FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Katiyar, SK AF Katiyar, Santosh K. TI Interleukin-12 and photocarcinogenesis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE interleukin-12; photocarcinogenesis; cyclobutane pyrimidine dimers; UV radiation ID RADIATION-INDUCED IMMUNOSUPPRESSION; CELL STIMULATORY FACTOR; ANTIGEN-PRESENTING CELLS; IFN-GAMMA PRODUCTION; SKIN-CANCER; ULTRAVIOLET-RADIATION; DNA-REPAIR; TUMOR-REGRESSION; IN-VIVO; T-CELL AB UV radiation induces immunosuppression and inflammatory responses, as well as oxidative stress and DNA damage, in skin cells and these various effects have been implicated in melanoma and nonmelanoma skin cancers, i.e., photocarcinogenesis. The cytokine interleukin (IL)-12 has been shown to possess potent antitumor activity in a wide variety of murine tumor models. In this review, we summarize the evidence that IL-12 plays a role in preventing photocarcinogenesis, and present a model of its possible mechanisms of action. Treatment of mice with IL-12 prevents UV-induced immunosuppression in a process mediated by repair of UV-induced damaged DNA. After exposure to the photocarcinogenesis protocol, the development of UV-induced tumors is more rapid and the tumor multiplicity and tumor size are significantly greater in IL-12deficient or knockout (KO) mice than their wild-type counterparts. IL-12-deficiency in mice enhances the proliferation potential of tumor cells, and this may be one of the reasons for the rapid growth of the tumors and their greater size. The rate of malignant transformation of UV-induced papillomas to carcinomas also is higher in the IL-12 KO mice than in their wild-type counterparts in terms of carcinoma incidence and carcinoma multiplicity. UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPDs) and sunburn cells is lower, or repaired more rapidly, in wild-type mice than IL-12 KO mice. The IL-12-associated reduction in UV-specific CPDs is due to induction of DNA repair, and particularly enhancement of nucleotide-excision repair. We suggest that endogenous stimulation of IL-12 may protect the skin from UV-induced immunosuppression, DNA damage, and, ultimately, the risk of photocarcinogenesis. Taken together, this information suggests that augmentation of IL-12 should be considered as a strategy for the prevention and treatment of photocarcinogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Alabama, Dept Dermatol, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Birmingham, AL USA. RP Katiyar, SK (reprint author), Univ Alabama, Dept Dermatol, 1670 Univ Blvd,Volker Hall 557,POB 202, Birmingham, AL 35294 USA. EM skatiyar@uab.edu FU NCCIH NIH HHS [R01 AT002536-01A2, R01 AT002536-02, AT002536, R01 AT002536]; NCI NIH HHS [CA104428, CA089738, R03 CA089738-02, R03 CA105368-02, R21 CA104428-01A2, R21 CA104428, R21 CA104428-02, R03 CA089738, R03 CA105368, CA105368, R03 CA105368-01]; NIAMS NIH HHS [P30 AR050948, AR050948-01]; NIEHS NIH HHS [ES11421] NR 61 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2007 VL 224 IS 3 BP 220 EP 227 DI 10.1016/j.taap.2006.11.017 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 227EF UT WOS:000250639300004 PM 17239911 ER PT J AU Keilin, WG Baker, J McCutcheon, S Peranson, E AF Keilin, W. Gregory Baker, Jeff McCutcheon, Stephen Peranson, Elliott TI A Growing Bottleneck: The Internship Supply-Demand Imbalance in 2007 and Its Impact on Psychology Training SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE predoctoral internship training; internship supply and demand; internship match AB This article provides a comprehensive analysis of the growing imbalance between the supply of predoctoral internship positions in psychology and the demand for such positions by graduate students. Data from the 2007 Match sponsored by the Association of Psychology Postdoctoral and Internship Centers (APPIC) are provided along with the results from several surveys of applicants from that year. An overview of applicant and program participation for the nine APPIC Matches that occurred between 1999 and 2007 is also provided. Implications of the increasing supply-demand imbalance for applicants, graduate and internship programs, and the profession are discussed. C1 [Keilin, W. Gregory] Univ Texas Austin, Counseling & Mental Hlth Ctr, Austin, TX 78712 USA. [Baker, Jeff] Univ Texas Med Branch Galveston, Div Rehabil Serv, Galveston, TX USA. [McCutcheon, Stephen] Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. [Peranson, Elliott] Natl Matching Serv Inc, Toronto, ON, Canada. RP Keilin, WG (reprint author), Univ Texas Austin, Counseling & Mental Hlth Ctr, 1 Univ Stn A3500, Austin, TX 78712 USA. EM gkeilin@mail.utexas.edu NR 11 TC 16 Z9 16 U1 0 U2 0 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD NOV PY 2007 VL 1 IS 4 SI SI BP 229 EP 237 DI 10.1037/1931-3918.1.4.229 PG 9 WC Psychology, Educational SC Psychology GA V29EA UT WOS:000208730500002 ER PT J AU Baker, J McCutcheon, S Keilin, WG AF Baker, Jeff McCutcheon, Stephen Keilin, W. Gregory TI The Internship Supply-Demand Imbalance: The APPIC Perspective SO TRAINING AND EDUCATION IN PROFESSIONAL PSYCHOLOGY LA English DT Article DE internship; supply-demand; APPIC; imbalance AB The internship has long been considered the capstone experience in the sequence of doctoral education in professional psychology. Since at least 1999, the number of available internship positions in the United States and Canada has been outstripped by the number of students seeking these positions. The resulting imbalance between supply and demand for internship positions has grown substantially since 2002 and now should be considered to have reached crisis proportions. Although no complete solution to this imbalance is imminently feasible, a comprehensive approach to addressing the crisis requires that both the supply of internships and the growth in demand be addressed. C1 [Baker, Jeff] Univ Texas Med Branch, Div Rehabil Sci, Galveston, TX 77555 USA. [McCutcheon, Stephen] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Keilin, W. Gregory] Univ Texas Austin, Counseling & Mental Hlth Ctr, Austin, TX 78712 USA. RP Baker, J (reprint author), Univ Texas Med Branch, UTMB Psychol Training Program, 301 Univ Blvd, Galveston, TX 77555 USA. EM jeff.baker@utmb.edu NR 6 TC 19 Z9 19 U1 1 U2 2 PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 1931-3918 J9 TRAIN EDUC PROF PSYC JI Train. Educ. Prof. Psychol. PD NOV PY 2007 VL 1 IS 4 SI SI BP 287 EP 293 DI 10.1037/1931-3918.1.4.287 PG 7 WC Psychology, Educational SC Psychology GA V29EA UT WOS:000208730500009 ER PT J AU Delmonico, FL AF Delmonico, Francis L. TI The Pakistani revelation - Commentary SO TRANSPLANT INTERNATIONAL LA English DT Editorial Material C1 Massachusetts Gen Hosp, Transplantat Unit, Boston, MA 02114 USA. RP Delmonico, FL (reprint author), Massachusetts Gen Hosp, Transplantat Unit, 55 Fruit St, Boston, MA 02114 USA. EM Francis_Delmonico@neob.org NR 1 TC 5 Z9 5 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0934-0874 J9 TRANSPL INT JI Transpl. Int. PD NOV PY 2007 VL 20 IS 11 BP 924 EP 925 DI 10.1111/j.1432-2277.2007.00540.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 218DE UT WOS:000249995400003 PM 17924932 ER PT J AU Krause, DS Van Etten, RA AF Krause, Daniela S. Van Etten, Richard A. TI Right on target: eradicating leukemic stem cells SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; ABILITY IN-VITRO; BLAST-CRISIS CML; BCR-ABL; IMATINIB MESYLATE; MURINE MODEL; HEMATOPOIETIC PROGENITORS AB Less than a third of adults with acute myeloid leukemia (AML) are cured by current treatments, emphasizing the need for new approaches to therapy. The discovery over a decade ago that myeloid leukemias originate from rare stem-like cells that can transfer the disease to immunodeficient mice suggested that these 'leukemia stem cells' (LSCs) are responsible for relapse of leukemia following conventional or targeted cancer therapy and that eradication of LSCs might be necessary to cure the disease permanently. Several recent studies have provided insight into the signaling pathways underlying the LSC phenotype and have also described approaches to eliminate LSCs with antibodies. Here, we review recent advances in LSC research and discuss novel therapeutic strategies to specifically target LSCs. C1 [Van Etten, Richard A.] Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. [Van Etten, Richard A.] Tufts Univ, New England Med Ctr, Div Hematol Oncol, Boston, MA 02111 USA. [Krause, Daniela S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Van Etten, RA (reprint author), Tufts Univ, New England Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. EM rvanetten@tufts-nemc.org FU NCI NIH HHS [CA090576, CA105043, R01 CA090576, R01 CA105043] NR 98 TC 74 Z9 83 U1 0 U2 12 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PD NOV PY 2007 VL 13 IS 11 BP 470 EP 481 DI 10.1016/j.molmed.2007.09.003 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 248EA UT WOS:000252133400003 PM 17981087 ER PT J AU Falade, C Mokuolu, O Okafor, H Orogade, A Falade, A Adedoyin, O Oguonu, T Aisha, M Hamer, DH Callahan, MV AF Falade, Catherine Mokuolu, Olugbenga Okafor, Henrietta Orogade, Adeola Falade, Adegoke Adedoyin, Olanrewaju Oguonu, Tagbo Aisha, Maman Hamer, Davidson H. Callahan, Michael V. TI Epidemiology of congenital malaria in Nigeria: a multi-centre study SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Article DE epidemiology; congenital falciparum malaria; Nigeria ID PLASMODIUM-FALCIPARUM; ETHNIC-GROUPS; BURKINA-FASO; WEST-AFRICA; INFECTION; INFANTS; SUSCEPTIBILITY; PYRIMETHAMINE; PREVALENCE; KENYA AB OBJECTIVE To determine the burden of congenital malaria in newborns in Nigeria. METHODS In a prospective multi-centre study, 1875 consecutive mother-baby pairs were enrolled over a continuous 12-month period. Blood smears were prepared from mothers, neonates, placental aspirates and cord blood within 4 h of delivery. Outcome variables were patent parasitaemia in the mother, placenta, cord and neonate in addition to maternal and neonatal haematocrit. RESULTS Patent parasitaemia was detected in 95 neonates (5.1%). The occurrence varied between study centres, but was found year round in all sites. The mean parasite density among infected neonates was low (48 asexual forms per mu l, range 8-200/mu l). Maternal and placental parasitaemia were the most important risk factors for patent neonatal parasitaemia (P < 0.0001). Spontaneous clearance of parasitaemia occurred in 62.1% of neonates before day 2. 33.7% were symptomatic within 3 days of birth. CONCLUSION Congenital malaria is often asymptomatic, clears spontaneously and may not warrant treatment. However, newborns with unexplained fever and refusal to feed in malaria endemic areas should be tested for malaria. C1 [Falade, Catherine] Univ Coll Ibadan Hosp, Dept Clin Pharmacol, Ibadan, Nigeria. [Mokuolu, Olugbenga; Adedoyin, Olanrewaju] Univ Ilorin, Teaching Hosp, Dept Pediat, Ilorin, Nigeria. [Okafor, Henrietta; Oguonu, Tagbo] Univ Nigeria, Teaching Hosp, Dept Pediat, Enugu, Nigeria. [Orogade, Adeola; Aisha, Maman] Ahmadu Bello Univ, Teaching Hosp, Dept Pediat, Kaduna, Nigeria. [Falade, Adegoke] Univ Coll Ibadan Hosp, Dept Pediat, Ibadan, Nigeria. [Hamer, Davidson H.] Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Boston, MA USA. [Hamer, Davidson H.] Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02118 USA. [Callahan, Michael V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Falade, C (reprint author), Univ Ibadan, Coll Med, Dept Therapeut & Pharmacol, Ibadan, Nigeria. EM fallady@skannet.com OI Hamer, Davidson/0000-0002-4700-1495 NR 31 TC 28 Z9 30 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD NOV PY 2007 VL 12 IS 11 BP 1279 EP 1287 DI 10.1111/j.1365-3156.2007.01931.x PG 9 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 242HT UT WOS:000251716900002 PM 17956542 ER PT J AU Stull, DE Krouse, J Meltzer, EO Roberts, L Kim, S Frank, L Naderio, R Lund, V Long, A AF Stull, Donald E. Krouse, John Meltzer, Eli O. Roberts, Laurie Kim, Susan Frank, Lori Naderio, Robert Lund, Valerie Long, Aidan TI Development and validation of the congestion quantifier seven-item test (CQ7): A screening tool for nasal congestion SO VALUE IN HEALTH LA English DT Article DE allergic rhinitis; congestion; self-administered screener ID QUALITY-OF-LIFE; ALLERGIC RHINITIS; ASTHMA CONTROL; QUESTIONNAIRE; PREVALENCE; RHINOCONJUNCTIVITIS; PRODUCTIVITY; INSTRUMENTS; DIAGNOSIS; TRIAL AB Objective: This study aimed to develop and validate a short, simple, patient-completed instrument for identifying patients with congestion in a 15-day study. Allergic rhinitis (AR) is the most common allergic condition worldwide, with congestion as one of the most salient symptoms. Nevertheless, there is no short screening tool designed specifically to identify congestion that can help patients make decisions about seeking treatment. Methods: Patients (N = 354) received a clinical exam to confirm congestion and assess its possible causes including confirmation of AR. They completed the 13-item draft of the Congestion Quantifier (CQ) and five additional patient-reported outcome instruments. Results: The 13-item draft CQ was reduced to a seven-item version, the CQ7. Internal consistency reliability was 0.93; test-retest reliability = 0.85. Construct validity was demonstrated by significant correlations with the Medical Outcomes Study Sleep Scale, the Work Productivity and Activity Impairment Questionnaire-Allergy Specific, and the Positive Affect and Negative Affect Scale Fatigue subscale (r = 0.23-0.67). The CQ7 can discriminate between controls and patients (AUC > 0.9). Moreover, it can discriminate between different levels of severity of symptoms of AR. A score of 7 provided optimum balance of sensitivity (91%), specificity (86%), and correct classification (90%) for detecting congestion. Conclusion: The CQ7 is reliable, valid, and responsive to differences in severity of nasal congestion. The CQ7 can identify patients with congestion that may need to be evaluated by a clinician. C1 [Stull, Donald E.; Roberts, Laurie; Frank, Lori] United Biosource Corp, Bethesda, MD 20814 USA. [Krouse, John] Wayne State Univ, Detroit, MI USA. [Meltzer, Eli O.] Univ Calif San Diego, San Diego, CA 92103 USA. [Meltzer, Eli O.] Asthma Med Grp & Res Ctr, San Diego, CA USA. [Kim, Susan] Schering Plough Corp, Kenilworth, NJ 07033 USA. [Naderio, Robert] Univ Chicago, Chicago, IL 60637 USA. [Lund, Valerie] UCL, London, England. [Long, Aidan] Massachusetts Gen Hosp, Allergy Assoc, Boston, MA 02114 USA. RP Stull, DE (reprint author), United Biosource Corp, 7101 Wisconsin Ave Suite 600, Bethesda, MD 20814 USA. EM donald.stull@unitedbiosource.com NR 32 TC 11 Z9 11 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2007 VL 10 IS 6 BP 457 EP 465 DI 10.1111/j.1524-4733.2007.00201.x PG 9 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 239HH UT WOS:000251508900003 PM 17970928 ER PT J AU Johnson, FR Ozdemir, S Mansfield, C Hauber, AB Hass, SL Siegel, CA Sands, BE Miller, DW AF Johnson, F. R. Ozdemir, S. Mansfield, C. Hauber, A. B. Hass, S. L. Siegel, C. A. Sands, B. E. Miller, D. W. TI Patients', parents', and physicians' risk-benefit trade-off preferences for Crohn's disease treatments SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Johnson, F. R.; Ozdemir, S.; Mansfield, C.; Hauber, A. B.] RTI Int, Res Triangle Pk, NC USA. [Hass, S. L.; Miller, D. W.] Elan Pharmaceut Inc, San Diego, CA USA. [Siegel, C. A.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Sands, B. E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2007 VL 10 IS 6 BP A225 EP A226 DI 10.1016/S1098-3015(10)64868-1 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 239HH UT WOS:000251508900026 ER PT J AU Zhu, B Montgomery, W Ascher-Svanum, H Faries, D Stephenson, DA McKendrick, J Brnabic, A Marder, SR AF Zhu, B. Montgomery, W. Ascher-Svanum, H. Faries, D. Stephenson, D. A. McKendrick, J. Brnabic, A. Marder, S. R. TI Treatment duration with oral and long acting injectable formulations of typical antipsychotics in the treatment of schizophrenia: Results across world geographies SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Zhu, B.; Ascher-Svanum, H.; Faries, D.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Montgomery, W.] Eli Lilly & Co, Sydney, NSW, Australia. [Stephenson, D. A.; McKendrick, J.] Eli Lilly & Co, Windlesham, Surrey, England. [Brnabic, A.] Eli Lilly & Co, N Ryde, NSW, Australia. [Marder, S. R.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2007 VL 10 IS 6 BP A289 EP A289 DI 10.1016/S1098-3015(10)65057-7 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 239HH UT WOS:000251508900215 ER PT J AU Ochoa, O Torres, FM Shireman, PK AF Ochoa, Oscar Torres, Francis M. Shireman, Paula K. TI Chemokines and diabetic wound healing SO VASCULAR LA English DT Article DE chemokines; chronic wounds; diabetes mellitus; inflammation ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; GROWTH-FACTOR EXPRESSION; FOOT ULCERS; INTERLEUKIN-8 RECEPTOR; ENDOTHELIAL-CELLS; GENE-EXPRESSION; IN-VITRO; ANGIOGENESIS; REPAIR; DISEASE AB Chemokines are critical for white blood cell recruitment to injured tissues and play an important role in normal wound healing processes. In contrast, impaired wound healing in diabetic patients is accompanied by decreased early inflammatory cell infiltration but persistence of neutrophils and macrophages in the chronic, nonhealing wounds. These changes in inflammatory cell recruitment occur in conjunction with alterations in chemokine and growth factor expression. In addition to leukocyte trafficking, many different cell types, including endothelial cells, fibroblasts, and keratinocytes, produce and respond to chemokines, and these interactions are altered in diabetic wounds. Thus, the chemokine system may have both direct and inflammatory-mediated effects on many different aspects of diabetic wound healing. The potential roles of chemokines and inflammatory or immune cells in nonhealing diabetic wounds, including impairments in growth factor expression, angiogenesis, extracellular matrix formation, and reepithelialization, are examined. C1 Univ Texas Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. [Shireman, Paula K.] Univ Texas Hlth Sci Ctr, Sam & Ann Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Shireman, Paula K.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Shireman, PK (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Div Vasc Surg, MC 7741,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Shireman@UTHSCSA.edu FU NHLBI NIH HHS [HL070158, HL074236] NR 60 TC 46 Z9 50 U1 1 U2 9 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 1708-5381 J9 VASCULAR JI Vascular PD NOV-DEC PY 2007 VL 15 IS 6 BP 350 EP 355 DI 10.2310/6670.2007.00056 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 241LU UT WOS:000251658700005 PM 18053419 ER PT J AU Ogura, M Abernethy, AD Blissett, RD Ruggiero, K Som, S Goodson, JM Kent, R Doukas, AG Soukos, NS AF Ogura, Makoto Abernethy, Abraham D. Blissett, Ryan D. Ruggiero, Karriann Som, Sovanda Goodson, J. Max Kent, Ralph Doukas, Apostolos G. Soukos, Nikolaos S. TI Photomechanical wave-assisted molecular delivery in oral biofilms SO WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE confocal scanning laser microscopy; drug delivery; oral biofilms; photodynamic therapy; photomechanical waves; stress waves; ultrasound ID PSEUDOMONAS-AERUGINOSA BIOFILMS; LOW-POWER LASER; INDUCED STRESS WAVES; TOLUIDINE-BLUE-O; PHOTODYNAMIC THERAPY; BACTERIAL BIOFILMS; IN-VITRO; STREPTOCOCCUS-MUTANS; PORPHYROMONAS-GINGIVALIS; ELECTRICAL ENHANCEMENT AB Photomechanical waves (PW), the product of an intense light beam interaction with a target material, enhance molecular delivery across biological membranes and skin. The ability to deliver methylene blue (MB), a fluorescent probe and photosensitizer, into bacterial biofilms was demonstrated by applying PW on saliva-derived multi-species biofilms that were developed on agar surfaces in 24-well plates. PW were generated with a Q-switched Nd:YAG laser and were directed into the biofilms in the presence of 25 mu g/ml MB. The biofilms were then irradiated with red light at 665 nm. After illumination, adherent bacteria were scraped and spread over the surface of blood agar plates. Survival fractions were calculated by counting bacterial colonies. Microbial analysis was performed via a colony lift method and a DNA checkerboard assay using whole genomic probes to 40 oral microorganisms. Visual analysis by confocal scanning laser microscopy demonstrated that the application of PW enhanced the penetration depth of MB in biofilms. Exposure to MB, PW and light led to a significant reduction of the mean levels of log(10) CFU counts compared with the group that received MB and light (P = 0.006). The DNA checkerboard assay showed some benefit from PW-assisted phototargeting in 25 biofilm microorganisms relative to phototreatment alone. Our data provide a basis for further exploration and optimization of PW parameters for complete eradication of microorganisms in oral microcosm biofilms. C1 Forsyth Inst, App Mol Photomed Lab, Boston, MA 02115 USA. Keio Univ, Dept Elect & Elect Engn, Yokohama, Kanagawa 2238522, Japan. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Forsyth Inst, Clin Collaborat, Boston, MA 02115 USA. Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Soukos, NS (reprint author), Forsyth Inst, App Mol Photomed Lab, 140 Fenway, Boston, MA 02115 USA. EM nsoukos@forsyth.org NR 58 TC 10 Z9 10 U1 2 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0959-3993 J9 WORLD J MICROB BIOT JI World J. Microbiol. Biotechnol. PD NOV PY 2007 VL 23 IS 11 BP 1637 EP 1646 DI 10.1007/s11274-007-9411-x PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 217AW UT WOS:000249921800017 ER PT J AU Burger, C Zwingmann, J Kabirl, K Tolba, RH Goost, H Wilhelm, KE AF Burger, C. Zwingmann, J. Kabirl, K. Tolba, R. H. Goost, H. Wilhelm, K. E. TI Faster diagnostics by digital X-ray imaging in the emergency room: A prospective study in multiple trauma patients SO ZEITSCHRIFT FUR ORTHOPADIE UND UNFALLCHIRURGIE LA German DT Article DE multiple trauma; digital X-rays; emergency room; emergency radiology; diagnostic time ID OF-THE-LITERATURE; SEVERELY INJURED PATIENTS; QUALITY MANAGEMENT; COMPUTED-TOMOGRAPHY; DAMAGE CONTROL; POLYTRAUMA; IMPROVEMENT; RELEVANCE; SURGEON; SYSTEM AB Aim: The object of this study was to provide evidence for a time-reduced diagnostic space in multiple trauma patients by use of a digital X-ray system in the emergency suite. Method: The same algorithm was used in the first attention of 66 severely injured patients. For 21 patients from October 2000 to March 2001 (group 1) conventional X-rays (thorax, pelvis, spine and extremities) were performed in the analogue way, for 45 patients from April to December 2001 (group 2) the new digital system (Philips Optimum and Philips PCR AC 500) was used. Results: The two groups were similar concerning age, sex and injury severity. The time-space from the patient's delivery in the emergency suite to the handing over in the operation theatre or intensive care unit was significantly lower in group 2 (87 +/- 33 min, p < 0.001) than in group 1(121 +/- 49 min). Conclusion: Digital imaging with conventional X-rays in the first attention of multiple trauma patients reduces the diagnostic time by more than half an hour, when applying the same diagnostic algorithm. C1 [Burger, C.; Kabirl, K.; Tolba, R. H.; Goost, H.] Univ Klinikum Bonn, Klin & Poliklin Orthopad & Unfallchirurg, Bonn, Germany. [Zwingmann, J.] Univ Freiburg Klinikum, Zentrale Klin Forschung, Labor Tissue Engn, Freiburg, Germany. [Wilhelm, K. E.] Univ Klinikum Bonn, Radiol Klin, Bonn, Germany. RP Burger, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthpaed Hand Serv, Boston, MA 02114 USA. NR 28 TC 2 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1864-6697 J9 Z ORTHOP UNFALLCHIR JI Z. Orthop. Unfallchir. PD NOV-DEC PY 2007 VL 145 IS 6 BP 772 EP 777 DI 10.1055/s-2007-989302 PG 6 WC Orthopedics SC Orthopedics GA 248WP UT WOS:000252188200025 PM 18072045 ER PT J AU Cinar, B Fang, PK Lutchman, M Di Vizio, D Adam, RM Pavlova, N Rubin, MA Yelick, PC Freeman, MR AF Cinar, Bekir Fang, Ping-Ke Lutchman, Mohini Di Vizio, Dolores Adam, Rosalyn M. Pavlova, Natalya Rubin, Mark A. Yelick, Pamela C. Freeman, Michael R. TI The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1 SO EMBO JOURNAL LA English DT Article DE apoptosis; kinases; lipid rafts; prostate cancer; protein complex ID PROSTATE-CANCER CELLS; TUMOR-SUPPRESSOR NETWORK; PROTEIN-KINASE; DISTINCT ROLES; LIPID RAFTS; ACTIVATION; CHOLESTEROL; GROWTH; TRANSLOCATION; SURVIVAL AB Akt kinases mediate cell growth and survival. Here, we report that a pro-apoptotic kinase, Mst1/STK4, is a physiological Akt1 interaction partner. Mst1 was identified as a component of an Akt1 multiprotein complex isolated from lipid raft-enriched fractions of LNCaP human prostate cancer cells. Endogenous Mst1, along with its paralog, Mst2, acted as inhibitors of endogenous Akt1. Surprisingly, mature Mst1 as well as both of its caspase cleavage products, which localize to distinct subcellular compartments and are not structurally homologous, complexed with and inhibited Akt1. cRNAs encoding full-length Mst1, and N- and C-terminal caspase Mst1 cleavage products, reverted an early lethal phenotype in zebrafish development induced by expression of membrane-targeted Akt1. Mst1 and Akt1 localized to identical subcellular sites in human prostate tumors. Mst1 levels declined with progression from clinically localized to hormone refractory disease, coinciding with an increase in Akt activation with transition from hormone naive to hormone-resistant metastases. These results position Mst1/2 within a novel branch of the phosphoinositide 3-kinase/Akt pathway and suggest an important role in cancer progression. C1 Childrens Hosp, Enders Res Labs, Urol Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Pathol, Boston, MA USA. Tufts Univ, Div Craniofacial & Mol Genet, Dept Oral & Maxillofacial Pathol, Boston, MA 02111 USA. Tufts Univ, Div Craniofacial & Mol Genet, Dept Biomed Engn, Boston, MA 02111 USA. RP Freeman, MR (reprint author), Childrens Hosp, Enders Res Labs, Urol Dis Res Ctr, Suite 1161,300 Longwood Ave, Boston, MA 02115 USA. EM michael.freeman@childrens.harvard.edu OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [R01 CA112303]; NIDDK NIH HHS [R37 DK47556, P50 DK065298, P50 DK65298, R37 DK047556] NR 51 TC 71 Z9 74 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 31 PY 2007 VL 26 IS 21 BP 4523 EP 4534 DI 10.1038/sj.emboj.7601872 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226GL UT WOS:000250575800010 PM 17932490 ER PT J AU Becker, JB Monteggia, LM Perrot-Sinal, TS Romeo, RD Taylor, JR Yehuda, R Bale, TL AF Becker, Jill B. Monteggia, Lisa M. Perrot-Sinal, Tara S. Romeo, Russell D. Taylor, Jane R. Yehuda, Rachel Bale, Tracy L. TI Stress and disease: Is being female a predisposing factor? SO JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; depression; HPA axis; animal models; sex; stress ID CORTICOTROPIN-RELEASING-FACTOR; DISCRETE TRIAL PROCEDURE; SEX-DIFFERENCES; GENDER-DIFFERENCES; HORMONE RECEPTOR-2; DEPRESSED-PATIENTS; DISORDER SYMPTOMS; BIOLOGICAL BASIS; TRAUMA EXPOSURE; PRENATAL STRESS C1 Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Dalhousie Univ, Dept Psychol, Halifax, NS B3H 4R2, Canada. Columbia Univ Barnard Coll, Dept Psychol, New York, NY 10027 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06510 USA. James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Bale, TL (reprint author), Univ Penn, Dept Anim Biol, 201E Vet 6046,3800 Spruce St, Philadelphia, PA 19104 USA. EM tbale@vet.upenn.edu FU NIDA NIH HHS [DA012677, DA016556, DA11717]; NIMH NIH HHS [MH070727, MH073030, R01 MH073030] NR 64 TC 79 Z9 82 U1 6 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 31 PY 2007 VL 27 IS 44 BP 11851 EP 11855 DI 10.1523/JNEUROSCI.3565-07.2007 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 226HB UT WOS:000250577600012 PM 17978023 ER PT J AU Lapierre, JL Kosenko, PO Lyamin, OI Kodama, T Mukhametov, LM Siegel, JM AF Lapierre, Jennifer L. Kosenko, Peter O. Lyamin, Oleg I. Kodama, Tohru Mukhametov, Lev M. Siegel, Jerome M. TI Cortical acetylcholine release is lateralized during asymmetrical slow-wave sleep in Northern fur seals SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sleep-wake cycle; acetylcholine; microdialysis; cerebral cortex; asymmetry; Callorhinus ursinus ID NUCLEUS BASALIS MAGNOCELLULARIS; CEREBRAL-CORTEX; FOREBRAIN; RAT; STIMULATION; ACTIVATION; DOLPHIN; EEG AB Fur seals are unique in that they display both bilateral slow-wave sleep (BSWS), as seen in all terrestrial mammals, and slow-wave sleep with interhemispheric electroencephalogram ( EEG) asymmetry, resembling the unihemispheric slow waves of cetaceans. Little is known about the underlying mechanisms of this phenomenon, which is also termed asymmetrical slow wave sleep (ASWS). However, we may begin to understand the expression of ASWS by studying the neurotransmitter systems thought to be involved in the generation and maintenance of sleep-wake states in terrestrial mammals. We examined bilaterally the release of cortical acetylcholine (ACh), a neurotransmitter implicated in the regulation of cortical EEG and behavioral arousal, across the sleep-wake cycle in four juvenile northern fur seals (Callorhinus ursinus). In vivo microdialysis and high-performance liquid chromatography coupled with electrochemical detection were used to measure cortical ACh levels during polygraphically defined behavioral states. Cortical ACh release was state-dependent, showing maximal release during active waking (AW), similar levels during quiet waking (QW), and rapid eye movement ( REM) sleep, and minimal release during BSWS. When compared with BSWS, cortical ACh levels increased similar to 300% during AW, and similar to 200% during QW and REM sleep. During these bilaterally symmetrical EEG states, ACh was synchronously released from both hemispheres. However, during ASWS, ACh release was lateralized with greater release in the hemisphere displaying lower voltage activity, at levels approximating those seen in QW. These findings demonstrate that cortical ACh release is tightly linked to hemispheric EEG activation. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat, Vet Affairs Greater Los Angeles Healthcare Syst, North Hills, CA 91343 USA. Utrish Dolphinarium Ltd, Moscow 119071, Russia. Tokyo Metropolitan Inst Neurosci, Dept Psychol, Tokyo 1838526, Japan. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, Vet Affairs Greater Los Angeles Healthcare Syst, 16111 Plummer St, North Hills, CA 91343 USA. EM jsiegel@ucla.edu FU NINDS NIH HHS [NS42947] NR 22 TC 17 Z9 17 U1 1 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 31 PY 2007 VL 27 IS 44 BP 11999 EP 12006 DI 10.1523/JNEUROSCI.2968-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 226HB UT WOS:000250577600030 PM 17978041 ER PT J AU Oh, M Lee, H Kim, YK Nam, JW Rhee, JK Zhang, BT Kim, VN Lee, I AF Oh, Mijin Lee, Horim Kim, Young-Kook Nam, Jin-Wu Rhee, Je-Keun Zhang, Byoung-Tak Kim, V. Narry Lee, Ilha TI Identification and characterization of small RNAs from vernalized Arabidopsis thaliana SO JOURNAL OF PLANT BIOLOGY LA English DT Article DE rnicroRNA; small interference RNA; vernalization ID TRANS-ACTING SIRNAS; DOUBLE-STRANDED-RNA; ANTISENSE TRANSCRIPTS; ENDOGENOUS SIRNAS; PLANT DEVELOPMENT; INTERFERING RNA; MICRORNAS; METHYLATION; BIOGENESIS; PATHWAY AB MicroRNAs (miRNAs) and small interfering RNAs (siRNAs) are two major classes of small non-coding RNAs with important roles in the regulation of gene expression, such as mRNA degradation and translational repression, heterochromatin formation, genome defense against transposons and viruses in eukaryotes. MiRNA- and siRNA-directed processes have emerged as a regulatory mechanism for growth and development in both animals and plants. To identify small RNAs that might be involved in vernalization, a process accelerating flowering brought on by a long period of cold, we generated a library of small RNAs from Arabidopsis that had been subject to vernalization. From the analysis of the library, 277 small RNAs were identified. They were distributed throughout all the five chromosomes. While the vast majority of small RNA genes locate on intergenic regions, others locate on repeat-rich regions, centromeric regions, transposon-related genes, and protein-coding genes. Five of them were mapped to convergent overlapping gene pairs. Two-hundred and forty of them were novel endogenous small RNAs that have not been cloned yet from plants grown under normal conditions and other environmental stresses. Seven putative miRNAs were up- or down-regulated by vernalization. In conclusion, many small RNAs were identified from vernalized Arabidopsis and some of these identified small RNAs may play roles in plant responses to vernalization. C1 Seoul Natl Univ, Natl Res Lab Plant Dev Genet, Dept Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ & UW, Global Res Lab Flower, Seoul 151742, South Korea. Seoul Natl Univ, Inst Mol Biol & Genet, Dept Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ, Ctr Bioinformat Technol, Seoul 151742, South Korea. Seoul Natl Univ, Sch Engn & Comp Sci, Lab Biointelligence, Seoul 151742, South Korea. RP Lee, I (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol & Genet, Boston, MA 02114 USA. EM ilhalee@snu.ac.kr NR 64 TC 4 Z9 4 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1226-9239 J9 J PLANT BIOL JI J. Plant Biol. PD OCT 31 PY 2007 VL 50 IS 5 BP 562 EP 572 DI 10.1007/BF03030710 PG 11 WC Plant Sciences SC Plant Sciences GA 232AP UT WOS:000250990800007 ER PT J AU Zou, J Hofer, AM Lurtz, MM Gadda, G Ellis, AL Chen, N Huang, Y Holder, A Ye, Y Louis, CF Welshhans, K Rehder, V Yang, JJ AF Zou, Jin Hofer, Aldebaran M. Lurtz, Monica M. Gadda, Giovanni Ellis, April L. Chen, Ning Huang, Yun Holder, Angela Ye, Yiming Louis, Charles F. Welshhans, Kristy Rehder, Vincent Yang, Jenny J. TI Developing sensors for real-time measurement of high Ca2+ concentrations SO BIOCHEMISTRY LA English DT Article ID GREEN FLUORESCENT PROTEIN; ENDOPLASMIC-RETICULUM CA2+; SMOOTH-MUSCLE-CELLS; INTRACELLULAR CALCIUM; INDICATOR PROTEINS; INTACT-CELLS; ENVIRONMENTAL SENSITIVITY; SARCOPLASMIC-RETICULUM; LANTHANIDE AFFINITY; ALZHEIMERS-DISEASE AB Ca2+ regulates numerous biological processes through spatiotemporal changes in the cytosolic Ca2+ concentration and subsequent interactions with Ca2+ binding proteins. The endoplasmic reticulum (ER) serves as an intracellular Ca2+ store and plays an essential role in cytosolic Ca2+ bomeostasis. There is a strong need to develop Ca2+ sensors capable of real-time quantitative Ca2+ concentration measurements in specific subcellular environments without using natural Ca2+ binding proteins such as calmodulin, which themselves participate as signaling molecules in cells. In this report, a strategy for creating such sensors by grafting a Ca2+-binding motif into chromophore sensitive locations in green fluorescence protein is described. The engineered Ca2+ sensors exhibit large ratiometric fluorescence and absorbance changes upon Ca2+ binding with affinities corresponding to the Ca2+ concentrations found in the ER (K-d values range from 0.4 to 2 mM). In addition to characterizing the optical and metal binding properties of the newly developed Ca2+ sensors with various spectroscopic methods, we also examined the kinetic properties using stopped-flow spectrofluorimetry to ensure accurate monitoring of dynamic Ca2+ changes. The developed Ca2+ sensor was successfully targeted to the ER of mammalian cell lines to monitor Ca2+ changes occurring in this compartment in response to stimulation with agonists. We envision that this class of Ca2+ sensors can be modified further to measure the Ca2+ concentration in other cellular compartments, providing tools for studying the contribution of these compartments to cellular Ca2+ signaling. C1 Georgia State Univ, Ctr Drug Design & Biotechnol, Dept Chem & Biol, Atlanta, GA 30303 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, W Roxbury, MA 02132 USA. Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. RP Yang, JJ (reprint author), Georgia State Univ, Ctr Drug Design & Biotechnol, Dept Chem & Biol, Atlanta, GA 30303 USA. EM chejjy@langate.gsu.edu OI Huang, Yun/0000-0001-5950-9168 FU NEI NIH HHS [EY-05684]; NIGMS NIH HHS [GM070555, GM62999] NR 86 TC 32 Z9 32 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 30 PY 2007 VL 46 IS 43 BP 12275 EP 12288 DI 10.1021/bi7007307 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 223OH UT WOS:000250379900028 PM 17924653 ER PT J AU Feskanich, D Bain, C Chan, AT Pandeya, N Speizer, FE Colditz, GA AF Feskanich, D. Bain, C. Chan, A. T. Pandeya, N. Speizer, F. E. Colditz, G. A. TI Aspirin and lung cancer risk in a cohort study of women: dosage, duration and latency SO BRITISH JOURNAL OF CANCER LA English DT Article DE lung cancer; aspirin; cohort; women ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; LOW-DOSE ASPIRIN; COLORECTAL-CANCER; PREVENTION; USERS; CHEMOPREVENTION; METAANALYSIS; HEALTH; TRIAL; COLON AB Aspirin may reduce the risk of cancer at some sites but its effect at the lung is unclear. We prospectively examined associations between aspirin use and risk of lung cancer in 109 348 women in the Nurses' Health study from 1980 to 2004. During this time, 1360 lung cancers were documented in participants 36-82 years of age. Aspirin use and smoking were assessed every 2 years. Risk of lung cancer was a non-significant 16% lower for regular aspirin users of one or two tablets per week and a significant 55% higher for users of 15 or more tablets per week compared with women who never regularly used aspirin. Results were similar when limited to never smokers. For both the low and high quantity aspirin users, risk of lung cancer did not decline or increase with longer durations of use, and associations attenuated as the latency period between aspirin assessment and lung cancer diagnosis was lengthened. Our findings, together with those from previous clinical trials and prospective studies, do not provide consistent evidence that aspirin influences the development of lung cancer and further investigation is required with adjustment for smoking. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Queensland, Sch Populat Hlth, Brisbane, Qld, Australia. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Queensland Inst Med Res, Populat Studies & Genet Res, Brisbane, Qld 4006, Australia. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Feskanich, D (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM diane.feskanich@channing.harvard.edu RI Colditz, Graham/A-3963-2009; Pandeya, Nirmala/F-8054-2010 OI Colditz, Graham/0000-0002-7307-0291; Pandeya, Nirmala/0000-0003-1462-4968 FU NCI NIH HHS [CA087969, P01 CA087969] NR 28 TC 20 Z9 21 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 30 PY 2007 VL 97 IS 9 BP 1295 EP 1299 DI 10.1038/sj.bjc.6603996 PG 5 WC Oncology SC Oncology GA 225SA UT WOS:000250536500017 PM 17895894 ER PT J AU Grabie, N Gotsman, I DaCosta, R Pang, H Stavrakis, G Butte, MJ Keir, ME Freeman, GJ Sharpe, AH Lichtman, AH AF Grabie, Nir Gotsman, Israel DaCosta, Rosa Pang, Hong Stavrakis, George Butte, Manish J. Keir, Mary E. Freeman, Gordon J. Sharpe, Arlene H. Lichtman, Andrew H. TI Endothelial programmed death-1 ligand 1 (PD-L1) regulates CD8(+) T-cell-mediated injury in the heart SO CIRCULATION LA English DT Article DE immune system; inflammation; lymphocytes; myocarditis; endothelium ID INDUCIBLE COSTIMULATOR LIGAND; RECEPTOR-DEFICIENT MICE; INTERFERON-GAMMA; AUTOIMMUNE MYOCARDITIS; IFN-GAMMA; DILATED CARDIOMYOPATHY; CARDIAC ALLOGRAFTS; EPITHELIAL-CELLS; EXPRESSION; RESPONSES AB Background - PD-L1 and PD-L2 are ligands for the inhibitory receptor programmed death-1 (PD-1), which is an important regulator of immune responses. PD-L1 is induced on cardiac endothelial cells under inflammatory conditions, but little is known about its role in regulating immune injury in the heart. Methods and Results - Cytotoxic T-lymphocyte - mediated myocarditis was induced in mice, and the influence of PD-L1 signaling was studied with PD-L1/L2 - deficient mice and blocking antibodies. During cytotoxic T-lymphocyte-induced myocarditis, the upregulation of PD-L1 on cardiac endothelia was dependent on T-cell- derived interferon-gamma, and blocking of interferon-gamma signaling worsened disease. Genetic deletion of both PD-1 ligands [PD-L1/2((-/-))], as well as treatment with PD-L1 blocking antibody, transformed transient myocarditis to lethal disease, in association with widespread polymorphonuclear leukocyte-rich microabscesses but without change in cytotoxic T-lymphocyte recruitment. PD-L1/2((-/-)) mice reconstituted with bone marrow from wild- type mice remained susceptible to severe disease, which demonstrates that PD-L1 on non-bone marrow-derived cells confers the protective effect. Finally, depletion of polymorphonuclear leukocytes reversed the enhanced susceptibility to lethal myocarditis attributable to PD-L1 deficiency. Conclusions - Myocardial PD-L1, mainly localized on endothelium, is critical for control of immune- mediated cardiac injury and polymorphonuclear leukocyte inflammation. C1 Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Lichtman, AH (reprint author), Brigham & Womens Hosp, Dept Pathol, Div Vasc Res, 77 Ave Louis Pasteur,NRB 752N, Boston, MA 02115 USA. EM alichtman@rics.bwh.harvard.edu OI Gotsman, Israel/0000-0001-9608-2298; Butte, Manish/0000-0002-4490-5595 FU NHLBI NIH HHS [HL072056, R01 HL087282]; NIAID NIH HHS [AI046414, AI059610, AI56299, K08 AI079268, K08 AI079268-01A1, K08 AI079268-02, K08 AI079268-03, K08 AI079268-04] NR 35 TC 60 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 30 PY 2007 VL 116 IS 18 BP 2062 EP 2071 DI 10.1161/CIRCULATIONAHA.107.709360 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225KY UT WOS:000250518000010 PM 17938288 ER PT J AU Pitteloud, N Zhang, C Pignatelli, D Li, JD Raivio, T Cole, LW Plummer, L Jacobson-Dickman, EE Mellon, PL Zhou, QY Crowley, WF AF Pitteloud, Nelly Zhang, Chengkang Pignatelli, Duarte Li, Jia-Da Raivio, Taneli Cole, Lindsay W. Plummer, Lacey Jacobson-Dickman, Elka E. Mellon, Pamela L. Zhou, Qun-Yong Crowley, William F., Jr. TI Loss-of-function mutation in the prokineticin 2 gene causes Kallmann syndrome and normosmic idiopathic hypogonadotropic hypogonadism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gonadotropin-releasing hormone deficiency ID OLFACTORY-BULB NEUROGENESIS; PROTEIN-COUPLED RECEPTORS; IDENTIFICATION; HETEROGENEITY; MOLECULES; ADHESION; SYSTEM; GPR54; MICE AB Gonadotropin-releasing hormone (GnRH) deficiency in the human presents either as normosmic idiopathic hypogonadotropic hypogonadism (nIHH) or with anosmia [Kallmann syndrome (KS)]. To date, several loci have been identified to cause these disorders, but only 30% of cases exhibit mutations in known genes. Recently, murine studies have demonstrated a critical role of the prokineticin pathway in olfactory bulb morphogenesis and GnRH secretion. Therefore, we hypothesize that mutations in prokineticin 2 (PROK2) underlie some cases of KS in humans and that animals deficient in Prok2 would be hypogonadotropic. One hundred IHH probands (50 nIHH and 50 KS) with no known mutations were examined for mutations in the PROK2 gene. Mutant PROK2s were examined in functional studies, and the reproductive phenotype of the Prok2(-/-) mice was also investigated. Two brothers with KS and their sister with nIHH harbored a homozygous deletion in the PROK2 gene (p.[155fsX1]+[155fsX1]). Another asymptomatic brother was heterozygous for the deletion, whereas both parents (deceased) had normal reproductive histories. The identified deletion results in a truncated PROK2 protein of 27 amino acids (rather than 81 in its mature form) that lacks bioactivity. In addition, Prok2(-/-) mice with olfactory bulb defects exhibited disrupted GnRH neuron migration, resulting in a dramatic decrease in GnRH neuron population in the hypothalamus as well as hypogonadotropic hypogonadism. Homozygous loss-of-function PROK2 mutations cause both KS and nIHH. C1 Massachusetts Gen Hosp, Dept Med, Reproduct Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Reproduct Endorine Sci Ctr, Boston, MA 02114 USA. Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. Univ Porto, San Joao Hosp, Inst Mol Pathol & Immunol, Cellular & Mol Biol Lab, P-4200465 Oporto, Portugal. Univ Calif San Diego, Dept Reprod Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Pitteloud, N (reprint author), Massachusetts Gen Hosp, Dept Med, Reproduct Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. EM npitteloud@partners.org RI ZHANG, CHENGKANG/A-8141-2008; PITTELOUD, Nelly/K-2709-2014; OI Pignatelli, Duarte/0000-0002-5555-7004 FU NICHD NIH HHS [U54 HD012303-270011, 5R01 HD015788, HD020377, P50 HD012303, R01 HD015788, R01 HD020377, R01 HD072754, R37 HD020377, U54 HD012303, U54 HD012303-27, U54 HD012303-28, U54 HD012303-280011, U54 HD028138, U54 HD029164]; NIDDK NIH HHS [DK044838, R01 DK044838, R01 DK044838-18, R01 DK044838-19]; NIMH NIH HHS [MH067753, R01 MH067753] NR 28 TC 135 Z9 141 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 30 PY 2007 VL 104 IS 44 BP 17447 EP 17452 DI 10.1073/pnas.0707173104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227DW UT WOS:000250638400040 PM 17959774 ER PT J AU Voss, SD Smith, SV DiBartolo, N Mclntos, LJ Cyr, EM Bonab, AA Dearling, JLJ Carter, EA Fischman, AJ Treves, ST Gillies, SD Sargeson, AM Huston, JS Packard, AB AF Voss, Stephan D. Smith, Suzanne V. DiBartolo, Nadine Mclntos, Lacey J. Cyr, Erika M. Bonab, Ali A. Dearling, Jason L. J. Carter, Edward A. Fischman, Alan J. Treves, S. Ted Gillies, Stephen D. Sargeson, Alan M. Huston, James S. Packard, Alan B. TI Positron emission tomography (PET) imaging of neuroblastoma and melanoma with Cu-64-SarAr immunoconjugates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 5th Conjoint Meeting of International Pediatric Radiology CY MAY, 2006 CL Montreal, CANADA ID MONOCLONAL-ANTIBODY; METAL-IONS; RADIOIMMUNOTHERAPY; COMPLEXES; COPPER-64; TUMOR; CAGE; FRAGMENTS; LYMPHOMA; ONCOLOGY AB The advancement of positron emission tomography (PET) depends on the development of new radiotracers that will complement F-18-FDG. Copper-64 (Cu-64) is a promising PET radionuclide, particularly for antibody-targeted imaging, but the high in vivo lability of conventional chelates has limited its clinical application. The objective of this work was to evaluate the novel chelating agent SarAr (1-N-(4-aminobenzyl)-3, 6,10,13,16,19-hexaazabicyclo[6.6.6]eicosane-1,8-diamine) for use in developing a new class of tumorspecific Cu-64 radiopharmaceuticals for imaging neuroblastoma and melanoma. The anti-GD2 monoclonal antibody (mAb) 14.G2a, and its chimeric derivative, ch14.18, target disialogangliosides that are overexpressed on neuroblastoma and melanoma. Both mAbs were conjugated to SarAr using carbodiimide coupling. Radiolabeling with Cu-64 resulted in >95% of the Cu-64 being chelated by the immunoconjugate. Specific activities of at least 10 mu Ci/mu g (1 Ci = 37 GBq) were routinely achieved, and no additional purification was required after Cu-64 labeling. Solid-phase radioimmunoassays and intact cell-binding assays confirmed retention of bioactivity. Biodistribution studies in athymic nude mice bearing s.c. neuroblastoma (IMR-6, NMB-7) and melanoma (M21) xenografts showed that 15-20% of the injected dose per gram accumulated in the tumor at 24 hours after, injection, and only 5-10% of the injected dose accumulated in the liver, a lower value than typically seen with other chelators. Uptake by a GD2-negative tumor xenograft was significantly lower (<5% injected dose per gram). MicroPET imaging confirmed significant uptake of the tracer in GID-2-positive tumors, with minimal uptake in GD-2-negative tumors and nontarget tissues such as liver. The Cu-64-SarAr-mAb system described here is potentially applicable to Cu-64-PET imaging with a broad range of antibody or peptide-based imaging agents. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Nucl Med, Childrens Hosp Boston, Boston, MA 02115 USA. Australian Nucl Sci & Technol Org, Menai, NSW 2234, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. EMD Serono, Lexigen Res Ctr, Billerica, MA 01821 USA. Australian Natl Univ, Res Sch Chem, Canberra, ACT 0200, Australia. RP Voss, SD (reprint author), Harvard Univ, Sch Med, Dept Radiol, 300 Longwood Ave, Boston, MA 02115 USA. EM stephan.voss@childrens.harvard FU NCI NIH HHS [K08 CA093554, 5K08CA093554, 5R01CA094338, R01 CA094338, R01 CA094338-03, R24 CA086307, R24CA86307] NR 33 TC 83 Z9 84 U1 1 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 30 PY 2007 VL 104 IS 44 BP 17489 EP 17493 DI 10.1073/pnas.0708436104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 227DW UT WOS:000250638400047 PM 17954911 ER PT J AU Gray, D Abramson, J Benoist, C Mathis, D AF Gray, Daniel Abramson, Jakub Benoist, Christophe Mathis, Diane TI Proliferative arrest and rapid turnover of thymic epithelial cells expressing Aire SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID PROMISCUOUS GENE-EXPRESSION; T-CELLS; CENTRAL TOLERANCE; MEDULLARY; ANTIGENS AB Expression of autoimmune regulator (Aire) by thymic medullary epithelial cells (MECs) is critical for central tolerance of self. To explore the mechanism by which such a rare cell population imposes tolerance on the large repertoire of differentiating thymocytes, we examined the proliferation and turnover of Aire(+) and Aire(-) MEC subsets through flow cytometric analysis of 5-bromo-2' deoxyuridine ( BrdU) incorporation. The Aire(-) MEC subset was almost entirely postmitotic and derived from cycling Aire(-) precursors. Experiments using reaggregate thymic organ cultures revealed the presence of such precursors among Aire(-) MECs expressing low levels of major histocompatibility complex class II and CD80. The kinetics of BrdU decay showed the Aire(-) population to have a high turnover. Aire did not have a direct impact on the division of MECs in vitro or in vivo but, rather, induced their apoptosis. We argue that these properties strongly favor a "terminal differentiation" model for Aire function in MECs, placing strict temporal limits on the operation of any individual Aire(-) MEC in central tolerance induction. We further speculate that the speedy apoptosis of Aire- expressing MECs may be a mechanism to promote cross-presentation of the array of peripheral-tissue antigens they produce. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu RI ABRAMSON, JAKUB/K-1348-2012; Gray, Daniel/A-3293-2013 OI Gray, Daniel/0000-0002-8457-8242 FU NIDDK NIH HHS [R01 DK060027, R01 DK60027] NR 18 TC 189 Z9 195 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 29 PY 2007 VL 204 IS 11 BP 2521 EP 2528 DI 10.1084/jem.20070795 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 227JE UT WOS:000250652200005 PM 17908938 ER PT J AU Pitskel, NB Merabet, LB Ramos-Estebanez, C Kauffman, T Pascual-Leone, A AF Pitskel, Naomi B. Merabet, Lotfi B. Ramos-Estebanez, Ciro Kauffman, Thomas Pascual-Leone, Alvaro TI Time-dependent changes in cortical excitability after prolonged visual deprivation SO NEUROREPORT LA English DT Article DE cortical excitability; transcranial magnetic stimulation; phosphenes; visual cortex; visual deprivation ID TRANSCRANIAL MAGNETIC STIMULATION; TERM LIGHT DEPRIVATION; PHOSPHENE THRESHOLDS; SOUND LOCALIZATION; BLIND SUBJECTS; CORTEX; BRAIN AB Transcranial magnetic stimulation applied to the occipital cortex can elicit phosphenes. Changes in the phosphene threshold provide a measure of visual cortex excitability. Phosphene threshold was measured in participants blindfolded for five consecutive days to assess the effects of prolonged visual deprivation on visual cortical excitability. After 48 In of blindfolding, an acute decrease in phosphene threshold was observed, followed by a significant increase by day 5. Phosphene threshold returned to preblindfold levels within 2 h of light re-exposure. Thus, light deprivation is characterized by a transient increase in visual cortical excitability, followed by a sustained decrease in visual cortex excitability that quickly returns to baseline levels after re-exposure to light. (C) 2007 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 Harvard Univ, Sch Med, BIDMC, Ctr Noninvas Brain Stimulat, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Berenson Allen Ctr Noninvas Stimulat, Dept Neurol, Boston, MA 02215 USA. RP Pascual-Leone, A (reprint author), Harvard Univ, Sch Med, BIDMC, Ctr Noninvas Brain Stimulat, 330 Brookline Ave, Boston, MA 02215 USA. EM apleone@bidmc.harvard.edu FU NCRR NIH HHS [K24-RR018875, MO1 RR01032]; NEI NIH HHS [K23-EY016131, R01-EY12091] NR 21 TC 25 Z9 25 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 29 PY 2007 VL 18 IS 16 BP 1703 EP 1707 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 222WS UT WOS:000250329300014 PM 17921872 ER PT J AU Monnard, PA Luptak, A Deamer, DW AF Monnard, Pierre-Alain Luptak, Andrej Deamer, David W. TI Models of primitive cellular life: polymerases and templates in liposomes SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Article DE encapsulated transcription; liposomes; nutrient uptake; origin of life; passive diffusion; protocell ID LIPID VESICLES; RNA; MACROMOLECULES; ENCAPSULATION; ENTRAPMENT; PERMEATION; EXPRESSION; MOLECULES; EVOLUTION; THICKNESS AB Nutrient transport, polymerization and expression of genetic information in cellular compartments are hallmarks of all life today, and must have appeared at some point during the origin and early evolution of life. Because the first cellular life lacked membrane transport systems based on highly evolved proteins, they presumably depended on simpler processes of nutrient uptake. Using a system consisting of an RNA polymerase and DNA template entrapped in submicrometre-sized lipid vesicles (liposomes), we found that the liposome membrane could be made sufficiently permeable to allow access of ionized substrate molecules as large as nucleoside triphosphates (NTPs) to the enzyme. The encapsulated polymerase transcribed the template-specific base sequences of the DNA to the RNA that was synthesized. These experiments demonstrate that units of genetic information can be associated with a functional catalyst in a single compartment, and that transcription of gene-sized DNA fragments can be achieved by relying solely on passive diffusion to supply NTPs substrates. C1 Univ Calif Berkeley, Dept Chem & Biochem, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Monnard, PA (reprint author), Los Alamos Natl Lab, EES 6,MS D-462, Los Alamos, NM 87545 USA. EM pmonnard@lanl.gov NR 38 TC 38 Z9 38 U1 1 U2 13 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD OCT 29 PY 2007 VL 362 IS 1486 BP 1741 EP 1750 DI 10.1098/rstb.2007.2066 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 211IE UT WOS:000249516700003 PM 17472931 ER PT J AU Kuebler, DL Illingworth, A Blenc, AM Wilbur, DC AF Kuebler, Diane L. Illingworth, Andrea Blenc, Ann Marie Wilbur, David C. TI A peer comparison program for the quality assurance of human papillomavirus DNA detection using the digene hybrid capture II/Surepath method shows excellent analytic interlaboratory correlation SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT Congress of the International-Academy-of-Cytology CY MAY 13-17, 2007 CL Vancouver, CANADA SP Int Acad Cytol DE human papillomavirus; cervical cytology; quality assurance; cancer screening AB BACKGROUND. Interlaboratory peer comparison programs are quality-assurance activities mandated by the Clinical Laboratory Improvement Amendments of 1988. No commercial program is available currently that was designed for cytology laboratories performing only human papillomavirus (HPV) DNA testing. In this report, the authors provide the results from a self-developed program between 2 cytology laboratories. METHODS. Between 4 and 11 SurePath liquid-based cervical cytology samples were selected at each of the 2 participating laboratories each quarter and exchanged without accompanying patient information. Samples were selected to test both positive and negative high-risk HPV DNA results in roughly equivalent numbers. Samples were run with the Hybrid Capture II method using each laboratory's standard procedure. The result obtained was compared with the originating laboratory's result. Correlation was compared on an ongoing basis as a method to assess analytic performance. RESULTS. over a 3-year period, 12 exchanges took place, constituting 113 total specimens. Overall, there were 9 exchanges of 76 specimens that had 100% correlation, and 3 exchanges in which 4 of 37 specimens had discordant results. Overall, this represented a 97% correlation (109 of 113 specimens) of results between laboratories. All 4 discordant cases were reported as negative by the original laboratory and positive by the exchange laboratory (2 in each direction). CONCLUSIONS. The interlaboratory peer comparison result of 97% concordance demonstrated excellent analytic agreement between the HPV DNA-detection procedures of each laboratory. All discordant cases were "negative to positive" and were distributed equally by originating laboratory. The procedure was easily set up and provided assurance to each laboratory of ongoing performance for the detection of the HPV DNA analyte. C1 Massachusetts Gen Hosp, Dept Pathol, Sch Med, Boston, MA USA. Dahl Chase Pathol, Bangor, Wales. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM dwilbur@partners.org NR 8 TC 8 Z9 8 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2007 VL 111 IS 5 BP 339 EP 343 DI 10.1002/cncr.22951 PG 5 WC Oncology; Pathology SC Oncology; Pathology GA 221UW UT WOS:000250253800011 PM 17879373 ER PT J AU Hysell, C Belsley, N Deshpande, V AF Hysell, Christopher Belsley, Nicole Deshpande, Vikram TI EUS guided fine needle aspiration biopsies of solid ductal adenocarcinomas of the pancreas: A critical look at the atypical and suspicious categories SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Hysell, Christopher; Belsley, Nicole; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2007 VL 111 IS 5 SU S MA PF10 BP 351 EP 352 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 222YV UT WOS:000250335700011 ER PT J AU Sauder, K AF Sauder, Kenan TI A morphologic study of post-radical trachelectomy cytology samples SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Sauder, Kenan] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2007 VL 111 IS 5 SU S MA 65 BP 393 EP 393 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 222YV UT WOS:000250335700080 ER PT J AU Posner, MR Hershock, DM Blajman, CR Mickiewicz, E Winquist, E Gorbounova, V Tjulandin, S Shin, DM Cullen, K Ervin, TJ Murphy, BA Raez, LE Cohen, RB Spaulding, M Tishler, RB Roth, B Viroglio, RD Venkatesan, V Romanov, I Agarwala, S Harter, KW Dugan, M Cmelak, A Markoe, AM Read, PW Steinbrenner, L Colevas, AD Norris, CM Haddad, RI AF Posner, Marshall R. Hershock, Diane M. Blajman, Cesar R. Mickiewicz, Elizabeth Winquist, Eric Gorbounova, Vera Tjulandin, Sergei Shin, Dong M. Cullen, Kevin Ervin, Thomas J. Murphy, Barbara A. Raez, Luis E. Cohen, Roger B. Spaulding, Monica Tishler, Roy B. Roth, Berta del Carmen Viroglio, Rosana Venkatesan, Varagur Romanov, Ilya Agarwala, Sanjiv Harter, K. William Dugan, Matthew Cmelak, Anthony Markoe, Arnold M. Read, Paul W. Steinbrenner, Lynn Colevas, A. Dimitrios Norris, Charles M., Jr. Haddad, Robert I. CA Tax 324 Study Grp TI Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PHASE-III TRIAL; INDUCTION CHEMOTHERAPY; RADIATION-THERAPY; I-II; RANDOMIZED-TRIAL; ACTIVE-DRUG; RADIOTHERAPY; PRESERVATION; CARBOPLATIN AB Background A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. Methods We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. Results With a minimum of 2 years of follow-up (greater/equal 3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group. Conclusions Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sanofi Aventis, Malvern, PA USA. Hosp Iturraspe, Buenos Aires, Santa Fe, Argentina. Inst Angel H Roffo, Buenos Aires, DF, Argentina. London Reg Canc Ctr, London, ON N6A 4L6, Canada. Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia. Emory Winship Canc Inst, Atlanta, GA USA. Univ Maryland, Greenbaum Canc Ctr, Baltimore, MD 21201 USA. Maine Ctr Canc Med & Blood Disorders, Scarborough, ME USA. Vanderbilt Univ, Nashville, TN USA. Metro Nashville Gen Hosp, Nashville, TN USA. Univ Miami, Sylvester Canc Ctr, Miami, FL 33152 USA. Univ Virginia, Charlottesville, VA USA. Vet Affairs Western New York Healthcare Syst, Buffalo, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. Vincent T Lombardi Canc Res Ctr, Washington, DC USA. RP Posner, MR (reprint author), Dana Farber Canc Inst, 44 Binney St,SW 430, Boston, MA 02115 USA. EM marshall_posner@dfci.harvard.edu RI Ray, Dana/C-3470-2013; Shin, Dong Moon/G-9649-2013 NR 30 TC 782 Z9 827 U1 0 U2 30 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 25 PY 2007 VL 357 IS 17 BP 1705 EP 1715 DI 10.1056/NEJMoa070956 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 223FN UT WOS:000250355100006 PM 17960013 ER PT J AU Attar, EC Aquino, SL Hasserjian, RP Harris, NL AF Attar, Eyal C. Aquino, Suzanne L. Hasserjian, Robert P. Harris, Nancy Lee TI A 49-year-old HIV-positive man with anemia - Pure red-cell aplasia associated with classic Hodgkin's lymphoma in an HIV-positive man. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PARVOVIRUS B19 INFECTION; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ERYTHROPOIETIN; DISEASE; PLASMA; THERAPY; ERYTHROBLASTOPENIA; EPIDEMIOLOGY; PATIENT; PROTEIN C1 Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Attar, EC (reprint author), Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. NR 28 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 25 PY 2007 VL 357 IS 17 BP 1745 EP 1754 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 223FN UT WOS:000250355100011 PM 17960016 ER PT J AU Li, WH Sui, JH Huang, IC Kuhn, JH Radoshitzky, SR Marasco, WA Choe, H Farzan, M AF Li, Wenhui Sui, Jianhua Huang, I-Chueh Kuhn, Jens H. Radoshitzky, Sheli R. Marasco, Wayne A. Choe, Hyeryun Farzan, Michael TI The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2 SO VIROLOGY LA English DT Article DE human coronavirus NL63; SARS coronavirus; angiotensin-converting enzyme 2; viral entry ID ANGIOTENSIN-CONVERTING ENZYME-2; SARS CORONAVIRUS; SPIKE PROTEIN; FUNCTIONAL-CHARACTERIZATION; MURINE CORONAVIRUS; NL63 INFECTION; YOUNG-CHILDREN; TRACT DISEASE; HONG-KONG; RECEPTOR AB The cellular receptor for human coronavirus NL63 (HCoV-NL63), a group I coronavirus, is angiotensin-converting enzyme2 (ACE2). ACE2 is also the receptor for the SARS coronavirus (SARS-CoV), a group It coronavirus. Here we describe the ability of HCoV-NL63 to utilize a number of ACE2 variants previously characterized as SARS-CoV receptors. Several ACE2 variants that reduced SARS-CoV S-protein association similarly reduced that of HCoV-NL63, whereas alteration of a number of solvent-exposed ACE2 residues did not interfere with binding by either S protein. One notable exception is ACE2 residue 354, at the boundary of the SARS-CoV binding site, whose alteration markedly inhibited utilization by the HCoV-NL63 but not SARS-CoV S proteins. In addition, the SARS-CoV S-protein receptor-binding domain inhibited entry mediated by the HCoV-NL63 S protein. These studies indicate that HCoV-NL63, like SARS-CoV, associates region of human ACE2 that includes a key loop formed by beta-strands 4 and 5. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Free Univ Berlin, Dept Biol, D-1000 Berlin, Germany. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Ina Sue Perlmutter Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Farzan, M (reprint author), 1 Pine Hall Dr, Southborough, MA 01772 USA. EM farzan@hms.harvard.edu RI Kuhn, Jens H./B-7615-2011; OI Kuhn, Jens H./0000-0002-7800-6045; Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [R01 AI061601, R01 AI061601-03] NR 46 TC 18 Z9 19 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 25 PY 2007 VL 367 IS 2 BP 367 EP 374 DI 10.1016/j.virol.2007.04.035 PG 8 WC Virology SC Virology GA 220NH UT WOS:000250162900014 PM 17631932 ER PT J AU Swirski, FK Berger, CR Figueiredo, JL Mempel, TR von Andrian, UH Pittet, MJ Weissleder, R AF Swirski, Filip K. Berger, Cedric R. Figueiredo, Jose-Luiz Mempel, Thorsten R. von Andrian, Ulrich H. Pittet, Mikael J. Weissleder, Ralph TI A Near-Infrared Cell Tracker Reagent for Multiscopic In Vivo Imaging and Quantification of Leukocyte Immune Responses SO PLOS ONE LA English DT Article AB The complexity of the tumor microenvironment necessitates that cell behavior is studied in a broad, multi-scale context. Although tomographic and microscopy-based far and near infrared fluorescence (NIRF, >650 nm) imaging methods offer high resolution, sensitivity, and depth penetration, there has been a lack of optimized NIRF agents to label and track cells in their native environments at different scales. In this study we labeled mammalian leukocytes with VivoTag 680 (VT680), an amine reactive N-hydroxysuccinimide (NHS) ester of a (benz) indolium-derived far red fluorescent probe. We show that VT680 diffuses into leukocytes within minutes, covalently binds to cellular components, remains internalized for days in vitro and in vivo, and does not transfer fluorescence to adjacent cells. It is biocompatible, keeps cells fully functional, and fluoresces at high intensities. In a tumor model of cytotoxic T lymphocyte (CTL) immunotherapy, we track and quantify VT680-labeled cells longitudinally at the whole-body level with fluorescence-mediated molecular tomography (FMT), within tissues at single cell resolutions by multiphoton and confocal intravital microscopy, and ex vivo by flow cytometry. Thus, this approach is suitable to monitor cells at multiple resolutions in real time in their native environments by NIR-based fluorescence imaging. C1 [Swirski, Filip K.; Berger, Cedric R.; Figueiredo, Jose-Luiz; Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Swirski, Filip K.; Berger, Cedric R.; Figueiredo, Jose-Luiz; Pittet, Mikael J.; Weissleder, Ralph] Harvard Univ, Sch Med, Charlestown, MA USA. [Mempel, Thorsten R.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. [von Andrian, Ulrich H.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Pittet, Mikael J.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA USA. RP Swirski, FK (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RI von Andrian, Ulrich/A-5775-2008 FU NIH [U54 CA126515, P01A154904, U01 HL080731, R24 CA69246, P50-CA086355]; American Heart Association [0525866T]; Novartis Foundation; Human Frontier Science Program Organization [LT00369/2003] FX This work was supported in part by NIH grants U54 CA126515, P01A154904, U01 HL080731 and R24 CA69246 (to RW), P50-CA086355 ( to RW and MJP). FKS was supported by a post-doctoral fellowship from American Heart Association (0525866T). CRB was supported by a fellowship from Novartis Foundation ( formerly the Ciba-Geigy Jubilee Foundation). MJP was supported by the Human Frontier Science Program Organization (LT00369/2003). NR 18 TC 37 Z9 37 U1 1 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 OCT 24 PY 2007 VL 2 IS 10 AR e1075 DI 10.1371/journal.pone.0001075 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10IU UT WOS:000207458500020 PM 17957257 ER PT J AU Forman, SA Zhou, QL Stewart, DS AF Forman, Stuart A. Zhou, Qiong L. Stewart, Deirdre S. TI Photoactivated 3-azioctanol irreversibly desensitizes muscle nicotinic ACh receptors via interactions at alpha E262 SO BIOCHEMISTRY LA English DT Article ID ACETYLCHOLINE-RECEPTOR; GENERAL-ANESTHETICS; CHANNEL; BINDING; ACTIVATION; MECHANISM; BLOCK; SITE; PORE; IDENTIFICATION AB 3-Azioctanol is a photoactivatable analogue of octanol that noncompetitively inhibits nicotinic acetylcholine receptors (nAChRs). Photolabeling studies using [H-3]-3-azioctanol in Torpedo nAChR identified alpha E262 as a site of desensitization-dependent incorporation. However, it is unknown whether photolabeling of alpha E262 causes functional effects in nAChRs and what other roles this residue plays in gating, desensitization, and channel block. We used ultrafast patch-perfusion electrophysiology and ultraviolet (UV) irradiation to investigate the state-dependence of both reversible nAChR inhibition by 3-azioctanol and the irreversible effects of photoactivated 3-azioctanol. Channels with mutations at alpha E262 were studied to determine ACh EC50s, desensitization rates, and sensitivities to reversible and photoirreversible 3-azioctanol inhibition. Exposure to 3-azioctanol in the presence of 365 nm UV light produced irreversible inhibition of wild-type nAChRs. Desensitization with ACh dramatically increased the degree of irreversible inhibition by photoactivated 3-azioctanol. Mutations at alpha E262 that reduce diazirine photomodification decreased the irreversible inhibition induced by photoactivated 3-azioctanol. Hydrophobic mutations at alpha E262 significantly slowed rapid ACh-induced desensitization and dramatically slowed fast resensitization. In contrast, alpha E262 mutations minimally affected 3-azioctanol channel block, and a half blocking concentration of 3-azioctanol did not alter the rate of ACh-induced fast desensitization. Our results indicate that position aE262 on muscle nAChRs contributes to an allosteric modulator site that is strongly coupled to desensitization. Occupation of this pocket by hydrophobic molecules stabilizes a desensitized state by slowing resensitization. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Univ Massachusetts, Sch Med, Program Mol Med, Worcester, MA 01605 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Jackson 4, Boston, MA 02114 USA. EM saforman@partners.org FU NIGMS NIH HHS [GM58448, GM66724] NR 33 TC 11 Z9 11 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 23 PY 2007 VL 46 IS 42 BP 11911 EP 11918 DI 10.1021/bi701287a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 221LI UT WOS:000250228400025 PM 17910479 ER PT J AU Lichtman, JH Spertus, JA Reid, KJ Radford, MJ Rumsfeld, JS Allen, NB Masoudi, FA Weintraub, WS Krumholz, HM AF Lichtman, Judith H. Spertus, John A. Reid, Kimberly J. Radford, Martha J. Rumsfeld, John S. Allen, Norrina B. Masoudi, Frederick A. Weintraub, William S. Krumholz, Harlan M. TI Acute noncardiac conditions and in-hospital mortality in patients with acute myocardial infarction SO CIRCULATION LA English DT Article DE comorbidity; mortality; myocardial infarction; prognosis ID TIMI RISK SCORE; INTERNATIONAL TRIAL; PRACTICE GUIDELINES; THROMBOLYSIS; PREDICTORS; REGISTRY; EVENTS; COMORBIDITY; COMMITTEE; SURVIVAL AB Background - Acute myocardial infarction may be accompanied by acute, severe, concomitant, noncardiac conditions, but their prevalence and prognostic importance is not well defined. We sought to evaluate the prevalence of acute, severe, noncardiac conditions present at the time of hospital admission with acute myocardial infarction and to assess the association of these conditions with in-hospital mortality. Methods and Results - A total of 3907 patients admitted with an acute myocardial infarction were prospectively enrolled in 19 US centers between January 2003 and June 2004. Acute noncardiac conditions present at admission with imminent threat to life were identified from medical record review within 24 hours of admission. Using multivariable analyses, we evaluated the relationship between these conditions and in- hospital mortality. We documented a concomitant acute, severe, noncardiac condition in 6.8% ( n = 267) of the study sample. The most common concomitant conditions were severe pneumonia ( potentially requiring intubation; 18.4%), severe gastrointestinal bleeding/anemia ( 15.7%), stroke ( 9.7%), and sepsis ( 9.4%). These patients were less likely to be ideal for or to receive evidence-based therapies at the time of admission. The in- hospital mortality was 21.3% ( 57 of 267) for patients with concomitant conditions versus 2.7% ( 100 of 3640) for those without these conditions. The presence of an acute noncardiac condition was associated with an increased risk of in- hospital mortality after adjustment for demographic and clinical characteristics and disease severity ( odds ratio, 5.0; 95% confidence interval, 3.3 to 7.7). Conclusions - Concomitant, acute, noncardiac conditions are common and associated with a marked increase in the risk of in- hospital mortality. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Chron Dis Epidemiol, New Haven, CT 06510 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. NYU, Med Ctr, Dept Med, Div Cardiol, New York, NY 10016 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver Hlth Med Ctr, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Colorado Hlth Outcomes Program, Denver, CO 80202 USA. Christiana Care Hlth Syst, Newark, DE USA. Jefferso Univ, Dept Med, Philadelphia, PA USA. Yale Univ, Sch Med, Dept Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Med, Robert Wood Johnson Clin Scholars Program, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT 06504 USA. RP Krumholz, HM (reprint author), 333 Cedar St,Room I-456 SHM,POB 208088, New Haven, CT 06520 USA. EM harlan.krumholz@yale.edu OI Radford, Martha/0000-0001-7503-9557 FU NCCDPHP CDC HHS [K01 DP000085-03] NR 22 TC 29 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 23 PY 2007 VL 116 IS 17 BP 1925 EP 1930 DI 10.1161/CIRCULATIONAHA.107.722090 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225KX UT WOS:000250517900011 PM 17923572 ER PT J AU Simon, KC Chen, H Schwarzschild, M Ascherio, A AF Simon, Kelly Claire Chen, Honglei Schwarzschild, Michael Ascherio, Alberto TI Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease SO NEUROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; URIC-ACID LEVELS; CARDIOVASCULAR REFLEXES; AUTONOMIC DYSFUNCTION; CHOLESTEROL LEVELS; WOMEN; POPULATION; QUESTIONNAIRE; DIAGNOSIS; ACCURACY AB Objective: To determine whether history of hypertension, hypercholesterolemia, or diabetes is associated with risk of Parkinson disease ( PD). Methods: Prospective study among participants in two large cohorts: the Nurses' Health Study ( 121,046 women) and the Health Professionals Follow- up Study ( 50,833 men). Mean duration of follow- up was 22.9 years in women, aged 30 to 55 years at baseline, and 12.6 years in men, aged 40 to 75 years at baseline. Relative risks ( RRs) of PD were estimated from a Cox proportional hazards model adjusting for potential confounders. Results: We identified a total of 530 incident cases of PD during the follow- up. Risk of PD was not associated with self- reported history of hypertension ( RR = 0.96, 95% CI = 0.80 to 1.15), high cholesterol ( RR = 0.98, 95% CI = 0.82 to 1.19), or diabetes ( RR = 1.04, 95% CI = 0.74 to 1.46), after adjusting for age and smoking in pack- years. Risk of PD decreased modestly with increasing levels of self- reported total cholesterol ( RR for a 50- mg/ dL increase in total cholesterol = 0.86, 95% CI = 0.78 to 0.95, p for trend = 0.02), but use of cholesterol- lowering drugs was not associated with PD risk ( RR comparing users with nonusers = 0.85, 95% CI = 0.59 to 1.23). Among individuals with PD, systolic blood pressure was similar to noncases up to the time of diagnosis but declined afterward. Conclusions: Results of this large prospective study suggest that Parkinson disease risk is not significantly related to history of hypertension, hypercholesterolemia, or diabetes but may modestly decline with increasing blood cholesterol levels. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Simon, KC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave,Bldg 2,Rm 305, Boston, MA 02115 USA. EM ksimon@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NIEHS NIH HHS [T32 ES007069, T32 ES007069-26, T32 ES07069-26]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2] NR 36 TC 94 Z9 97 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 23 PY 2007 VL 69 IS 17 BP 1688 EP 1695 DI 10.1212/01.wnl.0000271883.45010.8a PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 222ZZ UT WOS:000250340300009 PM 17761552 ER PT J AU Henson, JW Cascino, GD Post, ME AF Henson, John W. Cascino, Gregory D. Post, Mary E. TI International science at the annual meeting of the American Academy of Neurology SO NEUROLOGY LA English DT Article AB The annual meeting of the American Academy of Neurology ( AAN) is a major venue for presentation of the latest disease- related clinical and basic neurologic research and is attended by a large number of neurologists from countries outside the United States and Canada. One- third of annual meeting attendees and abstract submissions are international in origin, with wide variations between countries and world regions, and this proportion has remained stable for the past 5 years. By comparison, international neurologists constitute 12% ( n = 2,485) of AAN membership, and international membership has declined slightly over the past 5 years compared to a 15% increase from the United States and Canada. The scientific topics covered by international abstracts are similar to those from the United States and Canada. Abstract acceptance rates are 15% lower for international submissions than for those from the United States and Canada although variations between countries are seen. Three times more European neurologists attend the annual meeting than are AAN members whereas Asian neurologists are more likely to be AAN members than to attend the annual meeting. The AAN is working to understand and address the issues that affect international physicians' decisions to participate in the annual meeting. C1 Massachusetts Gen Hosp, Stephen E Catherine Pappas Ctr Neurooncol, Neurol Serv, Boston, MA 02114 USA. Amer Acad Neurol, Sci Comm, St Paul, MN USA. Amer Acad Neurol, Membership Comm, St Paul, MN USA. Mayo Clin, Dept Neurol, Rochester, MN USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Stephen E Catherine Pappas Ctr Neurooncol, Neurol Serv, Yawkey 9 E,55 Fruit St, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 23 PY 2007 VL 69 IS 17 BP 1712 EP 1714 DI 10.1212/01.wnl.0000285097.18750.cf PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 222ZZ UT WOS:000250340300012 PM 17954786 ER PT J AU Bodyak, N Ayus, JC Achinger, S Shivalingappa, V Ke, Q Chen, YS Rigor, DL Stillman, I Tamez, H Kroeger, PE Wu-Wong, RR Karumanchi, SA Thadhani, R Kang, PM AF Bodyak, Natalya Ayus, Juan Carlos Achinger, Steven Shivalingappa, Venkatesha Ke, Qingen Chen, Yee-Shiuan Rigor, Debra L. Stillman, Isaac Tamez, Hector Kroeger, Paul E. Wu-Wong, Ruth R. Karumanchi, S. Ananth Thadhani, Ravi Kang, Peter M. TI Activated vitamin D attenuates left ventricular abnormalities induced by dietary sodium in Dahl salt-sensitive animals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cardiac hypertrophy; heart failure; paricalcitol; renal failure ID RENIN-ANGIOTENSIN SYSTEM; NF-KAPPA-B; HEART-FAILURE; CARDIAC-HYPERTROPHY; 1,25-DIHYDROXYVITAMIN D-3; MYOCARDIAL HYPERTROPHY; HEMODIALYSIS-PATIENTS; GENE-EXPRESSION; BONE-DISEASE; RAT-HEART AB Observations in hemodialysis patients suggest a survival advantage associated with activated vitamin D therapy. Left ventricular (LV) structural and functional abnormalities are strongly linked with hemodialysis mortality. Here, we investigated whether paricalcitol (PC, 119-nor-1,25(OH)(2)D-2), an activated vitamin D compound, attenuates the development of LV abnormalities in the Dahl salt-sensitive (DSS) rat and whether humans demonstrate comparable findings. Compared with DSS rats fed a high-salt (HS) diet(6% NaCl for 6 weeks), HS+PC was associated with lower heart and lung weights, reduced LV mass, posterior wall thickness and end diastolic pressures, and increased fractional shortening. Blood pressures did not significantly differ between the HS groups. Plasma brain natriuretic peptide levels, and cardiac mRNA expression of brain natriuretic peptide, atrial natriuretic factor, and renin were significantly reduced in the HS+PC animals. Microarray analyses revealed 45 specific HS genes modified by PC. In a retrospective pilot study of hemodialysis patients, PC-treated subjects demonstrated improved diastolic function and a reduction in LV septal and posterior wall thickness by echocardiography compared with untreated patients. In summary, PC attenuates the development of LV alterations in DSS rats, and these effects should be examined in human clinical trials. C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, CeDAR, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA. Univ Texas, Hlth Sci Ctr, Div Nephrol, San Antonio, TX 78229 USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, Renal Unit, Bullfinch 127, Boston, MA 02114 USA. EM thadhani.ravi@mgh.harvard.edu FU NHLBI NIH HHS [R01 HL065742]; NIDDK NIH HHS [R21 DK071674] NR 41 TC 197 Z9 204 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2007 VL 104 IS 43 BP 16810 EP 16815 DI 10.1073/pnas.0611202104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224ZT UT WOS:000250487600018 PM 17942703 ER PT J AU Tsytsykova, AV Rajsbaum, R Falvo, JV Ligeiro, F Neely, SR Goldfeld, AE AF Tsytsykova, Alla V. Rajsbaum, Ricardo Falvo, James V. Ligeiro, Filipa Neely, Simon R. Goldfeld, Anne E. TI Activation-dependent intrachromosomal interactions formed by the TNF gene promoter and two distal enhancers SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromosome conformation capture assay; chromatin; nuclear factor of activated T cells I transcriptional regulation ID NECROSIS-FACTOR-ALPHA; BETA-GLOBIN LOCUS; MAJOR HISTOCOMPATIBILITY COMPLEX; ACTIVE CHROMATIN HUB; NF-KAPPA-B; T-CELLS; SPATIAL-ORGANIZATION; LYMPHOTOXIN-BETA; CONTROL REGION; EXPRESSION AB Here we provide a mechanism for specific, efficient transcription of the TNF gene and, potentially, other genes residing within multi-gene loci. We identify and characterize highly conserved noncoding elements flanking the TNF gene, which undergo activation-dependent intrachromosomal interactions. These elements, hypersensitive site (HSS)-9 and HSS+3 (9 kb upstream and 3 kb downstream of the TNF gene, respectively), contain DNase I hypersensitive sites in naive, T helper 1, and T helper 2 primary T cells. Both HSS-9 and HSS+3 inducibly associate with acetylated histones, indicative of chromatin remodeling, bind the transcription factor nuclear factor of activated T cells (NFAT)p in vitro and in vivo, and function as enhancers of NFAT-dependent transactivation mediated by the TNF promoter. Using the chromosome conformation capture assay, we demonstrate that upon T cell activation intrachromosomal looping occurs in the TNF locus. HSS-9 and HSS+3 each associate with the TNF promoter and with each other, circularizing the TNF gene and bringing NFAT-containing nucleoprotein complexes into close proximity. TNF gene regulation thus reveals a mode of intrachromosomal interaction that combines a looped gene topology with interactions between enhancers and a gene promoter. C1 Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Immune Dis Inst, 800 Hungtington Ave, Boston, MA 02115 USA. EM goldfeld@cbrinstitute.org RI Rajsbaum, Ricardo/F-2046-2014 FU NIGMS NIH HHS [R01 GM 076685, R01 GM076685] NR 55 TC 48 Z9 49 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2007 VL 104 IS 43 BP 16850 EP 16855 DI 10.1073/pnas.0708210104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224ZT UT WOS:000250487600025 PM 17940009 ER PT J AU Miao, J Wang, Z Provencher, H Muir, B Dahiya, S Carney, E Leong, CO Sgroi, DC Orsulic, S AF Miao, Jiangyong Wang, Zuncai Provencher, Heather Muir, Beth Dahiya, Sonika Carney, Erin Leong, Chee-Onn Sgroi, Dennis C. Orsulic, Sandra TI HOXB13 promotes ovarian cancer progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE estrogen; Ras; tamoxifen; homeobox; mouse model ID HOMEOBOX GENE-EXPRESSION; PATHWAY-TARGETED THERAPY; BREAST-CANCER; PROSTATE; CARCINOMA; TAMOXIFEN; CELLS; DIFFERENTIATION; FIBROBLASTS; SUPPRESSION AB Deregulated expression of HOXB13 in a subset of estrogen receptor-positive breast cancer patients treated with tamoxifen monotherapy is associated with an aggressive clinical course and poor outcome. Because the ovary is another hormone-responsive organ, we investigated whether HOXB13 plays a role in ovarian cancer progression. We show that HOXB13 is expressed in multiple human ovarian cancer cell lines and tumors and that knockdown of endogenous HOXB13 by RNA interference in human ovarian cancer cell lines is associated with reduced cell proliferation. Ectopic expression of HOXB13 is capable of transforming p53(-/-) mouse embryonic fibroblasts and promotes cell proliferation and anchorage-independent growth in mouse ovarian cancer cell lines that contain genetic alterations in p53, myc, and ras. In this genetically defined cell line model of ovarian cancer, we demonstrate that HOXB13 collaborates with activated ras to markedly promote tumor growth in vivo and that HOXB13 confers resistance to tamoxifen-mediated apoptosis. Taken together, our results support a pro-proliferative and pro-survival role for HOXB13 in ovarian cancer. C1 Massachusetts Gen Hosp, Mol Pathol Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp, Mol Pathol Res Unit, Charlestown, MA 02129 USA. EM dsgroi@partners.org; sorsulic@partners.org FU NCI NIH HHS [1R01 CA 112021-01, R01 CA112021, P50 CA 105009, P50 CA105009, R01 CA 103924, R01 CA103924] NR 34 TC 52 Z9 54 U1 1 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 OCT 23 PY 2007 VL 104 IS 43 BP 17093 EP 17098 DI 10.1073/pnas.0707938104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224ZT UT WOS:000250487600066 PM 17942676 ER PT J AU DiFiglia, M Sena-Esteves, M Chase, K Sapp, E Pfister, E Sass, M Yoder, J Reeves, P Pandey, RK Rajeev, KG Manoharan, M Sah, DWY Zamore, PD Aronin, N AF DiFiglia, M. Sena-Esteves, M. Chase, K. Sapp, E. Pfister, E. Sass, M. Yoder, J. Reeves, P. Pandey, R. K. Rajeev, K. G. Manoharan, M. Sah, D. W. Y. Zamore, P. D. Aronin, N. TI Therapeutic silencing of mutant huntingtin with siRNA attenuates striatal and cortical neuropathology and behavioral deficits SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene delivery; gene silencing; Huntington's disease; neurodegenerative disease; RNAi ID NEURONAL INTRANUCLEAR INCLUSIONS; MOUSE MODEL; RNA INTERFERENCE; IN-VIVO; MEDIATED DELIVERY; DISEASE; BRAIN; GENE; ABNORMALITIES; EXPRESSION AB Huntington's disease (HD) is a neurodegenerative disorder caused by expansion of a CAG repeat in the huntingtin (Htt) gene. HD is autosomal dominant and, in theory, amenable to therapeutic RNA silencing. We introduced cholesterol-conjugated small interfering RNA duplexes (cc-siRNA) targeting human Htt mRNA (siRNA-Htt) into mouse striata that also received adeno-associated virus containing either expanded (100 CAG) or wild-type (18 CAG) Htt cDNA encoding huntingtin (Htt) 1-400. Adeno-associated virus delivery to striatum and overlying cortex of the mutant Htt gene, but not the wild type, produced neuropathology and motor deficits. Treatment with cc-siRNA-Htt in mice with mutant Htt prolonged survival of striatal neurons, reduced neuropil aggregates, diminished inclusion size, and lowered the frequency of clasping and footslips on balance beam. cc-siRNA-Htt was designed to target human wild-type and mutant Htt and decreased levels of both in the striatum. Our findings indicate that a single administration into the adult striatum of an siRNIA targeting Htt can silence mutant Htt, attenuate neuronal pathology, and delay the abnormal behavioral phenotype observed in a rapid-onset, viral transgenic mouse model of HD. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Alnylam Pharmaceut, Cambridge, MA 02142 USA. RP Aronin, N (reprint author), Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01655 USA. EM neil.aronin@umassmed.edu RI Zamore, Phillip/A-8941-2013 FU NINDS NIH HHS [NS 38194, R01 NS038194] NR 41 TC 210 Z9 218 U1 1 U2 19 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2007 VL 104 IS 43 BP 17204 EP 17209 DI 10.1073/pnas.0708285104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224ZT UT WOS:000250487600085 PM 17940007 ER PT J AU Righart, R de Gelder, B AF Righart, Ruthger de Gelder, Beatrice TI Impaired face and body perception in developmental prosopagnosia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE face configuration; inversion effect; N1 70 ID EVENT-RELATED POTENTIALS; CONGENITAL PROSOPAGNOSIA; DETAILED EXPLORATION; PROCESSING DEVELOPS; OBJECT RECOGNITION; BRAIN POTENTIALS; INVERSION; N170; MECHANISMS; ERP AB Prosopagnosia is a deficit in face recognition in the presence of relatively normal object recognition. Together with older lesion studies, recent brain-imaging results provide evidence for the closely related representations of faces and objects and, more recently, for brain areas sensitive to faces and bodies. This evidence raises the issue of whether developmental prosopagnosics may also have an impairment in encoding bodies. We investigated the first stages of face, body, and object perception in four developmental prosopagnosics by comparing event-related potentials to canonically and upside-down presented stimuli. Normal configural encoding was absent in three of four developmental prosopagnosics for faces at the P1 and for both faces and bodies at the N170 component. Our results demonstrate that prosopagnosics do not have this normal processing routine readily available for faces or bodies. A profound face recognition deficit characteristic of developmental prosopagnosia may not necessarily originate in a category-specific face recognition deficit in the initial stages of development. It may also have its roots in anomalous processing of the configuration, a visual routine that is important for other stimuli besides faces. Faces and bodies trigger configuration-based visual strategies that are crucial in initial stages of stimulus encoding but also serve to bootstrap the acquisition of more feature-based visual skills that progressively build up in the course of development. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5037 AB Tilburg, Netherlands. RP de Gelder, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. EM degelder@nmr.mgh.harvard.edu NR 58 TC 63 Z9 67 U1 3 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 23 PY 2007 VL 104 IS 43 BP 17234 EP 17238 DI 10.1073/pnas.0707753104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 224ZT UT WOS:000250487600090 PM 17942679 ER PT J AU Nakazawa, G Finn, AV John, MC Kolodgie, FD Virmani, R AF Nakazawa, Gaku Finn, Aloke V. John, Michael C. Kolodgie, Frank D. Virmani, Renu TI The significance of preclinical evaluation of sirolimus-, paclitaxel-, and zotarolimus-eluting stents SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID NATIVE CORONARY-ARTERY; BARE-METAL STENTS; REDUCES NEOINTIMAL FORMATION; TRIAL; THROMBOSIS; DELIVERY; IMPLANTATION; ENDOTHELIALIZATION; REVASCULARIZATION; MECHANISMS AB Comparative preclinical histologic studies remain the most effective method for assessing the healing characteristics of vascular stents. The 2 most commonly used animal models to assess vascular responses to stent implantation are the porcine coronary artery and the rabbit iliac artery. Neither model alone is,comparable to the human response to the implantation,of a drug-eluting stent (DES). In the rabbit model at 28 days, the pathologies of the zotarolimus-eluting stent (ZES), the paclitaxel-eluting stent (PES), the sirolimus-eluting stent (SES), and a bare metal stent (BMS) were assessed. There was less inflammation with the ZES than with the SES or PES, and there were uncovered struts with the SES and PES but not with the ZES and BMS. In the pig model at 30, 90, and 180 days, the pathologies of the ZES, SES, and BMS were assessed. At 30 days, the thickness of neointima and the grade, of inflammation were less with the SES than with the ZES and BMS, but at 90 and 180 days, the measures increased for the SES and were greater than those with the ZES and BMS, whereas the measures for the ZES and BMS did not change over time. In the rabbit model, the endothelialization of overlapping the SES, PES, and ZES was assessed. There was significantly greater endothelialization in the area above stent struts in the overlapping segment for the ZES than for the SES (p = 0.028). The level of endothelialization for the PES was less than that for the ZES, but the difference was not significant. Because arterial healing is multifactorial, it is extremely important that the next generation of DESs undergo preclinical testing in pig and rabbit models to examine endothelialization, inflammation, release kinetics, and neointimal reduction to establish the safety of these devices in humans. (C) 2007 Elsevier Inc. All rights reserved. C1 CVPath Inst Inc, Gaithersburg, MD 20878 USA. Massachusetts Gen Hosp, Cardiac Unit, Dept Internal Med, Boston, MA 02114 USA. RP Virmani, R (reprint author), CVPath Inst Inc, 19 1st Field Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org NR 41 TC 81 Z9 83 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 22 PY 2007 VL 100 IS 8B SU S BP 36M EP 44M DI 10.1016/j.amjcard.2007.08.020 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 228UV UT WOS:000250759000006 PM 17950831 ER PT J AU Singh, H Thomas, EJ Petersen, LA Studdert, DM AF Singh, Hardeep Thomas, Eric J. Petersen, Laura A. Studdert, David M. TI Medical errors involving trainees - A study of closed malpractice claims from 5 insurers SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 25-28, 2007 CL Toronto, CANADA SP Soc Gen Internal Med ID ADVERSE EVENTS; PATIENT SAFETY; COMMUNICATION FAILURES; TEACHING HOSPITALS; DIAGNOSTIC ERRORS; INTERNAL-MEDICINE; RESIDENCY PROGRAM; CONTROLLED-TRIAL; HEALTH-CARE; TEAMWORK AB Background: Despite wide recognition that the delivery of medical care by trainees involves special risks, information about the types and causes of medical errors involving trainees is limited. To describe the characteristics of and factors contributing to trainee errors, we analyzed malpractice claims in which trainees were judged to have played an important role in harmful errors. Methods: The claims were closed between 1984 and 2004, and the errors occurred between 1979 and 2001. Specialist physicians reviewed random samples of closed malpractice claim files at 5 liability insurers from 2002 to 2004 and determined whether injuries had occurred, and if so, whether they were due to error. We described the clinical circumstances and contributing factors associated with harmful errors involving trainees ("cases"). We also compared the characteristics of cases with their nontrainee counterparts and probed trainee errors attributed to teamwork problems and lack of technical competence or knowledge. Results: Among 240 cases, errors in judgment (173 of 240 [72%]), teamwork breakdowns (167 of 240 [70%]), and lack of technical competence (139 of 240 [58%]) were the most prevalent contributing factors. Lack of supervision and handoff problems were most prevalent types of teamwork problems, and both were disproportionately more common among errors that involved trainees than those that did not (respectively, 54% vs 7% [P <.001] and 20% vs 12% [P=.009]). The most common task during which failures of technical competence occurred were diagnostic decision making and monitoring of the patient or situation. Trainee errors appeared more complex than nontrainee errors (mean of 3.8 contributing factors vs 2.5 [P <.001]). Conclusions: In addition to problems with handoffs, house staff are particularly vulnerable to medical errors owing to teamwork failures, especially lack of supervision. Graduate medical education reform should focus on strengthening these aspects of training. C1 Baylor Coll Med, Dept Med, Hlth Policy & Qual Program, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Ctr Inquiry Improve Outpatient Safety Through Eff, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas, Sch Med, Dept Med, Div Gen Med, Houston, TX 77030 USA. Univ Texas, Ctr Excellence Patient Safety Res & Practice, Houston, TX USA. Univ Melbourne, Sch Populat Hlth, Parkville, Vic 3052, Australia. Univ Melbourne, Melbourne Law Sch, Parkville, Vic 3052, Australia. RP Studdert, DM (reprint author), Univ Melbourne, Sch Populat Hlth, 207 Bouverie St, Parkville, Vic 3052, Australia. EM d.studdert@unimelb.edu.au FU AHRQ HHS [1P01HS1154401, HS011886-03, KO2HS11285]; NCI NIH HHS [K23CA125585] NR 55 TC 187 Z9 189 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 22 PY 2007 VL 167 IS 19 BP 2030 EP 2036 DI 10.1001/archinte.167.19.2030 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 222VX UT WOS:000250326900003 PM 17954795 ER PT J AU Liubov, Y Dmitriy, A Margarita, G Elena, C Paul, H AF Liubov, Yamova Dmitriy, Atochin Margarita, Glazova Elena, Chernigovskaya Paul, Huang TI Role of neuronal nitric oxide in the regulation of vasopressin expression and release in response to inhibition of catecholamine synthesis and dehydration SO NEUROSCIENCE LETTERS LA English DT Article DE vasopressin; nitric oxide; catecholamines ID PARAVENTRICULAR NUCLEUS; SUPRAOPTIC NUCLEUS; CHROMAFFIN CELLS; SYNTHASE GENE; RAT; SECRETION; OXYTOCIN; IMMUNOREACTIVITY; MODULATION; PEPTIDES AB We used neuronal nitric oxide synthase (nNOS) gene knockout mice to study the effects of catecholamines and neuronal nitric oxide on vasopressin expression in the hypothalamic neurosecretory centers. nNOS gene deletion did not change the level of vasopressin mRNA in the supraoptic or paraventricular nuclei. In contrast, vasopressin immunoreactivity was lower in nNOS deficient mice than in wild-type animals. Dehydration increased vasopressin mRNA levels and decreased vasopressin immunoreactivity in both wild-type and nNOS knockout mice, but these responses were more marked in the nNOS knockout mice. Treatment with alpha-mpt, a pharmacologic inhibitor of catecholamine synthesis, resulted in increased vasopressin rnRNA levels in wild-type mice and in reduced vasopressin immunoreactivity in both wild-type and nNOS knockout mice. From these results, we conclude: (1) neuronal nitric oxide suppresses vasopressin expression under basal conditions and during activation of the vasopressinergic system by dehydration; (2) catecholamines limit vasopressin expression; (3) nNOS is required for the effects of catecholamines on vasopressin expression. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Russian Acad Sci, IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Div Cardiol, Charlestown, MA 02129 USA. E Carolina Univ, Brody Sch Med, Dept Physiol, Greenville, NC 27834 USA. RP Paul, H (reprint author), Massachusetts Gen Hosp, 149 Thirteenth St, Charlestown, MA 02129 USA. EM phuang1@partners.org RI Glazova, Margarita/Q-8597-2016 OI Glazova, Margarita/0000-0001-6617-3404 NR 28 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 22 PY 2007 VL 426 IS 3 BP 160 EP 165 DI 10.1016/j.neulet.2007.08.066 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 232HL UT WOS:000251009200006 ER PT J AU Lambrecht, NWG Yakubov, I Sachs, G AF Lambrecht, Nils W. G. Yakubov, Iskandar Sachs, George TI Fasting-induced changes in ECL cell gene expression SO PHYSIOLOGICAL GENOMICS LA English DT Article DE enterochromaffin-like cell; oligonucleotide expression microarray; transcriptome; histamine; secretion ID VESICULAR MONOAMINE TRANSPORTER-2; GASTRIC-ACID SECRETION; HISTIDINE-DECARBOXYLASE; RAT; HISTAMINE; IDENTIFICATION; ACTIVATION; SITE; MUCOSA; FUNDUS AB Gastric enterochromaffin-like (ECL) cells release histamine in response to food because of elevation of gastrin and neural release of pituitary adenylate cyclase-activating peptide (PACAP). Acid secretion is at a basal level in the absence of food but is rapidly stimulated with feeding. Rats fasted for 24 h showed a significant decrease of mucosal histamine despite steady-state expression of the histamine-synthesizing enzyme histamine decarboxylase (HDC). Comparative transcriptomal analysis using gene expression oligonucleotide micro-arrays of 95% pure ECL cells from fed and 24-h fasted rats, thereby eliminating mRNA contamination from other gastric mucosal cell types, identified significantly increased gene expression of the enzymes histidase and urocanase catabolizing the HDC substrate L-histidine but significantly decreased expression of the cellular L-histidine uptake transporter SN2 and of the vesicular monoamine transporter 2 (VMAT-2) responsible for histamine uptake into secretory vesicles. This was confirmed by reverse transcriptase-quantitative polymerase chain reaction of gastric fundic mucosal samples from fed and 24-h fasted rats. The decrease of VMAT-2 gene expression was also shown by a decrease in VMAT-2 protein content in protein extracts from fed and 24-h fasted rats compared with equal amounts of HDC protein and Na-K- ATPase alpha(1)-subunit protein content. These results indicate that rat gastric ECL cells regulate their histamine content during 24-h fasting not by a change in HDC gene or protein expression but by regulation of substrate concentration for HDC and a decreased histamine secretory pool. C1 Wadsworth VA Hosp, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90024 USA. Med Ctr, W Los Angeles Dept Vet Affairs, Membrane Biol Lab, Los Angeles, CA USA. RP Lambrecht, NWG (reprint author), Wadsworth VA Hosp, Bldg 113 Rm 325A, Los Angeles, CA 90073 USA. EM nilslam@ucla.edu NR 25 TC 8 Z9 10 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD OCT 22 PY 2007 VL 31 IS 2 BP 183 EP 192 DI 10.1152/physiolgenomics.00252.2006 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 222ZX UT WOS:000250340100004 PM 17536021 ER PT J AU Tucker, JD Chang, SW Tulsky, JP AF Tucker, Joseph D. Chang, Suzanne W. Tulsky, Jacqueline P. TI The catch 22 of condoms in US correctional facilities SO BMC PUBLIC HEALTH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV TRANSMISSION; PRISONS; INFECTION; INMATES AB Background: Despite the high prevalence of sexually transmitted infections (STIs) and HIV infection in US correctional settings, most jails and prisons in the United States prevent inmates from using condoms to prevent STIs/HIV. Discussion: This article makes the following arguments to justify a scalable and feasible next step in the prevention of HIV/STIs among inmates: condoms are a basic and essential part of HIV/STI prevention, HIV/STI transmission occurs in the context of corrections, and several model programs show the feasibility of condom distribution in prisons. A lower end estimate for HIV incidence among incarcerated applied to 2,000,000 new inmates annually results in thousands of new HIV infections acquired each year in corrections that could be prevented with condoms in corrections facilities. Programs from parts of the United States, Canada, and much of Europe show how programs distributing condoms in correctional facilities can be safe and effective. Summary: Public health and corrections officials must work together to ensure that condoms and broader sexual disease prevention programs are integrated into US jail and prison health systems. C1 [Tucker, Joseph D.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02139 USA. [Chang, Suzanne W.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Tulsky, Jacqueline P.] Univ Calif San Francisco, Dept Med & Posit Hlth Program, San Francisco, CA 94143 USA. RP Tucker, JD (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02139 USA. EM Jtucker4@partners.org; Suzanne.Chang@ucsf.edu; jtulsky@php.ucsf.edu NR 26 TC 7 Z9 7 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2458 J9 BMC PUBLIC HEALTH JI BMC Public Health PD OCT 21 PY 2007 VL 7 AR 296 DI 10.1186/1471-2458-7-296 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 243TJ UT WOS:000251819900001 PM 17949507 ER PT J AU Cui, Y Dy, JG Sharp, GC Alexander, B Jiang, SB AF Cui, Ying Dy, Jennifer G. Sharp, Gregory C. Alexander, Brian Jiang, Steve B. TI Multiple template-based fluoroscopic tracking of lung tumor mass without implanted fiducial markers SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TRANSTHORACIC NEEDLE-BIOPSY; GATED RADIOTHERAPY; PULMONARY NODULES; RADIATION-THERAPY; PNEUMOTHORAX; SETUP AB Precise lung tumor localization in real time is particularly important for some motion management techniques, such as respiratory gating or beam tracking with a dynamic multi-leaf collimator, due to the reduced clinical tumor volume ( CTV) to planning target volume ( PTV) margin and/or the escalated dose. There might be large uncertainties in deriving tumor position from external respiratory surrogates. While tracking implanted fiducial markers has sufficient accuracy, this procedure may not be widely accepted due to the risk of pneumothorax. Previously, we have developed a technique to generate gating signals from fluoroscopic images without implanted fiducial markers using a template matching method ( Berbeco et al 2005 Phys. Med. Biol. 50 4481-90, Cui et al 2007 Phys. Med. Biol. 52 741-55). In this paper, we present an extension of this method to multiple-template matching for directly tracking the lung tumor mass in fluoroscopy video. The basic idea is as follows: ( i) during the patient setup session, a pair of orthogonal fluoroscopic image sequences are taken and processed off-line to generate a set of reference templates that correspond to different breathing phases and tumor positions; ( ii) during treatment delivery, fluoroscopic images are continuously acquired and processed; ( iii) the similarity between each reference template and the processed incoming image is calculated; ( iv) the tumor position in the incoming image is then estimated by combining the tumor centroid coordinates in reference templates with proper weights based on the measured similarities. With different handling of image processing and similarity calculation, two such multiple-template tracking techniques have been developed: one based on motion-enhanced templates and Pearson's correlation score while the other based on eigen templates and mean-squared error. The developed techniques have been tested on six sequences of fluoroscopic images from six lung cancer patients against the reference tumor positions manually determined by a radiation oncologist. The tumor centroid coordinates automatically detected using both methods agree well with the manually marked reference locations. The eigenspace tracking method performs slightly better than the motion-enhanced method, with average localization errors less than 2 pixels ( 1 mm) and the error at a 95% confidence level of about 2-4 pixels ( 1-2 mm). This work demonstrates the feasibility of direct tracking of a lung tumor mass in fluoroscopic images without implanted fiducial markers using multiple reference templates. C1 Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. RP Cui, Y (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM sbjiang@ucsd.edu FU NCI NIH HHS [1R21 CA 110177-01A1] NR 17 TC 54 Z9 56 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 EI 1361-6560 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 21 PY 2007 VL 52 IS 20 BP 6229 EP 6242 DI 10.1088/0031-9155/52/20/010 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 224JN UT WOS:000250443400010 PM 17921582 ER PT J AU Rogers, J Palacios, I Condado, J Low, R Rahdert, D AF Rogers, Jason Palacios, Igor Condado, Jose Low, Reginald Rahdert, David TI Long-term durability and safety of percutaneous septal-sinus shortening SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 19th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 20-25, 2007 CL Washington, DC C1 [Rogers, Jason; Low, Reginald] Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. [Palacios, Igor] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Condado, Jose] Ctr Med, Caracas, Venezuela. [Rahdert, David] Ample Med Inc, Foster City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 20 PY 2007 VL 100 IS 8A SU S BP 58L EP 58L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000250393900127 ER PT J AU Nadkarni, SK Yelin, D Bouma, BE Tearney, GJ AF Nadkarni, Seemantini K. Yelin, Dvir Bouma, Brett E. Tearney, Guillermo J. TI Laser speckle imaging using optical fiber bundles: Implications for the intravascular characterization of atherosclerotic plaque SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 19th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 20-25, 2007 CL Washington, DC C1 [Nadkarni, Seemantini K.; Yelin, Dvir; Bouma, Brett E.; Tearney, Guillermo J.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 20 PY 2007 VL 100 IS 8A SU S BP 138L EP 138L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000250393900343 ER PT J AU Liu, X Huang, Y Pokreisz, P Swinnen, M Verbeken, E Vermeersch, P Marsboom, G Pellens, M Gillijns, H De Werf, FV Bloch, KD Janssens, S AF Liu, Xiaoshun Huang, Yanining Pokreisz, Peter Swinnen, Marc Verbeken, Eric Vermeersch, Pieter Marsboom, Glenn Pellens, Marijke Gillijns, Hilde De Werf, Frons Van Bloch, Kenneth D. Janssens, Stefan TI Nitric oxide inhalation improves microvascular flow and decreases infarction size after myocardial ischemia and reperfusion SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 19th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 20-25, 2007 CL Washington, DC C1 [Liu, Xiaoshun; Huang, Yanining; Pokreisz, Peter; Swinnen, Marc; Verbeken, Eric; Vermeersch, Pieter; De Werf, Frons Van; Janssens, Stefan] Katholieke Univ Leuven, Louvain, Belgium. [Marsboom, Glenn; Pellens, Marijke; Gillijns, Hilde; Janssens, Stefan] Flanders Interuniv Inst Biotechnol, Louvain, Belgium. [Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RI Vermeersch, Pieter/M-8352-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 20 PY 2007 VL 100 IS 8A SU S BP 183L EP 183L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000250393900458 ER PT J AU Burjonroppa, SC Varosy, P Ou, FS Rao, SV Peterson, E Roe, M Shunk, KA AF Burjonroppa, Sukesh C. Varosy, Paul Ou, Fang-Shu Rao, Sunil V. Peterson, Eric Roe, Matthew Shunk, Kendrick A. CA Natl Cardiovascular Data Registry TI Incidence and predictors of bleeding among patients undergoing rescue percutaneous coronary intervention after failed fibrinolysis for ST-elevation myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 19th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 20-25, 2007 CL Washington, DC C1 [Burjonroppa, Sukesh C.; Varosy, Paul; Shunk, Kendrick A.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Ou, Fang-Shu; Rao, Sunil V.; Peterson, Eric; Roe, Matthew] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 20 PY 2007 VL 100 IS 8A SU S BP 192L EP 192L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000250393900481 ER PT J AU Cannon, CP Roe, MT Chen, AY Rumsfeld, JS Brindis, RG Ohman, EM Gibler, WB Fonarow, GC Lambrew, CT Penney, J Peterson, ED AF Cannon, Christopher P. Roe, Matthen T. Chen, Anita Y. Rumsfeld, John S. Brindis, Ralph G. Ohman, E. Magnus Gibler, W. Brian Fonarow, Gregg C. Lambrew, Costas T. Penney, Janice Peterson, Eric D. TI Temporal improvements in door-to-balloon times for primary percutaneous coronary intervention_results from the CRUSADE and ACTION registries SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 19th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 20-25, 2007 CL Washington, DC C1 [Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Roe, Matthen T.; Chen, Anita Y.; Ohman, E. Magnus; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Brindis, Ralph G.] Oakland Med Ctr, Oakland, CA USA. [Gibler, W. Brian] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Cardiomyopathy Ctr, Los Angeles, CA USA. [Lambrew, Costas T.] Maine Med Ctr, Portland, ME 04102 USA. [Penney, Janice] MidMichigan Reg Med Ctr, Midland, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 20 PY 2007 VL 100 IS 8A SU S BP 209L EP 209L PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223SZ UT WOS:000250393900528 ER PT J AU Fuchs, CS Marshall, J Mitchell, E Wierzbicki, R Ganju, V Jeffery, M Schulz, J Richards, D Soufi-Mahjoubi, R Wang, B Barrueco, J AF Fuchs, Charles S. Marshall, John Mitchell, Edith Wierzbicki, Rafal Ganju, Vinod Jeffery, Mark Schulz, Joseph Richards, Donald Soufi-Mahjoubi, Raoudha Wang, Benjamin Barrueco, Jose TI Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: Results from the BICC-C study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID 2 DIFFERENT SCHEDULES; PHASE-II TRIAL; FLUOROURACIL; CAPECITABINE; MULTICENTER; LEUCOVORIN; BEVACIZUMAB; EFFICACY; FOLFIRI; LIFE AB Purpose This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI). Patients and Methods A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI Bev; n = 57) or mILF plus bevacizumab (mIFL = Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity. Results Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of >= grade 3 hypertension than mIFL+Bev. Conclusion FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Virginia Oncol Associates, US Oncol Network, Newport News, VA USA. Tyler Canc Ctr, US Oncol Network, Tyler, TX USA. Pfizer Global Pharmaceut, New York, NY USA. Lakeridge Hlth Oshawa, Oshawa, ON, Canada. Frankston Hosp, Frankston, Australia. Christchurch Hosp, Christchurch, New Zealand. RP Fuchs, CS (reprint author), Dana Farber Canc Inst, 44 Binney St,Off Dana 1232, Boston, MA 02115 USA. EM charles_fuchs@dfci.harvard.edu NR 19 TC 455 Z9 475 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2007 VL 25 IS 30 BP 4779 EP 4786 DI 10.1200/JCO.2007.11.3357 PG 8 WC Oncology SC Oncology GA 233ET UT WOS:000251073900013 PM 17947725 ER PT J AU Kulke, MH Blaszkowsky, LS Ryan, DP Clark, JW Meyerhardt, JA Zhu, AX Enzinger, PC Kwak, EL Muzikansky, A Lawrence, C Fuchs, CS AF Kulke, Matthew H. Blaszkowsky, Lawrence S. Ryan, David P. Clark, Jeffrey W. Meyerhardt, Jeffrey A. Zhu, Andrew X. Enzinger, Peter C. Kwak, Eunice L. Muzikansky, Alona Lawrence, Colleen Fuchs, Charles S. TI Capecitabine plus erlotinib in gemcitabine-refractory advanced pancreatic cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID GROWTH-FACTOR RECEPTOR; MULTICENTER PHASE-II; CELL LUNG-CANCER; COOPERATIVE-ONCOLOGY-GROUP; TYROSINE KINASE INHIBITOR; 2ND-LINE TREATMENT; TRIAL; OXALIPLATIN; MUTATIONS; CHEMOTHERAPY AB Purpose The addition of either capecitabine or erlotinib to gemcitabine in the first-line treatment of advanced pancreatic cancer is associated with modest improvements in overall survival. We evaluated an oral regimen of capecitabine and erlotinib in patients with advanced pancreatic cancer who had experienced treatment failure with standard first-line therapy with gemcitabine. Patients and Methods Thirty patients with gemcitabine-refractory metastatic pancreatic cancer were treated with capecitabine, administered at a dose of 1,000 mg/ m(2) twice daily for 2 weeks, followed by a 1-week break. All patients also received erlotinib 150 mg daily. Patients were observed for evidence of response, toxicity, and survival. EGFR mutational status was assessed in available tumor blocks. Results Treatment with capecitabine and erlotinib in gemcitabine-refractory patients was associated with an overall objective radiologic response rate of 10% and a median survival duration of 6.5 months. In addition, 17% of the treated patients experienced decreases in tumor marker (CA 19-9) levels of more than 50% from baseline. Common toxicities included diarrhea, skin rash, fatigue, and hand-foot syndrome. EGFR mutations were detected in two of five available tumors; no association between treatment response and EGFR mutational status was evident. Conclusion The combination of capecitabine and erlotinib is active in patients with gemcitabine-refractory pancreatic cancer. This regimen may represent an acceptable treatment option in patients who experience treatment failure with standard first-line therapy with gemcitabine or for whom gemcitabine may not be an appropriate first-line treatment option. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Kulke, MH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Matthew_Kulke@dfci.harvard.edu NR 40 TC 118 Z9 125 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2007 VL 25 IS 30 BP 4787 EP 4792 DI 10.1200/JCO.2007.11.8521 PG 6 WC Oncology SC Oncology GA 233ET UT WOS:000251073900014 PM 17947726 ER PT J AU Ho, RC Fujii, N Witters, LA Hirshman, MF Goodyear, LJ AF Ho, Richard C. Fujii, Nobuharu Witters, Lee A. Hirshman, Michael F. Goodyear, Laurie J. TI Dissociation of AMP-activated protein kinase and p38 mitogen-activated protein kinase signaling in skeletal muscle SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE muscle contraction; exercise; glucose transport ID GLUCOSE-TRANSPORTER EXPRESSION; ACETYL-COA CARBOXYLASE; FAT-FED RATS; GLUT4 TRANSLOCATION; L6 MYOTUBES; AICAR; STIMULATION; INSULIN; CELLS; MAPK AB AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle. The p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. Here we used several different models of altered AMPK activity to determine whether p38 MAPK is a downstream intermediate of AMPK-mediated signaling in skeletal muscle. First, L6 myoblasts and myotubes were treated with AICAR, an AMPK stimulator. AMPK phosphorylation was significantly increased, but there was no change in p38 MAPK phosphorylation. Similarly, AICAR incubation of isolated rat extensor digitorum longus (EDL) muscles did not increase p38 phosphorylation. Next, we used transgenic mice expressing an inactive form of the AMPK alpha 2 catalytic subunit in skeletal muscle (AMPK alpha 2i TG mice). AMPK alpha 2i TG mice did not exhibit any defect in basal or contraction-induced p38 MAPK phosphorylation. We also used transgenic mice expressing an activating mutation in the AMPK gamma 1 subunit (gamma 1R70Q TG mice). Despite activated AMPK, basal p38 MAPK phosphorylation was not different between wild type and,gamma 1R70Q TG mice. In addition, muscle contraction-induced p38 MAPK phosphorylation was significantly blunted in the 'YIR70Q TG mice. In conclusion, increasing AMPK activity by AICAR and AMPK gamma 1 mutation does not increase p38 MAPK phosphorylation in skeletal muscle. Furthermore, AMPK alpha 2i TG mice lacking contraction-stimulated AMPK activity have normal p38 MAPK phosphorylation. These results suggest that p38 MAPK is not a downstream component of AMPK-mediated signaling in skeletal muscle. (C) 2007 Elsevier Inc. All rights reserved. C1 Joslin Diabet Ctr, Div Res, Metab Sect, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Med, Hanover, NH 03756 USA. Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Biochem, Hanover, NH 03756 USA. Dartmouth Coll, Dept Biol Sci, Hanover, NH 03755 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, Metab Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [R01 AR42238, R01 AR045670-10, R01 AR045670, AR45670, R01 AR042238, R01 AR042238-14]; NIDDK NIH HHS [DK35712, R01 DK035712] NR 38 TC 16 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 19 PY 2007 VL 362 IS 2 BP 354 EP 359 DI 10.1016/j.bbrc.2007.07.154 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 210OF UT WOS:000249464800023 PM 17709097 ER PT J AU Gesta, S Tseng, YH Kahn, CR AF Gesta, Stephane Tseng, Yu-Hua Kahn, C. Ronald TI Developmental origin of fat: Tracking obesity to its source SO CELL LA English DT Review ID BROWN ADIPOSE-TISSUE; GENE-EXPRESSION; ADIPOCYTE DIFFERENTIATION; BETA-CATENIN; STEM-CELLS; PREADIPOCYTE DIFFERENTIATION; MITOCHONDRIAL BIOGENESIS; UNCOUPLING PROTEIN-1; INSULIN-RESISTANCE; COREPRESSOR RIP140 AB The development of obesity not only depends on the balance between food intake and caloric utilization but also on the balance between white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specialized for energy expenditure. In addition, some sites of white fat storage in the body are more closely linked than others to the metabolic complications of obesity, such as diabetes. In this Review, we consider how the developmental origins of fat contribute to its physiological, cellular, and molecular heterogeneity and explore how these factors may play a role in the growing epidemic of obesity. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. EM c.ronald.kahn@joslin.harvard.edu NR 104 TC 576 Z9 600 U1 17 U2 88 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 19 PY 2007 VL 131 IS 2 BP 242 EP 256 DI 10.1016/j.cell.2007.10.004 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 225HM UT WOS:000250507700016 PM 17956727 ER PT J AU Vorup-Jensen, T Chi, LL Gjelstrup, LC Jensen, UB Jewett, CA Xie, C Shimaoka, M Linhardt, RJ Springer, TA AF Vorup-Jensen, Thomas Chi, Lianli Gjelstrup, Louise C. Jensen, Uffe B. Jewett, Craig A. Xie, Can Shimaoka, Motomu Linhardt, Robert J. Springer, Timothy A. TI Binding between the Integrin alpha X beta 2 (CD11c/CD18) and heparin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID I-DOMAIN; PROTEIN INTERACTIONS; MAC-1 CD11B/CD18; ACTIVATION; AFFINITY; CONFORMATION; RECOGNITION; DERIVATIVES; ADHESION; LIGAND AB The interactions between cell surface receptors and sulfated glucosamineglycans serve ubiquitous roles in cell adhesion and receptor signaling. Heparin, a highly sulfated polymer of uronic acids and glucosamine, binds strongly to the integrin receptor alpha X beta 2 (p150,95, CD11c/CD18). Here, we analyze the structural motifs within heparin that constitute high affinity binding sites for the I domain of integrin alpha X beta 2. Heparin oligomers with chain lengths of 10 saccharide residues or higher provide strong inhibition of the binding by the alpha X I domain to the complement fragment iC3b. By contrast, smaller oligomers or the synthetic heparinoid fondaparinux were not able to block the binding. Semipurified heparin oligomers with 12 saccharide residues identified the fully sulfated species as the most potent antagonist of iC3b, with a 1.3 mu M affinity for the alpha XI domain. In studies of direct binding by the alpha XI domain to immobilized heparin, we found that the interaction is conformationally regulated and requires Mg2+. Furthermore, the fully sulfated heparin fragment induced conformational change in the ectodomain of the alpha X beta 2 receptor, also demonstrating allosteric linkage between heparin binding and integrin conformation. C1 Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Univ Aarhus, Inst Med Microbiol & Immunol, Biophys Immunol Lab, DK-8000 Aarhus, Denmark. Univ Aarhus, Dept Human Genet, DK-8000 Aarhus C, Denmark. Rensselaer Polytech Inst, Ctr Biotechnol & Interdisciplinary Studies, Dept Chem & Chem Biol, Troy, NY 12180 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Dept Pathol, Immune Dis Inst, 200 Longwood Ave, Boston, MA 02115 USA. EM springeroffice@idi.harvard.edu RI Chi, Lianli/B-9149-2015; OI Chi, Lianli/0000-0003-1126-1022; Vorup-Jensen, Thomas/0000-0002-4140-6563 FU NHLBI NIH HHS [HL52622, R01 HL052622, R01 HL052622-09, R01 HL062244, R01 HL062244-05A1]; NIAID NIH HHS [AI72765, R01 AI072765]; NIGMS NIH HHS [GM038060, R01 GM038060, R01 GM038060-19] NR 28 TC 26 Z9 26 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2007 VL 282 IS 42 BP 30869 EP 30877 DI 10.1074/jbc.M706114200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220DE UT WOS:000250136300055 PM 17699512 ER PT J AU Rider, L Shatrova, A Feener, EP Webb, L Diakonova, M AF Rider, Leah Shatrova, Alla Feener, Edward P. Webb, Leslie Diakonova, Maria TI JAK2 tyrosine kinase phosphorylates PAK1 and regulates PAK1 activity and functions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; NF-KAPPA-B; P21-ACTIVATED KINASE-1-INTERACTING SUBSTRATE; GROWTH-FACTOR RECEPTOR; CONSTITUTIVE ACTIVATION; ADAPTER PROTEIN; P35/CDK5 KINASE; SH2-B-BETA; ACTIN; APOPTOSIS AB The serine-threonine kinase PAK1 is activated by small GTPase-dependent and -independent mechanisms and promotes cell survival. However, the role of tyrosyl phosphorylation in the regulation of PAK1 function is poorly understood. In this study, we have shown that the prolactin-activated tyrosine kinase JAK2 phosphorylates PAK1 in vivo. Wild type, but not kinase-dead, JAK2 directly phosphorylates PAK1 in cells and in an in vitro kinase assay. PAK1 tyrosines 153, 201, and 285 were identified as sites of JAK2 tyrosyl phosphorylation by mass spectrometry and two-dimensional peptide mapping. Mutation of PAK1 tyrosines 153, 201, and 285 to phenylalanines individually or in combination implicated these PAK1 tyrosines in the regulation of PAK1 kinase activity. Tyrosyl phosphorylation by JAK2 significantly increases PAK1 kinase activity, whereas similar phosphorylation of the PAK1 Y153F, Y201F, Y285F mutant has no effect on PAK1 activity. Tyrosyl phosphorylation of wild type PAK1 decreases apoptosis induced by serum deprivation and staurosporine treatment and increases cell motility. In contrast, these parameters are unaltered in the PAK1 Y153F, Y201F, Y285F mutant. Our findings indicate that JAK2 phosphorylates PAK1 at these specific tyrosines and that this phosphorylation plays an important role in cell survival and motility. C1 Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. Univ Michigan, Sch Med, Dept Mol Physiol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Integrat Physiol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Diakonova, M (reprint author), 2801 W Bancroft St, Toledo, OH 43606 USA. EM mdiakon@utnet.utoledo.edu RI Shatrova, Alla/R-8042-2016; OI Diakonova, Maria/0000-0002-4554-2730 FU NIDDK NIH HHS [P30 DK036836, P60 DK020572, P60 DK20572, R01 DK60165, R21 DK074689] NR 75 TC 27 Z9 29 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 19 PY 2007 VL 282 IS 42 BP 30985 EP 30996 DI 10.1074/jbc.M701794200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220DE UT WOS:000250136300066 PM 17726028 ER PT J AU Parisini, E Higgins, JMG Liu, JH Brenner, MB Wang, JH AF Parisini, Emilio Higgins, Jonathan M. G. Liu, Jin-huan Brenner, Michael B. Wang, Jia-huai TI The crystal structure of human E-cadherin domains 1 and 2, and comparison with other cadherins in the context of adhesion mechanism SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE cadherin; cell adhesion; crystal structure; adhesion arm ID CELL-CELL ADHESION; INTEGRIN ALPHA(E)BETA(7); RECOGNITION; PROTEIN; DIMERIZATION; ALPHA AB Cell adhesion mediated by type I cadherins involves homophilic "trans" interactions that are thought to be brought about by a strand exchange mechanism involving the N-terminal extracellular domain. Here, we present the high-resolution crystal structure of the N-terminal two domains of human E-cadherin. Comparison of this structure with other type I cadherin structures reveals features that are likely to be critical to facilitate dimerization by strand exchange as well as dimer flexibility. We integrate this structural knowledge to provide a model for type I cadherin adhesive interactions. Intra-molecular docking of the conserved N-terminal "adhesion arm" into the acceptor pocket in monomeric E-cadherin appears largely identical to inter-molecular docking of the adhesion arm in adhesive trans dimers. A strained conformation of the adhesion arm in the monomer, however, may create an equilibrium between "open" and "closed" forms that primes the cadherin for formation of adhesive interactions, which are then stabilized by additional dimer-specific contacts. By contrast, in type II cadherins, strain in the adhesion arm appears absent and a much larger surface area is involved in trans adhesion, which may compensate the activation energy required to peel off the intra-molecularly docked arm. It seems that evolution has selected slightly different adhesion mechanisms for type I and type II cadherins. (C) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Harvard Med Sch, Boston, MA 02115 USA. Harvard Med Sch, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Med Sch, Div Rheumatol Allergy & Clin Immunol, Boston, MA 02115 USA. Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA. Harvadr Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Wang, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Harvard Med Sch, Boston, MA 02115 USA. EM jwang@red.dfci.harvard.edu FU NHLBI NIH HHS [P01 HL048675-120003, P01 HL048675, P01 HL048675-135388] NR 34 TC 48 Z9 49 U1 0 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 19 PY 2007 VL 373 IS 2 BP 401 EP 411 DI 10.1016/j.jmb.2007.08.011 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 222MZ UT WOS:000250302900014 PM 17850815 ER PT J AU Sas, AR Rimonte-Nelson, HA Tyor, WR AF Sas, Andrew R. Rimonte-Nelson, Heather A. Tyor, William R. TI Cognitive dysfunction in HIV encephalitic SCID mice correlates with levels of interferon-alpha in the brain SO AIDS LA English DT Article DE animal model; cytokines; HIV; neurological; viral infections ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CENTRAL-NERVOUS-SYSTEM; AIDS DEMENTIA COMPLEX; TYPE-1 ENCEPHALITIS; FRONTAL-CORTEX; MOUSE MODEL; LONG-TERM; PATHOGENESIS; RAT AB Background: Interferon alpha (IFN alpha) is an antiviral cytokine produced in response to viral infection. IFN alpha also acts as a neuromodulatory molecule in the central nervous system (CNS). Elevated IFN alpha in the CNS causes cognitive deficits. Objective: To determine if elevated levels of IFN alpha in an HIV encephalitis mouse model correlate with cognitive deficits. Methods: C57BL/6J SCID mice were inoculated intracerebrally (i.c.) with HIV infected or uninfected (control) macrophages and cognitively tested in a water escape radial arm maze. After behavioral testing was completed, immunohistochemistry and ELISA were used to examine brain pathology and IFN alpha expression. Results: Mice injected i.c. with HIV infected macrophages exhibited significantly more working memory errors, particularly in trials with the highest memory load. Immunohistochemistry indicated increased mouse IFN alpha staining prevalent on neurons and glial cells in the brains of mice with HIV infected macrophages compared to mice with uninfected control macrophages. In addition, IFN alpha levels in the brain correlated directly with working memory errors for mice with HIV infected macrophages. Conclusions: These data suggest that the cognitive deficit noted for the C57BL/6J SCID mice with HIV infected macrophages is mediated by the infection induced increase in IFN alpha. (C) 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Tyor, WR (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. EM William.Tyor@va.gov FU NCRR NIH HHS [C06 RR015455]; NIMH NIH HHS [R01 MH62697-03] NR 48 TC 29 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 18 PY 2007 VL 21 IS 16 BP 2151 EP 2159 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 228ZX UT WOS:000250772200004 PM 18090041 ER PT J AU Li, XK Jiang, LJ Wang, Y Xiao, YC Huang, YD Yao, QF Yang, YG Wu, XP AF Li, Xiaokun Jiang, Lijuan Wang, Yi Xiao, Yechen Huang, Yadong Yao, Qiongfeng Yang, Yongguang Wu, Xiaoping TI Inhibition of angiogenesis by a novel small peptide consisting of the active fragments of platelet factor-4 and vasostatin SO CANCER LETTERS LA English DT Article DE angiogenesis; cancer; peptide; platelet factor-4; vasostatin ID TUMOR-GROWTH; CALRETICULIN; EFFICACY; CANCER AB Inhibition of angiogenesis provides a potential anti-cancer therapy. Here we describe a novel recombinant peptide composed of active fragments of two distinct angiogenesis inhibitors, platelet factor-4 (C-13 fragment) and vasostatin (N-terminal amino acids 135-164) with a nonpolar peptide bridge of Gly-Pro-Gly. This fusion peptide showed significantly enhanced efficacy compared with its parent peptides in inhibiting human endothelial cell proliferation and neovasculerization in chick embryo chorioallantoic membrane. The data suggest that making a single recombinant peptide containing the active fragments of multiple angiogenesis inhibitors is a promising approach to developing a better anti-angiogenetic therapy. (C) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Wenzhou Med Col, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China. Jinan Univ, Inst Tissue Transplantat & Immunol, Guangzhou 510632, Peoples R China. Jilin Agr Univ, Bioreactor Engn Res Ctr, Changchun 130118, Peoples R China. Jinan Univ, Natl Engn Res Ctr Gene Med, Guangzhou 510632, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Yang, YG (reprint author), Wenzhou Med Col, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China. EM yongguang.yang@tbre.mgh.harvard.edu; xp_wu2@yahoo.com.cn NR 12 TC 8 Z9 8 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 18 PY 2007 VL 256 IS 1 BP 29 EP 32 DI 10.1016/j.canlet.2007.05.002 PG 4 WC Oncology SC Oncology GA 218PS UT WOS:000250028000003 PM 17574330 ER PT J AU Frazer, KA Ballinger, DG Cox, DR Hinds, DA Stuve, LL Gibbs, RA Belmont, JW Boudreau, A Hardenbol, P Leal, SM Pasternak, S Wheeler, DA Willis, TD Yu, FL Yang, HM Zeng, CQ Gao, Y Hu, HR Hu, WT Li, CH Lin, W Liu, SQ Pan, H Tang, XL Wang, J Wang, W Yu, J Zhang, B Zhang, QR Zhao, HB Zhao, H Zhou, J Gabriel, SB Barry, R Blumenstiel, B Camargo, A Defelice, M Faggart, M Goyette, M Gupta, S Moore, J Nguyen, H Onofrio, RC Parkin, M Roy, J Stahl, E Winchester, E Ziaugra, L Altshuler, D Shen, Y Yao, ZJ Huang, W Chu, X He, YG Jin, L Liu, YF Shen, YY Sun, WW Wang, HF Wang, Y Wang, Y Xiong, XY Xu, L Waye, MMY Tsui, SKW Wong, JTF Galver, LM Fan, JB Gunderson, K Murray, SS Oliphant, AR Chee, MS Montpetit, A Chagnon, F Ferretti, V Leboeuf, M Olivier, JF Phillips, MS Roumy, S Sallee, C Verner, A Hudson, TJ Kwok, PY Cai, DM Koboldt, DC Miller, RD Pawlikowska, L Taillon-Miller, P Xiao, M Tsui, LC Mak, W Song, YQ Tam, PKH Nakamura, Y Kawaguchi, T Kitamoto, T Morizono, T Nagashima, A Ohnishi, Y Sekine, A Tanaka, T Tsunoda, T Deloukas, P Bird, CP Delgado, M Dermitzakis, ET Gwilliam, R Hunt, S Morrison, J Powell, D Stranger, BE Whittaker, P Bentley, DR Daly, MJ de Bakker, PIW Barrett, J Chretien, YR Maller, J McCarroll, S Patterson, N Pe'er, I Price, A Purcell, S Richter, DJ Sabeti, P Saxena, R Schaffner, SF Sham, PC Varilly, P Altshuler, D Stein, LD Krishnan, L Smith, AV Tello-Ruiz, MK Thorisson, GA Chakravarti, A Chen, PE Cutler, DJ Kashuk, CS Lin, S Abecasis, GR Guan, WH Li, Y Munro, HM Qin, ZHS Thomas, DJ McVean, G Auton, A Bottolo, L Cardin, N Eyheramendy, S Freeman, C Marchini, J Myers, S Spencer, C Stephens, M Donnelly, P Cardon, LR Clarke, G Evans, DM Morris, AP Weir, BS Tsunoda, T Johnson, TA Mullikin, JC Sherry, ST Feolo, M Skol, A AF Frazer, Kelly A. Ballinger, Dennis G. Cox, David R. Hinds, David A. Stuve, Laura L. Gibbs, Richard A. Belmont, John W. Boudreau, Andrew Hardenbol, Paul Leal, Suzanne M. Pasternak, Shiran Wheeler, David A. Willis, Thomas D. Yu, Fuli Yang, Huanming Zeng, Changqing Gao, Yang Hu, Haoran Hu, Weitao Li, Chaohua Lin, Wei Liu, Siqi Pan, Hao Tang, Xiaoli Wang, Jian Wang, Wei Yu, Jun Zhang, Bo Zhang, Qingrun Zhao, Hongbin Zhao, Hui Zhou, Jun Gabriel, Stacey B. Barry, Rachel Blumenstiel, Brendan Camargo, Amy Defelice, Matthew Faggart, Maura Goyette, Mary Gupta, Supriya Moore, Jamie Nguyen, Huy Onofrio, Robert C. Parkin, Melissa Roy, Jessica Stahl, Erich Winchester, Ellen Ziaugra, Liuda Altshuler, David Shen, Yan Yao, Zhijian Huang, Wei Chu, Xun He, Yungang Jin, Li Liu, Yangfan Shen, Yayun Sun, Weiwei Wang, Haifeng Wang, Yi Wang, Ying Xiong, Xiaoyan Xu, Liang Waye, Mary M. Y. Tsui, Stephen K. W. Wong, J. Tze-Fei Galver, Luana M. Fan, Jian-Bing Gunderson, Kevin Murray, Sarah S. Oliphant, Arnold R. Chee, Mark S. Montpetit, Alexandre Chagnon, Fanny Ferretti, Vincent Leboeuf, Martin Olivier, Jean-Franccois Phillips, Michael S. Roumy, Stephanie Sallee, Clementine Verner, Andrei Hudson, Thomas J. Kwok, Pui-Yan Cai, Dongmei Koboldt, Daniel C. Miller, Raymond D. Pawlikowska, Ludmila Taillon-Miller, Patricia Xiao, Ming Tsui, Lap-Chee Mak, William Song, You Qiang Tam, Paul K. H. Nakamura, Yusuke Kawaguchi, Takahisa Kitamoto, Takuya Morizono, Takashi Nagashima, Atsushi Ohnishi, Yozo Sekine, Akihiro Tanaka, Toshihiro Tsunoda, Tatsuhiko Deloukas, Panos Bird, Christine P. Delgado, Marcos Dermitzakis, Emmanouil T. Gwilliam, Rhian Hunt, Sarah Morrison, Jonathan Powell, Don Stranger, Barbara E. Whittaker, Pamela Bentley, David R. Daly, Mark J. de Bakker, Paul I. W. Barrett, Jeff Chretien, Yves R. Maller, Julian McCarroll, Steve Patterson, Nick Pe'er, Itsik Price, Alkes Purcell, Shaun Richter, Daniel J. Sabeti, Pardis Saxena, Richa Schaffner, Stephen F. Sham, Pak C. Varilly, Patrick Altshuler, David Stein, Lincoln D. Krishnan, Lalitha Smith, Albert Vernon Tello-Ruiz, Marcela K. Thorisson, Gudmundur A. Chakravarti, Aravinda Chen, Peter E. Cutler, David J. Kashuk, Carl S. Lin, Shin Abecasis, Goncalo R. Guan, Weihua Li, Yun Munro, Heather M. Qin, Zhaohui Steve Thomas, Daryl J. McVean, Gilean Auton, Adam Bottolo, Leonardo Cardin, Niall Eyheramendy, Susana Freeman, Colin Marchini, Jonathan Myers, Simon Spencer, Chris Stephens, Matthew Donnelly, Peter Cardon, Lon R. Clarke, Geraldine Evans, David M. Morris, Andrew P. Weir, Bruce S. Tsunoda, Tatsuhiko Johnson, Todd A. Mullikin, James C. Sherry, Stephen T. Feolo, Michael Skol, Andrew CA Int HapMap Consortium TI A second generation human haplotype map of over 3.1 million SNPs SO NATURE LA English DT Article ID GENOME-WIDE ASSOCIATION; LINKAGE DISEQUILIBRIUM; NATURAL-SELECTION; MEIOTIC RECOMBINATION; GENETIC ASSOCIATION; HUMAN-POPULATIONS; RECESSIVE TRAITS; HAPMAP PROJECT; HOT-SPOTS; TAG SNPS AB We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r(2) of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r(2) of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations. C1 Univ Oxford, Dept Stat, Oxford OX1 3TG, England. Scripps Res Inst, La Jolla, CA 92037 USA. Perlegen Sci Inc, Mountain View, CA 94043 USA. Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Pacific Biosci, Menlo Pk, CA 94025 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Chinese Acad Sci, Beijing Genom Inst, Beijing 100300, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. Chinese Natl Human Genome Ctr, Beijing Econ Technol Dev Area, Beijing 100176, Peoples R China. Chinese Natl Human Genome Ctr, Shanghai 201203, Peoples R China. Fudan Univ, Shanghai 201203, Peoples R China. CAS, SIBS, Sch Life Sci, MPG Partner Inst Computat Biol, Shanghai 201203, Peoples R China. Chinese Univ Hong Kong, Dept Biochem, Croucher Lab Human Genet, Shatin, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Appl Genom Ctr, Kowloon, Hong Kong, Peoples R China. Illumina, San Diego, CA 92121 USA. Complete Genom Inc, Sunnyvale, CA 94085 USA. Prognosys Biosci Inc, San Diego, CA 92121 USA. McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. Univ Montreal, Publ Law Res Ctr, Downtown Stn, Montreal, PQ H3C 3J7, Canada. Ontario Inst Canc Res, MaRS Ctr, Toronto, ON M5G 1L7, Canada. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Univ Hong Kong, Genome Res Ctr, Hong Kong, Hong Kong, Peoples R China. Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. RIKEN SNP Res Ctr, Tsurumi Ku, Kanagawa 2300045, Japan. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England. Solexa Ltd, Saffron Walden CB10 1XL, Essex, England. Columbia Univ, New York, NY 10027 USA. Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Int Epidemiol Inst, Rockville, MD 20850 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Univ Chicago, Dept Stat, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NHGRI, US NIH, Bethesda, MD 20892 USA. Natl Lib Med, US NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Univ Chicago, Dept Med, Med Genet Sect, Chicago, IL 60637 USA. Beijing Normal Univ, Beijing 100875, Peoples R China. Hlth Sci Univ Hokkaido, Ishikari, Hokkaido 0610293, Japan. Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 3908621, Japan. UNESCO Bangkok, Bangkok 10110, Thailand. Univ Tsukuba, Eubios Eth Inst, Tsukuba, Ibaraki 3058691, Japan. Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. Univ Ibadan, Coll Med, Ibadan, Oyo State, Nigeria. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Univ Utah, Dept Human Genet, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. Chinese Acad Social Sci, Inst Philosophy, Ctr Appl Eth, Beijing 100067, Peoples R China. Genet Interest Grp, London N13 0P, England. Kyoto Univ, Inst Res Humanities, Kyoto 6068501, Japan. Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan. Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 8528523, Japan. Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. Vanderbilt Univ, Ctr Genet & Hlth Policy, Nashville, TN 37232 USA. Wellcome Trust Res Labs, London NW1 2BE, England. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Chinese Acad Sci, Beijing 100864, Peoples R China. Genome Canada, Ottawa, ON K2P 1P1, Canada. McGill Univ, Off Technol Transfer, Montreal, PQ H3A 2A7, Canada. Genome Quebec, Montreal, PQ H3B 1S6, Canada. Minist Educ Culture Sports Sci & Technol, Chiyoda Ku, Tokyo 1008959, Japan. Minist Sci & Technol, Beijing 100862, Peoples R China. Human Genet Resource Adm China, Beijing 100081, Peoples R China. NHGRI, US NIH, Bethesda, MD 20892 USA. US NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. Novartis Pharmaceut Corp, Biomarker Dev, E Hanover, NJ 07936 USA. US NIH, Off Technol Transfer, Rockville, MD 20852 USA. Univ Maryland, Sch Law, Baltimore, MD 21201 USA. NHGRI, US NIH, Bethesda, MD 20892 USA. RP McVean, G (reprint author), Univ Oxford, Dept Stat, 1 S Parks Rd, Oxford OX1 3TG, England. EM mjdaly@chgr.mgh.harvard.edu; mcvean@stats.ox.ac.uk RI Smith, Albert/K-5150-2015; Osborne, Nicholas/N-4915-2015; Song, You-qiang/C-4401-2009; Auton, Adam/B-1159-2009; Jin, Li/C-1468-2009; Sham, Pak Chung/C-4388-2009; Tam, Paul/C-4405-2009; Abecasis, Goncalo/B-7840-2010; Thorisson, Gudmundur/E-7359-2010; Altshuler, David/A-4476-2009; MOE Key Lab at Fudan University, Contemp Anthropology/A-1772-2010; Fudan Anthropology, MOE KeyLab/A-9454-2010; Tsui, Lap-chee/A-1081-2010; Schaffner, Stephen/D-1189-2011; Song, You-Qiang/E-5207-2011; Qin, Zhaohui/E-8196-2011; 郑, 征/C-8514-2011; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; Varilly, Patrick/C-8118-2013; Evans, David/H-6325-2013; de Bakker, Paul/B-8730-2009; Kwok, Pui-Yan/F-7725-2014; Tsunoda, Tatsuhiko/K-2061-2014; Myers, Simon/A-6792-2015; Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tsui, Stephen Kwok-Wing/E-4385-2015; Tanaka, Toshihiro/J-9310-2014; OI Smith, Albert/0000-0003-1942-5845; Osborne, Nicholas/0000-0002-6700-2284; Clayton, Ellen/0000-0002-0308-4110; Belmont, John/0000-0001-7409-3578; Hudson, Thomas/0000-0002-1376-4849; Maller, Julian/0000-0002-1565-9559; Hunt, Sarah/0000-0002-8350-1235; Jin, Li/0000-0002-4546-2415; Thorisson, Gudmundur/0000-0001-5635-1860; Altshuler, David/0000-0002-7250-4107; Qin, Zhaohui/0000-0002-1583-146X; Deloukas, Panos/0000-0001-9251-070X; Varilly, Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858; Kwok, Pui-Yan/0000-0002-5087-3059; Myers, Simon/0000-0002-2585-9626; Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tsui, Stephen Kwok-Wing/0000-0003-0686-4259; Tanaka, Toshihiro/0000-0001-6201-9784; Abecasis, Goncalo/0000-0003-1509-1825; Johnson, Todd Andrew/0000-0003-3377-6692; Stranger, Barbara/0000-0001-9021-7331; He, Yungang/0000-0002-2931-2871; Evans, David/0000-0003-0663-4621; Adebamowo, Clement/0000-0002-6571-2880 NR 57 TC 2701 Z9 2775 U1 27 U2 267 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 18 PY 2007 VL 449 IS 7164 BP 851 EP U3 DI 10.1038/nature06258 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 221LY UT WOS:000250230600036 ER PT J AU Sabeti, PC Varilly, P Fry, B Lohmueller, J Hostetter, E Cotsapas, C Xie, XH Byrne, EH McCarroll, SA Gaudet, R Schaffner, SF Lander, ES AF Sabeti, Pardis C. Varilly, Patrick Fry, Ben Lohmueller, Jason Hostetter, Elizabeth Cotsapas, Chris Xie, Xiaohui Byrne, Elizabeth H. McCarroll, Steven A. Gaudet, Rachelle Schaffner, Stephen F. Lander, Eric S. CA Int HapMap Consortium TI Genome-wide detection and characterization of positive selection in human populations SO NATURE LA English DT Article ID DEATH DOMAIN; NMR STRUCTURE; GENE; RECOMBINATION; POLYMORPHISMS; PIGMENTATION; RECEPTOR; SCANS AB With the advent of dense maps of human genetic variation, it is now possible to detect positive natural selection across the human genome. Here we report an analysis of over 3 million polymorphisms from the International HapMap Project Phase 2 (HapMap2)(1). We used 'long-range haplotype' methods, which were developed to identify alleles segregating in a population that have undergone recent selection(2), and we also developed new methods that are based on cross-population comparisons to discover alleles that have swept to near-fixation within a population. The analysis reveals more than 300 strong candidate regions. Focusing on the strongest 22 regions, we develop a heuristic for scrutinizing these regions to identify candidate targets of selection. In a complementary analysis, we identify 26 non-synonymous, coding, single nucleotide polymorphisms showing regional evidence of positive selection. Examination of these candidates highlights three cases in which two genes in a common biological process have apparently undergone positive selection in the same population: LARGE and DMD, both related to infection by the Lassa virus(3), in West Africa; SLC24A5 and SLC45A2, both involved in skin pigmentation(4,5), in Europe; and EDAR and EDA2R, both involved in development of hair follicles(6), in Asia. C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Sabeti, PC (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pardis@broad.mit.edu RI Schaffner, Stephen/D-1189-2011; Qin, Zhaohui/E-8196-2011; 郑, 征/C-8514-2011; Deloukas, Panos/B-2922-2013; Varilly, Patrick/C-8118-2013; McCarroll, Steven/A-8433-2009; Evans, David/H-6325-2013; de Bakker, Paul/B-8730-2009; Jin, Li/C-1468-2009; Song, You-qiang/C-4401-2009; Tam, Paul/C-4405-2009; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Kwok, Pui-Yan/F-7725-2014; Gaudet, Rachelle/I-4133-2014; Tsunoda, Tatsuhiko/K-2061-2014; Myers, Simon/A-6792-2015; Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tsui, Stephen Kwok-Wing/E-4385-2015; Tanaka, Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; OI Qin, Zhaohui/0000-0002-1583-146X; Deloukas, Panos/0000-0001-9251-070X; Varilly, Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858; Jin, Li/0000-0002-4546-2415; Altshuler, David/0000-0002-7250-4107; Evans, David/0000-0003-0663-4621; Adebamowo, Clement/0000-0002-6571-2880; Cotsapas, Chris/0000-0002-7772-5910; Belmont, John/0000-0001-7409-3578; Hunt, Sarah/0000-0002-8350-1235; Johnson, Todd Andrew/0000-0003-3377-6692; Xue, Hong/0000-0002-8133-9828; Stranger, Barbara/0000-0001-9021-7331; He, Yungang/0000-0002-2931-2871; Kwok, Pui-Yan/0000-0002-5087-3059; Gaudet, Rachelle/0000-0002-9177-054X; Myers, Simon/0000-0002-2585-9626; Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tsui, Stephen Kwok-Wing/0000-0003-0686-4259; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; Clayton, Ellen/0000-0002-0308-4110; Maller, Julian/0000-0002-1565-9559; Abecasis, Goncalo/0000-0003-1509-1825; Thorisson, Gudmundur/0000-0001-5635-1860 FU Wellcome Trust [077008, 077011, 077046, 081682] NR 34 TC 702 Z9 730 U1 25 U2 172 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 18 PY 2007 VL 449 IS 7164 BP 913 EP U12 DI 10.1038/nature06250 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 221LY UT WOS:000250230600049 PM 17943131 ER PT J AU Winer, EP Harris, JR Smith, BL D'Alessandro, HA Brachtel, EF Barbie, DA Harris, NL AF Winer, Eric P. Harris, Jay R. Smith, Barbara L. D'Alessandro, Helen Anne Brachtel, Elena F. Barbie, David A. Harris, Nancy Lee TI A 62-year-old woman with a second breast cancer - Invasive ductal carcinoma, and ductal carcinoma in situ, of the right breast, grade 3 of 3, estrogen-receptor-positive and HER2-positive. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TRIAL COMPARING DOXORUBICIN; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIALS; 15-YEAR SURVIVAL; CANCER; THERAPY; TRASTUZUMAB; WOMEN; MAMMOGRAPHY; RECURRENCE C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Winer, EP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 40 TC 2 Z9 2 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 18 PY 2007 VL 357 IS 16 BP 1640 EP 1648 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 221AY UT WOS:000250200500011 PM 17942877 ER PT J AU Gilden, DH Tyler, KL AF Gilden, Donald H. Tyler, Kenneth L. TI Bell's palsy - Is glucocorticoid treatment enough?. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACYCLOVIR C1 Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. Univ Colorado, Sch Med, Dept Microbiol, Denver, CO USA. Univ Colorado, Sch Med, Dept Med, Denver, CO USA. Denver Vet Affairs Med Ctr, Neurol Serv, Denver, CO USA. RP Gilden, DH (reprint author), Univ Colorado, Sch Med, Dept Neurol, Denver, CO 80202 USA. OI Tyler, Kenneth/0000-0003-3294-5888 NR 14 TC 25 Z9 29 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 18 PY 2007 VL 357 IS 16 BP 1653 EP 1655 DI 10.1056/NEJMe078188 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 221AY UT WOS:000250200500013 PM 17942879 ER PT J AU Campbell, EG Weissman, JS Ehringhaus, S Rao, SR Moy, B Feibelmann, S Goold, SD AF Campbell, Eric G. Weissman, Joel S. Ehringhaus, Susan Rao, Sowmya R. Moy, Beverly Feibelmann, Sandra Goold, Susan Dorr TI Institutional academic-industry relationships SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CONFLICTS-OF-INTEREST; PHARMACEUTICAL-INDUSTRY; PHYSICIANS; COMPANIES; GIFTS AB Context Institutional academic-industry relationships have the potential of creating institutional conflicts of interest. To date there are no empirical data to support the establishment and evaluation of institutional policies and practices related to managing these relationships. Objective To conduct a national survey of department chairs about the nature, extent, and consequences of institutional-academic industry relationships for medical schools and teaching hospitals. Design, Setting, and Participants National survey of department chairs in the 125 accredited allopathic medical schools and the 15 largest independent teaching hospitals in the United States, administered between February 2006 and October 2006. Main Outcome Measure Types of relationships with industry. Results A total of 459 of 688 eligible department chairs completed the survey, yielding an overall response rate of 67%. Almost two-thirds (60%) of department chairs had some form of personal relationship with industry, including serving as a consultant (27%), a member of a scientific advisory board (27%), a paid speaker (14%), an officer (7%), a founder (9%), or a member of the board of directors (11%). Two-thirds (67%) of departments as administrative units had relationships with industry. Clinical departments were more likely than nonclinical departments to receive research equipment (17% vs 10%, P=.04), unrestricted funds (19% vs 3%, P<.001), residency or fellowship training support (37% vs 2%, P<.001), and continuing medial education support (65% vs 3%, P<.001). However, nonclinical departments were more likely to receive funding from intellectual property licensing(27% vs 16%, P=.01). More than two-thirds of chairs perceived that having a relationship with industry had no effect on their professional activities, 72% viewed a chair's engaging in more than 1 industry-related activity (substantial role in a start-up company, consulting, or serving on a company's board) as having a negative impact on a department's ability to conduct independent unbiased research. Conclusion Overall, institutional academic-industry relationships are highly prevalent and underscore the need for their active disclosure and management. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Assoc Amer Med Coll, Washington, DC 20037 USA. RP Campbell, EG (reprint author), Inst Hlth Policy, 50 Staniford St, Boston, MA 02114 USA. EM ecampbell@partners.org OI Goold, Susan Dorr/0000-0002-0258-9774 NR 19 TC 88 Z9 91 U1 2 U2 7 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 OCT 17 PY 2007 VL 298 IS 15 BP 1779 EP 1786 DI 10.1001/jama.298.15.1779 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 220WF UT WOS:000250187300021 PM 17940234 ER PT J AU Wodchis, WP Ross, JS Detsky, AS AF Wodchis, Walter P. Ross, Joseph S. Detsky, Allan S. TI Is P4P really FFS? SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PAY-FOR-PERFORMANCE; CLINICAL-PRACTICE GUIDELINES; HEALTH-CARE; QUALITY; IMPROVE; PLAN C1 Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. Univ Toronto, Dept Hlth Policy Management & Evaluat, Toronto Rehabil Inst, Inst Clin Evaluat Sci, Toronto, ON, Canada. Univ Toronto, Dept Med, Toronto Rehabil Inst, Inst Clin Evaluat Sci, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. James J Peters Vet Adm Med Ctr, Hlth Serv Res & Dev Targeted Res Enhancement Prog, Bronx, NY USA. James J Peters Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Bronx, NY USA. RP Detsky, AS (reprint author), Mt Sinai Hosp, Dept Med, 600 Univ Ave,Room 427, Toronto, ON M5G 1X5, Canada. EM allan.detsky@uhn.on.ca NR 16 TC 24 Z9 24 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 17 PY 2007 VL 298 IS 15 BP 1797 EP 1799 DI 10.1001/jama.298.15.1797 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 220WF UT WOS:000250187300024 PM 17940237 ER PT J AU Tsai, HK D'Annico, AV Sadetsky, N Chen, MH Carroll, PR AF Tsai, Henry K. D'Annico, Anthony V. Sadetsky, Natalia Chen, Ming-Hui Carroll, Peter R. TI Androgen deprivation therapy for localized prostate cancer and the risk of cardiovascular mortality SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NEOADJUVANT HORMONAL-THERAPY; RANDOMIZED CONTROLLED-TRIAL; RADICAL PROSTATECTOMY; RADIATION-THERAPY; FOLLOW-UP; METABOLIC SYNDROME; BODY-COMPOSITION; COMPETING RISK; CARCINOMA; SURVIVAL AB Background We investigated whether androgen deprivation therapy (ADT) use is associated with an increased risk of death from cardiovascular causes in patients treated for localized prostate cancer. Methods From the Cancer of the Prostate Strategic Urologic Research Endeavor database, data on 3262 patients treated with radical prostatectomy and 1630 patients treated with external beam radiation therapy, brachytherapy, or cryotherapy for localized prostate cancer were included in this analysis. Competing risks regression analyses were performed to assess whether use of ADT was associated with a shorter time to death from cardiovascular causes after controlling for age (as a continuous variable) and the presence of baseline cardiovascular disease risk factors. All tests for statistical significance were two-sided. Results The median follow-up time was 3.8 years (range = 0.1-11.3 years). Among the 1015 patients who received ADT, the median duration of ADT use was 4.1 months (range = 1.0-32.9 months). In a competing risks regression analysis that controlled for age and risk factors for cardiovascular disease, both ADT use (adjusted hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.4 to 4.7; P =.002) and age (adjusted HR = 1.07; 95% Cl = 1.02 to 1.1; P =.003) were associated with statistically significantly increased risks of death from cardiovascular causes in patients treated with radical prostatectomy. Among patients 65 years or older treated with radical prostatectomy, the 5-year cumulative incidence of cardiovascular death was 5.5% (95% Cl = 1.2% to 9.8%) in those who received ADT and 2.0% (95% Cl = 1.1% to 3.0%) in those who did not. Among patients 65 years or older treated with external beam radiation therapy, brachytherapy, or cryotherapy, ADT use was associated with a higher cumulative incidence of death from cardiovascular causes, but the difference did not reach statistical significance. Conclusions The use of ADT appears to be associated with an increased risk of death from cardiovascular causes in patients undergoing radical prostatectomy for localized prostate cancer. C1 Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Tsai, HK (reprint author), Harvard Univ, Sch Med, Harvard Radiat Oncol Program, 375 Longwood Ave, Boston, MA 02215 USA. EM hktsai@post.harvard.edu RI Jepsen, Peter/A-2593-2010 OI Jepsen, Peter/0000-0002-6641-1430 NR 28 TC 261 Z9 267 U1 5 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 17 PY 2007 VL 99 IS 20 BP 1516 EP 1524 DI 10.1093/jnci/djm168 PG 9 WC Oncology SC Oncology GA 223RW UT WOS:000250391000008 PM 17925537 ER PT J AU Kusakari, Y Xiao, CY Rosenzweig, A Matsui, T AF Kusakari, Yoichiro Xiao, Chun-Yang Rosenzweig, Anthony Matsui, Takashi TI Phenotypic spectrum caused by transgenic overexpression of mTOR in the heart SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Kusakari, Yoichiro; Xiao, Chun-Yang; Rosenzweig, Anthony; Matsui, Takashi] BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 5 EP 5 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300023 ER PT J AU Rigor, DL Bodyak, N Zhang, L Ter-Ovanesyan, D He, Z McMullen, JR Izumo, S King, GL Kang, PM AF Rigor, Debra L. Bodyak, Natalya Zhang, Li Ter-Ovanesyan, Dmitry He, Zhiheng McMullen, Julie R. Izumo, Seigo King, George L. Kang, Peter M. TI Phosphoinositide 3-kinase-AKT signaling pathway interacts with protein kinase C beta 2 in the determination of cardiomyocyte size and heart function SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Rigor, Debra L.; Bodyak, Natalya; Zhang, Li; Ter-Ovanesyan, Dmitry; Izumo, Seigo; Kang, Peter M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [He, Zhiheng; King, George L.] Joslin Diabet Ctr, Boston, MA 02215 USA. [Izumo, Seigo] Novartis Pharmaceut, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 6 EP 6 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300026 ER PT J AU Ponnuswamy, P Schrottle, A Ostermeier, E Gruner, S Varga-Szabo, D Huang, P Ertl, G Nieswandt, B Kuhlencordt, P AF Ponnuswamy, Padmapriya Schroettle, Angelka Ostermeier, Eva Gruener, Sabine Varga-Szabo, David Huang, Paul Ertl, Georg Nieswandt, Bernhard Kuhlencordt, Peter TI Endothelial nitric oxide production inhibits leukocyte endothelial cell- but not platelet endothelial cell interactions SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Ponnuswamy, Padmapriya; Schroettle, Angelka; Ostermeier, Eva; Ertl, Georg; Kuhlencordt, Peter] Herz Kreislaufzentrum, Med Klin 1, Wurzburg, Germany. [Gruener, Sabine; Varga-Szabo, David; Nieswandt, Bernhard] Rodulf Virchow Zentrum Expt Biomed, Wurzburg, Germany. [Huang, Paul] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 26 EP 27 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300120 ER PT J AU Ashida, N SenBanerjee, S Kodama, S Spencer, JA Zamiri, P Li, L Gerszten, RE Lin, CP Karin, M Rosenzweig, A AF Ashida, Noboru SenBanerjee, Sucharita Kodama, Shohta Spencer, Joel A. Zamiri, Parisa Li, Ling Gerszten, Robert E. Lin, Charles P. Karin, Michael Rosenzweig, Anthony TI Endothelial-specific deletion of inhibitor of kappa-B kinase-beta (IKK-beta) SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Ashida, Noboru; SenBanerjee, Sucharita; Li, Ling; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Kodama, Shohta] Brigham & Womens Hosp, Boston, MA 02115 USA. [Spencer, Joel A.; Zamiri, Parisa; Gerszten, Robert E.; Lin, Charles P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Karin, Michael] Univ Calif San Diego, San Diego, CA 92103 USA. RI Spencer, Joel/A-4590-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 36 EP 37 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300165 ER PT J AU Ly, HQ Kawase, Y Prunier, FA Lebeche, D Shi, Y Yoneyama, R Hoshino, K Takewa, Y Peluso, R Zsebo, K Tardif, JC Tanguay, JF Hajjar, RJ AF Ly, Hung Q. Kawase, Yoshiaki Prunier, Fabrice A. Lebeche, Djamel Shi, Yafen Yoneyama, Ryuichi Hoshino, Kozo Takewa, Yoshiaki Peluso, Richard Zsebo, Krisztina Tardif, Jean-Claude Tanguay, Jean-Francois Hajjar, Roger J. TI Cardiac function improvement following in vivo intracoronary adeno-associated virus type 1 vector gene transfer of SERCA2a in a pre-clinical model of heart failure SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Ly, Hung Q.; Shi, Yafen; Tardif, Jean-Claude; Tanguay, Jean-Francois] Montreal Heart Inst, Montreal, PQ, Canada. [Kawase, Yoshiaki; Prunier, Fabrice A.; Lebeche, Djamel; Yoneyama, Ryuichi; Hoshino, Kozo; Takewa, Yoshiaki; Hajjar, Roger J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Peluso, Richard] Target Genet, Seattle, WA USA. [Zsebo, Krisztina] Celladon Inc, La Jolla, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 46 EP 46 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300204 ER PT J AU Yu, PB Hong, CC Sachidanandan, C Deng, DY Hoyng, SA Bloch, KD Peterson, RT AF Yu, Paul B. Hong, Charles C. Sachidanandan, Chetana Deng, Donna Y. Hoyng, Stefan A. Bloch, Kenneth D. Peterson, Randall T. TI Dorsomorphin, a novel inhibitor of bone morphogenetic protein signaling SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Yu, Paul B.; Sachidanandan, Chetana; Deng, Donna Y.; Hoyng, Stefan A.; Bloch, Kenneth D.; Peterson, Randall T.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Hong, Charles C.] Vanderbilt Univ, Sch Med, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 60 EP 60 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300264 ER PT J AU Matthiesen, T Ott, HC Goh, SK Kren, SM Taylor, DA AF Matthiesen, Thomas Ott, Harald C. Goh, Sak-Kia Kren, Stefan M. Taylor, Doris A. TI Creating biocompatible 3-D scaffolds for engineering cardiovascular tissues: Heart, lung, and kidney SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Matthiesen, Thomas; Goh, Sak-Kia; Kren, Stefan M.; Taylor, Doris A.] Univ Minnesota, Minneapolis, MN 55455 USA. [Ott, Harald C.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 70 EP 70 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300311 ER PT J AU Xiong, JW Wang, C Yu, O Zhang, J Deng, H AF Xiong, Jing Wei Wang, Chengyan Yu, Oingming Zhang, Jiaojiao Deng, Hongkui TI An acyltransferase controls the generation of hematopoietic and endothelial lineages in zebrafish and mouse ES cells SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Xiong, Jing Wei; Yu, Oingming; Zhang, Jiaojiao] Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. [Wang, Chengyan; Deng, Hongkui] Peking Univ, Beijing, Peoples R China. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 71 EP 71 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300313 ER PT J AU Koelinberger, M Von Bruehl, ML Bergmeier, W Wagner, D Mackman, N Massberg, S AF Koelinberger, Maria Von Bruehl, Marie-Luise Bergmeier, Wolfgang Wagner, Denisa Mackman, Nigel Massberg, Steffen TI Platelets contribute to arterial and venous thrombosis in vivo SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Koelinberger, Maria; Von Bruehl, Marie-Luise] German Heart Ctr, Munich, Germany. [Bergmeier, Wolfgang; Wagner, Denisa] Harvard Med Sch, CBR Inst, Boston, MA USA. [Mackman, Nigel] Scripps Res Inst, La Jolla, CA USA. [Massberg, Steffen] Harvard Med Sch, Boston, MA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 75 EP 75 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300331 ER PT J AU Foo, SY Heller, E Wykrzykowska, J Gerszten, RE Rosenzweig, A AF Foo, Shi Yin Heller, Eric Wykrzykowska, Joanna Gerszten, Robert E. Rosenzweig, Anthony TI A low carbohydrate diet increases atherogenesis and decreases endothelial progenitor cells in ApoE(-/-) mice SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Foo, Shi Yin; Wykrzykowska, Joanna; Rosenzweig, Anthony] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Heller, Eric] Coll Phys & Surg, New York, NY USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 77 EP 77 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300343 ER PT J AU Matthiesen, TS Ott, HC Goh, SK Taylor, DA AF Matthiesen, Thomas S. Ott, Harald C. Goh, Sak-Kia Taylor, Doris A. TI Large solid organ perfusion decellularization - A start for human-sized tissue scaffolds? SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Matthiesen, Thomas S.; Goh, Sak-Kia; Taylor, Doris A.] Univ Minnesota, Minneapolis, MN USA. [Ott, Harald C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 103 EP 103 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300455 ER PT J AU Milan, DJ Jones, IL Amsterdam, AH Rosenbaum, DS Roden, D MacRae, CA AF Milan, David J. Jones, Ian L. Amsterdam, Adam H. Rosenbaum, David S. Roden, Dan MacRae, Calum A. TI A pharmacogenetic screen for modifiers of drug induced QT prolongation reveals 15 novel genes SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Milan, David J.; Jones, Ian L.; MacRae, Calum A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Amsterdam, Adam H.] MIT, Cambridge, MA 02139 USA. [Rosenbaum, David S.] Case Western Reserve Univ, MetroHlth Campus, Cleveland, OH 44106 USA. [Roden, Dan] Vanderbilt Univ, Med Ctr, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 117 EP 117 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300519 ER PT J AU Yu, PB Deng, DY Beppu, H Hoyng, SA Kawai, N Bloch, KD AF Yu, Paul B. Deng, Donna Y. Beppu, Hideyuki Hoyng, Stefan A. Kawai, Noriko Bloch, Kenneth D. TI Disruption of the BMP type II receptor alters the dynamics of BMP pathway activation, abrogating BMP-mediated growth inhibition and differentiation in pulmonary artery smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Yu, Paul B.; Deng, Donna Y.; Beppu, Hideyuki; Hoyng, Stefan A.; Kawai, Noriko; Bloch, Kenneth D.] Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 123 EP 123 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300546 ER PT J AU Okamoto, Y Minarm, M Wara, AKMK Feinberg, MW Sukhova, GK Kihara, S Funahashi, T Colvin, RA Luster, AD Libby, P AF Okamoto, Yoshihisa Minarm, Manabu Wara, A. K. M. K. Feinberg, Mark W. Sukhova, Galina K. Kihara, Shinji Funahashi, Tomu Colvin, Richard A. Luster, Andrew D. Libby, Peter TI Adiponectin reduces T lymphocyte accumulation in atherosclerotic lesions by inhibiting T lymphocytotropic CXC chemokines SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Okamoto, Yoshihisa; Minarm, Manabu; Wara, A. K. M. K.; Feinberg, Mark W.; Sukhova, Galina K.; Libby, Peter] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA USA. [Kihara, Shinji; Funahashi, Tomu] Osaka Univ, Grad Sch Med, Osaka, Japan. [Colvin, Richard A.; Luster, Andrew D.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 145 EP 145 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300640 ER PT J AU Lipskaia, L Lehoux, S Esposito, B Le Prince, P Bonnet, N Le Feuvre, C Hajjar, R Lompre, AM AF Lipskaia, Larissa Lehoux, Stephanie Esposito, Bruno Le Prince, Pascal Bonnet, Nicolas Le Feuvre, Claude Hajjar, Rene Lompre, Anne-Marie TI SERCA2a controls vascular smooth muscle cell proliferation in human arteries SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lipskaia, Larissa; Lompre, Anne-Marie] INSERM, UMR S 621, F-75654 Paris 13, France. [Lehoux, Stephanie; Esposito, Bruno] INSERM, CRCIL U 689, F-75654 Paris, France. [Le Prince, Pascal; Bonnet, Nicolas; Le Feuvre, Claude] AP HP, Paris, France. [Hajjar, Rene] Massachusetts Gen Hosp, CVRC, Charlestown, MA USA. RI LOMPRE, Anne-Marie/H-2872-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 148 EP 148 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300651 ER PT J AU Jaffer, FA Figueiredo, JL Wojtkiewicz, G Zhang, H Patel, P Nahrendorf, M Tung, CH Weissleder, R AF Jaffer, Farouc A. Figueiredo, Jose L. Wojtkiewicz, Gregory Zhang, Hanwen Patel, Purvish Nahrendorf, Matthias Tung, Ching-Hsuan Weissleder, Ralph TI Noninvasive integrated SPECT/CT molecular imaging of activated factor XIII activity in thrombosis SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Jaffer, Farouc A.; Figueiredo, Jose L.; Wojtkiewicz, Gregory; Zhang, Hanwen; Patel, Purvish; Nahrendorf, Matthias; Tung, Ching-Hsuan; Weissleder, Ralph] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 155 EP 155 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300686 ER PT J AU Zhao, H Xu, X Schmidt, U Chao, W AF Zhao, Huailong Xu, Xinhua Schmidt, Ulrich Chao, Wei TI Innate immune adaptor MyD88 mediates myocardial inflammation and infarction in a mouse model of ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Zhao, Huailong; Xu, Xinhua; Schmidt, Ulrich; Chao, Wei] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 198 EP 198 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300879 ER PT J AU Colston, JT de la Rosa, SD Bailey, SR Chandraselkar, B AF Colston, James T. de la Rosa, Sam D. Bailey, Steven R. Chandraselkar, Bysani TI Novel regulation of Wnt-inducible secreted protein 1 by TNF-alpha in primary human cardiac fibroblasts SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Colston, James T.; de la Rosa, Sam D.; Bailey, Steven R.] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [Chandraselkar, Bysani] Dept Vet Affairs, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 211 EP 212 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394300940 ER PT J AU Chan, JY Takeda, M Briggs, LE Lu, JT Horikoshi, N Weinberg, E Aoki, H Chien, KR Kasahara, H AF Chan, Jason Y. Takeda, Morihilko Briggs, Laura E. Lu, Jonathan T. Horikoshi, Nobuo Weinberg, Ellen Aoki, Hiroki Chien, Kenneth R. Kasahara, Hideko TI Cardiaic-specific myosin light chain kinase (MLCK), a third member of MLCK family, potentiates sarcomere formation and cardiac contraction SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Chan, Jason Y.; Takeda, Morihilko; Briggs, Laura E.; Kasahara, Hideko] Univ Florida, Gainesville, FL USA. [Lu, Jonathan T.] Univ Calif San Francisco, San Francisco, CA USA. [Horikoshi, Nobuo] Washington Univ, Sch Med, St Louis, MO USA. [Weinberg, Ellen] Boston Univ, Boston, MA 02215 USA. [Aoki, Hiroki] Yamaguchi Univ, Sch Med, Ube, Yamaguchi, Japan. [Chien, Kenneth R.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1102 BP 221 EP 221 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301029 ER PT J AU Fine, GC Oikonomopoulos, A Cullen, D Swirski, F Shaw, S Sereti, K Reynolds, F Josephson, L Weissleder, R Sosnovilk, D Liao, R AF Fine, Gabriel C. Oikonomopoulos, Angelos Cullen, Darragh Swirski, Filip Shaw, Stanley Sereti, Konstantra Reynolds, Fred Josephson, Lee Weissleder, Ralph Sosnovilk, David Liao, Ronglih TI Labeling with a novel magnetofluorescent molecular imaging probe does not affect the proliferation and cardiomyogenic potential of cardiac side population progenitor cells SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Fine, Gabriel C.; Oikonomopoulos, Angelos; Cullen, Darragh; Sereti, Konstantra; Liao, Ronglih] Brigham & Womens Hosp, Boston, MA USA. [Swirski, Filip; Reynolds, Fred; Josephson, Lee; Weissleder, Ralph; Sosnovilk, David] Massachusetts Gen Hosp, Charlestown, MA USA. [Shaw, Stanley] Massachusetts Gen Hosp, Broad Inst, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1107 BP 222 EP 222 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301034 ER PT J AU Fitzgerald, ML Tamehiro, N Zhou, SP Okuhira, K AF Fitzgerald, Michael L. Tamehiro, Norimasa Zhou, Suiping Okuhira, Keiichiro TI PDZ domain protein arrays define a network of ABCA1 and SPLTC1 protein-protein interactions that regulate ABCA1 trafficking and efflux activity SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Fitzgerald, Michael L.; Tamehiro, Norimasa; Zhou, Suiping] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Natl Inst Hlth Sci, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301114 ER PT J AU Korngold, EC McCarthy, JR Figueiredo, JL Aikawa, E Kohler, RH Weissleder, R Jaffer, FA AF Korngold, Ethan C. McCarthy, Jason R. Figueiredo, Jose-Luiz Aikawa, Elena Kohler, Rainer H. Weissleder, Ralph Jaffer, Farouc A. TI Imaging and photodynamic therapy of atherosclerotic plaque using a macrophage-targeted nanoparticle SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Korngold, Ethan C.; McCarthy, Jason R.; Figueiredo, Jose-Luiz; Aikawa, Elena; Kohler, Rainer H.; Weissleder, Ralph; Jaffer, Farouc A.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 241 EP 241 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301116 ER PT J AU Okamoto, H Aikawa, E Aikawa, M AF Okamoto, Hiroyuki Aikawa, Elena Aikawa, Masanori TI CD40 ligand induces pentraxin 3 (PTX3) expression in human macrophages SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Okamoto, Hiroyuki; Aikawa, Masanori] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. [Aikawa, Elena] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 243 EP 243 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301127 ER PT J AU Wu, GX Hu, WG Shahsafaei, A Bronson, RR Shi, GP Halperin, JA Qin, XB AF Wu, Gongxiong Hu, Weiguo Shahsafaei, Ahakbar Bronson, Rod R. Shi, Guo-ping Halperin, Jose A. Qin, Xuebin TI Protective role of complement regulator CD59 in the development of atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Wu, Gongxiong; Hu, Weiguo; Halperin, Jose A.; Qin, Xuebin] Harvard Med Sch, Cambridge, MA USA. [Shahsafaei, Ahakbar] Harvard Med Sch, Boston, MA USA. [Bronson, Rod R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. [Shi, Guo-ping] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 243 EP 243 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301125 ER PT J AU Aikawa, E Nahrendorf, M Figueredo, JL Swirski, FK Shtatland, T Kohler, R Jaffer, FA Aikawa, M Weissleder, R AF Aikawa, Elena Nahrendorf, Matthias Figueredo, Jose-Luiz Swirski, Filip K. Shtatland, Timor Kohler, Rainer Jaffer, Farouc A. Aikawa, Masanori Weissleder, Ralph TI In vivo molecular imaging links macrophage burden and microcalcifications in early atherosclerosis SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Aikawa, Elena; Swirski, Filip K.; Shtatland, Timor; Jaffer, Farouc A.; Weissleder, Ralph] Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA USA. [Figueredo, Jose-Luiz; Kohler, Rainer] Massachusetts Gen Hosp, Charlestown, MA USA. [Aikawa, Masanori] Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1207 BP 245 EP 245 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301134 ER PT J AU Andersson, KB Finsen, AV Sjaastad, I Wang, Y Cheri, J Molkentin, JD Chien, KR Sejersted, OM AF Andersson, Kristin B. Finsen, Alexandra V. Sjaastad, Ivar Wang, Yibin Cheri, Ju Molkentin, Jeffery D. Chien, Kenneth R. Sejersted, Ole M. TI Heart function is transiently sustained despite a near loss of SERCA2 protein in cardiomyocyte-specific Serca2(null) mice SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Andersson, Kristin B.; Finsen, Alexandra V.; Sejersted, Ole M.] Univ Oslo, Ullevaal Univ Hosp, Ctr Heart Failure Res, Expt Med Res Inst, Oslo, Norway. [Sjaastad, Ivar] Univ Oslo, Ullevaal Univ Hosp, Ctr Heart Failure Res, Dept Cardiol, Oslo, Norway. [Wang, Yibin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Anesthesiol, Dept Physiol,Dept Med, Los Angeles, CA USA. [Cheri, Ju] Univ Calif San Diego, Inst Mol Med, La Jolla, CA USA. [Molkentin, Jeffery D.] Univ Cincinnati, Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH USA. [Chien, Kenneth R.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 254 EP 254 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301174 ER PT J AU Buys, ES Sips, PY Raher, MJ Graveline, AR Searles, RJ Ichinose, F Brouckaert, P Bloch, KD AF Buys, Emmanuel S. Sips, Patrick Y. Raher, Michael J. Graveline, Amanda R. Searles, Robert J. Ichinose, Fumito Brouckaert, Peter Bloch, Kenneth D. TI Gender-specific and testosterone-dependent hypertension in soluble guanylate cyclase alpha(1)-deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Buys, Emmanuel S.; Raher, Michael J.; Graveline, Amanda R.; Searles, Robert J.; Ichinose, Fumito; Bloch, Kenneth D.] Massachusetts Gen Hosp, Boston, MA USA. [Sips, Patrick Y.; Brouckaert, Peter] Univ Ghent, Univ Ghent VIB, Ghent, Belgium. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 264 EP 264 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301220 ER PT J AU Lam, L Leen, S Filipe, C Billon, A Jalvy, S Daret, D Allieres, C Brouchet, L Dufourcq, P Rittling, SR Desgranges, C Gadeau, AP AF Lam, Laetitia Leen, Shang Filipe, Cedric Billon, Audrey Jalvy, Sandra Daret, Danile Allieres, Cecile Brouchet, Laurent Dufourcq, Pascale Rittling, Susan R. Desgranges, Claude Gadeau, Alain Pierre TI Osteopontin mediates the estradiol effect on endothelium regrowth by increasing the capacity of bone marrow-derived cells to adhere to endothelial cells SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lam, Laetitia; Leen, Shang; Jalvy, Sandra; Daret, Danile; Allieres, Cecile; Dufourcq, Pascale; Gadeau, Alain Pierre] Univ Bordeaux 2, INSERM, U828, Pessac, France. [Filipe, Cedric; Billon, Audrey; Brouchet, Laurent; Desgranges, Claude] CHU Rangueil, INSERM, U858, Toulouse, France. [Rittling, Susan R.] Harvard Univ, Forsyth Dent Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 264 EP 264 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301219 ER PT J AU Okuhira, K Fitzgerald, ML Tamehiro, N Freeman, MW Shigemoto-Mogami, Y Suzuki, K Nishimaki-Mogami, T AF Okuhira, Keiichiro Fitzgerald, Michael L. Tamehiro, Norimasa Freeman, Mason W. Shigemoto-Mogami, Yukari Suzuki, Kazuhiro Nishimaki-Mogami, Tomoko TI The guanine exchange factor 11 PDZ protein binds ABCA1 positively regulating transporter expression and cholesterol efflux via Rho activation SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Okuhira, Keiichiro; Shigemoto-Mogami, Yukari; Suzuki, Kazuhiro; Nishimaki-Mogami, Tomoko] Natl Inst Hlth Sci, Tokyo, Japan. [Fitzgerald, Michael L.; Tamehiro, Norimasa; Freeman, Mason W.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1393 BP 286 EP 286 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301320 ER PT J AU Jensen, BC Swigart, PM Myagmar, BE Shah, S DeMarco, T Hoopes, C Simpson, PC AF Jensen, Brian C. Swigart, Philip M. Myagmar, Bat-Erderre Shah, Sanjay DeMarco, Teresa Hoopes, Charles Simpson, Paul C. TI The alpha-1a is the predominant alpha-1-adrenergic receptor in the human heart at the mRNA but not the protein level SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Jensen, Brian C.; Simpson, Paul C.