim, H Alyea, EP Antin, JH Attar, E Avigan, D Cutler, CS Dey, B Ho, V Joyce, R Levine, JD McAfee, SL Rosenblatt, J Soiffer, RJ Spitzer, T Tzachanis, D Ballen, KK Ritz, J Boussiotis, V AF Brown, Julia McDonough, Sean Stevenson, Kristin Reynolds, Carol Kim, Haesook Alyea, Edwin P., III Antin, Joseph H. Attar, Eyal Avigan, David Cutler, Corey S. Dey, Bimalangshu Ho, Vincent Joyce, Robin Levine, James D. McAfee, Steven L. Rosenblatt, Jacalyn Soiffer, Robert J. Spitzer, Thomas Tzachanis, Dimitrios Ballen, Karen K. Ritz, Jerome Boussiotis, Vassiliki TI Development of CMV-SPECIFIC Immunity after Cord Blood Transplantation in Adults Depends on Reconstitution of Thymopoiesis and Regeneration of NAIVE CD8+T Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Julia; Boussiotis, Vassiliki] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA. [Alyea, Edwin P., III] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Antin, Joseph H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Attar, Eyal] Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med, Boston, MA 02114 USA. [Dey, Bimalangshu] Mass Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 426 EP 426 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701389 ER PT J AU Skert, C Prestini, K Peli, A Biasi, L Fili, C Malagola, M Bergonzi, C Mendeni, M Roccaro, AM Puoti, M Russo, D AF Skert, Cristina Prestini, Katia Peli, Annalisa Biasi, Luciano Fili, Carla Malagola, Michele Bergonzi, Cesare Mendeni, Monia Roccaro, Aldo M. Puoti, Massimo Russo, Domenico TI Assessment of Liver Damage with Transient Hepatic Elastography (FIBROSCAN) in patients with chronic Graft-Versus-Host Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Skert, Cristina; Peli, Annalisa; Fili, Carla] Univ Brescia, Chair Haematol, Stem Cell Transplantat Unit, Brescia, Italy. [Prestini, Katia; Biasi, Luciano; Mendeni, Monia; Puoti, Massimo] Univ Brescia, Dept Infect & Trop Dis, Brescia, Italy. [Roccaro, Aldo M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 432 EP 433 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701406 ER PT J AU Czibere, A Singh, R Bruns, I Zerbini, LF Haas, R AF Czibere, Akos Singh, Raminder Bruns, Ingmar Zerbini, Luiz Fernando Haas, Rainer TI Ap-1 Family Members C-Jun, JunB and Fra-2 Mediate Apoptosis and Differentiation in AML through Activation of GADD45 alpha and ADFP Following Non-Steroidal Anti-Inflammatory Drug Treatment SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Czibere, Akos; Singh, Raminder; Bruns, Ingmar; Haas, Rainer] Univ Dusseldorf, Dusseldorf, Germany. [Zerbini, Luiz Fernando] Beth Israel Deaconess Med Ctr, BIDMC Genom Ctr, Boston, MA 02215 USA. RI Zerbini, Luiz /B-7720-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 436 EP 436 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701418 ER PT J AU Rosenblatt, J Bissonnette, A Wu, ZK Vasir, B Zarwan, C Keefe, W Joyce, R Levine, JD Glotzbecker, B Rozenvayn, N Tzachanis, D Boussiotis, V Kufe, D Avigan, D AF Rosenblatt, Jacalyn Bissonnette, Adam Wu, Zekui Vasir, Baldev Zarwan, Corrine Keefe, Whitney Joyce, Robin Levine, James D. Glotzbecker, Brett Rozenvayn, Nataliya Tzachanis, Dimitrios Boussiotis, Vassiliki Kufe, Donald Avigan, David TI Immunomodulatory Effects of Vitamin D: Implications for the Prevention and Treatment of Graft Versus Host Disease. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rosenblatt, Jacalyn; Zarwan, Corrine; Joyce, Robin; Levine, James D.; Glotzbecker, Brett; Rozenvayn, Nataliya; Tzachanis, Dimitrios; Boussiotis, Vassiliki; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Bissonnette, Adam; Wu, Zekui; Vasir, Baldev; Keefe, Whitney; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 454 EP 454 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701473 ER PT J AU Waters, EK Bernimoulin, M Foy, M Steele, BM Sullivan, M Falet, H Hartwig, JH Maguire, PB Wagner, DD AF Waters, Emily K. Bernimoulin, Michael Foy, Martina Steele, Brian M. Sullivan, Matthew Falet, Herve Hartwig, John H. Maguire, Patricia B. Wagner, Denisa D. TI Differential Stimulation of Monocytic Cells Results in Distinct Populations of Microparticles SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Waters, Emily K.; Bernimoulin, Michael; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Foy, Martina; Steele, Brian M.; Sullivan, Matthew; Maguire, Patricia B.] UCD Conway Inst, Sch Biomol & Biomed Sci, Dublin 4, Ireland. [Falet, Herve; Hartwig, John H.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 456 EP 456 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701480 ER PT J AU Carbo, C Goerge, T Hattori, H Duerschmied, D Cifuni, SM Luo, HR Wagner, DD AF Carbo, Carla Goerge, Tobias Hattori, Hidenori Duerschmied, Daniel Cifuni, Stephen M. Luo, Hongbo R. Wagner, Denisa D. TI Integrin-Independent Role of CalDAG-GEFI in Neutrophil Chemotaxis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Carbo, Carla; Goerge, Tobias; Duerschmied, Daniel; Cifuni, Stephen M.; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Hattori, Hidenori; Luo, Hongbo R.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 458 EP 459 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701488 ER PT J AU Grace, RF Mednick, RE Neufeld, EJ AF Grace, Rachael F. Mednick, Rachel E. Neufeld, Ellis J. TI Compliance with Immunizations in Splenectomized Individuals: A Study of the Splenectomized Hereditary Spherocytosis Population SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Grace, Rachael F.; Mednick, Rachel E.; Neufeld, Ellis J.] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 476 EP 476 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701538 ER PT J AU Corneio, MG Mercher, T Growney, JD Jesneck, J Maillard, I Pear, WS Aster, J Gilliland, DG AF Corneio, Melanie G. Mercher, Thomas Growney, Joseph D. Jesneck, Jonathan Maillard, Ivan Pear, Warren S. Aster, Jon Gilliland, D. Gary TI Runx1 Is Required for Notch-Induced Specification of Megakaryocyte Development from Early Hematopoietic Stem and Progenitor Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Corneio, Melanie G.; Growney, Joseph D.; Gilliland, D. Gary] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Hematol, Boston, MA 02115 USA. [Mercher, Thomas] Univ Paris 5 Descartes, INSERM, EM10210, Paris, France. [Jesneck, Jonathan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Maillard, Ivan] Ctr Stem Cell Biol, Inst Life Sci, Ann Arbor, MI USA. [Pear, Warren S.] Univ Penn, Philadelphia, PA 19104 USA. RI Mercher, Thomas/J-2446-2014 OI Mercher, Thomas/0000-0003-1552-087X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 492 EP 492 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701592 ER PT J AU Wang, JF Dayyani, F Brynczka, C Sweetser, DA AF Wang, Jianfeng Dayyani, Farshid Brynczka, Christopher Sweetser, David A. TI Groucho/TLE Corepressors Regulate Myeloid Differentiation and Size of the Stem Cell/Progenitor Population. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wang, Jianfeng; Brynczka, Christopher] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Dayyani, Farshid] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 499 EP 499 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701618 ER PT J AU Tothova, Z Sykes, SM Leeman, DS Horner, JW Sharpless, N DePinho, RA Gilliland, DG AF Tothova, Zuzana Sykes, Stephen M. Leeman, Dena S. Horner, James W. Sharpless, Norman DePinho, Ronald A. Gilliland, D. Gary TI p16(INK4a) Is a Key Downstream Mediator of the Deleterious Effects of FoxO Deficiency on Maintenance of the Hematopoietic Stem Cell Compartment. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Tothova, Zuzana; Sykes, Stephen M.; Leeman, Dena S.; Gilliland, D. Gary] Harvard Univ, Sch Med, Howard Hughes Med Inst, Brigham & Womens Hosp,Div Hematol, Boston, MA 02115 USA. [Horner, James W.; DePinho, Ronald A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sharpless, Norman] Univ N Carolina, Sch Med, Lineberger Canc Res Ctr, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 502 EP 502 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701627 ER PT J AU Barnes, JA LaCasce, AS Toomey, CE Hochberg, E Lee, AI Canellos, GP Abramson, JS AF Barnes, Jeffrey A. LaCasce, Ann S. Toomey, Christiana E. Hochberg, Ephraim Lee, Alfred I. Canellos, George P. Abramson, Jeremy S. TI Early Interim FDG-PET Scan Predicts Outcome in Non-Bulky Limited Stage Hodgkin Lymphoma, but may Not Guide Use of Consolidative Radiotherapy SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Barnes, Jeffrey A.; Toomey, Christiana E.; Hochberg, Ephraim; Lee, Alfred I.; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [LaCasce, Ann S.; Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2008 VL 112 IS 11 BP 518 EP 518 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701675 ER PT J AU Kostakoglu, L Straus, DJ Schoder, H LaCasce, AS Bartlett, NL Hall, N Johnson, JL Jung, SH Canellos, GP Schwartz, LH Cheson, BD AF Kostakoglu, Lale Straus, David J. Schoeder, Heiko LaCasce, Ann S. Bartlett, Nancy L. Hall, Nathan Johnson, Jeffrey L. Jung, Sin-Ho Canellos, George P. Schwartz, Lawrence H. Cheson, Bruce D. TI Validation of the International Harmonization Project (IHP) Guidelines in Early Stage Hodgkin Lymphoma (HL) Treated with Adriamycin, Vinblastine and Gemcitabine (AVG) (CALGB 50203): Early Results SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol (ASH), Sanofi Aventis U.S. C1 [Kostakoglu, Lale] Mt Sinai Med Ctr, New York, NY 10029 USA. [Straus, David J.] MSKCC, New York, NY USA. [Schoeder, Heiko; Schwartz, Lawrence H.] Mem Sloan Kettering Canc Ctr, New York, NY USA. [LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bartlett, Nancy L.] Washington Univ, Sch Med, St Louis, MO USA. [Hall, Nathan] Ohio State Univ, Columbus, OH 43210 USA. [Johnson, Jeffrey L.; Jung, Sin-Ho] Duke Univ, Med Ctr, CALGB Stat Off, Durham, NC USA. [Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cheson, Bruce D.] Georgetown Univ Hosp, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 520 EP 520 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701682 ER PT J AU Song, WH Hideshima, T Tai, YT Anderson, KC Munshi, NC AF Song, Weihua Hideshima, Teru Tai, Yu-Tzu Anderson, Kenneth C. Munshi, Nikhil C. TI Phenotypic and Functional Effects of Novel Akt Inhibitor Perifosine on Immune System SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 551 EP 552 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701776 ER PT J AU Raab, MS Breitkreutz, I Rebacz, B Nguyen, T Hayden, PJ Clausen, MH Larsen, TO Fruehauf, J Anderson, KC Kraemer, A AF Raab, Marc S. Breitkreutz, Iris Rebacz, Blanca Nguyen, Thu Hayden, Patrick J. Clausen, Mads H. Larsen, Thomas O. Fruehauf, Johannes Anderson, Kenneth C. Kraemer, Alwin TI GF-15, a Novel Inhibitor of Centrosomal Clustering, Suppresses Tumor Growth in Vivo SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Raab, Marc S.; Breitkreutz, Iris; Hayden, Patrick J.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rebacz, Blanca; Kraemer, Alwin] German Canc Res Ctr, CCU Mol Hematol Oncol, D-6900 Heidelberg, Germany. [Nguyen, Thu; Fruehauf, Johannes] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Clausen, Mads H.; Larsen, Thomas O.] Univ Denmark, Bioctr, Lyngby, Denmark. RI Clausen, Mads/A-9656-2015 OI Clausen, Mads/0000-0001-9649-1729 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 578 EP 579 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701860 ER PT J AU Santini, V Fenaux, P Mufti, GJ Hellstrom-Lindberg, E Silverman, LB List, A Gore, SD Seymour, JF Backstrom, J McKenzie, D Beach, CL AF Santini, Valeria Fenaux, Pierre Mufti, Ghularn J. Hellstrom-Lindberg, Eva Silverman, Lewis B. List, Alan Gore, Steven D. Seymour, John F. Backstrom, Jay McKenzie, David Beach, C. L. TI Management and Supportive Care Measures of Adverse Events (AEs) in Higher-Risk MDS Patients (Pts) Treated with Azacitidine (AZA) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Santini, Valeria] Azienda Osped Careggi, Florence, Italy. [Fenaux, Pierre] Univ Paris 13, Hop Avicenne, AP HP, Hematol Clin, Bobigny, France. [Mufti, Ghularn J.] Kings Coll London, Dept Haematol Med, London, England. [Hellstrom-Lindberg, Eva] Karolinska Univ Hosp, Stockholm, Sweden. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [List, Alan] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Seymour, John F.] Peter MacCallum Canc Inst, Dept Haematol, Melbourne, Vic, Australia. [Backstrom, Jay; McKenzie, David; Beach, C. L.] Celgene, Overland Pk, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 583 EP 584 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701874 ER PT J AU Azab, AK Azab, F Pitsillides, CM Ngo, HT Jia, XY Melhem, MR Runnels, J Roccaro, AM Sacco, A Burwick, N Lin, CP Anderson, KC Ghobrial, IM AF Azab, Abdel Kareem Azab, Feda Pitsillides, Costas M. Ngo, Hai T. Jia, Xiaoying Melhem, Molly R. Runnels, Judith Roccaro, Aldo M. Sacco, Antonio Burwick, Nicholas Lin, Charles P. Anderson, Kenneth C. Ghobrial, Irene M. TI Rho-a and Rac-1 GTPases Play Major and Differential Roles in SDF1 alpha-Induced Cell Adhesion and Chemotaxis in Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Pitsillides, Costas M.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 588 EP 588 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701887 ER PT J AU Burwick, N Moreau, AS Jia, XY Leleu, X Runnels, J Ngo, HT Melhem, MR Roccaro, AM Azab, AK Ghobrial, IM AF Burwick, Nicholas Moreau, Anne-Sophie Jia, Xiaoying Leleu, Xavier Runnels, Judith Ngo, Hai T. Melhem, Molly R. Roccaro, Aldo M. Azab, Abdel Kareem Ghobrial, Irene M. TI CXCR7 Regulates SDF-1 Induced Adhesion and Homing in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Burwick, Nicholas; Moreau, Anne-Sophie; Jia, Xiaoying; Leleu, Xavier; Runnels, Judith; Ngo, Hai T.; Melhem, Molly R.; Roccaro, Aldo M.; Azab, Abdel Kareem; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 591 EP 592 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702008 ER PT J AU Kumar, S Zhang, L Dispenzieri, A Van Wier, S Katzmann, J Snyder, M Blood, E DeGoey, R Henderson, K Bradwell, A Kyle, R Greipp, P Rajkumar, SV Fonseca, R AF Kumar, Shaji Zhang, Lijun Dispenzieri, Angela Van Wier, Scott Katzmann, Jerry Snyder, Melissa Blood, Emily DeGoey, Roberta Henderson, Kim Bradwell, Arthur Kyle, Robert Greipp, Philip Rajkumar, S. Vincent Fonseca, Rafael TI Association of High Levels of Free Light Chain and the Presence of Igh Translocations in Multiple Myeloma and Prognostic Implications SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kumar, Shaji; Dispenzieri, Angela; Katzmann, Jerry; Snyder, Melissa; DeGoey, Roberta; Henderson, Kim; Kyle, Robert; Greipp, Philip; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Zhang, Lijun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Van Wier, Scott; Fonseca, Rafael] Mayo Clin Arizona, Scottsdale, AZ USA. [Blood, Emily] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Lebanon, NH 03756 USA. [Bradwell, Arthur] Univ Birmingham, Sch Med, Dept Immunol, Birmingham, W Midlands, England. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 592 EP 593 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702011 ER PT J AU Gorgun, G Calabrese, E Hideshima, T Ikeda, H Perrone, G Santo, L Cirstea, D Richardson, PG Anderson, KC AF Gorgun, Gullu Calabrese, Elisabetta Hideshima, Teru Ikeda, Hiroshi Perrone, Giulia Santo, Loredana Cirstea, Diana Richardson, Paul G. Anderson, Kenneth C. TI Immunomodulatory Effects of Lenalidomide and Bortezomib on Bone Marrow Stroma Cell and CD4 T Cell Interaction in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gorgun, Gullu; Calabrese, Elisabetta; Hideshima, Teru; Ikeda, Hiroshi; Perrone, Giulia; Santo, Loredana; Cirstea, Diana; Richardson, Paul G.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 597 EP 597 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702024 ER PT J AU Ma, S Zhan, FH Ma, CG Tessel, M Zhang, L Rajkumar, SV Singhal, S Barlogie, B Shaughnessy, J Rosen, ST Krett, N AF Ma, Shuo Zhan, Fenghuang Ma, Chunguang Tessel, Michael Zhang, Lijun Rajkumar, S. Vincent Singhal, Seema Barlogie, Bart Shaughnessy, John Rosen, Steven T. Krett, Nancy TI Glucocorticoid Receptor Expression Correlates with Clinical Outcome in Myeloma Patients Treated with Glucocorticoid-Containing Regimens SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ma, Shuo; Ma, Chunguang; Tessel, Michael; Krett, Nancy] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. [Zhan, Fenghuang] Univ Utah, Sch Med, Blood Marrow Transplant & Myeloma Program, Salt Lake City, UT USA. [Zhang, Lijun] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Singhal, Seema] Northwestern Univ, Sch Med, Chicago, IL USA. [Barlogie, Bart] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Shaughnessy, John] Univ AR Med Sci, Dept Med, Little Rock, AR USA. [Rosen, Steven T.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 600 EP 600 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702034 ER PT J AU Adamia, S Amin, SB Li, C Patterson, CJ AvetLoiseau, H Minvielle, S Moreau, P Anderson, KC Munshi, NC Treon, S AF Adamia, Sophia Amin, Samir B. Li, Cheng Patterson, Christopher J. AvetLoiseau, Herve Minvielle, Stephane Moreau, Philippe Anderson, Kenneth C. Munshi, Nikhil C. Treon, Steven TI High-Throughput Microrna Profiling in Patients with Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Amin, Samir B.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Patterson, Christopher J.] Dana Farber Canc Inst, Waldenstroms Macroglubulinemia Ctr, Boston, MA 02115 USA. [AvetLoiseau, Herve; Minvielle, Stephane; Moreau, Philippe] Hop Nantes, Dept Hematol, Nantes, France. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. RI Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 601 EP 601 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702038 ER PT J AU Ikeda, H Hideshima, T Lutz, RJ Vallet, S Pozzi, S Santo, L Calabrese, E Daelken, B Uherek, C Aigner, S Osterroth, F Fultiniti, M Okawa, Y Perrone, G Gorgon, G Yasui, H Cristia, D Raje, N Munshi, N Richardson, P Anderson, KC AF Ikeda, Hiroshi Hideshima, Tern Lutz, Robert J. Vallet, Sonia Pozzi, Samantha Santo, Loredana Calabrese, Elisabetta Daelken, Benjamin Uherek, Christoph Aigner, Silke Osterroth, Frank Fultiniti, Mariateresa Okawa, Yutaka Perrone, Giulia Gorgon, Gullu Yasui, Hiroshi Cristia, Diana Raje, Noopur Munshi, Nikhil Richardson, Paul Anderson, Kenneth C. TI The Monoclonal Antibody nBT062 Conjugated to Cytotoxic Maytansinoids Has Potent and Selective Cytotoxicity against CD138 Positive Multiple Myeloma Cells in Vitro and in Vivo SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Lutz, Robert J.] ImmunoGen Inc, Waltham, MA USA. [Pozzi, Samantha] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA USA. [Daelken, Benjamin; Uherek, Christoph; Aigner, Silke; Osterroth, Frank] Biotest AG, Dreieich, Germany. [Yasui, Hiroshi] Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 604 EP 605 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702050 ER PT J AU Gorgun, G Calabrese, E Mani, M Hideshima, T Ikeda, H Perrone, G Santo, L Cirstea, D Blotta, S Richardson, PG Ecsedy, J Anderson, KC AF Gorgun, Gullu Calabrese, Elisabetta Mani, Mala Hideshima, Teru Ikeda, Hiroshi Perrone, Giulia Santo, Loredana Cirstea, Diana Blotta, Simona Richardson, Paul G. Ecsedy, Jefrrey Anderson, Kenneth C. TI A Novel Aurora-a Kinase Inhibitor MLN8237 Induces Cytotoxicity and Cell Cycle Arrest in Experimental Multiple Myeloma Models SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hideshima, Teru] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Ecsedy, Jefrrey] Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 605 EP 606 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702053 ER PT J AU Dimopoulos, MA Richardson, P Schlag, R Khuageva, NK Shpilberg, O Kastritis, E Kropff, MH Petrucci, MT Delforge, M Alexeeva, JA Schots, R Masszi, T Mateos, MV Deraedt, W Liu, K Cakana, A van de Velde, H Miguel, JFS AF Dimopoulos, Meletios A. Richardson, Paul Schlag, Rudolf Khuageva, Nuriet K. Shpilberg, Ofer Kastritis, Efstathios Kropff, Martin H. Petrucci, Maria Teresa Delforge, Michel Alexeeva, Julia A. Schots, Rik Masszi, Tamas Mateos, Maria-Victoria Deraedt, William Liu, Kevin Cakana, Andrew van de Velde, Helgi Miguel, Jesus F. San TI Bortezomib-Melphalan-Prednisone (VMP) in Newly Diagnosed Multiple Myeloma Patients with Impaired Renal Function: Cohort Analysis of the Phase III VISTA Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Dimopoulos, Meletios A.; Kastritis, Efstathios] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, Rudolf] Praxis Hematol & Oncol, Wurzburg, Germany. [Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Dept Hematol, Moscow, Russia. [Shpilberg, Ofer] Comprehens Ctr Thalassemia & Hemoglobinopathies, Inst Hematol, Petah Tiqwa, Israel. [Kropff, Martin H.] Univ Munster, Munster, Germany. [Petrucci, Maria Teresa] Univ Roma La Sapienza, Rome, Italy. [Delforge, Michel; Schots, Rik] Belgian Hematol Soc, Myeloma Study Grp, Louvain, Belgium. [Alexeeva, Julia A.] St Petersburg City Hosp, Dept Haematol, St Petersburg, Russia. [Masszi, Tamas] St Laszlo Hosp Budapest, Budapest, Hungary. [Miguel, Jesus F. San] USAL CSIC, IBMCC, CIC, Hosp Univ Salamanca, Salamanca, Spain. [Deraedt, William; Cakana, Andrew; van de Velde, Helgi] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Liu, Kevin] Johnson & Johnson Pharmaceut, Res & Dev, Raritan, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 608 EP 609 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702061 ER PT J AU Jacobus, S Kumar, S Callander, NS Abonour, R Fonseca, R Siegel, D Greipp, P Rajkumar, SV AF Jacobus, Susanna Kumar, Shaji Callander, Natalie Scott Abonour, Rafat Fonseca, Rafael Siegel, David Greipp, Philip Rajkumar, S. Vincent TI Effect of Venous Thrombotic Events on Overall Survival in Multiple Myeloma: Analysis of Thrombotic Events Occurring in E4A03A Randomized Trial of Lenalidomide Plus High-Dose Dexamethasone (RD) Versus Lenalidomide Plus Low-Dose Dexamethasone (Rd) in Newly Diagnosed Multiple Myeloma, a Trial Coordinated by the Eastern Cooperative Oncology Group (ECOG). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Jacobus, Susanna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kumar, Shaji; Greipp, Philip; Rajkumar, S. Vincent] Mayo Clin, Rochester, MN USA. [Callander, Natalie Scott] Univ Wisconsin, Madison, WI USA. [Abonour, Rafat] Indiana Univ Canc, Indianapolis, IN USA. [Fonseca, Rafael] Mayo Clin, Scottsdale, AZ USA. [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. RI Kumar, Shaji/A-9853-2008 OI Kumar, Shaji/0000-0001-5392-9284 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 613 EP 614 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702074 ER PT J AU Richardson, P Schlag, R Khuageva, NK Dimopoulos, MA Shpilberg, O Kropff, MH Delforge, M Petrucci, MT Rossiev, VA Hou, J Robak, T Mateos, MV Anderson, KC Cakana, A Liu, K Deraedt, W van de Velde, H Miguel, JFS AF Richardson, Paul Schlag, Rudolf Khuageva, Nuriet K. Dimopoulos, Meletios A. Shpilberg, Ofer Kropff, Martin H. Delforge, Michel Petrucci, Maria Teresa Rossiev, Victor A. Hou, Jian Robak, Tadeusz Mateos, Maria-Victoria Anderson, Kenneth C. Cakana, Andrew Liu, Kevin Deraedt, William van de Velde, Heigi Miguel, Jesus F. San TI Erythropoiesis-Stimulating Agents Do Not Adversely Affect Long-Term Outcomes Nor Increase the Risk of Thromboembolic Events in Multiple Myeloma Patients Treated in the Phase III VISTA Trial SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, Rudolf] Praxis Hematol & Oncol, Wurzburg, Germany. [Khuageva, Nuriet K.] SP Botkin Moscow City Clin Hosp, Dept Hematol, Moscow, Russia. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, Martin H.] Univ Munster, Munster, Germany. [Delforge, Michel] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Petrucci, Maria Teresa] Univ Roma La Sapienza, Rome, Italy. [Rossiev, Victor A.] Samara Reg Clin Hosp, Dept Haematol, Samara, Russia. [Hou, Jian] Changzheng Hosp, Shanghai, Peoples R China. [Robak, Tadeusz] Med Univ Lodz, Dept Hematol, Lodz, Poland. [Miguel, Jesus F. San] USAL CSIC, IBMCC, CIC, Hosp Univ Salamanca, Salamanca, Spain. [Cakana, Andrew; Deraedt, William; van de Velde, Heigi] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Liu, Kevin] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 614 EP 614 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702075 ER PT J AU Richardson, P Jagannath, S Jakubowiak, A Lonial, S Raje, N Alsina, M Ghobrial, I Mazumder, A Munshi, NC Vesole, DH Colson, K McKenney, ML Lunde, L Kennedy, S Kosakowski, K Mitsiades, C Hideshima, T Knight, RD Esseltine, DL Anderson, KC AF Richardson, Paul Jagannath, Sundar Jakubowiak, Andrzej Lonial, Sagar Raje, Noopur Alsina, Melissa Ghobrial, Irene Mazumder, Amitabha Munshi, Nikhil C. Vesole, David H. Colson, Kathleen McKenney, Mary L. Lunde, Laura Kennedy, Sarah Kosakowski, Kara Mitsiades, Constantine Hideshima, Teru Knight, Robert D. Esseltine, Dixie-Lee Anderson, Kenneth C. TI Lenalidomide, Bortezomib, and Dexamethasone in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Encouraging Response Rates and Tolerability with Correlation of Outcome and Adverse Cytogenetics in a Phase II Study. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul; Ghobrial, Irene; Munshi, Nikhil C.; Colson, Kathleen; McKenney, Mary L.; Lunde, Laura; Mitsiades, Constantine; Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Jagannath, Sundar; Mazumder, Amitabha; Vesole, David H.; Kennedy, Sarah] St Vincents Comprehens Canc Ctr, New York, NY USA. [Jakubowiak, Andrzej] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Lonial, Sagar] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Alsina, Melissa; Kosakowski, Kara] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Knight, Robert D.] Celgene Inc, Summit, NJ USA. Takeda Oncol Co, Millennium Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 614 EP 615 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702076 ER PT J AU Yoda, A Sattler, M Weinstock, DM AF Yoda, Alcinori Sattler, Martin Weinstock, David M. TI Functional Oncogene Identification in Patient Leukemia Samples SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Yoda, Alcinori; Sattler, Martin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Weinstock, David M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 633 EP 633 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702124 ER PT J AU Peyvandi, F Spreafico, M Foco, L Bernardinelli, L Duga, S Asselta, R Ardissino, D Kathiresan, S Merlini, P Mannucci, PM AF Peyvandi, Flora Spreafico, Marta Foco, Luisa Bernardinelli, Luisa Duga, Stefano Asselta, Rosanna Ardissino, Diego Kathiresan, Sekar Merlini, Pierangelica Mannucci, Pier M. TI Factor V Leiden Is Associated with Premature Myocardial Infarction SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Peyvandi, Flora; Spreafico, Marta; Mannucci, Pier M.] Univ Milan, Maggiore Hosp, IRCCS, Dept Med & Med Specialties, Milan, Italy. [Foco, Luisa] Univ Pavia, Diparlimento Sci Sanitarie Applicate & Psicocompo, I-27100 Pavia, Italy. [Bernardinelli, Luisa] Univ Forvie Site, Inst Publ Hlth, Biostat Unit, MRC, Cambridge, England. [Duga, Stefano; Asselta, Rosanna] Univ Milan, Dept Biol & Genet Med Sci, Milan, Italy. [Ardissino, Diego] Univ Parma, Maggiore Hosp, Div Cardiol, I-43100 Parma, Italy. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Merlini, Pierangelica] Azienda Osped Niguarda Ca Granda, Div Cardiol, Milan, Italy. RI Mannucci, Pier/C-3102-2014 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 640 EP 640 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702150 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 Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bergmeier, Wolfgang; Roden, R. Claire; Bray, Paul F.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Oh-Hora, Masatsugu] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [McCarl, Christie-Ann; Feske, Stefan] NYU, Sch Med, Dept Pathol, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 647 EP 647 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702171 ER PT J AU Flaumenhaft, R Dilks, JR Rozenvayn, N Woronowicz, K AF Flaumenhaft, Robert Dilks, James R. Rozenvayn, Nataliya Woronowicz, Kamil TI The Platelet Actin Cytoskeleton Associates Directly with Syntaxin-4 and Participates in alpha-Granule Secretion SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Flaumenhaft, Robert; Dilks, James R.; Rozenvayn, Nataliya; Woronowicz, Kamil] Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 647 EP 647 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702172 ER PT J AU Raffel, GD Chu, GC Cullen, DE Bronson, RT Bernard, OA Gilliland, DG AF Raffel, Glen D. Chu, Gerry C. Cullen, Dana E. Bronson, Roderick T. Bernard, Olivier A. Gilliland, D. Gary TI Vascular Branching Morphogenesis of the Placenta Requires Expression of Ott1(Rbm15) in the Trophoblast Compartment. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Raffel, Glen D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Cullen, Dana E.] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Chu, Gerry C.; Cullen, Dana E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bronson, Roderick T.] Harvard Univ, Dept Rodent Pathol, Sch Med, Boston, MA 02115 USA. [Bernard, Olivier A.] Hop Necker Enfants Malad, Hematol Lab, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 663 EP 663 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702228 ER PT J AU Stam, RW Den Boer, ML Schneider, P de Boer, J Hagelstein, J Sallan, SE Brady, HJM Armstrong, S Pieters, R AF Stam, Ronald W. Den Boer, Monique L. Schneider, Pauline de Boer, Jasper Hagelstein, Jill Sallan, Stephen E. Brady, Hugh J. M. Armstrong, Scott Pieters, Rob TI Rearranged Infant Acute Lymphoblastic Leukemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Stam, Ronald W.; Den Boer, Monique L.; Schneider, Pauline; Hagelstein, Jill; Pieters, Rob] Sophia Childrens Univ Hosp, Erasmus MC, Rotterdam, Netherlands. [de Boer, Jasper; Brady, Hugh J. M.] UCL Inst Child Hlth, Mol Haematol & Canc Biol Unit, London, England. [de Boer, Jasper; Brady, Hugh J. M.] Great Ormond St Hosp Sick Children, London, England. [Sallan, Stephen E.; Armstrong, Scott] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 668 EP 668 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702246 ER PT J AU Rowe, JM Yao, XP Cassileth, PA Appelbaum, FR Wiernik, PH Schiffer, C Litzow, MR Luger, S Bennett, JM Lazarus, HM Tallman, MS AF Rowe, Jacob M. Yao, Xiaopan Cassileth, Peter A. Appelbaum, Frederick R. Wiernik, Peter H. Schiffer, Charles Litzow, Mark R. Luger, Selina Bennett, John M. Lazarus, Hillard M. Tallman, Martin S. TI The Pitfalls of Early Publication of Data in Acute Myeloid Leukemia: A Report from the Eastern Cooperative Oncology Group (ECOG). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rowe, Jacob M.] Technion Israel Inst Technol, Haifa, Israel. [Yao, Xiaopan] Dana Farber Canc Inst, Boston, MA 02115 USA. [Cassileth, Peter A.] Univ Miami, Sylvester Canc Ctr, Miami, FL USA. [Appelbaum, Frederick R.] Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Seattle, WA 98195 USA. [Wiernik, Peter H.] New York Med Coll, Our Lady Mercy Canc Ctr, Bronx, NY USA. [Schiffer, Charles] Wayne State Univ, Detroit, MI USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Luger, Selina] Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Bennett, John M.] Univ Rochester, Rochester, NY USA. [Lazarus, Hillard M.] Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 44106 USA. [Tallman, Martin S.] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 681 EP 681 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702285 ER PT J AU Ballen, KK Cutler, C Yeap, BY McAfee, SL Dey, BR Attar, EC Haspel, RL Liney, D Koreth, J Ho, V Alyea, EP Soiffer, RJ Spitzer, TR Antin, JH AF Ballen, Karen K. Cutler, Corey Yeap, Beow Y. McAfee, Steven L. Dey, Bimalangshu R. Attar, Eyal C. Haspel, Richard L. Liney, Deborah Koreth, John Ho, Vincent Alyea, Edwin P., III Soiffer, Robert J. Spitzer, Thomas R. Antin, Joseph H. TI High Rate of Second Malignancies after Reduced Intensity Double Cord Blood Transplants in Adults. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ballen, Karen K.; Yeap, Beow Y.; McAfee, Steven L.; Dey, Bimalangshu R.; Attar, Eyal C.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cutler, Corey; Liney, Deborah; Koreth, John; Ho, Vincent; Alyea, Edwin P., III; Soiffer, Robert J.; Antin, Joseph H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Haspel, Richard L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 683 EP 683 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702291 ER PT J AU Zhou, J Lu, CF Yu, HJ Hou, JX Liu, SC Ma, M Gilbert, G Shi, JL AF Zhou, Jin Lu, Chengfang Yu, Hongjuan Hou, Jinxiao Liu, Shuchuan Ma, Ming Gilbert, Gary Shi, Jialan TI Elevated Procoagulant Activity Due to Phosphatidylserine Exposure on Red Blood Cells during Storage SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhou, Jin; Lu, Chengfang; Yu, Hongjuan; Hou, Jinxiao; Liu, Shuchuan; Ma, Ming] Harbin Med Coll, Affiliated Hosp 1, Dept Med, Harbin, Peoples R China. [Gilbert, Gary; Shi, Jialan] Brigham & Womens Hosp, Dept Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Gilbert, Gary; Shi, Jialan] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 696 EP 696 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702329 ER PT J AU Ioakimidis, L Patterson, C Soumerai, J Manning, R Sheehy, P Treon, S AF Ioakimidis, Leukothea Patterson, Christopher Soumerai, Jacob Manning, Robert Sheehy, Patricia Treon, Steven TI Comparative Outcomes Following CP-R, CVP-R and CHOP-R in Patients with Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ioakimidis, Leukothea; Manning, Robert; Sheehy, Patricia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 702 EP 702 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702344 ER PT J AU Wierda, WG Kipps, TJ Keating, MJ Brown, JR Gribben, JG Rassenti, LZ Greaves, AW Neuberg, D O'Brien, SM AF Wierda, William G. Kipps, Thomas J. Keating, Michael J. Brown, Jennifer R. Gribben, John G. Rassenti, Lauta Z. Greaves, Andrew W. Neuberg, Donna O'Brien, Susan M. TI Plasma Alemtuzumab Levels at End of Treatment Correlate with Response and Response Duration in Patients with CLL Receiving Treatment for Residual Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wierda, William G.; Keating, Michael J.; O'Brien, Susan M.] UTMD Anderson Canc Ctr, Houston, TX USA. [Kipps, Thomas J.; Rassenti, Lauta Z.; Greaves, Andrew W.] Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. [Brown, Jennifer R.; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gribben, John G.] Ctr Med Oncol, Inst Canc, London, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 734 EP 734 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702442 ER PT J AU Wilson, WH O'Connor, O Czuczman, MS LaCasce, A Gerecitano, J Leonard, JP Tulpule, A Xiong, H Chiu, YL Busman, T Knight, RA Enschede, S Krivoshik, A Humerickhouse, R AF Wilson, Wyndham H. O'Connor, O. Czuczman, Myron S. LaCasce, Ann Gerecitano, J. Leonard, John P. Tulpule, Anil Xiong, Hao Chiu, Yi-Lin Busman, Todd Knight, Raymond A. Enschede, Sari Krivoshik, Andrew Humerickhouse, Rod TI Phase 1 Study of ABT-263, a Bcl-2 Family Inhibitor, in Relapsed or Refractory Lymphoid Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wilson, Wyndham H.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [O'Connor, O.] Columbia Univ, Med Ctr, New York, NY USA. [Czuczman, Myron S.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [LaCasce, Ann] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gerecitano, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Leonard, John P.] Weill Cornell Med Coll, Div Hem Onc, New York, NY USA. [Tulpule, Anil] USC, Norris Canc Ctr, Sch Med, Los Angeles, CA USA. [Xiong, Hao; Chiu, Yi-Lin; Busman, Todd; Knight, Raymond A.; Enschede, Sari; Krivoshik, Andrew; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 734 EP 734 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702441 ER PT J AU Duncan, C Vrooman, L Bechard, L Barry, E Lehmann, LE AF Duncan, Christine Vrooman, Lynda Bechard, Lori Barry, Elly Lehmann, Leslie E. TI The Prevalence of 25-Hydroxyvitamin D Deficiency in Post-HSCT Pediatric Patients SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Duncan, Christine; Vrooman, Lynda; Barry, Elly; Lehmann, Leslie E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bechard, Lori] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 745 EP 745 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702472 ER PT J AU Sorror, ML Storer, B Sandmaier, BM Maris, M Chauncey, T Maziarz, RT Pulsipher, M Shizuru, J Niederwieser, D Agura, E Wade, JC Langston, AA Storb, RF Maloney, DG AF Sorror, Mohamed L. Storer, Barry Sandmaier, Brenda M. Maris, Michael Chauncey, Thomas Maziarz, Richard T. Pulsipher, Michael Shizuru, Judith Niederwieser, Dietger Agura, Edward Wade, James C. Langston, Amelia A. Storb, Rainer F. Maloney, David G. TI Sustained Graft-Versus-Lymphoma Effect among Patients (pts) with Mantle Cell Lymphoma (MCL) Given Nonmyeloablative, Allogeneic Hematopoictic Cell Transplantation (HCT). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chauncey, Thomas] Univ Washington, Fred Hutchinson Canc Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Pulsipher, Michael] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Shizuru, Judith] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Niederwieser, Dietger] Univ Leipzig, Leipzig, Germany. [Agura, Edward] Baylor Univ, Med Ctr, Dallas, TX USA. [Wade, James C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Langston, Amelia A.] Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 747 EP 748 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702480 ER PT J AU Sorror, ML Storer, B Sandmaier, BM Maloney, DG Franke, G Shizuru, J Chauncey, T Agura, E Maziarz, RT Sahebi, F Langston, AA Wade, JC Maris, M Bruno, B Yeager, AM Pulsipher, M Petersen, F Bethge, WA McSweeney, PA Niederwieser, D Blume, KG Storb, RF AF Sorror, Mohamed L. Storer, Barry Sandmaier, Brenda M. Maloney, David G. Franke, Georg Shizuru, Judith Chauncey, Thomas Agura, Edward Maziarz, Richard T. Sahebi, Firoozeh Langston, Amelia A. Wade, James C. Maris, Michael Bruno, Benedetto Yeager, Andrew M. Pulsipher, Michael Petersen, Finn Bethge, Wolfgang A. McSweeney, Peter A. Niederwieser, Dietger Blume, Karl G. Storb, Rainer F. TI Allogeneic Hematopoietic Cell Transplantation (HCT) after Nonmyeloablative Conditioning for Patients (pts) Aged >= 60 Years SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chauncey, Thomas] Univ Washington, Fred Hutchinson Canc Res Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Agura, Edward] Baylor Univ, Med Ctr, Dallas, TX USA. [Franke, Georg] Univ Leipzig, Laipzig, Germany. [Shizuru, Judith; Blume, Karl G.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Maziarz, Richard T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Sahebi, Firoozeh] City Hope Natl Med Ctr, Duarte, CA 91010 USA. [Langston, Amelia A.] Emory Univ, Sch Med, Atlanta, GA USA. [Wade, James C.] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Maris, Michael; McSweeney, Peter A.] Rocky Mt Canc Ctr, Denver, CO USA. [Bruno, Benedetto] Univ Turin, Turin, Italy. [Yeager, Andrew M.] Univ Arizona, Tucson, AZ USA. [Pulsipher, Michael] Univ Utah, Med Ctr, Salt Lake City, UT USA. [Petersen, Finn] LDS Hosp, Salt Lake City, UT USA. [Bethge, Wolfgang A.] Univ Tubingen, Med Ctr, Tubingen, Germany. [Niederwieser, Dietger] Univ Leipzig, Leipzig, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 753 EP 754 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702495 ER PT J AU Keating, A Kukreja, M da Silva, GT Gupta, V Cutler, C Tallman, MS Sierra, J DiPersio, JF Horowitz, MM Weisdorf, DJ AF Keating, Armand Kukreja, Manisha da Silva, Gisela Tunes Gupta, Vikas Cutler, Corey Tallman, Martin S. Sierra, Jorge DiPersio, John F. Horowitz, Mary M. Weisdorf, Daniel J. TI Similar 5-Year Survival after Peripheral Blood Autotransplants (AutoPB) Versus HILA Matched Sibling Myeloablative Transplants (AlloBMT) for Acute Myeloid Leukemia (AML) in First Complete Remission (CRI) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Keating, Armand; Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Kukreja, Manisha; Horowitz, Mary M.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tallman, Martin S.] Northwestern Univ, Feinberg Sch Med, Chicago, IL USA. [Sierra, Jorge] Hosp Santa Creu & Sant Pau, Barcelona, Spain. [DiPersio, John F.] Washington Univ, Sch Med, St Louis, MO USA. [Weisdorf, Daniel J.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 756 EP 756 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702501 ER PT J AU Kao, G Stevenson, K Kim, E Spanjaard, E Kim, HT Ritz, J AF Kao, Grace Stevenson, Kristen Kim, Elliot Spanjaard, Elena Kim, Haesook T. Ritz, Jerome TI Autologous Peripheral Blood Stem Cell Products from Patients with Hematologic Malignancies Have Increased Frequency of Regulatory T Cells (CD4+FoxP3+Treg) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kao, Grace; Stevenson, Kristen; Kim, Elliot; Spanjaard, Elena; Kim, Haesook T.; Ritz, Jerome] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 806 EP 806 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702643 ER PT J AU Kirkorian, AY Collin, MP Mielcarek, M Zhang, WD Neuberg, D Wu, CJ Merad, M AF Kirkorian, A. Yasmine Collin, Matthew P. Mielcarek, Marco Zhang, Wandi Neuberg, Donna Wu, Catherine J. Merad, Miriam TI A Novel SNP-Based Method for Assessing Langerhans Cell Chimerism Following Hematopoietic Stem Cell Transplantation in Humans. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kirkorian, A. Yasmine; Collin, Matthew P.; Merad, Miriam] Mt Sinai Med Ctr, Dept Gene & Cell Med, New York, NY 10029 USA. [Mielcarek, Marco] Fred Hutchinson Canc Rsch Ctr, Seattle, WA USA. [Zhang, Wandi] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 811 EP 811 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702661 ER PT J AU Duran-Struuck, R Horner, BM Lutton, BV Teague, AGS Ferguson, KK Summers, JC Spitzer, T Jay, F Houser, S Sachs, DH Huang, CA AF Duran-Struuck, Raimon Horner, Banjamin M. Lutton, Bram V. Teague, Alex G. S. Ferguson, Kelly K. Summers, Jonathan C. Spitzer, Thomas Jay, Fishman Houser, Stuart Sachs, David H. Huang, Christene A. TI Conversion to Full Donor Chimerism without Gvhd Using High-Dose DLI in Minimally Conditioned Miniature Swine Recipients of Haploidentical HCT. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Duran-Struuck, Raimon; Horner, Banjamin M.; Lutton, Bram V.; Teague, Alex G. S.; Ferguson, Kelly K.; Summers, Jonathan C.; Spitzer, Thomas; Jay, Fishman; Houser, Stuart; Sachs, David H.; Huang, Christene A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 814 EP 814 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702669 ER PT J AU Li, LQ Wang, H Bronson, R Boussiotis, V AF Li, Lequn Wang, Hui Bronson, Roderick Boussiotis, Vassiliki TI Roscovitine Prevents Alloreactive T Cell Expansion and TNF-a-Mediated Proinflammatory Gene Expression and Protects against GvHD. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Li, Lequn; Boussiotis, Vassiliki] Beth Israel Deaconess Med Ctr, Harvard Inst Med, Boston, MA 02215 USA. [Wang, Hui] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bronson, Roderick] Harvard Univ, Sch Med, Dept Rodent Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 815 EP 816 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702674 ER PT J AU Flutter, BR Fallah-Arani, F Bennett, C Sivakumaran, J Freeman, GJ Sykes, M Chakraverty, R AF Flutter, Barry R. Fallah-Arani, Farnaz Bennett, Clare Sivakumaran, Janani Freeman, Gordon J. Sykes, Megan Chakraverty, Ronjon TI Peripheral Alloantigen Drives Early Dysfunction and Eventual Exhaustion of CTL Following Delayed Donor Leukocyte Infusions SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Flutter, Barry R.; Fallah-Arani, Farnaz; Bennett, Clare; Sivakumaran, Janani; Chakraverty, Ronjon] UCL, Transplantat Immunol Grp, London, England. [Freeman, Gordon J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplant Biol Res Ctr, Boston, MA USA. RI bennett, clare/J-5249-2013 OI bennett, clare/0000-0001-9146-2347 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 817 EP 817 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702679 ER PT J AU Van Bennekom, CM Raje, N Anderson, KC Anderson, TE Kaufman, DW AF Van Bennekom, Carla M. Raje, Noopur Anderson, Kenneth C. Anderson, Theresa E. Kaufman, David W. TI Treatment Patterns among Patients with Recently-Diagnosed Multiple Myeloma in a National Registry SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Van Bennekom, Carla M.; Anderson, Theresa E.; Kaufman, David W.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 827 EP 827 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702707 ER PT J AU Friese, CR Abel, GA Magazu, LS Neville, BA Hevelone, ND Richardson, LC Earle, CC AF Friese, Christopher R. Abel, Gregory A. Magazu, Lysa S. Neville, Bridget A. Hevelone, Nathanael D. Richardson, Lisa C. Earle, Craig C. TI Diagnostic Patterns of Care and Outcomes for Patients with Chronic.,and End-Results Lymphocytic Leukemia in the Surveillance, Epidemiology (SEER)-Medicare Database SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Friese, Christopher R.] Univ Michigan, Sch Nursing, Ann Arbor, MI 48109 USA. [Abel, Gregory A.; Magazu, Lysa S.; Neville, Bridget A.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Boston, MA 02115 USA. [Hevelone, Nathanael D.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Richardson, Lisa C.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Decatur, GA USA. [Earle, Craig C.] Sunnybrook Hlth Sci Ctr, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 836 EP 836 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702732 ER PT J AU Mizuno, SI Ozawa, H Iino, T Arinobu, Y Yong, C Shigematsu, H Akashi, K AF Mizuno, Shini-Ichi Ozawa, Hidetoshi Iino, Tadafumi Arinobu, Yojiro Yong, Chong Shigematsu, Hirokazu Akashi, Koichi TI Notch1 Expression Is Regulated at Post-Transcriptional Level by 3'UTR Region in Hematopoietic Stem Cell Development. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mizuno, Shini-Ichi; Ozawa, Hidetoshi; Iino, Tadafumi; Arinobu, Yojiro; Yong, Chong; Shigematsu, Hirokazu; Akashi, Koichi] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 854 EP 854 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702789 ER PT J AU Juszczynski, P Rodig, SJ Takeyama, K Ouyang, J Faber, J Armstrong, S Kutok, JL Shipp, MA AF Juszczynski, Przemyslaw Rodig, Scott J. Takeyama, Kunihiko Ouyang, Jing Faber, Jorg Armstrong, Scott Kutok, Jeffery L. Shipp, Margaret A. TI Selective Expression of the Immunoregulatory Lectin, Galectin-1, in Precursor B Cell Acute Lymphoblastic Leukemias (ALLs) with MLL Rearrangements. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Juszczynski, Przemyslaw; Takeyama, Kunihiko; Ouyang, Jing; Shipp, Margaret A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodig, Scott J.; Kutok, Jeffery L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Faber, Jorg; Armstrong, Scott] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 882 EP 882 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702871 ER PT J AU Peled, JU Yu, JJ Ding, BB Shaknovich, R Sicinski, P Scharff, MD Ye, BH AF Peled, Jonathan U. Yu, J. Jessica Ding, Beibei Belinda Shaknovich, Rita Sicinski, Piotr Scharff, Matthew D. Ye, B. Hilda TI Cyclin D3 Is Required for the Germinal Center Reaction. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Peled, Jonathan U.; Yu, J. Jessica; Ding, Beibei Belinda; Scharff, Matthew D.; Ye, B. Hilda] Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. [Shaknovich, Rita] Cornell Med Ctr, Dept Med, New York, NY USA. [Shaknovich, Rita] Cornell Med Ctr, Dept Pathol, New York, NY USA. [Sicinski, Piotr] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 895 EP 895 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703022 ER PT J AU Canellos, GP AF Canellos, George P. TI Chemotherapy Alone for Localized Non-Bulky Hodgkin Lymphoma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Canellos, George P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 898 EP 898 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703032 ER PT J AU Melhem, MR Roccaro, AM Azab, A Ngo, HT Sacco, A Jia, XY Azab, F Runnels, J Burwick, N Quang, P Husu, EN Leleu, X Anderson, KC Ghobrial, IM AF Melhem, Molly R. Roccaro, Aldo M. Azab, Abdelkareem Ngo, Hai T. Sacco, Antonio Jia, Xiaoying Azab, Feda Runnels, Judith Burwick, Nicolas Quang, Phong Husu, Emanuel N. Leleu, Xavier Anderson, Kenneth C. Ghobrial, Irene M. TI PKC412, a Small Molecule Tyrosine Kinase Inhibitor, Regulates Survival and Proliferation Pathways in Waldenstrom Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Melhem, Molly R.; Roccaro, Aldo M.; Azab, Abdelkareem; Ngo, Hai T.; Sacco, Antonio; Jia, Xiaoying; Azab, Feda; Runnels, Judith; Burwick, Nicolas; Quang, Phong; Husu, Emanuel N.; Leleu, Xavier; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 905 EP 905 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703055 ER PT J AU Jia, XY Roccaro, AM Azab, AK Ngo, HT Sacco, A Melhem, MR Azab, F Runnels, J Burwick, N Quang, P Husu, EN Leleu, X Anderson, KC Bradner, J Ghobrial, IM AF Jia, Xiaoying Roccaro, Aldo M. Azab, Abdel Kareem Ngo, Hai T. Sacco, Antonio Melhem, Molly R. Azab, Feda Runnels, Judith Burwick, Nicolas Quang, Phong Husu, Emanuel N. Leleu, Xavier Anderson, Kenneth C. Bradner, James Ghobrial, Irene M. TI Regulation of Histone Deacetylase in Waldenstrom Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Jia, Xiaoying; Roccaro, Aldo M.; Azab, Abdel Kareem; Ngo, Hai T.; Sacco, Antonio; Melhem, Molly R.; Azab, Feda; Runnels, Judith; Burwick, Nicolas; Quang, Phong; Husu, Emanuel N.; Leleu, Xavier; Anderson, Kenneth C.; Bradner, James; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 906 EP 906 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703058 ER PT J AU Ngo, HT Farag, M Jia, XY Burwick, N Methem, MR Leleu, X Runnels, J Azab, AK Roccaro, AM Azab, F Sacco, A Quang, P Tai, YT Anderson, KC Ghobrial, IM AF Ngo, Hai T. Farag, Mena Jia, Xiaoying Burwick, Nicolas Methem, Molly R. Leleu, Xavier Runnels, Judith Azab, Abdel Kareern Roccaro, Aldo M. Azab, Feda Sacco, Antonio Quang, Phong Tai, Yu-Tzu Anderson, Kenneth C. Ghobrial, Irene M. TI The Tyrosine Kinase Src Regulates Adhesion and Survival in Waldenstrom Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ngo, Hai T.; Farag, Mena; Jia, Xiaoying; Burwick, Nicolas; Methem, Molly R.; Runnels, Judith; Azab, Abdel Kareern; Roccaro, Aldo M.; Azab, Feda; Sacco, Antonio; Quang, Phong; Tai, Yu-Tzu; Anderson, Kenneth C.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Leleu, Xavier] Ctr Hosp Reg & Univ Lille, Hop Huriez, Serv Malad Sang, F-59037 Lille, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 906 EP 906 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703056 ER PT J AU Bernal, F Wade, M Silverstein, AM Verdine, GL Wahl, GM Walensky, LD AF Bernal, Federico Wade, Mark Silverstein, Amy M. Verdine, Gregory L. Wahl, Geoffrey M. Walensky, Loren D. TI A Stapled p53 Helix Targets HDMX to Overcome Nutlin-3 Resistance and Reactivate the p53 Tumor Suppressor Pathway in Cancer SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bernal, Federico; Silverstein, Amy M.; Walensky, Loren D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Childrens Hosp Boston,Dept Pediat Oncol, Boston, MA USA. [Wade, Mark; Wahl, Geoffrey M.] Salk Inst Biol Studies, Gene Express Lab, La Jolla, CA 92037 USA. [Verdine, Gregory L.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RI Wade, Mark /B-6719-2009 OI Wade, Mark /0000-0002-2688-5965 NR 0 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 915 EP 915 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703085 ER PT J AU Jakubikova, J Sedlak, J Klippel, S Leiba, M Tai, YT Hideshima, T Podar, K Chauhan, D Raje, N Richardson, PG Anderson, KC Mitsiades, CS AF Jakubikova, Jana Sedlak, Jan Klippel, Steffen Leiba, Merav Tai, Yu-Tzu Hideshima, Teru Podar, Klaus Chauhan, Dharminder Raje, Noopur Richardson, Paul G. Anderson, Kenneth C. Mitsiades, Constantine S. TI Sulforaphane and PEITC Augment Activity of Conventional and Novel Anti-Myeloma Drugs SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Jakubikova, Jana; Klippel, Steffen; Leiba, Merav; Tai, Yu-Tzu; Hideshima, Teru; Podar, Klaus; Chauhan, Dharminder; Raje, Noopur; Richardson, Paul G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Sedlak, Jan] Slovak Acad Sci, Canc Res Inst, Dept Tumor Immunol, Bratislava, Slovakia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 916 EP 916 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703088 ER PT J AU Ooi, MG Hayden, PJ McMillin, DW Negri, JM Delmore, J Raje, NS Munshi, NC Chauhan, D Hideshima, T Richardson, PG Mitsiades, CS Anderson, KC Mitsiades, N AF Ooi, Melissa G. Hayden, Patrick J. McMillin, Douglas W. Negri, Joseph M. Delmore, Jake Raje, Noopur S. Munshi, Nikhil C. Chauhan, Dharminder Hideshima, Teru Richardson, Paul G. Mitsiades, Constantine S. Anderson, Kenneth C. Mitsiades, Nicholas TI Interactions of the Mdm2/p53 and Proteasome Pathways: Implications for Combination Strategies to Enhance the Anti-Myeloma Activity of Bortezomib SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ooi, Melissa G.; Hayden, Patrick J.; McMillin, Douglas W.; Negri, Joseph M.; Delmore, Jake; Munshi, Nikhil C.; Chauhan, Dharminder; Hideshima, Teru; Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.; Mitsiades, Nicholas] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Raje, Noopur S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 917 EP 917 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703091 ER PT J AU Ooi, MG McMillin, DW Negri, JM Delmore, J Munshi, NC Chauhan, D Hideshima, T Richardson, PG Mitsiades, CS Anderson, KC Mitsiades, N AF Ooi, Melissa G. McMillin, Douglas W. Negri, Joseph M. Delmore, Jake Munshi, Nikhil C. Chauhan, Dharminder Hideshima, Teru Richardson, Paul G. Mitsiades, Constantine S. Anderson, Kenneth C. Mitsiades, Nicholas TI The Antidiabetic Biguanide Metformin Induces Growth Arrest in Multiple Myeloma Cells in Vitro, overcoming the Effect of Stromal Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ooi, Melissa G.; McMillin, Douglas W.; Negri, Joseph M.; Delmore, Jake; Munshi, Nikhil C.; Chauhan, Dharminder; Hideshima, Teru; Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.; Mitsiades, Nicholas] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Munshi, Nikhil C.] VA Bosto Healthcare Syst, Boston, MA USA. [Mitsiades, Nicholas] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 917 EP 918 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703092 ER PT J AU McMillin, DW Rickes, R Negri, J Delmore, J Ooi, MG Farwell, M Crowe, D Chen, M Avery, W Kansra, V Anderson, KC Lee, MS Mitsiades, CS AF McMillin, Douglas W. Rickes, Richard Negri, Joseph Delmore, Jake Ooi, Melissa G. Farwell, Melissa Crowe, David Chen, Mei Avery, William Kansra, Vikram Anderson, Kenneth C. Lee, Margaret S. Mitsiades, Constantine S. TI Synergistic Activity of Adenosine A2A and Beta-2 Adrenergic Receptor Agonists in Myeloma Cells in the Context of Tumor-Stromal Interactions. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [McMillin, Douglas W.; Negri, Joseph; Delmore, Jake; Ooi, Melissa G.; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Rickes, Richard; Farwell, Melissa; Crowe, David; Chen, Mei; Avery, William; Kansra, Vikram; Lee, Margaret S.] CombinatoRx Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 920 EP 921 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703103 ER PT J AU Armand, P Deeg, HJ Kim, HT Lee, H Armistead, P De Lima, M Gupta, V Soiffer, RJ AF Armand, Philippe Deeg, H. Joachim Kim, Haesook T. Lee, Hun Armistead, Paul De Lima, Marcos Gupta, Vikas Soiffer, Robert J. TI Transplantation-Specific Cytogenetics Grouping Scheme for Patients with Myelodysplastic Syndromes: A Multicenter Validation Study. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Armand, Philippe; Kim, Haesook T.; Soiffer, Robert J.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Deeg, H. Joachim] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Lee, Hun] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. [Armistead, Paul] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [De Lima, Marcos] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 924 EP 924 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703113 ER PT J AU Prabhala, R Pelluru, D Fulciniti, M Nanjappa, P Prabhala, HK Prabhala, NS Mitsiades, C Tai, YT Ghobrial, I Richardson, P Lefkimmiatis, K Daley, JF Efebera, YA Anderson, KC Munshi, NC AF Prabhala, Rao Pelluru, Dheeraj Fulciniti, Mariateresa Nanjappa, Puru Prabhala, Harsha K. Prabhala, Nithya S. Mitsiades, Constantine Tai, Yu-Tzu Ghobrial, Irene Richardson, Paul Lefkimmiatis, Konstantinos Daley, John F. Efebera, Yvonne A. Anderson, Kenneth C. Munshi, Nikhil C. TI TH17 Pathway Promotes Tumor Cell Growth and Suppresses Immune Function in Myeloma: Potential for Therapeutic Application. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Prabhala, Rao; Pelluru, Dheeraj; Prabhala, Nithya S.; Lefkimmiatis, Konstantinos; Efebera, Yvonne A.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. [Fulciniti, Mariateresa; Nanjappa, Puru; Mitsiades, Constantine; Tai, Yu-Tzu; Ghobrial, Irene; Richardson, Paul; Daley, John F.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Prabhala, Harsha K.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. [Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Efebera, Yvonne/E-3012-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 945 EP 946 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703177 ER PT J AU Pozzi, S Yan, H Vallet, S Vaghela, N Fulciniti, M Cirstea, D Santo, L Mukherjee, S Hideshima, T Schirtzinger, L Kuhstoss, S Munshi, NC Anderson, KC Scadden, D Raje, N AF Pozzi, Samantha Yan, Hua Vallet, Sonia Vaghela, Nileshwari Fulciniti, Mariateresa Cirstea, Diana Santo, Loredana Mukherjee, Siddhartha Hideshima, Teru Schirtzinger, Linda Kuhstoss, Stuart Munshi, Nikhil C. Anderson, Kenneth C. Scadden, David Raje, Noopur TI Promoting Osteoblastogenesis Using a Novel Dkk-1 Neutralizing Antibody in the Treatment of Multiple Myeloma Related Bone Disease. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Pozzi, Samantha; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA USA. [Schirtzinger, Linda; Kuhstoss, Stuart] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 946 EP 946 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703179 ER PT J AU Pelluru, D Wang, JY Prabhala, R Fulciniti, M Shammas, MA Amin, SB Anderson, KC Munshi, NC AF Pelluru, Dheeraj Wang, Jingyi Prabhala, Rao Fulciniti, Mariateresa Shammas, Masood A. Amin, Samirkumar B. Anderson, Kenneth C. Munshi, Nikhil C. TI Oncoprotein 18 (Op18) : A Differentially Expressed Gene Is a Novel Therapeutic Target in Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Pelluru, Dheeraj; Prabhala, Rao; Shammas, Masood A.] R&D, VA Boston Hlth Car Syst, DFCI, HMS, W Roxbury, MA USA. [Wang, Jingyi] Univ Arkansas, Little Rock, AR 72204 USA. [Fulciniti, Mariateresa; Amin, Samirkumar B.; Anderson, Kenneth C.; Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 947 EP 947 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703181 ER PT J AU Munshi, NC Li, C Minvielle, S Amin, SB Moreau, P Magrangeas, F Anderson, KC Avet-Loiseau, H AF Munshi, Nikhil C. Li, Cheng Minvielle, Stepliane Amin, Samir B. Moreau, Philippe Magrangeas, Florence Anderson, Kenneth C. Avet-Loiseau, Herve TI Expression Profile Signature to Predict Response to Bortezomib and Dexamethasone Combination Therapy in Newly-Diagnosed Myeloma: Moving towards Prospective Prediction. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, VA Canc Healthcare Syst, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Minvielle, Stepliane; Moreau, Philippe; Magrangeas, Florence; Avet-Loiseau, Herve] Hop Nantes, Dept Hematol, Nantes, France. [Amin, Samir B.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RI Magrangeas, Florence/L-3080-2015; Minvielle, Stephane/K-8251-2015; richard, chrystelle/K-8595-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 948 EP 948 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703186 ER PT J AU Blotta, S Podar, K Tai, YT Roccaro, AM Gorgun, G Franco, B Mitsiades, CS Venuta, S Anderson, KC AF Blotta, Simona Podar, Klaus Tai, Yu-Tzu Roccaro, Aldo M. Gorgun, Gullu Franco, Brunella Mitsiades, Constantine S. Venuta, Salvatore Anderson, Kenneth C. TI Canonical and Non Canonical Activation of Hedgehog Pathway in Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Blotta, Simona; Podar, Klaus; Tai, Yu-Tzu; Roccaro, Aldo M.; Gorgun, Gullu; Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Blotta, Simona; Podar, Klaus; Tai, Yu-Tzu; Roccaro, Aldo M.; Gorgun, Gullu; Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Farber Canc Inst, LeBow Inst Myeloma Therapeut, Boston, MA 02115 USA. [Franco, Brunella] Telethon Inst Genet & Med TIGEM, Naples, Italy. [Venuta, Salvatore] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Venuta, Salvatore] Ctr Canc, Catanzaro, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 949 EP 949 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703188 ER PT J AU Podar, K Zhang, J Tonon, G Grabher, C Lababidi, S Raab, MS Vallet, S Zhou, YM Cartron, MA Sattler, M Chauhan, D Anderson, KC AF Podar, Klaus Zhang, Jing Tonon, Giovanni Grabher, Clemens Lababidi, Samir Raab, Marc S. Vallet, Sonia Zhou, Yiming Cartron, Marie-Astrid Sattler, Martin Chauhan, Dharminder Anderson, Kenneth C. TI C-Myc- Dependent Stabilization of Hif-1alpha in MM: Therapeutic Implications. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Podar, Klaus] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lababidi, Samir] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Zhou, Yiming; Cartron, Marie-Astrid] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 949 EP 949 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703189 ER PT J AU Podar, K Zhang, J Zimmerhackl, A Barila, D Vallet, S Sattler, M Tai, YT Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Zhang, Jing Zimmerhackl, Alexander Barila, Daniela Vallet, Sonia Sattler, Martin Tai, Yu-Tzu Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI Mcl-1 Fragment Mcl-1(128-350) Induces Inhibition of Multiple Myeloma Cell Proliferation and Apoptosis Via Both Upregulation of C-Jun as Well as Modulation of Its Transcriptional Activity. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Barila, Daniela] Univ Roma Tor Vergata, Rome, Italy. [Barila, Daniela] Dulbecco Telethon Inst, Lab Cell Signaling, Rome, Italy. [Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Podar, Klaus] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 949 EP 950 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703190 ER PT J AU Ikeda, H Hideshima, T Okawa, Y Vallet, S Pozzi, S Santo, L Gorgun, G Fulciniti, M Raje, NS Perrone, G Munshi, N Richardson, P Lannutti, BJ Puri, KD Giese, NA Anderson, KC AF Ikeda, Hiroshi Hideshima, Teru Okawa, Yutaka Vallet, Sonia Pozzi, Samantha Santo, Loredana Gorgun, Gullu Fulciniti, Mariateresa Raje, Noopur S. Perrone, Giulia Munshi, Nikhil Richardson, Paul Lannutti, Brian J. Puri, Kamal D. Giese, Neill A. Anderson, Kenneth C. TI CAL-101, a Specific Inhibitor of the p110 delta Isoform of Phosphatidylinositide 3-Kinase Induces Cytotoxicity in Multiple Myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ikeda, Hiroshi; Hideshima, Teru; Okawa, Yutaka; Vallet, Sonia; Pozzi, Samantha; Santo, Loredana; Gorgun, Gullu; Fulciniti, Mariateresa; Raje, Noopur S.; Perrone, Giulia; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lannutti, Brian J.; Puri, Kamal D.; Giese, Neill A.] Calistoga Pharmaceut Inc, Sealle, WA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 950 EP 950 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703192 ER PT J AU Leiba, M Jakubikova, J Klippel, S Mitsiades, CS Hideshima, T Tai, YT Richardson, P Kawa, Y Ikeda, H Nagler, A Anderson, KC AF Leiba, Merav Jakubikova, Jana Klippel, Steffen Mitsiades, Constantine S. Hideshima, Teru Tai, Yu-Tzu Richardson, Paul Kawa, Yutaka Ikeda, Hiroshi Nagler, Amon Anderson, Kenneth C. TI Halofuginone, a Novel Antimyeloma Agent, Upregulates C-Jun, JNK and P-53 Protein in vitro, and Inhibits Tumor Growth and Improves Survival in in vivo Multiple Myeloma(MM) Animal Models. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Leiba, Merav; Jakubikova, Jana; Klippel, Steffen; Mitsiades, Constantine S.; Hideshima, Teru; Tai, Yu-Tzu; Richardson, Paul; Kawa, Yutaka; Ikeda, Hiroshi; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Nagler, Amon] Chaim Sheba Med Ctr, Div Hematol & Bone Marrow Transplantat, IL-52621 Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 950 EP 951 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703193 ER PT J AU Shen, JPYC Divakaran, S Ponduru, S Vogl, DT Amaravadi, RK Bradner, JE AF Shen, John Paul Y. C. Divakaran, Sanjay Ponduru, Sridevi Vogl, Dan T. Amaravadi, Ravi K. Bradner, James E. TI The Rationale for Combined Proteasome and Autophagy Inhibition in Multiple Myeloma Established Using Novel Translational Platforms. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Shen, John Paul Y. C.] Univ Calif San Diego, Dept Internal Med, San Diego, CA 92103 USA. [Divakaran, Sanjay; Ponduru, Sridevi; Bradner, James E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Vogl, Dan T.; Amaravadi, Ravi K.] Univ Penn, Sch Med, Abramson Canc Ctr, Myeloma Program, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 951 EP 951 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703194 ER PT J AU Vallet, S Vaghela, N Fulciniti, M Veiby, P Hideshima, T Pozzi, S Santo, L Mukherjee, S Cirstea, D Scadden, DT Anderson, KC Raje, N AF Vallet, Sonia Vaghela, Nileshwari Fulciniti, Mariateresa Veiby, Petter Hideshima, Tern Pozzi, Samantha Santo, Loredana Mukherjee, Siddhartha Cirstea, Diana Scadden, David T. Anderson, Kenneth C. Raje, Noopur TI CCR1 Inhibition Targets Osteoclast-Myeloma Adhesion and Exerts in Vivo Anti-Osteoclast Activity. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Vallet, Sonia; Vaghela, Nileshwari; Raje, Noopur] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Hematol & Oncol, Boston, MA USA. [Fulciniti, Mariateresa; Hideshima, Tern; Pozzi, Samantha; Santo, Loredana; Cirstea, Diana; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Veiby, Petter] Millennium Pharmaceut Inc, Cambridge, MA USA. [Mukherjee, Siddhartha; Scadden, David T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Regenerat Med, Boston, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 951 EP 952 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703196 ER PT J AU Cirstea, D Hideshima, T Pozzi, S Vallet, S Ikeda, H Santo, L Loferer, H Vaghela, N Okawa, Y Perrone, G Gorgun, G Calabrese, E Munshi, NC Anderson, KC Raje, N AF Cirstea, Diana Hideshima, Teru Pozzi, Samantha Vallet, Sonia Ikeda, Hiroshi Santo, Loredana Loferer, Hannes Vaghela, Nileshwari Okawa, Yutaka Perrone, Giulia Gorgun, Gullu Calabrese, Elisabetta Munshi, Nikhil C. Anderson, Kenneth C. Raje, Noopur TI RGB 286638, a Novel Multi-Targeted Small Molecule Inhibitor, Induces Multiple Myeloma (MM) Cell Death through Abrogation of CDK-Dependent and Independent Survival Mechanisms. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cirstea, Diana; Hideshima, Teru; Ikeda, Hiroshi; Santo, Loredana; Okawa, Yutaka; Perrone, Giulia; Gorgun, Gullu; Calabrese, Elisabetta; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Pozzi, Samantha; Vallet, Sonia; Vaghela, Nileshwari] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. [Loferer, Hannes] GPC Biotech AG, Munich, Germany. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 952 EP 952 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703198 ER PT J AU McMillin, DW Negri, J Delmore, J Ooi, MG Jakubikova, J Wright, R Gray, N Kung, A Anderson, KC Mitsiades, CS AF McMillin, Douglas W. Negri, Joseph Delmore, Jake Ooi, Melissa G. Jakubikova, Jana Wright, Renee Gray, Nathanael Kung, Andrew Anderson, Kenneth C. Mitsiades, Constantine S. TI Activity of Plk Inhibitor BI2536 on Myeloma Cells. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [McMillin, Douglas W.; Negri, Joseph; Delmore, Jake; Ooi, Melissa G.; Jakubikova, Jana; Anderson, Kenneth C.; Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Wright, Renee; Kung, Andrew] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Gray, Nathanael] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 953 EP 954 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703203 ER PT J AU Raab, MS Breitkreutz, I Tonon, G Zhang, J Fruehauf, J Lin, BK Chauhan, D Hideshima, T Munshi, N Anderson, KC Podar, K AF Raab, Marc S. Breitkreutz, Iris Tonon, Giovanni Zhang, Jing Fruehauf, Johannes Lin, Boris K. Chauhan, Dharminder Hideshima, Teru Munshi, Nikhil Anderson, Kenneth C. Podar, Klaus TI Targeting PKC: A Novel Role for Beta-catenin in ER Stress and Apoptotic Signaling. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Raab, Marc S.; Breitkreutz, Iris; Tonon, Giovanni; Zhang, Jing; Chauhan, Dharminder; Hideshima, Teru; Munshi, Nikhil; Anderson, Kenneth C.; Podar, Klaus] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fruehauf, Johannes] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Lin, Boris K.] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 953 EP 953 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703202 ER PT J AU Breitkreutz, I Raab, MS Christensen, O Zimmerhackl, A Zhang, J Blotta, S Hideshima, T Chauhan, D Wilhelm, S Anderson, KC Podar, K AF Breitkreutz, Iris Raab, Marc S. Christensen, Olaf Zimmerhackl, Alexander Zhang, Jing Blotta, Simona Hideshima, Teru Chauhan, Dharminder Wilhelm, Scott Anderson, Kenneth C. Podar, Klaus TI The Novel, Orally Available Multi-Kinase Inhibitor BAY 73-4506 in Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Christensen, Olaf; Wilhelm, Scott] Bayer Healthcare Pharmaceut Inc, Montville, NJ USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 954 EP 954 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703205 ER PT J AU Richardson, P Hofmeister, CC Zimmerman, TM Chanan-Khan, AA Spear, MA Palladino, MA Longenecker, AM Cropp, G Lloyd, GK Wear, S Hannah, AL Anderson, KC AF Richardson, Paul Hofmeister, Craig C. Zimmerman, Todd M. Chanan-Khan, Asher Alban Spear, Matthew A. Palladino, Michael A. Longenecker, Angie M. Cropp, Gillian Lloyd, G. Kenneth Wear, Sandra Hannah, Alison L. Anderson, Kenneth C. TI Phase 1 Clinical Trial of NPI-0052, a Novel Proteasome Inhibitor in Patients with Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Richardson, Paul; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Hofmeister, Craig C.] Ohio State Univ, Columbus, OH 43210 USA. [Zimmerman, Todd M.] Univ Chicago, Chicago, IL USA. [Chanan-Khan, Asher Alban] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Spear, Matthew A.; Palladino, Michael A.; Longenecker, Angie M.; Cropp, Gillian; Lloyd, G. Kenneth; Hannah, Alison L.] Nereus Pharmaceut Inc, San Diego, CA USA. [Wear, Sandra] Multiple Myeloma Res Consortium, Norwalk, CT USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 955 EP 956 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703209 ER PT J AU Zonder, JA Singhal, S Bensinger, W Mohrbacher, A Hussein, MA Munshi, NC Caras, I Singhal, A van Rhee, F AF Zonder, Jeffrey A. Singhal, Seema Bensinger, William Mohrbacher, Ann Hussein, Mohamad A. Munshi, Nikhil C. Caras, Ingrid Singhal, Anil van Rhee, Frits TI Phase I Study of Elotuzumab (HuLuc63) in Phase I Study of Elotuzumab (HuLuc63) in Relapsed/Refractory Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zonder, Jeffrey A.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Singhal, Seema] Northwestern Univ, Sch Med, Chicago, IL USA. [Bensinger, William] Fred Hutchinson Canc, Seattle, WA USA. [Mohrbacher, Ann] USC Keck Sch Med, Altadena, CA USA. [Hussein, Mohamad A.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Caras, Ingrid; Singhal, Anil] PDL BioPharma Inc, Redwood City, CA USA. [van Rhee, Frits] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 956 EP 957 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703212 ER PT J AU Wolf, JL Siegel, D Matous, J Lonial, S Goldschmidt, H Schmitt, S Vij, R De Malgalhaes-Silverman, M Abonour, R Jalaluddin, M Li, M Hazell, K Bourquelot, PM Mateos, MV Anderson, KC Spencer, A Harousseau, JL Blade, J AF Wolf, Jeffrey Lee Siegel, David Matous, Jeffrey Lonial, Sagar Goldschmidt, Hartmut Schmitt, Stefan Vij, Ravi De Malgalhaes-Silverman, Margarida Abonour, Rafat Jalaluddin, Muhammad Li, Martha Hazell, Katharine Bourquelot, Priscille M. Mateos, Maria-Victoria Anderson, Kenneth C. Spencer, Andrew Harousseau, Jean-Luc Blade, Joan TI A Phase II Study of Oral Panobinostat (LBH589) in Adult Patients with Advanced Refractory Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wolf, Jeffrey Lee] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Lonial, Sagar] Emory Univ, Atlanta, GA 30322 USA. [Goldschmidt, Hartmut] Natl Ctr Tumorerkrankungen, Heidelberg, Germany. [Schmitt, Stefan] Univ Hosp, Heidelberg, Germany. [Vij, Ravi] Washington Univ, Ballwin, MO USA. [De Malgalhaes-Silverman, Margarida] Univ Iowa, Iowa City, IA USA. [Abonour, Rafat] Indiana Univ Canc, Indianapolis, IN USA. [Jalaluddin, Muhammad] Novartis Pharmaceut, Florham Pk, NJ USA. [Li, Martha] Novartis Pharmaceut, E Hanover, NJ USA. [Hazell, Katharine; Bourquelot, Priscille M.] Novartis Pharmaceut, Basel, Switzerland. [Mateos, Maria-Victoria] Hosp Univ Salamanca, Salamanca, Spain. [Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Spencer, Andrew] Monash Univ, Alfred Hosp, Melbourne, Vic 3181, Australia. [Harousseau, Jean-Luc] Hop Hotel Dieu, Nantes, France. [Blade, Joan] IDIBAPS, Hosp Clin, Barcelona, Spain. NR 0 TC 0 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 957 EP 957 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703213 ER PT J AU Harousseau, JL Palumbo, A Richardson, P Schlag, R Dimopoulos, MA Shpilberg, O Kropff, MH Delforge, M Schots, R Cavo, M Golenkov, A Komarnicki, M Mateos, MV Cakana, A Liu, K Deraedt, W van de Velde, H Miguel, JFS AF Harousseau, Jean-Luc Palumbo, Antonio Richardson, Paul Schlag, Rudolf Dimopoulos, Meletios A. Shpilberg, Ofer Kropff, Martin H. Delforge, Michel Schots, Rik Cavo, Michele Golenkov, Anatoly Komarnicki, Mieczyslaw Mateos, Maria-Victoria Cakana, Andrew Liu, Kevin Deraedt, William van de Velde, Helgi Miguel, Jesus F. San TI Superior Outcomes Associated with Complete Response: Analysis of the Phase III VISTA Study of Bortezomib Plus Melphalan-Prednisone Versus Melphalan-Prednisone. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Harousseau, Jean-Luc] CHU Hotel Dieu, Serv Hematol, Nantes, France. [Palumbo, Antonio] Univ Turin, Turin, Italy. [Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. [Schlag, Rudolf] Praxis Hematol & Oncol, Wurzburg, Germany. [Dimopoulos, Meletios A.] Univ Athens, Sch Med, GR-10679 Athens, Greece. [Shpilberg, Ofer] Rabin Med Ctr, Petah Tiqwa, Israel. [Kropff, Martin H.] Univ Munster, Munster, Germany. [Delforge, Michel] Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. [Schots, Rik] Belgian Hematol Soc, Myeloma Study Grp, Brussels, Belgium. [Cavo, Michele] Univ Bologna, Bologna, Italy. [Komarnicki, Mieczyslaw] Karol Marcinkowski Univ Med Sci, Poznan, Poland. [Miguel, Jesus F. San] CSIC, USAL, IBMCC, Hosp Univ Salamanca,CIC, Salamanca, Spain. [Cakana, Andrew; Deraedt, William; van de Velde, Helgi] Johnson & Johnson Pharmaceut Res & Dev, Beerse, Belgium. [Liu, Kevin] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. NR 0 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 959 EP 959 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703217 ER PT J AU Siegel, D Sezer, O Miguel, JFS Mateos, MV Prosser, I Cavo, M Jalaluddin, M Hazell, K Bourquelot, PM Anderson, KC AF Siegel, David Sezer, Orhan Miguel, Jesus F. San Mateos, Maria-Victoria Prosser, Ian Cavo, Michele Jalaluddin, Muhammad Hazell, Katharine Bourquelot, Priscille M. Anderson, Kenneth C. TI A Phase IB, Multicenter, Open-Label, Dose-Escalation Study of Oral Panobinostat (LBH589) and IV Bortezomib in Patients with Relapsed Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Sezer, Orhan] Univ Hosp Charite, Berlin, Germany. [Miguel, Jesus F. San; Mateos, Maria-Victoria] Hosp Univ Salamanca, Salamanca, Spain. [Prosser, Ian] Canberra Hosp, Canberra, ACT, Australia. [Cavo, Michele] Univ Bologna, Bologna, Italy. [Jalaluddin, Muhammad] Novartis Pharmaceut, Florham Pk, NJ USA. [Hazell, Katharine; Bourquelot, Priscille M.] Novartis Pharmaceut, Basel, Switzerland. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 960 EP 961 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703220 ER PT J AU Alford, KA Vanes, L Li, Z Orkin, SH Fisher, EMC Tybulewicz, VLJ AF Alford, Kate A. Vanes, Lesley Li, Zhe Orkin, Stuart H. Fisher, Elizabeth M. C. Tybulewicz, Victor L. J. TI A Myeloproliferative Disorder in the Tel Mouse Model of Down Syndrome. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Alford, Kate A.; Vanes, Lesley; Tybulewicz, Victor L. J.] Natl Inst Med Res, London NW7 1AA, England. [Li, Zhe] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Elizabeth M. C.] UCL, Inst Neurol, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 964 EP 964 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703229 ER PT J AU Bellucci, R Nguyen, HN Martin, A Schinzel, A Daley, J Hansen, S Hahn, WC Ritz, J AF Bellucci, Roberto Nguyen, Hong-Nam Martin, Allison Schinzel, Anna Daley, John Hansen, Steen Hahn, William C. Ritz, Jerome TI Genetic Screening for Myeloma Cell Susceptibility to NK Cell Mediated Lysis Using Large Lentiviral shRNA Libraries SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Bellucci, Roberto; Schinzel, Anna; Hahn, William C.; Ritz, Jerome] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hansen, Steen] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 997 EP 998 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703337 ER PT J AU Rosenblatt, J Vasir, B Wu, ZK Zarwan, C Stone, R Bissonnette, A Friedman, TM Neuberg, D Rozenveyn, N Glotzbecker, B Levine, JD Joyce, R Boussiotis, V Tzachanis, D Spentzos, D Konstantinopoulos, P Kufe, D Avigan, D AF Rosenblatt, Jacalyn Vasir, Baldev Wu, Zekui Zarwan, Corrine Stone, Richard Bissonnette, Adam Friedman, Thea M. Neuberg, Donna Rozenveyn, Natalya Glotzbecker, Brett Levine, James D. Joyce, Robin Boussiotis, Vassiliki Tzachanis, Dimitrios Spentzos, Dimitrios Konstantinopoulos, Panagiotis Kufe, Donald Avigan, David TI Adoptive T Cell Therapy Using Educated T Cells Generated by the Sequential Stimulation with DC/Tumor Fusion Cells and Anti-CD3CD28 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rosenblatt, Jacalyn; Zarwan, Corrine; Rozenveyn, Natalya; Glotzbecker, Brett; Levine, James D.; Joyce, Robin; Boussiotis, Vassiliki; Tzachanis, Dimitrios; Spentzos, Dimitrios; Konstantinopoulos, Panagiotis; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Vasir, Baldev; Wu, Zekui; Stone, Richard; Bissonnette, Adam; Neuberg, Donna; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Friedman, Thea M.] Hackensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1002 EP 1002 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703350 ER PT J AU Huiya, N Gaynon, PS Femandez, M Silverman, LB Thomson, B Chu, R Cooper, T Kadota, R Rytting, M Steinherz, PG Shen, V Jeha, S Barry, E Carroll, WL AF Huiya, Nobuko Gaynon, Paul S. Femandez, Manuel Silverman, Lewis B. Thomson, Blythe Chu, Roland Cooper, Todd Kadota, Richard Rytting, Michael Steinherz, Peter G. Shen, Violet Jeha, Sima Barry, Elly Carroll, William L. TI Durable Remissions Observed in a Phase I/II Study of Clofarabine in Combination with Etoposide and Cyclophosphamide in Pediatric Patients with Refractory or Relapsed Acute Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Huiya, Nobuko] Childrens Mem Hosp, Chicago, IL 60614 USA. [Gaynon, Paul S.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Femandez, Manuel] Genzyme Corp, San Antonio, TX USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Thomson, Blythe] Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. [Chu, Roland] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Cooper, Todd] Univ Alabama, Birmingham, AL USA. [Kadota, Richard] Children Hosp San Diego, San Diego, CA USA. [Rytting, Michael] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Steinherz, Peter G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Shen, Violet] CHOC Pediat Subspecialty Fac, Orange, CA USA. [Jeha, Sima] St Jude Childrens Rsch Hosp, Memphis, TN USA. [Barry, Elly] Genzyme Corp, Boston, MA USA. [Carroll, William L.] NYU, Inst Canc, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1006 EP 1006 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703362 ER PT J AU Kapeller, R Han, JW Sun, KM Gangurde, P Kawahata, N Iadanza, M Guerlevais, V Horstick, J Noehre, J Annis, A Licklider, L Nash, HM Kong, A Sawyer, TK AF Kapeller, Rosana Han, Jiawen Sun, Kaiming Gangurde, Pranoti Kawahata, Nori Iadanza, Matt Guerlevais, Vincent Horstick, Jim Noehre, Justin Annis, Allen Licklider, Larry Nash, Huw M. Kong, Andrew Sawyer, Tomi K. TI Stapled Peptides: Leveraging the BH3 alpha-Helix to Create a New Class of Drugs to Treat Hematological Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kapeller, Rosana; Han, Jiawen; Sun, Kaiming; Gangurde, Pranoti; Kawahata, Nori; Iadanza, Matt; Guerlevais, Vincent; Horstick, Jim; Noehre, Justin; Annis, Allen; Licklider, Larry; Nash, Huw M.; Sawyer, Tomi K.] AILERON Therapeut Inc, Cambridge, MA USA. [Kong, Andrew] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1007 EP 1008 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703366 ER PT J AU Rodrigues, MS Reddy, MM Walz, C Salgia, R Podar, K Band, H Reiter, A Griffin, JD Sattler, M AF Rodrigues, Margret S. Reddy, Mamatha M. Walz, Christoph Salgia, Ravi Podar, Klaus Band, Hamid Reiter, Andreas Griffin, James D. Sattler, Martin TI Novel Transforming Mutations of CBL in Human Acute Myeloid Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Rodrigues, Margret S.; Reddy, Mamatha M.; Podar, Klaus; Griffin, James D.; Sattler, Martin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Walz, Christoph; Reiter, Andreas] Univ Heidelberg, Fak Med, Med Univ Klin 3, D-6800 Mannheim, Germany. [Salgia, Ravi] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Band, Hamid] Univ Nebraska Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1013 EP 1013 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703385 ER PT J AU Grant, S Kolla, S Sirulnik, LA Shapiro, G Supko, J Cooper, B Perkins, E Ramakrishnan, V Espinoza-Delgado, I Tombes, MB Roberts, JD AF Grant, Steven Kolla, Sarah Sirulnik, Leonardo Andres Shapiro, Geoffrey Supko, Jeffrey Cooper, Brenda Perkins, Edward Ramakrishnan, Viswanathan Espinoza-Delgado, Igor Tombes, M. B. Roberts, John D. TI Phase I Trial of Vorinostat (SAHA) in Combination with Alvocidib (Flavopiridol) in Patients with Relapsed, Refractory or (Selected) Poor Prognosis Acute Leukemia or Refractor), Anemia with Excess Blasts-2 (RAEB-2) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Grant, Steven; Kolla, Sarah; Perkins, Edward; Ramakrishnan, Viswanathan; Tombes, M. B.; Roberts, John D.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 02115 USA. [Sirulnik, Leonardo Andres; Shapiro, Geoffrey; Supko, Jeffrey] Dana Farber Canc Inst, Boston, MA 44106 USA. [Cooper, Brenda] Case Western Reserve Univ, Univ Hosp Cleveland, Ireland Canc Ctr, Cleveland, OH 20892 USA. [Espinoza-Delgado, Igor] NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1026 EP 1026 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703423 ER PT J AU Cserti-Gazdewich, C Dhabangi, A Musoke, C Nabukeera-Barungi, N Ddungu, H Mpimbaza, A Ssewanyana, I Dzik, WH AF Cserti-Gazdewich, Christine Dhabangi, Aggrey Musoke, Charles Nabukeera-Barungi, Nicolette Ddungu, Henry Mpimbaza, Arthur Ssewanyana, Isaac Dzik, Walter H. TI Hematologic Findings and Transfusion Therapy in Severe Pediatric Plasmodium Falciparum Malaria: Results from a Prospective Observational Study in Uganda SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cserti-Gazdewich, Christine] Toronto Gen Hosp, Toronto, ON, Canada. [Dhabangi, Aggrey; Musoke, Charles; Nabukeera-Barungi, Nicolette; Ddungu, Henry; Mpimbaza, Arthur] Mulago Hosp, Kampala, Uganda. [Ssewanyana, Isaac] Joint Clin Res Ctr, Kampala, Uganda. [Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1045 EP 1046 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703478 ER PT J AU Treon, S Branagan, A Ioakimidis, L Soumerai, J Patterson, C Wasi, P Emmanouilides, C Frankel, SR Lister, A Morel, P Matous, J Gregory, SA Kimby, EK AF Treon, Steven Branagan, Andrew Ioakimidis, Leukothea Soumerai, Jacob Patterson, Christopher Wasi, Parveen Emmanouilides, Christos Frankel, Stanley R. Lister, Andrew Morel, Pierre Matous, Jeffrey Gregory, Stephanie A. Kimby, Eva K. TI Long Term Responses to Fludarabine and Rituximab in Waldenstrom's Macroglobulinemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ioakimidis, Leukothea] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wasi, Parveen] McMaster Univ, Hamilton, ON, Canada. [Emmanouilides, Christos] Interbalkan Hosp, Pylaia, Greece. [Frankel, Stanley R.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Lister, Andrew] Ctr Med Oncol, London, England. [Morel, Pierre] Serv Hematol Clin, Lens, France. [Matous, Jeffrey] Rocky Mt Canc Ctr, Denver, CO USA. [Gregory, Stephanie A.] Rush Univ, Chicago, IL 60612 USA. [Kimby, Eva K.] Karolinska Inst, Hematol Ctr, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1051 EP 1051 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703494 ER PT J AU Novakovic, VA Baleja, JD Gilbert, GE AF Novakovic, Valerie A. Baleja, James D. Gilbert, Gary E. TI The Factor VIIII C2 Domain Shows Stereospecificity for Phosphatidyl-L-Serine and Increases Factor IXa Activity SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Novakovic, Valerie A.] VA Boston Healthcare Syst, W Roxbury, MA USA. [Baleja, James D.] Tufts Univ, Sackler Sch Biomed Sci, Boston, MA 02111 USA. [Gilbert, Gary E.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1061 EP 1061 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703527 ER PT J AU Zhou, J Liu, SC Ma, M Hou, JX Yu, HJ Lu, CF Gilbert, G Shi, JL AF Zhou, Jin Liu, Shuchuan Ma, Ming Hou, Jinxiao Yu, Hongjuan Lu, Chengfang Gilbert, Gary Shi, Jialan TI Procoagulant Activity and Phosphatidylserine of Amniotic Fluid Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhou, Jin; Liu, Shuchuan; Ma, Ming; Hou, Jinxiao; Yu, Hongjuan; Lu, Chengfang] Harbin Med Coll, Dept Med, Affiliated Hosp 1, Harbin, Peoples R China. [Gilbert, Gary; Shi, Jialan] Harvard Univ, Sch Med, Brigham & Womens Hosp, VA Boston Healthcare Syst,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1061 EP 1061 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703528 ER PT J AU Malek, S Ouillette, P Wright, W Dressel, A Karp, J Bockenstedt, P Al-Zoubi, A Talpaz, M Kujawski, L Shedden, K Shakhan, S Li, C Erba, H Parkin, B AF Malek, Sami Ouillette, Peter Wright, Whitney Dressel, Amanda Karp, Judy Bockenstedt, Paula Al-Zoubi, Ammar Talpaz, Moshe Kujawski, Lisa Shedden, Kerby Shakhan, Sajid Li, Cheng Erba, Harry Parkin, Brian TI Comprehensive Ultra High Resolution Analysis of Copy Number and Allele Status Including Novel Microdeletions Spanning NF1 in Acute Myelogenous Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Malek, Sami; Ouillette, Peter; Wright, Whitney; Dressel, Amanda; Bockenstedt, Paula; Al-Zoubi, Ammar; Talpaz, Moshe; Shedden, Kerby; Shakhan, Sajid; Erba, Harry; Parkin, Brian] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Karp, Judy] Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Li, Cheng] Harvard Univ, Sch Publ Hlth, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1066 EP 1066 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703544 ER PT J AU Malek, S Wright, W Li, C Shakhan, S Ouillette, P AF Malek, Sami Wright, Whitney Li, Cheng Shakhan, Sajid Ouillette, Peter TI Comparative Genomic Analysis of CLL Genomes Using Affymetrix 50K SNP Versus SNP 6.0 Arrays SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Malek, Sami; Wright, Whitney; Shakhan, Sajid; Ouillette, Peter] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Li, Cheng] Harvard Univ, Dept Biostat, Sch Publ Hlth, Cambridge, MA 02138 USA. [Li, Cheng] Harvard Univ, Dept Biostat & Computat Biol, Sch Publ Hlth, Cambridge, MA 02138 USA. [Li, Cheng] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1066 EP 1066 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703545 ER PT J AU Brown, JR Rassenti, L Neuberg, D Greaves, A Byrd, JC Grever, MR Gribben, JG Kay, NE Keating, M Rai, KR Wierda, WG Kipps, TJ AF Brown, Jennifer R. Rassenti, Laura Neuberg, Donna Greaves, Andrew Byrd, John C. Grever, Michael R. Gribben, John G. Kay, Neil E. Keating, Michael Rai, Kanti R. Wierda, William G. Kipps, Thomas J. TI Characteristics of Familial CLL Evaluated in the CLL Research Consortium Cohort SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Brown, Jennifer R.; Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rassenti, Laura; Greaves, Andrew; Kipps, Thomas J.] UCSD, Div Hematol Oncol, Dept Med, Moores Canc Ctr, La Jolla, CA USA. [Byrd, John C.; Grever, Michael R.] Ohio State Univ, James Canc Inst, Columbus, OH 43210 USA. [Gribben, John G.] Barts & London Queen Marys Sch Med & Dent, Inst Canc, Ctr Med Oncol, London, England. [Kay, Neil E.] Mayo Clin, Div Hematol, Rochester, MN USA. [Keating, Michael; Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Rai, Kanti R.] N Shore Long Isl Jewish Hlth Syst, New Hyde Pk, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1071 EP 1072 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703562 ER PT J AU Amrein, PC Attar, E Takvorian, T Hochberg, E Ballen, KK Leahy, KM Neuberg, D Brown, JR AF Amrein, Philip C. Attar, Eyal Takvorian, Tak Hochberg, Ephraim Ballen, Karen K. Leahy, Kathleen M. Neuberg, Donna Brown, Jennifer R. TI Dasatinib Has Activity in Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL/SLL), a Phase II Trial SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Amrein, Philip C.; Attar, Eyal; Takvorian, Tak; Hochberg, Ephraim; Ballen, Karen K.; Leahy, Kathleen M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neuberg, Donna; Brown, Jennifer R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1084 EP 1084 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703599 ER PT J AU Roberts, AW Brown, J Seymour, JF Wierda, WG Kipps, TJ Xiong, H Chiu, YL Busman, T Knight, RA Enschede, S Krivoshik, A Humerickhouse, R AF Roberts, Andrew W. Brown, Jennifer Seymour, John F. Wierda, William G. Kipps, Thomas J. Xiong, Hao Chiu, Yi-Lin Busman, Todd Knight, Raymond A. Enschede, Sari Krivoshik, Andrew Humerickhouse, Rod TI An Ongoing Phase 1 Study of ABT-263; Pharmacokineties, Safety and Anti-Tumor Activity in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Roberts, Andrew W.] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Canc & Haem, Parkville, Vic 3050, Australia. [Brown, Jennifer] Dana Farber Canc Inst, Boston, MA 02115 USA. [Seymour, John F.] Peter MacCallum Canc Ctr, Dept Haematol & Med Oncol, Melbourne, Australia. [Wierda, William G.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Kipps, Thomas J.] CLL Res Consortium, Moores UCSD Canc Ctr, La Jolla, CA USA. [Xiong, Hao; Chiu, Yi-Lin; Busman, Todd; Knight, Raymond A.; Enschede, Sari; Krivoshik, Andrew; Humerickhouse, Rod] Abbott Labs, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1089 EP 1090 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703614 ER PT J AU Cutler, C Aldridge, J Kim, HT Ayanian, S Bradwin, G Revta, C Murga, G Ho, V Alyea, E Koreth, J Armand, P Richardson, PG Soiffer, RJ Ritz, J Antin, JH AF Cutler, Corey Aldridge, J. Kim, H. T. Ayanian, S. Bradwin, G. Revta, C. Murga, G. Ho, V. Alyea, E. Koreth, J. Armand, P. Richardson, P. G. Soiffer, R. J. Ritz, J. Antin, J. H. TI Prediction of VOD Using Biomarkers of Endothelial Injury SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cutler, Corey; Aldridge, J.; Kim, H. T.; Revta, C.; Murga, G.; Ho, V.; Alyea, E.; Koreth, J.; Armand, P.; Richardson, P. G.; Soiffer, R. J.; Ritz, J.; Antin, J. H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ayanian, S.; Bradwin, G.] Childrens Hosp, Lab Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1122 EP 1122 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703703 ER PT J AU Melanson, SE Antin, JH Court, MH Ho, V Ritz, J Kim, HT Kuo, FC Longtine, JA Jarolim, P AF Melanson, Stacy E. Antin, Joseph H. Court, Michael H. Ho, Vincent Ritz, Jerome Kim, Haesook T. Kuo, Frank C. Longtine, Janina A. Jarolim, Petr TI Genetic Variations in CYP2B6 and Risk of Cyclophosphamide Toxicity in Patients Undergoing Myeloablative Stem Cell Transplantation SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Antin, Joseph H.] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Court, Michael H.] Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. [Ritz, Jerome] Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. [Jarolim, Petr] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1129 EP 1130 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104703725 ER PT J AU Hursting, MJ Jang, LK AF Hursting, Marcie J. Jang, Lk-Kyung TI Dosing Patterns and Outcomes in African American, Asian, and Hispanic Patients with Heparin-Induced Thrombocytopenia Treated with Argatroban SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hursting, Marcie J.] Clin Sci Consulting, Austin, TX USA. [Jang, Lk-Kyung] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1167 EP 1168 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704021 ER PT J AU Kuter, DJ Mufti, G Bain, B Hasserjian, R Rutstein, M AF Kuter, David J. Mufti, Ghulam Bain, Barbara Hasserjian, Robert Rutstein, Mark TI Evaluation of Bone Marrow Reticulin Formation in Romiplostim-Treated Adult Patients with Chronic Immune Thrombocytopenic Purpura (ITP) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol (ASH), Sanofi Aventis U.S. C1 [Kuter, David J.; Hasserjian, Robert] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mufti, Ghulam] Kings Coll Hosp London, London, England. [Bain, Barbara] St Marys Hosp, London, England. [Rutstein, Mark] Amgen Inc, Thousand Oaks, CA 91320 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1171 EP 1172 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704034 ER PT J AU Zakai, NA French, B Arnold, A Newman, A Fried, LF Robbins, J Chaves, P Cushman, M AF Zakai, Neil A. French, Benjamin Arnold, Alice Newman, Anne Fried, Linda F. Robbins, John Chaves, Paolo Cushman, Mary TI Hemoglobin Decline and Health Outcomes in the Elderly: the Cardiovascular Health Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zakai, Neil A.; Cushman, Mary] Univ Vermont, Colchester, VT USA. [French, Benjamin] Univ Penn, Philadelphia, PA 19104 USA. [Arnold, Alice] Univ Washington, Seattle, WA 98195 USA. [Fried, Linda F.] Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15260 USA. [Robbins, John] Univ Calif, David, CA USA. [Chaves, Paolo] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1183 EP 1183 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704066 ER PT J AU de Jong, JLO Burns, CE Tinmaung, A Pugach, E Mayhall, E Smith, ACH Feldman, HA Zhou, Y Zon, LI AF de Jong, Jill L. O. Burns, Caroline E. Tinmaung, Aye Pugach, Emily Mayhall, Elizabeth Smith, Alexandra C. H. Feldman, Henry A. Zhou, Yi Zon, Leonard I. TI Development of a Limiting Dilution Assay and MHC-Matched Transplantation Model to Detect Hematopoietic Stem Cell Activity in Zebrafish. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [de Jong, Jill L. O.; Burns, Caroline E.; Tinmaung, Aye; Pugach, Emily; Mayhall, Elizabeth; Smith, Alexandra C. H.; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [de Jong, Jill L. O.; Burns, Caroline E.; Tinmaung, Aye; Pugach, Emily; Mayhall, Elizabeth; Smith, Alexandra C. H.; Zhou, Yi; Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Feldman, Henry A.] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1196 EP 1196 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704107 ER PT J AU Andreola, G Chittenden, M Sykes, M AF Andreola, Giovanna Chittenden, Meredith Sykes, Megan TI Lack of "Bystander" Activation and Evidence for Competition for Resources among Gvh-Reactive CD4 T Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Andreola, Giovanna; Chittenden, Meredith; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplatat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1202 EP 1202 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704125 ER PT J AU Andreola, G Chittenden, M Sykes, M AF Andreola, Giovanna Chittenden, Meredith Sykes, Megan TI Host Environment Determines the Development of Gvhd but Not the Extent of Activation and Expansion of Gvh-Reactive CD4 T Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Andreola, Giovanna; Chittenden, Meredith; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Marrow Transplantat Sec, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1202 EP 1203 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704126 ER PT J AU Iino, T Chong, Y Mizuno, S Ito, K Tenen, DG Reizis, B Akashi, K AF Iino, Tadafumi Chong, Yong Mizuno, Shin-ichi Ito, Kyoko Tenen, Daniel G. Reizis, Boris Akashi, Koichi TI PU.1 Plays a Critical Role in Maintenance of Mature Dendritic Cell Pool. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Iino, Tadafumi; Chong, Yong; Mizuno, Shin-ichi; Ito, Kyoko; Akashi, Koichi] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tenen, Daniel G.] Harvard Univ, Inst Med, Boston, MA 02115 USA. [Reizis, Boris] Columbia Univ, Dept Microbiol, New York, NY 10032 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1217 EP 1217 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704172 ER PT J AU Schepers, K Mayack, SR Wagers, AJ Passegue, E AF Schepers, Koen Mayack, Shane R. Wagers, Amy J. Passegue, Emmanuelle TI Investigating the Complex Interplay Between Leukemic Stem Cells, Their Myeloid Progeny and Cells from the Bone Marrow Microenvironment in Generating Myeloproliferative Diseases. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Passegue, Emmanuelle] Univ Calif San Francisco, Inst Regenerat Med, Sch Med, San Francisco, CA 94143 USA. [Mayack, Shane R.; Wagers, Amy J.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1220 EP 1220 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704182 ER PT J AU Nombela-Arrieta, C Harley, B Levantini, E Mahoney, JE Pivarnik, G Protopopov, A Tenen, DG Silberstein, LE AF Nombela-Arrieta, Cesar Harley, Brendan Levantini, Elena Mahoney, John E. Pivarnik, Gregory Protopopov, Alexei Tenen, Daniel G. Silberstein, Leslie E. TI Spatial Analysis of Hematopoietic Stem and Progenitor Cells in the Bone Marrow SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Nombela-Arrieta, Cesar; Pivarnik, Gregory; Silberstein, Leslie E.] Childrens Hosp, Boston, MA 02115 USA. [Harley, Brendan] Univ Illinois, Dept Chem & Biomol Engn, Chicago, IL 60680 USA. [Levantini, Elena; Tenen, Daniel G.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Mahoney, John E.; Protopopov, Alexei] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1222 EP 1222 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704188 ER PT J AU Abramson, JS Barnes, JA Toomey, CE Jacobsen, ED Armand, P Takvorian, T Fisher, DC Reynolds, H Hochberg, EP LaCasce, AS AF Abramson, Jeremy S. Barnes, Jeffrey A. Toomey, Christiana E. Jacobsen, Eric D. Armand, Philippe Takvorian, Tak Fisher, David C. Reynolds, Hazel Hochberg, Ephraim P. LaCasce, Ann S. TI Rituximab Added to CODOX-M/IVAC Is Highly Effective in HIV-Negative and hiv-Positive Burkitt Lymphoma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Abramson, Jeremy S.; Barnes, Jeffrey A.; Toomey, Christiana E.; Takvorian, Tak; Hochberg, Ephraim P.] Massachusetts Gen Hosp, Ctr Canc, Ctr Lymphoma, Boston, MA USA. [Jacobsen, Eric D.; Armand, Philippe; Fisher, David C.; Reynolds, Hazel; LaCasce, Ann S.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1229 EP 1230 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704213 ER PT J AU Seymour, JF Fenaux, P Silverman, LB Mufti, GJ Hellstrom-Lindberg, E Santini, V List, AF Gore, SD Backstrom, J McKenzie, D Beach, CL AF Seymour, John F. Fenaux, Pierre Silverman, Lewis B. Mufti, Ghulam J. Hellstroem-Lindberg, Eva Santini, Valeria List, Alan F. Gore, Steven D. Backstrom, Jay McKenzie, David Beach, C. L. TI Effects of Azacitidine (AZA) Vs Conventional Care Regimens (CCR) in Elderly (>= 75 years) Patients (Pts) with Myelodysplastic Syndromes (MDS) from the AZA-001 Survival Trial SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Seymour, John F.] Peter MacCallum Canc Inst, Dept Haematol, Melbourne, Vic, Australia. [Fenaux, Pierre] Hosp Avicenne, Bobigny, France. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Mufti, Ghulam J.] Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. [Hellstroem-Lindberg, Eva] Karolinska Univ Hosp, Stockholm, Sweden. [Santini, Valeria] Azienda Osped Careggi, Florence, Italy. [List, Alan F.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Backstrom, Jay; McKenzie, David; Beach, C. L.] Celgene, Overland Pk, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1241 EP 1242 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704247 ER PT J AU Fenaux, P Mufti, GJ Hellstrom-Lindberg, E Santini, V Gattermann, N Sanz, G List, AF Gore, SD Seymour, JF Backstrom, J Zimmerman, L McKenzie, D Beach, CL Silverman, LB AF Fenaux, Pierre Mufti, Ghulam J. Hellstroem-Lindberg, Eva Santini, Valeria Gattermann, Norbert Sanz, Guillermo List, Alan F. Gore, Steven D. Seymour, John F. Backstrom, Jay Zimmerman, Linda McKenzie, David Beach, C. L. Silverman, Lewis B. TI Azacitidine Prolongs Overall Survival (OS) and Reduces Infections and Hospitalizations in Patients (Pts) with WHO-Defined Acute Myeloid Leukemia (AML) Compared with Conventional Care Regimens (CCR) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Fenaux, Pierre] Univ Paris 13, Hop Avicenne, Bobigny, France. [Mufti, Ghulam J.] Kings Coll London, Dept Haematol Med, London WC2R 2LS, England. [Hellstroem-Lindberg, Eva] Karolinska Univ Hosp, Stockholm, Sweden. [Santini, Valeria] Azienda Osped Careggi, Florence, Italy. [Gattermann, Norbert] Univ Dusseldorf, Dusseldorf, Germany. [Sanz, Guillermo] Hosp Univ La Fe, Dept Hematol, Valencia, Spain. [List, Alan F.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Gore, Steven D.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. [Seymour, John F.] Peter MacCallum Canc Inst, Dept Haematol, Melbourne, Vic, Australia. [Backstrom, Jay; Zimmerman, Linda; McKenzie, David; Beach, C. L.] Celgene, Overland Pk, KS USA. [Silverman, Lewis B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1244 EP 1244 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704254 ER PT J AU Chauhan, D Singh, AV Brahmandam, M Bianchi, G Podar, K Hideshima, T Munshi, N Richardson, P Palladino, MA Anderson, KC AF Chauhan, Dhapminder Singh, Ajita V. Brahmandam, Mohan Bianchi, Giada Podar, Klaus Hideshima, Teru Munshi, Nikhil Richardson, Paul Palladino, Michael A. Anderson, Kenneth C. TI Combination of a Novel Proteasome Inhibitor NPI-0052 and Lenalidomide Trigger in Vivo Synergistic Cytotoxicity in Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chauhan, Dhapminder; Singh, Ajita V.; Brahmandam, Mohan; Bianchi, Giada; Podar, Klaus; Hideshima, Teru; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Palladino, Michael A.] Nereus Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1254 EP 1254 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704280 ER PT J AU Cirstea, D Hideshima, T Pozzi, S Vallet, S Ikeda, H Santo, L Rodig, S Vaghela, N Currie, T Okawa, Y Chhetri, G Patel, CG Perrone, G Gorgun, G Calabrese, E Trieu, V Desai, N Sportelli, P Munshi, NC Anderson, KC Raje, N AF Cirstea, Diana Hideshima, Teru Pozzi, Samantha Vallet, Sonia Ikeda, Hiroshi Santo, Loredana Rodig, Scott Vaghela, Nileshwari Currie, Treeve Okawa, Yutaka Chhetri, Gaurav Patel, Chirayu G. Perrone, Giulia Gorgun, Gullu Calabrese, Elisabetta Trieu, Voung Desai, Neil Sportelli, Peter Munshi, Nikhil C. Anderson, Kenneth C. Raje, Noopur TI Combination of Nub-Rapamycin and Perifosine Induces Synergistic Cytotoxicity and Antitumor Activity Via Autophagy. and Apoptosis in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Cirstea, Diana; Hideshima, Teru; Ikeda, Hiroshi; Santo, Loredana; Okawa, Yutaka; Chhetri, Gaurav; Patel, Chirayu G.; Perrone, Giulia; Gorgun, Gullu; Calabrese, Elisabetta; Munshi, Nikhil C.; Anderson, Kenneth C.; Raje, Noopur] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Rodig, Scott; Currie, Treeve] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Pozzi, Samantha; Vallet, Sonia; Vaghela, Nileshwari] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. [Trieu, Voung; Desai, Neil] Abraxis Biosci LLC, Los Angeles, CA USA. [Sportelli, Peter] Keryx Biopharmaceut Inc, New York, NY USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1255 EP 1255 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704281 ER PT J AU Fulciniti, M Tassone, P Hideshima, T Nanjappa, P Podar, K Adamia, S Amin, SB Prabhala, R Lopez, R Anderson, KC Munshi, NC AF Fulciniti, Mariateresa Tassone, Pierfrancesco Hideshima, Teru Nanjappa, Puru Podar, Klaus Adamia, Sophia Amin, Samir B. Prabhala, Rao Lopez, Rocio Anderson, Kenneth C. Munshi, Nikhil C. TI Sp1 Transcription Factor as a Novel Therapeutic Target in Multiple Myeloma (MM) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Tassone, Pierfrancesco] Magna Graecia Univ Catanzaro, Catanzaro, Italy. [Amin, Samir B.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Prabhala, Rao] HMS, DFCI, VA Boston Hlth Care Syst, W Roxbury, MA USA. [Lopez, Rocio] Erimos Pharmaceut, Raleigh, NC USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1255 EP 1255 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704282 ER PT J AU Singh, AV Lloyd, GK Palladino, MA Chauhan, D Anderson, KC AF Singh, Ajita V. Lloyd, G. Kenneth Palladino, Michael A. Chauhan, Dharminder Anderson, Kenneth C. TI Pharmacodynamic and Efficacy Studies of a Novel Proteasome Inhibitor NPI-0052 in Human Plasmacytoma Xenograft Mouse Model SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Singh, Ajita V.; Chauhan, Dharminder; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lloyd, G. Kenneth; Palladino, Michael A.] Nereus Pharmaceut Inc, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1255 EP 1255 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704283 ER PT J AU Ponduru, S Moellering, R Greenberg, E Shen, JPYC Stanton, BZ Bradner, JE AF Ponduru, Sridevi Moellering, Raymond Greenberg, Edward Shen, John Paul Ying-Ching Stanton, Benjamin Z. Bradner, James E. TI Discovery and Characterization of Macrocyclic Thiopeptide Proteasome Inhibitors for Hematologic Malignancies SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ponduru, Sridevi; Greenberg, Edward; Bradner, James E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Moellering, Raymond; Stanton, Benjamin Z.] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. [Shen, John Paul Ying-Ching] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1257 EP 1257 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704287 ER PT J AU Vogl, DT Stadtmauer, EA Bradner, JE Davis, L Carroll, M Nichols, CW Shank, D Carberry, M Swider, CR Mangan, PA Shelly, BK Thompson, CB Amaravadi, RK AF Vogl, Dan T. Stadtmauer, Edward A. Bradner, James E. Davis, Lisa Carroll, Martin Nichols, Charles W. Shank, Doris Carberry, Mary Swider, Cezary R. Mangan, Patricia A. Shelly, Brenda K. Thompson, Craig B. Amaravadi, Ravi K. TI Combined Autophagy and Proteasome Inhibition for Multiple Myeloma: Preliminary Results of a Phase 1/2 Trial of Hydroxychloroquine and Standard Dose Bortezomib for Relapsed or Refractory Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Vogl, Dan T.; Stadtmauer, Edward A.; Carroll, Martin; Shank, Doris; Carberry, Mary; Swider, Cezary R.; Mangan, Patricia A.; Shelly, Brenda K.; Thompson, Craig B.; Amaravadi, Ravi K.] Univ Penn, Sch Med, Myeloma Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA. [Bradner, James E.] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. [Davis, Lisa] Univ Sci, Philadelphia, PA USA. [Nichols, Charles W.] Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 2 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 NOV 16 PY 2008 VL 112 IS 11 BP 1262 EP 1262 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704302 ER PT J AU Chanan-Khan, AA Munshi, NC Hussein, MA Elias, L Benedetti, F Smith, J Khor, SP Huff, CA AF Chanan-Khan, Asher Alban Munshi, Nikhil C. Hussein, Mohamad A. Elias, Laurence Benedetti, Fabio Smith, Jennifer Khor, Soo-Peang Huff, Carol A. TI Results of a Phase I Study of GRN163L, a Direct Inhibitor of Telomerase, in Patients with Relapsed and Refractory Multiple Myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chanan-Khan, Asher Alban] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Munshi, Nikhil C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. [Hussein, Mohamad A.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Huff, Carol A.] Johns Hopkins Univ, Baltimore, MD USA. [Elias, Laurence; Benedetti, Fabio; Smith, Jennifer; Khor, Soo-Peang] Geron Corp, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 8 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 NOV 16 PY 2008 VL 112 IS 11 BP 1263 EP 1263 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704306 ER PT J AU Chanan-Khan, AA Gharibo, M Jagannath, S Munshi, NC Anderson, KC DePaolo, D Lee, KP Miller, K Guild, R Zildjian, S Qin, A AF Chanan-Khan, Asher Alban Gharibo, Mecide Jagannath, Sundar Munshi, Nikhil C. Anderson, Kenneth C. DePaolo, Dawn Lee, Kelvin P. Miller, Kena Guild, Robin Zildjian, Sybil Qin, Albert TI Phase I Study of IMGN901 in Patients with Relapsed and Relapsed/Refractory CD56-Positive Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Chanan-Khan, Asher Alban; DePaolo, Dawn; Lee, Kelvin P.; Miller, Kena] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Gharibo, Mecide] Canc Inst NJ, Franklin Lakes, NJ USA. [Jagannath, Sundar] St Vincents Comp Canc Ctr, New York, NY USA. [Munshi, Nikhil C.; Lee, Kelvin P.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston VA Canc Healthcare Syst, Boston, MA 02115 USA. [Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA 02115 USA. [Guild, Robin; Zildjian, Sybil] Immunogen Inc, Waltham, MA USA. [Qin, Albert] Immunogen Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1263 EP 1264 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704307 ER PT J AU Perrone, G Hideshima, T Ikeda, H Okawa, Y Cristea, D Santo, L Gorgun, G Calabrese, E Raje, N Baccarani, M Cavo, M Anderson, KC AF Perrone, Giulia Hideshima, Teru Ikeda, Hiroshi Okawa, Yutaka Cristea, Diana Santo, Loredana Gorgun, Gullu Calabrese, Elisabetta Raje, Noopur Baccarani, Michele Cavo, Michele Anderson, Kenneth C. TI Dietary Supplement Vitamin C Significantly Abrogates Bortezomib-Induced Multiple Myeloma (MM) Cell Growth Inhibition. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Perrone, Giulia; Hideshima, Teru; Ikeda, Hiroshi; Okawa, Yutaka; Cristea, Diana; Santo, Loredana; Gorgun, Gullu; Calabrese, Elisabetta; Raje, Noopur; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Baccarani, Michele] Univ Bologna, Dept Hematol & Oncol Sci, Bologna, Italy. [Cavo, Michele] Univ Bologna, Dept Hematol & Med Oncol, Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1263 EP 1263 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704305 ER PT J AU Jakubowiak, A Richardson, P Zimmerman, TM Alsina, M Kaufman, JL Harvey, C Brozo, C Kendall, T McAllister, A Hideshima, T Sportelli, P Gardner, L Anderson, KC Giusti, K AF Jakubowiak, Andrzej Richardson, Paul Zimmerman, Todd M. Alsina, Melissa Kaufman, Jonathan L. Harvey, Colleen Brozo, Christine Kendall, Tara McAllister, Amanda Hideshima, Teru Sportelli, Peter Gardner, Lesa Anderson, Kenneth C. Giusti, Kathy TI Phase I Results of Perifosine (KRX-0401) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Jakubowiak, Andrzej; Harvey, Colleen; Brozo, Christine; Kendall, Tara; McAllister, Amanda] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Richardson, Paul; Hideshima, Teru; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Zimmerman, Todd M.] Univ Chicago, Chicago, IL 60637 USA. [Alsina, Melissa] Univ S Florida, H Lee Moffitt Canc Ctr, Hematol Malignancies Program, Tampa, FL 33682 USA. [Kaufman, Jonathan L.] Emory Univ, Sch Med, Atlanta, GA USA. [Sportelli, Peter; Gardner, Lesa] Keryx Biopharmaceut Inc, New York, NY USA. [Giusti, Kathy] MMRC, Norwalk, CT USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1264 EP 1265 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704309 ER PT J AU Ghobrial, IM Munshi, N Schlossman, R Chuma, S Leduc, R Nelson, M Sam, A O'Connor, K Harris, B Warren, D Dollard, AM Laubach, J Vij, R Campagnaro, E Birner, A Dixon-Lipscomb, V Anderson, KC Richardson, PG AF Ghobrial, Irene M. Munshi, Nikhil Schlossman, Robert Chuma, Stacey Leduc, Renee Nelson, Marybeth Sam, Amy O'Connor, Kelly Harris, Brianna Warren, Diane Dollard, Akari M. Laubach, Jacob Vij, Ravi Campagnaro, Erica Birner, Ann Dixon-Lipscomb, Virginia Anderson, Kenneth C. Richardson, Paul G. TI Phase I Trial of CCI-779 (Temsirolimus) and Weekly Bortezomib in Relapsed and/or Refractory Multiple Myeloma. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ghobrial, Irene M.; Munshi, Nikhil; Schlossman, Robert; Chuma, Stacey; Leduc, Renee; Nelson, Marybeth; Sam, Amy; O'Connor, Kelly; Harris, Brianna; Warren, Diane; Laubach, Jacob; Anderson, Kenneth C.; Richardson, Paul G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Dollard, Akari M.] MMRC, Norwalk, CT USA. [Vij, Ravi] Washington Univ, St Louis, MO USA. [Campagnaro, Erica] Univ Michigan, Ann Arbor, MI 48109 USA. [Birner, Ann] Millennium Pharmaceut Inc, Cambridge, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1266 EP 1266 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704314 ER PT J AU Mateos, MV Cibeira, T Richardson, P Blade, J Prosper, F Oriol, A de la Rubia, J Alegre, A Lahuerta, JJ Garcia-Sanz, R Mitsiades, CS Espinoza, J Anderson, KC Miguel, JFS AF Mateos, Maria-Victoria Cibeira, Teresa Richardson, Paul Blade, Joan Prosper, Felipe Oriol, Albert de la Rubia, Javier Alegre, Adrian Lahuerta, Juan Jose Garcia-Sanz, Ramon Mitsiades, Constantine S. Espinoza, Jose Anderson, Kenneth C. Miguel, J. F. San TI Final Results of a Phase II Trial with Plitidepsin (Aplidin) Alone and in Combination with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mateos, Maria-Victoria] Univ Hosp Salamanca, Salamanca, Spain. [Cibeira, Teresa] Hosp Clin Barcelona, Barcelona, Spain. [Mitsiades, Constantine S.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Blade, Joan] IDIBAPS, Hosp Clin, Barcelona, Spain. [Prosper, Felipe] Univ Navarra Clin, Pamplona, Spain. [Oriol, Albert] Hosp Germans Trials & Pujol, Badalona, Spain. [de la Rubia, Javier] Hosp La Fe, E-46009 Valencia, Spain. [Alegre, Adrian] Hosp La Princesa, Madrid, Spain. [Lahuerta, Juan Jose] Hosp 12 Octubre, E-28041 Madrid, Spain. [Garcia-Sanz, Ramon] Hosp Univ Salamanca, Salamanca, Spain. [Espinoza, Jose] PharmaMar, Madrid, Spain. [Miguel, J. F. San] CSIC, USAL, IBMCC, CIC, Salamanca, Spain. NR 0 TC 1 Z9 1 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 NOV 16 PY 2008 VL 112 IS 11 BP 1268 EP 1268 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704318 ER PT J AU Siegel, D Weber, D Mitsiades, CS Rizvi, S Garcia-Vargas, J Howe, J Reiser, D Anderson, KC Richardson, P AF Siegel, David Weber, Donna Mitsiades, Constantine S. Rizvi, Syed Garcia-Vargas, Jose Howe, Jason Reiser, David Anderson, Kenneth C. Richardson, Paul TI A Phase I Study of Vorinostat in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed or Refractory Multiple Myeloma SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Siegel, David] Hackensack Univ, Med Ctr, Hackensack, NJ USA. [Weber, Donna] Univ Texas MD Anderson Canc Ctr, Dept Lymphona & Myeloma, Houston, TX 77030 USA. [Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Rizvi, Syed; Garcia-Vargas, Jose; Howe, Jason; Reiser, David] Merck & Co Inc, Upper Gwynedd, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1270 EP 1270 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704323 ER PT J AU Treon, S Hunter, Z Ciccarelli, B Zhou, YS Hanzis, C Manning, R Ioakimidis, L Xu, L Patterson, C Morra, M AF Treon, Steven Hunter, Zachary Ciccarelli, Bryan Zhou, Yangsheng Hanzis, Christina Manning, Robert Ioakimidis, Leukothea Xu, Lian Patterson, Christopher Morra, Massimo TI IgA and IgG Hypogammaglobulinemia Is a Constitutive Feature in Most Waldenstrom's Macroglobulinemia Patients and May Be Related to Mutations Associated with Common Variable Immunodeficiency Disorder (CVID) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zhou, Yangsheng; Manning, Robert; Ioakimidis, Leukothea] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Morra, Massimo] Correlagen Diagnost Inc, Waltham, MA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1284 EP 1285 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704367 ER PT J AU Leleu, X Roccaro, AM Leduc, R Poulain, S Moreau, AS Gay, J Dulery, R Richardson, PG Ghobrial, IM AF Leleu, Xavier Roccaro, Aldo M. Leduc, Renee Poulain, Stephanie Moreau, Anne-Sophie Gay, Julie Dulery, Remy Richardson, Paul G. Ghobrial, Irene M. TI Early Response Using Serum Immunoglobulin Free Light Chain (sFLC) Measurement Predicts Response to Therapy in Waldenstrom Macroglobulinemia (WM) SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Leleu, Xavier; Poulain, Stephanie; Moreau, Anne-Sophie; Gay, Julie; Dulery, Remy] CHRU, Hop Huriez, Serv Malad Sang, Lille, France. [Leduc, Renee; Richardson, Paul G.; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2008 VL 112 IS 11 BP 1286 EP 1286 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704373 ER PT J AU Gritsman, K Kharas, MG Gilliland, DG AF Gritsman, Kira Kharas, Michael G. Gilliland, D. Gary TI Constitutively Active AKT Induces Myeloproliferative Disease, Acute Myeloid Leukemia, and T Cell Lymphoma despite Impaired Engraftment SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gritsman, Kira] Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1298 EP 1298 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704411 ER PT J AU Gutierrez, A Sanda, T Winter, S Larson, RS Silverman, LB Hunger, SP Sallan, SE Look, AT AF Gutierrez, Alejandro Sanda, Takaomi Winter, Stuart Larson, Richard S. Silverman, Lewis B. Hunger, Stephen P. Sallan, Stephen E. Look, A. Thomas TI LEF1 Is a Tumor Suppressor in T Cell Acute Lymphoblastic Leukemia SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gutierrez, Alejandro] Childrens Hosp, Boston, MA 02115 USA. [Gutierrez, Alejandro; Sanda, Takaomi; Silverman, Lewis B.; Sallan, Stephen E.; Look, A. Thomas] Dana Farber Canc Inst, Boston, MA 02115 USA. [Winter, Stuart] Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. [Larson, Richard S.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. [Hunger, Stephen P.] Univ Colorado, Denver Sch Med, Aurora, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1300 EP 1301 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704420 ER PT J AU Mueller, MR Robbs, BK Cruz, ALS Sasaki, Y Stevanovic, I Rajewsky, K Viola, JPB Rao, A AF Mueller, Martin R. Robbs, Bruno K. Cruz, Andre L. S. Sasaki, Yoshiteru Stevanovic, Irena Rajewsky, Klaus Viola, Joao P. B. Rao, Anjana TI Evidence for NFAT1 as a Tumor Suppressor in T-ALL SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mueller, Martin R.; Stevanovic, Irena; Rajewsky, Klaus; Rao, Anjana] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Robbs, Bruno K.; Cruz, Andre L. S.; Viola, Joao P. B.] Brazilian Natl Canc Inst INCA, Div Cell Biol, Rio De Janeiro, Brazil. [Sasaki, Yoshiteru] RIKEN, Ctr Dev Biol, Lab Stem Cell Biol, Kobe, Hyogo, Japan. RI Robbs, Bruno/H-5553-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1301 EP 1301 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704422 ER PT J AU Scholl, C Frohling, S Dunn, IF Barbie, DA Schinzel, AC Kim, SY Silver, SJ Bullinger, L Sandy, P Boehm, JS Root, DE Jacks, T Hahn, WC Gilliland, DG AF Scholl, Claudia Frohling, Stefan Dunn, Ian F. Barbie, David A. Schinzel, Anna C. Kim, So Young Silver, Serena J. Bullinger, Lars Sandy, Peter Boehm, Jesse S. Root, David E. Jacks, Tyler Hahn, William C. Gilliland, D. Gary TI High-Throughput RNA Interference Screening Identifies Synthetic Lethality Between Oncogenic KRAS Dependency and Suppression of STK33 SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Scholl, Claudia; Frohling, Stefan; Gilliland, D. Gary] Brigham & Womens Hosp, Boston, MA 02115 USA. [Dunn, Ian F.; Barbie, David A.; Silver, Serena J.; Sandy, Peter; Boehm, Jesse S.; Root, David E.; Jacks, Tyler] MIT, Cambridge, MA 02139 USA. [Dunn, Ian F.; Barbie, David A.; Silver, Serena J.; Boehm, Jesse S.; Root, David E.] Broad Inst Harvard, Cambridge, MA USA. [Schinzel, Anna C.; Kim, So Young; Hahn, William C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bullinger, Lars] Univ Hosp, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1301 EP 1302 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104704424 ER PT J AU Zwicker, J Liebman, HA Neuberg, D Bauer, K Barbara, F Bruce, F AF Zwicker, Jeffrey Liebman, Howard A. Neuberg, Donna Bauer, Kenneth Barbara, Furie Bruce, Furie TI Development of Venous Thromboembolic Events in Cancer Patients with Elevated Levels of Tissue Factor-Bearing Microparticles SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zwicker, Jeffrey; Bauer, Kenneth; Barbara, Furie; Bruce, Furie] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. [Liebman, Howard A.] Univ So Calif, Los Angeles, CA USA. [Neuberg, Donna] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1309 EP 1309 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704449 ER PT J AU Kwiatkowski, BA Dong, Z Richard, RE AF Kwiatkowski, Boguslaw A. Dong, ZhaoMing Richard, Robert E. TI The Identification of Genes Cooperating with Mpl Signaling Using Insertional Mutagenesis SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kwiatkowski, Boguslaw A.] VA Puget Sound Hlth Care Syst, Seattle Inst Biomed & Clin Res, Seattle, WA USA. [Richard, Robert E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1314 EP 1314 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704467 ER PT J AU Ho-Tin-Noe, BH Carbo, C Demers, M Cifuni, SM Goerge, T Wagner, DD AF Ho-Tin-Noe, Benoit H. Carbo, Carla Demers, Melanie Cifuni, Stephen M. Goerge, Tobias Wagner, Denisa D. TI Platelets Protect Tumors from Hemorrhage Induced by Stroma-Infiltrating Leukocytes SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Ho-Tin-Noe, Benoit H.; Carbo, Carla; Demers, Melanie; Cifuni, Stephen M.; Goerge, Tobias; Wagner, Denisa D.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1335 EP 1335 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704522 ER PT J AU Wagers, AJ Cerletti, M Mayack, SR Kim, FS Shadrach, JL AF Wagers, Amy J. Cerletti, Massimiliano Mayack, Shane R. Kim, Francis S. Shadrach, Jennifer L. TI Age-Related Changes in Tissue-Specific Stem Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Wagers, Amy J.; Cerletti, Massimiliano; Mayack, Shane R.; Kim, Francis S.; Shadrach, Jennifer L.] Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1343 EP 1343 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704545 ER PT J AU Zon, LI AF Zon, Leonard I. TI Transcription Factor Integration from Pathways Regulating Adult Blood Stem Cell Production and Self-Renewal SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Zon, Leonard I.] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Zon, Leonard I.] Harvard Stem Cell Inst, Howard Hughes Med Inst, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1346 EP 1346 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704556 ER PT J AU Dzik, WH AF Dzik, Walter H. TI Nitric Oxide: An Introductory Primer SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Dzik, Walter H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1354 EP 1354 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704588 ER PT J AU Golub, TR AF Golub, Todd R. TI Genomics and Systems Biology SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Golub, Todd R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1355 EP 1355 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104704592 ER PT J AU Esrailian, E Gralnek, IM Jensen, D Laine, L Dulai, GS Eisen, G Spiegel, BMR AF Esrailian, E. Gralnek, I. M. Jensen, D. Laine, L. Dulai, G. S. Eisen, G. Spiegel, B. M. R. TI Evaluating the process of care in nonvariceal upper gastrointestinal haemorrhage: a survey of expert vs. non-expert gastroenterologists SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ENDOSCOPY; QUALITY; METAANALYSIS; VIGNETTES; TRIAL AB Background When faced with the same facts, physicians often make different decisions. Aim To perform a survey to measure the process of care and variations in decision-making in nonvariceal upper gastrointestinal tract haemorrhage (NVUGIH) and compare results between experts and non-experts. Methods We administered a vignette survey to elicit knowledge and beliefs about NVUGIH, including 13 'best practice' guidelines. We compared guideline compliance between experts and non-experts. Results One hundred and eighty-eight gastroenterologists responded (46%). Experts endorsed more 'best practices' than non-experts (93% vs. 85%; P = 0.002). Non-experts were more likely to endorse incorrectly bolus dosing vs. continuous infusion of intravenous proton pump inhibitors (PPIs; 92% vs. 64%; P = 0.005) and to select standard-channel vs. large-channel endoscopes in high-risk bleeding (100% vs. 85%; P = 0.04). There were wide variations within groups regarding the timing of nasogastric lavage, use of promotility agents, use of hemoclips and appropriateness of snaring clots overlying ulcers. Conclusions Experts are more likely to comply with NVUGIH guidelines. Non-experts diverge from experts in the dosing of PPIs and choice of endoscope in high-risk bleeding. Moreover, there are wide variations in key practices even within groups. This suggests that best practices have been generally well disseminated, but that persistent disconnects exist that should be further investigated. C1 [Jensen, D.; Spiegel, B. M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Esrailian, E.; Jensen, D.; Spiegel, B. M. R.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Esrailian, E.; Spiegel, B. M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ CORE, Los Angeles, CA 90095 USA. [Laine, L.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. [Dulai, G. S.] Kaiser So Calif, Portland, OR USA. [Eisen, G.] Oregon Hlth & Sci Univ, Portland, OR USA. [Spiegel, B. M. R.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Gralnek, I. M.] Ramban Med Ctr, Haifa, Israel. RP Spiegel, BMR (reprint author), 11301 Wilshire Blvd,Bldg 115,Room 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition [RCD03-179-2]; CURE Digestive Disease Research Center [NIH 2P30 DK 041301-17]; NIH K24 [NIH-NIDDK 1K24DK02650]; NIH-NIDDK [AM41301]; AstraZeneca [ESOM0396] FX Declaration of personal interests: Dr Spiegel is supported by a Veteran's Affairs Health Services Research and Development (HSR&D) Career Development Transition Award (RCD03-179-2). Drs. Esrailian, Jensen and Spiegel are supported by the CURE Digestive Disease Research Center (NIH 2P30 DK 041301-17). Dr Jensen is supported by an NIH K24 grant (NIH-NIDDK 1K24DK02650), and NIH-NIDDK AM41301. This study was supported by an investigator-initiated research grant by AstraZeneca. The authors had complete authority over all aspects of the study, including development of the hypotheses and analysis plan, development of data collection instruments, collection of data, analysis and interpretation of data and writing of the manuscript. Declaration of funding interests: This investigator-iniated study was funded in full by AstraZeneca, grant number ESOM0396. All aspects of the study conduct, interpretation, and writing were performed by the study authors without influence by the sponsor. NR 17 TC 13 Z9 13 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-2813 J9 ALIMENT PHARM THER JI Aliment. Pharmacol. Ther. PD NOV 15 PY 2008 VL 28 IS 10 BP 1199 EP 1208 DI 10.1111/j.1365-2036.2008.03838.x PG 10 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 361MK UT WOS:000260131600003 PM 18729846 ER PT J AU Maron, BJ Bonow, RO Salberg, L Roberts, WC Braunwald, E AF Maron, Barry J. Bonow, Robert O. Salberg, Lisa Roberts, William C. Braunwald, Eugene TI The First Patient Clinically Diagnosed With Hypertrophic Cardiomyopathy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SURVIVAL; STENOSIS; PROFILE AB It has now been 50 years since the initial clinical description of hypertrophic cardiomyopathy. In this regard, it is noteworthy that the first patient diagnosed with this disease has survived to date in good health with an active and productive lifestyle-albeit with heart transplantation necessitated by an aggressive disease course with progression to the end-stage phase. (C) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1418-1420) C1 [Maron, Barry J.] Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. [Bonow, Robert O.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Salberg, Lisa] Hypertroph Cardiomyopathy Assoc, Hibernia, NJ USA. [Roberts, William C.] Baylor Heart & Vasc Inst, Dallas, TX USA. [Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Maron, BJ (reprint author), Minneapolis Heart Inst Fdn, Hypertroph Cardiomyopathy Ctr, Minneapolis, MN USA. EM hcm.maron@mhif.org NR 13 TC 3 Z9 3 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2008 VL 102 IS 10 BP 1418 EP 1420 DI 10.1016/j.amjcard.2008.08.024 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 376OX UT WOS:000261194000025 PM 18993166 ER PT J AU Mergenhagen, KA Sherman, O AF Mergenhagen, Kari A. Sherman, Olga TI Elevated International Normalized Ratio after concurrent ingestion of cranberry sauce and warfarin SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE Anticoagulants; Drug interactions; Geriatrics; International normalized ratio; Vaccinium macrocarpon; Warfarin sodium ID JUICE AB Purpose. A case of increased International Normalized Ratio (INR) values in a patient receiving warfarin who consumed a large amount of cranberry sauce is reported. Summary. A 75-year-old Caucasian man with atrial fibrillation was taking 22.5 mg of warfarin weekly for 10 months and had maintained stable INR values between 2 and 3. During a clinic visit one week after Thanksgiving, the patient's INR was 4.8. The patient was extensively questioned about any changes in his diet, medications, and health. The patient reported consuming approximately 113 g of cranberry sauce for seven consecutive days before the clinic visit. He reported no other diet or health changes. The patient denied alcohol consumption, had not taken nutritional supplements, and did not miss or double any medication doses during this time period. There were no dosing changes or discernible compliance issues in the 10 months preceding the change in INR. The patient's complete blood cell count and results of a chemistry panel and liver function tests were within normal limits. He did not have any bleeding or bruising. The only identifiable change was the addition of store-bought cranberry sauce to his diet. The patient's warfarin dose was held for two days. Subsequently, the patient resumed warfarin at a dosage of 20 mg per week. Seven days after the patient discontinued the cranberry sauce, his INR returned to 2.2 and remained stable over the next month. Conclusion. Consumption of cranberry sauce led to an increase in INR values in a patient receiving warfarin. C1 [Mergenhagen, Kari A.; Sherman, Olga] James J Peters Vet Affairs Med Ctr, Coagulat Warfarin Lipid Clin, Bronx, NY 10468 USA. RP Mergenhagen, KA (reprint author), James J Peters Vet Affairs Med Ctr, Coagulat Warfarin Lipid Clin, 130 W Kingsbridge Rd 119, Bronx, NY 10468 USA. EM kari.mergenhagen2@va.gov NR 23 TC 4 Z9 6 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 2008 VL 65 IS 22 BP 2113 EP 2116 DI 10.2146/ajhp080135 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 372LG UT WOS:000260902500012 PM 18997138 ER PT J AU Kozora, E Arciniegas, DB Filley, CM West, SG Brown, M Miller, D Grimm, A Devore, MD Wingrove, C Zhang, LN AF Kozora, Elizabeth Arciniegas, David B. Filley, Christopher M. West, Sterling G. Brown, Mark Miller, David Grimm, Alex Devore, Maria D. Wingrove, Christy Zhang, Lening TI Cognitive and Neurologic Status in Patients With Systemic Lupus Erythematosus Without Major Neuropsychiatric Syndromes SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID MULTIPLE-SCLEROSIS; RATING-SCALE; IMPAIRMENT; PREVALENCE; DYSFUNCTION; MANIFESTATIONS; DEFINITIONS; ANTIBODIES; DEFICITS; FLUENCY AB Objective. To examine neuropsychological and neurologic functioning in systemic lupus erythematosus (SLE) patients without histories of overt neuropsychiatric disorders (non-NPSLE patients). Methods. Sixty-seven non-NPSLE patients and 29 healthy controls were administered a standardized neurologic examination and measures of cognition, depression, and self-reported cognitive functioning. Results. Non-NPSLE patients scored lower than controls on the total score of the neurologic examination (P < 0.0001). Item analysis indicated that the physician's description of mentation and mood was the only item that differed significantly between patients with SLE and controls (P = 0.004). Compared with controls, non-NPSLE patients had significantly higher rates of impairment on logical reasoning (P = 0.012) and verbal memory (P = 0.03), and trends toward greater impairment on visual attention (P = 0.06) and working memory (P = 0.098). There were no significant differences between non-NPSLE patients and controls on a cognitive impairment index (CII): 20.9% of non-NPSLE patients and 13.8% of controls were impaired. Patients with SLE scored higher on depressive symptoms (P < 0.0001) and perceived cognitive difficulties (P = 0.001) compared with controls. Conclusion. The utility of a standardized neurologic examination in SLE for excluding overt neurologic dysfunction and assuring a non-NPSLE group selection was demonstrated. In contrast to our earlier study, we did not find differences between non-NPSLE patients and controls on the CII Slightly lower CII scores in non-NPSLE patients and higher CII scores in controls may have reduced cognitive differences between these groups. Non-NPSLE patients demonstrate specific decline in the areas of attention, memory, and reasoning; continued studies of associated brain regions are warranted. C1 [Kozora, Elizabeth; Devore, Maria D.; Wingrove, Christy; Zhang, Lening] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. [Kozora, Elizabeth; Arciniegas, David B.; Filley, Christopher M.; West, Sterling G.; Brown, Mark; Miller, David; Grimm, Alex; Zhang, Lening] Univ Colorado Denver, Hlth Sci Ctr, Denver, CO USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Med & Res Ctr, 1400 Jackson St, Denver, CO 80206 USA. EM Kozorae@njc.org RI Arciniegas, David/A-3792-2009 FU National Institute of Musculoskeletal and Skin Diseases; NIH [R01-AR04915202] FX Supported by a grant from National Institute of Musculoskeletal and Skin Diseases, NIH (R01-AR04915202). NR 47 TC 29 Z9 30 U1 1 U2 2 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 NOV 15 PY 2008 VL 59 IS 11 BP 1639 EP 1646 DI 10.1002/art.24189 PG 8 WC Rheumatology SC Rheumatology GA 371TC UT WOS:000260853200015 PM 18975359 ER PT J AU Hur, W Velentza, A Kim, S Flatauer, L Jiang, XN Valente, D Mason, DE Suzuki, M Larson, B Zhang, JM Zagorska, A DiDonato, M Nagle, A Warmuth, M Balk, SP Peters, EC Gray, NS AF Hur, Wooyoung Velentza, Anastasia Kim, Sungjoon Flatauer, Laura Jiang, Xinnong Valente, David Mason, Daniel E. Suzuki, Melissa Larson, Brad Zhang, Jianming Zagorska, Anna DiDonato, Michael Nagle, Advait Warmuth, Markus Balk, Steven P. Peters, Eric C. Gray, Nathanael S. TI Clinical stage EGFR inhibitors irreversibly alkylate Bmx kinase SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Irreversible inhibitors; Quinazoline scaffold; EFGR; Tec-family kinase; Bmx; Reactive cysteine ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE; PROSTATE-CANCER; ETK/BMX; DOMAIN AB Irreversible HER/erbB inhibitors selectively inhibit HER-family kinases by targeting a unique cysteine residue located within the ATP-binding pocket. Sequence alignment reveals that this rare cysteine is also present in ten other protein kinases including all five Tec-family members. We demonstrate that the Tec-family kinase Bmx is potently inhibited by irreversible modi. cation at Cys496 by clinical stage EGFR inhibitors such as CI-1033. This cross-reactivity may have significant clinical implications. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Zhang, Jianming; Gray, Nathanael S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Hur, Wooyoung] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Velentza, Anastasia; Kim, Sungjoon; Flatauer, Laura; Valente, David; Mason, Daniel E.; DiDonato, Michael; Nagle, Advait; Warmuth, Markus; Peters, Eric C.] Genom Inst Novartis Res Fdn, San Diego, CA 92121 USA. [Jiang, Xinnong; Balk, Steven P.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Suzuki, Melissa; Larson, Brad] Invitrogen Corp, Madison, WI 53719 USA. [Zagorska, Anna] Univ Dundee, Coll Life Sci, MRC, Prot Phosphorylat Unit, Dundee, Scotland. RP Gray, NS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Seeley G Mudd Bldg,Room 628A,250 Longwood Ave, Boston, MA 02115 USA. EM nathanael_gray@dfci.harvard.edu FU NCI NIH HHS [R01 CA130876, R01 CA130876-01A1]; NIGMS NIH HHS [P41 GM079575, P41 GM079575-01] NR 13 TC 23 Z9 24 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 15 PY 2008 VL 18 IS 22 BP 5916 EP 5919 DI 10.1016/j.bmcl.2008.07.062 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 373JB UT WOS:000260966800021 PM 18667312 ER PT J AU Westerberg, LS de la Fuente, MA Wermeling, F Ochs, HD Karlsson, MCI Snapper, SB Notarangelo, LD AF Westerberg, Lisa S. de la Fuente, Miguel A. Wermeling, Fredrik Ochs, Hans D. Karlsson, Mikael C. I. Snapper, Scott B. Notarangelo, Luigi D. TI WASP confers selective advantage for specific hematopoietic cell populations and serves a unique role in marginal zone B-cell homeostasis and function SO BLOOD LA English DT Article ID WISKOTT-ALDRICH-SYNDROME; SOCIETY-FOR-IMMUNODEFICIENCIES; REGULATORY T-CELLS; SYNDROME PROTEIN; IN-VIVO; MARROW TRANSPLANTATION; DEFICIENCY LEADS; APOPTOTIC CELLS; GENE-TRANSFER; X-CHROMOSOME AB Development of hematopoietic cells depends on a dynamic actin cytoskeleton. Here we demonstrate that expression of the cytoskeletal regulator WASP, mutated in the Wiskott-Aldrich syndrome, provides selective advantage for the development of naturally occurring regulatory T cells, natural killer T cells, CD4(+) and CD8(+) T lymphocytes, marginal zone (MZ) B cells, MZ macrophages, and platelets. To define the relative contribution of MZ B cells and MZ macrophages for MZ development, we generated wild-type and WASP-deficient bone marrow chimeric mice, with full restoration of the MZ. However, even in the presence of MZ macrophages, only 10% of MZ B cells were of WASP-deficient origin. We show that WASP-deficient MZ B cells hyperproliferate in vivo and fail to respond to sphingosine-1-phosphate, a crucial chemoattractant for MZ B-cell positioning. Abnormalities of the MZ compartment in WASP(-/-) mice lead to aberrant uptake of Staphylococcus aureus and to a reduced immune response to TNP-Ficoll. Moreover, WASP-deficient mice have increased levels of "natural" IgM antibodies. Our findings reveal that WASP regulates both development and function of hematopoietic cells. We demonstrate that WASP deficiency leads to an aberrant MZ that may affect responses to blood-borne pathogens and peripheral B-cell tolerance. (Blood. 2008; 112: 4139-4147) C1 [Westerberg, Lisa S.; Snapper, Scott B.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Westerberg, Lisa S.; Snapper, Scott B.] Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. [Westerberg, Lisa S.; Snapper, Scott B.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [de la Fuente, Miguel A.; Notarangelo, Luigi D.] Childrens Hosp, Div Immunol, Boston, MA 02115 USA. [de la Fuente, Miguel A.; Notarangelo, Luigi D.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Wermeling, Fredrik; Karlsson, Mikael C. I.] Karolinska Inst, Dept Med, Unit Clin Allergy Res, Stockholm, Sweden. [Ochs, Hans D.] Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Jackson 825C,55 Fruit St, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu; Luigi.Notarangelo@childrens.harvard.edu RI de la Fuente, Miiguel /C-7478-2013; Notarangelo, Luigi/F-9718-2016; OI de la Fuente, Miiguel /0000-0003-4619-8756; Notarangelo, Luigi/0000-0002-8335-0262; Wermeling, Fredrik/0000-0001-9633-677X; Westerberg, Lisa/0000-0003-2943-2192 FU Swedish Society for Medical Research; National Institutes of Health [HL59561, AI50950, P01HL059561-A11] FX This work was supported by a postdoctoral fellowship from the Swedish Society for Medical Research (L. W.) and National Institutes of Health grants HL59561 and AI50950 (S. B. S.) and grant P01HL059561-A11 (S. B. S. and L. S. N.). NR 49 TC 60 Z9 64 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 NOV 15 PY 2008 VL 112 IS 10 BP 4139 EP 4147 DI 10.1182/blood-2008-02-140715 PG 9 WC Hematology SC Hematology GA 369JU UT WOS:000260691300034 PM 18772454 ER PT J AU Kurtzberg, J Prasad, VK Carter, SL Wagner, JE Baxter-Lowe, LA Wall, D Kapoor, N Guinan, EC Feig, SA Wagner, EL Kernan, NA AF Kurtzberg, Joanne Prasad, Vinod K. Carter, Shelly L. Wagner, John E. Baxter-Lowe, Lee Ann Wall, Donna Kapoor, Neena Guinan, Eva C. Feig, Stephen A. Wagner, Elizabeth L. Kernan, Nancy A. CA COBLT Steering Comm TI Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; BONE-MARROW; ACUTE-LEUKEMIA; CHILDREN; RECONSTITUTION; RECIPIENTS; ADULTS AB Outcomes of unrelated donor cord blood transplantation in 191 hematologic malignancy children (median age, 7.7 years; median weight, 25.9 kg) enrolled between 1999 and 2003 were studied (median follow-up, 27.4 months) in a prospective phase 2 multicenter trial. Human leukocyte antigen (HLA) matching at enrollment was 6/6 (n = 17), 5/6 (n = 58), 4/6 (n = 111), or 3/6 (n = 5) by low-resolution HLA-A, -B, and high-resolution (HR) DRB1. Retrospectively, 179 pairs were HLA typed by HR. The median precryopreservation total nucleated cell (TNC) dose was 5.1 x 107 TNC/kg (range, 1.5-23.7) with 3.9 x 107 TNC/kg (range, 0.8-22.8) infused. The median time to engraftment (absolute neutrophil count > 500/mm(3) and platelets 50 000/mu L) was 27 and 174 days. The cumulative incidence of neutrophil engraftment by day 42 was 79.9% (95% confidence interval [CI], 75.1%-85.2%); acute grades III/IV GVHD by day 100 was 19.5% ( 95% CI, 13.9%-25.5%); and chronic GVHD at 2 years was 20.8% (95% CI, 14.8%-27.7%). HR matching decreased the probability of severe acute GVHD. The cumulative incidence of relapse at 2 years was 19.9% (95% CI, 14.8%-25.7%). The probabilities of 6-month and 2-year survivals were 67.4% and 49.5%. Unrelated donor cord blood transplantation from partially HLA-mismatched units can cure many children with leukemias. The study was registered at www. clinicaltrials. gov as #NCT00000603. (Blood. 2008; 112: 4318-4327) C1 [Kurtzberg, Joanne; Prasad, Vinod K.] Duke Univ, Med Ctr, Durham, NC 27710 USA. [Carter, Shelly L.] EMMES Corp, Rockville, MD USA. [Wagner, John E.] Univ Minnesota, Minneapolis, MN USA. [Baxter-Lowe, Lee Ann] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Wall, Donna] Texas Transplant Inst, San Antonio, TX USA. [Kapoor, Neena] Childrens Hosp, Los Angeles, CA 90027 USA. [Guinan, Eva C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Feig, Stephen A.] Mattel Childrens Hosp, Los Angeles, CA USA. [Wagner, Elizabeth L.] NHLBI, Bethesda, MD 20892 USA. [Kernan, Nancy A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Kurtzberg, J (reprint author), Duke Univ, Med Ctr, Box 3350, Durham, NC 27710 USA. EM kurtz001@mc.duke.edu OI Kernan, Nancy/0000-0003-1417-1823 FU NHLBI NIH HHS [N01-HB 67135, N01-HB 67139, N01-HB-67132, N01HB67132, N01HB67135, N01HB67138, N01HB67139] NR 25 TC 178 Z9 188 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2008 VL 112 IS 10 BP 4318 EP 4327 DI 10.1182/blood-2007-06-098020 PG 10 WC Hematology SC Hematology GA 369JU UT WOS:000260691300056 PM 18723429 ER PT J AU Benimetskaya, L Wu, S Voskresenskiy, AM Echart, C Zhou, JF Shin, J Iacobelli, M Richardson, P Ayyanar, K Stein, CA AF Benimetskaya, Luba Wu, Sijian Voskresenskiy, Anatoliy M. Echart, Cinara Zhou, Jin-Feng Shin, Joongho Iacobelli, Massimo Richardson, Paul Ayyanar, Kanyalakshmi Stein, C. A. TI Angiogenesis alteration by defibrotide: implications for its mechanism of action in severe hepatic veno-occlusive disease SO BLOOD LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; SUBENDOTHELIAL EXTRACELLULAR-MATRIX; SINUSOIDAL OBSTRUCTION SYNDROME; BONE-MARROW-TRANSPLANTATION; HEPARIN-LIKE MOLECULES; HIGH-RISK POPULATION; ENDOTHELIAL-CELLS; SIGNIFICANT TOXICITY; COMPASSIONATE-USE; RECEPTOR AB Defibrotide (DF) is a mixture of porcine-derived single-stranded phosphodiester oligonucleotides (9-80-mer; average, 50-mer) that has been successfully used to treat severe hepatic veno-occlusive disease (sVOD) with multiorgan failure (MOF) in patients who have received cytotoxic chemotherapy in preparation for bone marrow transplantation. However, its mechanism of action is unknown. Herein, we show that DF and phosphodiester oligonucleotides can bind to heparin-binding proteins (eg, basic fibroblast growth factor [bFGF] but not vascular endothelial growth factor [VEGF] 165) with low nanomolar affinity. This binding occurred in a length- and concentration-dependent manner. DF can mobilize proangiogenic factors such as bFGF from their depot or storage sites on bovine corneal endothelial matrix. However, these molecules do not interfere with high-affinity binding of bFGF to FGFR1 IIIc but can replace heparin as a required cofactor for binding and hence cellular mitogenesis. DF also protects bFGF against digestion by trypsin and chymotrypsin and from air oxidation. In addition, DF binds to collagen I with low nanomolar affinity and can promote human microvascular endothelial cell-1 (HMEC-1) cell mitogenesis and tubular morphogenesis in three-dimensional collagen I gels. Thus, our data suggest that DF may provide a stimulus to the sinusoidal endothelium of a liver that has suffered a severe angiotoxic event, thus helping to ameliorate the clinical sVOD/MOF syndrome. (Blood. 2008; 112: 4343-4352) C1 [Benimetskaya, Luba; Wu, Sijian; Voskresenskiy, Anatoliy M.; Zhou, Jin-Feng; Shin, Joongho; Ayyanar, Kanyalakshmi; Stein, C. A.] Montefiore Med Ctr, Albert Einstein Montefiore Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. [Echart, Cinara; Iacobelli, Massimo] Gentium SpA, Villa Guardia, Italy. [Richardson, Paul] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stein, CA (reprint author), Montefiore Med Ctr, Albert Einstein Montefiore Canc Ctr, Dept Oncol, 111 E 210th St, Bronx, NY 10467 USA. EM cstein@montefiore.org FU Gentium S. p. A (Como, Italy; C.S.); Rick Corman Foundation FX This work was supported by funding from Gentium S. p. A. (Como, Italy; C.S.), and from the Rick Corman Foundation (P.R. and C.S.). NR 58 TC 22 Z9 25 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2008 VL 112 IS 10 BP 4343 EP 4352 DI 10.1182/blood-2008-04-149682 PG 10 WC Hematology SC Hematology GA 369JU UT WOS:000260691300059 PM 18711003 ER PT J AU Schwartz, GF Hughes, KS Lynch, HT Fabian, CJ Fentiman, IS Robson, ME Domchek, SM Hartmann, LC Holland, R Winchester, DJ AF Schwartz, Gordon F. Hughes, Kevin S. Lynch, Henry T. Fabian, Carol J. Fentiman, Ian S. Robson, Mark E. Domchek, Susan M. Hartmann, Lynn C. Holland, Roland Winchester, David J. CA Consensus Conference Comm TI Proceedings of the International Consensus Conference on Breast Cancer Risk, Genetics, & Risk Management, April, 2007 SO CANCER LA English DT Editorial Material DE breast cancer; risk factors; BRCA mutations; international conference; patient management guidelines AB A consensus conference including 30 experts was held in April, 2007, to discuss risk factors for breast cancer and their management. Four categories of risk were outlined, from "average" through "very high" risk, the latter including individuals with high penetrance BRCA1/2 gene mutations. Guidelines for management of patients in each of these categories were discussed, with the major portion of the conference devoted to individuals with BRCA1/2 mutations. Prevalence of these mutations in the general population was estimated to be 1 in 250-500 individuals, with an increased prevalence in Ashkenazi Jews and other founder groups. Risk-reduction strategies for these individuals included surveillance, with or without chemoprevention drugs, or surgical procedures to remove the organs at risk, ie, bilateral mastectomy and/or bilateral salpingo-oophorectomy. These risk reduction strategies were evaluated fully, and recommendations were made for the care of patients in each risk category. These guidelines for patient care were approved by the entire group of experts. Cancer 2008;113:2627-37. (C) 2008 American Cancer Society. C1 [Schwartz, Gordon F.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, Philadelphia, PA 19107 USA. [Hughes, Kevin S.] Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. [Hughes, Kevin S.] Massachusetts Gen Hosp, Avon Comprehens Breast Ctr, Boston, MA 02114 USA. [Lynch, Henry T.] Creighton Univ, Sch Med, Dept Prevent Med, Omaha, NE 68178 USA. [Fabian, Carol J.] Univ Kansas, Med Ctr, Dept Med, Breast Canc Prevent Ctr, Kansas City, KS 66103 USA. [Fentiman, Ian S.] Guys & St Thomas NHS Trust, Dept Surg Oncol, London, England. [Robson, Mark E.] Mem Sloan Kettering Canc Ctr, Clin Genet Serv, New York, NY 10021 USA. [Domchek, Susan M.] Univ Penn, Med Ctr, Dept Canc Res, Philadelphia, PA 19104 USA. [Hartmann, Lynn C.] Mayo Clin, Ctr Canc, Dept Oncol, Rochester, MN USA. [Holland, Roland] Univ Nijmegen Hosp, Ctr Breast Canc Screening, NL-6500 HB Nijmegen, Netherlands. [Winchester, David J.] Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Schwartz, GF (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Surg, 1015 Chestnut St,Suite 510, Philadelphia, PA 19107 USA. EM gordonschwartz@yahoo.com OI Hughes, Kevin/0000-0003-4084-6484; Howell, Anthony/0000-0002-6233-719X; Robson, Mark/0000-0002-3109-1692 NR 0 TC 47 Z9 48 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 BP 2627 EP 2637 DI 10.1002/cncr.23903 PG 11 WC Oncology SC Oncology GA 372PV UT WOS:000260914400003 PM 18853415 ER PT J AU Lin, NU Claus, E Sohl, J Razzak, AR Arnaout, A Winer, EP AF Lin, Nancy U. Claus, Elizabeth Sohl, Jessica Razzak, Abdul R. Arnaout, Amal Winer, Eric P. TI Sites of Distant Recurrence and Clinical Outcomes in Patients With Metastatic Triple-negative Breast Cancer High Incidence of Central Nervous System Metastases SO CANCER LA English DT Article DE triple-negative breast cancer; basal-like breast cancer; brain metastases; survival; central nervous system recurrence ID TRASTUZUMAB-BASED THERAPY; BRAIN METASTASES; GENE-EXPRESSION; CNS METASTASES; PHASE-II; SURVIVAL; CARCINOMA; SUBTYPES; WOMEN; PATTERNS AB BACKGROUND. The purpose of the current study was to characterize the Outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence. METHODS. Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified. RESULTS. The median survival front time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death. CONCLUSIONS. Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed. Cancer 2008; 113:2638-45. (C) 2008 American Cancer Society. C1 [Lin, Nancy U.; Sohl, Jessica; Razzak, Abdul R.; Arnaout, Amal; Winer, Eric P.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Claus, Elizabeth] Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. [Claus, Elizabeth] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. RP Lin, NU (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM nlin@partners.org FU Breast Cancer Research Foundation; Hurricane Voices Junior Faculty Award; American Society of Clinical Oncology Career Development Award; Karen Webster and David Evans Research Fund; National Cancer Institute Specialized Program in Research Excellence in Breast Cancer at DF/HCC [CA89393]; Susan G. Komen Breast Cancer Foundation; NIH [R01-CA81393] FX Supported by the Breast Cancer Research Foundation, the Hurricane Voices Junior Faculty Award, the American Society of Clinical Oncology Career Development Award, the Karen Webster and David Evans Research Fund, the National Cancer Institute Specialized Program in Research Excellence in Breast Cancer at DF/HCC (CA89393), the Susan G. Komen Breast Cancer Foundation, and NIH R01-CA81393 (to E.C.). NR 39 TC 199 Z9 216 U1 2 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 BP 2638 EP 2645 DI 10.1002/cncr.23930 PG 8 WC Oncology SC Oncology GA 372PV UT WOS:000260914400004 PM 18833576 ER PT J AU Elting, LS Keefe, DM Sonis, ST Garden, AS Spijkervet, FKL Barasch, A Tishler, RB Canty, TP Kudrimoti, MK Vera-Lionch, M AF Elting, Linda S. Keefe, Dorothy M. Sonis, Stephen T. Garden, Adam S. Spijkervet, F. K. L. Barasch, Andrei Tishler, Roy B. Canty, Thomas P. Kudrimoti, Mahesh K. Vera-Lionch, Montserrat CA Burden Illness Head & Neck Writing TI Patient-reported Measurements of Oral Mucositis in Head and Neck Cancer Patients Treated With Radiotherapy With or Without Chemotherapy Demonstration of Increased Frequency, Severity, Resistance to Palliation, and Impact on Quality of Life SO CANCER LA English DT Article; Proceedings Paper CT 49th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology (ASTRO) CY OCT 27-NOV 01, 2007 CL Los Angeles, CA SP Amer Soc Therapeut Radiol & Oncol (ASTRO) DE mucositis; radiation therapy; head and neck cancer; patient-reported outcomes; quality of life ID MODULATED RADIATION-THERAPY; FUNCTIONAL ASSESSMENT; OROPHARYNGEAL CARCINOMA; MEANINGFUL CHANGE; QUESTIONNAIRE; OUTCOMES; TRIAL; CONSEQUENCES; FLUOROURACIL; DOCETAXEL AB BACKGROUND. I-lie risk, severity, and patient-reported outcomes of radiation-induced mucositis among head and neck cancer patients were prospectively estimated. METHODS. A validated, patient-reported questionnaire (OMDQ), the FACT quality of life (QOL), and the Functional Assessment of Chronic Illness Therapy (FACIT) fatigue scales Were used to measure mucositis (reported as mouth and throat Soreness), daily functioning, and Use of analgesics. Patients were studied before radiotherapy (RT), daily during RT, and for 4 weeks after RT. RESULTS. contrary to previous reports, the risk of mucositis was virtually identical in the 126 patients with oral cavity or oropharynx tumors (99% overall; 85% grade 3-4) compared with 65 patients with tumors of the larynx or hypopharynx (98% overall; 77% grade 3-4). The mean QOL score decreased significantly during RT, from 85.1 at baseline to 69.0 at Week 6, corresponding with the peak of mucositis severity The mean functional status score decreased by 33% from 18.3 at baseline to 12.3 at week 6. The impact of mucositis on QOL was proportional to its severity, although even a score of I or 2 (mild or moderate) was associated with a significant reduction in QOL (from 93.6 at baseline to 74.7 at Week 6). Despite increases in analgesic use from 34% at baseline to 80% at Week 6, mean mucositis scores exceeded 2.5 at Week 6. CONCLUSIONS. Mucositis occurs among virtually all patients who are Undergoing radiation treatment of head and neck cancers. The detrimental effects on QOL and functional status are significant, and opioid analgesia provides inadequate relief. Preventive rather than symptom palliation measures are needed. Cancer 2008;113:2704-13. (C) 2008 American Cancer Society. C1 [Elting, Linda S.] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. [Keefe, Dorothy M.] Royal Adelaide Hosp, Ctr Canc, Dept Oncol, Adelaide, SA 5000, Australia. [Sonis, Stephen T.] Harvard Univ, Sch Med, Dept Oral Med Infect & Immun, Boston, MA USA. [Sonis, Stephen T.] Dana Farber Canc Inst, Dept Surg, Div Oral Med, Boston, MA 02115 USA. [Garden, Adam S.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. [Spijkervet, F. K. L.] Univ Groningen, Univ Med Ctr Groningen, Dept Maxillofacial Surg, NL-9713 AV Groningen, Netherlands. [Barasch, Andrei] Univ Alabama, Med Ctr, Birmingham, AL 35294 USA. [Tishler, Roy B.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. [Tishler, Roy B.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Canty, Thomas P.] Arizona Oncol Serv Fdn, Phoenix, AZ USA. [Kudrimoti, Mahesh K.] Univ Kentucky, Coll Med, Chandler Med Ctr, Lexington, KY USA. [Vera-Lionch, Montserrat] Policy Anal Inc, Brookline, MA USA. RP Elting, LS (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Biostat, 1515 Holcombe Blvd,Unit 1411, Houston, TX 77030 USA. EM lelting@mdanderson.org NR 29 TC 103 Z9 108 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD NOV 15 PY 2008 VL 113 IS 10 BP 2704 EP 2713 DI 10.1002/cncr.23898 PG 10 WC Oncology SC Oncology GA 372PV UT WOS:000260914400012 PM 18973181 ER PT J AU Tu, C Ortega-Cava, CF Chen, GS Fernandes, ND Cavallo-Medved, D Sloane, BF Band, V Band, H AF Tu, Chun Ortega-Cava, Cesar F. Chen, Gengsheng Fernandes, Norvin D. Cavallo-Medved, Dora Sloane, Bonnie F. Band, Vimla Band, Hamid TI Lysosomal Cathepsin B Participates in the Podosome-Mediated Extracellular Matrix Degradation and Invasion via Secreted Lysosomes in v-Src Fibroblasts SO CANCER RESEARCH LA English DT Article ID OSTEOCLASTIC BONE-RESORPTION; PLASMINOGEN-ACTIVATOR; CYSTEINE CATHEPSINS; PLASMA-MEMBRANE; TRANSFORMED-CELLS; CARCINOMA-CELLS; MELANOMA-CELLS; CANCER-CELLS; H+-ATPASE; C-SRC AB Podosomes mediate cell migration and invasion by coordinating the reorganization of actin cytoskeleton and focal matrix degradation. MMP and serine proteases have been found to function at podosomes. The lysosomal cysteine cathepsins, a third major class of matrix-degrading enzymes involved in tumor invasion and tissue remodeling, have yet to be linked to podosomes with the exception of cathepsin K in osteoclasts. Using inhibitors and shRNA-mediated depletion, we show that cathepsin B participates in podosomes-mediated focal matrix degradation and invasion in v-Src-transformed fibroblasts. We observed that lysosomal marker LAMP-1 localized at the center of podosome rosettes protruding into extracellular matrix using confocal microscopy. Time-lapse live-cell imaging revealed that lysosomal vesicles moved to and fused with podosomes. Disruption of lysosomal pH gradient with Bafilomycin A1, chloroquine, or ammonium chloride greatly enhanced the formation of podosomes and increased the matrix degradation. Live-cell imaging showed that actin structures, induced shortly after Bafilomycin A1 treatment, were closely associated with lysosomes. Overall, our results suggest that cathepsin B, delivered by lysosomal vesicles, is involved in the matrix degradtion of podosomes. [Cancer Res 2008;68(22):9147-56] C1 [Tu, Chun; Ortega-Cava, Cesar F.; Band, Hamid] Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. [Tu, Chun; Ortega-Cava, Cesar F.; Band, Vimla; Band, Hamid] Univ Nebraska, Med Ctr, UNMC Eppley Canc Ctr, Omaha, NE 68198 USA. [Band, Hamid] Univ Nebraska, Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. [Band, Vimla] Univ Nebraska, Med Ctr, Coll Med, Dept Genet Coll Biol & Anat, Omaha, NE 68198 USA. [Cavallo-Medved, Dora; Sloane, Bonnie F.] Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. [Cavallo-Medved, Dora; Sloane, Bonnie F.] Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. [Tu, Chun; Ortega-Cava, Cesar F.; Chen, Gengsheng; Band, Vimla; Band, Hamid] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston NW Healthcare Res Inst, Dept Med,Div Mol Oncol,Feinberg Sch Med, Evanston, IL USA. [Tu, Chun; Ortega-Cava, Cesar F.; Chen, Gengsheng; Band, Vimla; Band, Hamid] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston NW Healthcare Res Inst, Dept Med,Div Canc Biol,Feinberg Sch Med, Evanston, IL USA. [Tu, Chun; Ortega-Cava, Cesar F.; Chen, Gengsheng; Band, Vimla; Band, Hamid] Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL USA. [Fernandes, Norvin D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Band, H (reprint author), Univ Nebraska, Med Ctr, Eppley Inst, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM hband@unmc.edu FU NIH [CA 87986, CA 76118, CA 99900, CA 116552, CA99163, CA94143, CA96844, CA81076]; Department of Defense Breast Cancer Research [DAMD17-02-1-0508]; National Cancer Institute (NCI) Cancer Center of Nanotechnology Excellence [NCI IU54, CA119341-01]; NCI Breast, Cancer Specialized programs of Research Excellence; AVON Breast Cancer Fund at Robert H. Luric Cancer Center, Northwestern University; H Foundation, Chicago, IL; Jean Ruggles-Romoser Chair of Cancer Research; Duckworth Family Chair of Breast Cancer Research; Nebraska Research Initiative; Eppley Cancer center FX Grant support: the NIH grants CA 87986, CA 76118, CA 99900, CA 116552, and CA99163 (H. Band), and CA94143, CA96844, and CA81076 (V. Band): Department of Defense Breast Cancer Research Grants DAMD17-02-1-0508 (V. Band); the National Cancer Institute (NCI) Cancer Center of Nanotechnology Excellence Grant NCI IU54 CA119341-01 (H. Band and V. Band); the NCI Breast, Cancer Specialized programs of Research Excellence and AVON Breast Cancer Fund at Robert H. Luric Cancer Center, Northwestern University; the H Foundation, Chicago, IL; and the Jean Ruggles-Romoser Chair of Cancer Research (H. Band) and the Duckworth Family Chair of Breast Cancer Research (V. Band).; 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.; We thank Dr. Joan Brugge for v-Src, plasmid, Dr. Qingshen Gao, Janice Taylor, and James Talaska of the Confocal laser Scanning microscope Core Facility at the University of Nebraska Medical Center; the latter is supported by the Nebraska Research Initiative and the Eppley Cancer center, and the members of the Band laboratories for helpful suggestions and discussion. NR 50 TC 48 Z9 49 U1 0 U2 7 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 NOV 15 PY 2008 VL 68 IS 22 BP 9147 EP 9156 DI 10.1158/0008-5472.CAN-07-5127 PG 10 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600009 PM 19010886 ER PT J AU Minkis, K Kavanagh, DG Alter, G Bogunovic, D O'Neill, D Adams, S Pavlick, A Walker, BD Brockman, MA Gandhi, RT Bhardwaj, N AF Minkis, Kira Kavanagh, Daniel G. Alter, Galit Bogunovic, Dusan O'Neill, David Adams, Sylvia Pavlick, Anna Walker, Bruce D. Brockman, Mark A. Gandhi, Rajesh T. Bhardwaj, Nina TI Type 2 Bias of T Cells Expanded from the Blood of Melanoma Patients Switched to Type 1 by IL-12p70 mRNA-Transfected Dendritic Cells SO CANCER RESEARCH LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-12; ANTITUMOR IMMUNITY; IN-VITRO; METASTATIC MELANOMA; MALIGNANT-MELANOMA; TUMOR; IMMUNOTHERAPY; RESPONSES; CANCER; LYMPHOCYTES AB Melanoma patients may exhibit a T(H)2-skewed cytokine profile within blood and tumor-infiltrating lymphocytes. Therapies that induce beneficial T(H)1-type tumor-specific immune responses, therefore, are highly desirable. Dendritic cells (DC) are widely used as immune adjuvants for cancer. Before their administration, DC are generally induced to mature with a cocktail of recombinant cytokines [interleukin (IL)-1 beta, tumor necrosis factor alpha, and IL-6] and prostaglandin E-2 (PGE(2)), which is added to preserve the ability of DC to migrate to draining lymph nodes. However, PGE(2) suppresses the production of IL-12p70, a cytokine essential for differentiation of T(H)1 responses. In this study, human DC were transfected with IL-12p70 mRNA and tested for their ability to alter the T(H)2 type bias manifested by blood T cells of patients with melanoma. Transfected DC secreted high levels of bioactive IL-12p70, as indicated by their capacity to enhance natural killer cell activity, skew T(H)1 responses in allogeneic mixed lymphocyte reactions through reduction of IL-4 and IL-5, and prime CD8(+) T cells to the melanoma-associated antigen Melan A/MART-1. Furthermore, T-cell lines primed in vitro from the blood of melanoma patients showed strong type 2 skewing that was dramatically reversed by IL-12p70 transfection of autologons DC. Thus, IL-12p70 transfection of clinical DC preparations may enhance type 1 antitumor responses and may thereby contribute to effective immune-based therapy. [Cancer Res 2008;68(22):9441-50] C1 [Bhardwaj, Nina] NYU, Med Ctr, Sch Med, New York, NY 10016 USA. [Walker, Bruce D.; Brockman, Mark A.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Kavanagh, Daniel G.; Alter, Galit; Walker, Bruce D.; Brockman, Mark A.; Gandhi, Rajesh T.; Bhardwaj, Nina] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Kavanagh, Daniel G.; Alter, Galit; Walker, Bruce D.; Brockman, Mark A.; Gandhi, Rajesh T.; Bhardwaj, Nina] Harvard Univ, Sch Med, Boston, MA USA. RP Bhardwaj, N (reprint author), NYU, Med Ctr, Sch Med, 550 1st Ave, New York, NY 10016 USA. EM Nina.Bhardwaj@nyumc.org OI Brockman, Mark/0000-0001-6432-1426 FU NIH [F32 AI058457-03, R01 AI066992-01AI, R01 044628]; Burroughs Wellcome Foundations; Elizabeth Glaser Pediatric AIDS Foundation; Howard Hughes Medical Institute FX Grant support: NIH grants F32 AI058457-03 (D.G. Kavanagh), R01 AI066992-01AI (R.T. Gandhi), R01 044628 (N. Bhardwaj), and R01 1061684 (N. Bhardwaj); the Doris Duke, Emerald, and Burroughs Wellcome Foundations and the Elizabeth Glaser Pediatric AIDS Foundation (N. Bhardwaj); and the Howard Hughes Medical Institute (M.A. Brockman and B.D. Walker). NR 49 TC 31 Z9 34 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 NOV 15 PY 2008 VL 68 IS 22 BP 9441 EP 9450 DI 10.1158/0008-5472.CAN-08-0900 PG 10 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600042 PM 19010919 ER PT J AU Nikolsky, Y Sviridov, E Yao, J Dosymbekov, D Ustyansky, V Kaznacheev, V Dezso, Z Mulvey, L Macconaill, LE Winckler, W Serebryiskaya, T Nikolskaya, T Polyak, K AF Nikolsky, Yuri Sviridov, Evgeny Yao, Jun Dosymbekov, Damir Ustyansky, Vadirn Kaznacheev, Valery Dezso, Zoltan Mulvey, Laura Macconaill, Laura E. Winckler, Wendy Serebryiskaya, Tatiana Nikolskaya, Tatiana Polyak, Kornelia TI Genome-Wide Functional Synergy between Amplified and Mutated Genes in Human Breast Cancer SO CANCER RESEARCH LA English DT Article ID COLORECTAL CANCERS; HYBRIDIZATION; PATTERNS; FREQUENT AB A single cancer cell contains large numbers of genetic alterations that in combination create the malignant phenotype. However, whether amplified and mutated genes form functional and physical interaction networks that could explain the selection for cells with combined alterations is unknown. To investigate this issue, we characterized copy number alterations in 191 breast tumors using dense single nucleotide polymorphism arrays and identified 1,747 genes with copy number gain organized into 30 amplicons. Amplicons were distributed unequally throughout the genome. Each amplicon had distinct enrichment pattern in pathways, networks, and molecular functions, but genes within individual amplicons did not form coherent functional units. Genes in amplicons included all major tumorigenic pathways and were highly enriched in breast cancer-causative genes. In contrast, 1,188 genes with somatic mutations in breast cancer were distributed randomly over the genome, did not represent a functionally cohesive gene set, and were relatively less enriched in breast cancer marker genes. Mutated and gained genes did not show statisticalty signifiicant overlap but were highly synergistic in populating key tumorigenic pathways including transforming growth factor beta, WNT, fibroblast growth factor, and PIP3 signaling. In general, mutated genes were more frequently upstream of gained genes in transcription regulation signaling than vice versa, suggesting that mutated genes are mainly regulators, whereas gained genes are mostly regulated. ESR1 was the major transcription factor regulating amplified but not mutated genes. Our results support the hypothesis that multiple genetic events, including copy number gains and somatic mutations, are necessary for establishing the malignant cell phenotype. [Cancer Res 2008;68(22):9532-40] C1 [Macconaill, Laura E.; Winckler, Wendy; Polyak, Kornelia] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Nikolsky, Yuri; Ustyansky, Vadirn; Dezso, Zoltan; Nikolskaya, Tatiana] GeneGo Inc, St Joseph, MI USA. [Yao, Jun; Mulvey, Laura; Polyak, Kornelia] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sviridov, Evgeny; Dosymbekov, Damir; Kaznacheev, Valery; Serebryiskaya, Tatiana; Nikolskaya, Tatiana] NI Vavilov Gen Genet Res Inst, Moscow 117809, Russia. [Yao, Jun; Polyak, Kornelia] Harvard Univ, Sch Med, Boston, MA USA. [Mulvey, Laura] Harvard Univ, Cambridge, MA 02138 USA. [Macconaill, Laura E.; Winckler, Wendy] Broad Inst, Cambridge, MA USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Ctr Canc Genome Discovery, 44 Binney St D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu RI Nikolskaya, Tatiana/M-5008-2013 FU National Cancer Institute [CA89393, CA94074]; NCI [CA134175, CA112828]; GeneGo, Inc FX Grant support: National Cancer Institute (CA89393 and CA94074) grants (K. Polyak). NCI (CA134175) to Y. Nikolsky, and NCI (CA112828) to T. Nikolskaya, and by GeneGo, Inc. NR 26 TC 51 Z9 53 U1 0 U2 6 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 NOV 15 PY 2008 VL 68 IS 22 BP 9532 EP 9540 DI 10.1158/0008-5472.CAN-08-3082 PG 9 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600053 PM 19010930 ER PT J AU Rocha-Singh, K Jaff, MR Kelley, EL AF Rocha-Singh, Krishna Jaff, Michael R. Kelley, E. Lynne CA RENAISSANCE Trial Investigators TI Renal Artery Stenting With Noninvasive Duplex Ultrasound Follow-up: 3-Year Results From the RENAISSANCE Renal Stent Trial SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE atherosclerosis; kidney disease; percutaneous intervention ID BALLOON ANGIOPLASTY; STENOSIS; ULTRASONOGRAPHY; HYPERTENSION; RESTENOSIS; DIAGNOSIS; INDEX AB Objective: The multicenter, single-arm RENAISSANCE trial evaluated outcomes in patients with progressive atherosclerotic renal artery stenosis (ARAS) treated with the Express (TM) Renal Premounted Stent System (Boston Scientific, Natick, MA). Background: Renal artery stenting may prevent the morbidity and mortality of surgical revascularization and high restenosis rates of percutaneous renal angioplasty (PTRA). Renal artery duplex ultrasonography (DUS) offers an alternative to traditional invasive poststenting angiographic surveillance, though concordance with angiography for in-stent restenosis has yet to be validated independently. Methods: RENAISSANCE enrolled 100 patients (117 lesions) with de novo or restenotic ostial atherosclerotic lesions <= 15 mm long in vessels >= 4.0 and <= 7.0 mm diameter with diameter stenosis >= 70%. The primary endpoint, 9-month binary restenosis, was compared to an objective performance criterion (OPC) of 40% for published PTRA results. Follow-up was conducted through 3 years. Results: Technical and procedural success was both 99%. Follow-up angiography, triggered clinically or by ultrasonography, revealed 21.3% binary restenosis at 9 months, which was superior to the OPC (P < 0.0001). Concordance between ultrasonography and angiography for detection of binary restenosis at 9 months was 87%. Peak systolic velocity and renal-to-aortic ratio were both significantly improved compared to baseline at 9 months and 2 years. The major adverse event (defined as device- or procedure-related death, target lesion revascularization or significant embolic event) rate was 10.5% at 9 months and 20.9% at 3 years. Conclusions: RENAISSANCE demonstrates that renal artery stenting is superior to the prespecified OPC at 9 months, and also shows that DUS can accurately identify in-stent restenosis. (C) 2008 Wiley-Liss, Inc. C1 [Rocha-Singh, Krishna] Prairie Vasc Inst, Springfield, IL 62719 USA. [Jaff, Michael R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kelley, E. Lynne] Boston Sci Corp, Natick, MA USA. RP Rocha-Singh, K (reprint author), Prairie Vasc Inst, 619 E Mason St, Springfield, IL 62719 USA. EM ksingh@prairieheart.com NR 24 TC 32 Z9 32 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 15 PY 2008 VL 72 IS 6 BP 853 EP 862 DI 10.1002/ccd.21749 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373QZ UT WOS:000260988400020 PM 19006254 ER PT J AU Schainfeld, RM AF Schainfeld, Robert M. TI IVUS: Cracking the "Code" in the Wall SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID INTRAVASCULAR ULTRASOUND; ANGIOPLASTY C1 Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02114 USA. RP Schainfeld, RM (reprint author), Massachusetts Gen Hosp, Sect Vasc Med, Div Cardiol, Boston, MA 02114 USA. EM rschainfeld@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV 15 PY 2008 VL 72 IS 6 BP 871 EP 872 DI 10.1002/ccd.21862 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 373QZ UT WOS:000260988400023 PM 19009631 ER PT J AU Bazzaro, M Lin, ZH Santillan, A Lee, MK Wang, MC Chan, KC Bristow, RE Mazitschek, R Bradner, J Roden, RBS AF Bazzaro, Martina Lin, Zhenhua Santillan, Antonio Lee, Michael K. Wang, Mei-Cheng Chan, Kwun C. Bristow, Robert E. Mazitschek, Ralph Bradner, James Roden, Richard B. S. TI Ubiquitin Proteasome System Stress Underlies Synergistic Killing of Ovarian Cancer Cells by Bortezomib and a Novel HDAC6 Inhibitor SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; PROTEIN-DEGRADATION; INDUCED APOPTOSIS; NEURODEGENERATION; TRANSFORMATION; EXPRESSION; AUTOPHAGY; DOMAIN; LAQ824 AB Purpose: Elevated metabolic activity of ovarian cancer cells causes increased ubiquitin-proteasome -system (UPS) stress, resulting in their greater sensitivity to the toxic effects of proteasomal inhibition. The proteasomes and a potentially compensatory histone deacetylase 6 (HDAC6)-dependent lysosomal pathway mediate eukaryotic protein turnover. We hypothesized that up-regulation of the HDAC6-dependent lysosomal pathway occurs in response to UPS stress and proteasomal inhibition, and thus, ovarian cancer cell death can be triggered most effectively by coinhibition of both the proteasome- and HDAC6-dependent protein degradation pathways. Experimental Design: To address this hypothesis, we examined HDAC6 expression patterns in normal and cancerous ovarian tissues and used a novel HDAC6-specific inhibitor, NK84, to address HDAC6 function in ovarian cancer. Results: Abnormally high levels of HDAC6 are expressed by ovarian cancer cells in situ and in culture relative to benign epithelium and immortalized ovarian surface epithelium, respectively. Specific HDAC6 inhibition acts in synergy with the proteasome inhibitor Bortezomib (PS-341) to cause selective apoptotic cell death of ovarian cancer cells at doses that do not cause significant toxicity when used individually. Levels of UPS stress regulate the sensitivity of ovarian cancer cells to proteasome/HDAC6 inhibition. Pharmacologic inhibition of HDAC6 also reduces ovarian cancer cell spreading and migration consistent with its known function in regulating microtubule polymerization via deacetylation of alpha-tubulin. Conclusion: Our results suggest the elevation of both the proteasomal and alternate HDAC6-dependent proteolytic pathways in ovarian cancer and the potential of combined inhibition of proteasome and HDAC6 as a therapy for ovarian cancer. C1 [Bazzaro, Martina; Lin, Zhenhua; Santillan, Antonio; Lee, Michael K.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. [Santillan, Antonio; Bristow, Robert E.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol Obstet & Gynecol, Baltimore, MD 21231 USA. [Wang, Mei-Cheng; Chan, Kwun C.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21231 USA. [Mazitschek, Ralph; Bradner, James] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. [Mazitschek, Ralph; Bradner, James] MIT, Cambridge, MA 02139 USA. [Bradner, James] Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. RP Roden, RBS (reprint author), Johns Hopkins Univ, Dept Pathol, Canc Res Bldg 2,Room 308,1550 Orleans St, Baltimore, MD 21231 USA. EM roden@jhmi.edu RI Lee, Michael/D-9491-2013; Mazitschek, Ralph/E-3741-2013 OI Lee, Michael/0000-0001-5865-9682; Mazitschek, Ralph/0000-0002-1105-689X FU US Public Health Service [R01CA122581, P50 CA098252]; HERA foundation FX US Public Health Service grants R01CA122581 (R.B.S. Roden), P50 CA098252 (R. B.S. Roden, R.E. Bristow, and M.C. Wang), and the HERA foundation (M. Bazzaro, Z. Lin, and A. Santillan). NR 32 TC 52 Z9 60 U1 0 U2 10 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 NOV 15 PY 2008 VL 14 IS 22 BP 7340 EP 7347 DI 10.1158/1078-0432.CCR-08-0642 PG 8 WC Oncology SC Oncology GA 374AL UT WOS:000261014500022 PM 19010849 ER PT J AU Shimazaki, K Lepin, EJ Wei, B Nagy, AK Coulam, CP Mareninov, S Fu, MY Wu, AM Marks, JD Braun, J Gordon, LK Wadehra, M AF Shimazaki, Kaori Lepin, Eric J. Wei, Bo Nagy, Agnes K. Coulam, Catherine P. Mareninov, Sergey Fu, Maoyong Wu, Anna M. Marks, James D. Braun, Jonathan Gordon, Lynn K. Wadehra, Madhuri TI Diabodies Targeting Epithelial Membrane Protein 2 Reduce Tumorigenicity of Human Endometrial Cancer Cell Lines SO CLINICAL CANCER RESEARCH LA English DT Article ID SINGLE-CHAIN FV; FOCAL ADHESION KINASE; ANTIBODY FRAGMENTS; SURFACE EXPRESSION; GYNECOLOGIC MALIGNANCIES; INTEGRIN FUNCTION; LIPID RAFTS; EMP2; GENE; CARCINOGENESIS AB Purpose: Endometrial cancer is the most common gynecologic malignancy. One promising biomarker is epithelial membrane protein 2 (EMP2), and its expression is an independent prognostic indicator for tumors with poor clinical outcome expression. The present study assesses the suitability of EMP2 as a therapeutic target. Experimental Design: Human monovalent anti-EMP2 antibody fragments were isolated from a human phage display library and engineered as bivalent antibody fragments (diabodies) with specificity and avidity to both EMP2 peptides and native cell-surface EMP2 protein. Diabodies were assessed using cell death and apoptosis assays. In addition, the efficacy of EMP2 diabodies on endometrial cancer tumors was determined using mouse xenograft models. Results: Treatment of human endometrial adenocarcinoma cell lines with anti-EMP2 diabodies induced significant cell death and caspase-3 cleavage in vitro. These responses correlated with cellular EMP2 expression and were augmented by progesterone, which physiologically induces EMP2 expression. In vivo, treatment of subcutaneous human xenografts of HEC-1A cell lines with anti-EMP2 diabodies suppressed tumor growth and induced cell death in the xenograft. Conclusions: These findings suggest that EMP2 may be a potential pharmacologic target for human endometrial cancer. C1 [Wei, Bo; Nagy, Agnes K.; Coulam, Catherine P.; Mareninov, Sergey; Fu, Maoyong; Braun, Jonathan; Wadehra, Madhuri] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab, Los Angeles, CA 90095 USA. [Shimazaki, Kaori; Braun, Jonathan] Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Univ Calif Los Angeles, Jules Stein Eye Inst, Los Angeles, CA 90095 USA. [Gordon, Lynn K.] Greater Los Angeles Vet Affairs Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Marks, James D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Wadehra, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab, 14-127 Ctr Hlth Sci, Los Angeles, CA 90095 USA. EM mwadehra@mednet.ucla.edu RI Fu, Maoyong/E-9201-2010 FU NIH [HD48540, CA86306, CA009120, 2-T32-Al-07323]; University of California at Los Angeles Jonsson Comprehensive Cancer Center flow cytometry core [CA016042]; Iris Cantor Seed Grant, Giannini Family Foundation [U54 CA119367]; Oppenheimer Family Foundation; Center for the Prevention of Eye Disease FX NIH grants HD48540 (J. Braun), CA86306 (A.M. Wu and J. Braun), CA009120 (M. Wadehra), 2-T32-Al-07323 (K. Shimazaki), and CA016042 (University of California at Los Angeles Jonsson Comprehensive Cancer Center flow cytometry core); Iris Cantor Seed Grant, Giannini Family Foundation, and U54 CA119367 (M.Wadehra), unrestricted gift of Dr. Richard and Barbara Braun (J. Braun); and Oppenheimer Family Foundation Grant Center for the Prevention of Eye Disease (L.K. Gordon). NR 50 TC 15 Z9 16 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2008 VL 14 IS 22 BP 7367 EP 7377 DI 10.1158/1078-0432.CCR-08-1016 PG 11 WC Oncology SC Oncology GA 374AL UT WOS:000261014500025 PM 19010852 ER PT J AU Jackson, LA Janoff, EN AF Jackson, Lisa A. Janoff, Edward N. TI Pneumococcal Vaccination of Elderly Adults: New Paradigms for Protection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; POLYSACCHARIDE VACCINE; CONJUGATE VACCINE; HIGH-RISK; UNITED-STATES; OLDER-ADULTS; CLINICAL-EFFICACY; PHASE-1 TRIAL; DISEASE; POPULATION AB Pneumococcal polysaccharide vaccine has been licensed for use in the United States for 130 years, and two-thirds of the elderly population in the United States have received this vaccine. Observational studies have demonstrated that pneumococcal polysaccharide vaccine reduces the risk of invasive pneumococcal disease in immunocompetent elderly individuals, but neither observational studies nor clinical trials have demonstrated consistent evidence for a reduction in the incidence of pneumonia in vaccinated older adults. The introduction of pneumococcal protein conjugate vaccine among children has led to a herd immunity effect that has resulted in a 38% decrease in the rate of invasive pneumococcal disease among elderly adults. The high efficacy of pneumococcal protein conjugate vaccine in children has renewed interest in evaluating pneumococcal protein conjugate vaccines in adults for prevention of invasive pneumococcal disease and pneumonia. Moreover, the recognition of the presence and function of noncapsular pneumococcal protein antigens and the increasing availability of adjuvants highlight the promise of new vaccination strategies to decrease the burden of pneumococcal infection in this high-risk population. C1 [Jackson, Lisa A.] Grp Hlth Ctr Hlth Studies, Seattle, WA 98101 USA. [Janoff, Edward N.] Univ Colorado, Denver Sch Med, Mucosal & Vaccine Res Program Colorado, Div Infect Dis,Denver Vet Affairs Med Ctr, Denver, CO USA. RP Jackson, LA (reprint author), Grp Hlth Ctr Hlth Studies, 1730 Minor Ave,Ste 1600, Seattle, WA 98101 USA. EM Jackson.L@ghc.org FU Veterans Affairs Research Service; Mucosal and Vaccine Research Program Colorado; National Institutes of Health [R21-AI077069, R01-AI48796] FX Financial support. Veterans Affairs Research Service, Mucosal and Vaccine Research Program Colorado ( to E.N.J.), and the National Institutes of Health (R21-AI077069 and R01-AI48796 to E.N.J.). NR 63 TC 73 Z9 74 U1 0 U2 1 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 NOV 15 PY 2008 VL 47 IS 10 BP 1328 EP 1338 DI 10.1086/592691 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 360ST UT WOS:000260078800014 PM 18844484 ER PT J AU Kamiya, N Ye, L Kobayashi, T Mochida, Y Yamauchi, M Kronenberg, HM Feng, JQ Mishina, Y AF Kamiya, Nobuhiro Ye, Ling Kobayashi, Tatsuya Mochida, Yoshiyuki Yamauchi, Mitsuo Kronenberg, Henry M. Feng, Jian Q. Mishina, Yuji TI BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway SO DEVELOPMENT LA English DT Article DE BMP receptor IA; Bone mass; Canonical Wnt signaling; Osteoblast; Osteoclastogenesis; Sclerostin; Mouse ID RECEPTOR-RELATED PROTEIN-5; TAMOXIFEN-INDUCIBLE FORM; VAN-BUCHEM-DISEASE; MORPHOGENETIC PROTEIN; BETA-CATENIN; OSTEOBLAST LINEAGE; OSTEOCLAST DIFFERENTIATION; CELL-DIFFERENTIATION; SOST GENE; LRP5 GENE AB Bone morphogenetic proteins (BMPs) are known to induce ectopic bone. However, it is largely unknown how BMP signaling in osteoblasts directly regulates endogenous bone. This study investigated the mechanism by which BMP signaling through the type IA receptor (BMPR1A) regulates endogenous bone mass using an inducible Cre-loxP system. When BMPR1A in osteoblasts was conditionally disrupted during embryonic bone development, bone mass surprisingly was increased with upregulation of canonical Wnt signaling. Although levels of bone formation markers were modestly reduced, levels of resorption markers representing osteoclastogenesis were severely reduced, resulting in a net increase in bone mass. The reduction of osteoclastogenesis was primarily caused by Bmpr1a-deficiency in osteoblasts, at least through the RANKL-OPG pathway. Sclerostin (Sost) expression was downregulated by about 90% and SOST protein was undetectable in osteoblasts and osteocytes, whereas the Wnt signaling was upregulated. Treatment of Bmpr1a-deficient calvariae with sclerostin repressed the Wnt signaling and restored normal bone morphology. By gain of Smad-dependent BMPR1A signaling in mice, Sost expression was upregulated and osteoclastogenesis was increased. Finally, the Bmpr1a-deficient bone phenotype was rescued by enhancing BMPR1A signaling, with restoration of osteoclastogenesis. These findings demonstrate that BMPR1A signaling in osteoblasts restrain endogenous bone mass directly by upregulating osteoclastogenesis through the RANKL-OPG pathway, or indirectly by downregulating canonical Wnt signaling through sclerostin, a Wnt inhibitor and a bone mass mediator. C1 [Kamiya, Nobuhiro; Mishina, Yuji] NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. [Mishina, Yuji] Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. [Ye, Ling; Feng, Jian Q.] Univ Missouri, Sch Dent, Kansas City, MO 64108 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. [Kobayashi, Tatsuya; Kronenberg, Henry M.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Mochida, Yoshiyuki; Yamauchi, Mitsuo] Univ N Carolina, Dent Res Ctr, Chapel Hill, NC 27599 USA. RP Mishina, Y (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM mishina@umich.edu OI Mochida, Yoshiyuki/0000-0002-2115-4303 FU NIH [P01 DK56246, R01 AR051587, R21 AR052824, ES071003- 11]; RIKEN Brain Science Institute; Lilly Fellowship Foundation FX We gratefully thank Tomokazu Fukuda and Greg Scott for generation of caBmpr1a mouse line and Donald Lucas for critical reading of this manuscript. This work was supported by NIH grants P01 DK56246 (H. K.), R01 AR051587 (J. F.), R21 AR052824 (M. Y.), ES071003- 11 and a conditional gift from RIKEN Brain Science Institute (Y. M.) and Lilly Fellowship Foundation (N. K.). NR 74 TC 130 Z9 136 U1 0 U2 10 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 15 PY 2008 VL 135 IS 22 BP 3801 EP 3811 DI 10.1242/dev.025825 PG 11 WC Developmental Biology SC Developmental Biology GA 364MV UT WOS:000260340700016 PM 18927151 ER PT J AU Ozsolak, F Poling, LL Wang, ZX Liu, H Liu, XS Roeder, RG Zhang, XM Song, JS Fisher, DE AF Ozsolak, Fatih Poling, Laura L. Wang, Zhengxin Liu, Hui Liu, X. Shirley Roeder, Robert G. Zhang, Xinmin Song, Jun S. Fisher, David E. TI Chromatin structure analyses identify miRNA promoters SO GENES & DEVELOPMENT LA English DT Article DE Transcription; microRNA; promoter; chromatin ID RNA-POLYMERASE-III; GENOME-WIDE ANALYSIS; MICRORNA EXPRESSION; GENE-EXPRESSION; ALPHA-AMANITIN; C-MYC; CAENORHABDITIS-ELEGANS; HISTONE MODIFICATIONS; ANIMAL DEVELOPMENT; TRANSCRIPTION AB Although microRNAs (miRNAs) are key regulators of gene expression in normal human physiology and disease, transcriptional regulation of miRNAs is poorly understood, because most miRNA promoters have not yet been characterized. We identified the proximal promoters of 175 human miRNAs by combining nucleosome mapping with chromatin signatures for promoters. We observe that one-third of intronic miRNAs have transcription initiation regions independent from their host promoters and present a list of RNA polymerase II- and III-occupied miRNAs. Nucleosome mapping and linker sequence analyses in miRNA promoters permitted accurate prediction of transcription factors regulating miRNA expression, thus identifying nine miRNAs regulated by the MITF transcription factor/oncoprotein in melanoma cells. Furthermore, DNA sequences encoding mature miRNAs were found to be preferentially occupied by positioned-nucleosomes, and the 3' end sites of known genes exhibited nucleosome depletion. The high-throughput identification of miRNA promoter and enhancer regulatory elements sheds light on evolution of miRNA transcription and permits rapid identification of transcriptional networks of miRNAs. C1 [Song, Jun S.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. [Ozsolak, Fatih; Poling, Laura L.; Fisher, David E.] Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. [Ozsolak, Fatih; Poling, Laura L.; Fisher, David E.] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. [Ozsolak, Fatih; Poling, Laura L.; Fisher, David E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02114 USA. [Wang, Zhengxin] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Liu, Hui; Zhang, Xinmin] Roche NimbleGen Inc, Madison, WI 53719 USA. [Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Roeder, Robert G.] Rockefeller Univ, Biochem & Mol Biol Lab, New York, NY 10021 USA. RP Song, JS (reprint author), Inst Adv Study, Simons Ctr Syst Biol, Einstein Dr, Princeton, NJ 08540 USA. EM jssong@ias.edu; dfisher3@partners.org FU NIH; Doris Duke Medical Foundation FX We thank C. S. Chan, R. Cui, V. Igras, A. Kawakami, M. Khaled, A. J. Levine, E. Makino, V. Nanda, and S. Yokoyama for discussions and support. This work was supported by a grant from NIH to D. E. F. D. E. F. is a Distinguished Clinical Scholar of the Doris Duke Medical Foundation. H. L. and X. Z. are employees of Roche NimbleGen, Inc. D. E. F. wishes to disclose consulting relationships with Novartis Pharmaceuticals, Magen BioSciences, and Source MDx. NR 80 TC 330 Z9 344 U1 2 U2 27 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2008 VL 22 IS 22 BP 3172 EP 3183 DI 10.1101/gad.1706508 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 378UJ UT WOS:000261349400009 PM 19056895 ER PT J AU Kundu, ST Gosavi, P Khapare, N Patel, R Hosing, AS Maru, GB Ingle, A DeCaprio, JA Dalal, SN AF Kundu, Samrat T. Gosavi, Prajakta Khapare, Nileema Patel, Rachana Hosing, Amol S. Maru, Girish B. Ingle, Arvind DeCaprio, James A. Dalal, Sorab N. TI Plakophilin3 downregulation leads to a decrease in cell adhesion and promotes metastasis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE plakophilin3; cell adhesion; desmosome; transformation; metastasis ID LARGE-T-ANTIGEN; PLAQUE PROTEIN; MEDIATED TRANSFORMATION; DESMOSOMAL CADHERINS; EPITHELIAL-CELLS; LUNG-CANCER; BINDING; GENE; MICE; LOCALIZATION AB Plakophilin3 is a desmosomal plaque protein whose levels are reduced in poorly differentiated tumors of the oropharyngeal cavity and in invasive colon carcinomas. To test the hypothesis that plakophilin3 loss stimulates neoplastic progression, plakophilin3 expression was inhibited by DNA vector driven RNA interference in 3 epithelial cell lines, HCT116, HaCaT and fetal buccal mucosa. The plakophilin3-knockdown clones showed a decrease in cell-cell adhesion as assessed in a hanging drop assay, which was accompanied by an increase in cell migration. The HCT116 plakophilin3-knockdown clones showed a decrease in desmosome size as revealed by electron microscopy. These altered desmosomal properties were accompanied by colony formation in soft agar and growth to high density in culture. The HCT116-derived clones showed accelerated tumor formation in nude mice and increased metastasis to the lung, a phenotype consistent with the increased migration observed in vitro and is consistent with data from human tumors that suggests that plakophililn3 is lost in invasive and metastatic tumors. These data indicate that plakophilin3 loss leads to a decrease in cell-cell adhesion leading to the stimulation of neoplastic progression and metastasis. (C) 2008 Wiley-Liss, Inc. C1 [Kundu, Samrat T.; Gosavi, Prajakta; Khapare, Nileema; Patel, Rachana; Hosing, Amol S.; Maru, Girish B.; Ingle, Arvind; Dalal, Sorab N.] ACTREC, Tata Mem Ctr, Kharghar Node 410210, Navi Mumbai, India. [DeCaprio, James A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Dalal, SN (reprint author), ACTREC, Tata Mem Ctr, Kharghar Node 410210, Navi Mumbai, India. EM sdalal@actrec.gov.in RI Patel, Rachana/G-2274-2010 FU University Grants Commission; Council for Scientific and Industrial Research; Lady Tata Memorial Trust; Department of Science and Technology (DST); ACTREC FX Grant sponsors: University Grants Commission, Council for Scientific and Industrial Research, Lady Tata Memorial Trust, Department of Science and Technology (DST) and ACTREC. NR 40 TC 38 Z9 39 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 15 PY 2008 VL 123 IS 10 BP 2303 EP 2314 DI 10.1002/ijc.23797 PG 12 WC Oncology SC Oncology GA 365XQ UT WOS:000260443300010 PM 18729189 ER PT J AU Caglar, HB Tishler, RB Othus, M Burke, E Li, Y Goguen, L Wirth, LJ Haddad, RI Norris, CM Court, LE Aninno, DJ Posner, MR Allen, AM AF Caglar, Hale B. Tishler, Roy B. Othus, Megan Burke, Elaine Li, Yi Goguen, Laura Wirth, Lori J. Haddad, Robert I. Norris, Carl M. Court, Laurence E. Aninno, Donald J. Posner, Marshall R. Allen, Aaron M. TI DOSE TO LARYNX PREDICTS FOR SWALLOWING COMPLICATIONS AFTER INTENSITY-MODULATED RADIOTHERAPY SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Aspiration; Intensity-modulated radiotherapy; Head and neck cancer ID QUALITY-OF-LIFE; SQUAMOUS-CELL CARCINOMA; FLUOROURACIL INDUCTION CHEMOTHERAPY; TRIAL COMPARING RADIOTHERAPY; STAGE OROPHARYNX CARCINOMA; RADIATION-THERAPY IMRT; NECK-CANCER; ORGAN PRESERVATION; ADVANCED HEAD; CONCOMITANT CHEMORADIOTHERAPY AB Purpose: To evaluate early swallowing after intensity-modulated radiotherapy for head and neck squamous cell carcinoma and determine factors correlating with aspiration and/or stricture. Methods and Materials: Consecutive patients treated with intensity-modulated radiotherapy with or without chemotherapy between September 2004 and August 2006 at the Dana Farber Cancer Institute/Brigham and Women's Hospital were evaluated with institutional review board approval. Patients underwent swallowing evaluation after completion of therapy; including video swallow studies. The clinical- and treatment-related variables were examined for correlation with aspiration or strictures, as well as doses to the larynx, pharyngeal constrictor muscles, and cervical esophagus. The correlation was assessed with logistic regression analysis. Results: A total of 96 patients were evaluated. Their median age was 55 years, and 79 (82%) were men. The primary site of cancer was the oropharynx in 43, hypopharynx/larynx in 17, oral cavity in 13, nasopharynx in 11, maxillary sinus in 2, and unknown primary in 10. Of the 96 patients, 85% underwent definitive RT and 15% postoperative RT. Also, 28 patients underwent induction chemotherapy followed by concurrent chemotherapy, 59 received concurrent chemotherapy, and 9 patients underwent RT alone. The median follow-up was 10 months. Of the 96 patients, 31 (32%) had clinically significant aspiration and 36 (37%) developed a stricture. The radiation dose-volume metrics, including the volume of the larynx receiving >= 50 Gy (p = 0.04 and p = 0.03, respectively) and volume of the inferior constrictor receiving >= 50 Gy (p = 0.05 and p = 0.02, respectively) were significantly associated with both aspiration and stricture. The mean larynx dose correlated with aspiration (p = 0.003). Smoking history was the only clinical factor to correlate with stricture (P = 0.05) but not aspiration. Conclusion: Aspiration and stricture are common side effects after intensity-modulated radiotherapy for head-and-neck squamous cell carcinoma. The dose given to the larynx and inferior constrictors correlated with these side effects. (C) 2008 Elsevier Inc. C1 [Caglar, Hale B.; Tishler, Roy B.; Court, Laurence E.; Allen, Aaron M.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. [Goguen, Laura; Norris, Carl M.; Aninno, Donald J.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Otolaryngol, Boston, MA 02115 USA. [Othus, Megan; Li, Yi] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. [Burke, Elaine; Wirth, Lori J.; Haddad, Robert I.; Posner, Marshall R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Allen, AM (reprint author), Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM aallen@lroc.harvard.edu FU NCI NIH HHS [T32 CA009337] NR 43 TC 116 Z9 117 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2008 VL 72 IS 4 BP 1110 EP 1118 DI 10.1016/j.ijrobp.2008.02.048 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 368AB UT WOS:000260592600021 PM 18468812 ER PT J AU Hong, TS Craft, DL Carlsson, F Bortfeld, TR AF Hong, Theodore S. Craft, David L. Carlsson, Fredrik Bortfeld, Thomas R. TI MULTICRITERIA OPTIMIZATION IN INTENSITY-MODULATED RADIATION THERAPY TREATMENT PLANNING FOR LOCALLY ADVANCED CANCER OF THE PANCREATIC HEAD SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Pancreatic cancer; Multicriteria optimization; IMRT ID PENCIL BEAM; IMRT; RADIOTHERAPY; CONCURRENT AB Purpose: Intensity-modulated radiation therapy (IMRT) affords the potential to decrease radiation therapy-associated toxicity by creating highly conformal dose distributions. However, the inverse planning process can create a suboptimal plan despite meeting all constraints. Multicriteria optimization (MCO) may reduce the time-consuming iteration loop necessary to develop a satisfactory plan while providing information regarding trade-offs between different treatment planning goals. In this exploratory study, we examine the feasibility and utility of MCO in physician plan selection in patients with locally advanced pancreatic cancer (LAPC). Methods and Materials: The first 10 consecutive patients with LAPC treated with IMRT were evaluated. A database of plans (Pareto surface) was created that met the inverse planning goals. The physician then navigated to an "optimal" plan from the point on the Pareto surface at which kidney dose was minimized. Results: Pareto surfaces were created for all 10 patients. A physician was able to select a plan from the Pareto surface within 10 minutes for all cases. Compared with the original (treated) IMRT plans, the plan selected from the Pareto surface had a lower stomach mean dose in 9 of 10 patients, although often at the expense of higher kidney dose than with the treated plan. Conclusion: The MCO is feasible in patients with LAPC and allows the physician to choose a satisfactory plan quickly. Generally, when given the opportunity, the physician will choose a plan with a lower stomach dose. The MCO enables a physician to provide greater active clinical input into the IMRT planning process. (c) 2008 Elsevier Inc. C1 [Hong, Theodore S.; Craft, David L.; Bortfeld, Thomas R.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Hong, Theodore S.; Craft, David L.; Bortfeld, Thomas R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Carlsson, Fredrik] RaySearch Labs, Stockholm, Sweden. RP Hong, TS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox 3, Boston, MA 02114 USA. EM tshong1@partners.org FU National Cancer Institute [CA103904-01A1] FX Supported by 1 RO1 CA103904-01A1 from the National Cancer Institute. NR 14 TC 31 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2008 VL 72 IS 4 BP 1208 EP 1214 DI 10.1016/j.ijrobp.2008.07.015 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 368AB UT WOS:000260592600034 PM 18954714 ER PT J AU Chakraverty, R Flutter, B Fallah-Arani, F Eom, HS Means, T Andreola, G Schwarte, S Buchli, J Cotter, P Zhao, GL Sykes, M AF Chakraverty, Ronjon Flutter, Barry Fallah-Arani, Farnaz Eom, Hyeon-Seok Means, Terry Andreola, Giovanna Schwarte, Sebastian Buchli, Jennifer Cotter, Pete Zhao, Guiling Sykes, Megan TI The Host Environment Regulates the Function of CD8(+) Graft-versus-Host-Reactive Effector Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; ANTIGEN-PRESENTING CELLS; TOTAL-BODY IRRADIATION; T-CELLS; CUTTING EDGE; ALLOGENEIC CHIMERAS; LEUKOCYTE INFUSIONS; LEUKEMIA RESPONSES; DENDRITIC CELLS AB We have examined how the host environment influences the graft-vs-leukemia (GVL) response following transfer of donor T cells to allogeneic chimeras. Donor T cells induce significant GVL when administered in large numbers to established mixed chimeras (MC). However, when using limiting numbers of T cells, we found that late transfer to MC induced less GVL than did early transfer to freshly irradiated allogeneic recipients. Late donor T cell transfer to MC was associated with marked accumulation of anti-host CD8 cells within the spleen, but delayed kinetics of differentiation, reduced expression of effector molecules including IFN-gamma, impaired cytotoxicity, and higher rates of sustained apoptosis. Furthermore, in contrast to the spleen, we observed a significant delay in donor CD8 cell recruitment to the bone marrow, a key location for hematopoietic tumors. Increasing the numbers of T cells transferred to MC led to the enhancement of CTL activity and detectable increases in absolute numbers of IFN-gamma(+) cells without inducing graft-vs-host disease (GVHD). TLR-induced systemic inflammation accelerated differentiation of functional CTL in MC but was associated with severe GVHD. In the absence of inflammation, both recipient T and non-T cell populations impeded the full development of GVHD-inducing effector function. We conclude that per-cell deficits in the function of donor CD8 cells activated in MC may be overcome by transferring larger numbers of T cells without inducing GVHD. The Journal of Immunology, 2008, 181: 6820-6828. C1 [Andreola, Giovanna; Schwarte, Sebastian; Cotter, Pete; Zhao, Guiling; Sykes, Megan] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplatat, Boston, MA 02129 USA. [Eom, Hyeon-Seok; Means, Terry] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. [Chakraverty, Ronjon; Flutter, Barry; Fallah-Arani, Farnaz; Buchli, Jennifer] UCL, Transplantat Immunol Grp, Dept Hematol, London, England. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Bone Marrow Transplatat, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM Megan.Sykes@tbrc.mgh.harvard.edu FU Leukemia Research, U.K; National Institutes of Health [PO1 CA111519, RO1 CA79989]; Multiple Myeloma Foundation FX This work was supported by the Leukemia Research, U.K., and by National Institutes of Health Grants PO1 CA111519 and RO1 CA79989, and by a Senior Research Award from the Multiple Myeloma Foundation. NR 45 TC 23 Z9 24 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 6820 EP 6828 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900019 PM 18981100 ER PT J AU Divangahi, M Mostowy, S Coulombe, F Kozak, R Guillot, L Veyrier, F Kobayashi, KS Flavell, RA Gros, P Behr, MA AF Divangahi, Maziar Mostowy, Serge Coulombe, Francois Kozak, Robert Guillot, Loic Veyrier, Frederic Kobayashi, Koichi S. Flavell, Richard A. Gros, Philippe Behr, Marcel A. TI NOD2-Deficient Mice Have Impaired Resistance to Mycobacterium tuberculosis Infection through Defective Innate and Adaptive Immunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AVIUM SUBSPECIES PARATUBERCULOSIS; INTERFERON-GAMMA; DENDRITIC CELLS; CROHNS-DISEASE; NOD2; RESPONSES; RECOGNITION; SUSCEPTIBILITY; PEPTIDOGLYCAN; ACTIVATION AB NOD2/CARD15 mediates innate immune responses to mycobacterial infection. However, its role in the regulation of adaptive immunity has remained unknown. In this study, we examined host defense, T cell responses, and tissue pathology in two models of pulmonary mycobacterial infection, using wild-type and Nod2-deficient mice. During the early phase of aerosol infection with Mycobacterium tuberculosis, Nod2(-/-) mice had similar bacterial counts but reduced inflammatory response on histopathology at 4 and 8 wk postchallenge compared with wild-type animals. These findings were confirmed upon intratracheal infection of mice with attenuated Mycobacterium bovis bacillus Calmette-Guerin. Analysis of the lungs 4 wk after bacillus Calmette-Guerin infection demonstrated that Nod2(-/-) mice had decreased production of type 1 cytokines; and reduced recruitment of CD8(+) and CD4(+) T cells. Ag-specific T cell responses in both the spleens and thoracic lymph nodes were diminished in Nod2(-/-) mice, indicating impaired adaptive antimycobacterial immunity. The immune regulatory role of NOD2 was not restricted to the lung since Nod2 disruption also led to reduced type 1 T cell activation following i.m. bacillus Calmette-Guerin infection. To determine the importance of diminished innate and adaptive immunity, we measured bacterial burden 6 mo after aerosol infection with M. tuberculosis and followed a second infected group for assessment of survival. Nod2(-/-) mice had a higher bacterial burden in the lungs 6 mo after infection and succumbed sooner than did wild-type controls. Taken together, these data indicate that NOD2 mediates resistance to mycobacterial infection via both innate and adaptive immunity. The Journal of Immunology, 2008, 181: 7157-7165. C1 [Divangahi, Maziar; Mostowy, Serge; Coulombe, Francois; Kozak, Robert; Guillot, Loic; Veyrier, Frederic; Behr, Marcel A.] McGill Univ, Dept Med, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. [Kobayashi, Koichi S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kobayashi, Koichi S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Flavell, Richard A.] Howard Hughes Med Inst, New Haven, CT 06510 USA. [Flavell, Richard A.] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06510 USA. [Gros, Philippe] McGill Univ, Dept Biochem, Montreal, PQ H3G 1A4, Canada. RP Behr, MA (reprint author), McGill Univ, Dept Med, Ctr Hlth, A5-156,1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada. EM marcel.behr@mcgill.ca RI Guillot, Loic/D-8893-2011; OI Guillot, Loic/0000-0001-6853-7945; Mostowy, Serge/0000-0002-7286-6503 FU Canadian Genetic Diseases Network; Canadian Institutes for Health Research [MOP-86536]; Fonds de la Recherche en Sante du Quebec (FRSQ) FX This work was funded by a group grant from the Canadian Genetic Diseases Network to P.G. and M.B. and an operating grant (MOP-86536) from the Canadian Institutes for Health Research to M.B. F.C. was supported by a studentship award of the Fonds de la Recherche en Sante du Quebec (FRSQ). R.A.F. is an investigator of the Howard Hughes Medical Institute. P.G. is a James McGill Professor of McGill University. M.B. is a William Dawson Scholar of McGill University and a Chercheur-Boursier Senior of the FRSQ. NR 42 TC 116 Z9 120 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 NOV 15 PY 2008 VL 181 IS 10 BP 7157 EP 7165 PG 9 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900056 PM 18981137 ER PT J AU Purdon, PL Millan, H Fuller, PL Bonmassar, G AF Purdon, Patrick L. Millan, Hernan Fuller, Peter L. Bonmassar, Giorgio TI An open-source hardware and software system for acquisition and real-time processing of electrophysiology during high field MRI SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE EEG; Local field potentials; fMRI; Multimodal imaging; Real-time signal processing; Sleep; Anesthesia; Hyperbaric medicine; Neuropharmacology; Learning; Attention ID SIMULTANEOUS EEG; EXPERT-SYSTEM; SLEEP EXPERIMENT; FUNCTIONAL MRI; FMRI; ARTIFACT; CLASSIFICATION; ELECTRODES; REMOVAL; SIGNAL AB Simultaneous recording of electrophysiology and functional magnetic resonance imaging (fMRI) is a technique of growing importance in neuroscience. Rapidly evolving clinical and scientific requirements have created a need for hardware and software that can be customized for specific applications. Hardware may require customization to enable a variety of recording types (e.g., electroencephalogram, local field potentials, or multi-unit activity) while meeting the stringent and costly requirements of MRI safety and compatibility. Real-time signal processing tools are an enabling technology for studies of learning, attention, sleep, epilepsy, neurofeedback, and neuropharmacology, yet real-time signal processing tools are difficult to develop. We describe an open-source system for simultaneous electrophysiology and fMRI featuring low-noise (< 0.6 mu V p-p input noise), electromagnetic compatibility for MRI (tested up to 7T), and user-programmable real-time signal processing. The hardware distribution provides the complete specifications required to build an MRI-compatible electrophysiological data acquisition system, including circuit schematics, print circuit board (PCB) layouts, Gerber files for PCB fabrication and robotic assembly, a bill of materials with part numbers, data sheets, and vendor information, and test procedures. The software facilitates rapid implementation of real-time signal processing algorithms. This system has been used in human EEG/fMRI studies at 3 and 7T examining the auditory system, visual system, sleep physiology, and anesthesia, as well as in intracranial electrophysiological studies of the non-human primate visual system during 3T fMRI, and in human hyperbaric physiology studies at depths of up to 300 feet below sea level. Published by Elsevier B.V. C1 [Purdon, Patrick L.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, Boston, MA 02129 USA. [Millan, Hernan; Bonmassar, Giorgio] MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Boston, MA 02129 USA. [Fuller, Peter L.] PLF Consulting, Brookline, MA 02446 USA. RP Purdon, PL (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Neurosci Stat Res Lab, 149 13th St,Room 4005, Boston, MA 02129 USA. EM patrickp@nmr.mgh.harvard.edu FU NIH/NINDS [K25-NS05758]; NIH/NCRR [M01-RR-01066, P41-RR14075]; NIH/NIBIB [R01-EB006385]; NIH/NEI [R03-EY16047]; Naval Submarine Medical Research Laboratory [N66596-07-IPA-001] FX This work was supported by grants from the United Stated Department of Health and Human Services, grant numbers NIH/NINDS K25-NS05758 (Purclon), NIH/NCRR M01-RR-01066 (Bonmassar), P41-RR14075 (Bonmassar), NIH/NIBIB R01-EB006385 (Bonmassar), NIH/NEI R03-EY16047 (Bonmassar), and Naval Submarine Medical Research Laboratory Grant N66596-07-IPA-001 (Bonmassar). The technologies described in this manuscript are protected by two patents: Bonmassar G, Belliveau JW, inventors. Electroencephalograph sensor for use with magnetic resonance imaging and methods using such arrangements. US patent PCT/US03/05614,2 February 2003; Bonmassar G, Purdon PL, inventors. Apparatuses and methods for electrophysiological signal delivery and recording during MRI. PCT/US2005/042401. NR 60 TC 12 Z9 12 U1 4 U2 18 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 NOV 15 PY 2008 VL 175 IS 2 BP 165 EP 186 DI 10.1016/j.jneumeth.2008.07.017 PG 22 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 374XJ UT WOS:000261076700001 PM 18761038 ER PT J AU Tan, AT Loggi, E Boni, C Chia, A Gehring, AJ Sastry, KSR Goh, V Fisicaro, P Andreone, P Brander, C Lim, SG Ferrari, C Bihl, F Bertoletti, A AF Tan, Anthony Tanoto Loggi, Elisabetta Boni, Carolina Chia, Adeline Gehring, Adam J. Sastry, Konduru S. R. Goh, Vera Fisicaro, Paola Andreone, Pietro Brander, Christian Lim, Seng Gee Ferrari, Carlo Bihl, Florian Bertoletti, Antonio TI Host Ethnicity and Virus Genotype Shape the Hepatitis B Virus-Specific T-Cell Repertoire SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CLASS-I SUPERTYPES; LYMPHOCYTE RESPONSES; NUCLEOCAPSID ANTIGEN; IMMUNE-RESPONSE; HLA-A2 SUBTYPES; HBV INFECTION; CTL EPITOPES; IMMUNOGENICITY; DISTINCT AB Repertoire composition, quantity, and qualitative functional ability are the parameters that define virus-specific T-cell responses and are linked with their potential to control infection. We took advantage of the segregation of different hepatitis B virus (HBV) genotypes in geographically and genetically distinct host populations to directly analyze the impact that host and virus variables exert on these virus-specific T-cell parameters. T-cell responses against the entire HBV proteome were analyzed in a total of 109 HBV-infected subjects of distinct ethnicities (47 of Chinese origin and 62 of Caucasian origin). We demonstrate that HBV-specific T-cell quantity is determined by the virological and clinical profiles of the patients, which outweigh any influence of race or viral diversity. In contrast, HBV-specific T-cell repertoires are divergent in the two ethnic groups, with T-cell epitopes frequently found in Caucasian patients seldom detected in Chinese patients. In conclusion, we provide a direct biological evaluation of the impact that host and virus variables exert on virus-specific T-cell responses. The discordance between HBV-specific CD8 T-cell repertoires present in Caucasian and Chinese subjects shows the ability of HLA micropolymorphisms to diversify T-cell responses and has implications for the rational development of therapeutic and prophylactic vaccines for worldwide use. C1 [Bertoletti, Antonio] ASTAR, Singapore Inst Clin Sci, Brenner Ctr Mol Med, Singapore 117609, Singapore. [Tan, Anthony Tanoto; Lim, Seng Gee; Bertoletti, Antonio] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore 117595, Singapore. [Loggi, Elisabetta; Andreone, Pietro] Univ Bologna, Osped S Orsola Malpighi, Dept Internal Med Cardioangiol & Hepatol, Bologna, Italy. [Boni, Carolina; Fisicaro, Paola; Ferrari, Carlo] Univ Parma, Azienda Osped, Unit Infect Dis & Hepatol, I-43100 Parma, Italy. [Brander, Christian; Bihl, Florian] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA USA. [Brander, Christian] Hosp Badalona Germans Trias & Pujol, IrsiCaixa Fdn, Badalona, Spain. [Brander, Christian] ICREA, Barcelona, Spain. [Bihl, Florian] Univ Hosp Geneva, Div Gastroenterol & Hepatol, Geneva, Switzerland. [Bertoletti, Antonio] ASTAR, Singapore Immunol Network, Singapore, Singapore. RP Bertoletti, A (reprint author), ASTAR, Singapore Inst Clin Sci, Brenner Ctr Mol Med, 30 Med Dr, Singapore 117609, Singapore. EM antonio_bertoletti@sics.a-star.edu.sg RI Boni, Carolina/J-5249-2016; Ferrari, Carlo/D-5663-2017; Loggi, Elisabetta/K-7848-2016; OI Boni, Carolina/0000-0002-7630-5180; Ferrari, Carlo/0000-0002-7843-4963; Brander, Christian/0000-0002-0548-5778; Loggi, Elisabetta/0000-0003-4985-9783; Bertoletti, Antonio/0000-0002-2942-0485; ANDREONE, PIETRO/0000-0002-4794-9809 NR 48 TC 49 Z9 51 U1 1 U2 9 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 NOV 15 PY 2008 VL 82 IS 22 BP 10986 EP 10997 DI 10.1128/JVI.01124-08 PG 12 WC Virology SC Virology GA 364XD UT WOS:000260368000003 PM 18799575 ER PT J AU Richardson, MW Carroll, RG Stremlau, M Korokhov, N Humeau, LM Silvestri, G Sodroski, J Riley, JL AF Richardson, Max W. Carroll, Richard G. Stremlau, Matthew Korokhov, Nikolay Humeau, Laurent M. Silvestri, Guido Sodroski, Joseph Riley, James L. TI Mode of Transmission Affects the Sensitivity of Human Immunodeficiency Virus Type 1 to Restriction by Rhesus TRIM5 alpha SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; HIV-1 INFECTION; RETROVIRUS RESTRICTION; VIROLOGICAL SYNAPSE; LENTIVIRAL VECTOR; IN-VITRO; EXPRESSION; PROTEIN; DOMAIN; ENTRY AB Rhesus TRIM5 alpha (rhTRIM5 alpha), but not human TRIM5 alpha (huTRIM5 alpha), potently inhibits human immunodeficiency virus (HIV) infection and is thus a potentially valuable therapeutic tool. Primary human CD4 T cells engineered to express rhTRIM5 alpha were highly resistant to cell-free HIV type 1 (HIV-1) infection. However, when cocultured with unmodified T cells, rhTRIM5 alpha-expressing cells became highly permissive to HIV-1 infection. Physical separation of rhTRIM5 alpha-expressing cells and unmodified cells revealed that rhTRIM5 alpha efficiently restricts cell-free but not cell-associated HIV transmission. Furthermore, we observed that HIV-infected human cells could infect rhesus CD4 T cells by cell-to-cell contact, but the infection was self-limiting. Subsequently, we noted that a spreading infection ensued when HIV-1-infected rhTRIM5 alpha-expressing human cells were cultured with huTRIM5 alpha- but not rhTRIM5 alpha-expressing cells. Our results suggest that cell-associated HIV transmission in humans is blocked only when both donor and recipient cells express rhTRIM5 alpha. These studies further define the role of rhTRIM5 alpha in cell-free and cell-associated HIV transmission and delineate the utility of rhTRIM5 alpha in anti-HIV therapy. C1 [Richardson, Max W.; Silvestri, Guido; Riley, James L.] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Richardson, Max W.; Carroll, Richard G.; Riley, James L.] Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. [Stremlau, Matthew; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Div AIDS, Boston, MA 02115 USA. [Korokhov, Nikolay; Humeau, Laurent M.] VIRxSYS Corp, Gaithersburg, MD 20877 USA. [Sodroski, Joseph] Harvard Univ, Sch Med, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Riley, JL (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. EM rileyj@mail.med.upenn.edu OI Riley, James/0000-0002-1057-576X FU NIH/NIAID [U19AI066290, AI63987]; National Defense Science and Engineering Fellowship; Ryan Foundation FX This work was supported by NIH/NIAID grant U19AI066290. M. S. and J. S. were funded by a grant (AI63987) from the National Institutes of Health. M. S. was supported by a National Defense Science and Engineering Fellowship and was a Fellow of the Ryan Foundation.; We thank Tatiana Golovina, Tatiana Mikheeva, and Chanelle Case from the Penn-CFAR Immunology Core for providing primary human T cells and Farida Shaheen from Penn-CFAR Virology Core for p24 analysis; Paul Hallberg from the BSL3 Cell Sorting Facility for sorting the HIV-1-infected T cells; James Blanchard and Andrew Lackner from the Tulane National Primate Center for reagents and expertise pertaining to the use of rhesus T cells; and Angel Varela-Rohena, Carl June, Gwen Binder, Bob Doms, and Jim Hoxie for helpful suggestions and discussions. NR 43 TC 41 Z9 42 U1 0 U2 1 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 NOV 15 PY 2008 VL 82 IS 22 BP 11117 EP 11128 DI 10.1128/JVI.01046-08 PG 12 WC Virology SC Virology GA 364XD UT WOS:000260368000015 PM 18768965 ER PT J AU Rodrigues, GGR Walker, RH Brice, A Cazeneuve, C Russaouen, O Teive, HAG Munhoz, RP Becker, N Raskin, S Werneck, LC Marques, W Tumas, V AF Rodrigues, Guilherme G. Riccioppo Walker, Ruth H. Brice, Alexis Cazeneuve, Cecile Russaouen, Odile Teive, Helio A. G. Munhoz, Renato Puppi Becker, Nilson Raskin, Salino Werneck, Lineu Cesar Marques, Wilson Junior Tumas, Vitor TI Huntington's Disease-Like 2 in Brazil-Report of 4 Patients SO MOVEMENT DISORDERS LA English DT Article DE Huntington's disease; junctophilin 3; Huntington's disease like ID REPEAT EXPANSION; CAG EXPANSION; HUNTINGTON-DISEASE-LIKE-2; FEATURES; HUNTINGTONS-DISEASE-LIKE-2; PHENOCOPIES; ANCESTRY; FAMILY AB Huntington's disease-like 2 (HDL2) is a neurodegenerative disorder found in people of African ancestry with clinical, radiological, and neuropathological manifestations similar to Huntington's disease (HD). HDL2 is caused by a pathological expansion of CAG/CTG triplets in exon 2A of the JPH3 gene. We describe four cases of HDL2 from four unrelated families, and discuss their clinical findings. HDL2 should be considered in every patient with an HD-like phenotype who tests negative for the HD mutation, even if African ancestry is not immediately apparent. (C) 2008 Movement Disorder Society C1 [Rodrigues, Guilherme G. Riccioppo; Marques, Wilson Junior; Tumas, Vitor] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurol, Ribeirao Preto, SP, Brazil. [Walker, Ruth H.] James J Peters Vet Affairs Med Ctr, Dept Neurol, Bronx, NY USA. [Walker, Ruth H.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. [Brice, Alexis; Cazeneuve, Cecile; Russaouen, Odile] Grp Hosp Pitie Salpetriere, Neurogenet Unit, Dept Genet & Cytogenet, AP HP, F-75634 Paris, France. [Teive, Helio A. G.; Munhoz, Renato Puppi; Becker, Nilson; Raskin, Salino; Werneck, Lineu Cesar] Univ Fed Parana, Hosp Clin, Neurol Serv, Movement Disorders Unit, BR-80060000 Curitiba, Parana, Brazil. RP Tumas, V (reprint author), Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Neurol, Ribeirao Preto, SP, Brazil. EM tumasv@rnp.fmrp.usp.br RI Rodrigues, Guilherme/D-3547-2009; Marques, Wilson/G-4240-2012; Tumas, Vitor/C-9949-2014 OI Rodrigues, Guilherme/0000-0002-4296-1016; Marques, Wilson/0000-0002-4589-2749; NR 17 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV 15 PY 2008 VL 23 IS 15 BP 2244 EP 2247 DI 10.1002/mds.22223 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 380CF UT WOS:000261442600015 PM 18816802 ER PT J AU Gow, DW Segawa, JA Ahlfors, SP Lin, FH AF Gow, David W., Jr. Segawa, Jennifer A. Ahlfors, Seppo P. Lin, Fa-Hsuan TI Lexical influences on speech perception: A Granger causality analysis of MEG and EEG source estimates SO NEUROIMAGE LA English DT Article ID SURFACE-BASED ANALYSIS; EVENT-RELATED FMRI; CORTICAL SURFACE; HUMAN BRAIN; COORDINATE SYSTEM; CEREBRAL-CORTEX; WORD; LOCALIZATION; ACTIVATION; MODEL AB Behavioral and functional imaging studies have demonstrated that lexical knowledge influences the categorization of perceptually ambiguous speech sounds. However, methodological and inferential constraints have so far been unable to resolve the question of whether this interaction takes the form of direct top-down influences on perceptual processing, or feedforward convergence during a decision process. We examined top-down lexical influences on the categorization of segments in a/s/-/integral/ continuum presented in different lexical contexts to produce a robust Ganong effect. Using integrated MEG/EEG and MRI data we found that, within a network identified by 40 Hz gamma phase locking, activation in the supramarginal gyrus associated with wordform representation influences phonetic processing in the posterior superior temporal gyrus during a period of time associated with lexical processing. This result provides direct evidence that lexical processes influence lower level phonetic perception, and demonstrates the potential value of combining Granger causality analyses and high spatiotemporal resolution multimodal imaging data to explore the functional architecture of cognition. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gow, David W., Jr.; Segawa, Jennifer A.] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. [Gow, David W., Jr.] Salem State Coll, Dept Psychol, Salem, MA 01970 USA. [Gow, David W., Jr.; Segawa, Jennifer A.; Ahlfors, Seppo P.; Lin, Fa-Hsuan] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Cambridge, MA 02129 USA. [Gow, David W., Jr.; Ahlfors, Seppo P.] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Lin, Fa-Hsuan] Natl Taiwan Univ, Inst Biomed Engn, Taipei 106, Taiwan. RP Gow, DW (reprint author), Cognit Behav Neurol Grp, 175 Cambridge St,Suite S340, Boston, MA 02114 USA. EM gow@helix.mgh.harvard.edu RI Lin, Fa-Hsuan/G-6988-2012; Ahlfors, Seppo/P-3644-2016 OI Lin, Fa-Hsuan/0000-0002-9539-1731; FU NIDCD [R013108]; MIND Institute; NCRR [P41RR14075, R21EB007298] FX This work was supported by NIDCD grant R013108 and also benefited from funding from the MIND Institute and NCRR grants P41RR14075 and R21EB007298 which support the development of technology and analysis tools at the Athinoula A. Martinos Center for Biomedical Imaging. We thank Eric Halgren, Matti H m l inen, Deirdre von Pechman, and Christina Congleton for their assistance in implementing the experiment and Gina Kuperberg, Steven Stufflebeam, Catherine Stoodley, David Cohen and David Caplan for their comments on earlier versions of the manuscript. NR 63 TC 64 Z9 64 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2008 VL 43 IS 3 BP 614 EP 623 DI 10.1016/j.neuroimage.2008.07.027 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 392JY UT WOS:000262300200020 PM 18703146 ER PT J AU Gold, JM Burstein, HJ AF Gold, Julie M. Burstein, Harold J. TI Aromatase Inhibitor-Associated Musculoskeletal Symptoms: Etiology and Strategies for Management The Henry/Giles/Stearns Article Reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID POSITIVE BREAST-CANCER; ADJUVANT THERAPY C1 [Gold, Julie M.; Burstein, Harold J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Gold, JM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV 15 PY 2008 VL 22 IS 12 BP 1416 EP + PG 2 WC Oncology SC Oncology GA 395NP UT WOS:000262531100009 PM 19322949 ER PT J AU Medarova, Z Kumar, M Ng, SW Yang, JZ Barteneva, N Evgenov, NV Petkova, V Moore, A AF Medarova, Zdravka Kumar, Mohanraja Ng, Shu-wing Yang, Junzheng Barteneva, Natasha Evgenov, Natalia V. Petkova, Victoria Moore, Anna TI Multifunctional Magnetic Nanocarriers for Image-Tagged SiRNA Delivery to Intact Pancreatic Islets SO TRANSPLANTATION LA English DT Article DE Magnetic resonance imaging; Optical imaging; RNA interference; Pancreatic islets ID IN-VIVO; BETA-CELLS; GENE-EXPRESSION; ADENOASSOCIATED VIRUS; HIGH GLUCOSE; TRANSDUCTION; INSULIN; EFFICIENT; VECTORS; TRANSPLANTATION AB Background. With the ultimate hope of finding a cure for diabetes, researches are looking into altering the genetic profile of the beta cell as a way to manage metabolic dysregulation. One of the most powerful new approaches for the directed regulation of gene expression uses the phenomenon of RNA interference. Methods. Here, we establish the feasibility of a novel technology centered around multifunctional magnetic nanocarriers, which concurrently deliver siRNA to intact pancreatic islets and can be detected by magnetic resonance and optical imaging. Results. In the proof-of-principle studies described here, we demonstrate that, after in vitro incubation, magnetic nanoparticles carrying siRNA designed to target the model gene for enhanced green fluorescent protein are efficiently taken up by murine pancreatic islets, derived from egfp transgenic animals. This uptake can be visualized by magnetic resonance imaging and near-infrared fluorescence optical imaging and results in suppression of the target gene. Conclusions. These results illustrate the value of our approach in overcoming the challenges associated with genetic modification of intact pancreatic islets in a clinically acceptable manner. Furthermore, an added advantage of our technology derives from the combined capability of our magnetic nanoparticles for siRNA delivery and magnetic labeling of pancreatic islets. C1 [Medarova, Zdravka; Kumar, Mohanraja; Evgenov, Natalia V.; Moore, Anna] Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab, MGH MIT HMS,Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. [Ng, Shu-wing; Yang, Junzheng] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Petkova, Victoria] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Mol Imaging Lab, MGH MIT HMS,Athinoula A Martinos Ctr Biomed Imagi, Bldg 75,13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIDDK NIH HHS [R01 DK080784, R01 DK064850, 5R01DK080784, R01 DK080784-01A1, R01 DK064850-01] NR 41 TC 25 Z9 26 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2008 VL 86 IS 9 BP 1170 EP 1177 DI 10.1097/TP.0b013e31818a81b2 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 373BI UT WOS:000260945600004 PM 19005396 ER PT J AU Xu, CQ Gagnon, E Call, ME Schnell, JR Schwieters, CD Carman, CV Chou, JJ Wucherpfennig, KW AF Xu, Chenqi Gagnon, Etienne Call, Matthew E. Schnell, Jason R. Schwieters, Charles D. Carman, Christopher V. Chou, James J. Wucherpfennig, Kai W. TI Regulation of T Cell Receptor Activation by Dynamic Membrane Binding of the CD3 epsilon Cytoplasmic Tyrosine-Based Motif SO CELL LA English DT Article ID EFFECTOR DOMAIN; PROTEIN; PHOSPHORYLATION; BICELLES; BILAYER; COMPLEX; ZAP-70; ZETA AB Many immune system receptors signal through cytoplasmic tyrosine-based motifs (ITAMs), but how receptor ligation results in ITAM phosphorylation remains unknown. Live-cell imaging studies showed a close interaction of the CD3 epsilon cytoplasmic domain of the T cell receptor (TCR) with the plasma membrane through fluorescence resonance energy transfer between a C-terminal fluorescent protein and a membrane fluorophore. Electrostatic interactions between basic CD3 epsilon residues and acidic phospholipids enriched in the inner leaflet of the plasma membrane were required for binding. The nuclear magnetic resonance structure of the lipid-bound state of this cytoplasmic domain revealed deep insertion of the two key tyrosines into the hydrophobic core of the lipid bilayer. Receptor ligation thus needs to result in unbinding of the CD3 epsilon ITAM from the membrane to render these tyrosines accessible to Src kinases. Sequestration of key tyrosines into the lipid bilayer represents a previously unrecognized mechanism for control of receptor activation. C1 [Call, Matthew E.; Schnell, Jason R.; Chou, James J.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Xu, Chenqi; Gagnon, Etienne; Wucherpfennig, Kai W.] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Carman, Christopher V.] Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Wucherpfennig, Kai W.] Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. [Schwieters, Charles D.] Natl Inst Hlth, Imaging Sci Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Chou, JJ (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM james_chou@hms.harvard.edu; kai_wucherpfennig@dfci.harvard.edu RI Carman, Christopher/L-8108-2016; Chou, James/N-9840-2013 OI Carman, Christopher/0000-0001-7358-2548; FU Intramural NIH HHS; NIAID NIH HHS [AI054520, R01 AI054520, R01 AI054520-05] NR 33 TC 182 Z9 188 U1 0 U2 24 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 14 PY 2008 VL 135 IS 4 BP 702 EP 713 DI 10.1016/j.cell.2008.09.044 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 372FG UT WOS:000260886900020 PM 19013279 ER PT J AU Hill, JA Hall, JA Sun, CM Cai, Q Ghyselinck, N Chambon, P Belkaid, Y Mathis, D Benoist, C AF Hill, Jonathan A. Hall, Jason A. Sun, Cheng-Ming Cai, Qi Ghyselinck, Norbert Chambon, Pierre Belkaid, Yasmine Mathis, Diane Benoist, Christophe TI Retinoic Acid Enhances Foxp3 Induction Indirectly by Relieving Inhibition from CD4(+)CD44(hi) Cells SO IMMUNITY LA English DT Article ID REGULATORY T-CELLS; IOXP-FLANKED ALLELE; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; SIGNALING PATHWAY; NUCLEAR RECEPTORS; DENDRITIC CELLS; ORAL TOLERANCE; RAR-GAMMA; DIFFERENTIATION AB CD4(+)Foxp3(+) regulatory T (Treg) cells originate primarily from thymic differentiation, but conversion of mature T lymphocytes to Foxp3 positivity can be elicited by several means, including in vitro activation in the presence of TGF-beta. Retinoic acid (RA) increases TGF-beta-induced expression of Foxp3, through unknown molecular mechanisms. We showed here that, rather than enhancing TGF-beta signaling directly in naive CD4(+) T cells, RA negatively regulated an accompanying population of CD4(+) T cells with a CD44(hi) memory and effector phenotype. These memory cells actively inhibited the TGF-beta-induced conversion of naive CD4(+) T cells through the synthesis of a set of cytokines (IL-4, IL-21, IFN-gamma) whose expression was coordinately curtailed by RA. This indirect effect was evident in vivo and required the expression of the RA receptor alpha. Thus, cytokine-producing CD44(hi) cells actively restrain TGF-beta-mediated Foxp3 expression in naive T cells, and this balance can be shifted or fine-tuned by RA. C1 [Hill, Jonathan A.; Mathis, Diane; Benoist, Christophe] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. [Hall, Jason A.; Sun, Cheng-Ming; Belkaid, Yasmine] NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Hall, Jason A.] Univ Penn, Immunol Grad Grp, Philadelphia, PA 19104 USA. [Cai, Qi; Ghyselinck, Norbert; Chambon, Pierre] Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Joslin Diabet Ctr,Sect Immunol & Immunog, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu; cbdm@joslin.harvard.edu RI Cai, Qi/E-4357-2014; GHYSELINCK, Norbert/I-6999-2015 OI Cai, Qi/0000-0002-2598-542X; GHYSELINCK, Norbert/0000-0003-4042-6818 FU Juvenile Diabetes Research Foundation [4-2007-1057]; National Institutes of Health (NIH) [1R01A151530-5]; Young Chair; National Institute of Diabetes and Digestive and Kidney Diseases; Canadian Institutes of Health Research; Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH FX We thank S. Vitolo and K. Hattori for assistance with mice, J. LaVecchio and G. Buruzala for help with cytometry, J. Perez and K. Leatherbee for microarrays, and C. Laplace for graphics. This work was supported by grants from the Juvenile Diabetes Research Foundation (4-2007-1057) and the National Institutes of Health (NIH) (1R01A151530-5), by Young Chair funds to D.M. and C.B., and by the National Institute of Diabetes and Digestive and Kidney Diseases-funded Joslin Diabetes and Endocrinology Research Center core facilities. J.A. Hill was supported by a postdoctoral fellowship from the Canadian Institutes of Health Research, and C.M.S. and J.A. Hall were supported by the Division of Intramural Research of the National Institute of Allergy and Infectious Diseases, NIH. NR 54 TC 204 Z9 208 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV 14 PY 2008 VL 29 IS 5 BP 758 EP 770 DI 10.1016/j.immuni.2008.09.018 PG 13 WC Immunology SC Immunology GA 374IC UT WOS:000261036000013 PM 19006694 ER PT J AU Shi, W Ma, ZF Willers, H Akhtar, K Scott, SP Zhang, JQ Powell, S Zhang, JR AF Shi, Wei Ma, Zhefu Willers, Henning Akhtar, Kamal Scott, Shaun P. Zhang, Jiuqin Powell, Simon Zhang, Junran TI Disassembly of MDC1 Foci Is Controlled by Ubiquitin-Proteasome-dependent Degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE RESPONSE; DOUBLE-STRAND BREAKS; REPAIR PROTEINS; HOMOLOGOUS RECOMBINATION; CONJUGATED UBIQUITIN; SIGNALING PATHWAYS; MAMMALIAN-CELLS; HISTONE H2AX; REPLICATION; CHECKPOINT AB The orderly recruitment, retention, and disassembly of DNA damage response proteins at sites of damaged DNA is a conserved process throughout eukaryotic evolution. The recruitment and retention of DNA repair factors in foci is mediated by a complex network of protein-protein interactions; however, the mechanisms of focus disassembly remain to be defined. Mediator of DNA damage checkpoint protein 1 (MDC1) is an early and key component of the genome surveillance network activated by DNA double-strand breaks (DSBs). Here, we investigated the disassembly of MDC1 foci. First, we show that ubiquitylation directs the MDC1 protein for proteasome-dependent degradation. Ubiquitylated MDC1 associates with chromatin before and after exposure of cells to ionizing radiation (IR). In addition, increased MDC1 ubiquitylation in the chromatin fraction is observed in response to IR, which is correlated with a reduction in total MDC1 protein levels. We demonstrate that blocking MDC1 degradation by proteasome inhibitors leads to a persistence of MDC1 foci. Consistent with this observation, chromatin immunoprecipitation experiments reveal increased MDC1 protein at site-specific DSBs. Interestingly, we show that the persistence of MDC1 foci is associated with an abrogated recruitment of the downstream factor BRCA1 in a manner that is RNF8 independent. Collectively, the evidence presented here supports a novel mechanism for the disassembly of MDC1 foci via ubiquitin-proteasome dependent degradation, which appears to be a key step for the efficient assembly of BRCA1 foci. C1 [Shi, Wei; Akhtar, Kamal; Scott, Shaun P.; Zhang, Jiuqin; Zhang, Junran] Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. [Ma, Zhefu] Nanchang Univ, Affiliated Hosp 1, Dept Surg, Breast Ctr, Nanchang 330006, Peoples R China. [Willers, Henning] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Powell, Simon] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10065 USA. RP Zhang, JR (reprint author), Washington Univ, Sch Med, Dept Radiat Oncol, 4511 Forest Pk Blvd, St Louis, MO 63108 USA. EM jzhang@radonc.wustl.edu FU Department of Radiation Oncology, Washington University School of Medicine; Dr. Joseph Roti Roti and Stephanie Pagano Fund for Mesothelioma Research [IRG-58-010-51]; American Cancer Society FX This work was supported by a seed grant and startup fund from the Department of Radiation Oncology, Washington University School of Medicine, by the Dr. Joseph Roti Roti and Stephanie Pagano Fund for Mesothelioma Research, and by Grant IRG-58-010-51 from the American Cancer Society (to J. Z.). 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 63 TC 37 Z9 38 U1 0 U2 3 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 NOV 14 PY 2008 VL 283 IS 46 BP 31608 EP 31616 DI 10.1074/jbc.M801082200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800041 PM 18757370 ER PT J AU Mckee, CJ Kessl, JJ Shkriabai, N Dar, MJ Engelman, A Kvaratskhelia, M AF McKee, Christopher J. Kessl, Jacques J. Shkriabai, Nikolozi Dar, Mohd Jamal Engelman, Alan Kvaratskhelia, Mamuka TI Dynamic Modulation of HIV-1 Integrase Structure and Function by Cellular Lens Epithelium-derived Growth Factor (LEDGF) Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DNA-BINDING-DOMAIN; IN-VITRO; TYPE-1 INTEGRASE; PREINTEGRATION COMPLEXES; ENZYMATIC-ACTIVITY; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; TERMINAL DOMAINS; CDNA INTEGRATION AB The mandatory integration of the reverse-transcribed HIV-1 genome into host chromatin is catalyzed by the viral protein integrase (IN), and IN activity can be regulated by numerous viral and cellular proteins. Among these, LEDGF has been identified as a cellular cofactor critical for effective HIV-1 integration. The x-ray crystal structure of the catalytic core domain (CCD) of IN in complex with the IN binding domain (IBD) of LEDGF has furthermore revealed essential protein-protein contacts. However, mutagenic studies indicated that interactions between the full-length proteins were more extensive than the contacts observed in the co-crystal structure of the isolated domains. Therefore, we have conducted detailed biochemical characterization of the interactions between full-length IN and LEDGF. Our results reveal a highly dynamic nature of IN subunit-subunit interactions. LEDGF strongly stabilized these interactions and promoted IN tetramerization. Mass spectrometric protein footprinting and molecular modeling experiments uncovered novel intra- and inter-protein-protein contacts in the full-length IN-LEDGF complex that lay outside of the observable IBD-CCD structure. In particular, our studies defined the IN tetramer interface important for enzymatic activities and high affinity LEDGF binding. These findings provide new insight into how LEDGF modulates HIV-1 IN structure and function, and highlight the potential for exploiting the highly dynamic structure of multimeric IN as a novel therapeutic target. C1 [McKee, Christopher J.; Kessl, Jacques J.; Shkriabai, Nikolozi; Kvaratskhelia, Mamuka] Ohio State Univ, Ctr Retrovirus Res, Coll Pharm, Columbus, OH 43210 USA. [McKee, Christopher J.; Kessl, Jacques J.; Shkriabai, Nikolozi; Kvaratskhelia, Mamuka] Ohio State Univ, Ctr Comprehens Canc, Coll Pharm, Columbus, OH 43210 USA. [Dar, Mohd Jamal; Engelman, Alan] Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. [Dar, Mohd Jamal; Engelman, Alan] Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. RP Kvaratskhelia, M (reprint author), Ohio State Univ, Ctr Retrovirus Res, Coll Pharm, 500 W 12th Ave,238 LM Pk Hall, Columbus, OH 43210 USA. EM kvaratskhelia.1@osu.edu RI Kessl, Jacques/J-6073-2015 FU National Institutes of Health AIDS Research [118-D-24]; Reference Reagent Program; Division of AIDS; NIAID; National Institutes of Health FX We thank Jocelyn Norris for help with purifying LEDGF proteins. The integrase strand transfer inhibitor (118-D-24) was obtained through the National Institutes of Health AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, National Institutes of Health. NR 76 TC 76 Z9 77 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2008 VL 283 IS 46 BP 31802 EP 31812 DI 10.1074/jbc.M805843200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800063 PM 18801737 ER PT J AU Cooper, MP Uldry, M Kajimura, S Arany, Z Spiegelman, BM AF Cooper, Marcus P. Uldry, Marc Kajimura, Shingo Arany, Zoltan Spiegelman, Bruce M. TI Modulation of PGC-1 Coactivator Pathways in Brown Fat Differentiation through LRP130 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL UNCOUPLING PROTEIN; C-OXIDASE DEFICIENCY; ADIPOSE CELL LINE; MESSENGER-RNA; ADIPOCYTE DIFFERENTIATION; TRANSGENIC MICE; IN-VIVO; ADAPTIVE THERMOGENESIS; INDUCIBLE COACTIVATOR; ENERGY-METABOLISM AB The PGC-1 coactivators are important regulators of oxidative metabolism. We previously demonstrated that LRP130 is a binding partner of PGC-1 alpha, required for hepatic gluconeogenesis. LRP130 is the gene mutated in Leigh syndrome French Canadian variant, a rare neurodegenerative disease. The importance of LRP130 in other, non-hepatocyte biology remains obscure. To better understand PGC-1 coactivator function in brown fat development, we explored the metabolic role of LRP130 in brown adipocyte differentiation. We show that LRP130 is preferentially enriched in brown fat compared with white, and induced in a PGC-1-dependent manner during differentiation. Despite intact PGC-1 coactivator expression, brown fat cells deficient for LRP130 exhibit attenuated expression of several genes characteristic of brown fat, including uncoupling protein 1. Oxygen consumption studies support a specific defect in proton leak due to attenuated uncoupling protein 1 expression. Notably, brown fat cell development common to both PGC-1 coactivators is governed by LRP130. Conversely, the cAMP response controlled by PGC-1 alpha is not regulated by LRP130. These data implicate LRP130 in brown fat cell development and differentiation. C1 [Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM marcus.cooper@umassmed.edu; bruce_spiegelman@dfci.harvard.edu FU National Institutes of Health [R01DK61562, K08DK071017] FX This work was supported, in whole or in part, by National Institutes of Health Grants R01DK61562 (to B. M. S.) and K08DK071017 (to M. P. C.). 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 50 TC 22 Z9 24 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2008 VL 283 IS 46 BP 31960 EP 31967 DI 10.1074/jbc.M805431200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800078 PM 18728005 ER PT J AU Orsi, RH Borowsky, ML Lauer, P Young, SK Nusbaum, C Galagan, JE Birren, BW Ivy, RA Sun, Q Graves, LM Swaminathan, B Wiedmann, M AF Orsi, Renato H. Borowsky, Mark L. Lauer, Peter Young, Sarah K. Nusbaum, Chad Galagan, James E. Birren, Bruce W. Ivy, Reid A. Sun, Qi Graves, Lewis M. Swaminathan, Bala Wiedmann, Martin TI Short-term genome evolution of Listeria monocytogenes in a non-controlled environment SO BMC GENOMICS LA English DT Article ID FIELD GEL-ELECTROPHORESIS; ENCODING CHOLERA-TOXIN; GROUP-A STREPTOCOCCUS; ESCHERICHIA-COLI; PROCESSING PLANTS; BACILLUS-SUBTILIS; VIBRIO-CHOLERAE; UNITED-STATES; EXPERIMENTAL POPULATIONS; CONTAMINATION PATTERNS AB Background: While increasing data on bacterial evolution in controlled environments are available, our understanding of bacterial genome evolution in natural environments is limited. We thus performed full genome analyses on four Listeria monocytogenes, including human and food isolates from both a 1988 case of sporadic listeriosis and a 2000 listeriosis outbreak, which had been linked to contaminated food from a single processing facility. All four isolates had been shown to have identical subtypes, suggesting that a specific L. monocytogenes strain persisted in this processing plant over at least 12 years. While a genome sequence for the 1988 food isolate has been reported, we sequenced the genomes of the 1988 human isolate as well as a human and a food isolate from the 2000 outbreak to allow for comparative genome analyses. Results: The two L. monocytogenes isolates from 1988 and the two isolates from 2000 had highly similar genome backbone sequences with very few single nucleotide (nt) polymorphisms (1-8 SNPs/isolate; confirmed by re-sequencing). While no genome rearrangements were identified in the backbone genome of the four isolates, a 42 kb prophage inserted in the chromosomal comK gene showed evidence for major genome rearrangements. The human-food isolate pair from each 1988 and 2000 had identical prophage sequence; however, there were significant differences in the prophage sequences between the 1988 and 2000 isolates. Diversification of this prophage appears to have been caused by multiple homologous recombination events or possibly prophage replacement. In addition, only the 2000 human isolate contained a plasmid, suggesting plasmid loss or acquisition events. Surprisingly, besides the polymorphisms found in the comK prophage, a single SNP in the tRNA Thr-4 prophage represents the only SNP that differentiates the 1988 isolates from the 2000 isolates. Conclusion: Our data support the hypothesis that the 2000 human listeriosis outbreak was caused by a L. monocytogenes strain that persisted in a food processing facility over 12 years and show that genome sequencing is a valuable and feasible tool for retrospective epidemiological analyses. Short-term evolution of L. monocytogenes in non-controlled environments appears to involve limited diversification beyond plasmid gain or loss and prophage diversification, highlighting the importance of phages in bacterial evolution. C1 [Orsi, Renato H.; Ivy, Reid A.; Wiedmann, Martin] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Borowsky, Mark L.; Young, Sarah K.; Nusbaum, Chad; Galagan, James E.; Birren, Bruce W.] MIT, Broad Inst, Genome Sequencing & Anal Program, Cambridge, MA 02139 USA. [Galagan, James E.] Boston Univ, Dept Biomed Engn & Microbiol, Boston, MA 02215 USA. [Sun, Qi] Cornell Univ, Ctr Adv Comp, Computat Biol Serv Unit, Ithaca, NY 14853 USA. [Graves, Lewis M.; Swaminathan, Bala] Ctr Dis Control & Prevent, Enter Dis Lab Branch, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA USA. [Borowsky, Mark L.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Lauer, Peter] Anza Therapeut, Concord, MA USA. [Borowsky, Mark L.; Young, Sarah K.; Nusbaum, Chad; Galagan, James E.; Birren, Bruce W.] Harvard Univ, Cambridge, MA 02138 USA. RP Wiedmann, M (reprint author), Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. EM rho2@cornell.edu; borowsky@molbio.mgh.harvard.edu; plauer@anzatherapeutics.com; stowey@broad.mit.edu; chad@broad.mit.edu; jgalag@mit.edu; bwb@broad.mit.edu; rai6@cornell.edu; qisun@tc.cornell.edu; lmg2@cdc.gov; balas7780@gmail.com; mw16@cornell.edu RI Wiedmann, Martin/A-9683-2008; OI Wiedmann, Martin/0000-0002-4168-5662; Galagan, James/0000-0003-0542-3291 FU USDA Special Research [2005-34459-15625, 34459-16952-06] FX This work was partially supported by USDA Special Research Grants 2005-34459-15625 and 34459-16952-06 (to MW). We thank USDA FSIS and Kitty Pupedis for providing isolate J2818 and for providing information on the history of this isolate. We also thank Yesim Soyer for help with PFGE analyses and Barbara Bowen for help with the rhamnose tests. NR 77 TC 80 Z9 80 U1 5 U2 20 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 13 PY 2008 VL 9 AR 539 DI 10.1186/1471-2164-9-539 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 417VE UT WOS:000264105800001 PM 19014550 ER PT J AU Zhang, Y Shin, H Song, JS Lei, Y Liu, XS AF Zhang, Yong Shin, Hyunjin Song, Jun S. Lei, Ying Liu, X. Shirley TI Identifying Positioned Nucleosomes with Epigenetic Marks in Human from ChIP-Seq SO BMC GENOMICS LA English DT Article ID HUMAN GENOME; HISTONE MODIFICATIONS; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; HUMAN PROMOTERS; ACTIVE GENES; CHROMATIN; METHYLATION; RESOLUTION; PATTERNS AB Background: In vivo positioning and covalent modifications of nucleosomes play an important role in epigenetic regulation, but genome-wide studies of positioned nucleosomes and their modifications in human still remain limited. Results: This paper describes a novel computational framework to efficiently identify positioned nucleosomes and their histone modification profiles from nucleosome-resolution histone modification ChIP-Seq data. We applied the algorithm to histone methylation ChIP-Seq data in human CD4(+) T cells and identified over 438,000 positioned nucleosomes, which appear predominantly at functionally important regions such as genes, promoters, DNase I hypersensitive regions, and transcription factor binding sites. Our analysis shows the identified nucleosomes play a key role in epigenetic gene regulation within those functionally important regions via their positioning and histone modifications. Conclusion: Our method provides an effective framework for studying nucleosome positioning and epigenetic marks in mammalian genomes. The algorithm is open source and available at http://liulab.dfci.harvard.edu/NPS/. C1 [Zhang, Yong; Shin, Hyunjin; Lei, Ying; Liu, X. Shirley] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Song, Jun S.] Inst Adv Study, Simons Ctr Syst Biol, Princeton, NJ 08540 USA. RP Liu, XS (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, 44 Binney St, Boston, MA 02115 USA. EM zy@jimmy.harvard.edu; shin@jimmy.harvard.edu; jssong@ias.edu; ylei@jimmy.harvard.edu; xsliu@jimmy.harvard.edu RI Zhang, Yong/B-4838-2011 OI Zhang, Yong/0000-0001-6316-2734 FU NIH [HG004069-02]; Martin A. and Helen Chooljian Membership in Biology FX We thank Myles Brown, Kevin Struhl, Keji Zhao, Jerome Eeckhoute, Mathieu Lupien, Dustin Schones and Wei Li for their insightful discussions and critical readings of this manuscript. The project was partially funded by NIH grant HG004069-02. JSS was supported in part by the Martin A. and Helen Chooljian Membership in Biology. NR 37 TC 73 Z9 76 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 13 PY 2008 VL 9 AR 537 DI 10.1186/1471-2164-9-537 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 382MB UT WOS:000261609000001 PM 19014516 ER PT J AU Fish, KN Sweet, RA Deo, AJ Lewis, DA AF Fish, Kenneth N. Sweet, Robert A. Deo, Anthony J. Lewis, David A. TI An automated segmentation methodology for quantifying immunoreactive puncta number and fluorescence intensity in tissue sections SO BRAIN RESEARCH LA English DT Article DE Quantitative fluorescence microscopy; Immunoreactive puncta; Segmentation; Synaptic structure; Fluorescent immunohistochemistry ID MONKEY PREFRONTAL CORTEX; GAD(67) MESSENGER-RNAS; POSTNATAL-DEVELOPMENT; AXON TERMINALS; LOCALIZATION; MICROSCOPY; PERFORMANCE; SYNAPSES; PROTEINS; SUPPORTS AB A number of human brain diseases have been associated with disturbances in the structure and function of cortical synapses. Answering fundamental questions about the synaptic machinery in these disease states requires the ability to image and quantify small synaptic structures in tissue sections and to evaluate protein levels at these major sites of function. We developed a new automated segmentation imaging method specifically to answer such fundamental questions. The method takes advantage of advances in spinning disk confocal microscopy, and combines information from multiple iterations of a fluorescence intensity/morphological segmentation protocol to construct three-dimensional object masks of immunoreactive (IR) puncta. This new methodology is unique in that high- and low-fluorescing IR puncta are equally masked, allowing for quantification of the number of fluorescently-labeled puncta in tissue sections. In addition, the shape of the final object masks highly represents their corresponding original data. Thus, the object masks can be used to extract information about the IR puncta (e.g., average fluorescence intensity of proteins of interest). Importantly, the segmentation method presented can be easily adapted for use with most existing microscopy analysis packages. (C) 2008 Elsevier B.V. All rights reserved. C1 [Fish, Kenneth N.] Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. [Lewis, David A.] Univ Pittsburgh, Sch Med, Dept Neurosci, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. [Sweet, Robert A.] VA Pittsburgh Healthcare Syst, VISN Mental Illness Res Educ & Clin Ctr MIRECC 4, Pittsburgh, PA USA. [Deo, Anthony J.] Univ Pittsburgh, Sch Med, Phys Sci Training Program, Pittsburgh, PA 15213 USA. RP Fish, KN (reprint author), Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Biomed Sci Tower,Room W165, Pittsburgh, PA 15213 USA. EM fishkn@upmc.edu RI Lewis, David/G-4053-2014 OI Lewis, David/0000-0002-3225-6778 FU NIH [MHOS1234, MH071533]; University of Pittsburgh FX Supported by NIH grant MHOS1234 (DAL), MH071533 (RAS), and University of Pittsburgh CMRF award (KNF). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. We are extremely grateful to Mrs. Kelly Rogers and Heidi Scriven for their technical assistance. We are also grateful to Olympus American and B and B Microscopes for their advice. NR 25 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 13 PY 2008 VL 1240 BP 62 EP 72 DI 10.1016/j.brainres.2008.08.060 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 379SD UT WOS:000261415600008 PM 18793619 ER PT J AU Ford, AC Talley, NJ Spiegel, BMR Foxx-Orenstein, AE Schiller, L Quigley, EMM Moayyedi, P AF Ford, Alexander C. Talley, Nicholas J. Spiegel, Brennan M. R. Foxx-Orenstein, Amy E. Schiller, Lawrence Quigley, Eamonn M. M. Moayyedi, Paul TI Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis SO BRITISH MEDICAL JOURNAL LA English DT Review ID CLINICAL-TRIALS; VISCERAL SENSATION; NATURAL-HISTORY; SMOOTH-MUSCLE; PREVALENCE; DISORDERS; QUALITY; POPULATION; MANAGEMENT; TRANSIT AB Objective To determine the effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome. Design Systematic review and meta- analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane controlled trials register up to April 2008. Review methods Randomised controlled trials comparing fibre, antispasmodics, and peppermint oil with placebo or no treatment in adults with irritable bowel syndrome were eligible for inclusion. The minimum duration of therapy considered was one week, and studies had to report either a global assessment of cure or improvement in symptoms, or cure of or improvement in abdominal pain, after treatment. A random effects model was used to pool data on symptoms, and the effect of therapy compared with placebo or no treatment was reported as the relative risk (95% confidence interval) of symptoms persisting. Results 12 studies compared fibre with placebo or no treatment in 591 patients (relative risk of persistent symptoms 0.87, 95% confidence interval 0.76 to 1.00). This effect was limited to ispaghula (0.78, 0.63 to 0.96). Twenty two trials compared antispasmodics with placebo in 1778 patients (0.68, 0.57 to 0.81). Various antispasmodics were studied, but otilonium (four trials, 435 patients, relative risk of persistent symptoms 0.55, 0.31 to 0.97) and hyoscine (three trials, 426 patients, 0.63, 0.51 to 0.78) showed consistent evidence of efficacy. Four trials compared peppermint oil with placebo in 392 patients ( 0.43, 0.32 to 0.59). Conclusion Fibre, antispasmodics, and peppermint oil were all more effective than placebo in the treatment of irritable bowel syndrome. C1 [Ford, Alexander C.; Moayyedi, Paul] McMaster Univ, Hlth Sci Ctr, Div Gastroenterol, Hamilton, ON L8N 3Z5, Canada. [Talley, Nicholas J.] Mayo Clin, Dept Med, Jacksonville, FL 32224 USA. [Spiegel, Brennan M. R.] Univ Calif Los Angeles, VA Ctr Outcomes Res & Educ, Los Angeles, CA USA. [Spiegel, Brennan M. R.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Foxx-Orenstein, Amy E.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Schiller, Lawrence] Baylor Univ, Med Ctr, Digest Hlth Assoc Texas, Dallas, TX USA. [Quigley, Eamonn M. M.] Cork Univ Hosp, Dept Med, Cork, Ireland. RP Ford, AC (reprint author), McMaster Univ, Hlth Sci Ctr, Div Gastroenterol, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM alexf12399@yahoo.com RI Ford, Alexander/K-5491-2012; Talley, nicholas/D-5399-2013; Moayyedi, Paul/M-6178-2014 OI Ford, Alexander/0000-0001-6371-4359; Talley, nicholas/0000-0003-2537-3092; Moayyedi, Paul/0000-0002-3616-9292 FU American College of Gastroenterology FX This study was funded by the American College of Gastroenterology. The authors' work was independent of the funders. NR 32 TC 167 Z9 170 U1 4 U2 25 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 13 PY 2008 VL 337 AR a2313 DI 10.1136/bmj.a2313 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 385AE UT WOS:000261784500003 PM 19008265 ER PT J AU Rosolowsky, ET Niewczas, MA Ficociello, LH Perkins, BA Warram, JH Krolewski, AS AF Rosolowsky, Elizabeth T. Niewczas, Monika A. Ficociello, Linda H. Perkins, Bruce A. Warram, James H. Krolewski, Andrzej S. TI Between hyperfiltration and impairment: Demystifying early renal functional changes in diabetic nephropathy SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT International Symposium on Diabetic Nephropathy CY 2008 CL Shiga, JAPAN DE Type 1 Diabetes; Microalbuminuria; Early renal function decline; Cystatin C ID GLOMERULAR-FILTRATION-RATE; URINARY ALBUMIN EXCRETION; CREATININE-BASED METHODS; SERUM CYSTATIN-C; URIC-ACID; SERIAL MEASUREMENTS; FUNCTION DECLINE; BLOOD-PRESSURE; MELLITUS; MICROALBUMINURIA AB Renal functional changes in diabetic nephropathy conventionally have been linked to progression of urinary albumin excretion. This paradigm was based on historic evidence noting that hyperfiltration occurred in the setting of normoalbuminuria and microalbuminuria and that loss of renal function began in the context of proteinuria. More contemporaneous research findings, using serum cystatin-C-based estimates of glomerular filtration rate (cC-GFR), have challenged this paradigm. Rather, the process of renal function loss appears to begin prior to the onset of proteinuria. In the 2nd Joslin Kidney Study on the Natural History of Microalbuminuria, over one-third of type I diabetes (T1DM) patients with microalbuminuria at the time of enrollment already had evidence of mild (cC-GFR < 90) or moderate (cC-GFR < 60 ml/min) renal function impairment. Understanding the mechanisms underlying this phenomenon of early renal function impairment may allow for interventions directed at altering or retarding early renal function decline. To date, serum uric acid and components of the TNF alpha pathway appear to be involved. (C) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Krolewski, Andrzej S.] Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. [Rosolowsky, Elizabeth T.] Childrens Hosp Boston, Div Endocrinol, Boston, MA USA. [Niewczas, Monika A.; Krolewski, Andrzej S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. [Perkins, Bruce A.] Univ Toronto, Div Endocrinol & Metab, Toronto, ON, Canada. [Niewczas, Monika A.] Warsaw Med Univ, Dept Immunol Transplant Med & Internal Dis, Warsaw, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Andrzej.Krolewski@joslin.harvard.edu FU AHRQ HHS [T32 HS00063]; NIDDK NIH HHS [DK41526] NR 54 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD NOV 13 PY 2008 VL 82 SU 1 BP S46 EP S53 DI 10.1016/j.diabres.2008.09.018 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 381RM UT WOS:000261553600010 PM 18849087 ER PT J AU Cadwell, K Liu, JY Brown, SL Miyoshi, H Loh, J Lennerz, JK Kishi, C Kc, W Carrero, JA Hunt, S Stone, CD Brunt, EM Xavier, RJ Sleckman, BP Li, E Mizushima, N Stappenbeck, TS Virgin, HW AF Cadwell, Ken Liu, John Y. Brown, Sarah L. Miyoshi, Hiroyuki Loh, Joy Lennerz, Jochen K. Kishi, Chieko Kc, Wumesh Carrero, Javier A. Hunt, Steven Stone, Christian D. Brunt, Elizabeth M. Xavier, Ramnik J. Sleckman, Barry P. Li, Ellen Mizushima, Noboru Stappenbeck, Thaddeus S. Virgin, Herbert W. TI A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; MESENTERIC ADIPOSE-TISSUE; CROHNS-DISEASE; SUSCEPTIBILITY LOCI; PATHOGENESIS; PROTEIN; PROLIFERATION; EXPRESSION; MEMBRANE AB Susceptibility to Crohn's disease, a complex inflammatory disease involving the small intestine, is controlled by over 30 loci(1). One Crohn's disease risk allele is in ATG16L1, a gene homologous to the essential yeast autophagy gene ATG16 ( ref. 2). It is not known how ATG16L1 or autophagy contributes to intestinal biology or Crohn's disease pathogenesis. To address these questions, we generated and characterized mice that are hypomorphic for ATG16L1 protein expression, and validated conclusions on the basis of studies in these mice by analysing intestinal tissues that we collected from Crohn's disease patients carrying the Crohn's disease risk allele of ATG16L1. Here we show that ATG16L1 is a bona fide autophagy protein. Within the ileal epithelium, both ATG16L1 and a second essential autophagy protein ATG5 are selectively important for the biology of the Paneth cell, a specialized epithelial cell that functions in part by secretion of granule contents containing antimicrobial peptides and other proteins that alter the intestinal environment(3). ATG16L1- andATG5- deficient Paneth cells exhibited notable abnormalities in the granule exocytosis pathway. In addition, transcriptional analysis revealed an unexpected gain of function specific to ATG16L1- deficient Paneth cells including increased expression of genes involved in peroxisome proliferator- activated receptor ( PPAR) signalling and lipid metabolism, of acute phase reactants and of two adipocytokines, leptin and adiponectin, known to directly influence intestinal injury responses. Importantly, Crohn's disease patients homozygous for the ATG16L1 Crohn's disease risk allele displayed Paneth cell granule abnormalities similar to those observed in autophagy- protein- deficient mice and expressed increased levels of leptin protein. Thus, ATG16L1, and probably the process of autophagy, have a role within the intestinal epithelium of mice and Crohn's disease patients by selective effects on the cell biology and specialized regulatory properties of Paneth cells. C1 [Cadwell, Ken; Liu, John Y.; Brown, Sarah L.; Miyoshi, Hiroyuki; Loh, Joy; Lennerz, Jochen K.; Kc, Wumesh; Carrero, Javier A.; Brunt, Elizabeth M.; Sleckman, Barry P.; Stappenbeck, Thaddeus S.; Virgin, Herbert W.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. [Hunt, Steven] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Stone, Christian D.; Li, Ellen] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. [Virgin, Herbert W.] Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. [Kishi, Chieko; Mizushima, Noboru] Tokyo Med & Dent Univ, Grad Sch, Dept Physiol & Cell Biol, Tokyo 1138519, Japan. [Kishi, Chieko; Mizushima, Noboru] Tokyo Med & Dent Univ, Fac Med, Dept Physiol & Cell Biol, Tokyo 1138519, Japan. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Xavier, Ramnik J.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Virgin, HW (reprint author), Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. EM stappenb@wustl.edu; virgin@wustl.edu RI Mizushima, Noboru/C-3635-2009; OI Mizushima, Noboru/0000-0002-6258-6444; Cadwell, Ken/0000-0002-5860-0661 FU Broad Foundation; NIH [T32 AR07279, R01 AI062832, AI062773, DK43351]; Lallage Feazel Wall Fellowship [DRG-1972-08]; Damon Runyon Cancer Research Foundation; Pew Foundation; Washington University Digestive Diseases Research Core Center [P30 DK52574]; Barnes Jewish Foundation; Johnson and Johnson Translational Seed Award; Crohn's Colitis Foundation of America; Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan; Toray Science Foundation; [U54 AI057160 Project 6] FX We thank N. Abe for technical assistance with fluorescence microscopy, V. Cavalli for microscope use, J. Eisenberg and A. Ng for help with bioinformatics analysis, A. J. Ouellette for technical advice, and I. Mysorekar and J. Mills for help with antibodies. This research was supported by grant U54 AI057160 Project 6 and the Broad Foundation (K.C., J. Loh and H.W.V.), training grant NIH T32 AR07279 (K.C.), the Lallage Feazel Wall Fellowship DRG-1972-08 (K.C.) from the Damon Runyon Cancer Research Foundation; the Pew Foundation (J. Liu, S.L.B., H.M., W.K. and T.S.S.); the Washington University Digestive Diseases Research Core Center P30 DK52574, Barnes Jewish Foundation, Johnson and Johnson Translational Seed Award, and the Crohn's Colitis Foundation of America (E.L., S.H. and C.S.); grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the Toray Science Foundation (C.K. and N.M.); NIH R01 AI062832 (J.A.C.); and NIH AI062773 and DK43351 (R.J.X.). NR 29 TC 689 Z9 704 U1 13 U2 65 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 13 PY 2008 VL 456 IS 7219 BP 259 EP U62 DI 10.1038/nature07416 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 374JJ UT WOS:000261039300044 PM 18849966 ER PT J AU Treadway, K AF Treadway, Katharine TI The Future of Primary Care: Sustaining Relationships SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Treadway, Katharine] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Treadway, Katharine] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Treadway, K (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 13 PY 2008 VL 359 IS 20 BP 2086 EP + DI 10.1056/NEJMp0805762 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 371IB UT WOS:000260823900002 PM 19005191 ER PT J AU Goroll, AH AF Goroll, Allan H. TI The Future of Primary Care: Reforming Physician Payment SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PERFORMANCE; QUALITY; HEALTH; PAY C1 [Goroll, Allan H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Goroll, Allan H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goroll, AH (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 5 TC 9 Z9 11 U1 1 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 NOV 13 PY 2008 VL 359 IS 20 BP 2087 EP + DI 10.1056/NEJMp0805765 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 371IB UT WOS:000260823900004 PM 19005194 ER PT J AU Daffner, KR Sherman, JC Gonzalez, RG Hasserjian, RP Alcalay, RN Cole, AJ Hedley-Whyte, ET AF Daffner, Kirk R. Sherman, Janet C. Gonzalez, R. Gilberto Hasserjian, Robert P. Alcalay, Roy N. Cole, Andrew J. Hedley-Whyte, E. Tessa TI A Man with Confusion and Memory Loss Atypical carcinoid tumor (well-differentiated neuroendocrine carcinoma) of the thymus, associated with paraneoplastic limbic encephalitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HERPES-SIMPLEX ENCEPHALITIS; POTASSIUM CHANNEL ANTIBODIES; LUNG-CANCER; NERVOUS-SYSTEM; TEMPORAL-LOBE; AUTOIMMUNITY; MRI; PATIENT; ENCEPHALOMYELITIS; DIAGNOSIS C1 [Daffner, Kirk R.] Brigham & Womens Hosp, Div Cognit & Behav Neurol, Boston, MA 02115 USA. [Sherman, Janet C.] Massachusetts Gen Hosp, Psychol Assessment Ctr, Boston, MA 02114 USA. [Sherman, Janet C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Gonzalez, R. Gilberto] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hasserjian, Robert P.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Daffner, Kirk R.; Sherman, Janet C.] Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. [Gonzalez, R. Gilberto] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Hasserjian, Robert P.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Daffner, KR (reprint author), Brigham & Womens Hosp, Div Cognit & Behav Neurol, 75 Francis St, Boston, MA 02115 USA. FU Bayer; General Electric FX Dr. Gonzalez reports receiving lecture fees from Bayer and General Electric. No other potential conflict of interest relevant to this article was reported. NR 42 TC 5 Z9 7 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 NOV 13 PY 2008 VL 359 IS 20 BP 2155 EP 2164 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 371IB UT WOS:000260823900015 PM 19005200 ER PT J AU Ciaranello, AL Seage, GR Freedberg, KA Weinstein, MC Lockman, S Walensky, RP AF Ciaranello, Andrea L. Seage, George R., III Freedberg, Kenneth A. Weinstein, Milton C. Lockman, Shahin Walensky, Rochelle P. TI Antiretroviral drugs for preventing mother-to-child transmission of HIV in sub-Saharan Africa: balancing efficacy and infant toxicity SO AIDS LA English DT Article DE antiretroviral therapy; decision analysis; HIV/AIDS; mitochondrial toxicity; pediatric HIV; PMTCT; sub-Saharan Africa ID IMMUNODEFICIENCY-VIRUS TYPE-1; RANDOMIZED CONTROLLED-TRIAL; SINGLE-DOSE NEVIRAPINE; PERSISTENT MITOCHONDRIAL DYSFUNCTION; LATE POSTNATAL TRANSMISSION; PLACEBO-CONTROLLED TRIAL; SHORT-COURSE ZIDOVUDINE; BREAST-FED CHILDREN; IN-UTERO EXPOSURE; UNINFECTED CHILDREN AB Objective: Antiretroviral drugs can prevent mother-to-child transmission of HIV infection, but in-utero antiretroviral exposure may be associated with neurologic symptoms due to mitochondrial toxicity. We sought to identify the currently recommended regimen to prevent mother-to-child transmission that optimally balances risks of pediatric HIV infection and neurologic mitochondrial toxicity. Design: Published MTCT and mitochondrial toxicity data were used in a decision analytic model of MTCT among women in sub-Saharan Africa. Methods: We investigated the HIV and mitochondrial toxicity risks associated with no antiretroviral prophylaxis and five recommended regimens ranging from single-dose nevirapine to three-drug antiretroviral therapy (ART). Sensitivity analyses varied all parameters, including infant feeding strategy and the disability of mitochondrial toxicity relative to HIV. Results: Provision of no antiretroviral drugs is the least effective and least toxic strategy, with 18-month HIV risk of 30.4% and mitochondrial toxicity risk of 0.2% (breastfed infants). With increasing drug number and duration, HIV risk decreases markedly (to 4.9% with three-drug ART), but mitochondrial toxicity risk also increases (to 2.2%, also with three-drug ART). Despite increased toxicity, three-drug ART minimizes total adverse pediatric outcomes (HIV plus mitochondrial toxicity), unless the highest published risks are true for both HIV and mitochondrial toxicity, or the disability from mitochondrial toxicity exceeds 6.4 times that of HIV infection. Conclusion: The risk of pediatric mitochondrial toxicity from effective regimens to prevent mother-to-child transmission is at least an order of magnitude lower than the risk of HIV infection associated with less-effective regimens. Concern regarding mitochondrial toxicity should not currently limit the use of three-drug ART to prevent mother-to-child transmission where it is available. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Ciaranello, Andrea L.; Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. [Lockman, Shahin; Walensky, Rochelle P.] Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Walensky, Rochelle P.] Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. [Seage, George R., III] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Freedberg, Kenneth A.; Weinstein, Milton C.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Lockman, Shahin] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Ciaranello, AL (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM aciaranello@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU National Institute of Allergy and Infectious Disease [T32 A107433, R01 A1058736, 11-37 A142006-10A1, U01 Al 069456-01]; National Institute of Child Health and Human Development [U01 HD052102-03, K01 HD044391]; Doris Duke Charitable Foundation FX The authors gratefully acknowledge Jennifer Chu, BS, and Brandon Morris, BA, for assistance with manuscript preparation. Funding for this work was provided by the National Institute of Allergy and Infectious Disease [T32 A107433 (A.L.C.; PI: K.A.F.); R01 A1058736 and 11-37 A142006-10A1 (K.A.E, M.C.W, R.P.W); and U01 Al 069456-01 (S.L.)]; the National Institute of Child Health and Human Development [Cooperative Agreement U01 HD052102-03 (G.R.S.); K01 HD044391 (S.L.)]; and the Doris Duke Charitable Foundation [Clinical Scientist Development Award (R.P.W)]. NR 95 TC 16 Z9 16 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 2008 VL 22 IS 17 BP 2359 EP 2369 DI 10.1097/QAD.0b013e3283189bd7 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 377SH UT WOS:000261270400016 PM 18981776 ER PT J AU Sesso, HD Buring, JE Christen, WG Kurth, T Belanger, C MacFadyen, J Bubes, V Manson, JE Glynn, RJ Gaziano, JM AF Sesso, Howard D. Buring, Julie E. Christen, William G. Kurth, Tobias Belanger, Charlene MacFadyen, Jean Bubes, Vadim Manson, Joann E. Glynn, Robert J. Gaziano, J. Michael TI Vitamins E and C in the Prevention of Cardiovascular Disease in Men The Physicians' Health Study II Randomized Controlled Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; NUTRITION EXAMINATION SURVEY; LONG-TERM SUPPLEMENTATION; BETA-CAROTENE; ANTIOXIDANT VITAMINS; MYOCARDIAL-INFARCTION; POSTMENOPAUSAL WOMEN; SECONDARY PREVENTION; ALPHA-TOCOPHEROL AB Context Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease. However, few long- term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease. Objective To evaluate whether long- term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men. Design, Setting, and Participants The Physicians' Health Study II was a randomized, double- blind, placebo- controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14 641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men ( 5.1%) with prevalent cardiovascular disease at randomization. Intervention Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily. Main Outcome Measures A composite end point of major cardiovascular events ( nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death). Results During a mean follow- up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events ( both active and placebo vitamin E groups, 10.9 events per 1000 person- years; hazard ratio [ HR], 1.01 [ 95% confidence interval {CI}, 0.90- 1.13]; P=. 86), as well as total myocardial infarction ( HR, 0.90 [ 95% CI, 0.75- 1.07]; P=. 22), total stroke ( HR, 1.07 [ 95% CI, 0.89- 1.29]; P=. 45), and cardiovascular mortality ( HR, 1.07 [ 95% CI, 0.90- 1.28]; P=. 43). There also was no significant effect of vitamin C on major cardiovascular events ( active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [ 95% CI, 0.89- 1.11]; P=. 91), as well as total myocardial infarction ( HR, 1.04[ 95% CI, 0.87- 1.24]; P=. 65), total stroke ( HR, 0.89[ 95% CI, 0.74- 1.07]; P=. 21), and cardiovascular mortality ( HR, 1.02 [ 95% CI, 0.85- 1.21]; P=. 86). Neither vitamin E ( HR, 1.07 [ 95% CI, 0.97- 1.18]; P=. 15) nor vitamin C ( HR, 1.07 [ 95% CI, 0.97-1.18]; P=. 16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke ( HR, 1.74 [ 95% CI, 1.04- 2.91]; P=. 04). Conclusions In this large, long- term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle- aged and older men. Trial Registration clinicaltrials. gov Identifier: NCT00270647. C1 [Sesso, Howard D.; Buring, Julie E.; Christen, William G.; Kurth, Tobias; Belanger, Charlene; MacFadyen, Jean; Bubes, Vadim; Manson, Joann E.; Glynn, Robert J.; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. [Sesso, Howard D.; Buring, Julie E.; Kurth, Tobias; Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02215 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Dis, Boston, MA 02215 USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Sesso, Howard D.; Buring, Julie E.; Kurth, Tobias; Manson, Joann E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Gaziano, J. Michael] VA Boston Healthcare Syst, Boston, MA USA. RP Sesso, HD (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM hsesso@hsph.harvard.edu 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 59 TC 368 Z9 385 U1 3 U2 42 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 NOV 12 PY 2008 VL 300 IS 18 BP 2123 EP 2133 DI 10.1001/jama.2008.600 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 370WM UT WOS:000260793800022 PM 18997197 ER PT J AU Metin, C Vallee, RB Rakic, P Bhide, PG AF Metin, Christine Vallee, Richard B. Rakic, Pasko Bhide, Pradeep G. TI Modes and Mishaps of Neuronal Migration in the Mammalian Brain SO JOURNAL OF NEUROSCIENCE LA English DT Article ID LATERAL GANGLIONIC EMINENCE; NERVOUS-SYSTEM DEVELOPMENT; LISSENCEPHALY GENE LIS1; ONSET TORSION DYSTONIA; CYTOPLASMIC DYNEIN; CEREBRAL-CORTEX; CELL-MIGRATION; PRENATAL EXPOSURE; CORTICAL DEVELOPMENT; GABAERGIC NEURONS AB The ability of neurons to migrate to their appropriate positions in the developing brain is critical to brain architecture and function. Recent research has elucidated different modes of neuronal migration and the involvement of a host of signaling factors in orchestrating the migration, as well as vulnerabilities of this process to environmental and genetic factors. Here we discuss the role of cytoskeleton, motor proteins, and mechanisms of nuclear translocation in radial and tangential migration of neurons. We will also discuss how these and other events essential for normal migration of neurons can be disrupted by genetic and environmental factors that contribute to neurological disease in humans. C1 [Metin, Christine] INSERM, Inst Fer Moulin, UMR S 839, F-75005 Paris, France. [Vallee, Richard B.] Columbia Univ, Dept Pathol, New York, NY 10032 USA. [Rakic, Pasko] Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. [Bhide, Pradeep G.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02129 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM bhide@helix.mgh.harvard.edu RI Metin, Christine/E-4995-2017 FU NIDA NIH HHS [R01 DA020796-03, R01 DA020796]; NINDS NIH HHS [P01 NS037409, P01 NS037409-08, P30 NS045776, P30 NS045776-05, R01 NS043426, R01 NS043426-05] NR 78 TC 75 Z9 75 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 12 PY 2008 VL 28 IS 46 BP 11746 EP 11752 DI 10.1523/JNEUROSCI.3860-08.2008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600002 PM 19005035 ER PT J AU Kuznetsova, MS Higgs, MH Spain, WJ AF Kuznetsova, Marina S. Higgs, Matthew H. Spain, William J. TI Adaptation of Firing Rate and Spike-Timing Precision in the Avian Cochlear Nucleus SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sound localization; nucleus magnocellularis; potassium channel; phase-locking; spike-timing precision; coincidence detection ID INTERAURAL TIME DIFFERENCES; STEM AUDITORY NUCLEI; INACTIVATING POTASSIUM CURRENT; NEOCORTICAL PYRAMIDAL NEURONS; BRAIN-STEM; COINCIDENCE DETECTION; TEMPORAL INTEGRATION; MEMBRANE-PROPERTIES; BARN OWL; FEEDFORWARD INHIBITION AB Adaptation is commonly defined as a decrease in response to a constant stimulus. In the auditory system such adaptation is seen at multiple levels. However, the first-order central neurons of the interaural time difference detection circuit encode information in the timing of spikes rather than the overall firing rate. We investigated adaptation during in vitro whole-cell recordings from chick nucleus magnocellularis neurons. Injection of noisy, depolarizing current caused an increase in firing rate and a decrease in spike time precision that developed over similar to 20 s. This adaptation depends on sustained depolarization, is independent of firing, and is eliminated by alpha-dendrotoxin (0.1 mu M), implicating slow inactivation of low-threshold voltage-activated K+ channels as its mechanism. This process may alter both firing rate and spike-timing precision of phase-locked inputs to coincidence detector neurons in nucleus laminaris and thereby adjust the precision of sound localization. C1 [Kuznetsova, Marina S.; Higgs, Matthew H.; Spain, William J.] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98105 USA. [Kuznetsova, Marina S.] Univ Washington, Interdisciplinary Grad Program Neurobiol & Behav, Seattle, WA 98105 USA. [Spain, William J.] Univ Washington, Dept Neurol, Seattle, WA 98105 USA. [Spain, William J.] Vet Affairs Puget Sound Hlth Care Syst, Neurol Sect, Seattle, WA 98108 USA. RP Spain, WJ (reprint author), Neurol 127,1660 S Columbian Way, Seattle, WA 98108 USA. EM spain@u.washington.edu FU Veterans Affairs Merit Review; National Institute on Deafness and Other Communication Disorders [5F31DC009176] FX This work was supported by a Veterans Affairs Merit Review (W.J.S.) and by National Research Service Award 5F31DC009176 from the National Institute on Deafness and Other Communication Disorders (M.S.K.). We thank Sean Slee, Adrienne Fairhall, Marc Binder, David Perkel, and Ed Rubel for helpful discussions, Carol Robbins, and Sue Usher for excellent technical assistance. NR 79 TC 17 Z9 17 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 12 PY 2008 VL 28 IS 46 BP 11906 EP 11915 DI 10.1523/JNEUROSCI.3827-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 371JM UT WOS:000260827600023 PM 19005056 ER PT J AU Lee, PS Patel, SR Christiani, DC Bajwa, E Stossel, TP Waxman, AB AF Lee, Po-Shun Patel, Sanjay R. Christiani, David C. Bajwa, Ednan Stossel, Thomas P. Waxman, Aaron B. TI Plasma Gelsolin Depletion and Circulating Actin in Sepsis-A Pilot Study SO PLOS ONE LA English DT Article AB Background: Depletion of the circulating actin-binding protein, plasma gelsolin (pGSN) has been described in septic patients and animals. We hypothesized that the extent of pGSN reduction correlates with outcomes of septic patients and that circulating actin is a manifestation of sepsis. Methodology/Principal Findings: We assayed pGSN in plasma samples from non-surgical septic patients identified from a pre-existing database which prospectively enrolled patients admitted to adult intensive care units at an academic hospital. We identified 21 non-surgical septic patients for the study. Actinemia was detected in 17 of the 21 patients, suggesting actin released into circulation from injured tissues is a manifestation of sepsis. Furthermore, we documented the depletion of pGSN in human clinical sepsis, and that the survivors had significantly higher pGSN levels than the non-survivors (163 +/- 47 mg/L vs. 89 +/- 48 mg/L, p = 0.01). pGSN levels were more strongly predictive of 28-day mortality than APACHE III scores. For every quartile reduction in pGSN, the odds of death increased 3.4-fold. Conclusion: We conclude that circulating actin and pGSN deficiency are associated with early sepsis. The degree of pGSN deficiency correlates with sepsis mortality. Reversing pGSN deficiency may be an effective treatment for sepsis. C1 [Lee, Po-Shun] Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. [Lee, Po-Shun; Christiani, David C.; Bajwa, Ednan; Stossel, Thomas P.; Waxman, Aaron B.] Harvard Univ, Sch Med, Boston, MA USA. [Lee, Po-Shun; Stossel, Thomas P.] Brigham & Womens Hosp, Translat Med Div, Boston, MA USA. [Patel, Sanjay R.] Case Western Reserve Univ, Univ Hosp Cleveland, Div Pulmonary & Critical Care Med, Cleveland, OH USA. [Christiani, David C.; Bajwa, Ednan; Waxman, Aaron B.] Mass Gen Hosp, Pulmonary & Critical Care Unit, Boston, MA USA. RP Lee, PS (reprint author), Brigham & Womens Hosp, Div Pulm & Crit Care, 75 Francis St, Boston, MA 02115 USA. EM plee4@partners.org OI Patel, Sanjay/0000-0002-9142-5172 FU NIH [5R01HL074859-04]; AHA [0735620N] FX NIH 5R01HL074859-04, AHA Scientist Development Grant 0735620N. The funding institutions played no role in the designed of the study or in the preparation of this manuscript. NR 28 TC 31 Z9 37 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 12 PY 2008 VL 3 IS 11 AR e3712 DI 10.1371/journal.pone.0003712 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432WW UT WOS:000265166000012 PM 19002257 ER PT J AU Nosho, K Irahara, N Shima, K Kure, S Kirkner, GJ Schernhammer, ES Hazra, A Hunter, DJ Quackenbush, J Spiegelman, D Giovannucci, EL Fuchs, CS Ogino, S AF Nosho, Katsuhiko Irahara, Natsumi Shima, Kaori Kure, Shoko Kirkner, Gregory J. Schernhammer, Eva S. Hazra, Aditi Hunter, David J. Quackenbush, John Spiegelman, Donna Giovannucci, Edward L. Fuchs, Charles S. Ogino, Shuji TI Comprehensive Biostatistical Analysis of CpG Island Methylator Phenotype in Colorectal Cancer Using a Large Population-Based Sample SO PLOS ONE LA English DT Article AB Background: The CpG island methylator phenotype (CIMP) is a distinct phenotype associated with microsatellite instability (MSI) and BRAF mutation in colon cancer. Recent investigations have selected 5 promoters (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1) as surrogate markers for CIMP-high. However, no study has comprehensively evaluated an expanded set of methylation markers (including these 5 markers) using a large number of tumors, or deciphered the complex clinical and molecular associations with CIMP-high determined by the validated marker panel. Metholodology/Principal Findings: DNA methylation at 16 CpG islands [the above 5 plus CDKN2A (p16), CHFR, CRABP1, HIC1, IGFBP3, MGMT, MINT1, MINT31, MLH1, p14 (CDKN2A/ARF) and WRN] was quantified in 904 colorectal cancers by real-time PCR (MethyLight). In unsupervised hierarchical clustering analysis, the 5 markers (CACNA1G, IGF2, NEUROG1, RUNX3 and SOCS1), CDKN2A, CRABP1, MINT31, MLH1, p14 and WRN were generally clustered with each other and with MSI and BRAF mutation. KRAS mutation was not clustered with any methylation marker, suggesting its association with a random methylation pattern in CIMP-low tumors. Utilizing the validated CIMP marker panel ( including the 5 markers), multivariate logistic regression demonstrated that CIMP-high was independently associated with older age, proximal location, poor differentiation, MSI-high, BRAF mutation, and inversely with LINE-1 hypomethylation and beta-catenin (CTNNB1) activation. Mucinous feature, signet ring cells, and p53-negativity were associated with CIMP-high in only univariate analysis. In stratified analyses, the relations of CIMP-high with poor differentiation, KRAS mutation and LINE-1 hypomethylation significantly differed according to MSI status. Conclusions: Our study provides valuable data for standardization of the use of CIMP-high-specific methylation markers. CIMP-high is independently associated with clinical and key molecular features in colorectal cancer. Our data also suggest that KRAS mutation is related with a random CpG island methylation pattern which may lead to CIMP-low tumors. C1 [Nosho, Katsuhiko; Irahara, Natsumi; Shima, Kaori; Kure, Shoko; Fuchs, Charles S.; Ogino, Shuji] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Kirkner, Gregory J.; Schernhammer, Eva S.; Hazra, Aditi; Hunter, David J.; Spiegelman, Donna; Giovannucci, Edward L.; Fuchs, Charles S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Schernhammer, Eva S.] Applied Canc Res Inst Translat Res, Ludwig Boltzmann Inst Applied Canc Res, Vienna, Austria. [Schernhammer, Eva S.; Hazra, Aditi; Hunter, David J.; Spiegelman, Donna; Giovannucci, Edward L.; Ogino, Shuji] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Quackenbush, John] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. [Quackenbush, John; Spiegelman, Donna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Ogino, Shuji] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. RP Nosho, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU U.S. National Institute of Health (NIH) [P01 CA87969, P01 CA55075, P50 CA127003, K07 CA122826]; Bennett Family Fund; Entertainment Industry Foundation (EIF) through the EIF National Colorectal Cancer Research Alliance (NCCRA); Japanese Society for Promotion of Science FX This work was supported by U.S. National Institute of Health (NIH) grants P01 CA87969, P01 CA55075, P50 CA127003 and K07 CA122826 (to S.O.), and in part by grants from the Bennett Family Fund and from the Entertainment Industry Foundation (EIF) through the EIF National Colorectal Cancer Research Alliance (NCCRA). K.N. was supported by a fellowship grant from the Japanese Society for Promotion of Science. The content is solely the responsibility of the authors and does not necessarily represent the official views of NCI or NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 50 TC 176 Z9 177 U1 2 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 12 PY 2008 VL 3 IS 11 AR e3698 DI 10.1371/journal.pone.0003698 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432WW UT WOS:000265166000004 PM 19002263 ER PT J AU Madani, N Schon, A Princiotto, AM LaLonde, JM Courter, JR Soeta, T Ng, D Wang, LP Brower, ET Xiang, SH Do Kwon, Y Huang, CC Wyatt, R Kwong, PD Freire, E Smith, AB Sodroski, J AF Madani, Navid Schoen, Arne Princiotto, Amy M. LaLonde, Judith M. Courter, Joel R. Soeta, Takahiro Ng, Danny Wang, Liping Brower, Evan T. Xiang, Shi-Hua Do Kwon, Young Huang, Chih-Chin Wyatt, Richard Kwong, Peter D. Freire, Ernesto Smith, Amos B., III Sodroski, Joseph TI Small-Molecule CD4 Mimics Interact with a Highly Conserved Pocket on HIV-1 gp120 SO STRUCTURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; RECEPTOR-BINDING; MONOCLONAL-ANTIBODY; ACCURATE DOCKING; SITE; NEUTRALIZATION; DESIGN; CCR5; MINIPROTEIN AB Human immunodeficiency virus (HIV-1) interaction with the primary receptor, CD4, induces conformational changes in the viral envelope glycoproteins that allow binding to the CCR5 second receptor and virus entry into the host cell. The small molecule NBD-556 mimics CD4 by binding the gp120 exterior envelope glycoprotein, moderately inhibiting virus entry into CD4-expressing target cells and enhancing CCR5 binding and virus entry into CCR5-expressing cells lacking CD4. Studies of NBD-556 analogs and gp120 mutants suggest that (1) NBD-556 binds within the Phe 43 cavity, a highly conserved, functionally important pocket formed as gp120 assumes the CD4-bound conformation; (2) the NBD-556 phenyl ring projects into the Phe 43 cavity; (3) enhancement of CD4-independent infection by NBD-556 requires the induction of conformational changes in gp120; and (4) increased affinity of NBD-556 analogs for gp120 improves antiviral potency during infection of CD4-expressing cells. C1 [Madani, Navid; Princiotto, Amy M.; Wang, Liping; Xiang, Shi-Hua; Sodroski, Joseph] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Madani, Navid; Sodroski, Joseph] Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. [Schoen, Arne; Brower, Evan T.; Freire, Ernesto] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. [LaLonde, Judith M.] Bryn Mawr Coll, Dept Chem, Bryn Mawr, PA 19010 USA. [Courter, Joel R.; Soeta, Takahiro; Ng, Danny; Smith, Amos B., III] Univ Penn, Dept Chem, Philadelphia, PA 19104 USA. [Do Kwon, Young; Huang, Chih-Chin; Wyatt, Richard; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Kwon, Young Do/A-6957-2010; SOETA, Takahiro/E-7060-2015 OI SOETA, Takahiro/0000-0001-9883-4772 FU National Institutes of Health [GM56550, AI24755I60354]; International AIDS Vaccine Initiative; William F. McCarty-Cooper FX We thank Wayne Hendrickson and Irwin Chaiken for valuable discussion. We thank Yvette McLaughlin and Elizabeth Carpelan for manuscript preparation, and Jonathan Stuckey for preparation of figures. This study was supported by the National Institutes of Health (Grants GM56550, AI24755, and AI60354), the International AIDS Vaccine Initiative, and William F. McCarty-Cooper. NR 39 TC 100 Z9 102 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV 12 PY 2008 VL 16 IS 11 BP 1689 EP 1701 DI 10.1016/j.str.2008.09.005 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 374GQ UT WOS:000261032200012 PM 19000821 ER PT J AU Becker, V Sengupta, D Ketteler, R Ullmann, GM Smith, JC Klingmuller, U AF Becker, Verena Sengupta, Durba Ketteler, Robin Ullmann, G. Matthias Smith, Jeremy C. Klingmueller, Ursula TI Packing Density of the Erythropoietin Receptor Transmembrane Domain Correlates with Amplification of Biological Responses SO BIOCHEMISTRY LA English DT Article ID PRIMARY FAMILIAL POLYCYTHEMIA; SIGNAL-TRANSDUCTION; MEMBRANE-PROTEINS; PROGENITOR CELLS; POINT MUTATION; DIMERIZATION; ACTIVATION; OLIGOMERIZATION; GENE; ERYTHROCYTOSIS AB The formation of signal-promoting dimeric or oligomeric receptor complexes at the cell surface is modulated by self-interaction of their transmembrane (TM) domains. To address the importance of TM domain packing density for receptor functionality, we examined a set of asparagine mutants in the TM domain of the erythropoietin receptor (EpoR). We identified EpoR-T242N as a receptor variant that is present at the cell surface similar to wild-type EpoR but lacks visible localization in vesicle-like structures and is impaired in efficient activation of specific signaling cascades. Analysis by a molecular modeling approach indicated an increased interhelical distance for the EpoR-T242N TM dimer. By employing the model, we designed additional mutants with increased or decreased packing volume and confirmed a correlation between packing volume and biological responsiveness. These results propose that the packing density of the TM domain provides a novel layer for fine-tuned regulation of signal transduction and cellular decisions. C1 [Becker, Verena; Klingmueller, Ursula] German Canc Res Ctr, DKFZ ZMBH Alliance, Div Syst Biol Signal Transduct, D-6900 Heidelberg, Germany. [Sengupta, Durba; Smith, Jeremy C.] Univ Heidelberg, Interdisciplinary Ctr Sci Comp, Heidelberg, Germany. [Ketteler, Robin] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. [Ullmann, G. Matthias] Univ Bayreuth, Bayreuth, Germany. [Smith, Jeremy C.] Univ Tennessee, ORNL Ctr Mol Biophys, Oak Ridge Natl Lab, Oak Ridge, TN 37831 USA. RP Klingmuller, U (reprint author), German Canc Res Ctr, DKFZ ZMBH Alliance, Div Syst Biol Signal Transduct, D-6900 Heidelberg, Germany. EM u.klingmueller@dkfz-heidelberg.de RI smith, jeremy/B-7287-2012; Klingmuller, Ursula/G-8477-2013; Ullmann, Matthias/H-1361-2014; OI smith, jeremy/0000-0002-2978-3227; Klingmuller, Ursula/0000-0001-9845-3099; Ullmann, Matthias/0000-0002-6350-798X; Ketteler, Robin/0000-0002-2786-7291 FU European Commission Sixth Framework Programme COSBICS [LSHG-CT-2004-512060]; Deutsche Forschungsgemeinschaft [DFG/Ke904] FX This work was supported by the European Commission Sixth Framework Programme COSBICS project (LSHG-CT-2004-512060) (to V.B.) and by the Deutsche Forschungsgemeinschaft (DFG/Ke904) (to R. K.). NR 49 TC 11 Z9 11 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 11 PY 2008 VL 47 IS 45 BP 11771 EP 11782 DI 10.1021/bi801425e PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 368JH UT WOS:000260616900009 PM 18855427 ER PT J AU Jesser, C Mucci, L Farmer, D Moon, C Li, H Gaziano, JM Stampfer, M Ma, J Kantoff, P AF Jesser, C. Mucci, L. Farmer, D. Moon, C. Li, H. Gaziano, J. M. Stampfer, M. Ma, J. Kantoff, P. TI Effects of G/A polymorphism, rs266882, in the androgen response element I of the PSA gene on prostate cancer risk, survival and circulating PSA levels SO BRITISH JOURNAL OF CANCER LA English DT Article DE prostate cancer; PSA gene; AREI-158 G/A polymorphism (rs266882); androgen receptor; Physicians' Health Study ID GROWTH-FACTOR-I; ANTIGEN LEVELS; RECEPTOR GENE; SUSCEPTIBILITY; BINDING; PSA/KLK3; REPEATS; REGION; CELLS AB Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA - 158 G/A, rs266882) in AREI of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case - control analysis of 500 white cases and 676 age- and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR = 1.21, 95% confidence intervals (CI): 0.88 - 1.67) or prostate cancer-specific survival (RR = 0.94, 95% CI: 0.56 - 1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null. C1 [Jesser, C.; Mucci, L.; Gaziano, J. M.; Stampfer, M.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mucci, L.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Farmer, D.; Moon, C.; Kantoff, P.] Dana Farber Canc Inst, Div Solid Tumor Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. [Gaziano, J. M.] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. RP Mucci, L (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM lorelei.mucci@channing.harvard.edu FU National Cancer Institute [CA-34944, CA-40360, CA-097193]; National Heart, Lung and Blood Institute, Bethesda, MD [HL-26490, HL-34595]; Cancer Epidemiology [T32 CA 09001]; NCI/NIH [R01 CA 090598] FX We thank the participants of the Physicians' Health Study for their longstanding commitment and participation in the study. The Physicians' Health Study is supported by grants CA-34944, CA-40360 and CA-097193 from the National Cancer Institute and grants HL-26490 and HL-34595 from the National Heart, Lung and Blood Institute, Bethesda, MD. Ms Jesser was supported by the National Research Service Award Training Program in Cancer Epidemiology (T32 CA 09001). Project supported by R01 CA 090598 (NCI/NIH). NR 28 TC 17 Z9 17 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV 11 PY 2008 VL 99 IS 10 BP 1743 EP 1747 DI 10.1038/sj.bjc.6604690 PG 5 WC Oncology SC Oncology GA 371LI UT WOS:000260832400026 PM 18827812 ER PT J AU Velagaleti, RS Pencina, MJ Murabito, JM Wang, TJ Parikh, NI D'Agostino, RB Levy, D Kannel, WB Vasan, RS AF Velagaleti, Raghava S. Pencina, Michael J. Murabito, Joanne M. Wang, Thomas J. Parikh, Nisha I. D'Agostino, Ralph B. Levy, Daniel Kannel, William B. Vasan, Ramachandran S. TI Long-Term Trends in the Incidence of Heart Failure After Myocardial Infarction SO CIRCULATION LA English DT Article DE heart failure; myocardial infarction; prognosis; risk factors; epidemiology ID LEFT-VENTRICULAR DYSFUNCTION; TEMPORAL TRENDS; FRAMINGHAM; DISEASE; EPIDEMIOLOGY; PERSPECTIVE; MORTALITY; SURVIVAL; RATES; DEATH AB Background - Although mortality after myocardial infarction (MI) has declined in the United States in recent decades, there have been few community-based investigations of the long-term trends in the incidence of heart failure after MI, and their results appear to be conflicting. Methods and Results - We evaluated 676 Framingham Heart Study participants between 45 and 85 years of age (mean age 67 years, 34% women) who developed a first MI between 1970 and 1999. We assessed the incidence rates of heart failure and of death without heart failure in each of 3 decades (1970 to 1979, 1980 to 1989, and 1990 to 1999). We estimated the multivariable-adjusted risk of events in the latter 2 decades, with the period 1970 to 1979 serving as the referent. The 30-day incidence of heart failure after MI rose from 10% in 1970 to 1979 to 23.1% in 1990 to 1999 (P for trend 0.003), whereas 30-day mortality after MI declined from 12.2% (1970 to 1979) to 4.1% (1990 to 1999). The 5-year incidence of heart failure after MI rose from 27.6% in 1970 to 1979 to 31.9% in 1990 to 1999 (P for trend 0.02), whereas 5-year mortality after MI declined from 41.1% (1970 to 1979) to 17.3% (1990 to 1999). In multivariable analyses, compared with the period 1970 to 1979, we observed higher 30-day (risk ratio 2.05, 95% confidence interval 1.25 to 3.36) and 5-year (risk ratio 1.74, 95% confidence interval 1.07 to 2.84) risks of heart failure in the decade 1990 to 1999. These trends were accompanied by lower 30-day (risk ratio 0.21, 95% confidence interval 0.09 to 0.47) and 5-year (risk ratio 0.31, 95% confidence interval 0.18 to 0.54) mortality rates in 1990 to 1999. Conclusions - In the present community-based sample, we observed an increase in the incidence of heart failure in recent decades that paralleled the decrease in mortality after MI. (Circulation. 2008; 118: 2057-2062.) C1 [Velagaleti, Raghava S.; Pencina, Michael J.; Murabito, Joanne M.; Wang, Thomas J.; Parikh, Nisha I.; D'Agostino, Ralph B.; Levy, Daniel; Kannel, William B.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Wang, Thomas J.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Div Cardiol, Boston, MA USA. [Pencina, Michael J.; D'Agostino, Ralph B.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Prevent Med Sect, Boston Med Ctr, Boston, MA 02118 USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Univ, Sch Med, Cardiol Sect, Boston Med Ctr, Boston, MA 02118 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston Med Ctr, Boston, MA 02118 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970 FU National Institutes of Health/National Heart, Lung, and Blood Institute [N01-HC-25195, 2K24HL4334] FX This work was supported by National Institutes of Health/National Heart, Lung, and Blood Institute contract No. N01-HC-25195 and 2K24HL4334 (Dr Vasan). NR 23 TC 187 Z9 196 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 11 PY 2008 VL 118 IS 20 BP 2057 EP 2062 DI 10.1161/CIRCULATIONAHA.108.784215 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 370XG UT WOS:000260795800007 PM 18955667 ER PT J AU Terranova, R Yokobayashi, S Stadler, MB Otte, AP van Lohuizen, M Orkin, SH Peters, AHFM AF Terranova, Rrni Yokobayashi, Shihori Stadler, Michael B. Otte, Arie P. van Lohuizen, Maarten Orkin, Stuart H. Peters, Antoine H. F. M. TI Polycomb Group Proteins Ezh2 and Rnf2 Direct Genomic Contraction and Imprinted Repression in Early Mouse Embryos SO DEVELOPMENTAL CELL LA English DT Article ID NONCODING RNAS; EPIGENETIC DYNAMICS; HISTONE METHYLATION; DNA METHYLATION; X-INACTIVATION; CONTROL REGION; STEM-CELLS; GENES; RECRUITMENT; COMPLEXES AB Genomic imprinting regulates parental-specific expression of particular genes and is required for normal mammalian development. How imprinting is established during development is, however, largely unknown. To address this question, we studied the mouse Kcnq1 imprinted cluster at which paternal-specific silencing depends on expression of the non-coding RNA Kcnq1ot1. We show that Kcnq1ot1 is expressed from the zygote stage onward and rapidly associates with chromatin marked by Polycomb group (PcG) proteins and repressive histone modifications, forming a discrete repressive nuclear compartment devoid of RNA polymerase II, a configuration also observed at the Igf2r imprinted cluster. In this compartment, the paternal Kcnq1 cluster exists in a three-dimensionally contracted state. In vivo the PcG proteins Ezh2 and Rnf2 are independently required for genomic contraction and imprinted silencing. We propose that the formation of a parental-specific higher-order chromatin organization renders imprint clusters competent for monoallelic silencing and assign a central role to PcG proteins in this process. C1 [Terranova, Rrni; Yokobayashi, Shihori; Stadler, Michael B.; Peters, Antoine H. F. M.] Friedrich Miescher Inst Biomed Res, CH-4058 Basel, Switzerland. [Otte, Arie P.] Univ Amsterdam, Swammerdam Inst Life Sci, NL-1098 SM Amsterdam, Netherlands. [van Lohuizen, Maarten] Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. [van Lohuizen, Maarten] Netherlands Canc Inst, Ctr Biomed Genet, NL-1066 CX Amsterdam, Netherlands. [Orkin, Stuart H.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat,Div Hematol Oncol,Childrens Hosp, Boston, MA 02115 USA. RP Peters, AHFM (reprint author), Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland. EM antoine.peters@fmi.ch FU HFSP; Novartis Research Foundation; NoE network FX We thank Miguel Vidal, Haruhiko Koseki, Christian Seiser, and Thomas Jenu-wein for providing antisera; Barbara Knowles and Robert Fell for making available Zp3-Cre transgenic mice and SD7P11 congenic mice, respectively. We thank Edith Heard and Julie Chaumeil for helpful technical advice. We acknowledge FMI colleagues Laurent Gelman. Jens Rietdorf, and Patrick Schwarb for excellent microscopy and imaging assistance; Aaron Ponti for generating the random-spot algorithms Fred Zilbermann and Carolin Kolb for technical assistance and the FMI animal facility. We thank Ruth Williams, Philip Hublitz, and Dirk Schblbeler for critical reading of the manuscript and all members of the Peters lab for fruitful discussions. R.T., S.Y., and A.H.F.M.P. conceived and designed the experiments. R.T. and S.Y. performed the experiments. R.T., S.Y., M.B.S., and A.H.F.M.P. analyzed the data. A.P.O. provided antibodies; NI and S.H.O provided Rnf2 and Ezh2 conditionally deficient mice, respectively. R.T. and A.H.F.M.P. wrote the manuscript. S.Y. is a recipient of a HFSP fellowship. Research in the Peters lab is supported by the Novartis Research Foundation and the NoE network "The Epigenome." NR 37 TC 181 Z9 197 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD NOV 11 PY 2008 VL 15 IS 5 BP 668 EP 679 DI 10.1016/j.devcel.2008.08.015 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 371XW UT WOS:000260867000008 PM 18848501 ER PT J AU Kalinchuk, AV McCarley, RW Stenberg, D Porkka-Heiskanen, T Basheer, R AF Kalinchuk, A. V. McCarley, R. W. Stenberg, D. Porkka-Heiskanen, T. Basheer, R. TI THE ROLE OF CHOLINERGIC BASAL FOREBRAIN NEURONS IN ADENOSINE-MEDIATED HOMEOSTATIC CONTROL OF SLEEP: LESSONS FROM 192 IGG-SAPORIN LESIONS SO NEUROSCIENCE LA English DT Article DE sleep deprivation; cholinergic lesion; delta activity; stereology; rat; immunotoxin ID BEHAVIORAL STATE; RECOVERY SLEEP; NGF RECEPTOR; TIME-COURSE; WAKE CYCLE; C-FOS; RAT; MICRODIALYSIS; DEPRIVATION; WAKEFULNESS AB A topic of high current interest and controversy is the basis of the homeostatic sleep response, the increase in non-rapid-eye-movement (NREM) sleep and NREM-delta activity following sleep deprivation (SD). Adenosine, which accumulates in the cholinergic basal forebrain (BF) during SD, has been proposed as one of the important homeostatic sleep factors. It is suggested that sleep-inducing effects of adenosine are mediated by inhibiting the wake-active neurons of the BF, including cholinergic neurons. Here we examined the association between SD-induced adenosine release, the homeostatic sleep response and the survival of cholinergic neurons in the BF after injections of the immunotoxin 192 immunoglobulin G (IgG)-saporin (saporin) in rats. We correlated SD-induced adenosine level in the BF and the homeostatic sleep response with the cholinergic cell loss 2 weeks after local saporin injections into the BF, as well as 2 and 3 weeks after i.c.v. saporin injections. Two weeks after local saporin injection there was an 88% cholinergic cell loss, coupled with nearly complete abolition of the SD-induced adenosine increase in the BF, the homeostatic sleep response, and the sleep-inducing effects of BF adenosine infusion. Two weeks after i.c.v. saporin injection there was a 59% cholinergic cell loss, correlated with significant increase in SD-induced adenosine level in the BF and an intact sleep response. Three weeks after i.c.v. saporin injection there was an 87% cholinergic cell loss, nearly complete abolition of the SD-induced adenosine increase in the BF and the homeostatic response, implying that the time course of i.c.v. saporin lesions is a key variable in interpreting experimental results. Taken together, these results strongly suggest that cholinergic neurons in the BF are important for the SD-induced increase in adenosine as well as for its sleep-inducing effects and play a major, although not exclusive, role in sleep homeostasis. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Kalinchuk, A. V.; McCarley, R. W.; Basheer, R.] Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab, Boston, MA 02132 USA. [Kalinchuk, A. V.; McCarley, R. W.; Basheer, R.] VA Boston Healthcare Syst, Boston, MA 02132 USA. [Stenberg, D.; Porkka-Heiskanen, T.] Univ Helsinki, Inst Biomed, Helsinki, Finland. RP Kalinchuk, AV (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Neurosci Lab, 1400 VFW Pkwy, Boston, MA 02132 USA. EM anna_kalinchuk@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU Department of Veterans Affairs Medical Research Service; ESRS Sanoff-Synthelabo Research; National Institute of Mental Health [NIMH39683]; Academy of Finland, European Union [LSHM-CT-2005-518189]; European Union [MCRTN-CT-2004-512362]; Finska Lakaresallskapet, the Sigrid Juselius Foundation FX We dedicate this paper to the late Dr. Dag Stenberg. This work was supported by the Department of Veterans Affairs Medical Research Service Award to R.B., the ESRS Sanoff-Synthelabo Research Award to A. V. K., the National Institute of Mental Health (NIMH39683) to R. W.M., and the Academy of Finland, European Union grant LSHM-CT-2005-518189, European Union grant MCRTN-CT-2004-512362, Finska Lakaresallskapet, the Sigrid Juselius Foundation to T.P.-H. We thank Drs. James T. McKenna and Robert E. Strecker for helpful discussion. We thank Dr. rer. Nat. Ernst Mecke, Mrs. Pirjo Saarelainen and Mrs. Sari Levo-Siitari for excellent technical assistance and Peter Hirsch and Dewayne Williams for help with animal care. NR 60 TC 42 Z9 43 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV 11 PY 2008 VL 157 IS 1 BP 238 EP 253 DI 10.1016/j.neuroscience.2008.08.040 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 369UE UT WOS:000260718600024 PM 18805464 ER PT J AU Irazoqui, JE Ng, A Xavier, RJ Ausubel, FM AF Irazoqui, Javier E. Ng, Aylwin Xavier, Ramnik J. Ausubel, Frederick M. TI Role for beta-catenin and HOX transcription factors in Caenorhabditis elegans and mammalian host epithelial-pathogen interactions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE homeobox protein; host-pathogen interactions; Staphylococcus aureus ID NF-KAPPA-B; INNATE IMMUNITY; C-ELEGANS; STAPHYLOCOCCUS-AUREUS; GENES; PATHWAY; WNT; CELLS; MODEL; DIFFERENTIATION AB We used the model nematode Caenorhabditis elegans infected with the human pathogen Staphylococcus aureus to identify components of epithelial immunity. Transcriptional profiling and reverse genetic analysis revealed that mutation of the C elegans beta-catenin homolog bar-1 or the downstream homeobox gene egl-5 results in a defective response and hypersensitivity to S. aureus infection. Epistasis analysis showed that bar-1 and egi-5 function in parallel to previously described C elegans immune-response pathways. Overexpression of human homologs of egl-5 modulated NF-kappa B-dependent TLR2 signaling in epithelial cells. These data suggest that beta-catenin and homeobox genes play an important and conserved role in innate immune defense. C1 [Irazoqui, Javier E.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Irazoqui, Javier E.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Dept Genet, Boston, MA 02114 USA. [Irazoqui, Javier E.; Ng, Aylwin; Xavier, Ramnik J.; Ausubel, Frederick M.] Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. RP Ausubel, FM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Simches Res Bldg,185 Cambridge St CPZN7250, Boston, MA 02114 USA. EM ausubel@molbio.mgh.harvard.edu RI Irazoqui, Javier/A-8028-2013; OI Irazoqui, Javier/0000-0001-6553-1329 FU National Institutes of Health [DK43351, DK57521, AI062773, AI064332]; National Center for Research Resources; Jane Coffin Childs Memorial FX We thank E. Troemel, L. Stanek, S. Margolis, and D. Colon-Ramos for critical reading of the manuscript and J.Powell for help designing qRT-PCR primers. TEM was performed by M. McKee in the Microscopy Core of the Center for Systems Biology supported by National Institutes of Health Grants DK43351 and DK57521. Nematode strains were provided by the Caenorhabditis Genetics Center funded by the National Institutes of Health National Center for Research Resources. This work was funded by National Institutes of Health Grants A1062773 (to RAX) and AI064332 (to F.M.A.) and by postdoctoral fellowships from the Jane Coffin Childs Memorial Fund for Medical Research and the Charles A. King Trust, Bank of America, Co-Trustee (Boston, MA) (to J.E.I.), and from the Crohn's and Colitis Foundation of America (to A.N.). NR 39 TC 52 Z9 77 U1 3 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 2008 VL 105 IS 45 BP 17469 EP 17474 DI 10.1073/pnas.0809527105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 373OP UT WOS:000260981800056 PM 18981407 ER PT J AU Kita, T Hata, Y Arita, R Kawahara, S Miura, M Nakao, S Mochizuki, Y Enaida, H Goto, Y Shimokawa, H Hafezi-Moghadam, A Ishibashi, T AF Kita, Takeshi Hata, Yasuaki Arita, Ryoichi Kawahara, Shuhei Miura, Muneki Nakao, Shintaro Mochizuki, Yasutaka Enaida, Hiroshi Goto, Yoshinobu Shimokawa, Hiroaki Hafezi-Moghadam, Ali Ishibashi, Tatsuro TI Role of TGF-beta in proliferative vitreoretinal diseases and ROCK as a therapeutic target SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE proliferative diabetic retinopathy; proliferative vitreoretinopathy; fibrosis; wound healing ID GROWTH-FACTOR-BETA; COLLAGEN GEL CONTRACTION; RHO-KINASE PATHWAY; SMOOTH-MUSCLE; CELLS; EYE; HYALOCYTES; MIGRATION; MYOFIBROBLAST; INVOLVEMENT AB Cicatricial contraction of preretinal fibrous membrane is a cause of severe vision loss in proliferative vitreoretinal diseases such as proliferative diabetic retinopathy (PDR) and proliferative vitreoretinopathy (PVR). TGF-beta is overexpressed in the vitreous of patients with proliferative vitreoretinal diseases and is also detectable in the contractile membranes. Therefore, TGF-beta is presumed to contribute to the cicatricial contraction of the membranes, however, the underlying mechanisms and TGF-beta's importance among various other factors remain to be elucidated. Vitreous samples from PDR or PVR patients caused significantly larger contraction of hyalocyte-containing collagen gels, compared with nonproliferative controls. The contractile effect was strongly correlated with the vitreal concentration of activated TGF-beta 2 (r = 0.82, P < 0.0001). PDR or PVR vitreous promoted expression of a-smooth muscle actin (a-SMA) and phosphorylation of myosin light chain (MLC), a downstream mediator of Rho-kinase (ROCK), both of which were dramatically but incompletely suppressed by TGF-beta blockade. In contrast, fasudil, a potent and selective ROCK inhibitor, almost completely blocked the vitreous-induced MLC phosphorylation and collagen gel contraction. Fasudil disrupted a-SMA organization, but it did not affect its vitreal expression. in vivo, fasudil significantly inhibited the progression of experimental PVR in rabbit eyes without affecting the viability of retinal cells by electroretinographic and histological analyses. These results elucidate the critical role of TGF-beta in mediating cicatricial contraction in proliferative vitreoretinal diseases. ROCK, a key downstream mediator of TGF-beta and other factors might become a unique therapeutic target in the treatment of proliferative vitreoretinal diseases. C1 [Kita, Takeshi; Hata, Yasuaki; Arita, Ryoichi; Kawahara, Shuhei; Miura, Muneki; Nakao, Shintaro; Mochizuki, Yasutaka; Enaida, Hiroshi; Ishibashi, Tatsuro] Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, Fukuoka 8128582, Japan. [Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Angiogenesis Lab, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. [Nakao, Shintaro; Hafezi-Moghadam, Ali] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Goto, Yoshinobu] Int Univ Hlth & Welf, Fac Rehabil, Dept Occupat Therapy, Fukuoka 8318501, Japan. [Shimokawa, Hiroaki] Tohoku Univ, Grad Sch Med, Dept Cardiol, Aoba Ku, Sendai, Miyagi 9808575, Japan. RP Hata, Y (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Ophthalmol, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM hatachan@med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016; OI Hafezi-Moghadam, Ali/0000-0002-5336-0697 FU Asahi Kasei Pharma Corporation, Tokyo, Japan; Ministry of Education, Science, Sports and Culture, Japan [19592026, 18791283, 18591925]; National Institutes of Health [Al-050775, EY-14104, HL-086933] FX We thank Marion W. Knight and Edward F. Knight and Research to Prevent Blindness. We acknowledge Asahi Kasei Pharma Corporation, Tokyo, Japan for its generous provision of fasudil. This study was supported in part by grants from the Ministry of Education, Science, Sports and Culture, Japan (Grant-in-Aid for Scientific Research nos. 19592026, 18791283, and 18591925). This work was supported by National Institutes of Health Grants Al-050775, EY-14104, and HL-086933, a Research Fellowship Award from Bausch & Lomb, and a Fellowship Award from the Japan Eye Bank Association (to S.N.). NR 38 TC 63 Z9 72 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 NOV 11 PY 2008 VL 105 IS 45 BP 17504 EP 17509 DI 10.1073/pnas.0804054105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 373OP UT WOS:000260981800062 PM 18952846 ER PT J AU Roffman, JL Gollub, RL Calhoun, VD Wassink, TH Weiss, AP Ho, BC White, T Clark, VP Fries, J Andreasen, NC Goff, DC Manoach, DS AF Roffman, Joshua L. Gollub, Randy L. Calhoun, Vince D. Wassink, Thomas H. Weiss, Anthony P. Ho, Beng C. White, Tonya Clark, Vincent P. Fries, Jill Andreasen, Nancy C. Goff, Donald C. Manoach, Dara S. TI MTHFR 677C -> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val -> Met SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE dopamine; folate; functional MRI; genetics; methylation ID CATECHOL-O-METHYLTRANSFERASE; WORKING-MEMORY PERFORMANCE; EXECUTIVE FUNCTION; VAL(108/158) MET; CORTEX; BRAIN; GENE; VAL(158)MET; METHYLATION; DYSFUNCTION AB Understanding how risk genes cumulatively impair brain function in schizophrenia could provide critical insights into its pathophysiology. Working memory impairment in schizophrenia has been associated with abnormal dopamine signaling in the prefrontal cortex, which is likely under complex genetic control. The catechol-O-methyltransferase (COMT) 158Val -> Met polymorphism (rs4680), which affects the availability of prefrontal dopamine signaling, consistently stratifies prefrontal activation during working memory performance. However, the low-dopamine COMT 158Val allele does not confer increased risk for schizophrenia, and its effects on prefrontal function are not specific to the disorder. In the setting of other genetic variants influencing prefrontal dopamine signaling, COMT 158Val -> Met genotype may exert disease-specific effects. A second polymorphism, methylenetetrahydrofolate reductase (MTHFR) 677C -> T (rs1801133), has been associated with overall schizophrenia risk and executive function impairment in patients, and may influence dopamine signaling through mechanisms upstream of COMT effects. We found that the hypofunctional 677T variant was associated with decreased working memory load-dependent activation in the prefrontal and insular cortices in 79 schizophrenia patients, but not in 75 demographically matched healthy controls. Further, significant MTHFR x COMT genotype interactions were observed, which differed by diagnostic group: Reduced prefrontal activation was associated with the 677T and 158Val alleles in patients, but with 677C/C and 158Met/Met genotype in controls. These findings are consistent with epistatic effects of the COMT and MTHFR polymorphisms on prefrontal dopamine signaling, and suggest that in schizophrenia patients, the MTHFR 677T allele exacerbates prefrontal dopamine deficiency. The findings also suggest the importance of weighing COMT effects on prefrontal function within the context of MTHFR genotype. C1 [Roffman, Joshua L.; Gollub, Randy L.; Weiss, Anthony P.; Goff, Donald C.; Manoach, Dara S.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Roffman, Joshua L.; Gollub, Randy L.; Weiss, Anthony P.; Goff, Donald C.; Manoach, Dara S.] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. [Calhoun, Vince D.] Univ New Mexico, Dept Elect & Comp Engn, Albuquerque, NM 87131 USA. [Calhoun, Vince D.; Clark, Vincent P.; Fries, Jill] MIND Res Network, Albuquerque, NM 87131 USA. [Wassink, Thomas H.; Ho, Beng C.; Andreasen, Nancy C.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA. [White, Tonya] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Clark, Vincent P.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. RP Roffman, JL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 149 13th St,Room 2656, Charlestown, MA 02129 USA. EM jroffman@partners.org RI Ho, Beng-Choon/D-6959-2011; Calhoun, Vince/H-7146-2013; Clark, Vincent/B-3343-2010 OI Ho, Beng-Choon/0000-0003-3976-1555; Calhoun, Vince/0000-0001-9058-0747; Clark, Vincent/0000-0002-9151-2102 FU MIND Institute; SFNR; Department of Energy [DE-F02-99ER62764-AO12]; MIND Research Network; National Institutes of Health [EB001 632-04] FX The authors thank all of the participants as well as the investigators and support staff of the MIND Institute who made this study possible. we also thank Dr. Doug Greve for his assistance with the SFNR analysis. This research was supported by a grant from the Department of Energy (DE-F02-99ER62764-AO12) to the MIND Research Network and National Institutes of Health Grant EB001 632-04 (to J.L.R.). NR 38 TC 65 Z9 67 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 11 PY 2008 VL 105 IS 45 BP 17573 EP 17578 DI 10.1073/pnas.0803727105 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 373OP UT WOS:000260981800074 PM 18988738 ER PT J AU Rifkin, DE Shlipak, MG Katz, R Fried, LF Siscovick, D Chonchol, M Newman, AB Sarnak, MJ AF Rifkin, Dena E. Shlipak, Michael G. Katz, Ronit Fried, Linda F. Siscovick, David Chonchol, Michel Newman, Anne B. Sarnak, Mark J. TI Rapid Kidney Function Decline and Mortality Risk in Older Adults SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID SERUM CYSTATIN-C; GLOMERULAR-FILTRATION-RATE; BODY-COMPOSITION; ELDERLY PERSONS; CARDIOVASCULAR-DISEASE; RENAL-INSUFFICIENCY; POOLED ANALYSIS; CREATININE; INDIVIDUALS; PROGNOSIS AB Background: Impaired kidney function is associated with increased mortality risk in older adults. It remains unknown, however, whether longitudinal declines in kidney function are independently associated with increased cardiovascular and all-cause mortality in older adults. Methods: The Cardiovascular Health Study evaluated a cohort of community-dwelling older adults enrolled from 1989 to 1993 in 4 US communities with follow-up through 2005. Among 4380 participants, the slope of annual decline in estimated glomerular filtration rate (eGFR) was estimated using both serum creatinine (eGFR(creat)) and cystatin C (eGFR(cys)) rates, which were measured at baseline, year 3, and year 7 of follow-up. Rapid decline in eGFR was defined as a loss greater than 3 mL/min/1.73 m(2) per year, and cardiovascular and all-cause mortality were assessed over a mean of 9.9 years of follow-up. Results: Mean (SD) levels of creatinine and cystatin C were 0.93 (0.30) mg/dL and 1.03 (0.25) mg/L, respectively; mean (SD) eGFR(creat) and eGFR(cys) were 79 (23) mL/min/1.73 m(2) and 79 (19) mL/min/1.73m(2), respectively. Individuals with rapid decline measured by eGFR(creat) (n = 714; 16%) had increased risk of cardiovascular (adjusted hazard ratio [AHR], 1.70; 95% confidence interval [CI], 1.40-2.06) and all-cause (AHR, 1.73; 95% CI, 1.54-1.94) mortality. Individuals with rapid decline measured by eGFR(cys) (n = 1083; 25%) also had increased risk of cardiovascular (AHR, 1.53; 95% CI, 1.29-1.80) and all-cause (AHR, 1.53; 95% CI, 1.38-1.69) mortality. The association of rapid decline in eGFR with elevated mortality risk did not differ across subgroups based on baseline kidney function, age, sex, race, or prevalent coronary heart disease. Conclusion: Rapid decline in eGFR is associated with an increased risk of cardiovascular and all-cause mortality in older adults, independent of baseline eGFR and other demographic variables. C1 [Rifkin, Dena E.; Sarnak, Mark J.] Tufts Med Ctr, Div Nephrol, Boston, MA 02111 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, San Francisco, CA 94143 USA. [Shlipak, Michael G.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. [Katz, Ronit] Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. [Fried, Linda F.] Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Med Serv, Pittsburgh, PA USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. [Fried, Linda F.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Med, Pittsburgh, PA USA. [Siscovick, David] Univ Washington, Dept Med, Seattle, WA USA. [Siscovick, David] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Chonchol, Michel] Univ Colorado, Hlth Sci Ctr, Div Renal Dis & Hypertens, Denver, CO USA. RP Rifkin, DE (reprint author), Tufts Med Ctr, Div Nephrol, 750 Washington St,Box 391, Boston, MA 02111 USA. EM drifkin@tuftsmedicalcenter.org RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland [R01-AG-027002, K24DK078204, N01-HC-35129, N01-HC-45133, N01HC-75150, N01-HC-85079, N01-HC-85086, N01-HC-15103, N01-HC-55222, U01 HL080295]; National Institute of Neurological Disorders and Stroke, Bethesda FX The research reported in this article was supported by contracts R01-AG-027002, K24DK078204, N01-HC-35129, N01-HC-45133, N01HC-75150, N01-HC-85079 through N01-HC-85086, N01-HC-15103, N01-HC-55222, and U01 HL080295 from the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, Maryland, with additional contribution from the National Institute of Neurological Disorders and Stroke, Bethesda. NR 25 TC 165 Z9 166 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 10 PY 2008 VL 168 IS 20 BP 2212 EP 2218 DI 10.1001/archinte.168.20.2212 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 370XS UT WOS:000260797000005 PM 19001197 ER PT J AU Levanon, K Crum, C Drapkin, R AF Levanon, Keren Crum, Christopher Drapkin, Ronny TI New Insights Into the Pathogenesis of Serous Ovarian Cancer and Its Clinical Impact SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; HUMAN FALLOPIAN-TUBE; REDUCING SALPINGO-OOPHORECTOMY; NECROSIS-FACTOR-ALPHA; GERMLINE MUTATION CARRIERS; EPITHELIAL-CELLS; SURFACE EPITHELIUM; FOLLOW-UP; LOW-GRADE; INTRAEPITHELIAL CARCINOMA AB There are only a handful of concepts concerning cancer and carcinogenesis that are currently beyond dispute. One such dogma is the adenoma-carcinoma sequence and that a multistep accumulation of genetic alterations is required for transformation from a benign to a neoplastic tissue. The inevitable derivative of this dogma is that every invasive carcinoma is in fact a missed intraepithelial tumor, and furthermore, a late evolutionary stage in the sequence of development from a precursor lesion. Until fairly recently, high-grade serous ovarian carcinoma seemed to be one of the only known deviants of these concepts. In this article, we discuss the emergence of the fallopian tube fimbria as a field of origin for high-grade serous carcinomas and present a binary model of ovarian cancer pathogenesis that takes into consideration prior epidemiologic, morphologic, and genetic data. With the rise of the fallopian tube secretory epithelial cell as a cell of origin for high-grade pelvic serous carcinomas, the need to develop tools and model systems to characterize the biology and physiology of this cell is recognized. C1 [Drapkin, Ronny] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Drapkin, R (reprint author), Dana Farber Canc Inst, Dept Med Oncol, JF215D,44 Binney St, Boston, MA 02115 USA. EM ronny_drapkin@dfci.harvard.edu RI Drapkin, Ronny/E-9944-2016 OI Drapkin, Ronny/0000-0002-6912-6977 FU National Cancer Institute [P50 CA105009, K08 CA108748, R21 CA12468]; Ovarian Cancer Research Fund; Phi Beta Psi Sorority Charitable Trust; Fannie E. Ripple Foundation; Robert and Deborah First Fund; Randi and Joei Cutler Ovarian Cancer Research Fund; Columbia Hospital for Women Research Foundation FX Supported by Grants No. P50 CA105009, K08 CA108748, R21 CA12468 from the National Cancer Institute, Ovarian Cancer Research Fund (individual investigator award and program project development award), Phi Beta Psi Sorority Charitable Trust, Fannie E. Ripple Foundation, Robert and Deborah First Fund, Randi and Joei Cutler Ovarian Cancer Research Fund, and the Columbia Hospital for Women Research Foundation. NR 119 TC 203 Z9 215 U1 0 U2 11 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 NOV 10 PY 2008 VL 26 IS 32 BP 5284 EP 5293 DI 10.1200/JCO.2008.18.1107 PG 10 WC Oncology SC Oncology GA 369MK UT WOS:000260698400023 PM 18854563 ER PT J AU Zhou, XH Lin, HZ AF Zhou, Xiao-Hua Lin, Huazhen TI Semi-parametric maximum likelihood estimates for ROC curves of continuous-scale tests SO STATISTICS IN MEDICINE LA English DT Article DE ROC curves; sensitivity and specificity; semi-parametric maximum likelihood estimators ID COMPARING DIAGNOSTIC MARKERS; TRANSFORMATION MODELS AB In this paper, we propose a new semi-parametric maximum likelihood (ML) estimate of a receiver operating characteristic (ROC) curve that satisfies the property of invariance of the ROC curve and is easy to compute. We show that our new estimator is root n-consistent and has an asymptotically normal distribution. Our extensive Simulation studies show that the proposed method is efficient and robust. Finally, we illustrate the application of the proposed estimator in a real data set. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Zhou, Xiao-Hua; Lin, Huazhen] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Zhou, Xiao-Hua] VA Puget Sound Hlth Care Syst, HSR&D Ctr Excellence, Seattle, WA 98108 USA. [Lin, Huazhen] Sichuan Univ, Sch Math, Chengdu 610064, Sichuan, Peoples R China. RP Zhou, XH (reprint author), Univ Washington, Dept Biostat, Seattle, WA 98195 USA. EM azhou@u.washington.edu FU NIH [R01EB005829]; NSF [DMS 0603913]; Fund of National Natural Science [10771148] FX Contract/grant sponsor: NIH; contract/grant number: R01EB005829; Contract/grant sponsor: NSF; contract/grant number: DMS 0603913; Contract/grant sponsor: Fund of National Natural Science; contract/grant number: 10771148 NR 17 TC 5 Z9 5 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 10 PY 2008 VL 27 IS 25 BP 5271 EP 5290 DI 10.1002/sim.3349 PG 20 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 368RS UT WOS:000260640800010 PM 18613272 ER EF