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA USA. [Swigart, Philip M.] San Francisco VA Med Ctr, San Francisco, CA USA. [Myagmar, Bat-Erderre] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA USA. [Shah, Sanjay; DeMarco, Teresa; Hoopes, Charles] Univ Calif San Francisco, San Francisco, CA USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1405 BP 289 EP 289 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301332 ER PT J AU Nagasaka, Y Fernandez, BO Garcia-Saura, MF Petersen, B Ichinose, F Bloch, KD Feelisch, M Zapol, WM AF Nagasaka, Yasuko Fernandez, Bernadette O. Garcia-Saura, Maria F. Petersen, Bodil Ichinose, Fumito Bloch, Kenneth D. Feelisch, Martin Zapol, Warren M. TI Inhaled NO in myocardial ischemia/reperfusion injury: Pharmacokinetics and pharmacodynamics of protective NO metabolites SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nagasaka, Yasuko; Petersen, Bodil; Ichinose, Fumito; Bloch, Kenneth D.; Zapol, Warren M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Fernandez, Bernadette O.; Garcia-Saura, Maria F.; Feelisch, Martin] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1484 BP 306 EP 306 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301410 ER PT J AU Bamberg, F Dannemann, N Shapiro, MD Seneviratne, S Ferencilk, M Butler, J Koenig, W Nasir, K Cury, RC Tawakol, A Achenbach, S Brady, TJ Hoffmann, U AF Bamberg, Fabian Dannemann, Nina Shapiro, Michael D. Seneviratne, Sujith Ferencilk, Maros Butler, Javed Koenig, Wolfgang Nasir, Khurram Cury, Ricardo C. Tawakol, Ahmed Achenbach, Stephan Brady, Thomas J. Hoffmann, Udo TI Association between cardiovascular risk profiles and the presence and extent of different types of coronary atherosclerotic plaque as detected by multidetector computed tomography SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Bamberg, Fabian; Dannemann, Nina; Shapiro, Michael D.; Seneviratne, Sujith; Ferencilk, Maros; Butler, Javed; Nasir, Khurram; Cury, Ricardo C.; Tawakol, Ahmed; Achenbach, Stephan; Brady, Thomas J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koenig, Wolfgang] Univ Ulm, Ulm, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 343 EP 343 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301562 ER PT J AU Gibson, CM Pride, YB Buros, JL Murphy, SA Cannon, CP Salbatine, MS Braunwald, E AF Gibson, C. Michael Pride, Yuri B. Buros, Jacqueline L. Murphy, Sabina A. Cannon, Christopher P. Salbatine, Marc S. Braunwald, Eugene TI Variable association of hyperemic epicardial flow with adverse outcomes among patients treated with fibrinolytic therapy for ST-segment elevation myocardial infarction: An analysis from CLARITY-TIMI 28 SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Gibson, C. Michael; Buros, Jacqueline L.; Murphy, Sabina A.; Cannon, Christopher P.; Salbatine, Marc S.] Beth Israel Deaconess Med Ctr, Harvard Med Sch, TIMI Study Grp, Boston, MA USA. [Pride, Yuri B.; Braunwald, Eugene] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1677 BP 352 EP 352 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301600 ER PT J AU Pride, YB Bores, JL Lord, E Harrigan, CJ Lew, M Abraham, J Murphy, SA Cannon, CP Sabatine, MS Gibson, M AF Pride, Yuri B. Bores, Jacqueline L. Lord, Erin Harrigan, Caitlin J. Lew, Michelle Abraham, JoEllyn Murphy, Sabina A. Cannon, Christopher P. Sabatine, Marc S. Gibson, Michael TI Angiographic perfusion score in patients treated with PCl at late angiography following fibrinolytic administration for ST-Segment elevation myocardial infarction is associated with morbidity and mortality at 30 days SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Pride, Yuri B.; Abraham, JoEllyn] Beth Israel Deaconess Med Ctr, Med Ctr, Harvard Med Sch, Boston, MA 02215 USA. [Bores, Jacqueline L.; Lord, Erin; Harrigan, Caitlin J.; Lew, Michelle; Gibson, Michael] Beth Israel Deaconess Med Ctr, Havard Med Sch, TIMI Study Grp, Boston, MA 02215 USA. [Murphy, Sabina A.; Cannon, Christopher P.; Sabatine, Marc S.] Brigham & Womens Hosp, Harvard Med Sch, TIMI Study Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1678 BP 352 EP 352 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301601 ER PT J AU Sabatine, MS Morrow, DA Jiang, S Rifai, N Cannon, CP Gerszten, RE AF Sabatine, Marc S. Morrow, David A. Jiang, Songtao Rifai, Nader Cannon, Christopher P. Gerszten, Robert E. TI Elevated levels of the atherosclerotic lesion metalloproteinase PAPPA are an independent predictor of cardiovascular death or CHF in STEMI: Results from the CLARITY-TIMI 28 biomarker study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Sabatine, Marc S.; Morrow, David A.; Cannon, Christopher P.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Jiang, Songtao] Harvard Clin Res Inst, Boston, MA USA. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 363 EP 363 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301645 ER PT J AU Taylor, MV Bohachick, P Sereika, SM Schlenk, EA Brown, C Burke, LE AF Taylor, Melissa V. Bohachick, Patricia Sereika, Susan M. Schlenk, Elizabeth A. Brown, Charlotte Burke, Lora E. TI Social support, personal control, and psychological functioning among individuals with heart failure SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Taylor, Melissa V.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Bohachick, Patricia; Sereika, Susan M.; Schlenk, Elizabeth A.; Burke, Lora E.] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. [Brown, Charlotte] Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1731 BP 365 EP 365 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301652 ER PT J AU Das, S Palacios, I Vlahakes, GJ Picard, MH Sanborn, DY Lowry, PA Ruskin, JN Fifer, MA Mela, T AF Das, Saumya Palacios, Igor Vlahakes, Gus J. Picard, Michael H. Sanborn, Danita Y. Lowry, Patricia A. Ruskin, Jeremy N. Fifer, Michael A. Mela, Theofanie TI Risk of proarrhythmia following alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Das, Saumya; Palacios, Igor; Vlahakes, Gus J.; Picard, Michael H.; Sanborn, Danita Y.; Lowry, Patricia A.; Ruskin, Jeremy N.; Fifer, Michael A.; Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1740 BP 367 EP 367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301661 ER PT J AU Chaput, M Handschumacher, MD Tournoux, F Hua, L Vlahakes, GJ Guerrero, JL Levine, RA AF Chaput, Miguel Handschumacher, Mark D. Tournoux, Francois Hua, Lanci Vlahakes, Gus J. Guerrero, J. L. Levine, Robert A. TI Mitral leaflet adaptation to ventricular remodeling: occurrence and adequacy in 80 patients with functional mitral regurgitation SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Chaput, Miguel; Handschumacher, Mark D.; Tournoux, Francois; Hua, Lanci; Vlahakes, Gus J.; Guerrero, J. L.; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1745 BP 368 EP 368 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301666 ER PT J AU Lewis, GD Wei, R Sabatine, MS Asnani, A Martinovic, ME Farrell, LA Liu, E Palacios, IF Carr, SA Mootha, VK Fifer, MA Gerszten, RE AF Lewis, Gregory D. Wei, Ru Sabatine, Marc S. Asnani, Aarti Martinovic, Maryann E. Farrell, Laurie A. Liu, Emerson Palacios, Igor F. Carr, Steven A. Mootha, Vamsi K. Fifer, Michael A. Gerszten, Robert E. TI Metabolic changes in plasma revealed by planned heart attacks SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lewis, Gregory D.; Asnani, Aarti; Martinovic, Maryann E.; Farrell, Laurie A.; Liu, Emerson; Palacios, Igor F.; Mootha, Vamsi K.; Fifer, Michael A.; Gerszten, Robert E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wei, Ru; Carr, Steven A.] Broad Inst, Boston, MA USA. [Sabatine, Marc S.] Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1755 BP 371 EP 371 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301676 ER PT J AU O'Donoghue, M Maree, AO Garasic, JM Sabatine, MS AF O'Donoghue, Michelle Maree, Andrew O. Garasic, Joseph M. Sabatine, Marc S. TI 3 acute coronary syndromes, 5 Stents and 8 antithrombotics in 12 days in a 59-year-old woman SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [O'Donoghue, Michelle; Maree, Andrew O.; Garasic, Joseph M.; Sabatine, Marc S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1758 BP 371 EP 372 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301679 ER PT J AU Bogaev, RC Chen, L Russell, SD Rogers, JG Farrar, DJ Moore, SA AF Bogaev, Roberta C. Chen, Leway Russell, Stuart D. Rogers, Joseph G. Farrar, David J. Moore, Stephanie A. TI An emerging option for women with advanced heart failure: Results of the HeartMate II continuous flow left ventricular assist device bridge to transplant trial SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Bogaev, Roberta C.] Texas Heart Inst, Houston, TX 77025 USA. [Chen, Leway] Univ Rochester, Rochester, NY USA. [Russell, Stuart D.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Rogers, Joseph G.] Duke Univ, Durham, NC USA. [Farrar, David J.; Moore, Stephanie A.] Thoratec, Pleasanton, CA USA. [Moore, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1762 BP 372 EP 372 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301683 ER PT J AU Merchant, FM Cury, RC Houser, S Mamuya, W AF Merchant, Faisal M. Cury, Ricardo C. Houser, Stuart Mamuya, Wilfred TI An uncommon cause of stroke in a 41-year-old female SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Merchant, Faisal M.; Cury, Ricardo C.; Houser, Stuart; Mamuya, Wilfred] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1761 BP 372 EP 372 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301682 ER PT J AU Manini, A Ilgen, J Noble, VE Moselewski, F Koenig, W Bohan, JS Hoffmann, U AF Manini, Alex Ilgen, Jon Noble, Vicki E. Moselewski, Fabian Koenig, Wolfgang Bohan, J. S. Hoffmann, Udo TI Ischemia modified albumin adds sensitivity to the initial workup of patients with acute chest pain SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Manini, Alex] NYU, Sch Med, New York, NY USA. [Ilgen, Jon] Harvard Affiliated Emergency Med Residency, Boston, MA USA. [Noble, Vicki E.; Moselewski, Fabian; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koenig, Wolfgang] Univ Ulm, Med Ctr, D-89069 Ulm, Germany. [Bohan, J. S.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1793 BP 381 EP 381 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301714 ER PT J AU O'Donoghue, M Sabatine, MS Boden, WE Braunwald, E Cannon, CP Clayton, TC de Winter, RJ Fox, KA McCullough, PA Murphy, SA Spacek, R Swahn, E Wallentin, L Winchausen, F AF O'Donoghue, Michelle Sabatine, Marc S. Boden, William E. Braunwald, Eugene Cannon, Christopher P. Clayton, Tim C. de Winter, Robbert J. Fox, Keith A. McCullough, Peter A. Murphy, Sabina A. Spacek, Rudolf Swahn, Eva Wallentin, Lars Winchausen, Fons TI The benefit of an early invasive strategy in women versus men with non-ST-elevation acute coronary syndromes: A collaborative meta-analysis of randomized trials SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [O'Donoghue, Michelle] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sabatine, Marc S.; Braunwald, Eugene; Cannon, Christopher P.; Murphy, Sabina A.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Boden, William E.] Buffalo Gen Hosp, Buffalo, NY 14203 USA. [de Winter, Robbert J.] London Sch Hyg & Trop Med, London WC1, England. [de Winter, Robbert J.; Winchausen, Fons] Acad Med Ctr, Amsterdam, Netherlands. [Fox, Keith A.] Univ & Royal Infirm, Edinburgh, Midlothian, Scotland. [McCullough, Peter A.] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Spacek, Rudolf] Hosp Na Frantisku, Prague, Czech Republic. [Swahn, Eva] Univ Hosp, Linkoping, Sweden. [Wallentin, Lars] Univ Uppsala Hosp, Uppsala, Sweden. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1801 BP 383 EP 383 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301721 ER PT J AU Corvera-Tindel, T Doering, LV Mody, FV Roper, J AF Corvera-Tindel, Teresita Doering, Lynn V. Mody, Freny V. Roper, Janice TI Diabetes reduces reactivation of vagal tone after peak exercise in heart failure patients SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Corvera-Tindel, Teresita] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Doering, Lynn V.; Mody, Freny V.; Roper, Janice] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1816 BP 387 EP 387 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301736 ER PT J AU Stevens, LM Wolf, RE Agnihotri, AK Torchiana, DF Lovett, A Normand, SL AF Stevens, Louis M. Wolf, Robert E. Agnihotri, Arvind K. Torchiana, David F. Lovett, Ann Normand, Sharon L. TI Coronary artery bypass grafting after uneventful percutaneous coronary intervention in the commonwealth of Massachusetts SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Stevens, Louis M.; Agnihotri, Arvind K.; Torchiana, David F.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Wolf, Robert E.; Lovett, Ann; Normand, Sharon L.] Harvard Med Sch, Harvard Sch Publ Hlth, Boston, MA USA. RI Stevens, Louis-Mathieu/E-6453-2016 OI Stevens, Louis-Mathieu/0000-0003-3372-3419 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 395 EP 395 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301768 ER PT J AU Zenati, M Sonel, A Bjerke, R Shroyer, L Collins, J AF Zenati, Marco Sonel, Ali Bjerke, Richard Shroyer, Laurie Collins, Joseph CA ROOBY Invest TI Safety of aprotinin in CABG patients: Results of the VA multicenter prospective randomized ROOBY trial SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Zenati, Marco] Univ Pittsburgh, Pittsburgh, PA USA. [Sonel, Ali; Bjerke, Richard] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Shroyer, Laurie] VA Denver, Denver, CO USA. [Collins, Joseph] VA Cooperat Study Program, Perry Point, MD USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 396 EP 396 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301771 ER PT J AU Passeri, JJ Inglessis, I Palacios, IF Picard, MH AF Passeri, Jonathan J. Inglessis, Ignacio Palacios, Igor F. Picard, Michael H. TI Initial experience with real-time three-dimensional transesophageal echocardiography in patients undergoing transcatheter atrial septal defect closure SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Passeri, Jonathan J.; Inglessis, Ignacio; Palacios, Igor F.; Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 1873 BP 401 EP 401 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301793 ER PT J AU Upadhyay, GA Choudhry, NK Auricchio, A Ruskin, JN Singh, JP AF Upadhyay, Gaurav A. Choudhry, Niteesh K. Auricchio, Angelo Ruskin, Jeremy N. Singh, Jagmeet P. TI Cardiac resynchronization in patients with atrial fibrillation: A meta-analysis of prospective cohort studies SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Upadhyay, Gaurav A.; Ruskin, Jeremy N.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Choudhry, Niteesh K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Auricchio, Angelo] Cardio Ctr Ticino, Lugano, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1896 BP 407 EP 407 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301814 ER PT J AU Hoffmann, U Bamberg, F Seneviratne, S Rogers, IS Truong, QA Nichols, JH Shapiro, MD Abbara, S Cury, RC Brady, TJ Achenbach, S Nagurney, JT AF Hoffmann, Udo Bamberg, Fabian Seneviratne, Sujith Rogers, Ian S. Truong, Quynh A. Nichols, John H. Shapiro, Michael D. Abbara, Suhny Cury, Ricardo C. Brady, Thomas J. Achenbach, Stephan Nagurney, John T. TI Coronary MDCT based detection of coronary stenosis and plaque in the assessment of patients with acute chest pain: Update from ROMICAT I SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Hoffmann, Udo; Bamberg, Fabian; Seneviratne, Sujith; Rogers, Ian S.; Truong, Quynh A.; Nichols, John H.; Shapiro, Michael D.; Abbara, Suhny; Cury, Ricardo C.; Brady, Thomas J.; Achenbach, Stephan; Nagurney, John T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 1900 BP 408 EP 408 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301818 ER PT J AU Rogers, IS Figueroa, AL Nasir, K Vermylen, D Cury, RC Hoffmann, U Fischman, AJ Brady, TJ Tawalkol, A AF Rogers, Ian S. Figueroa, Amparo L. Nasir, Khurram Vermylen, David Cury, Ricardo C. Hoffmann, Udo Fischman, Alan J. Brady, Thomas J. Tawalkol, Ahmed TI Assessment of coronary segment inflammation with combined 18-fluorodeoxyglucose positron emission tomography and 64-slice multidetector computed tomography. SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Rogers, Ian S.; Figueroa, Amparo L.; Nasir, Khurram; Cury, Ricardo C.; Hoffmann, Udo; Fischman, Alan J.; Brady, Thomas J.; Tawalkol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vermylen, David] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 410 EP 410 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301826 ER PT J AU Nakazawa, B Ladich, E Mont, EK Finn, AV Kutys, R Burke, A Kolodgie, FD Virmani, R AF Nakazawa, Baku Ladich, Elena Mont, Erik K. Finn, Aloke V. Kutys, Robert Burke, Allen Kolodgie, Frank D. Virmani, Renu TI Incidence and predictors of drug eluting stent fracture in human coronary artery - Pathologic analysis SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nakazawa, Baku; Ladich, Elena; Kutys, Robert; Burke, Allen; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA. [Mont, Erik K.] Miami Dade Cty Med Examiner Dept, Miami, FL USA. [Finn, Aloke V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 414 EP 414 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301843 ER PT J AU Nakazawa, G Joner, M Finn, AV Ladich, E Mont, EK Kutys, R Burke, A Kolodgie, FD Virmani, R AF Nakazawa, Gaku Joner, Michael Finn, Aloke V. Ladich, Elena Mont, Erik K. Kutys, Robert Burke, Allen Kolodgie, Frank D. Virmani, Renu TI Differences in vascular response following Sirolimus and paclitaxel eluting stents SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nakazawa, Gaku; Joner, Michael; Ladich, Elena; Kutys, Robert; Burke, Allen; Kolodgie, Frank D.; Virmani, Renu] CVPath Inst Inc, Gaithersburg, MD USA. [Finn, Aloke V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mont, Erik K.] Miami Dade Cty Med Examiner Dept, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 415 EP 415 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301845 ER PT J AU Baggish, AL Wang, F Elinoff, J Weiner, RB Hutter, AM Wood, MJ AF Baggish, Aaron L. Wang, Francis Elinoff, Jason Weiner, Rory B. Hutter, Adolph M., Jr. Wood, Malissa J. TI The effects of vigorous athletic training on right ventricular structure and function SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Baggish, Aaron L.; Elinoff, Jason; Weiner, Rory B.; Hutter, Adolph M., Jr.; Wood, Malissa J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wang, Francis] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 422 EP 422 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394301877 ER PT J AU Shah, RV Lewis, GD Semigran, MJ AF Shah, Ravi V. Lewis, Gregory D. Semigran, Marc J. TI Ventilatory efficiency correlates with exercise pulmonary hemodynamics in chronic heart failure due to LV systolic dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Shah, Ravi V.; Lewis, Gregory D.; Semigran, Marc J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 474 EP 474 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302188 ER PT J AU Nguyen, MC Murphy, SA Mega, JL Brieger, D Antman, EM Gibson, CM AF Nguyen, Michael C. Murphy, Sabina A. Mega, Jessica L. Brieger, David Antman, Elliott M. Gibson, C. M. TI Triple therapy (TTx): ASA, thienopyridine and oral anticoagulation (OA) therapy following ST elevation myocardial infarction (STEMI): Is it safe? SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nguyen, Michael C.; Gibson, C. M.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Murphy, Sabina A.] Perfuse Coordinating Ctr, Core Labs, Boston, MA USA. [Mega, Jessica L.] TIMI Study Grp, Boston, MA USA. [Brieger, David] Concord Hosp, Sydney, NSW, Australia. [Antman, Elliott M.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 483 EP 483 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302224 ER PT J AU Thiagalingam, A D'Avila, A Foley, L Lambert, H Leo, G Ruskin, JN Reddy, VY AF Thiagalingam, Aravinda D'Avila, Andre Foley, Lori Lambert, Hendrik Leo, Giovanni Ruskin, Jeremy N. Reddy, Vivek Y. TI The relationship between impedance change and catheter contact force during radiofrequency ablation: Evaluation in a porcine Ex Vivo cardiac model using a novel force-sensing irrigated tip ablation catheter SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Thiagalingam, Aravinda; D'Avila, Andre; Foley, Lori; Ruskin, Jeremy N.; Reddy, Vivek Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lambert, Hendrik; Leo, Giovanni] Endosense Inc, Meyrin, Switzerland. RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 2239 BP 487 EP 487 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302242 ER PT J AU Thiagalingam, A D'Avila, A Foley, L Miller, D Rothe, C Saadat, V Ruskin, JN Reddy, VY AF Thiagalingam, Aravincla D'Avila, Andre Foley, Lori Miller, David Rothe, Chris Saadat, Vahid Ruskin, Jeremy N. Reddy, Vivek Y. TI Direct visualization of the fossa ovalis for transeptal puncture: In vivo evaluation of the IRIS catheter in a porcine model SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Thiagalingam, Aravincla; D'Avila, Andre; Foley, Lori; Ruskin, Jeremy N.; Reddy, Vivek Y.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, David; Rothe, Chris; Saadat, Vahid] Voyage Med Inc, Campbell, CA USA. RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2241 BP 488 EP 488 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302244 ER PT J AU Hung, J Solis, J Guerrero, JL Braithwaite, G Muratoglu, OK Chaput, M Sullivan, S Fernandez-Friera, L Handschumacher, MD Wedeen, VJ Vlahakes, GJ Levine, RA AF Hung, Judy Solis, Jorge Guerrero, J. L. Braithwaite, Gavin Muratoglu, Orhun K. Chaput, Miguel Sullivan, Suzanne Fernandez-Friera, Leticia Handschumacher, Mark D. Wedeen, Van J. Vlahakes, Gus J. Levine, Robert A. TI Injection of a biomaterial polymer results in reverse remodeling of displaced papillary muscles and reduction in acute ischemic mitral regurgitation SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Hung, Judy; Solis, Jorge; Guerrero, J. L.; Muratoglu, Orhun K.; Chaput, Miguel; Sullivan, Suzanne; Fernandez-Friera, Leticia; Handschumacher, Mark D.; Wedeen, Van J.; Vlahakes, Gus J.; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Braithwaite, Gavin] Cambridge Polymer Grp Inc, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302268 ER PT J AU Jensen, MO Jensen, H Smerup, M Levine, RA Yoganathan, AP Nygaard, H Hasenkam, JM Nielsen, SL AF Jensen, Morten O. Jensen, Henrik Smerup, Morten Levine, Robert A. Yoganathan, Ajit P. Nygaard, Hans Hasenkam, J. Michael Nielsen, Sten L. TI Saddle-shaped mitral valve annuloplasty rings provide superior annular force distribution SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Jensen, Morten O.; Jensen, Henrik; Smerup, Morten; Nygaard, Hans; Hasenkam, J. Michael; Nielsen, Sten L.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Levine, Robert A.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Yoganathan, Ajit P.] Emory Univ, Georgia Inst Technol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 494 EP 494 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302267 ER PT J AU Rogers, IS Figueroa, AL Nasir, K Vermylen, DA Cury, RC Hoffmann, U Fischman, AJ Brady, TJ Tawakol, A AF Rogers, Ian S. Figueroa, Amparo L. Nasir, Khurram Vermylen, David A. Cury, Ricardo C. Hoffmann, Udo Fischman, Alan J. Brady, Thomas J. Tawakol, Ahmed TI Detection of inflamed coronary culprit lesions in patients using PET-CT SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Rogers, Ian S.; Figueroa, Amparo L.; Nasir, Khurram; Cury, Ricardo C.; Hoffmann, Udo; Fischman, Alan J.; Brady, Thomas J.; Tawakol, Ahmed] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vermylen, David A.] Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 2331 BP 510 EP 510 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302334 ER PT J AU Reddy, VY Neuzil, P Themistoclakis, S Bonso, A Rossillo, A Raviele, A Saliba, W Schwiekerl, R Ernst, S Kuck, KH Ruskin, JN Natale, A AF Reddy, Vivek Y. Neuzil, Petr Themistoclakis, Sakis Bonso, Aldo Rossillo, Antonio Raviele, Antonio Saliba, Walid Schwiekerl, Robert Ernst, Sabine Kuck, Karl-Heinz Ruskin, Jeremy N. Natale, Andrea TI Visually-guided pulmonary vein isolation using a balloon ablation catheter to treat patients with paroxysmal atrial fibrillation: One-year clincial outcome following a single ablation procedure SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Reddy, Vivek Y.; Ruskin, Jeremy N.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Neuzil, Petr] Homolka Hosp, Prague, Czech Republic. [Themistoclakis, Sakis; Bonso, Aldo; Rossillo, Antonio; Raviele, Antonio] Umberto Hosp, Venice, Italy. [Saliba, Walid; Schwiekerl, Robert; Natale, Andrea] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Ernst, Sabine] St Georg Hosp, Hamburg, Germany. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2439 BP 536 EP 536 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302441 ER PT J AU Pagani, FD Miller, LW Russell, SD John, R Boyle, AJ Aaronson, KD Conte, JV Naka, Y Mancini, D Delgado, RM MacGillivray, TE Farrar, DJ Frazier, OH AF Pagani, Francis D. Miller, Leslie W. Russell, Stuart D. John, Ranjit Boyle, Andrew J. Aaronson, Keith D. Conte, John V. Naka, Yoshifumi Mancini, Donna Delgado, Reynolds M. MacGillivray, Thomas E. Farrar, David J. Frazier, O. H. TI Left ventricular assist device therapy with the HeartMate II continuous flow rotary pump as a bridge to heart transplantation SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Pagani, Francis D.; Aaronson, Keith D.] Univ Michigan, Ann Arbor, MI 48109 USA. [Miller, Leslie W.] Georgetown Univ, Washington, DC USA. [Russell, Stuart D.; Conte, John V.] Johns Hopkins Univ, Baltimore, MD USA. [Boyle, Andrew J.] Univ Minnesota, Minneapolis, MN USA. [Naka, Yoshifumi; Mancini, Donna] Columbia Univ, New York, NY USA. [Delgado, Reynolds M.] Texas Heart Inst, Houston, TX 77025 USA. [MacGillivray, Thomas E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farrar, David J.] Thoratec Corp, Pleasanton, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2457 BP 540 EP 541 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302459 ER PT J AU Boyle, AJ Russell, SD Teuteberg, JJ Moazami, N Moore, SA Slaughter, M Farrar, DJ John, R AF Boyle, Andrew J. Russell, Stuart D. Teuteberg, Jeffrey J. Moazami, Nader Moore, Stephanie A. Slaughter, Mark Farrar, David J. John, Ranjit CA HeartMate II Clin Investigators TI Low thromboembolism and pump thrombosis potential of the HeartMate II (HM) LVAD SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Boyle, Andrew J.; John, Ranjit] Univ Minnesota, Minneapolis, MN USA. [Russell, Stuart D.] Johns Hopkins Univ, Baltimore, MD USA. [Teuteberg, Jeffrey J.] Univ Pittsburgh, Pittsburgh, PA USA. [Moazami, Nader] Washington Univ, St Louis, MO USA. [Moore, Stephanie A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Slaughter, Mark] Advocate Christ Med Ctr, Chicago, IL USA. [Farrar, David J.] Thoratec Corp, Pleasanton, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2461 BP 541 EP 542 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302463 ER PT J AU Senior, R Zabalgoitia, M Monaghan, M Main, M Zamorano, JL Tiemann, K Agati, L Weissman, NJ Klein, AL Marwick, TH Ahmad, M DeMaria, AN Becher, H Kaul, S Udelson, JE Wackers, FJ Walovitch, RC Picard, MH AF Senior, Roxy Zabalgoitia, Miguel Monaghan, Mark Main, Michael Zamorano, Jose L. Tiemann, Klaus Agati, Luciano Weissman, Neil J. Klein, Allan L. Marwick, Thomas H. Ahmad, Masood DeMaria, Anthony N. Becher, Harald Kaul, Sanjiv Udelson, James E. Wackers, Frans J. Walovitch, Richard C. Picard, Michael H. TI Accurate detection of coronary artery disease by echocardiography using perflubutane polymer microspheres, a novel contrast agent: Comparison with nuclear perfusion Imaging in two phase three multicenter clinical trials SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association (AHA) CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc (AHA) C1 [Senior, Roxy] Northwick Pk Hosp & Clin Res Ctr, Harrow, Middx, England. [Zabalgoitia, Miguel] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [Monaghan, Mark] Kings Coll Hosp London, London, England. [Main, Michael] Mid Amer Heart Inst, Kansas City, MO USA. [Zamorano, Jose L.] Univ Clin San Carlos, Madrid, Spain. [Tiemann, Klaus] Univ Bonn, D-5300 Bonn, Germany. [Agati, Luciano] Univ Roma La Sapienza, Rome, Italy. [Weissman, Neil J.] Cardiovasc Res Inst, Washington, DC USA. [Klein, Allan L.] Cleveland Clin, Cleveland, OH 44106 USA. [Marwick, Thomas H.] Princess Alexandra Hosp, Brisbane, Qld 4102, Australia. [Ahmad, Masood] Univ Texas, Galveston, TX 77555 USA. [DeMaria, Anthony N.] Univ Calif San Diego, San Diego, CA 92103 USA. [Becher, Harald] John Radcliffe Hosp, Oxford OX3 9DU, England. [Kaul, Sanjiv] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Udelson, James E.] Tufts Univ New England Med Ctr, Boston, MA USA. [Wackers, Frans J.] Yale Univ, Sch Med, New Haven, CT USA. [Walovitch, Richard C.] Acuspehre Inc, Watertown, MA USA. [Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Marwick, Thomas/C-7261-2013 OI Marwick, Thomas/0000-0001-9065-0899 NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2479 BP 546 EP 546 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302481 ER PT J AU Tournoux, F Chan, RC Manzke, R Solis, J Chen-Tournoux, A Gerard, O Heist, EK Allain, P Reddy, VY Weyman, AE Ruskin, JN Picard, MH Singh, JP AF Tournoux, Francois Chan, Raymond C. Manzke, Robert Solis, Jorge Chen-Tournoux, Annabel Gerard, Olivier Heist, E. Kevin Allain, Pascal Reddy, Vivek Y. Weyman, Arthur E. Ruskin, Jeremy N. Picard, Michael H. Singh, Jagmeet P. TI Integrating functional and anatomical information to guide cardiac resynchronization therapy using a computed heart model SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Tournoux, Francois; Solis, Jorge; Chen-Tournoux, Annabel; Heist, E. Kevin; Reddy, Vivek Y.; Weyman, Arthur E.; Ruskin, Jeremy N.; Picard, Michael H.; Singh, Jagmeet P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chan, Raymond C.; Manzke, Robert] Philips Res N Amer, Boston, MA 02114 USA. [Gerard, Olivier; Allain, Pascal] Philips Med Syst, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 553 EP 553 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302509 ER PT J AU Rogers, IS Seneviratne, SK Shapiro, MD Bamberg, F Lehman, SJ Hoffmann, U AF Rogers, Ian S. Seneviratne, Sujith K. Shapiro, Michael D. Bamberg, Fabian Lehman, Sam J. Hoffmann, Udo TI Resting regional left ventricular function as assessed using cardiac 64-slice computed tomography to predict acute coronary syndrome in patients with acute chest pain SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Rogers, Ian S.; Seneviratne, Sujith K.; Shapiro, Michael D.; Bamberg, Fabian; Lehman, Sam J.; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2546 BP 562 EP 563 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302548 ER PT J AU Lipshultz, SE Lipsitz, SR Scully, RE Miller, TL Barry, E Rifai, N Dalton, VM Silverman, LB Colan, SD Asselin, BL Athale, L Clavell, LA Larsen, E Moghrabi, A Samson, Y Schorin, MA Gelber, RD Sallan, SE AF Lipshultz, Steven E. Lipsitz, Stuart R. Scully, Rebecca E. Miller, Tracie L. Barry, Elly Rifai, Nader Dalton, Virginia M. Silverman, Lewis B. Colan, Steven D. Asselin, Barbara L. Athale, Lima Clavell, Luis A. Larsen, Eric Moghrabi, Albert Samson, Yvan Schorin, Marshall A. Gelber, Richard D. Sallan, Stephen E. TI N-terminal pro-brain natriuretic peptide-defined cardiomyopathy in doxorubicin-treated children with acute lymphoblastic leukemia SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lipshultz, Steven E.; Scully, Rebecca E.; Miller, Tracie L.] Univ Miami, Miami, FL 33152 USA. [Lipsitz, Stuart R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Barry, Elly; Dalton, Virginia M.; Silverman, Lewis B.; Gelber, Richard D.; Sallan, Stephen E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rifai, Nader; Colan, Steven D.] Childrens Hosp, Boston, MA 02115 USA. [Asselin, Barbara L.] Univ Rochester, Med Ctr, Rochester, NY 14627 USA. [Athale, Lima] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Clavell, Luis A.] San Jorge Childrens Hosp, San Juan, PR USA. [Larsen, Eric] Maine Childrens Canc Program, Portland, ME USA. [Moghrabi, Albert] St Justine Hosp, Montreal, PQ, Canada. [Samson, Yvan] Univ Quebec, Le Ctr Hosp, Quebec City, PQ, Canada. [Schorin, Marshall A.] Inova Fairfax Hosp Children, Falls Church, VA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2550 BP 563 EP 564 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302552 ER PT J AU Shapiro, MD Nieman, K Nomura, CH Sarwar, A Nasir, K Abbara, S Hoffmann, U Brady, TJ Cury, RC AF Shapiro, Michael D. Nieman, Koeri Nomura, Cesar H. Sarwar, Ammar Nasir, Khurram Abbara, Suhny Hoffmann, Udo Brady, Thomas J. Cury, Ricardo C. TI Cardiac computed tomography for prediction of myocardial viability after reperfused acute myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Shapiro, Michael D.; Nieman, Koeri; Nomura, Cesar H.; Sarwar, Ammar; Nasir, Khurram; Abbara, Suhny; Hoffmann, Udo; Brady, Thomas J.; Cury, Ricardo C.] Massachusetts Gen Hosp, Boston, MA USA. RI Nomura, Cesar/H-1636-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2548 BP 563 EP 563 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302550 ER PT J AU Harris, KM Pastorius, CA Harwood, EM Duval, S Hirsch, AT Carabello, BA AF Harris, Kevin M. Pastorius, Catherine A. Harwood, Eileen M. Duval, Sue Hirsch, Alan T. Carabello, Blase A. TI How do cardiologists and cardiothoracic surgeons treat asymptomatic mitral regurgitation in clinical practice? An international survey SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Harris, Kevin M.; Pastorius, Catherine A.; Harwood, Eileen M.; Duval, Sue; Hirsch, Alan T.] Abbott NW Hosp, Minneapolis Heart Inst Fdn, Minneapolis, MN 55407 USA. [Carabello, Blase A.] Baylor Coll Med, VA Med Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2663 BP 590 EP 590 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302664 ER PT J AU Chen-Tournoux, A Nandigam, V Tournoux, F Solis-Martin, J McCarty, D Orencole, M Hames, M Heist, EK Moore, S Semigran, MJ Ruskin, JN Singh, JP Picard, MH AF Chen-Tournoux, Annabel Nandigam, Veena Tournoux, Francois Solis-Martin, Jorge McCarty, David Orencole, Mary Hames, Maureen Heist, E. Kevin Moore, Stephanie Semigran, Marc J. Ruskin, Jeremy N. Singh, Jagmeet P. Picard, Michael H. TI Severe left ventricular dilation is associated with lack of long-term clinical, response to cardiac resynchronization therapy SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Chen-Tournoux, Annabel; Nandigam, Veena; Tournoux, Francois; Solis-Martin, Jorge; McCarty, David; Orencole, Mary; Hames, Maureen; Heist, E. Kevin; Moore, Stephanie; Semigran, Marc J.; Ruskin, Jeremy N.; Singh, Jagmeet P.; Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2720 BP 603 EP 603 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302721 ER PT J AU Gonen, D Bamberg, F AF Gonen, David Bamberg, Fabian TI 24-hour ambulatory blood pressure and cardiovascular disease: A systematic review and meta-analysis SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Gonen, David] Brigham & Womens Hosp, Boston, MA 02115 USA. [Bamberg, Fabian] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2740 BP 608 EP 608 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302741 ER PT J AU Ouga, S Guella, I Asselta, R Rimoldi, V Peyvandi, F Fetiveau, R Merlini, PA Kathiresan, S Ardissino, D Mannucci, PM AF Ouga, Stefano Guella, Ilaria Asselta, Rosanna Rimoldi, Valeria Peyvandi, Flora Fetiveau, Raffaella Merlini, Pier Angelica Kathiresan, Sekar Ardissino, Diego Mannucci, Pier Mannuccio CA ATVB TI The proprotein convertase subtilisin-kexin type 9 (PCSK9) R46L variant is associated with reduced serum low-density lipoprotein cholesterol in the Italian population SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Ouga, Stefano; Guella, Ilaria; Asselta, Rosanna; Rimoldi, Valeria] Univ Milan, Milan, Italy. [Peyvandi, Flora; Mannucci, Pier Mannuccio] Univ Milan, IRCCS Maggiore Hosp, Mangiagalli & Regina Elena Fdn, Milan, Italy. [Fetiveau, Raffaella] Osped Civil Legnano, Milan, Italy. [Merlini, Pier Angelica] Osped Niguarda Ca Granda, Milan, Italy. [Kathiresan, Sekar] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ardissino, Diego] Univ Parma, Maggiore Hosp, I-43100 Parma, Italy. RI Mannucci, Pier/C-3102-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2739 BP 608 EP 608 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302740 ER PT J AU Chia, S Raffel, C Merchant, F Wackers, FJ Senatore, F Jang, IK AF Chia, Stanley Raffel, Christopher Merchant, Faisal Wackers, Frans J. Senatore, Fred Jang, Ik-Kyung CA EVOLVE Invest TI Which cardiac marker is most useful to predict final infarct size and cardiac function following primary percutaneous coronary intervention for acute myocardial infarction? SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Chia, Stanley; Raffel, Christopher; Merchant, Faisal; Jang, Ik-Kyung] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Wackers, Frans J.] Yale Univ, Sch Med, New Haven, CT USA. [Senatore, Fred] Misubishi Pharma America Inc, Warren, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 2832 BP 630 EP 630 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302831 ER PT J AU Nishida, T Searles, RJ Buys, ES Brouckaert, P Bloch, KD Ichinose, F AF Nishida, Taketurni Searles, Robert J. Buys, Emmanuel S. Brouckaert, Peter Bloch, Kenneth D. Ichinose, Fumito TI Protective role of soluble guanylate cyclase on the outcome of cardiac arrest and resuscitation in mice SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nishida, Taketurni; Searles, Robert J.; Buys, Emmanuel S.; Bloch, Kenneth D.; Ichinose, Fumito] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Brouckaert, Peter] Univ Ghent, B-9000 Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2842 BP 632 EP 632 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302841 ER PT J AU Syed, Z Stultz, CM Scirica, BM Cannon, CP Attia, K Stebletsova, I Mohanavelu, S Stone, PH Guttag, JV AF Syed, Zeeshan Stultz, Collin M. Scirica, Benjamin M. Cannon, Christopher P. Attia, Khaled Stebletsova, Irma Mohanavelu, Satishkumar Stone, Peter H. Guttag, John V. TI Morphological variability: A new electrocardiographic technique for risk stratification after NSTEACS SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Syed, Zeeshan; Stultz, Collin M.; Scirica, Benjamin M.; Cannon, Christopher P.; Attia, Khaled; Stebletsova, Irma; Mohanavelu, Satishkumar] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA USA. [Stone, Peter H.] Brigham & Womens Hosp, Boston, MA USA. [Guttag, John V.] MIT, Cambridge, MA 02139 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 2850 BP 634 EP 634 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394302849 ER PT J AU Angheloiu, G Wright, DM Starling, RC Dec, GW Torre-Amione, G Alexis, J Sheppard, R Mann, D McTiernan, C McNamara, DM AF Angheloiu, George Wright, Dana M. Starling, Randall C. Dec, G. William Torre-Amione, Guillermo Alexis, Jeffrey Sheppard, Richard Mann, Douglas McTiernan, Charles McNamara, Dennis M. TI Circulating Fas in subjects with acute cardiomyopathy and myocarditis: Results from IMAC 1 SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Angheloiu, George; Wright, Dana M.; McTiernan, Charles; McNamara, Dennis M.] Univ Pittsburgh, Pittsburgh, PA USA. [Starling, Randall C.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Dec, G. William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Torre-Amione, Guillermo] Methodist Hosp, Houston, TX 77030 USA. [Alexis, Jeffrey] Univ Rochester, Rochester, NY USA. [Sheppard, Richard] McGill Univ, Montreal, PQ, Canada. [Mann, Douglas] Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 650 EP 650 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303014 ER PT J AU Gulcher, J Gudbjartsson, D Helgadottir, A Gretarsdottir, S Arnar, D Thorleifsson, G Thorgeirsson, G Hillert, J Ma, R Rosand, J Ellinor, P Holm, H Thorsteinsdottir, U Kong, A Stefansson, K AF Gulcher, Jeffrey Gudbjartsson, Daniel Helgadottir, Anna Gretarsdottir, Solveig Arnar, David Thorleifsson, Gudmar Thorgeirsson, Gudmundur Hillert, Jan Ma, Ronald Rosand, Jonathan Ellinor, Patrick Holm, Hilma Thorsteinsdottir, Unnur Kong, Augustine Stefansson, Kari TI Genome-wide association reveals sequence variants on 4q25 that affect the risk of atrial fibrillation and stroke SO CIRCULATION LA English DT Meeting Abstract C1 [Gulcher, Jeffrey; Gudbjartsson, Daniel; Helgadottir, Anna; Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Kong, Augustine; Stefansson, Kari] Decode Genet, Reykjavik, 02114, Iceland. [Arnar, David; Holm, Hilma] Univ Hosp, Reykjavik, Iceland. [Thorgeirsson, Gudmundur] Natl Hosp, Reykjavik, Iceland. [Hillert, Jan] Karolinska Inst, Stockholm, Sweden. [Ma, Ronald] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Rosand, Jonathan; Ellinor, Patrick] Massachusetts Gen Hosp, Boston, MA USA. RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X NR 0 TC 0 Z9 0 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 OCT 16 PY 2007 VL 116 IS 16 SU S BP 652 EP 652 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303023 ER PT J AU Lehtinen, AB Newton-Cheh, C Ziegler, JT Langefeld, CD Freedman, BI Daniel, KR Herrington, DM Bowden, DW AF Lehtinen, Allison B. Newton-Cheh, Christopher Ziegler, Julie T. Langefeld, Carl D. Freedman, Barry I. Daniel, Kurt R. Herrington, David M. Bowden, Donald W. TI Association of NOS1AP genetic variants with QT interval duration in families from the diabetes heart study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Lehtinen, Allison B.; Ziegler, Julie T.; Langefeld, Carl D.; Freedman, Barry I.; Daniel, Kurt R.; Herrington, David M.; Bowden, Donald W.] Wake Forest Univ, Sch Med, Winston Salem, NC USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 652 EP 653 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303022 ER PT J AU Albert, CM Nam, EG Rimm, EB Jin, HW Hunter, DJ MacRae, CA Ellinor, PT AF Albert, Christine M. Nam, Edwin G. Rimm, Eric B. Jin, Hong Wei Hunter, David J. MacRae, Calum A. Ellinor, Patrick T. TI Cardiac sodium channel mutations and sudden cardiac death in women SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Albert, Christine M.; Rimm, Eric B.; Hunter, David J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Nam, Edwin G.; Jin, Hong Wei; MacRae, Calum A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 653 EP 654 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303028 ER PT J AU Kolm, P Boden, WE Spertus, JA Maron, DJ O'Rourke, R Dada, M Zhang, W Hartigan, PM Weintraub, WS AF Kolm, Paul Boden, William E. Spertus, John A. Maron, David J. O'Rourke, Robert Dada, Marcin Zhang, Wei Hartigan, Pamela M. Weintraub, William S. TI Sex differences in quality of life and health status in the COURAGE trial SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Kolm, Paul; Zhang, Wei; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Boden, William E.] Kaleida Hlth, Buffalo, NY USA. [Spertus, John A.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Maron, David J.] Vanderbilt Univ, Nashville, TN USA. [O'Rourke, Robert] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Hartigan, Pamela M.] VA Connecticut Hlth Care Syst, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2983 BP 666 EP 667 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303081 ER PT J AU Kolm, P Boden, WE Spertus, JA Maron, DJ O'Rourke, R Teo, KK Zhao, LP Hartigan, PM Weintraub, WS AF Kolm, Paul Boden, William E. Spertus, John A. Maron, David J. O'Rourke, Robert Teo, Koon K. Zhao, Liping Hartigan, Pamela M. Weintraub, William S. TI Age-related quality of life and health status outcomes of COURAGE trial patients during long-term follow-up SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Kolm, Paul; Zhao, Liping; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Boden, William E.] Kaleida Hlth, Buffalo, NY USA. [Spertus, John A.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. [Maron, David J.] Vanderbilt Univ, Nashville, TN USA. [O'Rourke, Robert] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Teo, Koon K.] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Hartigan, Pamela M.] VA Connecticut Hlth Care Syst, West Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 2984 BP 667 EP 667 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303082 ER PT J AU Maron, DJ Spertus, JA Mancini, GBJ Hartigan, PM Dacia, M Teo, KK O'Rourke, RA Weintraub, WS Boden, WE AF Maron, David J. Spertus, John A. Mancini, G. B. John Hartigan, Pamela M. Dacia, Marcin Teo, Koon K. O'Rourke, Robert A. Weintraub, William S. Boden, William E. TI Impact of PCI in patients with recent onset severe angina or stabilized ACS treated with optimal medical therapy: a COURAGE trial high risk subset SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Maron, David J.] Vandervilt Heart & Vasc Inst, Nashville, TN USA. [Spertus, John A.] Mid Amer Heart Inst, Kansas City, MO USA. [Mancini, G. B. John] Vancouver Hosp & Hlth Syst Sci Ctr, Vancouver, BC, Canada. [Hartigan, Pamela M.] Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Dacia, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON L8S 4L8, Canada. [O'Rourke, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Boden, William E.] SUNY Buffalo, Buffalo Gen Hosp, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 667 EP 667 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303083 ER PT J AU Starling, RC Cooper, LT Dec, GW Boehmer, J Liu, P Pauly, D Gorscan, J Tanabe, M Kip, K McNamara, DM AF Starling, Randall C. Cooper, Leslie T. Dec, G. W. Boehmer, John Liu, Peter Pauly, Daniel Gorscan, John Tanabe, Masaki Kip, Kevin McNamara, Dennis M. CA IMAC II Invest TI Left ventricular diameter predicts recovery in acute cardiomyopathy: Results of the IMAC 2 trial SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Starling, Randall C.] Cleveland Clin, Cleveland, OH 44106 USA. [Cooper, Leslie T.] Mayo Clin, Rochester, MN USA. [Dec, G. W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Boehmer, John] Penn State Univ, University Pk, PA 16802 USA. [Liu, Peter] Univ Toronto, Toronto, ON, Canada. [Pauly, Daniel] Univ Florida, Gainesville, FL 32611 USA. [Gorscan, John; Tanabe, Masaki; Kip, Kevin; McNamara, Dennis M.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 671 EP 672 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303100 ER PT J AU Burjonroppa, SC Varosy, PD Rao, SV Ou, FS Peterson, E Roe, M Shunk, KA AF Burjonroppa, Sukesh C. Varosy, Paul D. Rao, Sunil V. Ou, Fang-Shu Peterson, Eric Roe, Matthew Shunk, Kendrick A. CA Amer Coll Cardiol Natl CDR TI Incidence and predictors of mortality among patients undergoing rescue percutaneous coronary intervention after failed filbrinolysis for ST-elevation myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Burjonroppa, Sukesh C.; Varosy, Paul D.; Shunk, Kendrick A.] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA. [Rao, Sunil V.; Ou, Fang-Shu; Peterson, Eric; Roe, Matthew] Duke Univ, Duke Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3011 BP 674 EP 674 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303109 ER PT J AU Slotwiner, D Alder, S Fuenzalida, C McCowan, R McPherson, C Mela, T Merliss, A Mobarek, S Nayak, H Shoukfeh, F AF Slotwiner, David Alder, Stuart Fuenzalida, Charles McCowan, Ronald McPherson, Craig Mela, Theofanie Merliss, Andrew Mobarek, Sameh Nayak, Hemal Shoukfeh, Fawwah TI The pocket protector study: Use of D-Star (R) flowable hemostat in pulse generator pectoral pockets reduces the rate of clinically relevant hematomas SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Slotwiner, David] Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. [Alder, Stuart] St Paul Heart Ctr, St Paul, MN USA. [Fuenzalida, Charles] Aurora Denver Cardiol Grp, Aurora, CO USA. [McCowan, Ronald] Clin Trials Ctr, Charleston, WV USA. [McPherson, Craig] Bridgeport Hosp, Bridgeport, CT USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merliss, Andrew] Bryan LGH Heart Inst, Lincoln, NE USA. [Mobarek, Sameh] Wake Heart Associates, Raleigh, NC USA. [Nayak, Hemal] Univ Penn, Philadelphia, PA 19104 USA. [Shoukfeh, Fawwah] Texas Cardiac Ctr, Lubbock, TX USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3027 BP 678 EP 678 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303125 ER PT J AU Bamberg, F Koenig, W Kurtz, EG Nichols, JH Trischler, G Nagurney, TJ Seneviratne, S Butler, J Hoffmann, U AF Bamberg, Fabian Koenig, Wolfgang Kurtz, Emily G. Nichols, John H. Trischler, Gerlinde Nagurney, Tobias J. Seneviratne, Sujith Butler, Javed Hoffmann, Udo TI Association between coronary plaque burden as measured by multidetector computed tomography and inflammatory biomarkers patients with acute chest pain SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Bamberg, Fabian; Nichols, John H.; Nagurney, Tobias J.; Seneviratne, Sujith; Butler, Javed; Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Koenig, Wolfgang; Trischler, Gerlinde] Univ Ulm, D-89069 Ulm, Germany. [Kurtz, Emily G.] Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3088 BP 692 EP 692 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303185 ER PT J AU Aggarwal, A Dal, D Rumsfeld, JS Klein, L Roe, MT AF Aggarwal, Atul Dal, David Rumsfeld, John S. Klein, LloydW Roe, Matthew T. CA AMCC NCDR TI Characteristics and outcomes of patients taking warfarin prior to percutaneous coronary intervention SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Aggarwal, Atul] Nebraska Inst Heart, Hastings, NE USA. [Dal, David; Roe, Matthew T.] Duke Clin Res Inst, Durham, NC USA. [Rumsfeld, John S.] Univ Colorado, Denver VA Med Ctr, Denver, CO USA. [Klein, LloydW] Rush Med Coll, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 702 EP 702 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303228 ER PT J AU Chaput, M Hung, J Holmvang, F Guerrero, JL Tournoux, F Sullivan, S Levine, RA AF Chaput, Miguel Hung, Judy Holmvang, Fred Guerrero, J. L. Tournoux, Francois Sullivan, Suzanne Levine, Robert A. TI Inferior infarct patching reduces mitral regurgitation, decreases infarct expansion, and maintains global and remote-zone contractility: An echo-MRI study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Chaput, Miguel; Hung, Judy; Holmvang, Fred; Guerrero, J. L.; Tournoux, Francois; Sullivan, Suzanne; Levine, Robert A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 3170 BP 712 EP 712 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303267 ER PT J AU Messes, E Bel, A Szymanski, C Cohen, I Touchot, B Handschumacher, MD Trinquart, L Desnos, M Carpentier, A Menasche, P Hagege, AA Levine, R AF Messes, Emmanuel Bel, Alain Szymanski, Catherine Cohen, Iris Touchot, Bernard Handschumacher, Marc D. Trinquart, Ludovic Desnos, Michel Carpentier, Alain Menasche, Philippe Hagege, Albert A. Levine, Robert TI Chordal cuffing to relieve mitral leaflet tethering diminishes LV remodeling following chronic inferior myocardial infarction SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Messes, Emmanuel; Bel, Alain; Szymanski, Catherine; Cohen, Iris; Touchot, Bernard] Univ Paris 05, Hop Europpen Georges Pompidou, Fac Med, INSERM,U 633, Paris, France. [Handschumacher, Marc D.; Levine, Robert] Massachusetts Gen Hosp, Harvard Med Sch, Ultrasound Lab, Boston, MA 02114 USA. [Trinquart, Ludovic] Hop Europeen Georges Pompidou, INSERM, CIC 92010, Paris, France. [Desnos, Michel; Carpentier, Alain; Menasche, Philippe; Hagege, Albert A.] Univ Paris 05, Hope Europeen Georges Pompidou, Fac Med, INSERM,U 633, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3171 BP 712 EP 712 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303268 ER PT J AU Jensen, M Jensen, H Smerup, M Levine, RA Yoganathan, AP Nygaard, H Hasenkam, JM Nielsen, SL AF Jensen, Morten Jensen, Henrik Smerup, Morten Levine, Robert A. Yoganathan, Ajit P. Nygaard, Hans Hasenkam, J. Michael Nielsen, Sten L. TI Saddle-shaped mitral valve annuloplasty rings improve leaflet coaptation geometry SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Jensen, Morten; Jensen, Henrik; Smerup, Morten; Nygaard, Hans; Hasenkam, J. Michael; Nielsen, Sten L.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Levine, Robert A.] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. [Yoganathan, Ajit P.] Emory Univ, Georgia Inst Technol, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 3177 BP 713 EP 713 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303274 ER PT J AU Scirica, B Aroesty, J Budaj, A Verheugt, F Karwatowska-Prokopczuk, E Murphy, SA McCabe, CH Morrow, DA AF Scirica, Benjamin Aroesty, Julian Budaj, Andrzej Verheugt, Freek Karwatowska-Prokopczuk, Ewa Murphy, Sabina A. McCabe, Carolyn H. Morrow, David A. TI Baseline clinical risk and recurrent ischemia as detected on continuous ECG (CECG) monitoring in patients with non-ST-Elevation acute coronary syndrome in the MERLIN-TIMI 36 trial SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Scirica, Benjamin; Aroesty, Julian; Murphy, Sabina A.; McCabe, Carolyn H.; Morrow, David A.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Budaj, Andrzej] CMKP Hosp, Warsaw, Poland. [Verheugt, Freek] Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. [Karwatowska-Prokopczuk, Ewa] CV Therapeut, Palo Alto, CA USA. RI Verheugt, F.W.A./H-8105-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 722 EP 722 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303308 ER PT J AU Durst, R Frera, LF Avelar, E Poh, KK Llano, MF Chu, J Rodriguez, LL Mack, MJ Hanzel, G Kodali, SK Hung, J Picard, MH AF Durst, Ronen Frera, Leticia Fernandez Avelar, Erick Poh, Kian K. Llano, Miguel F. Chu, John Rodriguez, Leonardo L. Mack, Michael J. Hanzel, George Kodali, Susheel K. Hung, Judy Picard, Michael H. CA Revival II Invest TI Natural history and predictors of improvement of mitral regurgitation after percutaneous aortic valve replacement SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Durst, Ronen; Frera, Leticia Fernandez; Avelar, Erick; Poh, Kian K.; Llano, Miguel F.; Chu, John; Hung, Judy; Picard, Michael H.] Massachusetts Gen Hosp, Boston, MA USA. [Rodriguez, Leonardo L.] Cleveland Clin, Cleveland, OH USA. [Mack, Michael J.] CSANT, Dallas, TX USA. [Hanzel, George] William Beaumont Hosp, Royal Oak, MI USA. [Kodali, Susheel K.] Columbia Univ, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3384 BP 764 EP 764 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303479 ER PT J AU Hoffmann, U Massaro, JM Fox, CS Manders, E O'Donnell, CJ AF Hoffmann, Udo Massaro, Joseph M. Fox, Caroline S. Manders, Emily O'Donnell, Christopher J. TI Formal comparison between absolute and relative cut points for coronary artery calcification in at intermediate risk community-based men and women: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Massaro, Joseph M.; Fox, Caroline S.; Manders, Emily; O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 790 EP 790 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303584 ER PT J AU Nasir, K Budoff, MJ Shaw, LJ Callister, TO Rumberger, J Sarwar, O Raggi, P Berman, D Blumenthal, RS AF Nasir, Khurram Budoff, Matthew J. Shaw, Leslee J. Callister, Tracy O. Rumberger, John Sarwar, Orakzai Raggi, Poalo Berman, Daniel Blumenthal, Roger S. TI Presence of thoracic aorta calcification predicts all cause mortality independent of traditional cardiovascular risk factors and coronary artery calcification SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Nasir, Khurram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Budoff, Matthew J.] Univ Calif Los Angeles, Torrance, CA USA. [Shaw, Leslee J.; Raggi, Poalo] Emory Univ, Atlanta, GA 30322 USA. [Callister, Tracy O.] EBT Res Fdn, Nashville, TN USA. [Rumberger, John] Ohio State Univ, Columbus, OH 43210 USA. [Sarwar, Orakzai] Univ Pittsburgh, Pittsburgh, PA USA. [Berman, Daniel] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Blumenthal, Roger S.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 790 EP 790 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303583 ER PT J AU Sedlis, SP Jurkovitz, CT Hartigan, PM Lorin, JD Dada, M Maron, DJ Teo, BK O'Rourke, RA Boden, WE AF Sedlis, Steven P. Jurkovitz, Claudine T. Hartigan, Pamela M. Lorin, Jeffrey D. Dada, Mancin Maron, David J. Teo, Koon K. O'Rourke, Robert A. Boden, William E. TI Optimal medical therapy with or without percutaneous coronary intervention for stable coronary artery disease is effective in patients with chronic kidney disease SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Sedlis, Steven P.; Lorin, Jeffrey D.] New York VA Med Ctr, New York, NY USA. [Jurkovitz, Claudine T.] Christiana Care Hlth Syst, Newark, DE USA. [Hartigan, Pamela M.] VA Cooperat Studies Program, West Haven, CT USA. [Dada, Mancin] Hartford Hosp, Hartford, CT 06115 USA. [Maron, David J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada. [O'Rourke, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Boden, William E.] Buffalo Gen Hosp, Western New York Vet Affairs Healthcare Network, Buffalo, NY 14203 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 794 EP 794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303600 ER PT J AU Frutkin, AD Mehta, SK House, J Cohen, DJ Spertus, JA Rumsfeld, J Marso, SP AF Frutkin, Andrew D. Mehta, Sameer K. House, John Cohen, David J. Spertus, John A. Rumsfeld, John Marso, Steven P. TI The use of percutaneous coronary intervention in patients with class I indications for coronary artery bypass graft surgery: Data from the national cardiovascular data registry SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Frutkin, Andrew D.; Mehta, Sameer K.; House, John; Cohen, David J.; Spertus, John A.; Marso, Steven P.] Mid Amer Heart Inst, Kansas City, MO USA. [Rumsfeld, John] Univ Colorado, Hlth Sci Ctr, Denver VA Med Ctr, Denver, CO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3510 BP 795 EP 795 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303603 ER PT J AU Maron, DJ Spertus, JA Kolm, PG Sedlis, SP Mancini, GBJ Hartigan, PM Shaw, LJ Dada, M Teo, KK O'Rourke, RA Boden, WE Weintraub, WS AF Maron, David J. Spertus, John A. Kolm, Paul G. Sedlis, Steven P. Mancini, G. B. John Hartigan, Pamela M. Shaw, Leslee J. Dada, Marcin Teo, Koon K. O'Rourke, Robert A. Boden, William E. Weintraub, William S. TI Quality of life in COURAGE trial patients with diabetes SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Maron, David J.] Vanderbilt Heart & Vasc Inst, Nashville, TN USA. [Spertus, John A.] Mid Amer Heart Inst, Kansas City, MO USA. [Kolm, Paul G.; Weintraub, William S.] Christiana Care Hlth Syst, Newark, DE USA. [Sedlis, Steven P.] VA Hlth Care Syst, New York, NY USA. [Mancini, G. B. John] Vancouver Hosp, Hlth Sci Ctr, Vancouver, BC, Canada. [Hartigan, Pamela M.] VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. [Shaw, Leslee J.] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. [Dada, Marcin] Hartford Hosp, Hartford, CT 06115 USA. [Teo, Koon K.] McMaster Univ, Med Ctr, Hamilton, ON, Canada. [O'Rourke, Robert A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Boden, William E.] SUNY Buffalo, Gen Hosp, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3511 BP 795 EP 795 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303604 ER PT J AU Ho, PM Magid, DJ Shetterly, SM Olson, KL Maddox, TM Peterson, PN Masoudi, FA Rumsfeld, JS AF Ho, P. Michael Magid, David J. Shetterly, Susan M. Olson, Karl L. Maddox, Thomas M. Peterson, Pamela N. Masoudi, Frederick A. Rumsfeld, John S. TI Medication non-adherence is associated with a broad range of adverse outcomes in patients with coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Ho, P. Michael; Maddox, Thomas M.; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Magid, David J.; Shetterly, Susan M.; Olson, Karl L.] Kaiser Permanente, Denver, CO USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3526 BP 798 EP 798 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303619 ER PT J CA Myocardial Infarct Genet C TI Proprotein convertase subtilisin/kexin type 9 (PCSK9) missense variant is reproducibly associated with early-onset myocardial infarction in > 1500 cases and 1500 controls SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 806 EP 806 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303655 ER PT J AU Maddox, TM Reid, KJ Sperlus, JA Parashar, S Krumholz, HM Ho, M Rumsfeld, JS AF Maddox, Thomas M. Reid, Kimberly J. Sperlus, John A. Parashar, Susmita Krumholz, Harlan M. Ho, Michael Rumsfeld, John S. TI The prevalence and factors associated with 1-year angina among post-ml patients SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Maddox, Thomas M.; Ho, Michael; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Denver VAMC, Denver, CO 80202 USA. [Reid, Kimberly J.; Sperlus, John A.] Univ Missouri, Mid Amer Heart Inst, Kansas City, MO 64110 USA. [Parashar, Susmita] Emory Univ, Atlanta, GA 30322 USA. [Krumholz, Harlan M.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 811 EP 811 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303676 ER PT J AU Go, AS Fang, MC Chang, Y Borowsky, LH Pomernacki, NK Singer, DE AF Go, Alan S. Fang, Margaret C. Chang, Yuchiao Borowsky, Leila H. Pomernacki, Niela K. Singer, Daniel E. TI Warfarin therapy, anticoagulation intensity and outcomes in older vs. younger patients with atrial fibrillation: The ATRIA study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Go, Alan S.; Pomernacki, Niela K.] Kaiser Permanente No Calif, Oakland, CA USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 813 EP 813 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303681 ER PT J AU Go, AS Fang, MC Chang, Y Borowsky, LH Pomemacki, NK Udaltsova, N Singer, DE AF Go, Alan S. Fang, Margaret C. Chang, Yuchiao Borowsky, Leila H. Pomemacki, Niela K. Udaltsova, Natalia Singer, Daniel E. TI Defining a threshold of anticoagulation. quality that leads to net clinical benefit in-atrial fibrillation: The ATRIA study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Go, Alan S.; Pomemacki, Niela K.; Udaltsova, Natalia] Kaiser Permanente No Calif, Oakland, CA USA. [Fang, Margaret C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Chang, Yuchiao; Borowsky, Leila H.; Singer, Daniel E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S BP 813 EP 813 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303682 ER PT J AU Asselbergs, FW Mozaffarian, D Katz, R Kestenbaum, B Fried, LF Gottidener, JS Shlipak, MG Siscovick, DS AF Asselbergs, Folkert W. Mozaffarian, Dariush Katz, Ronit Kestenbaum, Bryan Fried, Linda F. Gottidener, John S. Shlipak, Michael G. Siscovick, David S. TI Cystatin C is associated with mitral annular calcification in elderly adults: Results from the cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Asselbergs, Folkert W.] Univ Groningen, Med Ctr, Groningen, Netherlands. [Mozaffarian, Dariush] Harvard Sch Publ Hlth, Boston, MA USA. [Katz, Ronit; Kestenbaum, Bryan; Siscovick, David S.] Univ Washington, Seattle, WA 98195 USA. [Fried, Linda F.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [Gottidener, John S.] St Francis Hosp, Roslyn, NY USA. [Shlipak, Michael G.] Univ Calif San Francisco, Vet Affairs Med Ctr, San Francisco, CA 94143 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3744 BP 851 EP 851 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303835 ER PT J AU Levitzky, YS Massaro, J Fox, CS Manders, E Hoffman, U O'Donnell, CJ AF Levitzky, Yamini S. Massaro, Joe Fox, Caroline S. Manders, Emily Hoffman, Udo O'Donnell, Christopher J. TI Distribution of subclinical aortic atherosclerosis detected as abdominal aortic calcification in the Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Levitzky, Yamini S.] Case Western Reserve Univ, NHLBI, Heart & Vasc Ctr, Framingham Heart Study, Cleveland, OH 44106 USA. [Massaro, Joe] Boston Univ, Dept Math, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Harvard Med Sch, Dept Med, Div Endocrinol Metab & Diabet,NHLBI, Boston, MA USA. [Manders, Emily] NHLBI, Framingham Heart Study, Framingham, MA USA. [Hoffman, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET CT Program, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Harvard Med Sch, NHLBI, Dept Med,Cardiol Div,Framingham Heart Study, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 3754 BP 853 EP 854 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303845 ER PT J AU Parikh, N Hwang, SJ Larson, MG Hoffmann, U Levy, D O'Donnell, CJ Fox, CS AF Parikh, Nisha Hwang, Shih-Jen Larson, Martin G. Hoffmann, Udo Levy, Daniel O'Donnell, Christopher J. Fox, Caroline S. TI The association of indices of kidney function with coronary artery and abdominal aortic calcification: The Framingham Offspring study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Parikh, Nisha] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Hwang, Shih-Jen; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Larson, Martin G.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 MA 3755 BP 854 EP 854 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303846 ER PT J AU Januzzi, J Bajwa, E Gong, M Thompson, BT Christiani, D AF Januzzi, James Bajwa, Ednan Gong, Michelle Thompson, B. T. Christiani, David TI NT-proBNP elevations in adult respiratory distress syndrome strongly predict morbidity and mortality: An analysis from the molecular epidemiology of ARDS study SO CIRCULATION LA English DT Meeting Abstract CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc C1 [Januzzi, James; Bajwa, Ednan; Gong, Michelle; Thompson, B. T.; Christiani, David] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 SU S MA 20 BP 927 EP 927 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223TD UT WOS:000250394303907 ER PT J AU Vlahakes, GJ AF Vlahakes, Gus J. TI Mechanical heart valves - The test of time... SO CIRCULATION LA English DT Editorial Material ID REPLACEMENT C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA 02114 USA. RP Vlahakes, GJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, 55 Fruit St,COX652, Boston, MA 02114 USA. EM vlahakes.gus@mgh.harvard.edu NR 9 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 16 PY 2007 VL 116 IS 16 BP 1759 EP 1760 DI 10.1161/CIRCULATIONAHA.107.729582 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 223PW UT WOS:000250385800002 PM 17938299 ER PT J AU Givertz, MM Massie, BM Fields, TK Pearson, LL Dittrich, HC AF Givertz, Michael M. Massie, Barry M. Fields, Tara K. Pearson, Leeanne L. Dittrich, Howard C. CA CKI-201 CKI-202 Investigators TI The effects of KW-3902, an adenosine A1-receptor antagonist, on diuresis and renal function in patients with acute decompensated heart failure and renal impairment or diuretic resistance SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RECEPTOR ANTAGONIST; ANESTHETIZED DOGS; ADENOSINE; ACTIVATION; OUTCOMES; IMPACT; MODEL; CREATININE; EPILEPSY; KIDNEY AB Objectives: This study sought to evaluate the dose-dependent effects of adenosine A1-receptor blockade on diuresis and renal function in patients with acute decompensated heart failure (ADHF) and renal impairment or diuretic resistance. Background: Intravenous loop diuretics are the mainstay of therapy for patients with ADHF. Treatment, however, may be complicated by diuretic resistance and/or worsening renal function. Methods: We carried out a pair of randomized, double-blind, placebo-controlled, proof-of-concept studies in 2 clinically challenging ADHF populations. Results In the ADHF protocol, 146 patients with volume overload and an estimated creatinine clearance (CrCI) of 20 to 80 ml/mln were randomized to placebo or I of 4 doses of KW-3902 (rolofylline) infused over 2 h daily for up to 3 days. On day 1, KW-3902 monotherapy increased urine output during the first 6 h (445, 531, 631, and 570 ml in the 2.5-, 15-, 30-, and 60-mg groups, respectively) compared with placebo (374 ml; p = 0.02). On day 2, serum creatinine decreased in all KW-3902 groups and increased with placebo (p = 0.04). By day 4 or day of discharge if earlier, intravenous furosemide administration tended to be lower in the KW-3902 groups compared with placebo (p = 0.10). In the diuretic-resistant protocol, 35 patients with an average CrCl of 34 ml/min were randomized to a single infusion of placebo, 10, 30, or 60 mg of KW-3902. Compared with placebo, KW-3902 increased hourly urine volume and estimated CrCl with peak effects occurring at 2 to 3 h and at 24 h, respectively. Adverse events were not different between placebo and KW-3902. Conclusions: In patients with ADHF and volume overload, KW-3902, an adenosine A1-receptor antagonist, enhances the response to loop diuretics and may have a renal protective effect. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. San Francisco VA Med Ctr, Div Cardiol, San Francisco, CA USA. NovaCardia Inc, San Diego, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP Givertz, MM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM mgivertz@partners.org NR 21 TC 104 Z9 111 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 16 PY 2007 VL 50 IS 16 BP 1551 EP 1560 DI 10.1016/j.jacc.2007.07.019 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 223ZX UT WOS:000250415900005 PM 17936154 ER PT J AU Meschia, JF Rosand, J AF Meschia, James F. Rosand, Jonathan TI Fragile vessels - Handle with care SO NEUROLOGY LA English DT Editorial Material ID MUTATIONS C1 Mayo Clin, Dept Neurol, Div Cerebrovasc Dis, Jacksonville, FL 32224 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. RP Meschia, JF (reprint author), Mayo Clin, Cannaday Bldg,2 E,4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM meschia.james@mayo.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 16 PY 2007 VL 69 IS 16 BP 1560 EP 1561 DI 10.1212/01.wnl.0000295992.00845.5a PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 221AM UT WOS:000250198800001 PM 17938365 ER PT J AU Ghaffari, R Aranyosi, AJ Freeman, DM AF Ghaffari, Roozbeh Aranyosi, Alexander J. Freeman, Dennis M. TI Longitudinally propagating traveling waves of the mammalian tectorial membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cochlear mechanics; dynamic mechanical properties; longitudinal; mechanical coupling ID OUTER HAIR-CELLS; COCHLEAR MICROMECHANICS; MECHANICAL RESPONSES; BUNDLE MOTION; INNER-EAR; IN-VITRO; HEARING; MOUSE; AMPLIFICATION; TRANSDUCTION AB Sound-evoked vibrations transmitted into the mammalian cochlea produce traveling waves that provide the mechanical tuning necessary for spectral decomposition of sound. These traveling waves of motion that have been observed to propagate longitudinally along the basilar membrane (BM) ultimately stimulate the mechano-sensory receptors. The tectorial membrane (TM) plays a key role in this process, but its mechanical function remains unclear. Here we show that the TM supports traveling waves that are an intrinsic feature of its visco-elastic structure. Radial forces applied at audio frequencies (2-20 kHz) to isolated TM segments generate longitudinally propagating waves on the TM with velocities similar to those of the BM traveling wave near its best frequency place. We compute the dynamic shear storage modulus and shear viscosity of the TM from the propagation velocity of the waves and show that segments of the TM from the basal turn are stiffer than apical segments are. Analysis of loading effects of hair bundle stiffness, the limbal attachment of the TM, and viscous damping in the subtectorial space suggests that TM traveling waves can occur in vivo. Our results show the presence of a traveling wave mechanism through the TM that can functionally couple a significant longitudinal extent of the cochlea and may interact with the BM wave to greatly enhance cochlear sensitivity and tuning. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Freeman, DM (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave,Room 36-889, Cambridge, MA 02139 USA. EM freeman@mit.edu OI Aranyosi, Alexander/0000-0002-8133-5026 FU NIDCD NIH HHS [R01 DC000238, R01-DC00238] NR 48 TC 99 Z9 102 U1 1 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 16 PY 2007 VL 104 IS 42 BP 16510 EP 16515 DI 10.1073/pnas.0703665104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223MA UT WOS:000250373400024 PM 17925447 ER PT J AU Chopra, V Fox, JH Lieberman, G Dorsey, K Matson, W Waldmeier, P Housman, DE Kazantsev, A Young, AB Hersch, S AF Chopra, Vanita Fox, Jonathan H. Lieberman, Greg Dorsey, Kathryn Matson, Wayne Waldmeier, Peter Housman, David E. Kazantsev, Aleksey Young, Anne B. Hersch, Steven TI A small-molecule therapeutic lead for Huntington's disease: Preclinical pharmacology and efficacy of C2-8 in the R6/2 transgenic mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; COENZYME Q(10); IN-VIVO; MODEL; MICE; SYMPTOMS; CREATINE; SURVIVAL; CHEMOTHERAPY; AGGREGATION AB Huntington's disease (HID) is a progressive neuroclegenerative disease caused by a glutamine expansion within huntingtin protein. The exact pathological mechanisms determining disease onset and progression remain unclear. However, aggregates of insoluble mutant huntingtin (mhtt), a hallmark of HID, are readily detected within neurons in HID brain. Although aggregated polyglutamines may not be inherently toxic, they constitute a biomarker for mutant huntingtin useful for developing therapeutics. We previously reported that the small molecule, C2-8, inhibits polyglutamine aggregation in cell culture and brain slices and rescues degeneration of photoreceptors in a Drosophila model of HID. In this study, we assessed the therapeutic potential of C2-8 in the R6/2 mouse model of HD, which has been used to provide proof-of-concept data in considering whether to advance therapies to human HID. We show that, at nontoxic doses, C2-8 penetrates the blood-brain barrier and is present in brain at a high concentration. C2-8-treated mice showed improved motor performance and reduced neuronal atrophy and had smaller huntingtin aggregates. There have been no prior drug-like, non-toxic, brain-penetrable aggregation inhibitors to arise from cell-based high-throughput screens for reducing huntingtin aggregation that is efficacious in preclinical in vivo models. C2-8 provides an essential tool to help elucidate mechanisms of neuroclegeneration in HD and a therapeutic lead for further optimization and development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Charlestown, MA 02129 USA. Bedford Vet Affairs Med Ctr, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Boston Univ, Sch Med, Boston, MA 02180 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Housman, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, B114 16th St, Charlestown, MA 02129 USA. EM dhousman@mit.edu NR 30 TC 69 Z9 69 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 16 PY 2007 VL 104 IS 42 BP 16685 EP 16689 DI 10.1073/pnas.0707842104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 223MA UT WOS:000250373400054 PM 17925440 ER PT J AU Jiang, SS Rasmussen, RA Nolan, KM Frankel, FR Lieberman, J McClure, HM Williams, KM Babu, US Raybourne, RB Strobert, E Ruprecht, RM AF Jiang, Shisong Rasmussen, Robert A. Nolan, Katrina M. Frankel, Fred R. Lieberman, Judy McClure, Harold M. Williams, Kristina M. Babu, Uma S. Raybourne, Richard B. Strobert, Elizabeth Ruprecht, Ruth M. TI Live attenuated Listeria monocytogenes expressing HIV Gag: Immunogenicity in rhesus monkeys SO VACCINE LA English DT Article DE rhesus monkey; Listeria monocytogenes; D-alanine; cellular immunity; vaccine ID HUMAN-IMMUNODEFICIENCY-VIRUS; CELLULAR IMMUNE-RESPONSE; MONOCLONAL-ANTIBODIES; IN-VIVO; NEONATAL MACAQUES; VACCINE VECTOR; T-CELLS; INDUCTION; INFECTION; MICE AB Induction of strong cellular immunity will be important for AIDS vaccine candidates. Natural infection with wild-type Listeria itionocyto-genes (Lm), an orally transmitted organism, is known to generate strong cellular immunity, thus raising the possibility that live attenuated Lm could serve as a vaccine vector. We sought to examine the potential of live attenuated Lm to induce cellular immune responses to HIV Gag. Rhesus macaques were immunized with Lmdd-gag that expresses HIV gag and lacks two genes in the D-alanine (D-ala) synthesis pathway. Without this key component of the bacterial cell wall, vaccine vector replication critically depends on exogenous D-ala. Lmdd-gag was given to animals either solely orally or by oral priming followed by intramuscular (i.m.) boosting; D-ala was co-administered with all vaccinations. Lmdd-gag and D-ala were well tolerated. Oral priming/oral boosting induced (Gag-specific cellular immune responses, whereas oral priming/i.m. boosting induced systemic as well as mucosal anti-Gag antibodies. These. results suggest that the route of vaccination may bias anti-Gag immune responses either towards T-helper type 1 (Th 1) or Th2 responses; overall, our data show that live attenuated, recombinant Lmdd-gag is safe and immunogenic in primates. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Div Res Resources & Microbiol & Immunol, Atlanta, GA 30329 USA. US FDA, Ctr Food Safety & Appl Nutr, Immunobiol Branch, Laurel, MD 20708 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu RI Lieberman, Judy/A-2717-2015 FU NCRR NIH HHS [P51 RR000165, P51 RR000165-47, RR-00165]; NIAID NIH HHS [P01 AI054558, P01 AI054558-010003, R21 AI054183, R21 AI054183-01] NR 54 TC 26 Z9 28 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 16 PY 2007 VL 25 IS 42 BP 7470 EP 7479 DI 10.1016/j.vaccine.2007.08.013 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 227JV UT WOS:000250653900024 PM 17854955 ER PT J AU Huang, E Esrailian, E Spiegel, BMR AF Huang, E. Esrailian, E. Spiegel, B. M. R. TI The cost-effectiveness and budget impact of competing therapies in hepatic encephalopathy - a decision analysis SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PORTAL-SYSTEMIC ENCEPHALOPATHY; PROTON PUMP INHIBITORS; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND; CIRRHOTIC-PATIENTS; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; TREATMENT ALTERNATIVES; LIVER-TRANSPLANTATION; PROGNOSTIC INDICATORS AB Background Treatment options for hepatic encephalopathy have disparate risks and benefits. Non-absorbable disaccharides and neomycin are limited by uncertain efficacy and common dose-limiting side effects. In contrast, rifaximin is safe and effective in hepatic encephalopathy, but is more expensive. Methods We conducted a decision analysis to calculate the cost-effectiveness of six strategies in hepatic encephalopathy: (i) no hepatic encephalopathy treatment, (ii) lactulose monotherapy, (iii) lactitol monotherapy, (iv) neomycin monotherapy, (v) rifaximin monotherapy and (vi) up-front lactulose with crossover to rifaximin if poor response or intolerance of lactulose ('rifaximin salvage'). The primary outcome was cost per quality-adjusted life-year gained. Results Under base-case conditions, 'do nothing' was least effective and rifaximin salvage was most effective. Lactulose monotherapy was least expensive, and rifaximin monotherapy was most expensive. When balancing cost and effectiveness, lactulose monotherapy and rifaximin salvage dominated alternative strategies. Compared to lactulose monotherapy, rifaximin salvage cost an incremental US$2315 per quality-adjusted life-year-gained. The cost of rifaximin had to fall below US$1.03/tab in order for rifaximin monotherapy to dominate lactulose monotherapy. Conclusions Rifaximin monotherapy is not cost-effective in the treatment of chronic hepatic encephalopathy at current average wholesale prices. However, a hybrid salvage strategy, reserving rifaximin for lactulose-refractory patients, may be highly cost-effective. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Outcomes Res & Educ, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Ctr Outcomes Res & Educ, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115 Rm 215, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu FU NIDDK NIH HHS [P30 DK 041301-17] NR 98 TC 37 Z9 39 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT 15 PY 2007 VL 26 IS 8 BP 1147 EP 1161 DI 10.1111/j.1365-2036.2007.03464.x PG 15 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 213XD UT WOS:000249699700007 PM 17894657 ER PT J AU Kumar, R Lee, TT Jeremias, A Ruisi, CP Sylvia, B Magallon, J Kirtane, AJ Bigelow, B Abrahamson, M Pinto, DS Ho, KKL Cohen, DJ Carrozza, JP Cutlip, DE AF Kumar, Ramon Lee, Tobias T. Jeremias, Allen Ruisi, Christopher P. Sylvia, Brett Magallon, Jorge Kirtane, Ajay J. Bigelow, Brian Abrahamson, Martin Pinto, Duane S. Ho, Kalon K. L. Cohen, David J. Carrozza, Joseph P., Jr. Cutlip, Donald E. TI Comparison of outcomes using Sirolimus-Eluting stenting in diabetic versus nondiabetic patients with comparison of insulin versus non-insulin therapy in the diabetic patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PLATELET DYSFUNCTION; CORONARY ANGIOPLASTY; CLINICAL-OUTCOMES; NATIONAL HEART; MELLITUS; REGISTRY; RESTENOSIS; LESIONS; TRIALS; INJURY AB The effect of insulin therapy on adverse cardiovascular outcomes in diabetic patients has been debated and a reduced benefit in clinical restenosis outcomes after sirolimus stenting has been reported among diabetic patients requiring insulin therapy. We analyzed 297 diabetic patients receiving sirolimus-eluting stents, including 115 (39%) on insulin therapy, and compared outcomes with 541 nondiabetic patients treated consecutively during the same interval. The rates of target lesion revascularization (9.5% vs 3.5%, p = 0.003) and cardiac death or myocardial infarction (MI, 7.1% vs 3.1%, p = 0.012) were significantly higher for diabetic patients. Insulin treatment was independently associated with increased risk for target lesion revascularization (odds ratio [OR] 2.48, 95% confidence interval [CI] 1.22 to 5.00) and cardiac death or MI (hazard ratio [HR] 2.85, 95% Cl 1.41 to 5.77), whereas the adjusted risk for diabetic patients not treated with insulin was not significantly different from patients without diabetes-for target lesion revascularization (OR 1132, 95% Cl 0.66 to 2.62) or cardiac death or MI (HR 1.04, 95% Cl 0.50 to 2.17). In conclusion, diabetes rriellitus is associated with increased risk for target lesion revascularization and cardiac death or MI after receiving sirolimus-eluting stenting, and is significantly exaggerated by the requirement for insulin therapy. (C) 2007 Elsevier Inc. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, New York, NY 10003 USA. Joslin Clin, Boston, MA USA. RP Cutlip, DE (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiol, New York, NY 10003 USA. EM dcutlip@bidmc.harvard.edu NR 19 TC 33 Z9 34 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2007 VL 100 IS 8 BP 1187 EP 1191 DI 10.1016/j.amjcard.2007.05.038 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 222SH UT WOS:000250316900001 PM 17920355 ER PT J AU Alexeeff, SE Litonjua, AA Sparrow, D Vokonas, PS Schwartz, J AF Alexeeff, Stacey E. Litonjua, Augusto A. Sparrow, David Vokonas, Pantel S. Schwartz, Joel TI Statin use reduces decline in lung function - VA normative aging study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE statins; lung function; FVC; FEV(1); smoking ID C-REACTIVE PROTEIN; OBSTRUCTIVE PULMONARY-DISEASE; COENZYME-A REDUCTASE; SYSTEMIC INFLAMMATION; GENERAL-POPULATION; NADPH OXIDASE; HOST-DEFENSE; MORTALITY; PRAVASTATIN; ASSOCIATION AB Rationale Decreased lung function has been linked to increased inflammation and oxidative stress. Statins have demonstrated anti-inflammatory and antioxidant properties. Objectives: We investigated the effect of statin use on decline in lung function in the elderly, and whether smoking modified this effect. Methods: Our study population included 2,136 measurements on 803 elderly men from the Normative Aging Study whose lung function (FVC and FEV(1)) was measured two to four times between 1995 and 2005. Subjects indicated statin use and smoking history at each visit. We used mixed linear models to estimate the effects of each covariate, adjusting for subject and possible confounders. Measurements and Main Results: For those not using statins, the estimated decline in FEV(1) was 23.9 ml/year (95% confidence interval [Cl], -27.8 to -20.1 ml/yr), whereas those taking statins had an estimated 10.9-ml/year decline in FEV(1) (95% Cl, -16.9 to -5.0 ml/ yr). We also examined the effect of statins with smoking by dividing the cohort into four groups: never-smokers, longtime quitters (quit 10 yr ago), recent quitters (quit < 10 yr ago), and current smokers. We found a significant three-way interaction between time since first visit, statin use, and smoking status (P < 0.001). Within each smoking category, the effect of statins was always estimated to be beneficial, but the size of the improvement in the decline rate varied among smoking groups. We found similar results for FVC decline. Conclusions: Our results indicate that statin use attenuates decline in lung function in the elderly, with the size of the beneficial effect modified by smoking status. C1 Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Boston Univ, Sch Med, VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. RP Alexeeff, SE (reprint author), Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Dept Environm Hlth, Landmark Ctr W,415,401 Pk Dr, Boston, MA 02215 USA. EM sackerma@hsph.harvard.edu FU NIEHS NIH HHS [ES0002, ES015172-01] NR 31 TC 105 Z9 110 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2007 VL 176 IS 8 BP 742 EP 747 DI 10.1164/rccm.200705-6560C PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 220DF UT WOS:000250136400005 PM 17673694 ER PT J AU Villar, J Perez-Mendez, L Lopez, J Belda, J Blanco, J Saralegui, I Suarez-Sipmann, F Lopez, J Lubillo, S Kacmarek, RM AF Villar, Jesus Perez-Mendez, Lina Lopez, Jose Belda, Javier Blanco, Jesus Saralegui, Inaki Suarez-Sipmann, Fernando Lopez, Julia Lubillo, Santiago Kacmarek, Robert M. CA HELP Network TI An early PEEP/Fio(2) trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; acute lung injury; positive end-expiratory pressure; standard ventilator settings; definitions; inclusion criteria ID RANDOMIZED CONTROLLED-TRIAL; END-EXPIRATORY PRESSURE; CLINICAL-TRIAL; VENTILATORY STRATEGY; OXYGEN; FAILURE; VOLUME; DEFINITIONS; MORTALITY; SEVERITY AB Rationale. Current American-European Consensus Conference definitions for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inadequate for inclusion into clinical trials due to the lack of standardization for measuring the oxygenation defect. Objectives: We questioned whether an early assessment of oxygenation on specific ventilator settings would identify patients with established ARDS (persisting over 24 h). Methods: At the time of meeting ARDS criteria (Day 0) and 24 hours later (Day 1), arterial blood gases were obtained on standard ventilator settings, V-T 7 ml/kg predicted body weight plus the following positive end-expiratory pressure (PEEP) and F-Io2 settings in sequence: (1) PEEP >= 5 cm H2O and FIo2 >= 0.5, (2) PEEP >= 5 cm H2O and F-Io2 1.0, (3) PEEP >= 10 cm H2O and F-Io2 >= 0.5, and (4) PEEP >= 10 cm H2O and F-Io2 1.0. Measurements and Main Results: One hundred seventy patients meeting ARDS criteria (Pa-o2/F-Io2 128 +/- 33 mm Hg) were enrolled. Overall hospital mortality was 34.1%a. The standard ventilator settings that best identified patients with established ARDS and predicted differences in intensive care unit (ICU) mortality were PEEP >= 10 cm H2O and Floe >= 0.5 at Day 1 (P = 0.0001). Only 99 (58.2%) patients continued to meet ARDS criteria (Pao(2)/F-Io2, 155.8 +/- 29.8 mm Hg; ICU mortality, 45.5%), whereas 55 patients were reclassified as having ALI (Pa-o2/F-Io2, 246.5 +/- 25.6 mm Hg; ICU mortality, 20%) and 16 patients as having acute respiratory failure (Pa-o2/F-Io2, 370 +/- 54 mm Hg; ICU mortality, 6.3%) (P = 0.0001) on these settings. Conclusions: Patients meeting current American-European Consensus Conference ARDS criteria may have highly variable levels of lung injury and outcomes. A systematic method of assessing severity of lung injury is required for enrollment of patients with ARDS into randomized controlled trials. C1 Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Univ Dr Negrin, Multidisciplinary Organ Dyfunct Evaluat Res Netwo, Las Palmas Gran Canaria, Canary Isl, Spain. Hosp Univ NS Candelaria, Div Clin & Genet Epidemiol, Tenerife, Spain. Hosp Gen Leon, Intens Care Unit, Leon, Spain. Hosp Clin Valencia, Dept Anesthesia, Valencia, Spain. Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. Hosp Santiago Apostol, Vitoria, Spain. Fdn Jimenez Diaz, Intens Care Unit, Madrid, Spain. Hosp Univ La Paz, Intens Care Unit, Madrid, Spain. Hosp Univ NS Candelaria, Intens Care Unit, Santa Cruz De Teneriffe, Spain. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, 55 Fruit St,Ellison 401, Boston, MA 02114 USA. EM rkacmarek@partners.org NR 35 TC 132 Z9 146 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2007 VL 176 IS 8 BP 795 EP 804 DI 10.1164/rccm.200610-15340C PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 220DF UT WOS:000250136400012 PM 17585106 ER PT J AU Bedri, S Cizek, SM Rastarhuyeva, I Stone, JR AF Bedri, Shahinaz Cizek, Stephanie M. Rastarhuyeva, Iryna Stone, James R. TI Regulation of protein kinase CK1 alpha LS by dephosphorylation in response to hydrogen peroxide SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE casein kinase; protein kinase CK1; hydrogen peroxide; reactive oxygen species; RNA binding proteins; protein kinases; hnRNP-C; dephosphorylation; Pre-mRNA processing ID NUCLEAR RIBONUCLEOPROTEIN C1/C2; MESSENGER-RNA-BINDING; I-ALPHA; PHYSIOLOGICAL LEVELS; CELL-PROLIFERATION; INDUCED APOPTOSIS; SPLICED ISOFORMS; MITOTIC SPINDLE; CASEIN; PHOSPHORYLATION AB Low levels of hydrogen peroxide (H2O2) are mitogenic to mammalian cells and stimulate the hyperphosphorylation of heterogeneous nuclear ribonucleoprotein C (hnRNP-C) by protein kinase CK 1 alpha. However, the mechanisms by which CK 1 alpha is regulated have been unclear. Here it is demonstrated that low levels of H2O2 stimulate the rapid dephosphorylation of CK 1 alpha LS, a nuclear splice form of CK 1 alpha. Furthermore, it is demonstrated that either treatment of endothelial cells with H2O2, or dephosphorylation of CK 1 alpha LS in vitro enhances the association of CK 1 alpha LS with hnRNP-C. In addition, dephosphorylation of CK 1 alpha LS in vitro enhances the kinase's ability to phosphorylate hnRNP-C. While CK 1 alpha( appears to be present in all metazoans, analysis of CK 1 alpha genomic sequences from several species reveals that the alternatively spliced nuclear localizing L-insert is unique to vertebrates, as is the case for hnRNP-C. These observations indicate that CK 1 alpha LS and hnRNP-C represent conserved components of a vertebrate-specific H2O2-responsive nuclear signaling pathway. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Stone, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Simches Res Bldg,Room 8236,185 Cambridge St CPZN, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [HL074324, R01 HL074324, R01 HL074324-01, R01 HL074324-02, R01 HL074324-03, R01 HL074324-04, R01 HL074324-05] NR 49 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 15 PY 2007 VL 466 IS 2 BP 242 EP 249 DI 10.1016/j.abb.2007.06.010 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 219EO UT WOS:000250067700011 PM 17626781 ER PT J AU Johnson, SR Goek, ON Singh-Grewal, D Vlad, SC Feldman, BM Felson, DT Hawker, GA Singh, JA Solomon, DH AF Johnson, Sindhu R. Goek, Oemer-Necmi Singh-Grewal, Davinder Vlad, Steven C. Feldman, Brian M. Felson, David T. Hawker, Gillian A. Singh, Jasvinder A. Solomon, Daniel H. TI Classification criteria in rheumatic diseases: A review of methodologic properties SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Review DE classification criteria; methodologic properties; rheumatic disease ID JUVENILE IDIOPATHIC ARTHRITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AMERICAN-HEART-ASSOCIATION; LONG-TERM MANAGEMENT; DIAGNOSTIC-CRITERIA; POLYMYALGIA RHEUMATICA; PSORIATIC-ARTHRITIS; KAWASAKI-DISEASE; INFLAMMATORY MYOPATHIES; CARDIOVASCULAR-DISEASE AB Objective. To identify classification criteria for the rheumatic diseases and to evaluate their measurement properties and methodologic rigor using current measurement standards. Methods. We performed a systematic review of published literature and evaluated criteria sets for stated purpose, derivation and validation sample characteristics, methods of criteria generation and reduction, and consideration of validity, and reliability. Results. We identified 47 classification criteria sets encompassing 13 conditions. Approximately 50% of the criteria sets were developed based on expert opinion rather than patient data. Of the 47 criteria sets, control samples were derived from patients with rheumatic disease in 15 (32%) sets, from patients with nonrheumatic diseases in 4 (9%) sets, and from healthy participants in 2 (4%) sets. Where patient data were used, the number of cases ranged from 20-588 and the number of controls from 50-787. In only 1 (2%) criteria set was there a distinct separation between investigators who derived the criteria set and clinicians who provided cases and controls. Authors commented on the need for individual criterion to be reliable in 5 (11%) sets, precise in 5 (11%) sets; authors noted the importance of content validity in 12 (26%) sets, and construct validity in 12 (26%) sets. Conclusion. The variation in methodologic rigor used in sample selection affects the validity and reliability of the criteria sets in different clinical and research settings. Despite potential deficiencies in the methods used for some criteria development, the sensitivity and specificity of many criteria sets is moderate to strong. C1 Univ Hlth Network, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Childrens Hosp Westmead, Sydney, NSW, Australia. Boston Univ, Med Ctr, Boston, MA USA. Womens Coll Hosp, Toronto, ON M5S 1B2, Canada. VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN 55455 USA. Brigham & Womens Hosp, Boston, MA 02120 USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org RI Feldman, Brian/A-8586-2011; OI Felson, David/0000-0002-2668-2447 FU NIA NIH HHS [AG-028066]; NIAMS NIH HHS [AR-47785, AR-48616] NR 108 TC 44 Z9 48 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2007 VL 57 IS 7 BP 1119 EP 1133 DI 10.1002/art.23018 PG 15 WC Rheumatology SC Rheumatology GA 221ZF UT WOS:000250265200004 PM 17907227 ER PT J AU Diaz-Torne, C Schumacher, HR Yu, X Gomez-Vaquero, C Dai, L Chen, LX Clayburne, G Einhorn, E Sachdeva, RM Singh, JA Pessler, F AF Diaz-Torne, C. Schumacher, H. R. Yu, X. Gomez-Vaquero, C. Dai, L. Chen, L. X. Clayburne, G. Einhorn, E. Sachdeva, R. M. Singh, J. A. Pessler, F. TI Absence of histologic evidence of synovitis in patients with Gulf War veterans' illness with joint pain SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID HISTOPATHOLOGICAL GRADING SYSTEM; RHEUMATOID-ARTHRITIS; SQUALENE; TISSUE; HEALTH AB Objective. An unexplained multisymptom illness, Gulf War veterans' illness (GWVI), has been described among allied force veterans of the first Gulf War (1990-1991). It has been proposed that some of its symptoms reflect an immune dysfunction, and rheumatologic symptoms including joint pain and stiffness are reported frequently. However, it is unknown whether synovial inflammation causes the articular symptoms. We examined synovial tissue from individuals with GWVI and joint pain for evidence of inflammation. Methods. We compared synovial biopsy samples from 6 individuals with GWVI and joint pain with samples from 9 clinically asymptomatic controls (hematoxylin and eosin [H&E] stains only) and biopsy samples or surgically obtained specimens from 10 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Inflammatory changes were quantified in H&E stained sections with a modified synovitis score by immunostaining for CD3, CD20, CD38, CD68, Ki-67, and von Willebrand factor, and with a composite inflammation score based on these markers. Results. Normal histology was seen in the GWVI specimens, except for mild focal lining hyperplasia and rare low-grade perivascular infiltrates in 1 specimen each. Mean SEM synovitis scores were lowest and nearly identical in control (1.38 +/- 0.30) and GWVI specimens (1.41 +/- 0.29), intermediate in OA specimens (2.64 +/- 0.39), and highest in RA specimens (6.0 +/- 0.19). Likewise, inflammatory cells, cell division, vascular density, and composite inflammation score were lowest in the GWVI specimens. Conclusion. Despite significant joint pain, the GWVI synovia did not differ from normal controls. These results agree with other studies that have failed to document inflammatory or immunologic etiologies in GWVI. C1 Childrens Hosp Philadelphia, Div Rheumatol, Philadelphia, PA 19104 USA. Hosp Univ Bellvitge, Barcelona, Spain. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Tradit Chinese Med Western Med Hosp, Cangzhou, Hebei, Peoples R China. Sun Yat Sen Univ, Guangzhou, Peoples R China. Univ Minnesota, Minneapolis, MN USA. RP Pessler, F (reprint author), Childrens Hosp Philadelphia, Div Rheumatol, 3405 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM pessler@email.chop.edu OI Cesar, Diaz-Torne/0000-0001-6275-7699; singh, jasvinder/0000-0003-3485-0006 FU NCI NIH HHS [T32-CA-09140]; NIAMS NIH HHS [T32-AR-007442] NR 25 TC 15 Z9 15 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2007 VL 57 IS 7 BP 1316 EP 1323 DI 10.1002/art.23006 PG 8 WC Rheumatology SC Rheumatology GA 221ZF UT WOS:000250265200027 PM 17907214 ER PT J AU Wilens, TE Decker, MW AF Wilens, Timothy E. Decker, Michael W. TI Neuronal nicotinic receptor agonists for the treatment of attentioon-deficit/hyperactivity disorder: Focus on cognition SO BIOCHEMICAL PHARMACOLOGY LA English DT Review DE ADHD; ABT-418; ABT-089; children; adolescents; cognitive deficits; treatment ID DEFICIT-HYPERACTIVITY DISORDER; CHOLINERGIC CHANNEL MODULATOR; REACTION-TIME-TASK; 15-YEAR FOLLOW-UP; ACETYLCHOLINE-RECEPTOR; CIGARETTE-SMOKING; STIMULANT MEDICATION; SUSTAINED ATTENTION; POTENTIAL TREATMENT; ALZHEIMERS-DISEASE AB Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder in children and adolescents, and in about half of these patients, significant symptomology continues into adulthood. Although impulsivity and hyperactivity are the most salient features of ADHD, cognitive deficits, particularly impairments in attention and executive function, are an important component, particularly in adolescents and adults, with over 90% of adults seeking treatment for ADHD manifesting cognitive dysfunction. Currently available medications treat the core ADHD symptoms but typically do not adequately address cognitive aspects of ADHD, underscoring the need for new therapeutics. Dopamine and norepinephrine are hypothesized to be particularly important in ADHD, but there is emerging evidence that cholinergic neurotransmission, particularly involving neuronal nicotinic acetylcholine receptors (nAChRs), may play a role in the pathophysiology of ADHD. Nicotine has demonstrated procognitive effects in both humans and experimental animals and has produced signals of efficacy in small proof-of-concept adult ADHD trials. Although adverse effects associated with nicotine preclude its development as a therapeutic, a number of novel nAChR agonists with improved safety/tolerability profiles have been discovered. Of these, ABT-418 and ABT-089 have both demonstrated signals of efficacy in adults with ADHD. Notably, tolerability issues that might be expected of a nAChR agonist, such as nausea and emesis, were not observed at efficacious doses of ABT-089. Further understanding of the effects of novel neuronal nAChR agonists on specific aspects of cognitive functioning in ADHD is required to assess the full potential of this approach. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Global Pharmaceut Res & Dev, Neurosci Drug Discovery, Dept R4N5, Abbott Pk, IL 60064 USA. RP Wilens, TE (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Unit, Yawkey Ctr Outpatient Care, YAW 6A,32 Fruit St, Boston, MA 02114 USA. EM twilens@partners.org; michael.w.decker@abbott.com FU NIDA NIH HHS [K24 DA016264-02, 2 R01 DA12945-06, 5 K24 DA01624-02, K24 DA016264, R01 DA012945, R01 DA012945-06A2] NR 167 TC 89 Z9 91 U1 7 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 15 PY 2007 VL 74 IS 8 BP 1212 EP 1223 DI 10.1016/j.bcp.2007.07.002 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 220WV UT WOS:000250188900014 PM 17689498 ER PT J AU Shin, J Monti, S Aires, DJ Duvic, M Golub, T Jones, DA Kupper, TS AF Shin, Jessica Monti, Stefano Aires, Daniel J. Duvic, Madeleine Golub, Todd Jones, David A. Kupper, Thomas S. TI Lesional gene expression profiling in cutaneous T-cell lymphoma reveals natural clusters associated with disease outcome SO BLOOD LA English DT Article ID MYCOSIS-FUNGOIDES; SIGNALING PATHWAY; GENOMIC ANALYSIS; CLASS DISCOVERY; CLASSIFICATION; PREDICTION; PATTERNS; CANCER; SKIN; IDENTIFICATION AB Cutaneous T-cell lymphoma (CTCL) is defined by infiltration of activated and malignant T cells in the skin. The clinical manifestations and prognosis in CTCL are highly variable. In this study, we hypothesized that gene expression analysis in lesional skin biopsies can improve understanding of the disease and its management. Based on 63 skin samples, we performed consensus clustering, revealing 3 patient clusters. Of these, 2 clusters tended to differentiate limited CTCL (stages IA and IB) from more extensive CTCL (stages IB and III). Stage IB patients appeared in both clusters, but those in the limited CTCL cluster were more responsive to treatment than those in the more extensive CTCL cluster. The third cluster was enriched in lymphocyte activation genes and was associated With a high proportion of tumor (stage IIB) lesions. Survival analysis revealed significant differences in event-free survival between clusters, with poorest survival seen in the activated lymphocyte cluster. Using supervised analysis, we further characterized genes significantly associated with lower-stage/treatment-responsive CTCL versus higher-stage/treatment-resistant CTCL. We conclude that transcriptional profiling of CTCL skin lesions reveals clinically relevant signatures, correlating with differences in survival and response to treatment. Additional prospective long-term studies to validate and refine these findings appear warranted. C1 Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Jones, DA (reprint author), Brigham & Womens Hosp, Dept Dermatol, Harvard Skin Dis Res Ctr, 77 Ave Louis Pasteur,HIM Room 660, Boston, MA 02115 USA. EM dajones@partners.org; tkupper@partners.org OI Monti, Stefano/0000-0002-9376-0660 FU NCI NIH HHS [P50 CA093683] NR 48 TC 54 Z9 55 U1 2 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2007 VL 110 IS 8 BP 3015 EP 3027 DI 10.1182/blood-2006-12-061507 PG 13 WC Hematology SC Hematology GA 224DQ UT WOS:000250426700041 PM 17638852 ER PT J AU Miovic, M Block, S AF Miovic, Michael Block, Susan TI Psychiatric disorders in advanced cancer SO CANCER LA English DT Review DE cancer; terminal illness; anxiety; depression; distress; coping; communication; end of life ID QUALITY-OF-LIFE; SERIOUS MENTAL-ILLNESS; STEM-CELL TRANSPLANTATION; METASTATIC BREAST-CANCER; TERMINALLY-ILL PATIENTS; BRAIN-TUMOR PATIENTS; HEALTH-SERVICE USE; PALLIATIVE CARE; FOLLOW-UP; PROSTATE-CANCER AB BACKGROUND. Emotional distress and psychiatric disorders are common among patients with advanced cancer. Oncologists play an important role in screening for these conditions, providing first-line treatment and referring patients for further evaluation and treatment when indicated. METHODS. The literature on psycho-oncology was reviewed, focusing on the epidemiology, assessment, and treatment of psychiatric disorders (adjustment disorders, major depression, anxiety and post-traumatic stress, personality disorders, substance abuse, and major mental disorders such as schizophrenia and bipolar disorder) in patients with advanced cancer. Communication skills and the role of the oncologist in dealing with end-of-life issues were also reviewed. Relevant data were summarized from the most recent systematic reviews, epidemiological studies, and intervention trials. Clinical recommendations are provided. RESULTS. About 50% of patients with advanced cancer meet criteria for a psychiatric disorder, the most common being adjustment disorders (11%-35%) and major depression (5%-26%). Both psychosocial and pharmacological treatments are effective for anxiety and depression, although existing studies have methodological limitations. Collaboration with mental health specialists is recommended for patients with personality disorders, major mental illness, and substance abuse problems. Effective communication involves active listening, exploring emotion and meaning, addressing prognosis, and discussing end-of-life issues when relevant. CONCLUSIONS. Treating psychiatric conditions improves quality of life in patients with advanced cancer. Oncologists play a key role in screening for psychiatric disorders, initiating first-line treatments for depression and anxiety, and communicating with patients and caregivers about prognosis and end-of-life issues. C1 Dana Farber Canc Inst, Div Psychol Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Brigham & Womens Hosp, Boston, MA USA. RP Miovic, M (reprint author), Dana Farber Canc Inst, Div Psychol Oncol & Palliat Care, G-442B,44 Binney St, Boston, MA 02115 USA. EM mmiovic@partners.org NR 121 TC 135 Z9 143 U1 7 U2 31 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2007 VL 110 IS 8 BP 1665 EP 1676 DI 10.1002/cncr.22980 PG 12 WC Oncology SC Oncology GA 218RT UT WOS:000250033300006 PM 17847017 ER PT J AU D'Amico, AV Renshaw, AA Loffredo, B Chen, MH AF D'Amico, Anthony V. Renshaw, Andrew A. Loffredo, Brittany Chen, Ming-Hui TI Duration of testosterone suppression and the risk of death from prostate cancer in men treated using radiation and 6 months of hormone therapy SO CANCER LA English DT Article DE baseline testosterone level; prostate cancer; mortality; androgen suppression therapy ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; SERUM TESTOSTERONE; COMPETING RISK; TIME; NORMALIZATION; SCHEDULE AB BACKGROUND. The authors evaluated whether the duration of androgen suppression (AS) after the completion of hormone therapy (HT) was associated with the risk of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). METHODS. The study cohort was comprised of 220 men who received radiation therapy (RT) and 6 months of HT for prostate cancer between 1996 and 2005. The duration of AS was defined as the time to return to the baseline testosterone level after the completion of HT. Grays and Cox regression analyses were used to evaluate whether the duration of AS after the completion of HT was associated with the time to PCSM and ACM, respectively, after adjusting for known prognostic factors. RESULTS. An increasing duration of AS was associated with a decreased risk of PCSM (adjusted hazards ratio [HR], 0.89; P = .003) and ACM (HR, 0.94; P = .007). Men who had prostate cancer with Gleason scores from 8 to 10 had significantly lower cumulative incidence estimates of PCSM (P = .04) if the duration of AS plus the length of HT administration was >= 2 years compared with <2 years. After a median follow-up of 6.1 years, the respective 5-year estimates were 0% and 38%. CONCLUSIONS. The duration of AS after 6 months of HT was associated with the risk of PCSM and ACM. This duration could be used to identify men who have prostate cancer with Gleason scores from 8 to 10 in whom 6 months of HT produces long-term testosterone suppression, which may provide the cancer-specific survival benefit observed with long-term HT. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@partners.org NR 25 TC 20 Z9 20 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2007 VL 110 IS 8 BP 1723 EP 1728 DI 10.1002/cncr.22972 PG 6 WC Oncology SC Oncology GA 218RT UT WOS:000250033300012 PM 17828774 ER PT J AU Saad, F Lipton, A Cook, R Chen, YM Smith, M Coleman, R AF Saad, Fred Lipton, Allan Cook, Richard Chen, Yin-Miao Smith, Matthew Coleman, Robert TI Pathologic fractures correlate with reduced survival in patients with malignant bone disease SO CANCER LA English DT Article DE bisphosphonate; zoledronic acid; skeletal metastases; breast carcinoma; prostate carcinoma; lung carcinoma; multiple myeloma ID PLACEBO-CONTROLLED TRIAL; LONG-TERM EFFICACY; ADVANCED MULTIPLE-MYELOMA; METASTATIC BREAST-CANCER; QUALITY-OF-LIFE; ZOLEDRONIC ACID; SKELETAL COMPLICATIONS; PROSTATE-CANCER; DOUBLE-BLIND; PHASE-III AB BACKGROUND. Data from randomized, controlled trials of zoledronic acid were retrospectively analyzed to assess the effect of pathologic fractures on survival in patients with malignant bone disease. METHODS. A Cox regression model was used to estimate the effect of fractures (time-dependent variable) on survival in patients with stage III multiple myeloma or bone metastases from solid tumors enrolled in 3 large trials. Patients were randomized to receive zoledronic acid, pamidronate, or placebo every 3-4 weeks for up to 24 months (prostate cancer, breast cancer, and multiple myeloma) or up to 21 months (lung and other solid tumors). RESULTS. A total of 3049 patients with multiple myeloma (n = 513), breast (n = 1130), prostate (n = 640), or lung cancer or other solid tumors (n = 766) were included in this analysis. patients with multiple myeloma had the highest fracture incidence (43%), followed by breast (35%), prostate (19%), and lung cancer (17%). In all tumor types except lung, pathologic fracture was associated with a significant increase in risk of death, and breast cancer patients had the greatest increased risk. After adjustment for baseline characteristics, including performance status and prior skeletal complications, breast cancer patients who developed a pathologic fracture on study had a significant 32% increased risk of death relative to patients without a fracture (hazard ratio = 1.32; P < .01); patients with multiple myeloma or prostate cancer had a > 20% increased risk of death. CONCLUSIONS. These results suggest that fractures are associated with increased risk of death in patients with malignant bone disease. Therefore, preventing fractures is an important goal of therapy. C1 Univ Montreal, Hop Notre Dame de Bon Secours, Ctr Hosp, Montreal, PQ H2L 4M1, Canada. Milton S Hershey Med Ctr, Penn State Canc Ctr, Hershey, PA USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. Nova Pharmaceut Corp, E Hanover, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Weston Pk Hosp, Sheffield, S Yorkshire, England. RP Saad, F (reprint author), Univ Montreal, Hop Notre Dame de Bon Secours, Ctr Hosp, 1560 Rue Sherbrooke E, Montreal, PQ H2L 4M1, Canada. EM fred.saad@umontreal.ca NR 34 TC 237 Z9 245 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2007 VL 110 IS 8 BP 1860 EP 1867 DI 10.1002/cncr.22991 PG 8 WC Oncology SC Oncology GA 218RT UT WOS:000250033300029 PM 17763372 ER PT J AU Shen, L Catalano, PJ Benson, AB O'Dwyer, P Hamilton, SR Issa, JPJ AF Shen, Lanlan Catalano, Paul J. Benson, Al B., III O'Dwyer, Peter Hamilton, Stanley R. Issa, Jean-Pierre J. TI Association between DNA methylation and shortened survival in patients with advanced colorectal cancer treated with 5-fluorouracil - Based chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID CPG ISLAND METHYLATION; MICROSATELLITE INSTABILITY; COLON-CANCER; POOR-PROGNOSIS; PHENOTYPE; HYPERMETHYLATION; EPIGENETICS; CARCINOMA; THERAPY; DISEASE AB Purpose: There are no good genomic markers of survival in patients with advanced colorectal cancer. The CpG island methylator phenotype (CIMP) marks a distinctive pathway in colorectal cancer. We sought to determine the prognostic significance of CIMP in advanced colorectal cancer patients treated with 5-fluorouracil (5-FU) in an Eastern Cooperative Oncology Group clinical trial. Experimental Design: We studied 188 patients enrolled on protocol E2290, a five-arm trial comparing 5-FU, 5-FU in combination with N-phosphonoacetyl-L-aspartic acid, oral leucovorin, i.v.. leucovorin, or IFN alpha-2 alpha in patients with advanced colorectal cancer. Methylation of MINT1, MINT31, hMLH1, p14(ARF) and p16(INK4a) in DNA extracted from formalin-fixed paraffin-embedded specimens was evaluated by combined bisulfite restriction analysis, and methylation of MINT2 was studied by methylation-specific PCR. Results: Methylation frequencies were 21% for MINT1, 23%for MINT2, 24% for MINT31,4% for WK4, R hMLH1, 11% for p14ARF, and 17% for p16. Methylation of MINT1, MINT31, p14(ARF), and p16(INK4a) were correlated, as expected. There was no association between methylation and clinicopathologic factors or response to therapy. Methylation of MINT1, MINT31, p14(ARF) or p16(INK4a) was associated individually with shortened overall survival. Hazard ratios were 1.51 (P = 0.05) for MINT1, 1.70 (P = 0.006) for MINT31, 2.22 (P = 0.001) for p144RF, and 1.51 (P = 0.05) for p16(INK4a). Concurrent methylation of two or more genes of the CIMP-associated subset (MINT1, MINT31, p144RF and p16(INK4a)) defined a group of cases with markedly reduced overall survival and hazard ratio was 3.22 (P < 0.0001 in multivariate analyses). Conclusions: CIMP is associated with poor survival in advanced colorectal cancer patients. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77030 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Eastern Cooperat Oncol Grp Stat Ctr, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. RP Issa, JPJ (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jpissa@mdanderson.org FU NCI NIH HHS [CA098006, CA105346, CA89425, R01 CA089245, R01 CA098006, R01 CA105346] NR 39 TC 107 Z9 107 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2007 VL 13 IS 20 BP 6093 EP 6098 DI 10.1158/1078-0432.CCR-07-1011 PG 6 WC Oncology SC Oncology GA 224CG UT WOS:000250422700017 PM 17947473 ER PT J AU Sarantopoulos, S Stevenson, KE Kim, HT Bhuiya, NS Cutler, CS Soiffer, RJ Antin, JH Ritz, J AF Sarantopoulos, Stefanie Stevenson, Kristen E. Kim, Haesook T. Bhuiya, Nazmim S. Cutler, Corey S. Soiffer, Robert J. Antin, Joseph H. Ritz, Jerome TI High levels of B-cell activating factor in patients with active chronic graft-versus-host disease SO CLINICAL CANCER RESEARCH LA English DT Article ID MINOR HISTOCOMPATIBILITY ANTIGEN; CYTOTOXIC T-LYMPHOCYTES; RHEUMATOID-ARTHRITIS; MONOCLONAL-ANTIBODY; SJOGRENS-SYNDROME; SELF-TOLERANCE; SYSTEMIC-LUPUS; CHRONIC GVHD; BAFF-R; TRANSPLANTATION AB Purpose: Recent studies suggest that donor B cells as well as T cells contribute to immune pathology in patients with chronic graft-versus-host disease (GVHD). B-cell activating factor (BAFF) promotes survival and differentiation of activated B cells. Thus, we tested whether BAFF correlated with chronic GVHD disease activity and time of onset after allogeneic hematopoietic stem cell transplantation (HSCT). Experimental Design: Patients who had undergone allogeneic HSCT between 1994 and 2005 for hematologic malignancies were studied. ELISA was used to measure plasma BAFF levels and flow cytometry was used to assess BAFF receptor expression on B cells in patients with or without chronic GVHD. Results: In 104 patients, BAFF levels were significantly higher in patients with active chronic GVHD compared with those without disease (P = 0.02 and 0.0004, respectively). Treatment with high-dose prednisone (>= 30 mg/d) was associated with reduced BAFF levels in patients with active chronic GVHD (P = 0.0005). Serial studies in 24 patients showed that BAFF levels were high in the first 3 months after HSCT but subsequently decreased in 13 patients who never developed chronic GVHD. In contrast, BAFF levels remained elevated in 11 patients who developed chronic GVHD. Six-month BAFF levels >= 10 ng/mL were strongly associated with subsequent development of chronic GVHD (P < 0.0001). Following transplant, plasma BAFF levels correlated inversely with BAFF receptor expression on B cells (P = 0.01), suggesting that soluble BAFF affected B cells through this receptor. Conclusion: These results suggest that elevated BAFF levels contribute to B-cell activation in patients with active chronic GVHD. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Ritz, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Hematol malignancies, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu FU NCI NIH HHS [P01 CA142106, P01 CA142106-06A1, T32 CA009172]; NHLBI NIH HHS [P01 HL070149, HL70149]; NIAID NIH HHS [AI29530, P01 AI029530, U19 AI029530] NR 50 TC 110 Z9 118 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2007 VL 13 IS 20 BP 6107 EP 6114 DI 10.1158/1078-0432.CCR-07-1290 PG 8 WC Oncology SC Oncology GA 224CG UT WOS:000250422700019 PM 17947475 ER PT J AU Rajkumar, SV Richardson, PG Lacy, MQ Dispenzieri, A Greipp, PR Witzig, TE Schlossman, R Sidor, CF Anderson, KC Gertz, MA AF Rajkumar, S. Vincent Richardson, Paul G. Lacy, Martha Q. Dispenzieri, Angela Greipp, Philip R. Witzig, Thomas E. Schlossman, Robert Sidor, Carolyn F. Anderson, Kenneth C. Gertz, Morie A. TI Novel therapy with 2-methoxyestradiol for the treatment of relapsed and plateau phase multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOGENOUS ESTROGEN METABOLITE; BONE-MARROW ANGIOGENESIS; ORAL 2-METHOXYESTRADIOL; INHIBITS ANGIOGENESIS; ANTITUMOR-ACTIVITY; ENDOTHELIAL-CELLS; CLINICAL-TRIAL; CANCER-CELLS; TUMOR-GROWTH; APOPTOSIS AB Purpose: 2-Methoxyestradiol (2ME2) is an endogenous product of estradiol metabolism with antiangiogenic and antineoplastic properties. We report on the first phase 11 trial of 2ME2 in multiple myeloma. Experimental Design: 2ME2 was administered orally at a dose of 1,000 mg daily. Sixty patients (31 men and 29 women) were treated. After 39 patients were accrued, the dose was increased to 800 mg twice daily for the remaining patients. Results: Thirty-one patients had relapsed or refractory multiple myeloma, and 29 had plateau phase multiple myeloma. Median age was 60 years (range, 27-84 years). Therapy was well tolerated. Common adverse events included anemia (35%), fatigue (35%), nausea (25%), diarrhea (20%), hot flushes (20%), headache (17%), muscle cramps (15%), and upper respiratory tract infection (15%). Most adverse events were mild (gradel-2); 12% experienced grade 3-4 adverse events. Median time to progression was 3.8 months, with 5.6 months for plateau phase disease and 2.3 months for relapsed multiple myeloma. Estimated progression-free survival rates for all patients atl, 2, and 3 years were 24%,17%, and 11%, respectively. Three patients, all with plateau phase disease, have been on study for over 4 years without progression at 50, 60, and 63 months, respectively. Minor response was noted in 2 patients. Conclusions: Although no partial responses have been seen thus far, the minor responses and prolonged stable disease seen with 2ME2 therapy are promising. Plasma levels indicate that the dose of 2ME2 was inadequate. A new formulation with better bioavailability will betested soon in multiple myeloma. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. EntreMed, Rockville, MD USA. RP Rajkumar, SV (reprint author), Mayo Clin, Div Hematol, 200 First St SW, Rochester, MN 55905 USA. EM rajks@mayo.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833; Dispenzieri, Angela/0000-0001-8780-9512 FU NCI NIH HHS [CA62242, CA100080, CA50947, CA78378, CA93842] NR 44 TC 41 Z9 43 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2007 VL 13 IS 20 BP 6162 EP 6167 DI 10.1158/1078-0432.CCR-07-0807 PG 6 WC Oncology SC Oncology GA 224CG UT WOS:000250422700026 PM 17947482 ER PT J AU Herbst, RS Davies, AM Natale, RB Dang, TP Schiller, JH Garland, LL Miller, VA Mendelson, D Van den Abbeele, AD Melenevsky, Y de Vries, DJ Eberhard, DA Lyons, B Lutzker, SG Johnson, BE AF Herbst, Roy S. Davies, Angela M. Natale, Ronald B. Dang, Thao P. Schiller, Joan H. Garland, Linda L. Miller, Vincent A. Mendelson, David Van den Abbeele, Annick D. Melenevsky, Yulia de Vries, Daniel J. Eberhard, David A. Lyons, Benjamin Lutzker, Stuart G. Johnson, Bruce E. TI Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; POSITRON-EMISSION-TOMOGRAPHY; PHASE-II TRIAL; MONOCLONAL-ANTIBODY; SIGNALING NETWORK; TUMOR RESPONSE; BREAST-CANCER; CHEMOTHERAPY; GEFITINIB; ERLOTINIB AB Purpose: Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) climerization inhibitor, is a humanized monoclonal anti-HER2 antibody that binds HER2s climerization domain and inhibits HER2 signaling. Based on supporting preclinical studies, we undertook a Phase 11 trial of pertuzumab in patients with recurrent non - small cell lung cancer (NSCLC). Experimental Design: Patients with previously treated NSCLC accessible for core biopsy and naive to HER pathway inhibitors were treated with pertuzumab i.v. once every 3 weeks. Tumor assessments were done at 6 and 12 weeks and then every 3 months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria in Solid Tumors. Measurement of tumor glucose metabolism (SUVmax) by F-18-fluorodeoxyglucose positron emission tomography was used as an exploratory pharmacodynamic marker of drug activity. Results: Of 43 patients treated with pertuzumab, no responses were seen; 18 of 43 (41.9%) and 9 of 43 (20.9%) patients had stable disease at 6 and 12 weeks, respectively. The median and 3-month progression-free survival rates (PFS) were 6.1 weeks (95% confidence interval, 5.3-11.3 weeks) and 28.4% (95% confidence interval, 14.4-44.2%), respectively. Of 22 patients who underwent F-18-fluorodeoxyglucose positron emission tomography, six (27.3%) had a metabolic response to pertuzumab as evidenced by decreased SUVmax. These patients had prolonged PFS (HR = 0.11, log-rank P value = 0.018) compared with the 16 patients who had no metabolic response. Four patients (9.3%) experienced a grade 3/grade 4 adverse event judged related to pertuzumab; none exhibited grade 3/grade 4 cardiac toxicity. Conclusions: Pertuzumab is well tolerated as monotherapy. Pharmacodynamic activity correlated with prolonged PFS was detected in a moderate percentage of patients (27.3%). Further clinical development of pertuzumab should focus on rational combinations of pertuzumab with other drugs active in NSCLC. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Cedars Sinai Canc Ctr, Los Angeles, CA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Wisconsin, Madison, WI USA. Arizona Canc Ctr, Tucson, AZ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1234, Boston, MA 02115 USA. EM bruce_johnson@dfci.harvard.edu NR 42 TC 46 Z9 48 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2007 VL 13 IS 20 BP 6175 EP 6181 DI 10.1158/1078-0432.CCR-07-0460 PG 7 WC Oncology SC Oncology GA 224CG UT WOS:000250422700028 PM 17947484 ER PT J AU Schackman, BR Scott, CA Sax, PE Losina, E Wilkin, TJ McKinnon, JE Swindells, S Weinstein, MC Freedberg, KA AF Schackman, Bruce R. Scott, Callie A. Sax, Paul E. Losina, Elena Wilkin, Timothy J. McKinnon, John E. Swindells, Susan Weinstein, Milton C. Freedberg, Kenneth A. TI Potential risks and benefits of HIV treatment simplification: A simulation model of a proposed clinical trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LOPINAVIR/RITONAVIR LPV/R MONOTHERAPY; ANTIRETROVIRAL THERAPY; COST-EFFECTIVENESS; UNITED-STATES; VIRAL SUPPRESSION; INFECTED PATIENTS; MAINTENANCE; RITONAVIR; ATAZANAVIR AB Background. In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a "boosted" protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial. Methods. We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy. Results. Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%-70% of subjects. Projected lifetime costs are $26,500-$72,400 per person lower for the simplification strategy than for the SOC strategy. Conclusions. An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy. C1 Weill Cornell Med Coll, Dept Publ Hlth, New York, NY 10021 USA. Weill Cornell Med Coll, Dept Med, New York, NY USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA USA. Harvard Univ, Sch Med, Ctr AIDS Res, Boston, MA USA. Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68182 USA. RP Schackman, BR (reprint author), Weill Cornell Med Coll, Dept Publ Hlth, 411 E 69th St, New York, NY 10021 USA. EM brs2006@med.cornell.edu FU NCATS NIH HHS [KL2 TR000146]; NCRR NIH HHS [M01-RR00047, M01 RR000047, KL2 RR024154, KL2 RR024154-02]; NIAID NIH HHS [U01 AO069472, K23 AI55038, P30 AI060354, U01 AI069472-02, U01 AI068636, K25 AI050436, K25 AI050436-05, U01 AI068636-01, U01 AI027661, U01 AI046383-05, U01 AI27661, U01 AI69419, U01 AI069419-01, R37 AI042006-10A1, K23 AI055038, R37 AI042006, P30 AI060354-03, K23 AI055038-05, U01 AI046383, U01 AI069419, K24 AI062476-01, U01 AI68636, U01 AI069472, U01 AI46383, K24 AI062476, K25 AI50436]; NIDA NIH HHS [K01 DA017179, K01 DA017179-05] NR 46 TC 19 Z9 19 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2007 VL 45 IS 8 BP 1062 EP 1070 DI 10.1086/521933 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 211YT UT WOS:000249560900024 PM 17879926 ER PT J AU Kaplan, RC Kingsley, LA Sharrett, AR Li, XH Lazar, J Tien, PC Mack, WJ Cohen, MH Jacobson, L Gange, SJ AF Kaplan, Robert C. Kingsley, Lawrence A. Sharrett, A. Richey Li, Xiuhong Lazar, Jason Tien, Phyllis C. Mack, Wendy J. Cohen, Mardge H. Jacobson, Lisa Gange, Stephen J. TI Ten-year predicted coronary heart disease risk in HIV-infected men and women SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; PROTEASE INHIBITORS; INTERAGENCY HIV; ASSOCIATION; EVENTS; COHORT; LIPIDS; HAART AB Background. Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. Methods. Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. Results. Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of >= 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income <$10,000 vs. >$40,000: OR, 2.32; 95% CI, 1.51-3.56). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI >= 30: OR, 1.79 [95% CI, 1.25-2.56]). Conclusions. Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol, Bronx, NY 10461 USA. Suny Downstate Med Ctr, Dept Med, Brooklyn, NY 11203 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Stroger House, CORE Ctr, Chicago, IL 60612 USA. Stroger House, Dept Med, Chicago, IL 60612 USA. Rush Med Coll, Dept Med, Chicago, IL 60612 USA. RP Kaplan, RC (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM rkaplan@aecom.yu.edu RI Kaplan, Robert/A-2526-2011; OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [5-MO1-RR-00722, M01-RR00079, M01-RR00083]; NHLBI NIH HHS [1R01HL083760-01]; NIAID NIH HHS [UO1-AI-35042, K23 AI066943, K23 AI066943-05, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984]; NICHD NIH HHS [U01-HD-32632] NR 30 TC 89 Z9 92 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2007 VL 45 IS 8 BP 1074 EP 1081 DI 10.1086/521935 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 211YT UT WOS:000249560900026 PM 17879928 ER PT J AU Subbaraman, R Chaguturu, SK Mayer, KH Flanigan, TP Kumarasamy, N AF Subbaraman, Ramnath Chaguturu, Sreekanth Krishna Mayer, Kenneth H. Flanigan, Timothy P. Kumarasamy, Nagalingeswaran TI Adverse effects of highly active antiretroviral therapy in developing countries SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HIV-INFECTED PATIENTS; HUMAN-IMMUNODEFICIENCY-VIRUS; RECONSTITUTION INFLAMMATORY SYNDROME; REVERSE-TRANSCRIPTASE INHIBITOR; RESOURCE-POOR SETTINGS; IMMUNE RECONSTITUTION; RISK-FACTORS; HIV-1-INFECTED PATIENTS; PERIPHERAL NEUROPATHY; COMBINATION THERAPY AB Recent increases in access to highly active antiretroviral therapy (HAART) have made the management of drug toxicities an increasingly crucial component of human immunodeficiency virus (HIV) care in developing countries. The spectrum of adverse effects related to HAART in developing countries may differ from that in developed countries because of the high prevalence of conditions such as anemia, malnutrition, and tuberculosis and frequent initial presentation with advanced HIV disease. The severity of adverse effects may vary as a result of host genetics and diagnostic delays attributable to inadequate laboratory monitoring. This article reviews current knowledge about toxicities related to HAART in resource-limited regions, which are in the process of rapid treatment scale-up. We conclude that initiating HAART before advanced immunosuppression, titrating doses in single-pill drug combinations to differences in patients' body weights, providing more intensive laboratory monitoring during the initial months of therapy, and providing access to less-toxic nucleoside reverse-transcriptase inhibitors may decrease the incidence of toxicities related to HAART in resource-limited regions. C1 YR Gaitonde Ctr AIDS Res & Educ, Voluntary Hlth Serv, Madras 600113, Tamil Nadu, India. Brown Univ, Miriam Hosp, Div Infect Dis, Providence, RI USA. Yale Univ, Sch Med, New Haven, CT USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP Kumarasamy, N (reprint author), YR Gaitonde Ctr AIDS Res & Educ, Voluntary Hlth Serv, Tidel Pk Rd, Madras 600113, Tamil Nadu, India. EM kumarasamy@yrgcare.org FU FIC NIH HHS [D43 TW000237, 3 D43 TW000237-13S1]; NIAID NIH HHS [5P30AI042853-09] NR 136 TC 43 Z9 44 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2007 VL 45 IS 8 BP 1093 EP 1101 DI 10.1086/521150 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 211YT UT WOS:000249560900029 PM 17879931 ER PT J AU Kim, BM Miletich, I Mao, JH McMahon, AP Sharpe, PA Shivdasani, RA AF Kim, Byeong-Moo Miletich, Isabelle Mao, Junhao McMahon, Andrew P. Sharpe, Paul A. Shivdasani, Ramesh A. TI Independent functions and mechanisms for homeobox gene Barx1 in patterning mouse stomach and spleen SO DEVELOPMENT LA English DT Article DE Barx1; mesenchyme-epithelium interactions; stomach development; spleen development; Wnt signaling; organogenesis; Wt1 ID MAMMALIAN SPLEEN; AXIAL SKELETON; SONIC-HEDGEHOG; MESSENGER-RNA; TRANSCRIPTION; DIFFERENTIATION; PANCREAS; HOX11; MICE; MORPHOGENESIS AB Homeobox genes convey positional information in embryos and their role in patterning the mammalian gut is a topic of considerable interest. Barx1 is expressed selectively in fetal stomach mesenchyme and directs differentiation of overlying endoderm. Recombinant tissue cultures and study of young mouse embryos previously suggested that Barx1 controls expression of secreted Wnt antagonists, which suppress endodermal Wnt signaling, to enable stomach epithelial differentiation. We overcame mid- gestational lethality of Barx1(-/ -) mouse embryos and report here the spectrum of anomalies in a distinctive and unprecedented model of gastrointestinal homeotic transformation. Using various mouse models, we confirm the importance of attenuated Wnt signaling in stomach development and the role of Barx1 in suppressing endodermal Wnt activity. Absence of Barx1 also results in fully penetrant defects in positioning and expansion of the spleen, an organ that originates within the mesothelial lining of the stomach. Barx1 is absent from the spleen primordium but highly expressed in the mesogastrium, indicating an indirect effect on spleen development. However, our results argue against a role for Wnt antagonism in genesis of the spleen. Mouse spleen development relies on several homeodomain transcriptional regulators that are expressed in the spleen primordium. Loss of Barx1 does not affect expression of any of these genes but notably reduces expression of Wt1, a transcription factor implicated in spleen morphogenesis and expressed in the mesothelium. These observations place Barx1 proximally within a Wt1 pathway of spleen development and reveal how a homeotic regulator employs different molecular mechanisms to mold neighboring organs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Kings Coll London, Inst Dendrol, Dept Craniofacial Dev, London SE1 9RT, England. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU Medical Research Council [G0200709]; NIDDK NIH HHS [R01DK61139]; NINDS NIH HHS [R01NS033642] NR 38 TC 35 Z9 37 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 15 PY 2007 VL 134 IS 20 BP 3603 EP 3613 DI 10.1242/dev.009308 PG 11 WC Developmental Biology SC Developmental Biology GA 215MM UT WOS:000249812700005 PM 17855428 ER PT J AU Xu, HS Chen, L Baldini, A AF Xu, Huansheng Chen, Li Baldini, Antonio TI In vivo genetic ablation of the periotic mesoderm affects cell proliferation survival and differentiation in the cochlea SO DEVELOPMENTAL BIOLOGY LA English DT Article DE inner ear development; periotic mesoderm; Tbxl; mouse genetics; conditional metation ID INNER-EAR DEVELOPMENT; CARDIO-FACIAL SYNDROME; CARDIOVASCULAR DEFECTS; MAMMALIAN COCHLEA; PHARYNGEAL ARCH; OUTFLOW TRACT; NEURAL CREST; TBX1; EXPRESSION; FATE AB Tbx1 is required for ear development in humans and mice. Gene manipulation in the mouse has discovered multiple consequences of loss of function on early development of the inner ear, some of which are attributable to a cell autonomous role in maintaining cell proliferation of epithelial progenitors of the cochlear and vestibular apparata. However, ablation of the mesodermal domain of the gene also results in severe but more restricted abnormalities. Here we show that Tbx1 has a dynamic expression during late development of the ear, in particular, is expressed in the sensory epithelium of the vestibular organs but not of the cochlea. Vice versa, it is expressed in the condensed mesenchyme that surrounds the cochlea but not in the one that surrounds the vestibule. Loss of Tbx1 in the mesoderm disrupts this peri-cochlear capsule by strongly reducing the proliferation of mesenchymal cells. The organogenesis of the cochlea, which normally occurs inside the capsule, was dramatically affected in terms of growth of the organ, as well as proliferation, differentiation and survival of its epithelial cells. This model provides a striking demonstration of the essential role played by the periotic mesenchyme in the organogenesis of the cochlea. (C) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Harvard Med Sch, Cardiovasc Res Ctr, Boston, MA 02114 USA. Texas A & M Hlth Sci Ctr, Inst Biosci & Technol, Houston, TX 77030 USA. Baylor Coll Med, Program Cardiovasc Sci, Houston, TX 77030 USA. Telethon Inst Genet & Med, Naples, Italy. RP Baldini, A (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Cardiovasc Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM abaldini@ibt.tamhsc.edu RI genes, anthony/F-2541-2012 FU NIDCD NIH HHS [R01 DC006248, R01 DC006248-05]; Telethon [TGM06S01] NR 41 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 15 PY 2007 VL 310 IS 2 BP 329 EP 340 DI 10.1016/j.ydbio.2007.08.006 PG 12 WC Developmental Biology SC Developmental Biology GA 219ZS UT WOS:000250127300012 PM 17825816 ER PT J AU Davis, ME Blicharz, AP Hart, JE Laden, F Garshick, E Smith, TJ AF Davis, M. E. Blicharz, A. P. Hart, J. E. Laden, F. Garshick, E. Smith, T. J. TI Occupational exposure to volatile organic compounds and aldehydes in the US trucking industry SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID POSITIVE MATRIX FACTORIZATION; COMPOUNDS VOCS; HONG-KONG; DIESEL EXHAUST; LUNG-CANCER; AIR TOXICS; IDENTIFICATION; ATMOSPHERE AB Diesel exhaust is a complex chemical mixture that has been linked to lung cancer mortality in a number of epidemiologic studies. However, the dose-response relationship remains largely undefined, and the specific components responsible for carcinogenicity have not been identified. Although previous focus has been on the particulate phase, diesel exhaust includes a vapor phase of numerous volatile organic compounds (VOCs) and aldehydes that are either known or suspected carcinogens, such as 1,3-butadiene, benzene, and formaldehyde. However, there are relatively few studies that quantify exposure to VOCs and aldehydes in diesel-heavy and other exhaust-related microenvironments. As part of a nationwide assessment of exposure to diesel exhaust in the trucking industry, we collected measurements of VOCs and aldehydes at 15 different U.S. trucking terminals and in city truck drivers (with 6 repeat site visits), observing average shift concentrations in truck cabs and at multiple background and work area locations within each terminal. In this paper, we characterize occupational exposure to 18 different VOCs and aldehydes, as well as relationships with particulate mass (elemental carbon in PM < 1 mu m and PM2.5) across locations to determine source characteristics. Our results show that occupational exposure to VOCs and aldehydes varies significantly across the different sampling locations within each terminal, with significantly higher exposures noted in the work environments over background levels (p < 0.01). A structural equation model performed well in predicting terminal exposures to VOCs and aldehydes as a function of job, background levels, weather conditions, proximity to a major road, and geographic location (R-2 = 0.2-0.4 work area; R-2 = 0.5-0.9 background). C1 Univ Maine, Orono, ME 04469 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, Pulm & Crit Care Med Sect, W Roxbury, MA 02132 USA. RP Davis, ME (reprint author), Univ Maine, Orono, ME 04469 USA. EM mary.davis@umit.maine.edu FU NCI NIH HHS [R01 CA090792, R01 CA090792-05, R01 CA90792] NR 29 TC 21 Z9 21 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD OCT 15 PY 2007 VL 41 IS 20 BP 7152 EP 7158 DI 10.1021/es071041z PG 7 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 219TJ UT WOS:000250110800046 PM 17993162 ER PT J AU Yates, B Zetterberg, C Rajeev, V Reiss, M Rittling, SR AF Yates, Bradley Zetterberg, Craig Rajeev, Vaishali Reiss, Michael Rittling, Susan R. TI Promoter-independent regulation of vimentin expression in mammary epithelial cells by val(12) ras and TGF beta SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE EMT; TGF beta; vimentin; suppression; metastasis ID GROWTH-FACTOR-BETA; BREAST-CANCER CELLS; MESENCHYMAL TRANSITION; GENE-EXPRESSION; E-CADHERIN; TRANSCRIPTION FACTOR; FUNCTIONAL-ANALYSIS; PROSTATE CARCINOMA; TUMOR PROGRESSION; NEGATIVE ELEMENT AB The 1029 series of mammary epithelial cell lines (D6, GP+E, r3 and r3T) are progressively more transformed: the latter two by val(12) ras. These cell lines respond to TGF beta by undergoing early events of epithelial-mesenchymal transition (EMT), including morphological changes and redistribution of E-cadherin. Tumors formed by r3T cells in the choroid of the eye express vimentin, a late marker of EMT, possibly in response to TGF beta. In vitro, vimentin expression is induced in all the cell lines by TGF beta treatment, whereas cytokeratin expression is only slightly affected. Surprisingly, ras transformation results in a 10-fold suppression of vimentin expression. Neither suppression of vimentin by ras transformation nor induction by TGF beta is mediated by the vimentin promoter in r3T cells. In transient transfection assays, several human vimentin promoter constructs are more active in the low-expressing r3T cell line than in the vimentin-expressing mesenchymal cell line NIH3T3. In the r3T cells, there is no effect of TGF beta treatment for 9 days on the activity of either promoter. Azacytidine treatment does not affect vimentin expression in either NIH3T3 or r3T, suggesting that promoter methylation is not the mechanism of suppression by ras. Finally, the half-life of the vimentin mRNA is similar in both the r3T cells and NIH3T3 cells. We conclude that the suppression of vimentin expression by ras, and the relief of this suppression by TGF beta, occurs in a promoter-independent fashion, possibly through sequences in the first or second intron. (C) 2007 Elsevier Inc. All rights reserved. C1 Forsyth Inst, Boston, MA 02115 USA. Inst Canc Res, New Brunswick, NJ USA. RP Rittling, SR (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM srittling@forsyth.org RI Reiss, Michael/A-8314-2009 FU NIDDK NIH HHS [DK067685, R01 DK067685, R01 DK067685-02, R01 DK067685-03, R01 DK067685-04] NR 59 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 15 PY 2007 VL 313 IS 17 BP 3718 EP 3728 DI 10.1016/j.yexcr.2007.07.026 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 220PW UT WOS:000250169700005 PM 17719575 ER PT J AU Potente, M Ghaeni, L Baldessari, D Mostoslavsky, R Rossig, L Dequiedt, F Haendeler, J Mione, M Dejana, E Alt, FW Zeiher, AM Dimmeler, S AF Potente, Michael Ghaeni, Laleh Baldessari, Danila Mostoslavsky, Raul Rossig, Lothar Dequiedt, Franck Haendeler, Judith Mione, Marina Dejana, Elisabetta Alt, Frederick W. Zeiher, Andreas M. Dimmeler, Stefanie TI SIRT1 controls endothelial angiogenic functions during vascular growth SO GENES & DEVELOPMENT LA English DT Article DE SIRT1; HDAC; endothelial cells; angiogenesis; Foxo ID FOXO TRANSCRIPTION FACTORS; NITRIC-OXIDE SYNTHASE; DEACETYLASE ACTIVITY; SHEAR-STRESS; HISTONE MODIFICATIONS; PROTEIN DEACETYLASES; DEPENDENT REGULATION; CALORIE RESTRICTION; SIR2-LIKE PROTEINS; BHLH REPRESSORS AB The nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase Sir2 regulates life-span in various species. Mammalian homologs of Sir2 are called sirtuins (SIRT1-SIRT7). In an effort to define the role of sirtuins in vascular homeostasis, we found that among the SIRT family, SIRT1 uniquely regulates angiogenesis signaling. We show that SIRT1 is highly expressed in the vasculature during blood vessel growth, where it controls the angiogenic activity of endothelial cells. Loss of SIRT1 function blocks sprouting angiogenesis and branching morphogenesis of endothelial cells with consequent down-regulation of genes involved in blood vessel development and vascular remodeling. Disruption of SIRT1 gene expression in zebrafish and mice results in defective blood vessel formation and blunts ischemia-induced neovascularization. Through gain-and loss-of-function approaches, we show that SIRT1 associates with and deacetylates the forkhead transcription factor Foxo1, an essential negative regulator of blood vessel development to restrain its anti-angiogenic activity. These findings uncover a novel and unexpected role for SIRT1 as a critical modulator of endothelial gene expression governing postnatal vascular growth. C1 Univ Frankfurt, Dept Med 3, D-60590 Frankfurt, Germany. Zebrafish Grp, Fdn Italiana Ricerca Cancrol Inst Mol Oncol Fdn, European Inst Oncol, I-20139 Milan, Italy. Harvard Univ, Med Ctr, Childrens Hosp, Biomed Res Inst,Ctr Blood Res, Boston, MA 02115 USA. Cell & Mol Biol Unit, FUSAGx, B-5030 Gembloux, Belgium. Inst Mol Oncol, IFOM, FIRC, I-20139 Milan, Italy. RP Dimmeler, S (reprint author), Massachusetts Gen Hosp, Ctr Canc, Harvard Med Sch, Boston, MA 02114 USA. EM Dimmeler@em.uni-frankfurt.de RI Mione, Maria Caterina /I-3073-2013 NR 52 TC 278 Z9 296 U1 1 U2 24 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 2007 VL 21 IS 20 BP 2644 EP 2658 DI 10.1101/gad.435107 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 220JE UT WOS:000250152200011 PM 17938244 ER PT J AU Devalapally, H Duan, ZF Seiden, MV Amiji, MM AF Devalapally, Harikrishna Duan, Zhenfeng Seiden, Michael V. Amiji, Mansoor M. TI Paclitaxel and ceramide co-administration in biodegradable polymeric nanoparticulate delivery system to overcome drug resistance in ovarian cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ovarian cancer; drug resistance; paclitaxel; C-6-ceramide; biodegradable polymeric nanoparticles; poly(ethylene oxide)-modified poly(epsilon-caprolactone) ID NECROSIS-FACTOR-ALPHA; POLY(BETA-AMINO ESTER) NANOPARTICLES; TUMOR-TARGETED DELIVERY; PH-SENSITIVE SYSTEM; MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS; SPHINGOLIPID METABOLISM; VASCULAR-PERMEABILITY; HYDROPHOBIC DRUGS; BREAST-CANCER AB The objective of this study was to overcome drug resistance upon systemic administration of combination paclitaxel (PTX) and the apoptotic signaling molecule C-6-ceramide (CER) in biodegradable poly(ethylene oxide)-modified poly(epsilon-caprolactone (PEO-PCL) nanoparticles. Subcutaneous sensitive (wild-type) and multidrug resistant (MDR-1 positive) SKOV-3 human ovarian adenocarcinoma xenografts were established in female Nu/Nu mice. PTX and CER were administered intravenously either as a single agent or in combination in aqueous solution and in PEO-PCL nanoparticles to the tumor-bearing mice. There was significant (p < 0.05) tumor growth suppression in both wild-type SKOV-3 and multidrug resistant SKOV-3(TR) models upon single dose co-administration of PTX (20 mg/kg) and CER (100 mg/kg) in nanoparticle formulations as compared to the individual agents and administration in aqueous solutions. For instance, in SKOV-3 wild-type model, more than 4.3-fold increase (p < 0.05) in tumor growth delay and 3.6-fold (p < 0.05) increase in tumor volume doubling time (DT) were observed with the combination treatment in nanoparticles as compared to untreated animals. Similarly, 3-fold increase (p < 0.05) in tumor growth delay and tumor volume DT was observed in SKOV-3(TR) model. Body weight changes and blood cells counts were used as measures of safety and, except for an increase in platelet counts (p < 0.05) in PTX + CER treated animals, there was no difference between various treatment strategies. The results of this study show that combination of PTX and CER in biodegradable polymeric nanoparticles can serve as a very effective therapeutic strategy to overcome drug resistance in ovarian cancer. (C) 2007 Wiley-Liss, Inc. C1 Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Hematol & Oncol, Boston, MA 02114 USA. RP Amiji, MM (reprint author), Northeastern Univ, Dept Pharmaceut Sci, Sch Pharm, 360 Huntington Ave, Boston, MA 02115 USA. EM m.amiji@neu.edu RI Amiji, Mansoor/A-4365-2014 OI Amiji, Mansoor/0000-0001-6170-881X FU NCI NIH HHS [R01-CA119617] NR 55 TC 68 Z9 72 U1 1 U2 14 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 OCT 15 PY 2007 VL 121 IS 8 BP 1830 EP 1838 DI 10.1002/ijc.22886 PG 9 WC Oncology SC Oncology GA 211EX UT WOS:000249508200026 PM 17557285 ER PT J AU Keir, ME Freeman, GJ Sharpe, AH AF Keir, Mary E. Freeman, Gordon J. Sharpe, Arlene H. TI PD-1 regulates self-reactive CD8(+) T cell responses to antigen in lymph nodes and tissues SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CROSS-PRESENTATION; VIRAL-INFECTION; IN-VIVO; TOLERANCE; EXPRESSION; GENERATION; INDUCTION; APOPTOSIS; BLOCKADE; LIGANDS AB PD-1, an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. We tested the role of PD-1:PD-1 ligand (PD-L) interactions in cross-presentation and the generation and control of CD8(+) responses against self-Ag. Ag-naive PD-1(-/-) OVA-specific OT-I CD8(+) T cells exhibited exacerbated responses to cross-presented Ag in mice expressing soluble OVA under the control of the rat insulin promoter (RIP-ova high). Following adoptive transfer into RIP-ova high recipients, PD-1(-/-) OT-I T cells expanded in the pancreatic lymph node. In contrast to wild-type OT-I cells, PD-1(-/-) OT-I T cells secreted IFN-gamma and migrated into the pancreas, ultimately causing diabetes. Loss of PD-1 affected CD8(+) cells intrinsically, and did not significantly alter the responses of wild-type OT-I T cells adoptively transferred into the same RIP-ova high recipient mouse. PD-1:PD-L interactions also limited CD8(+) effector cells, and PD-L1 expression on parenchymal tissues protected against effector OT-I T cell attack. Finally, we found that the loss of PD-1 on effector OT-I cells lowers the threshold for Ag recognition in peripheral tissues. These findings indicate two checkpoints where PD-1 attenuates self-reactive T cell responses: presentation of self-Ag to naive self-reactive T cells by dendritic cells in the draining lymph node and reactivation of pathogenic self-reactive T cells in the target organ. C1 Harvard Univ, Dept Pathol, Sch Med, Div Immunol Res, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Sharpe, AH (reprint author), Harvard Univ, Dept Pathol, Sch Med, Div Immunol Res, Boston, MA 02115 USA. EM ariene_sharpe@hms.harvard.edu FU NIAID NIH HHS [AI40614, AI056229, AI39671] NR 28 TC 100 Z9 103 U1 0 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2007 VL 179 IS 8 BP 5064 EP 5070 PG 7 WC Immunology SC Immunology GA 219QJ UT WOS:000250099400013 PM 17911591 ER PT J AU Choudhury, A Cohen, PL Eisenberg, RA AF Choudhury, Arpita Cohen, Philip L. Eisenberg, Robert A. TI Mature B cells preferentially lose tolerance in the chronic graft-versus-host disease model of systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4 T-CELLS; MARGINAL-ZONE; AUTOANTIBODY PRODUCTION; NEGATIVE SELECTION; LYMPHOCYTES-B; CHAIN GENE; MICE; EXPRESSION; RECEPTORS; PATHOGENESIS AB Chronic graft-vs-host (cGVH) disease is a well-characterized systemic lupus crythematosus (SLE) model. Induction of cGVH in anti-DNA H chain knockin (3H9KI) transgenic mice results in specific activation of anti-dsDNA B cells. In this study, we show that B cells from 3119KI mice were activated by cGVH even when adoptively transferred into irradiated JHT-/- recipients that lack endogenous B cells. This process of activation was reflected by high autoantibody titers and changes in phenotypic markers. We have used this system to characterize the particular B cell subsets that were responsible for secreting autoantibodies during cGVH response. We isolated splenic B cell subsets based on their expression of specific cell surface markers and used them in our adoptive transfer studies. We found that mature B cells were the most vulnerable to the allostimulus and were the major source of autoantibodies compared with immature B cells. The greater susceptibility of mature B cells to become activated and thereby lose tolerance was unanticipated and has implications for maintenance of peripheral tolerance and for the development of autoimmunity. Furthermore, of the mature B cells, marginal zone B cells were particularly responsible for mounting the initial response to the cGVH stimulus. This observation underscores the critical role of marginal zone B cells in activation and production of autoantibodies. C1 Univ Penn, Div Rheumatol, Dept Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Eisenberg, RA (reprint author), Univ Penn, Div Rheumatol, Dept Med, 421 Curie Blvd, Philadelphia, PA 19104 USA. EM raemd@mail.med.upenn.edu FU NIAID NIH HHS [U19-AI-46358, R01-AI063626]; NIAMS NIH HHS [R01-AR34156, R01 AR034156] NR 33 TC 5 Z9 5 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2007 VL 179 IS 8 BP 5564 EP 5570 PG 7 WC Immunology SC Immunology GA 219QJ UT WOS:000250099400065 PM 17911643 ER PT J AU Ostrem, JL Marks, WJ Volz, MM Heath, SL Starr, PA AF Ostrem, Jill L. Marks, William J. Volz, Monica M. Heath, Susan L. Starr, Philip A. TI Pallidal deep brain stimulation in patients with cranial-cervical dystonia (Meige syndrome) SO MOVEMENT DISORDERS LA English DT Article DE dystonia; deep brain stimulation; Meige syndrome; globus pallidus; cranial-cervical dystonia ID GLOBUS-PALLIDUS; GENERALIZED DYSTONIA; PARKINSONS-DISEASE; OROMANDIBULAR DYSTONIA; SPASMODIC TORTICOLLIS; SUBTHALAMIC NUCLEUS; TECHNICAL APPROACH; BOTULINUM-TOXIN; FOLLOW-UP; INTERNUS AB Idiopathic cranial-cervical dystonia (ICCD) is an adult-onset dystonia syndrome affecting orbicularis oculi, facial, oromandibular, and cervical musculature. ICCD is frequently difficult to treat medically. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective treatment for idiopathic generalized dystonia, however less is known about the effect of GPi DBS on ICCD. In this article, we present the results from a pilot study assessing the effect of GPi DBS in a series of patients with ICCD. Six patients underwent bilateral stereotactic implantation of DBS leads into the sensorimotor GPi. Patients were evaluated with the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) and Toronto western spamodic torticollis rating scale (TWSTRS) before surgery and 6 months postoperatively. At 6 months, patients showed a 72% mean improvement in the. BFMDRS total movement score (P < 0.028, Wilcoxin signed rank test). The mean BFMDRS disability score showed a trend toward improvement (P < 0.06). The total TWSTRS score improved 54% (P < 0.043). Despite improvement in dystonia, mild worsening of motor function was reported in previously nondystonic body regions with stimulation in 4 patients. Although GPi DBS was effective in these patients, the influence of GPi DBS on nondystonic body regions deserves further investigation. (C) 2007 Movement Disorder Society. C1 Univ Calif San Francisco, Ctr Med, Dept Neurol, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, PADRECC, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Ostrem, JL (reprint author), Univ Calif San Francisco, Ctr Med, Dept Neurol, 400 Parnassus Ave,Box 0348, San Francisco, CA 94143 USA. EM jill.ostrem@ucsf.edu FU PHS HHS [K08] NR 29 TC 75 Z9 80 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 15 PY 2007 VL 22 IS 13 BP 1885 EP 1891 DI 10.1002/mds.21580 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 228NR UT WOS:000250737100008 PM 17618522 ER PT J AU Hogarth, P Lovrecic, L Krainc, D AF Hogarth, Penelope Lovrecic, Luca Krainc, Dimitri TI Sodium phenylbutyrate in Huntington's disease: A dose-finding study SO MOVEMENT DISORDERS LA English DT Article DE huntington's disease; histone deacetylase inhibitor; sodium phenylbutyrate ID TRANSGENIC MOUSE MODEL; EXPRESSION AB Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. (C) 2007 Movement Disorder Society. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,MIND, Charlestown, MA USA. RP Hogarth, P (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk Rd,OP-32, Portland, OR 97239 USA. EM hogarthp@ohsu.edu FU NCRR NIH HHS [5 M01 RR000334] NR 8 TC 43 Z9 45 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 15 PY 2007 VL 22 IS 13 BP 1962 EP 1964 DI 10.1002/mds.21632 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 228NR UT WOS:000250737100020 PM 17702032 ER PT J AU Novak, J Puoris'haag, M AF Novak, J. Puoris'haag, M. TI Two-color, double-slit in vivo flow cytometer SO OPTICS LETTERS LA English DT Article ID CELLS AB The in vivo flow cytometer enables the real-time detection and quantification of fluorescent cells circulating within a live animal without the need for incisions or extraction of blood. It has been used in demonstrating flow velocity disparities in biological flows, and in the investigation of the circulation kinetics of various types of cells. However, a shortcoming of this in vivo flow cytometer is that it provides only one excitation slit at one wavelength, resulting in several performance limitations. Therefore, a second in vivo flow cytometer that provides two different laser wavelengths, 473 and 633 nm, and one or two excitation slits has been designed and built. Thus far, the two-color system has been used to acquire circulation kinetics data of two different cell populations each labeled with a different marker, one cell population labeled with two different markers, and one cell population expressing the green-fluorescent protein gene. In addition, accurate arterial red blood cell velocities within a mouse have been determined using the cytometer. (C) 2007 Optical Society of America C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Novak, J (reprint author), MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jpnovak@alum.mit.edu NR 4 TC 8 Z9 8 U1 2 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 15 PY 2007 VL 32 IS 20 BP 2993 EP 2995 DI 10.1364/OL.32.002993 PG 3 WC Optics SC Optics GA 229BG UT WOS:000250775700031 PM 17938677 ER PT J AU Gu, XP Wang, SX Yang, LL Sung, BC Lim, GW Mao, J Zeng, Q Chang, Y Mao, JR AF Gu, Xiaopinq Wang, Shuxing Yang, Liling Sung, Backil Lim, Grewo Mao, Ji Zeng, Qing Chang, Yang Mao, Jianren TI Time-dependent effect of epidural steroid on pain behavior induced by chronic compression of dorsal root ganglion in rats SO BRAIN RESEARCH LA English DT Article DE epidural; steroid; glucocorticoid receptor; dorsal root ganglia; hyperalgesia; allodynia; sciatica; radicular pain; neuropathic pain ID INTRACTABLE POSTHERPETIC NEURALGIA; CORTICOSTEROID INJECTIONS; NEUROPATHIC PAIN; PERIPHERAL MONONEUROPATHY; GLIAL ACTIVATION; METHYLPREDNISOLONE; SCIATICA; HYPERALGESIA; LUMBAR; MODEL AB Although epidural steroid injection has been commonly used to treat radicular pain, its clinical efficacy remains controversial. In a rat model of radicular pain induced by chronic compression of lumbar dorsal root ganglion (CCD), we examined the effect of epidural steroid on CCD-induced pain behavior. Triamcinolone [a glucocorticoid receptor (GR) agonist] or RU38486 (a GR antagonist) was given epidurally once either on day 3 (early treatment) or day 10 (late treatment) after CCD. The results showed that 1) early treatment with triamcinolone and RU38486 alone, respectively, reduced and exacerbated mechanical allodynia and thermal hyperalgesia, 2) late treatment with triamcinolone alone failed to improve mechanical allodynia and only transiently attenuated thermal hyperalgesia, and 3) late treatment with RU38486 alone improved mechanical allodynia and thermal hyperalgesia in CCD rats. Moreover, a second dose of triamcinolone given on day 10 paradoxically exacerbated pain behavior in CCD rats that received a first dose of triamcinolone on day 3. These results indicate that the effect of epidural steroid on radicular pain maybe time-dependent. Clinical implications for epidural steroid treatment are discussed in light of these preclinical findings. (c) 2007 Elsevier B.V. All rights reserved. C1 Harvard Univ, Dept Anesthesia & Crit Care, MGH Ctr Translat Pain Res,Med Sch, Massachusetts Gen Hosp, Boston, MA 02114 USA. Nanjing Univ, Dept Med, Dept Anesthesiol, Drum Tower Hosp, Nanjing 210008, Peoples R China. RP Mao, JR (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, MGH Ctr Translat Pain Res,Med Sch, Massachusetts Gen Hosp, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDCR NIH HHS [R01 DE018538, DE18538, R01 DE018214]; NINDS NIH HHS [NS45681, R01 NS042661, R01 NS045681, NS42661] NR 35 TC 10 Z9 14 U1 1 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 OCT 12 PY 2007 VL 1174 BP 39 EP 46 DI 10.1016/j.brainres.2007.08.030 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 226TU UT WOS:000250612200005 PM 17869229 ER PT J AU Handschin, C Chin, S Li, P Liu, F Maratos-Flier, E LeBrasseur, NK Yan, Z Spiegelman, BM AF Handschin, Christoph Chin, Sherry Li, Ping Liu, Fenfen Maratos-Flier, Eleftheria LeBrasseur, Nathan K. Yan, Zhen Spiegelman, Bruce M. TI Skeletal muscle fiber-type switching, exercise intolerance, and myopathy in PGC-1 alpha muscle-specific knock-out animals SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DUCHENNE MUSCULAR-DYSTROPHY; MITOCHONDRIAL BIOGENESIS; OXIDATIVE-PHOSPHORYLATION; INFLAMMATORY MYOPATHIES; SIGNALING PATHWAYS; ENERGY-METABOLISM; GENE-EXPRESSION; RECEPTOR-ALPHA; PGC-1 FAMILY; MDX MOUSE AB The transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha) is a key integrator of neuromuscular activity in skeletal muscle. Ectopic expression of PGC-1 alpha in muscle results in increased mitochondrial number and function as well as an increase in oxidative, fatigue-resistant muscle fibers. Whole body PGC-1 alpha knock-out mice have a very complex phenotype but do not have a marked skeletal muscle phenotype. We thus analyzed skeletal muscle-specific PGC-1 alpha knock-out mice to identify a specific role for PGC-1 alpha in skeletal muscle function. These mice exhibit a shift from oxidative type I and IIa toward type IIx and IIb muscle fibers. Moreover, skeletal muscle-specific PGC-1 alpha knock-out animals have reduced endurance capacity and exhibit fiber damage and elevated markers of inflammation following treadmill running. Our data demonstrate a critical role for PGC-1 alpha in maintenance of normal fiber type composition and of muscle fiber integrity following exertion. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Zurich, Inst Physiol, CH-8057 Zurich, Switzerland. Univ Zurich, Zurich Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. Duke Univ, Med Ctr, Dept Med, Durham, NC 27704 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Diabet & Metab Unit, Boston, MA 02118 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Smith Bldg,1 Jimmy Fund Way, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu RI Handschin, Christoph/E-6886-2015; OI Handschin, Christoph/0000-0003-0603-1097; LeBrasseur, Nathan/0000-0002-2002-0418 FU NIAMS NIH HHS [AR050429, R01 AR050429]; NIDDK NIH HHS [P30 DK040561, DK54477, DK61562, P30 DK040561-12, R01 DK054477] NR 31 TC 282 Z9 299 U1 1 U2 35 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 12 PY 2007 VL 282 IS 41 BP 30014 EP 30021 DI 10.1074/jbc.M704817200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 217XS UT WOS:000249981200031 PM 17702743 ER PT J AU Yang, H Minamishima, YA Yan, Q Schlisio, S Ebert, BL Zhang, X Zhang, L Kim, WY Olumi, AF Kaelin, WG AF Yang, Haifeng Minamishima, Yoji Andrew Yan, Qin Schlisio, Susanne Ebert, Benjamin L. Zhang, Xiaoping Zhang, Liang Kim, William Y. Olumi, Aria F. Kaelin, William G., Jr. TI pVHL acts as an adaptor to promote the inhibitory phosphorylation of the NF-kappa B agonist Card9 by CK2 SO MOLECULAR CELL LA English DT Article ID RENAL-CELL CARCINOMA; LINDAU TUMOR-SUPPRESSOR; HYPOXIA-INDUCIBLE FACTOR; HEREDITARY CANCER SYNDROME; INDUCED APOPTOSIS; PROLYL HYDROXYLASE; PROTEIN; GENE; SENSITIZES; DISEASE AB The VHL tumor suppressor protein (pVHL) is part of an E3 ubiquitin ligase that targets HIF for destruction. pVHL-defective renal carcinoma cells exhibit increased NF-B-K activity but the mechanism is unclear. NF-KB affects tumorigenesis and therapeutic resistance in some settings. We found that pVHL associates with the NF-KB agonist Card9 but does not target Card9 for destruction. Instead, pVHL serves as an adaptor that promotes the phosphorylation of the Card9 C terminus by CK2. Elimination of these sites markedly enhanced Card9's ability to activate NF-B-K in VHL+/+ cells, and Card9 siRNA normalized NF-B-K activity in VHL-/- cells and restored their sensitivity to cytokine-induced apoptosis. Furthermore, downregulation of Card9 in VHL-/- cancer cells reduced their tumorigenic potential. Therefore pVHL can serve as an adaptor for both a ubiquitin conjugating enzyme and a kinase. The latter activity, which promotes Card9 phosphorylation, links pVHL to control of NF-B-K activity and tumorigenesis. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Beth Israel Med Ctr, Dept Urol, Boston, MA 02115 USA. Univ N Carolina, Lineberger Canc Res Ctr, Div Hematol Oncol, Chapel Hill, NC 27599 USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu RI Yan, Qin/E-8893-2012; Minamishima, Yoji/E-5380-2010; OI Yan, Qin/0000-0003-4077-453X; Minamishima, Yoji/0000-0001-7995-9318; Schlisio, Susanne/0000-0002-2605-3771 FU NCI NIH HHS [R01 CA068490-09, R01 CA068490, R01 CA068490-06, R01 CA068490-07, R01 CA068490-08, R01 CA068490-10, R01 CA068490-11A1, R01 CA068490-12, T32 CA009172] NR 47 TC 87 Z9 92 U1 0 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 12 PY 2007 VL 28 IS 1 BP 15 EP 27 DI 10.1016/j.molcel.2007.09.010 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 224UT UT WOS:000250472800002 PM 17936701 ER PT J AU Stommel, JM Kimmelman, AC Ying, HQ Nabioullin, R Ponugoti, AH Wiedemeyer, R Stegh, AH Bradner, JE Ligon, KL Brennan, C Chin, L DePinho, RA AF Stommel, Jayne M. Kimmelman, Alec C. Ying, Haoqiang Nabioullin, Roustem Ponugoti, Aditya H. Wiedemeyer, Ruprecht Stegh, Alexander H. Bradner, James E. Ligon, Keith L. Brennan, Cameron Chin, Lynda DePinho, Ronald A. TI Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies SO SCIENCE LA English DT Article ID CONFERS ENHANCED TUMORIGENICITY; DIFFUSE GLIOMAS; INHIBITORS; CANCER; GLIOBLASTOMA; MARKER; COMMON; BRAIN; GENE; MET AB Targeted therapies that inhibit receptor tyrosine kinases (RTKs) and the downstream phosphatidylinositol 3-kinase (PI3K) signaling pathway have shown promising anticancer activity, but their efficacy in the brain tumor glioblastoma multiforme (GBM) and other solid tumors has been modest. We hypothesized that multiple RTKs are coactivated in these tumors and that redundant inputs drive and maintain downstream signaling, thereby limiting the efficacy of therapies targeting single RTKs. Tumor cell lines, xenotransplants, and primary tumors indeed show multiple concomitantly activated RTKs. Combinations of RTK inhibitors and/or RNA interference, but not single agents, decreased signaling, cell survival, and anchorage-independent growth even in glioma cells deficient in PTEN, a frequently inactivated inhibitor of PI3K. Thus, effective GBM therapy may require combined regimens targeting multiple RTKs. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02115 USA. Cornell Univ, Dept Neurosurg, Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Neurol Surg, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP DePinho, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu RI leng, xianwei/F-9073-2011; OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [5P01CA95616, R01CA99041] NR 20 TC 555 Z9 575 U1 12 U2 34 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 12 PY 2007 VL 318 IS 5848 BP 287 EP 290 DI 10.1126/science.1142946 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 219LG UT WOS:000250086100051 PM 17872411 ER PT J AU Lan, F Bayliss, PE Rinn, JL Whetstine, JR Wang, JK Chen, SZ Iwase, S Alpatov, R Issaeva, I Canaani, E Roberts, TM Chang, HY Shi, Y AF Lan, Fei Bayliss, Peter E. Rinn, John L. Whetstine, Johnathan R. Wang, Jordon K. Chen, Shuzhen Iwase, Shigeki Alpatov, Roman Issaeva, Irina Canaani, Eli Roberts, Thomas M. Chang, Howard Y. Shi, Yang TI A histone H3 lysine 27 demethylase regulates animal posterior development SO NATURE LA English DT Article ID EMBRYONIC STEM-CELLS; METHYLTRANSFERASE ACTIVITY; X-INACTIVATION; BREAST-CANCER; TARGET GENES; Y-CHROMOSOME; POLYCOMB; METHYLATION; PROTEIN; REPRESSION AB The recent discovery of a large number of histone demethylases suggests a central role for these enzymes in regulating histone methylation dynamics. Histone H3K27 trimethylation (H3K27me3) has been linked to polycomb-group-protein-mediated suppression of Hox genes and animal body patterning, X-chromosome inactivation and possibly maintenance of embryonic stem cell (ESC) identity. An imbalance of H3K27 methylation owing to overexpression of the methylase EZH2 has been implicated in metastatic prostate and aggressive breast cancers. Here we show that the JmjC-domain-containing related proteins UTX and JMJD3 catalyse demethylation of H3K27me3/2. UTX is enriched around the transcription start sites of many HOX genes in primary human fibroblasts, in which HOX genes are differentially expressed, but is selectively excluded from the HOX loci in ESCs, in which HOX genes are largely silent. Consistently, RNA interference inhibition of UTX led to increased H3K27me3 levels at some HOX gene promoters. Importantly, morpholino oligonucleotide inhibition of a zebrafish UTX homologue resulted in mis-regulation of hox genes and a striking posterior developmental defect, which was partially rescued by wild-type, but not by catalytically inactive, human UTX. Taken together, these findings identify a small family of H3K27 demethylases with important, evolutionarily conserved roles in H3K27 methylation regulation and in animal anterior-posterior development. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Dermatol, Program Epithelial Biol, Stanford, CA 94305 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM yshi@hms.harvard.edu NR 40 TC 374 Z9 393 U1 4 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 11 PY 2007 VL 449 IS 7163 BP 689 EP U3 DI 10.1038/nature06192 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 218VV UT WOS:000250045000036 PM 17851529 ER PT J AU Hayes, DF Thor, AD Dressler, LG Weaver, D Edgerton, S Cowan, D Broadwater, G Goldstein, LJ Martino, S Ingle, JN Henderson, IC Norton, L Winer, EP Hudis, CA Ellis, MJ Berry, DA AF Hayes, Daniel F. Thor, Ann D. Dressler, Lynn G. Weaver, Donald Edgerton, Susan Cowan, David Broadwater, Gloria Goldstein, Lori J. Martino, Silvana Ingle, James N. Henderson, I. Craig Norton, Larry Winer, Eric P. Hudis, Clifford A. Ellis, Matthew J. Berry, Donald A. CA CALGB Investigators TI HER2 and response to paclitaxel in node-positive breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; ADJUVANT CHEMOTHERAPY; C-ERBB-2 EXPRESSION; PREDICT RESPONSE; DOSE INTENSITY; THERAPY; TRASTUZUMAB; HER-2/NEU; DOCETAXEL; CELLS AB Background The status of human epidermal growth factor receptor type 2 (HER2) in breast-cancer cells predicts clinical outcomes in women who receive adjuvant anthracycline-based chemotherapy. We hypothesized that HER2 positivity predicts a benefit from adjuvant doxorubicin doses above standard levels, from the addition of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide, or from both. Methods We randomly selected 1500 women from 3121 women with node-positive breast cancer who had been randomly assigned to receive doxorubicin (60, 75, or 90 mg per square meter of body-surface area) plus cyclophosphamide (600 mg per square meter) for four cycles, followed by four cycles of paclitaxel (175 mg per square meter) or observation. Tissue blocks from 1322 of these 1500 women were available. Immunohistochemical analyses of these tissue specimens for HER2 with the CB11 monoclonal antibody against HER2 or with a polyclonal-antibody assay kit and fluorescence in situ hybridization for HER2 amplification were performed. Results No interaction was observed between HER2 positivity and doxorubicin doses above 60 mg per square meter. HER2 positivity was, however, associated with a significant benefit from paclitaxel. The interaction between HER2 positivity and the addition of paclitaxel to the treatment was associated with a hazard ratio for recurrence of 0.59 (P=0.01). Patients with a HER2-positive breast cancer benefited from paclitaxel, regardless of estrogen-receptor status, but paclitaxel did not benefit patients with HER2-negative, estrogen-receptor-positive cancers. Conclusions The expression or amplification, or both, of HER2 by a breast cancer is associated with a benefit from the addition of paclitaxel after adjuvant treatment with doxorubicin (<60 mg per square meter) plus cyclophosphamide in node-positive breast cancer, regardless of estrogen-receptor status. Patients with HER2-negative, estrogen-receptor-positive, node-positive breast cancer may gain little benefit from the administration of paclitaxel after adjuvant chemotherapy with doxorubicin plus cyclophosphamide. C1 Univ Michigan, Canc Ctr 6312, Breast Oncol Program, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Univ Colorado, Ctr Comprehens Canc, Aurora, CO USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ Vermont, Ctr Canc, Fletcher Allen Hlth Care, Burlington, VT USA. Duke Univ, Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Mayo Clin, Rochester, MN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Hayes, DF (reprint author), Univ Michigan, Canc Ctr 6312, Breast Oncol Program, Ctr Comprehens Canc, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM hayesdf@umich.edu FU NCI NIH HHS [CA092461, CA31946, CA33601] NR 46 TC 357 Z9 374 U1 1 U2 20 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 11 PY 2007 VL 357 IS 15 BP 1496 EP 1506 DI 10.1056/NEJMoa071167 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 218TE UT WOS:000250037000006 PM 17928597 ER PT J AU Rabb, H Colvin, RB Arnaout, MA Steinman, TI Haupert, HD Haupert, GT Niles, JL AF Rabb, Hamid Colvin, Robert B. Arnaout, M. Amin Steinman, Theodore I. Haupert, Harris Dr. Haupert, Garner T. Niles, John L. TI A 41-year-old man with abdominal pain and elevated serum creatinine - Acute tubular injury (acute tubular necrosis) and glomerular podocyte injury, both caused by NSAIDs in association with dehydration. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ACUTE-RENAL-FAILURE; ACUTE KIDNEY INJURY; BIOMARKER C1 Johns Hopkins Univ Hosp, Div Nephrol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rabb, H (reprint author), Johns Hopkins Univ Hosp, Div Nephrol, Baltimore, MD 21287 USA. NR 24 TC 8 Z9 8 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 11 PY 2007 VL 357 IS 15 BP 1531 EP 1541 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 218TE UT WOS:000250037000013 PM 17928602 ER PT J AU Perrin, JM Homer, CJ AF Perrin, James M. Homer, Charles J. TI The quality of children's health care matters - Time to pay attention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID EVENTS; UNIT C1 Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. MassGen Hosp Children, Boston, MA USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Natl Initiat Childrens Healthcare Qual, Cambridge, MA USA. RP Perrin, JM (reprint author), Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 13 TC 9 Z9 9 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 11 PY 2007 VL 357 IS 15 BP 1549 EP 1551 DI 10.1056/NEJMe078178 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 218TE UT WOS:000250037000017 PM 17928606 ER PT J AU Sargent, DJ Patiyil, S Yothers, G Haller, DG Gray, R Benedetti, J Buyse, M Labianca, R Seitz, JF O'Callaghan, CJ Francini, G Grothey, A O'Connell, M Catalano, PJ Kerr, D Green, E Wieand, HS Goldberg, RM de Gramont, A AF Sargent, Daniel J. Patiyil, Smitha Yothers, Greg Haller, Daniel G. Gray, Richard Benedetti, Jacqueline Buyse, Marc Labianca, Roberto Seitz, Jean Francois O'Callaghan, Christopher J. Francini, Guido Grothey, Axel O'Connell, Michael Catalano, Paul J. Kerr, David Green, Erin Wieand, Harry S. Goldberg, Richard M. de Gramont, Aimery TI End points for colon cancer adjuvant trials: Observations and recommendations based on individual patient data from 20,898 patients enrolled onto 18 Randomized trials from the ACCENT group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC COLORECTAL-CANCER; STAGE-II; PLUS IRINOTECAN; DUKES B; FLUOROURACIL; LEUCOVORIN; EFFICACY; CHEMOTHERAPY; LEVAMISOLE; THERAPY AB Purpose The traditional end point for colon adjuvant clinical trials is overall survival (OS). We previously validated disease-free survival (DFS) after 3-year follow-up as an excellent predictor of 5-year OS results. Here we explore shorter term DFS and OS end points, as well as stage dependency. Methods Individual patient data from 18 phase III trials including 43 arms and 20,898 patients were pooled. Association measures included correlation of event rates within arms, correlation of hazard ratios (HRs) between arms, trial level significance comparisons (via log-rank testing), and a formal surrogacy model. Results DFS at earlier times was less accurate in predicting OS than 3-year DFS, but 2-year DFS remained a strong predictor. DFS with 1-year minimum follow-up demonstrated perfect negative predicted value; all trials negative at 1 year for DFS were negative for 5-year OS. OS with 3-year minimum follow-up was also an excellent predictor for 5-year OS; OS at earlier time points provided inaccurate prediction. The association between 3-year DFS and 5-year OS was greater for stage III patients; correlation of HR within trials was 0.92 (95% CI, 0.85 to 0.95) for stage III patients and 0.70 (95% CI, 0.44 to 0.80) for stage II patients. Conclusion DFS outcomes after 2- or 3-year median follow- up are excellent predictors of 5-year OS. DFS outcomes are appropriate for trials in which the majority of patients are stage III. DFS after 2-or 3-year median follow-up should be considered as the primary end point in future colon adjuvant trials. C1 Mayo Clin, N Cent Canc Treatment Grp, Dept Hlth Sci Res, Rochester, MN 55905 USA. Mayo Clin, N Cent Canc Treatment Grp, Dept Med Oncol, Rochester, MN 55905 USA. Natl Surg Adjuvant Breast & Bowel Project Stat Ct, Ctr Biostat, Pittsburgh, PA USA. Operat Off, Pittsburgh, PA USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Allegheny Gen Hosp, Dept Human Oncol, Philadelphia, PA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Harvard Univ, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Eastern Cooperat Oncol Grp Stat Ctr, Boston, MA USA. Univ N Carolina, Dept Hematol Oncol, Chapel Hill, NC USA. Univ Oxford, Dept Clin Pharmacol, Oxford, England. Int Inst Drug Dev, Brussels, Belgium. Osped Riuniti Bergamo, Med Oncol Unit, I-24100 Bergamo, Italy. Univ Siena, Inst Internal Med, Div Med Oncol, Siena, Italy. Univ Mediterranean, CHU Timone, Gastroenterol Unit, Marseille, France. Hosp St Antoine, Paris, France. Queens Univ, Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON, Canada. RP Sargent, DJ (reprint author), Mayo Clin, N Cent Canc Treatment Grp, Dept Hlth Sci Res, 200 1st St SW,Harwick 8-27, Rochester, MN 55905 USA. EM sargent.daniel@mayo.edu RI Goldberg , Richard/M-1311-2013; Labianca, Roberto/N-1847-2016; OI Labianca, Roberto/0000-0001-7149-822X; Yothers, Greg/0000-0002-7965-7333; Sargent, Daniel/0000-0002-2684-4741 FU NCI NIH HHS [CA25224] NR 19 TC 124 Z9 127 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2007 VL 25 IS 29 BP 4569 EP 4574 DI 10.1200/JCO.2006.10.4323 PG 6 WC Oncology SC Oncology GA 233EQ UT WOS:000251073600013 PM 17876008 ER PT J AU Albritton, KH Wiggins, CH Nelson, HE Weeks, JC AF Albritton, Karen H. Wiggins, Charles H. Nelson, Harold E. Weeks, Jane C. TI Site of oncologic Specialty care for older adolescents in Utah SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER; RETROSPECTIVE ANALYSIS; SINGLE INSTITUTION; YOUNG-ADULTS; SURVIVAL; PATTERNS; PROTOCOL; CHILDREN; SURVEILLANCE AB Purpose Adolescents with cancer may access oncologic care from pediatric or adult medical centers, given overlapping age eligibility. However, some recent data suggest a benefit to adolescents with certain cancers when treated at pediatric centers or on pediatric protocols. We used a population-based registry to determine the site of care of children, adolescents, and young adults (age 0 to 24 years) with newly diagnosed cancer. Patients and Methods From the Utah Cancer Registry 1994 to 2000, new malignant cases in patients aged 0 to 24 years were chosen; data including diagnosis, home ZIP code and sites of oncologic care were abstracted. Distance between home ZIP code and Primary Children's Medical Center (PCMC; Salt Lake City, Utah), the state's sole site of pediatric oncology care, was determined. Results Sixty-six percent of Utah 15- to 19-year-olds with cancer were never seen by a PCMC oncologist. Even among this narrow age range, utilization of the pediatric center dropped with each additional year of age. Not unexpectedly, few of those with epithelial malignancies in this age group were seen at PCMC. But surprisingly, 47% of the older adolescents with leukemia, 66% with brain tumors, and 71% with lymphoma never saw a pediatric oncologist. After consideration of age and diagnosis, distance the patient lived from PCMC had a negligible effect on the likelihood of an adolescent being seen there. Conclusion The referral of adolescents with cancer to a pediatric oncology center diminishes greatly with age, and is moderately influenced by diagnosis and minimally by distance from center. Further study should investigate reasons for referral patterns, and impact on outcomes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Utah, Salt Lake City, UT USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Albritton, KH (reprint author), Dana Farber Canc Inst, 44 Binny St, Boston, MA 02115 USA. EM karen_albritton@dfci.harvard.edu FU NCI NIH HHS [N01-PC-35141, N01-PC-35138] NR 28 TC 43 Z9 43 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2007 VL 25 IS 29 BP 4616 EP 4621 DI 10.1200/JCO.2006.08.4103 PG 6 WC Oncology SC Oncology GA 233EQ UT WOS:000251073600020 PM 17925557 ER PT J AU Fullerton, BC Pandya, DN AF Fullerton, Barbara C. Pandya, Deepak N. TI Architectonic analysis of the auditory-related areas of the superior temporal region in human brain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Review DE cytoarchitecture; auditory cortex; Heschl's gyrus; koniocortex; primate ID HUMAN CEREBRAL-CORTEX; MEDIAL BELT REGIONS; HIGH-RESOLUTION MRI; RHESUS-MONKEY; CORTICAL CONNECTIONS; TONOTOPIC ORGANIZATION; MACAQUE MONKEYS; HIERARCHICAL ORGANIZATION; CYTOCHROME-OXIDASE; PREFRONTAL CORTEX AB Architecture of auditory areas of the superior temporal region (STR) in the human was analyzed in Nissl-stained material to see whether auditory cortex is organized according to principles that have been described in the rhesus monkey. Based on shared architectonic features, the auditory cortex in human and monkey is organized into three lines: areas in the cortex of the circular sulcus (root), areas on the supratemporal plane (core), and areas on the superior temporal gyrus (belt). The cytoarchitecture of the auditory area changes in a stepwise manner toward the koniocortical area, both from the direction of the temporal polar proisocortex as well as from the caudal temporal cortex. This architectonic dichotomy is consistent with differences in cortical and subcortical connections of STR and may be related to different functions of the rostral and caudal temporal cortices. There are some differences between rhesus monkey and human auditory anatomy. For instance, the koniocortex, root area Pal, and belt area PaA show further differentiation into subareas in the human brain. The relative volume of the core area is larger than that of the belt area in the human, but the reverse is true in the monkey. The functional significance of these differences across species is not known but may relate to speech and language functions. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Ctr Geriatr Res Educ & Clin, Edith Nourse Rogers Mem VA Med Ctr, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. RP Fullerton, BC (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. EM Barbara_Fullerton@meei.harvard.edu FU NIDCD NIH HHS [P01DC 00119] NR 110 TC 63 Z9 63 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD OCT 10 PY 2007 VL 504 IS 5 BP 470 EP 498 DI 10.1002/cne.21432 PG 29 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 208VN UT WOS:000249347400003 PM 17701981 ER PT J AU Sfakianos, MK Eisman, A Gourley, SL Bradley, WD Scheetz, AJ Settleman, J Taylor, JR Greer, CA Williamson, A Koleske, AJ AF Sfakianos, Mindan K. Eisman, Aaron Gourley, Shannon L. Bradley, William D. Scheetz, Alfred J. Settleman, Jeffrey Taylor, Jane R. Greer, Charles A. Williamson, Anne Koleske, Anthony J. TI Inhibition of rho via arg and p190RhoGAP in the postnatal mouse hippocampus regulates dendritic spine maturation, synapse and dendrite stability, and behavior SO JOURNAL OF NEUROSCIENCE LA English DT Article DE arg tyrosine kinase; dendrite; synapse; hippocampus; p190RhoGAP; Rho ID ABL TYROSINE KINASE; RETINAL GANGLION-CELLS; MENTAL-RETARDATION; NMDA RECEPTOR; SMALL GTPASES; IN-VIVO; C-ABL; ACTIN CYTOSKELETON; PYRAMIDAL NEURONS; ESSENTIAL ROLES AB The RhoA (Rho) GTPase is a master regulator of dendrite morphogenesis. Rho activation in developing neurons slows dendrite branch dynamics, yielding smaller, less branched dendrite arbors. Constitutive activation of Rho in mature neurons causes dendritic spine loss and dendritic regression, indicating that Rho can affect dendritic structure and function even after dendrites have developed. However, it is unclear whether and how endogenous Rho modulates dendrite and synapse morphology after dendrite arbor development has occurred. We demonstrate that a Rho inhibitory pathway involving the Arg tyrosine kinase and p190RhoGAP is essential for synapse and dendrite stability during late postnatal development. Hippocampal CA1 pyramidal dendrites develop normally in arg(-/-) mice, reaching their mature size by postnatal day 21 (P21). However, dendritic spines do not undergo the normal morphological maturation in these mice, leading to a loss of hippocampal synapses and dendritic branches by P42. Coincident with this synapse and dendrite loss, arg(-/-) mice exhibit progressive deficits in a hippocampus-dependent object recognition behavioral task. p190RhoGAP localizes to dendritic spines, and its activity is reduced in arg(-/-) hippocampus, leading to increased Rho activity. Although mutations in p190rhogap enhance dendritic regression resulting from decreased Arg levels, reducing gene dosage of the Rho effector ROCKII can suppress the dendritic regression observed in arg(-/-) mice. Together, these data indicate that signaling through Arg and p190RhoGAP acts late during synaptic refinement to promote dendritic spine maturation and synapse/dendrite stability by attenuating synaptic Rho activity. C1 Yale Univ, Sch Med, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Sch Med, Interdept Neurosci Program, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Neurobiol, Connecticut Mental Hlth Ctr, New Haven, CT 06520 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Koleske, AJ (reprint author), Yale Univ, Sch Med, Dept Mol Biophys & Biochem, 333 Cedar St SHMC-E31, New Haven, CT 06520 USA. EM anthony.koleske@yale.edu RI Bradley, William/C-3151-2011 FU NIMH NIH HHS [MH77306]; NINDS NIH HHS [R01 NS039475, NS39475, NS058086] NR 56 TC 68 Z9 68 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 10 PY 2007 VL 27 IS 41 BP 10982 EP 10992 DI 10.1523/JNEUROSCI.0793-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 219KK UT WOS:000250083300008 PM 17928439 ER PT J AU Wu, HQ Neilson, JR Kumar, P Manocha, M Shankar, P Sharp, PA Manjunath, N AF Wu, Haoquan Neilson, Joel R. Kumar, Priti Manocha, Monika Shankar, Premlata Sharp, Phillip A. Manjunath, N. TI miRNA Profiling of Naive, Effector and Memory CD8 T Cells SO PLOS ONE LA English DT Article AB microRNAs have recently emerged as master regulators of gene expression during development and cell differentiation. Although profound changes in gene expression also occur during antigen-induced T cell differentiation, the role of miRNAs in the process is not known. We compared the miRNA expression profiles between antigen-specific naive, effector and memory CD8+ T cells using 3 different methods-small RNA cloning, miRNA microarray analysis and real-time PCR. Although many miRNAs were expressed in all the T cell subsets, the frequency of 7 miRNAs (miR-16, miR-21, miR-142-3p, miR-142-5p, miR-150, miR-15b and let-7f) alone accounted for similar to 60% of all miRNAs, and their expression was several fold higher than the other expressed miRNAs. Global downregulation of miRNAs (including 6/7 dominantly expressed miRNAs) was observed in effector T cells compared to naive cells and the miRNA expression levels tended to come back up in memory T cells. However, a few miRNAs, notably miR-21 were higher in effector and memory T cells compared to naive T cells. These results suggest that concomitant with profound changes in gene expression, miRNA profile also changes dynamically during T cell differentiation. Sequence analysis of the cloned mature miRNAs revealed an extensive degree of end polymorphism. While 3' end polymorphisms dominated, heterogeneity at both ends, resembling drosha/dicer processing shift was also seen in miR-142, suggesting a possible novel mechanism to generate new miRNA and/or to diversify miRNA target selection. Overall, our results suggest that dynamic changes in the expression of miRNAs may be important for the regulation of gene expression during antigen-induced T cell differentiation. Our study also suggests possible novel mechanisms for miRNA biogenesis and function. C1 [Wu, Haoquan; Kumar, Priti; Manocha, Monika; Shankar, Premlata; Manjunath, N.] Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. [Wu, Haoquan; Kumar, Priti; Manocha, Monika; Shankar, Premlata; Manjunath, N.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Neilson, Joel R.; Sharp, Phillip A.] MIT, Ctr Canc Res, Cambridge, MA 02139 USA. [Sharp, Phillip A.] MIT, Dept Biol, Cambridge, MA 02139 USA. RP Manjunath, N (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM swamy@cbrinstitute.org RI Kumar, Priti/C-5699-2009; OI Kumar, Priti/0000-0002-6901-5601 FU NIH [U19 AI 056900, R21 AI 066197] FX Funding: This work was supported by NIH grant U19 AI 056900 and R21 AI 066197 to N. M. NR 53 TC 274 Z9 308 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 10 PY 2007 VL 2 IS 10 AR e1020 DI 10.1371/journal.pone.0001020 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HV UT WOS:000207456000019 PM 17925868 ER PT J AU Javanbakht, HN Diaz-Griffero, F Yuan, W Yeung, DF Li, X Song, B Sodroski, J AF Javanbakht, Hassa. N. Diaz-Griffero, Felipe Yuan, Wen Yeung, Darwin F. Li, Xing Song, Byeongwoon Sodroski, Joseph TI The ability of multimerized cyclophilin A to restrict retrovirus infection SO VIROLOGY LA English DT Article DE cyclophilin A; HIV-1; FIV; retroviral capsid; coiled-coil domain; multimerization; restriction; TRIMS; TRIMCyp ID IMMUNODEFICIENCY-VIRUS TYPE-1; MURINE LEUKEMIA-VIRUS; MONKEY TRIM5-ALPHA; HIV-1 VIRIONS; HUMAN-CELLS; CAPSIDS; BINDING; RETROTRANSPOSITION; RECOGNITION; RESISTANCE AB In owl monkeys, the typical retroviral restriction factor of primates, TRIM5 alpha, is replaced by TRIMCyp. TRIMCyp consists of the TRIMS RING, B-box 2 and coiled-coil domains, as well as the intervening linker regions, fused with cyclophilin A. TRIMCyp restricts infection of retroviruses, such as human immunodeficiency virus (HIV-1) and feline immunodeficiency virus (FIV), with capsids that can bind cyclophilin A. The TRIMS coiled coil promotes the trimerization of TRIMCyp. Here we show that cyclophilin A that is oligomeric as a result of fusion with a heterologous multimer exhibits substantial antiretroviral activity. The addition of the TRIMS RING, B-box 2 and Linker 2 to oligomeric cyclophilin A generated a protein with antiretroviral activity approaching that of wild-type TRIMCyp. Multimerization increased the binding of cyclophilin A to the HIV-1 capsid, promoting accelerated uncoating of the capsid and restriction of infection. (C) 2007 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Dana Farber Canc Inst, AIDS, 44 Binney St,Jfb 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009 FU NHLBI NIH HHS [P50 HL054785, HL54785]; NIAID NIH HHS [R01 AI063987-03, AI063987, R01 AI063987, AI28691, P30 AI028691] NR 36 TC 34 Z9 35 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2007 VL 367 IS 1 BP 19 EP 29 DI 10.1016/j.virol.2007.04.034 PG 11 WC Virology SC Virology GA 216TS UT WOS:000249902500003 PM 17574642 ER PT J AU Dunfee, RL Thomas, ER Wang, JB Kunstman, K Wolinsky, SM Gabuzda, D AF Dunfee, Rebecca L. Thomas, Elaine R. Wang, Jianbin Kunstman, Kevin Wolinsky, Steven M. Gabuzda, Dana TI Loss of the N-linked glycosylation site at position 386 in the HIV envelope V4 region enhances macrophage tropism and is associated with dementia SO VIROLOGY LA English DT Article DE human immunodeficiency virus type 1 (HIV); envelope; CD4; macrophage tropism; neurotropism; neutralization; b12 antibody; neuropathogenesis; glycosylation ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CENTRAL-NERVOUS-SYSTEM; MONOCYTE-DERIVED MACROPHAGES; HUMAN MONOCLONAL-ANTIBODY; CHEMOKINE RECEPTORS CCR3; NEUTRALIZATION SENSITIVITY; NEUROLOGIC DISEASE; LYMPHOID-TISSUES; TYPE-1 INFECTION AB HIV infects macrophages and microglia in the central nervous system (CNS). Mechanisms that enhance HIV macrophage/microglial tropism are not well understood. Here, we identify an HIV Env variant in the V4 region of gp120, Asp 386 (D386), that eliminates an N-linked glycosylation site at position 386, enhances viral replication in macrophages, and is present at a higher frequency in AIDS patients with HIV-associated dementia (HAD) compared with non-HAD patients. D386 enhances HIV entry and replication in macrophages but not in microglia or peripheral blood mononuclear cells, possibly due to differential glycosylation in these cell types. A D386N mutation in the UK1br Env, which restores the N-linked glycan site, reduced neutralization sensitivity to the IgG1b12 (b12) monoclonal antibody, which recognizes a conserved neutralization epitope that overlaps the CD4 binding site. Molecular modeling suggested that loss of the glycan at position 386 increases exposure of the CD4 and b 12 binding sites on gp 120. Loss of a glycan at 386 was more frequent in Envs from HAD patients (26%; n=185) compared with non-HAD patients (7%; n=99; p<0.001). The most significant association of these Env variants with HAD was in blood or lymphoid tissue rather than brain. These findings suggest that increased exposure of the b12 epitope overlapping the CD4 binding site via elimination of a glycan at position 386 is associated with enhanced HIV macrophage tropism, and provide evidence that determinants of macrophage and microglia tropism are overlapping but distinct. (C) 2007 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Canc Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Gabuzda, D (reprint author), Dana Farber Canc Inst, Dept Canc Immunol, JFB 816,44 Binney St, Boston, MA 02115 USA. EM dana_gabuzda@dfci.harvard.edu RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NINDS NIH HHS [R01 NS037277-07, R01 NS037277-08, R01 NS037277-06, R01 NS037277, R01 NS037277-09, NS37277] NR 77 TC 59 Z9 62 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2007 VL 367 IS 1 BP 222 EP 234 DI 10.1016/j.virol.2007.05.029 PG 13 WC Virology SC Virology GA 216TS UT WOS:000249902500022 PM 17599380 ER PT J AU Li, FH Zhou, XB Zhu, JM Ma, JW Huang, XD Wong, STC AF Li, Fuhai Zhou, Xiaobo Zhu, Jinmin Ma, Jinwen Huang, Xudong Wong, Stephen T. C. TI High content image analysis for human H4 neuroglioma cells exposed to CuO nanoparticles SO BMC BIOTECHNOLOGY LA English DT Article ID AUTOMATIC SEGMENTATION; MICROSCOPY; NUCLEI; CLASSIFICATION; ALGORITHMS AB Background: High content screening (HCS)-based image analysis is becoming an important and widely used research tool. Capitalizing this technology, ample cellular information can be extracted from the high content cellular images. In this study, an automated, reliable and quantitative cellular image analysis system developed in house has been employed to quantify the toxic responses of human H4 neuroglioma cells exposed to metal oxide nanoparticles. This system has been proved to be an essential tool in our study. Results: The cellular images of H4 neuroglioma cells exposed to different concentrations of CuO nanoparticles were sampled using IN Cell Analyzer 1000. A fully automated cellular image analysis system has been developed to perform the image analysis for cell viability. A multiple adaptive thresholding method was used to classify the pixels of the nuclei image into three classes: bright nuclei, dark nuclei, and background. During the development of our image analysis methodology, we have achieved the followings: (1) The Gaussian filtering with proper scale has been applied to the cellular images for generation of a local intensity maximum inside each nucleus; (2) a novel local intensity maxima detection method based on the gradient vector field has been established; and (3) a statistical model based splitting method was proposed to overcome the under segmentation problem. Computational results indicate that 95.9% nuclei can be detected and segmented correctly by the proposed image analysis system. Conclusion: The proposed automated image analysis system can effectively segment the images of human H4 neuroglioma cells exposed to CuO nanoparticles. The computational results confirmed our biological finding that human H4 neuroglioma cells had a dose-dependent toxic response to the insult of CuO nanoparticles. C1 [Li, Fuhai; Zhou, Xiaobo; Wong, Stephen T. C.] Weill Cornell Med Coll, Methodist Hosp, Res Inst, Ctr Biomed Informat, Houston, TX 77030 USA. [Li, Fuhai; Ma, Jinwen] Peking Univ, Sch Math Sci, Dept Informat Sci, Beijing 100871, Peoples R China. [Li, Fuhai; Ma, Jinwen] Peking Univ, LMAM, Beijing 100871, Peoples R China. [Li, Fuhai; Wong, Stephen T. C.] Weill Cornell Med Coll, Methodist Hosp, Dept Radiol, Div Res, Houston, TX 77030 USA. [Zhu, Jinmin; Huang, Xudong] Harvard Univ, Sch Med, Brigham & Womens Hosp, Funct & Mol Imaging Ctr, Boston, MA 02115 USA. [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat & Genet, Neurochem Lab, Boston, MA 02114 USA. [Huang, Xudong] Massachusetts Gen Hosp, Aging Res Unit, Boston, MA 02114 USA. [Huang, Xudong] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wong, STC (reprint author), Weill Cornell Med Coll, Methodist Hosp, Res Inst, Ctr Biomed Informat, Houston, TX 77030 USA. EM robert.fh.li@gmail.com; XZhou@tmhs.org; jzhu2@partners.org; jwma@math.pku.edu.cn; xhuang3@partners.org; STWong@tmhs.org FU NIMH NIH HHS [K12 MH069281, K01 MH002001, 5K12MH069281-04, 5K01MH002001] NR 19 TC 26 Z9 28 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD OCT 9 PY 2007 VL 7 AR 66 DI 10.1186/1472-6750-7-66 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 244ZA UT WOS:000251902800001 PM 17925027 ER PT J AU Scirica, BM Morrow, DA Hod, H Murphy, SA Belardinelli, L Hedgepeth, CM Molhoek, P Verheugt, FWA Gersh, BJ McCabe, CH Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Hod, Hanoch Murphy, Sabina A. Belardinelli, Luiz Hedgepeth, Chester M. Molhoek, Peter Verheugt, Freek W. A. Gersh, Bernard J. McCabe, Carolyn H. Braunwald, Eugene TI Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of Arrhythmias in patients with Non-ST-Segment-Elevation acute coronary syndrome - Thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36) Randomized controlled trial SO CIRCULATION LA English DT Article DE coronary disease; antiarrhythmia agents; tachyarrhythmias ID MYOCARDIAL-INFARCTION; CHRONIC ANGINA; DYSFUNCTION; AMLODIPINE; SURVIVAL AB Background - Ranolazine, a piperazine derivative, reduces ischemia via inhibition of the late phase of the inward sodium current (late I-Na) during cardiac repolarization, with a consequent reduction in intracellular sodium and calcium overload. Increased intracellular calcium leads to both mechanical dysfunction and electric instability. Ranolazine reduces proarrhythmic substrate and triggers such as early afterdepolarization in experimental models. However, the potential antiarrhythmic actions of ranolazine have yet to be demonstrated in humans. Methods and Results - The Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST- Elevation Acute Coronary Syndrome ( MERLIN) - Thrombolysis in Myocardial Infarction ( TIMI) 36 ( MERLIN- TIMI 36) trial randomized 6560 patients hospitalized with a non-ST- elevation acute coronary syndrome to ranolazine or placebo in addition to standard therapy. Continuous ECG ( Holter) recording was performed for the first 7 days after randomization. A prespecified set of arrhythmias were evaluated by a core laboratory blinded to treatment and outcomes. Of the 6560 patients in MERLIN- TIMI 36, 6351 ( 97%) had continuous ECG recordings that could be evaluated for arrhythmia analysis. Treatment with ranolazine resulted in significantly lower incidences of arrhythmias. Specifically, fewer patients had an episode of ventricular tachycardia lasting >= 8 beats ( 166 [5.3%] versus 265 [8.3%]; P < 0.001), supraventricular tachycardia ( 1413 [ 44.7%] versus 1752 [ 55.0%]; P < 0.001), or new- onset atrial fibrillation ( 55 [ 1.7%] versus 75 [ 2.4%]; P = 0.08). In addition, pauses >= 3 seconds were less frequent with ranolazine ( 97 [ 3.1%] versus 136 [ 4.3%]; P = 0.01). Conclusions - Ranolazine, an inhibitor of late INa, appears to have antiarrhythmic effects as assessed by continuous ECG monitoring of patients in the first week after admission for acute coronary syndrome. Studies specifically designed to evaluate the potential role of ranolazine as an antiarrhythmic agent are warranted. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CV Therapeut, Palo Alto, CA USA. Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Medisch Spectrum Twente, Enschede, Netherlands. HaertLung Ctr, Nijmegen, Netherlands. Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM bscirica@partners.org RI Verheugt, F.W.A./H-8105-2014 NR 17 TC 231 Z9 238 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 9 PY 2007 VL 116 IS 15 BP 1647 EP 1652 DI 10.1161/CIRCULATIONAHA.107.724880 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 218HX UT WOS:000250007700002 PM 17804441 ER PT J AU El-Serag, HB Lau, M Eschbach, K Davila, J Goodwin, J AF El-Serag, Hashem B. Lau, Melvin Eschbach, Karl Davila, Jessica Goodwin, James TI Epidemiology of hepatocellular carcinoma in Hispanics in the United States SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID INCREASING INCIDENCE; MORTALITY; RATES AB Background: To our knowledge, no detailed analysis exists of the incidence and mortality of hepatocellular carcinoma (HCC) among Hispanics in the United States. In previous studies, the rates for Hispanics have not been reported separately from other racial or ethnic groups. Methods: We used information on patients diagnosed as having HCC from 13 registries in the Surveillance Epidemiology and End Results (SEER) database of the National Cancer Institute to calculate race-specific, age-adjusted incidence rates (AIR) between 1992 and 2002. We also used California and Texas state death records from between 1979 and 2001 to calculate race-specific, age-adjusted mortality rates for liver cancer excluding intrahepatic cholangiocarcinoma. For Hispanics and Asians/ Pacific Islanders, the rates were calculated for native-born subjects and immigrants separately. Results: In SEER, the yearly AIRs were higher by 1.2-fold in Hispanics than in blacks (6.3 vs 5.0 per 100 000 person-years of the underlying US population) and by 2.7-fold than in non-Hispanic whites (2.4 per 100 000 person-years) but lower than in Asians/Pacific Islanders (10.8 per 100 000 person-years). The median age at HCC diagnosis in Hispanics (64 years) was intermediate between whites (the oldest) and blacks (the youngest). Between the periods 1992-1995 and 2000-2002, there was a 31% increase in the incidence of HCC in Hispanic men and a 63% increase in Hispanic women. The race-specific, age-adjusted mortality rates were remarkably similar in California and Texas and were highest in immigrant Asian/Pacific Islanders followed by native Hispanics. The rates for native Hispanic men were more than twice as high as those for immigrant Hispanic men. For Texas, the rates for native Hispanic men were 65% higher than those for immigrant Hispanic men. Conclusion: Hispanics in the United States have high rates of HCC that are second only to Asians/Pacific Islanders. C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Internal Med, Div Geriatr, Galveston, TX 77550 USA. RP El-Serag, HB (reprint author), Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU NCI NIH HHS [P50 CA 10563-03] NR 18 TC 64 Z9 64 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 8 PY 2007 VL 167 IS 18 BP 1983 EP 1989 DI 10.1001/archinte.167.18.1983 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 217LC UT WOS:000249948400010 PM 17923599 ER PT J AU Gheorghiade, M Rossi, JS Cotts, W Shin, DD Hellkamp, AS Pina, IL Fonarow, GC DeMarco, T Pauly, DF Rogers, J DiSalvo, TG Butler, J Hare, JM Francis, GS Stough, WG O'Connor, CM AF Gheorghiade, Mihai Rossi, Joseph S. Cotts, William Shin, David D. Hellkamp, Anne S. Pina, Ileana L. Fonarow, Gregg C. DeMarco, Teresa Pauly, Daniel F. Rogers, Joseph DiSalvo, Thomas G. Butler, Javed Hare, Joshua M. Francis, Gary S. Stough, Wendy Gattis O'Connor, Christopher M. TI Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ARTERY CATHETERIZATION EFFECTIVENESS; RANDOMIZED CONTROLLED-TRIAL; VASOPRESSIN ANTAGONIST; INTRAVENOUS MILRINONE; SERUM SODIUM; DOUBLE-BLIND; TOLVAPTAN; OUTCOMES; MECHANISMS; EVEREST AB Background: Mild hyponatremia is relatively common in patients hospitalized with heart failure (HF). To our knowledge, the association of hyponatremia with outcomes has not been evaluated in the context of in-hospital clinical course including central hemodynamics and changes in serum sodium level. Methods: The ESCAPE trial (Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness) was a randomized, controlled study designed to evaluate the utility of a pulmonary artery catheter plus clinical assessment vs clinical assessment alone in guiding therapy in patients hospitalized with New York Heart Association class IV HF due to systolic dysfunction (left ventricular ejection fraction <30%). A Cox proportional hazards model with baseline serum sodium level as a continuous variable was used to examine the association of serum sodium level with 6-month postdischarge mortality, HF rehospitalization, and death or rehospitalization. A categorical analysis was also performed comparing persistent and corrected hyponatremia. Results: A total of 433 hospitalized patients with HF were enrolled in ESCAPE. Hyponatremia (serum sodium level <= 134 mEq/L) was present in 103 patients (23.8%). (To convert serum sodium to millimoles per liter, multiply by 1.0.) Of these, 71 had persistent hyponatremia (68.9%). Hyponatremia was associated with higher 6-month mortality after covariate adjustment (hazard ratio [HR] for each 3-mEq/L decrease in sodium level, 1.23; 95% confidence interval [CI], 1.05-1.43) (P=.01),. After controlling for baseline variables and clinical response, we found that patients with persistent hyponatremia had an increased risk of all-cause mortality (31% vs 16%; HR, 1.82) (P=.04), HF rehospitalization (62% vs 43%; HR, 1.52) (P=.03), and death or rehospitalization (73% vs 50%; HR, 1.54) (P=.01) compared with normonatremic patients. Conclusion: Persistent hyponatremia was an independent predictor of mortality, HF hospitalization, and death or rehospitalization despite clinical and hemodynamic improvements that were similar to those in patients without hyponatremia. C1 Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Duke Univ, Med Ctr, Durham, NC USA. Campbell Univ, Sch Pharm, Dept Clin Res, Res Triangle Pk, NC USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Florida, Shands Hosp, Gainesville, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Johns Hopkins Univ, Baltimore, MD USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Gheorghiade, M (reprint author), Northwestern Univ, Feinberg Sch Med, Div Cardiol, Galter 10-240,201 E Huron St, Chicago, IL 60611 USA. EM m-gheorghiade@northwestern.edu RI Stough, Wendy/R-4287-2016 OI Stough, Wendy/0000-0001-8290-1205 FU NHLBI NIH HHS [N01 HV 98177] NR 26 TC 140 Z9 149 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 8 PY 2007 VL 167 IS 18 BP 1998 EP 2005 DI 10.1001/archinte.167.18.1998 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 217LC UT WOS:000249948400012 PM 17923601 ER PT J AU Gordon, AJ Trafton, JA Saxon, AJ Gifford, AL Goodman, F Calabrese, VS McNicholas, L Liberto, J AF Gordon, Adam J. Trafton, Jodie A. Saxon, Andrew J. Gifford, Allen L. Goodman, Francine Calabrese, Vincent S. McNicholas, Laura Liberto, Joseph TI Implementation of buprenorphine in the Veterans Health administration: Results of the first 3 years SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article ID OFFICE-BASED TREATMENT; OPIOID DEPENDENCE; PRIMARY-CARE; ADDICTION; NALOXONE AB Background: Compared to non-veterans, veterans are disproportionately diagnosed with opioid dependence. Sublingual buprenorphine provides greater access to opioid agonist therapy. To understand the diffusion of this innovative treatment within a large healthcare system, we describe the introduction of buprenorphine, within the Veterans Health Administration (VHA) during the first 3 years of its approval as a VHA non-formulary medication. Methods: Using VHA pharmacy databases, we examined the number of physicians who have prescribed buprenorphine and the number of veterans who have received office-based buprenorphine within VHA veterans integrated service networks (VISN) from fiscal years (FY) 2003 through FY 2005 (October 2002 through September 2005). Results: From FY2003 through FY2005 the number of veterans with opioid dependence increased from 25,031 to 26,859 (>7.3%) and the number of veterans prescribed office-based buprenorphine increased from 53 to 739. During this interval, 16 of 21 VISNs had prescribed buprenorphine. In FY2005, two VISNs accounted for 31% of buprenorphine prescriptions. The number of buprenorphine prescriptions varied widely by VISN, but increased from 212 to 7076 from FY2003 through FY2005. During this interval, prescriptions per patient increased from 4.0 to 9.6 and physicians prescribing buprenorphine increased from 14 to 170. The ratio of patients prescribed buprenorphine to providers prescribing buprenorphine increased from 3.8 to 4.3 with an average increase of 15.1-41.6 of prescriptions per provider. Conclusions: VHA increased, but not uniformly, the non-formulary use of office-based buprenorphine during the first 3 years of availability. Published by Elsevier Ireland Ltd. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, VISN Mental Illness Res Educ & Clin Ctr 4, Pittsburgh, PA 15240 USA. VA Palo Alto Hlth Care Syst, Program Evaluat & Resource Ctr, Menlo Pk, CA 94025 USA. VA Puget Sound Hlth Care Syst S 116 ATC, Seattle, WA 98108 USA. VA New England Healthcare, VA Bedford Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA 01730 USA. VACO Pharm Benefits Management Strateg Healthcare, Hines, IL 60141 USA. Philadelphia VAMC, Philadelphia, PA 19104 USA. VA Maryland Hlth Care Syst, Mental Hlth Clin Ctr, Baltimore, MD 21201 USA. RP Gordon, AJ (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, VISN Mental Illness Res Educ & Clin Ctr 4, Mailcode 151-C,Univ Dr C, Pittsburgh, PA 15240 USA. EM adam.gordon@va.gov; Jodie.Trafton@va.gov; asaxon@u.washington.edu; allen.gifford@va.gov; Francine.Goodman@va.gov; vincent.calabrese@va.gov; Laura.McNicholas@va.gov; joseph.liberto@va.gov NR 17 TC 21 Z9 21 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 8 PY 2007 VL 90 IS 2-3 BP 292 EP 296 DI 10.1016/j.drugalcdep.2007.03.010 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 213GD UT WOS:000249653600022 PM 17493771 ER PT J AU Sharp, GC Kandasamy, N Singh, H Folkert, M AF Sharp, G. C. Kandasamy, N. Singh, H. Folkert, M. TI GPU-based streaming architectures for fast cone-beam CT image reconstruction and demons deformable registration SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID PARALLEL-BEAM; ALGORITHM; BACKPROJECTION; IMPLEMENTATION; RADIOTHERAPY; VALIDATION; HARDWARE; SYSTEMS AB This paper shows how to significantly accelerate cone-beam CT reconstruction and 3D deformable image registration using the stream-processing model. We describe data-parallel designs for the Feldkamp, Davis and Kress (FDK) reconstruction algorithm, and the demons deformable registration algorithm, suitable for use on a commodity graphics processing unit. The streaming versions of these algorithms are implemented using the Brook programming environment and executed on an NVidia 8800 GPU. Performance results using CT data of a preserved swine lung indicate that the GPU-based implementations of the FDK and demons algorithms achieve a substantial speedup-up to 80 times for FDK and 70 times for demons when compared to an optimized reference implementation on a 2.8 GHz Intel processor. In addition, the accuracy of the GPU-based implementations was found to be excellent. Compared with CPU-based implementations, the RMS differences were less than 0.1 Hounsfield unit for reconstruction and less than 0.1 mm for deformable registration. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Drexel Univ, Dept Elect & Comp Engn, Philadelphia, PA 19104 USA. RP Sharp, GC (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 25 TC 109 Z9 117 U1 5 U2 17 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2007 VL 52 IS 19 BP 5771 EP 5783 DI 10.1088/0031-9155/52/19/003 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 224JL UT WOS:000250443200003 PM 17881799 ER PT J AU Lorenz, F Nalichowski, A Rosca, F Kung, J Wenz, F Zygmanski, P AF Lorenz, Friedlieb Nalichowski, Adrian Rosca, Florin Kung, Jong Wenz, Frederik Zygmanski, Piotr TI Spatial dependence of MLC transmission in IMRT delivery SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INTENSITY-MODULATED RADIOTHERAPY; MULTILEAF COLLIMATOR; MONTE-CARLO; RADIATION-THERAPY; DOSE CALCULATION; VERIFICATION; SIMULATION; SCATTER; ENERGY; SYSTEM AB In complex intensity-modulated radiation therapy cases, a considerable amount of the total dose may be delivered through closed leaves. In such cases an accurate knowledge of spatial characteristics of multileaf collimator ( MLC) transmission is crucial, especially for the treatment of large targets with split fields. Measurements with an ionization chamber, radiographic films ( EDR2, EBT) and EPID are taken to characterize all relevant effects related to MLC transmission for various field sizes and depths. Here we present a phenomenological model to describe MLC transmission, whereby the main focus is the off-axis decrease of transmission for symmetric and asymmetric fields as well as on effects due to the tongue and groove design of the leaves, such as interleaf transmission and the tongue and groove effect. Data obtained with the four different methods are presented, and the utility of each measurement method to determine the necessary model parameters is discussed. With the developed model, it is possible to predict the relevant MLC effects at any point in the phantom for arbitrary jaw settings and depths. C1 Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-68167 Mannheim, Germany. Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Lorenz, F (reprint author), Univ Heidelberg, Mannheim Med Ctr, Dept Radiat Oncol, D-68167 Mannheim, Germany. NR 22 TC 12 Z9 13 U1 0 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2007 VL 52 IS 19 BP 5985 EP 5999 DI 10.1088/0031-9155/52/19/018 PG 15 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 224JL UT WOS:000250443200018 PM 17881814 ER PT J AU Garrett, WS Lord, GM Punit, S Lugo-Villarino, G Mazmanian, SK Ito, S Glickman, JN Glimcher, LH AF Garrett, Wendy S. Lord, Graham M. Punit, Shivesh Lugo-Villarino, Geanncarlo Mazmanian, Sarkis K. Ito, Susumu Glickman, Jonathan N. Glimcher, Laurie H. TI Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system SO CELL LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; COLONY-STIMULATING FACTOR; DENDRITIC CELLS; HUMAN INTESTINE; CROHNS-DISEASE; ACTIVATION; GUT; HOMEOSTASIS; MUTUALISM; CULTURES AB Inflammatory bowel disease (IBD) has been attributed to overexuberant host immunity or the emergence of harmful intestinal flora. The transcription factor T-bet orchestrates inflammatory genetic programs in both adaptive and innate immunity. We describe a profound and unexpected function for T-bet in influencing the behavior of host inflammatory activity and commensal bacteria. T-bet deficiency in the innate immune system results in spontaneous and communicable ulcerative colitis in the absence of adaptive immunity and increased susceptibility to colitis in immunologically intact hosts. T-bet controls the response of the mucosal immune system to commensal bacteria by regulating TNF-alpha production in colonic dendritic cells, critical for colonic epithelial barrier maintenance. Loss of T-bet influences bacterial populations to become colitogenic, and this colitis is communicable to genetically intact hosts. These findings reveal a novel function for T-bet as a peacekeeper of host-commensal relationships and provide new perspectives on the pathophysiology of IBD. C1 Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Guys & St Thomas NHS Fdn Trust, NIHR Biomed Res Ctr, London SE1 9RT, England. Kings Coll London, London WC2R 2LS, England. RP Lord, GM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. EM graham.lord@kcl.ac.uk; lglimche@hsph.harvard.edu RI Lord, Graham/B-3797-2011; OI Mazmanian, Sarkis/0000-0003-2713-1513; Lugo, Geanncarlo/0000-0003-4620-8491 FU Medical Research Council [G108/380]; NCI NIH HHS [R01 CA112663, R01 CA112663-06, R01 CA112663-07, CA112663]; NIAID NIH HHS [AI56296, P01 AI056296, P01 AI056296-01, P01 AI056296-010001, P01 AI056296-02, P01 AI056296-03, P01 AI056296-04, P01 AI056296-05] NR 36 TC 456 Z9 469 U1 4 U2 30 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 5 PY 2007 VL 131 IS 1 BP 33 EP 45 DI 10.1016/j.cell.2007.08.017 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 217FV UT WOS:000249934700009 PM 17923086 ER PT J AU Xiao, CC Calado, DP Galler, G Thai, TH Patterson, HC Wang, J Rajewsky, N Bender, TP Rajewsky, K AF Xiao, Changchun Calado, Dinis Pedro Galler, Gunther Thai, To-Ha Patterson, Heide Christine Wang, Jing Rajewsky, Nikolaus Bender, Timothy P. Rajewsky, Klaus TI MiR-150 controls B cell differentiation by targeting the transcription factor c-myb SO CELL LA English DT Article ID POSTTRANSCRIPTIONAL REGULATION; PERITONEAL-CELLS; GENE-EXPRESSION; MARGINAL ZONE; T-CELLS; PROLIFERATION; MICRORNAS; ELEGANS; MOTIFS; SYSTEM AB MiR-150 is a microRNA ( miRNA) specifically expressed in mature lymphocytes, but not their progenitors. A top predicted target of miR-150 is c-Myb, a transcription factor controlling multiple steps of lymphocyte development. Combining loss- and gain-of-function gene targeting approaches for miR-150 with conditional and partial ablation of c-Myb, we show that miR150 indeed controls c-Myb expression in vivo in a dose-dependent manner over a narrow range of miRNA and c-Myb concentrations and that this dramatically affects lymphocyte development and response. Our results identify a key transcription factor as a critical target of a stage-specifically expressed miRNA in lymphocytes and suggest that this and perhaps other miRNAs have evolved to control the expression of just a few critical target proteins in particular cellular contexts. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. Univ Virginia Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA. RP Rajewsky, K (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu FU NCI NIH HHS [CA85842, R01 CA085842]; NIAID NIH HHS [AI054636, AI059294, AI064345, R01 AI059294] NR 39 TC 589 Z9 639 U1 5 U2 37 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 5 PY 2007 VL 131 IS 1 BP 146 EP 159 DI 10.1016/j.cell.2007.07.021 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 217FV UT WOS:000249934700018 PM 17923094 ER PT J AU Shenoy, SK Barak, LS Xiao, KH Ahn, S Berthouze, M Shukla, AK Luttrell, LM Lefkowitz, RJ AF Shenoy, Sudha K. Barak, Larry S. Xiao, Kunhong Ahn, Seungkirl Berthouze, Magali Shukla, Arun K. Luttrell, Louis M. Lefkowitz, Robert J. TI Ubiquitination of beta-arrestin links seven-transmembrane receptor endocytosis and ERK activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR; ADRENERGIC-RECEPTOR; DEPENDENT ENDOCYTOSIS; CLATHRIN ADAPTER; VISUAL ARRESTIN; CELL; BETA-ARRESTIN2; KINASE; MONOUBIQUITINATION AB beta-Arrestin2 and its ubiquitination play crucial roles in both internalization and signaling of seven-transmembrane receptors (7TMRs). To understand the connection between ubiquitination and the endocytic and signaling functions of beta-arrestin, we generated a beta-arrestin2 mutant that is defective in ubiquitination (beta-arrestin2(OK)), by mutating all of the ubiquitin acceptor lysines to arginines and compared its properties with the wild type and a stably ubiquitinated beta-arrestin2-ubiquitin (Ub) chimera. In vitro translated beta-arrestin2 and beta-arrestin2(OK) displayed equivalent binding to recombinant beta(2)-adrenergic receptor (beta(2)AR) reconstituted in vesicles, whereas beta-arrestin2-Ub bound similar to 4-fold more. In cellular coimmunoprecipitation assays, beta-arrestin2(OK) bound nonreceptor partners, such as AP-2 and c-Raf and scaffolded phosphorylated ERK robustly but displayed weak binding to clathrin. Moreover, beta-arrestin2(OK) was recruited only transiently to activated receptors at the membrane, did not enhance receptor internalization, and decreased the amount of phosphorylated ERK assimilated into isolated beta(2)AR complexes. Although the wild type beta-arrestin2 formed ERK signaling complexes with the beta(2)AR at the membrane, a stably ubiquitinated beta-arrestin2-Ub chimera not only stabilized the ERK signalosomes but also led to their endosomal targeting. Interestingly, in cellular fractionation assays, the ubiquitination state of beta-arrestin2 favors its distribution in membrane fractions, suggesting that ubiquitination increases the propensity of beta-arrestin for membrane association. Our findings suggest that although beta-arrestin ubiquitination is dispensable for beta-arrestin cytosol to membrane translocation and its "constitutive" interactions with some cytosolic proteins, it nevertheless is a prerequisite both for the formation of tight complexes with 7TMRs in vivo and for membrane compartment interactions that are crucial for downstream endocytic and signaling processes. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Med Univ S Carolina, Dept Med Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29401 USA. RP Shenoy, SK (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. EM sudha@receptor-biol.duke.edu FU NHLBI NIH HHS [HL16037, R01 HL080525-02, R01 HL080525, R01 HL016037, HL080525]; NIDDK NIH HHS [R56 DK055524, DK55524, R01 DK055524] NR 45 TC 64 Z9 66 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 5 PY 2007 VL 282 IS 40 BP 29549 EP 29562 DI 10.1074/jbc.M700852200 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 215DH UT WOS:000249788000052 PM 17666399 ER PT J AU Muller, B Sheen, J AF Mueller, Bruno Sheen, Jen TI Advances in cytokinin signaling SO SCIENCE LA English DT Editorial Material ID RESPONSE REGULATORS; TRANSCRIPTION FACTORS; ARABIDOPSIS-THALIANA; TRANSDUCTION; DIFFERENTIATION; RECEPTOR; PATHWAY; AHK3; ARR2 C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu RI Mueller, Bruno/E-9888-2017 OI Mueller, Bruno/0000-0003-2664-7219 NR 19 TC 89 Z9 93 U1 1 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 OCT 5 PY 2007 VL 318 IS 5847 BP 68 EP 69 DI 10.1126/science.1145461 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 216YR UT WOS:000249915400039 PM 17916725 ER PT J AU Karnoub, AE Dash, AB Vo, AP Sullivan, A Brooks, MW Bell, GW Richardson, AL Polyak, K Tubo, R Weinberg, RA AF Karnoub, Antoine E. Dash, Ajeeta B. Vo, Annie P. Sullivan, Andrew Brooks, Mary W. Bell, George W. Richardson, Andrea L. Polyak, Kornelia Tubo, Ross Weinberg, Robert A. TI Mesenchymal stem cells within tumour stroma promote breast cancer metastasis SO NATURE LA English DT Article ID EXPRESSION; PROGRESSION; CARCINOMA; DELIVERY; GROWTH; RANTES; MICROENVIRONMENT; CHEMOKINES; VEHICLES; REVEALS AB Mesenchymal stem cells have been recently described to localize to breast carcinomas, where they integrate into the tumour-associated stroma. However, the involvement of mesenchymal stem cells (or their derivatives) in tumour pathophysiology has not been addressed. Here, we demonstrate that bone-marrow-derived human mesenchymal stem cells, when mixed with otherwise weakly metastatic human breast carcinoma cells, cause the cancer cells to increase their metastatic potency greatly when this cell mixture is introduced into a subcutaneous site and allowed to form a tumour xenograft. The breast cancer cells stimulate de novo secretion of the chemokine CCL5 (also called RANTES) from mesenchymal stem cells, which then acts in a paracrine fashion on the cancer cells to enhance their motility, invasion and metastasis. This enhanced metastatic ability is reversible and is dependent on CCL5 signalling through the chemokine receptor CCR5. Collectively, these data demonstrate that the tumour microenvironment facilitates metastatic spread by eliciting reversible changes in the phenotype of cancer cells. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Genzyme Corp, Framingham, MA 01701 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Weinberg, RA (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM weinberg@wi.mit.edu FU NCI NIH HHS [P50 CA089393, P50 CA089393-060014, P50 CA089393-070014, P50 CA089393-080014, R01 CA116235, R01 CA116235-01A1, R01 CA116235-02, R01 CA116235-03] NR 36 TC 1509 Z9 1598 U1 31 U2 221 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 4 PY 2007 VL 449 IS 7162 BP 557 EP U4 DI 10.1038/nature06188 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 216QG UT WOS:000249893500036 PM 17914389 ER PT J AU Binshtok, AM Bean, BP Woolf, CJ AF Binshtok, Alexander M. Bean, Bruce P. Woolf, Clifford J. TI Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers SO NATURE LA English DT Article ID LOCAL-ANESTHETICS; RECEPTOR; TETRODOTOXIN; CAPSAICIN; LIDOCAINE; CURRENTS; NEURONS; ACCESS; SITE; RATS AB Most local anaesthetics used clinically are relatively hydrophobic molecules that gain access to their blocking site on the sodium channel by diffusing into or through the cell membrane(1). These anaesthetics block sodium channels and thereby the excitability of all neurons, not just sensory neurons. We tested the possibility of selectively blocking the excitability of primary sensory nociceptor (pain-sensing) neurons by introducing the charged, membrane-impermeant lidocaine derivative QX-314 through the pore of the noxious-heat-sensitive TRPV1 channel. Here we show that charged sodium-channel blockers can be targeted into nociceptors by the application of TRPV1 agonists to produce a pain-specific local anaesthesia. QX-314 applied externally had no effect on the activity of sodium channels in small sensory neurons when applied alone, but when applied in the presence of the TRPV1 agonist capsaicin, QX-314 blocked sodium channels and inhibited excitability. Inhibition by co-applied QX-314 and capsaicin was restricted to neurons expressing TRPV1. Injection of QX-314 together with capsaicin into rat hindpaws produced a long-lasting (more than 2 h) increase in mechanical and thermal nociceptive thresholds. Long-lasting decreases in pain sensitivity were also seen with regional injection of QX-314 and capsaicin near the sciatic nerve; however, in contrast to the effect of lidocaine, the application of QX-314 and capsaicin together was not accompanied by motor or tactile deficits. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Bean, BP (reprint author), Harvard Univ, Sch Med, Dept Neurobiol, 220 Longwood Ave, Boston, MA 02115 USA. EM bruce_bean@hms.harvard.edu RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 NR 16 TC 196 Z9 202 U1 0 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 4 PY 2007 VL 449 IS 7162 BP 607 EP U13 DI 10.1038/nature06191 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 216QG UT WOS:000249893500047 PM 17914397 ER PT J AU Yehuda, R Ledoux, J AF Yehuda, Rachel Ledoux, Joseph TI Response variation following trauma: A translational neuroscience approach to understanding PTSD SO NEURON LA English DT Review ID POSTTRAUMATIC-STRESS-DISORDER; MEDIAL PREFRONTAL CORTEX; NATIONAL COMORBIDITY SURVEY; SPRAGUE-DAWLEY RATS; ANIMAL-MODEL; HIPPOCAMPAL VOLUME; RISK-FACTORS; INDIVIDUAL-DIFFERENCES; ANXIETY DISORDERS; FEAR EXTINCTION AB Exposure to traumatic stress is a requirement for the development of posttraumatic stress disorder (PTSD). However, because the majority of trauma-exposed persons do not develop PTSD, examination of the typical effects of a stressor will not identify the critical components of PTSD risk or pathogenesis. Rather, PTSD represents a specific phenotype associated with a failure to recover from the normal effects of trauma. Thus, research must focus on identifying pre- and posttraumatic risk factors that explain the development of the disorder and the failure to reinstate physiological homeostasis. In this review, we summarize what is known about the clinical and biological characteristics of PTSD and articulate some of the gaps in knowledge that can be addressed by basic neuroscience research. We emphasize how knowledge about individual differences related to genetic and epigenetic factors in behavioral and brain responses to stress offers the hope of a deeper understanding of PTSD. C1 Mt Sinai Sch Med, James J Peters Vet Affairs, Div Traumat Stress Studies, Bronx, NY 10468 USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. RP Yehuda, R (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs, Div Traumat Stress Studies, Bronx, NY 10468 USA. EM rachel.yehuda@med.va.gov FU NIMH NIH HHS [R01 MH46516, K05 MH067048, P50 MH58911, R01 MH064675-02, R01 MH64104-01, R37 MH38774, R56 MH077321] NR 130 TC 268 Z9 276 U1 15 U2 47 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 4 PY 2007 VL 56 IS 1 BP 19 EP 32 DI 10.1016/j.neuron.2007.09.006 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 222IN UT WOS:000250289800007 PM 17920012 ER PT J AU Feder, HM Johnson, BJB O'Connell, S Shapiro, ED Steere, AC Wormser, GP AF Feder, Henry M., Jr. Johnson, Barbara J. B. O'Connell, Susan Shapiro, Eugene D. Steere, Allen C. Wormser, Gary P. CA Ad Hoc Int Lyme Dis Grp TI Current concepts - A critical appraisal of "chronic Lyme disease'' SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID BORRELIA-BURGDORFERI; CHRONIC-FATIGUE; ANTIBIOTIC-TREATMENT; REFERRAL CENTER; SYMPTOMS; CULTURE; FIBROMYALGIA; PREVENTION; DIAGNOSIS; ARTHRITIS C1 Univ Connecticut, Ctr Hlth, Dept Family Med, Farmington, CT 06030 USA. Connecticut Childrens Med Ctr, Dept Family Med, Hartford, CT USA. Connecticut Childrens Med Ctr, Dept Pediat, Hartford, CT USA. Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Microbiol Lab, Ft Collins, CO USA. Southampton Gen Hosp, Hlth Protect Agcy Microbiol Lab, Lyme Borreliosis Unit, Southampton SO9 4XY, Hants, England. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA. RP Feder, HM (reprint author), Univ Connecticut, Ctr Hlth, Dept Family Med, Farmington, CT 06030 USA. EM hfeder@nso2.uchc.edu FU NCATS NIH HHS [UL1 TR000142] NR 59 TC 211 Z9 221 U1 7 U2 40 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 4 PY 2007 VL 357 IS 14 BP 1422 EP 1430 DI 10.1056/NEJMra072023 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 216QA UT WOS:000249892900008 PM 17914043 ER PT J AU Cornia, PB Lipsky, BA Saint, S Gonzales, R AF Cornia, Paul B. Lipsky, Benjamin A. Saint, Sanjay Gonzales, Ralph TI Nothing to cough at SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID UNITED-STATES; PERTUSSIS; ADULTS; EPIDEMIOLOGY; OUTBREAKS; INFANTS C1 Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Ann Arbor Vet Affairs Med Ctr, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan Hlth Syst, Patient Safety Enhancement Program, Ann Arbor, MI USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. RP Cornia, PB (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, 1660 S Columbian Way S-111, Seattle, WA 98108 USA. EM paul.cornia@med.va.gov RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 18 TC 7 Z9 7 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 4 PY 2007 VL 357 IS 14 BP 1432 EP 1437 DI 10.1056/NEJMcps062357 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 216QA UT WOS:000249892900010 PM 17914045 ER PT J AU Patel, AA Chen, MH Renshaw, AA D'Amico, AV AF Patel, Abhijit A. Chen, Ming-Hui Renshaw, Andrew A. D'Amico, Anthony V. TI PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CONFORMAL RADIATION-THERAPY; PROGNOSTIC-SIGNIFICANCE; RADICAL PROSTATECTOMY; BIOCHEMICAL RECURRENCE; ANDROGEN SUPPRESSION; CONSENSUS CONFERENCE; RADIOTHERAPY; ADENOCARCINOMA; CARCINOMA AB Context In 2005, the International Society of Urologic Pathology consensus conference recommended that men with biopsy Gleason score 3 + 4 or 4 + 3 prostate cancer and tertiary pattern 5 should have their cancer classified as Gleason score 8 or 9, respectively. Yet, the management of men with Gleason score 7 vs 8 or 9 prostate cancer differs. Objective To compare the prognostic significance of Gleason score 7 with tertiary grade 5 vs other Gleason scores with respect to time to prostate-specific antigen (PSA) failure in men with prostate cancer. Design, Setting, and Patients From 1989 to 2005, 2370 men with clinical tumor category 1c to 3b, node-negative, and nonmetastatic prostate cancer underwent definitive therapy with surgery or radiation therapy with or without hormonal therapy. A pathologist with expertise in genitourinary cancers assigned Gleason scores to the prostate needle biopsy specimens. Cox regression was used to assess whether a significant association existed between the presence of tertiary grade 5 in men with Gleason score 7 disease and time to recurrence compared with men with Gleason score 7 without tertiary grade 5, Gleason score 5 to 6, or 8 to 10 disease, adjusting for known prognostic factors and treatment. Main Outcome Measure Time to PSA failure. Results Men with Gleason score 7 and tertiary grade 5 disease had a significantly shorter time to PSA failure than men with 7 without tertiary grade 5 (median time, 5.0 vs 6.7 years, respectively; adjusted hazard ratio (HR), 0.56; 95% confidence interval [CI], 0.32-0.97; P = .04) or score of 6 or less (median time, 15.4 years; adjusted HR, 0.24; 95% CI, 0.13-0.43; P < .001). However, a significant difference was not observed when these men were compared with men with Gleason score 8 to 10 disease (median time, 5.1 years; adjusted HR, 0.96; 95% CI, 0.54-1.71; P = .90). Conclusion In this study population, men with prostate cancer having biopsy Gleason score 7 and tertiary grade 5 had a higher risk of PSA-failure when compared with men with Gleason score 7 without tertiary grade 5 and had a comparable risk with men with Gleason score 8 to 10. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Patel, AA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. EM aapatel@partners.org FU NCI NIH HHS [CA 74015]; NIGMS NIH HHS [GM 70335] NR 28 TC 46 Z9 48 U1 1 U2 3 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 OCT 3 PY 2007 VL 298 IS 13 BP 1533 EP 1538 DI 10.1001/jama.298.13.1533 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 216EE UT WOS:000249860500025 PM 17911498 ER PT J AU Koushik, A Hunter, DJ Spiegelman, D Beeson, WL van den Brandt, PA Buring, JE Calle, EE Cho, E Fraser, GE Freudenheim, JL Fuchs, CS Giovannucci, EL Goldbohm, RA Harnack, L Jacobs, DR Kato, I Krogh, V Larsson, SC Leitzmann, MF Marshall, JR McCullough, ML Miller, AB Pietinen, P Rohan, TE Schatzkin, A Sieri, S Virtanen, MJ Wolk, A Zeleniuch-Jacquotte, A Zhang, SM Smith-Warner, SA AF Koushik, Anita Hunter, David J. Spiegelman, Donna Beeson, W. Lawrence van den Brandt, Piet A. Buring, Julie E. Calle, Eugenia E. Cho, Eunyoung Fraser, Gary E. Freudenheim, Jo L. Fuchs, Charles S. Giovannucci, Edward L. Goldbohm, R. Alexandra Harnack, Lisa Jacobs, David R., Jr. Kato, Ikuko Krogh, Vittorio Larsson, Susanna C. Leitzmann, Michael F. Marshall, James R. McCullough, Marjorie L. Miller, Anthony B. Pietinen, Pirjo Rohan, Thomas E. Schatzkin, Arthur Sieri, Sabina Virtanen, Mikko J. Wolk, Alicja Zeleniuch-Jacquotte, Anne Zhang, Shumin M. Smith-Warner, Stephanie A. TI Fruits, vegetables, and colon cancer risk in a pooled analysis of 14 cohort studies SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FOOD-FREQUENCY QUESTIONNAIRE; COLORECTAL-CANCER; UNITED-STATES; RECTAL CANCERS; WOMENS HEALTH; PLANT FOODS; DIET; CONSUMPTION; PREVENTION; FIBER AB Background Fruit and vegetable intakes have been associated with a reduced risk of colon cancer; however, in more recent studies associations have been less consistent. Statistical power to examine associations by colon site has been limited in previous studies. Methods Fruit and vegetable intakes in relation to colon cancer risk were examined in the Pooling Project of Prospective Studies of Diet and Cancer. Relative risks (RRs) and 95% confidence intervals (Cis) were estimated separately in 14 studies using Cox proportional hazards model and then pooled using a randomeffects model. Intakes of total fruits and vegetables, total fruits, and total vegetables were categorized according to quintiles and absolute cutpoints. Analyses were conducted for colon cancer overall and for proximal and distal colon cancer separately. All statistical tests were two-sided. Results Among 756217 men and women followed for up to 6 to 20 years, depending on the study, 5838 were diagnosed with colon cancer. The pooled multivariable RRs (95% Cis) of colon cancer for the highest versus lowest quintiles of intake were 0.91 (0.82 to 1-01 1 P-trend =.19) for total fruits and vegetables, 0.93 (0.85 to 1.02, P-trend =.28) for total fruits, and 0.94 (0.86 to 1.02, P-trend =.17) for total vegetables. Similar results were observed when intakes were categorized by identical absolute cut points across studies (pooled multivariable FIR = 0.90, 95% CI = 0.77 to 1.05 for 800 or more versus <200 g/day of total fruits and vegetables, P-trend =.06). The age-standardized incidence rates of colon cancer for these two intake categories were 54 and 61 per 100000 person-years, respectively. When analyzed by colon site, the pooled multivariable RRs (95% Cis) comparing total fruit and vegetable intakes of 800 or more versus less than 200 g/day were 0.74 (0.57 to 0.95, P-trend =.02) for distal colon cancers and 1.02 (0.82 to 1.27, P-trend =.57) for proximal colon cancers. Similar site-specific associations were observed for total fruits and total vegetables. Conclusion Fruit and vegetable intakes were not strongly associated with colon cancer risk overall but may be associated with a lower risk of distal colon cancer. C1 Univ Montreal, CHUM, Ctr Rech, Dept Social & Prevent Med, Montreal, PQ H2W 1V1, Canada. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Loma Linda Univ, Ctr Hlth Res, Loma Linda, CA 92350 USA. Maastricht Univ, Dept Epidemiol, Maastricht, Netherlands. Amer Canc Soc, Atlanta, GA 30329 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Univ Buffalo State Univ New York, Dept Social & Prevent Med, Buffalo, NY 14222 USA. Roswell Pk Canc Inst, Dept Canc Prevent & Populat Sci, Buffalo, NY 14263 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. TNO, Dept Food & Chem Risk Anal, Zeist, Netherlands. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Wayne State Univ, Sch Med, Dept Pathol, Karmanos Canc Inst, Detroit, MI 48201 USA. Natl Canc Inst, Nutr Epidemiol Unit, I-20133 Milan, Italy. Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Toronto, Fac Med, Dept Publ Hlth Sci, Toronto, ON, Canada. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. AZJ, Div Epidemiol, Dept Environm Med, New York, NY USA. RP Koushik, A (reprint author), Univ Montreal, CHUM, Ctr Rech, Dept Social & Prevent Med, 3875 Rue St Urbain,3rd Floor, Montreal, PQ H2W 1V1, Canada. EM anita.koushik@umontreal.ca; pooling@hsphsun2.harvard.edu RI Larsson, Susanna/F-6065-2015; Krogh, Vittorio/K-2628-2016; Sieri, Sabina/K-4667-2016; OI Larsson, Susanna/0000-0003-0118-0341; Krogh, Vittorio/0000-0003-0122-8624; Sieri, Sabina/0000-0001-5201-172X; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU NCI NIH HHS [CA55075] NR 57 TC 122 Z9 127 U1 1 U2 17 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD OCT 3 PY 2007 VL 99 IS 19 BP 1471 EP 1483 DI 10.1093/jnci/djm155 PG 13 WC Oncology SC Oncology GA 219SO UT WOS:000250105300012 PM 17895473 ER PT J AU Jones, SR Pritchett, DL Stufflebeam, SM Hamalainen, M Moore, CI AF Jones, Stephanie R. Pritchett, Dominique L. Stufflebeam, Steven M. Haemaelaeinen, Matti Moore, Christopher I. TI Neural correlates of tactile detection: A combined magnetoencephalography and biophysically based computational modeling study SO JOURNAL OF NEUROSCIENCE LA English DT Review DE computational model; magnetoencephalography; dendritic processes; conscious perception; network dynamics; somatosensory cortex ID SOMATOSENSORY-EVOKED-POTENTIALS; MEDIAN NERVE-STIMULATION; EXTRACELLULAR FIELD POTENTIALS; SUBJECTIVE SENSORY EXPERIENCE; BACKWARD CORTICAL PROJECTIONS; PRIMARY VISUAL-CORTEX; MOUSE BARREL CORTEX; MAGNETIC-FIELDS; SYNAPTIC CONNECTIONS; HUMAN-BRAIN AB Previous reports conflict as to the role of primary somatosensory neocortex ( SI) in tactile detection. We addressed this question in normal human subjects using whole-head magnetoencephalography ( MEG) recording. We found that the evoked signal ( 0-175 ms) showed a prominent equivalent current dipole that localized to the anterior bank of the postcentral gyrus, area 3b of SI. The magnitude and timing of peaks in the SI waveform were stimulus amplitude dependent and predicted perception beginning at similar to 70 ms after stimulus. To make a direct and principled connection between the SI waveform and underlying neural dynamics, we developed a biophysically realistic computational SI model that contained excitatory and inhibitory neurons in supragranular and infragranular layers. The SI evoked response was successfully reproduced from the intracellular currents in pyramidal neurons driven by a sequence of lamina-specific excitatory input, consisting of output from the granular layer ( similar to 25 ms), exogenous input to the supragranular layers ( similar to 70 ms), and a second wave of granular output ( similar to 135 ms). The model also predicted that SI correlates of perception reflect stronger and shorter-latency supragranular and late granular drive during perceived trials. These findings strongly support the view that signatures of tactile detection are present in human SI and are mediated by local neural dynamics induced by lamina-specific synaptic drive. Furthermore, our model provides a biophysically realistic solution to the MEG signal and can predict the electrophysiological correlates of human perception. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Jones, SR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM srjones@nmr.mgh.harvard.edu RI Moore, Christopher/C-5588-2009; Hamalainen, Matti/C-8507-2013; OI Pritchett, Dominique/0000-0003-1187-1162 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIGMS NIH HHS [T32 GM007484]; NIMH NIH HHS [K25 MH072941, K25 MH072941-01, K25 MH072941-02, K25 MH072941-03, K25 MH072941-04, K25 MH072941-05, K25MH072941]; NINDS NIH HHS [1R01-NS045130-01, R01 NS045130] NR 130 TC 65 Z9 66 U1 2 U2 13 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 3 PY 2007 VL 27 IS 40 BP 10751 EP 10764 DI 10.1523/JNEUROSCI.0482-07.2007 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 217XU UT WOS:000249981400013 PM 17913909 ER PT J AU Suter, B Nowakowski, RS Bhide, PG Caviness, VS AF Suter, Bernhard Nowakowski, Richard S. Bhide, Pradeep G. Caviness, Verne S. TI Navigating neocortical neurogenesis and neuronal specification: A positional information system encoded by neurogenetic gradients SO JOURNAL OF NEUROSCIENCE LA English DT Article DE positional information; neocortex; neurogenesis; cell cycle; Lhx2 expression; transverse neurogenetic gradient ID CENTRAL-NERVOUS-SYSTEM; MURINE CEREBRAL WALL; CELL-CYCLE; REGULATORY GENES; PROLIFERATIVE EPITHELIUM; EXPRESSION PATTERNS; LIM-HOMEODOMAIN; MODEL; NEURONOGENESIS; P27(KIP1) AB The projection neurons of the neocortex are produced in the pseudostratified ventricular epithelium ( PVE) lining the embryonic lateral ventricles. Over a 7 d period in mouse, these neurons arise in an overlapping layer VI-to-II sequence and in an anterolateral to posteromedial gradient [ the transverse neurogenetic gradient ( TNG)]. At any time in the 7 d neurogenetic interval, a given PVE cell must know what class of precursor cell or neuron to form next. How this information is encoded in the PVE is not known. With comparative experiments in wild-type and double-transgenic mice, overexpressing the cell cycle inhibitor p27(Kip1), we show that a gradient of expression of Lhx2 ( inferred from its mRNA levels), a LIM homeodomain transcription factor, together with a gradient in duration of the G(1) phase of the cell cycle ( T-G1), are sufficient to specify a positional mapping system that informs the PVE cell what class of neuron to produce next. Lhx2 likely is representative of an entire class of transcription factors expressed along the TNG. This mapping system consisting of a combination of signals from two different sources is a novel perspective on the source of positional information for neuronal specification in the developing CNS. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Cell Biol & Neurosci, Piscataway, NJ 08854 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,VBK 901, Boston, MA 02114 USA. EM caviness@helix.mgh.harvard.edu RI Nowakowski, Richard/C-3217-2016; OI Nowakowski, Richard/0000-0002-5006-3670 FU NEI NIH HHS [EY15647, R01 EY015647]; NIDA NIH HHS [DA20796, R01 DA020796, R01 DA020796-03]; NINDS NIH HHS [NS43246, R01 NS012005, R01 NS049445, NS12005, NS49445, P30 NS045776, P30 NS045776-05, R01 NS043246, R01 NS043426, R01 NS043426-05] NR 40 TC 15 Z9 15 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 3 PY 2007 VL 27 IS 40 BP 10777 EP 10784 DI 10.1523/JNEUROSCI.3091-07.2007 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 217XU UT WOS:000249981400015 PM 17913911 ER PT J AU Gopalan, S AF Gopalan, Suresh TI A Multidirectional Non-Cell Autonomous Control and a Genetic Interaction Restricting Tobacco Etch Virus Susceptibility in Arabidopsis SO PLOS ONE LA English DT Article AB Background. Viruses constitute a major class of pathogens that infect a variety of hosts. Understanding the intricacies of signaling during host-virus interactions should aid in designing disease prevention strategies and in understanding mechanistic aspects of host and pathogen signaling machinery. Methodology/Principal Findings. An Arabidopsis mutant, B149, impaired in susceptibility to Tobacco etch virus (TEV), a positive strand RNA virus of picoRNA family, was identified using a high-throughput genetic screen and a counterselection scheme. The defects include initiation of infection foci, rate of cell-to-cell movement and long distance movement. Conclusions/Significance. The defect in infectivity is conferred by a recessive locus. Molecular genetic analysis and complementation analysis with three alleles of a previously published mutant lsp1 (loss of susceptibility to potyviruses) indicate a genetic interaction conferring haploinsufficiency between the B149 locus and certain alleles of lsp1 resulting in impaired host susceptibility. The pattern of restriction of TEV foci on leaves at or near the boundaries of certain cell types and leaf boundaries suggest dysregulation of a multidirectional non-cell autonomous regulatory mechanism. Understanding the nature of this multidirectional signal and the molecular genetic mechanism conferring it should potentially reveal a novel arsenal in the cellular machinery. C1 [Gopalan, Suresh] Washington State Univ, Inst Biol Chem, Pullman, WA 99164 USA. RP Gopalan, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02115 USA. EM gopalans2@hotmail.com FU National Institutes of Health [AI43288, AI27832]; United States Department of Agriculture [NRI 2002-3531911560] FX Funded by grants from National Institutes of Health (AI43288 and AI27832) and the United States Department of Agriculture (NRI 2002-3531911560) to James C. Carrington while at the Institute of Biological Chemistry, Washington State University, USA. NR 57 TC 2 Z9 2 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 3 PY 2007 VL 2 IS 10 AR e985 DI 10.1371/journal.pone.0000985 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HU UT WOS:000207455900021 PM 17912362 ER PT J AU Hartman, MCT Josephson, K Lin, CW Szostak, JW AF Hartman, Matthew C. T. Josephson, Kristopher Lin, Chi-Wang Szostak, Jack W. TI An Expanded Set of Amino Acid Analogs for the Ribosomal Translation of Unnatural Peptides SO PLOS ONE LA English DT Article AB Background. The application of in vitro translation to the synthesis of unnatural peptides may allow the production of extremely large libraries of highly modified peptides, which are a potential source of lead compounds in the search for new pharmaceutical agents. The specificity of the translation apparatus, however, limits the diversity of unnatural amino acids that can be incorporated into peptides by ribosomal translation. We have previously shown that over 90 unnatural amino acids can be enzymatically loaded onto tRNA. Methodology/Principal Findings. We have now used a competition assay to assess the efficiency of tRNA-aminoacylation of these analogs. We have also used a series of peptide translation assays to measure the efficiency with which these analogs are incorporated into peptides. The translation apparatus tolerates most side chain derivatives, a few alpha,alpha disubstituted, N-methyl and alpha-hydroxy derivatives, but no beta-amino acids. We show that over 50 unnatural amino acids can be incorporated into peptides by ribosomal translation. Using a set of analogs that are efficiently charged and translated we were able to prepare individual peptides containing up to 13 different unnatural amino acids. Conclusions/Significance. Our results demonstrate that a diverse array of unnatural building blocks can be translationally incorporated into peptides. These building blocks provide new opportunities for in vitro selections with highly modified drug-like peptides. C1 [Hartman, Matthew C. T.; Josephson, Kristopher; Lin, Chi-Wang; Szostak, Jack W.] Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Ctr Computat & Integrat Biol,Simches Res Ctr, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Ctr Computat & Integrat Biol,Simches Res Ctr, Boston, MA 02114 USA. EM szostak@molbio.mgh.harvard.edu FU Howard Hughes Medical Institute FX This work was supported by the Howard Hughes Medical Institute. Jack Szostak is an Investigator, and Matthew Hartman, Kris Josephson, and Chi-Wang Lin are/were HHMI Research Associates. NR 70 TC 77 Z9 79 U1 2 U2 33 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 3 PY 2007 VL 2 IS 10 AR e972 DI 10.1371/journal.pone.0000972 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10HU UT WOS:000207455900010 PM 17912351 ER PT J AU Conlin, PR AF Conlin, Paul R. TI Eat your fruits and vegetables but hold the salt SO CIRCULATION LA English DT Editorial Material DE editorials; blood pressure; diet; hypertension; sodium ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; DIETARY PATTERNS; SODIUM REDUCTION; WEIGHT-LOSS; HYPERTENSION; RISK; POPULATION; PREVENTION; TRIAL C1 Harvard Univ, Div Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, VA Boston Healthcare Syst, Brigham & Womens Hosp, Sch Med,Endocrinol Sect, Boston, MA 02115 USA. RP Conlin, PR (reprint author), Harvard Univ, Div Endocrinol Diabet & Hypertens, Brigham & Womens Hosp, Sch Med, 221 Longwood Ave, Boston, MA 02115 USA. EM pconlin@partners.org NR 20 TC 10 Z9 12 U1 3 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 OCT 2 PY 2007 VL 116 IS 14 BP 1530 EP 1531 DI 10.1161/CIRCULATIONAHA.107.729574 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 218KA UT WOS:000250013200002 PM 17909114 ER PT J AU Lewis, GD Shah, R Shahzad, K Camuso, JM Pappagianopoulos, PP Hung, J Tawakol, A Gerszten, RE Systrom, DM Bloch, KD Semigran, MJ AF Lewis, Gregory D. Shah, Ravi Shahzad, Khurram Camuso, Janice M. Pappagianopoulos, Paul P. Hung, Judy Tawakol, Ahmed Gerszten, Robert E. Systrom, David M. Bloch, Kenneth D. Semigran, Marc J. TI Sildenafil improves exercise capacity and quality of life in patients with systolic heart failure and secondary pulmonary hypertension SO CIRCULATION LA English DT Article DE exercise; heart failure; hypertension, pulmonary ID VENTRICULAR EJECTION FRACTION; INHALED NITRIC-OXIDE; CORONARY-ARTERY-DISEASE; OXYGEN-CONSUMPTION; CONTROLLED TRIAL; DOUBLE-BLIND; DYSFUNCTION; HEMODYNAMICS; MORTALITY; PRESSURE AB Background - Patients with systolic heart failure (HF) who develop secondary pulmonary hypertension (PH) have reduced exercise capacity and increased mortality compared with HF patients without PH. We tested the hypothesis that sildenafil, an effective therapy for pulmonary arterial hypertension, would lower pulmonary vascular resistance and improve exercise capacity in patients with HF complicated by PH. Methods and Results - Thirty-four patients with symptomatic HF and PH were randomized to 12 weeks of treatment with sildenafil (25 to 75 mg orally 3 times daily) or placebo. Patients underwent cardiopulmonary exercise testing before and after treatment. The change in peak VO2 from baseline, the primary end point, was greater in the sildenafil group (1.8 +/- 0.7 mL center dot kg(-1) center dot min(-1)) than in the placebo group (-0.27 mL center dot kg(-1) center dot min(-1); P=0.02). Sildenafil reduced pulmonary vascular resistance and increased cardiac output with exercise (P<0.05 versus placebo for both) without altering pulmonary capillary wedge or mean arterial pressure, heart rate, or systemic vascular resistance. The ability of sildenafil treatment to augment peak VO2 correlated directly with baseline resting pulmonary vascular resistance (r=0.74, P=0.002) and indirectly with baseline resting right ventricular ejection fraction (r=-0.64, P=0.01). Sildenafil treatment also was associated with improvement in 6-minute walk distance (29 m versus placebo; P=0.047) and Minnesota Living With Heart Failure score (-14 versus placebo; P=0.01). Subjects in the sildenafil group experienced fewer hospitalizations for HF and a higher incidence of headache than those in the placebo group without incurring excess serious adverse events. Conclusions - Phosphodiesterase 5 inhibition with sildenafil improves exercise capacity and quality of life in patients with systolic HF with secondary PH. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiol Div, Heart Failure & Cardiac Transplantat Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Cardiol Div, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org OI Systrom, David/0000-0002-9610-6330 FU EAPO CDC HHS [R21EP005294]; NHLBI NIH HHS [5K23HL004504, HL04021, HL04022, HL070896] NR 38 TC 238 Z9 252 U1 2 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 2 PY 2007 VL 116 IS 14 BP 1555 EP 1562 DI 10.1161/CIRCULATIONAHA.107.716373 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 218KA UT WOS:000250013200006 PM 17785618 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, Robert P. Braunwald, Eugene TI The year in non-ST-segment elevation acute coronary syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID GLYCOPROTEIN-IIB/IIIA INHIBITORS; LONG-TERM MORTALITY; RANDOMIZED CLINICAL-TRIALS; SUPPRESS ADVERSE OUTCOMES; RAPID RISK STRATIFICATION; INTENSIVE STATIN THERAPY; ISCHEMIC-HEART-DISEASE; COLLEGE-OF-CARDIOLOGY; C-REACTIVE PROTEIN; MYOCARDIAL-INFARCTION C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc Med, Dept Med, 350 Longwood Ave, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 96 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 2 PY 2007 VL 50 IS 14 BP 1386 EP 1395 DI 10.1016/j.jacc.2007.05.044 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 217HK UT WOS:000249938800015 PM 17903640 ER PT J AU Baumann, BM McCans, K Stahmer, SA Leonard, MB Shults, J Holmes, WC AF Baumann, Brigitte M. McCans, Kathryn Stahmer, Sarah A. Leonard, Mary B. Shults, Justine Holmes, William C. TI Caregiver and health care provider satisfaction with volumetric bladder ultrasound SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE ultrasound; bladder; catheterization; pediatrics; nurse; emergency medicine; satisfaction ID CATHETERIZATION AB Objectives: Conventional (nonimaged) bladder catheterization has lower first-attempt success rates (67%-72%) when compared with catheterization aided by volumetric bladder ultrasonography (US) (92%-100%), yet the total time to urine sample collection with US can be quite lengthy. Given the advantage and disadvantages, the authors assessed caregiver and health care provider satisfaction with these two methods. Methods: Caregivers and health care providers of children enrolled in a prospective, randomized, controlled trial examining the first-attempt urine collection success rates with these two methods completed standardized questionnaires. Each child's caregiver, nurse, and physician noted their perceptions, satisfaction, and future preferences using Likert-scale assessments. Results: Of 93 caregivers, 45 had children randomized to the conventional arm and 48 to the US arm. Nine physicians and three nurses participated. Both caregiver groups had similar previous catheterization experience; none had children undergo volumetric bladder sonography. Caregivers in the conventional group rated their children's discomfort higher (4.4 vs. 3.4; p = 0.02) and were less satisfied (4.5 vs. 6.4; p < 0.0001) than those in the US group. Nurses' satisfaction with catheterization in the conventional group was lower than in the US group (3.0 vs. 5.5), as was physicians' satisfaction (4.3 vs. 5.7; p < 0.0001). Both nurses and physicians indicated that they would be less likely to use conventional catheterization in future attempts. Conclusions: Caregivers in the conventional group rated their children's discomfort higher than did caregivers in the US group. Both caregivers and health care providers expressed greater satisfaction with US and were more likely to prefer this imaging modality with future catheterization attempts. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Baumann, BM (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Camden, NJ 08103 USA. EM baumann-b@cooperhealth.edu NR 5 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2007 VL 14 IS 10 BP 903 EP 907 DI 10.1197/j.aem.2007.06.041 PG 5 WC Emergency Medicine SC Emergency Medicine GA 218MX UT WOS:000250020700012 PM 17898252 ER PT J AU Peters, EC Gray, NS AF Peters, Eric C. Gray, Nathanael S. TI Chemical proteomics identifies unanticipated targets of clinical kinase inhibitors SO ACS CHEMICAL BIOLOGY LA English DT Article AB Kinases, represent one of the most important target classes of current drug discovery efforts. However, because the vast majority of potential small-molecule therapeutics is directed toward the highly conserved ATP-binding cleft, kinase inhibitors often exhibit significant unintended off-target effects. A recent report describes a chemical proteomics methodology that enables the simultaneous in vivo quantification of the on- and off-binding targets of kinase inhibitors across hundreds of nucleotide-dependent enzymes. C1 Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Peters, EC (reprint author), Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. EM epeters@gnf.org; nathanael_gray@dfci.harvard.edu NR 10 TC 15 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2007 VL 2 IS 10 BP 661 EP 664 DI 10.1021/cb700203j PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224BT UT WOS:000250421300012 PM 18041816 ER PT J AU Helstrom, A Hutchison, K Bryan, A AF Helstrom, Amy Hutchison, Kent Bryan, Angela TI Motivational enhancement therapy for high-risk adolescent smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE adolescent; smoking cessation; motivational enhancement therapy; juvenile offender ID SMOKING; CESSATION AB The majority of regular adult smokers begin smoking in adolescence and there is a clear need for youth-targeted smoking cessation interventions. The present randomized, controlled trial tested the effectiveness of motivational enhancement therapy (MET) to reduce smoking among 8 1 adjudicated adolescents. Participants received either MET or an education control. Smoking abstinence, quantity, and frequency were assessed at I and 6 months post treatment. Results suggest that although between-group differences on outcome measures were not significant at follow-up, smoking behavior decreased in both groups with approximately 10% achieving 1-month smoking abstinence at 6-month follow-up. Furthermore, participant response to MET varied by level of alcohol use and impulsivity such that participants with lower levels of alcohol use and impulsivity had significantly greater response to MET. In contrast, participants who endorsed higher rates of alcohol use and impulsivity responded better to the control than the MET condition. Results suggest that MET may be an effective intervention for some adolescent smokers but may be contraindicated for adolescents who have concomitant problems with alcohol use or impulsivity. (c) 2007 Elsevier Ltd. All rights reserved. C1 VA Boston Healthcare Syst, Psychol Serv 116B, Boston, MA 02130 USA. Univ Colorado, Boulder, CO 80309 USA. RP Helstrom, A (reprint author), VA Boston Healthcare Syst, Psychol Serv 116B, 150 S Huntington Ave, Boston, MA 02130 USA. EM amy.helstrom@med.va.gov FU NIDA NIH HHS [DA13182-02, R03 DA013182-01] NR 10 TC 19 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD OCT PY 2007 VL 32 IS 10 BP 2404 EP 2410 DI 10.1016/j.addbeh.2007.02.009 PG 7 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 207VK UT WOS:000249279000046 PM 17428617 ER PT J AU Weisbord, SD McGill, JB Kimmel, PL AF Weisbord, Steven D. McGill, Janet B. Kimmel, Paul L. TI Psychosocial factors in patients with chronic kidney disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Editorial Material ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; CHRONIC-HEMODIALYSIS PATIENTS; SYMPTOM ASSESSMENT SYSTEM; PALLIATIVE CARE; SURVIVAL; DEPRESSION; OUTCOMES; MORTALITY C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Mailstop 111F-U,7E Rm 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 24 TC 5 Z9 5 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2007 VL 14 IS 4 BP 316 EP 318 DI 10.1053/j.ackd.2007.07.012 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 220PS UT WOS:000250169300002 PM 17904497 ER PT J AU Weisbord, SD AF Weisbord, Steven D. TI Symptoms and their correlates in chronic kidney disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE symptoms; quality of life; pain; sexual dysfunction; sleep disturbance ID QUALITY-OF-LIFE; STAGE RENAL-DISEASE; CHRONIC-HEMODIALYSIS PATIENTS; RANDOMIZED CONTROLLED-TRIAL; DIALYSIS PATIENTS; ERECTILE DYSFUNCTION; BEHAVIORAL COMPLIANCE; PSYCHOSOCIAL FACTORS; TRANSPLANT PATIENTS; ASSESSMENT SYSTEM AB While there is a significant body of literature documenting the impairments in health-related quality of life (HRQOL) experienced by patients with end-stage renal disease (ESRD), recent work has helped to elucidate the mediators of impaired well-being in this patient group. Physical and emotional symptoms have been shown to be common, frequently severe, and directly linked with impaired HRQOL. The following review explores the process of symptom assessment in patients with chronic kidney disease (CKD), presents an overview of the composite burden and importance of symptoms in patients with ESRD, highlights particularly common and distressing symptoms for which existing treatment strategies may be applicable, and discusses future directions for efforts to address and alleviate symptoms in the growing population of patients who suffer from CKD. (C) 2007 by the National Kidney Foundation, Inc. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equi Res & Promot, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Mailstop 111F-U,7E Rm 120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu NR 51 TC 10 Z9 10 U1 2 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2007 VL 14 IS 4 BP 319 EP 327 DI 10.1053/j.ackd.2007.07.004 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 220PS UT WOS:000250169300003 PM 17904498 ER PT J AU Sauce, D Almeida, JR Larsen, M Haro, L Autran, B Freeman, GJ Appay, V AF Sauce, Delphine Almeida, Jorge R. Larsen, Martin Haro, Laurine Autran, Brigitte Freeman, Gordon J. Appay, Victor TI PD-1 expression on human CD8 T cells depends on both state of differentiation and activation status SO AIDS LA English DT Article DE activation; CD8 T cells; differentiation; HIV; PD-1 ID CHRONIC VIRAL-INFECTION; HIV-INFECTION; LYMPHOCYTE-ACTIVATION; ANTIGEN; TOLERANCE; PATHWAY; LOAD; AUTOIMMUNITY; PROGRESSION; EXHAUSTION AB Objective and design: PD-1 expression on HIV-specific CD8 T cells was recently reported to reflect functional exhaustion, resulting in uncontrolled HIV-1 replication. Assessing PD-1 expression on T cells may be highly relevant in T-cell immunology and vaccine monitoring. However, this requires us to gain further insights into the significance of PD-1 expression on CD8 T cells in humans. Methods: We performed a detailed analysis of PD-1 expression pattern on various CD8 T cell subsets from healthy or HIV infected donors. Results: PD-1 expression has two facets in vivo. On the one hand, it is linked to T-cell differentiation: PD-1 is up-regulated on early/intermediate differentiated subsets, which include HIV and Epstein-Barr virus-specific CD8 T-cell populations, but is down-regulated during late stages of differentiation. On the other hand, it is linked to T-cell activation: on PD-1 positive cells, PD-1 over-expression occurs along with the up-regulation of activation markers such as CD38 or HLA-DR. Conclusions: PD-1 expression on CD8 T cells, including those specific for HIV, can be related both to their differentiation stage and their activation status. It is important to consider these findings when assessing the expression of PD-1 on T cells. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Paris 06, Hop Pitie Salpetriere, INSERM, Cellular Immunol Lab,U543,Avenir Grp, Paris, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Dept Med Oncol, Boston, MA 02115 USA. RP Appay, V (reprint author), Univ Paris 06, Hop Pitie Salpetriere, INSERM, Cellular Immunol Lab,U543,Avenir Grp, Paris, France. EM appay@chups.jussieu.fr RI sauce, delphine/H-1990-2014; Larsen, Martin/A-7316-2014 OI sauce, delphine/0000-0003-4596-7373; Larsen, Martin/0000-0003-1375-4816 FU NIAID NIH HHS [AI 56299] NR 37 TC 83 Z9 86 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 1 PY 2007 VL 21 IS 15 BP 2005 EP 2013 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 217OL UT WOS:000249957100002 PM 17885290 ER PT J AU Lee, D Benson, CA Lewis, CE Grunfeld, C Scherzer, R AF Lee, Daniel Benson, Constance A. Lewis, Cora E. Grunfeld, Carl Scherzer, Rebecca TI Prevalence and factors associated with dry skin in HIV infection: the FRAM study SO AIDS LA English DT Article DE complication; dermatology; opportunistic infection; protease inhibitors; retinoid ID IMMUNODEFICIENCY-SYNDROME AIDS; CUTANEOUS MANIFESTATIONS; DERMATOLOGICAL FINDINGS; INGROWN TOENAILS; INDINAVIR; PARONYCHIA; DISEASE; GRANULOMA; THERAPY; XEROSIS AB Objective: Complaints of dry skin in HIV-infected individuals were reported after the advent of HAART. The objective of the study was to evaluate the prevalence of dry skin and associated factors in HIV-infected and control subjects. Design: Cross-sectional. Methods: A total of 1026 HIV-infected subjects and 274 controls [from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based study of cardiovascular risk assessment] in the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) had skin assessed by self-report and examination. Multivariable logistic regression identified factors associated with dry skin. Results: Self-reported dry skin was more prevalent in HIV-infected subjects than controls. In multivariable analysis, HIV infection was associated with self-reported dry skin. In HIV-infected men, current indinavir use, CD4 cell count less than 200 cells/mu l and recent opportunistic infections were associated with dry skin. Indinavir use had an elevated risk in men with CD4 cell counts of 200 cells/mu l or greater but not with CD4 cell counts less than 200 cells/mu l. In HIV-infected women, a CD4 cell count less than 200 cells/mu l was associated with dry skin; indinavir use did not reach statistical significance but, as in men, indinavir use had an elevated risk in those with higher CD4 cell counts than in those with CD4 cell counts less than 200 cells/mu l. Conclusion: Dry skin is more common in HIV-infected individuals than controls. In HIV-infected individuals, low CD4 cell counts and indinavir use in those with higher CD4 cell counts are associated with dry skin. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Calif San Francisco, Vet Affairs Med Ctr, Off Principle Investigator, Dept Med,FRAM Study,Metab Sect 111F, San Francisco, CA 94121 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. San Francisco VA Med Ctr, Metab Sect, San Francisco, CA USA. RP Grunfeld, C (reprint author), Univ Calif San Francisco, Vet Affairs Med Ctr, Off Principle Investigator, Dept Med,FRAM Study,Metab Sect 111F, 4150 Clement St, San Francisco, CA 94121 USA. EM carl.grunfeld@ucsf.edu FU NCRR NIH HHS [RR 00054, RR 00083, RR 00052, M01 RR000051, M01 RR 00036, RR 0636, RR 00051, M01 RR000036, M01 RR000865, RR 00865, M01 RR000083, M01 RR000054, M01 RR000052]; NHLBI NIH HHS [HL 53359, R01 HL074814, HL 74814, R01 HL074814-04, R01 HL074814-07, R01 HL074814-06, R01 HL074814-05]; NIDDK NIH HHS [R01 DK057508-01S1, R01 DK 57508, R01 DK057508-02, R01 DK057508-03, R01 DK057508, R01 DK057508-03S2, R01 DK057508-03S1, R01 DK057508-01] NR 25 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD OCT 1 PY 2007 VL 21 IS 15 BP 2051 EP 2057 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 217OL UT WOS:000249957100007 PM 17885295 ER PT J AU Mayben, JK Giordano, TP AF Mayben, J. K. Giordano, T. P. TI Internet use among low-income persons recently diagnosed with HIV infection SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID HEALTH INFORMATION; HIV/AIDS; ADULTS; AIDS; MAIL; CARE AB Patients are increasingly using the Internet to obtain health-related information, communicate with providers and access research. Use of the Internet to obtain health-related information by low-income patients recently diagnosed with HIV infection has not been examined. In 2005, we surveyed 126 low-income patients diagnosed with HIV infection within the last three years. Eighty-five percent of the patients were <50 years old, 63% were male, 68% were minority race, 27% were Hispanic and 61% acquired HIV through heterosexual intercourse. Twenty-eight percent never completed high school and 74% earned <$15,000 in 2004. While 89% indicated they would like to use the Internet to access information about HIV, 52% had ever used the Internet, 28% had ever used it to obtain health-related information and only 18% had done so at least monthly for the last six months. Two-thirds of the population studied would need instruction on how to use the Internet. In multivariable regression, 2004 income :$15,000 predicted monthly Internet use to obtain health-related information. Older age, heterosexual intercourse as HIV risk factor and inadequate health literacy were independent predictors of needing instruction. The low-income population with HIV infection lags behind the general population in Internet access and may not benefit from Internet-dependent advances in health communication, including HIV-related interventions. C1 [Mayben, J. K.] Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. [Giordano, T. P.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Mayben, J. K.; Giordano, T. P.] Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Mayben, J. K.] Women & Children First Hill Country Med Clin, Frederick, TX USA. RP Giordano, TP (reprint author), Michael E Debakey VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX USA. EM tpg@bcm.tmc.edu FU NIMH NIH HHS [MH067505]; PHS HHS [HP10031] NR 16 TC 14 Z9 14 U1 5 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT PY 2007 VL 19 IS 9 BP 1182 EP 1187 DI 10.1080/09540120701402806 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 251TN UT WOS:000252398200016 PM 18058404 ER PT J AU Lieber, CS Cao, Q DeCarli, LM Leo, MA Mak, KM Ponomarenko, A Ren, CL Wang, XL AF Lieber, Charles S. Cao, Qi DeCarli, Leonore M. Leo, Maria A. Mak, Ki M. Ponomarenko, Anatoly Ren, Chaoling Wang, Xiaolei TI Role of medium-chain triglycerides in the alcohol-mediated cytochrome p450 2E1 induction of mitochondria SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; CYP2E1; mitochondria; long-chain triglycerides; medium-chain triglycerides ID ETHANOL-OXIDIZING SYSTEM; NONALCOHOLIC STEATOHEPATITIS; DIMINISHED DEPOSITION; OXIDATIVE STRESS; LIVER-DISEASE; RATS; FAT; THERMOGENESIS; ACETALDEHYDE; HEPATOCYTES AB Chronic alcohol consumption is known to induce cytochrome P450 2E1 (CYP2E1) leading to lipid peroxidation, mitochondrial dysfunction and hepatotoxicity. We showed that replacement of dietary long-chain triglycerides (LCT) by medium-chain triglycerides (MCT) could be protective. We now wondered whether the induction of mitochondrial CYP2E1 plays a role and whether liver injury could be avoided through mitochondrial intervention. Rats were fed 4 different isocaloric liquid diets. The control group received our standard dextrin-maltose diet with intake limited to the average consumption of the 3 alcohol groups fed ad libitum the alcohol containing Lieber-DeCarli liquid diet. The fat was either 32% of calories as LCT (alcohol), or 16% as LCT + 16% as MCT (alcohol-MCT 16%), or 32% as MCT only (alcohol-MCT 32%). After 21 days, compared to the controls, the alcohol and both alcohol-MCT groups had a significant increase in mitochondrial CYP2E1 (p < 0.05 for both). As shown before, the same was found for the microsomal CYP2E1. When MCT replaced all the fat, like in the alcohol-MCT 32% group, CYP2E1 was significantly reduced by 40% in mitochondria (p < 0.05) and 30% in microsomes (p < 0.01). In mitochondria, 4-hydroxynonenal (4-HNE), a parameter of oxidative stress, paralleled CYP2E1. Compared to controls, alcohol and alcohol-MCT 16% significantly raised mitochondrial 4-HNE (p < 0.001), whereas the alcohol-MCT 32% diet brought it down to control levels (p < 0.001). Mitochondrial reduced glutathione (GSH) was also significantly lowered by alcohol consumption (p < 0.05), and it increased to almost normal levels with alcohol-MCT 32% (p = 0.006). These changes in the mitochondria reflected the reduction observed in total liver in which alcohol-MCT 32% decreased the alcohol-induced steatosis with a diminution of triglycerides (p < 0.001) and of the pro-inflammatory cytokine tumor necrosis factor-alpha (p < 0.001). Mitochondria participate in the induction of CYP2E1 by alcohol and contribute to lipid peroxidation and GSH depletion. Thus, lipid composition of the diet is an important determinant for the beneficial effect of MCT, with a diet containing a mixture of LCT/MCT being ineffective. C1 James J Peters VA Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, New York, NY USA. RP Lieber, CS (reprint author), James J Peters VA Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM liebercs@aol.com FU NIAAA NIH HHS [R01 AA011115] NR 40 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2007 VL 31 IS 10 BP 1660 EP 1668 DI 10.1111/j.1530-0277.2007.00475.x PG 9 WC Substance Abuse SC Substance Abuse GA 209GH UT WOS:000249376500006 PM 17681033 ER PT J AU Esrailian, E Spiegel, BMR Targownik, LE Dubinsky, MC Targan, SR Gralnek, IM AF Esrailian, E. Spiegel, B. M. R. Targownik, L. E. Dubinsky, M. C. Targan, S. R. Gralnek, I. M. TI Differences in the management of Crohn's disease among experts and community providers, based on a national survey of sample case vignettes SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; STANDARDIZED PATIENTS; CHART ABSTRACTION; MEASURING QUALITY; CARE; METAANALYSIS; PERSPECTIVE; PATTERNS; ADULTS AB Background When faced with the same set of facts, healthcare providers often make different diagnoses, employ different tests and prescribe disparate therapies. Aim To perform a national survey to measure process of care and variations in decision-making in Crohn's disease, and the compared results between experts and community providers. Methods We constructed a survey with five vignettes to elicit provider beliefs regarding the appropriateness of diagnostic tests and therapies in Crohn's disease. We measured agreement between community gastroenterologists and Crohn's disease experts, and measured variation within each group using the RAND Disagreement Index (DI), which is a validated measure of provider variation. Results We received 186 responses (42% response rate). Experts and community providers generally agreed on diagnostic testing decisions in Crohn's disease. However, there was a significant disagreement between groups for several decisions (use of 5-aminosalicylate in particular), and there was evidence of 'extreme variation' (defined as DI > 1.0) within groups across a range of decisions. Conclusions Although experts and community providers are in general consensus about diagnostic decision-making in Crohn's disease, extreme variation exists both between and within groups for key therapeutic decisions in Crohn's disease. We must understand and decrease this variation prior to future efforts of creating explicit quality indicators in Crohn's disease. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90095 USA. CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Ctr outcomes Res & Educat, Los Angeles, CA USA. VA Greater Los Angeles Hltcare Syst, Dept Gastroenterol & Hepatol, Los Angeles, CA USA. Univ Manitoba, Div Gastroenterol, Winnipeg, MB, Canada. Cedars Sinai Med Ctr, Ctr Inflammatory Bowel Dis, Los Angeles, CA 90048 USA. Technion Israel Inst Technol, Rambam Med Ctr, Dept Gastroenterol, GI Outcomes Unit, Haifa, Israel. RP Esrailian, E (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, 100 UCLA Med Plaza,Suite 265, Los Angeles, CA 90095 USA. EM eesrailian@mednet.ucla.edu FU NIDDK NIH HHS [P30 DK 041301-17, T32 DK07180-30] NR 32 TC 32 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD OCT 1 PY 2007 VL 26 IS 7 BP 1005 EP 1018 DI 10.1111/j.1365-2036.2007.03445.x PG 14 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 210UV UT WOS:000249482000004 PM 17877507 ER PT J AU Wiviott, SD de Lemos, JA AF Wiviott, Stephen D. de Lemos, James A. TI Antiplatelet agents make a comeback in ST-elevation myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION; FIBRINOLYTIC THERAPY; SEGMENT ELEVATION; RANDOMIZED TRIAL; UNSTABLE ANGINA; CLOPIDOGREL RESISTANCE; REPERFUSION THERAPY; PRASUGREL CS-747; DOSE RETEPLASE; TIMI 14 C1 Brigham & Womens Hosp, Div Cardiol, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. RP de Lemos, JA (reprint author), Brigham & Womens Hosp, Div Cardiol, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM james.delemos@utsouthwestern.edu NR 33 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2007 VL 154 IS 4 BP 603 EP 606 DI 10.1016/j.ahj.2005.04.036 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 217KR UT WOS:000249947300001 PM 17892976 ER PT J AU Fearon, WF Tonino, PAL De Bruyne, B Siebert, U Pijls, NHJ AF Fearon, William F. Tonino, Pim. A. L. De Bruyne, Bernard Siebert, Uwe Pijls, Nico H. J. CA FAME Study Investigators TI Rationale and design of the fractional flow reserve versus angiography for multivessel evaluation (FAME) study SO AMERICAN HEART JOURNAL LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; DRUG-ELUTING STENTS; ARTERY-DISEASE; RANDOMIZED-TRIALS; CARDIAC-SURGERY; FOLLOW-UP; CARDIOLOGY; SEVERITY; STENOSIS AB Background Although its limitations for diagnosing critical coronary artery disease are well described, coronary angiography remains the predominant method for guiding decisions about stent implantation in patients with multivessel coronary artery disease. However, some have suggested that invasive physiologic guidance may improve decision making. Trial design The objective of this multicenter, randomized clinical trial is to compare the efficacy of 2 strategies, one based on angiographic guidance to one based on physiologic guidance with fractional flow reserve (FFR), for deciding which coronary lesions to stent in patients with multivessel coronary disease. Eligible patients must have coronary narrowings >50% diameter stenosis in >= 2 major epicardial vessels, >= 2 of which the investigator feels require drug-eluting stent placement. Patients-with previous coronary bypass surgery or left main coronary disease are excluded. Based on angiographic evaluation, the investigator notes the lesions that require stenting. The patient is then randomly assigned to either angiographic guidance or FFR guidance. Patients assigned to angiographic guidance undergo stenting as planned. Patients assigned to FFR guidance first have FFR measured in each diseased vessel and only undergo stenting if the FFR is <= 0.80. The primary end point of the study is a composite of major adverse cardiac events, including death, myocardial infarction, and repeat coronary revascularization, at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, 2-year, and 5-year outcomes. Conclusion The FAME study will examine for the first time in a large, multicenter, randomized fashion the role of measuring FFR in patients undergoing multivessel percutaneous coronary intervention. C1 Stanford Univ, Med Ctr, Ctr Cardiovasc Technol, Div Cardiovasc Med, Stanford, CA 94305 USA. Catharina Hosp, Eindhoven, Netherlands. Ctr Cardiovasc, Aalst, Belgium. UMIT, Dept Publ Hlth, Hall In Tirol, Austria. Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Inst Technol Assessment, Boston, MA USA. RP Fearon, WF (reprint author), Stanford Univ, Med Ctr, Ctr Cardiovasc Technol, Div Cardiovasc Med, 300 Pasteur Dr, Stanford, CA 94305 USA. EM wfearon@stanford.edu NR 26 TC 49 Z9 49 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2007 VL 154 IS 4 BP 632 EP 636 DI 10.1016/j.ahj.2007.06.012 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 217KR UT WOS:000249947300008 PM 17892983 ER PT J AU Ho, V Ross, JS Nallamothu, BK Krumholz, HM AF Ho, Vivian Ross, Joseph S. Nallamothu, Brahmajee K. Krumholz, Harlan M. TI Cardiac Certificate of Need regulations and the availability and use of revascularization services SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE-SYSTEMS; MARKET FORCES; SURGERY; ANGIOPLASTY; MORTALITY; DISEASE; STATES AB Background Many states enforce Certificate of Need (CON) regulations for cardiac procedures, but little is known about how CON affects utilization. We assessed the association between cardiac CON regulations, availability of revascularization facilities, and. revascularization rates. Methods We determined when state cardiac CON regulations were active and obtained data for Medicare beneficiaries >= 65 years old who received coronary artery bypass graft surgery (CABG) or a percutaneous coronary intervention (PCI) between 1989 and 2002. We compared the number of hospitals performing revascularization and patient utilization in states with and without CON regulations, and in states which discontinued CON regulations during 1989 to 2002. Results Each year, the per capita number of hospitals performing CABG and PCI was higher in states without CON (3.7 per 100000 elderly for CABG, 4.5 for PCI in 2002), compared with CON states (2.5 for CABG, 3.0 for PCI in 2002). Multivariate regressions that adjusted for market and population characteristics found no difference in CABG utilization rates between states with and without CON (P = .7). However, CON was associated with 19.2% fewer PCIs per 1000 elderly (P = .01), equivalent to 322 526 fewer PCIs for 1989 to 2002. Among most states that discontinued CON, the number of hospitals performing PCI rose in the mid 1990s, but there were no consistent trends in the number of hospitals performing CABG or in PCIs or CABGs per capita. Conclusions Certificate of Need restricts the number of cardiac facilities, but its effect on utilization rates may vary by procedure. C1 Rice Univ, BIPP, Houston, TX 77005 USA. Rice Univ, Baker Inst Public Policy, Houston, TX 77251 USA. Baylor Coll Med, Mt Sinai Sch Med, Dept Med, Dept Geriatr & Adult Dev, New York, NY USA. Educ & Clin Ctr, James J Peters VA Med Ctr, Bronx, NY USA. Ann Arbor VA Med Ctr, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Robert Wood Johnson Clin Sch Program, Dept Med, Sect Cardiovasc Med, New Haven, CT USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT 06510 USA. Yale New Haven Med Ctr, Ctr Outcomes Res & Evaluat, New Haven, CT USA. RP Ho, V (reprint author), Rice Univ, BIPP, MS 40,6100 Main St, Houston, TX 77005 USA. RI Ho, Vivian/A-2827-2008 FU NCI NIH HHS [R21 CA118452-01A1, R21 CA118452]; NHLBI NIH HHS [R01 HL073825-01A1, R01 HL073825] NR 22 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2007 VL 154 IS 4 BP 767 EP 775 DI 10.1016/j.ahj.2007.06.031 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 217KR UT WOS:000249947300034 PM 17893007 ER PT J AU Murphy, SA Cannon, CP Wiviott, SD de Lemos, JA Blazing, MA McCabe, CH Califf, RM Braunwald, E AF Murphy, Sabina A. Cannon, Christopher P. Wiviott, Stephen D. de Lemos, James A. Blazing, Michael A. McCabe, Carolyn H. Califf, Robert M. Braunwald, Eugene TI Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and pravastatin or atorvastatin evaluation and infection therapy - Thrombolysis in myocardial infarction 22 trials) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TO-Z TRIAL; STATIN THERAPY; SIMVASTATIN; METAANALYSIS; CHOLESTEROL; EFFICACY; OUTCOMES; DISEASE AB Compared with moderate lipid lowering with standard-dose statin therapy, intensive lipid lowering with high-dose statin therapy after acute coronary syndromes (ACS) significantly reduces cardiovascular events. However, the 2 trials of high-dose versus standard-dose statin therapy in patients with ACS, Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE-IT-TIMI 22), were not individually powered to evaluate the impact on mortality alone. In this study, a pooled, patient-level analysis of these trials of 8,658 post-ACS patients was performed to provide a more robust estimate of the impact of intensive statin therapy on mortality. By 8 months, achieved low-density lipoprotein levels were lower in the group with intensive statin therapy (median 64 mg/dl, interquartile range 51 to 81) than in the group with moderate statin therapy (median 87 mg/dl, interquartile range 71 to W) (p < 0.001). All-cause mortality was significantly reduced in the group with intensive statin therapy compared with the group with moderate statin therapy (3.6% vs 4.9%, hazard ratio 0.77, 95% confidence interval 0.63 to 0.95, p = 0.015), without significant interaction by trial (interaction p = 0.63). The reduction in all-cause mortality with intensive statin therapy was consistent across key subgroups. In conclusion, in this analysis of > 8,600 patients, intensive lipid lowering with high-dose statin therapy after ACS was associated with reduced mortality compared with moderate lipid lowering with standard-dose statin therapy. On the basis of these findings, 1 death was prevented for every 95 patients treated with high-dose statin therapy for 2 years. The results of this pooled analysis provide further evidence for early intensive statin therapy after ACS. (C) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, SW Med Sch, Donald W Reynolds Cardiovasc Clin Res Ctr, Dallas, TX 75230 USA. Duke Clin Res Inst, Durham, NC USA. RP Murphy, SA (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. EM smurphy@perfuse.org NR 12 TC 45 Z9 50 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2007 VL 100 IS 7 BP 1047 EP 1051 DI 10.1016/j.amjcard.2007.04.053 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 216RW UT WOS:000249897700001 PM 17884359 ER PT J AU Fogli-Cawley, JJ Dwyer, JT Saltzman, E McCullough, ML Troy, LM Meigs, JB Jacques, PF AF Fogli-Cawley, Jeanene J. Dwyer, Johanna T. Saltzman, Edward McCullough, Marjorie L. Troy, Lisa M. Meigs, James B. Jacques, Paul F. TI The 2005 Dietary Guidelines for Americans and risk of the metabolic syndrome SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE dietary pattern; metabolic syndrome; Dietary Guidelines forAmericans; 2005 Dietary Guidelines for Americans Index ID DENSITY-LIPOPROTEIN CHOLESTEROL; FOOD FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; TYPE-2 DIABETES-MELLITUS; CORONARY-HEART-DISEASE; MAJOR CHRONIC DISEASE; HEALTHY EATING INDEX; BODY-MASS INDEX; A-I LEVELS; CARDIOVASCULAR-DISEASE AB Background: The 2005 Dietary Guidelines for Americans index (DGAI) was created to assess adherence to the dietary recommendations of the 2005 Dietary Guidelines for Americans (DGA) in relation to chronic disease risk. Objective: The objective was to assess the relation between dietary patterns consistent with the 2005 DGA as measured by the DGAI and both the prevalence of the metabolic syndrome (MetS) and individual MetS risk factors. Design: DGAI scores and metabolic risk factors for MetS were assessed in a cross-sectional study of 3177 participants from the Framingham Heart Study Offspring Cohort. MetS was defined on the basis of the National Cholesterol Education Program Adult Treatment Panel III criteria. Results: After adjustment for potential confounders, the DGAI score was inversely related to waist circumference (P for trend < 0.001), triacylglycerol concentration (P for trend = 0.005), both diastolic (P for trend = 0.002) and systolic (P for trend = 0.01) blood pressure, the prevalence of abdominal adiposity (P for trend < 0.001), and hyperglycemia (P for trend = 0.03). The prevalence of MetS was significantly lower in individuals in the highest DGAI quintile category than in those in the lowest category (odds ratio: 0.64; 95% CI: 0.47, 0.88; P for trend = 0.005) when those being treated for any of the risk factors were excluded. There was a significant interaction between DGAI score and age; the association between the DGAI score and MetS was confined largely to adults younger than 55 y (odds ratio: 0.57; 95% CI: 0.36, 0.92; P for trend < 0.01). Conclusions: A dietary pattern consistent with the 2005 DGA was associated with a lower prevalence of MetS-a potential risk factor for CVD. C1 Tufts Univ, USDA, Human Nutr Res Ctr Aging, Program Epidemiol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ, Freidman Sch Nutr Sci & Policy, Boston, MA 02111 USA. Beth Israel Deaconess Med Ctr, Gen Clin Res Ctr, Boston, MA 02215 USA. Tufts New England Med Ctr Hosp, Boston, MA 02215 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jacques, PF (reprint author), Tufts Univ, USDA, Human Nutr Res Ctr Aging, Program Epidemiol, 711 Washington St, Boston, MA 02111 USA. EM paul.jacques@tufts.edu OI Dwyer, Johanna/0000-0002-0783-1769 FU NHLBI NIH HHS [N01-HC-25195] NR 46 TC 63 Z9 67 U1 0 U2 9 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2007 VL 86 IS 4 BP 1193 EP 1201 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 220CN UT WOS:000250134600042 PM 17921402 ER PT J AU Maroto, M Barberia, E Vera, V Garcia-Godoy, F AF Maroto, Myriam Barberia, Elena Vera, Vicente Garcia-Godoy, Franklin TI Mineral trioxide aggregate as pulp dressing agent in pulpotomy treatment of primary molars: 42-month clinical study SO AMERICAN JOURNAL OF DENTISTRY LA English DT Article ID DENTIN BRIDGE FORMATION; PRIMARY TEETH; CALCIUM HYDROXIDE; MTA PULPOTOMIES; FORMOCRESOL; THERAPY AB To evaluate the long-term clinical and radiographical results of using gray mineral trioxide aggregate (MTA) in pulpotomy treatments in primary molars. Methods: A total of 69 primary molars were treated with pulpotomy procedures using NITA and follow-up every 6 months up to 42 months. Results: Clinical success was 100% as none of the molars showed clinical pathologic signs; radiographical success was 98.5% as one case of internal resorption was recorded. Reparative dentin deposition was found as stenosis of the pulp canals in 84% of the cases 42 months after treatment and as dentin bridge formation in 83% of the cases 42 months after treatment. Moreover, 11 permanent successors erupted at their normal exfoliation time without pathology after pulpotomy treatment with gray NITA of the primary molars. C1 Univ Complutense Madrid, Dept Prevent Pediat Dent & Orthodont, Fac Dent, E-28040 Madrid, Spain. Univ Complutense Madrid, Dept Conservat Dent, Fac Dent, E-28040 Madrid, Spain. Nova SE Univ, Biosci Res Ctr, Coll Dent Med, Ft Lauderdale, FL 33314 USA. Forsyth Inst, Boston, MA USA. RP Maroto, M (reprint author), Univ Complutense Madrid, Dept Prevent Pediat Dent & Orthodont, Fac Dent, Avda Complutense Sn,Ciudad Univ, E-28040 Madrid, Spain. EM myriammaroto@yahoo.com NR 36 TC 23 Z9 23 U1 0 U2 3 PU MOSHER & LINDER, INC PI WESTON PA 318 INDIAN TRACE SUITE 500, WESTON, FL 33326 USA SN 0894-8275 J9 AM J DENT JI Am. J. Dent. PD OCT PY 2007 VL 20 IS 5 BP 283 EP 286 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 223RQ UT WOS:000250390400001 PM 17993022 ER PT J AU Khalid, A Brugge, W AF Khalid, Asif Brugge, William TI ACG practice guidelines for the diagnosis and management of neoplastic pancreatic cysts SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID FINE-NEEDLE-ASPIRATION; PAPILLARY-MUCINOUS TUMORS; SOLID-PSEUDOPAPILLARY TUMOR; MAGNETIC-RESONANCE CHOLANGIOPANCREATOGRAPHY; MACROCYSTIC SEROUS CYSTADENOMA; INTRADUCTAL PAPILLARY; DIFFERENTIAL-DIAGNOSIS; LYMPHOEPITHELIAL CYST; FLUID ANALYSIS; CLINICOPATHOLOGICAL FEATURES AB The diagnosis and management of pancreatic cystic lesions is a common problem. At least 1% of hospitalized patients at major medical centers will have a pancreatic cystic lesion on cross sectional imaging. Up to a quarter of all pancreata examined in an autopsy series contained a pancreatic cyst, 16% of which were lined by an "atypical" epithelium and 3% of which had progressed to carcinoma-in-situ (high grade dysplasia). in the past, it was thought these cystic lesions were benign, but increasing evidence points to the cystic lesions as being the origin of some pancreatic malignancies. The most important clinical tools in the diagnosis and management of pancreatic cystic lesions are cross sectional imaging, endoscopic ultrasound, and cyst fluid analysis. The most important differential diagnosis is distinguishing mucinous (pre-malignant) and non-mucinous cystic lesions. The findings of a macrocystic lesion containing viscous fluid rich in CEA are supportive of a diagnosis of a mucinous lesion. Serous lesion are the most common non-mucinous cyst and are characterized by a microcystic morphology, non-viscous fluid and a low concentration of CEA in the cyst fluid. The following document includes a description of neoplastic pancreatic cysts, a critical review of relevant diagnostic tests, and a discussion of treatment options. We have proposed a set of guidelines for the diagnonis and management of patients with neoplastic pancreatic cysts. The guidelines are based on published data backed by an analysis of the quality of the data and are designed to address the most frequent and important clinical scenarios. In addition to providing a summary of the diagnostic data, we offer diagnostic and management suggestions based on 13 common clinical problems. Although the field is rapidly evolving, a set of core principles is provided based on a balance between the risk of malignancy and the benefit of pancreatic resection. C1 Massachusetts Gen Hosp, Gi Unit, Boston, MA 02114 USA. Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. RP Brugge, W (reprint author), Massachusetts Gen Hosp, Gi Unit, Boston, MA 02114 USA. NR 66 TC 162 Z9 165 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2007 VL 102 IS 10 BP 2339 EP 2349 DI 10.1111/j.1572-0241.2007.01516.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 215QN UT WOS:000249824200033 PM 17764489 ER PT J AU Saito, AM Kami, M Mori, SI Kanda, Y Suzuki, R Mineishi, S Takami, A Taniguchi, S Takemoto, Y Hara, M Yamaguchi, M Hino, M Yoshida, T Kim, SW Hori, A Ohashi, Y Takaue, Y AF Saito, Akiko M. Kami, Masahiro Mori, Shin-Ichiro Kanda, Yoshinobu Suzuki, Ritsuro Mineishi, Shin Takami, Akiyoshi Taniguchi, Shuichi Takemoto, Yoshinobu Hara, Masamichi Yamaguchi, Masaki Hino, Masayuki Yoshida, Takashi Kim, Sung-Won Hori, Akiko Ohashi, Yasuo Takaue, Yoichi TI Prospective phase II trial to evaluate the complications and kinetics of chimerism induction following allogeneic hematopoietic stem cell transplantation with fludarabine and busulfan SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE-MYELOID-LEUKEMIA; MYELOABLATIVE CONDITIONING REGIMEN; REDUCED-INTENSITY; HEMATOLOGIC MALIGNANCIES; UNRELATED DONORS; ELDERLY-PATIENTS; MYELODYSPLASTIC-SYNDROME; ANTITHYMOCYTE GLOBULIN AB This prospective trial assessed the safety and efficacy of allogeneic hematopoietic stem cell transplantation from a HLA-matched donor with a reduced-intensity regimen (RIST) consisting of iv fludarabine 30 rng/m(2) for 6 days and oral busulfan 4 mg/kg/day for 2 days in patients older than 50 years with hematological malignancies. Cyclosporine alone or cyclosporine with short-term methotrexate was randomized for graft-versus-host disease prophylaxis. After 30 patients had been enrolled, an interim analysis was performed, and this report focuses on a precise evaluation of the toxicity profile and chimerism kinetics. Sustained engraftment in all patients, no severe regimen-related toxicity (RRT) within 20 days, and no transplant-related mortality through Day 100 were observed. T-cell (CD3+) full-donor (over 90%) chimerism was observed in 22 of the 30 patients, while the remaining eight had mixed-donor chimerism over 77% on Day 90. Thereafter, five subsequently converted to full-donor chimerism without donor lymphocyte infusion by day 120 (n = 4) or Day 180 (n = 1). Two showed persistent mixed chimerism without relapse through Day 180. Grade III-IV acute graft-versus-host disease and extensive chronic graft-versus-host disease occurred in 10% and 73%, respectively. With a median follow-up of 1.5 years, overall survival and disease-free survival at 1 year was 83% and 62%, respectively. Seven patients hematologically relapsed overall, and five of them had myelodysplastic syndrome with poor prognostic factors. In older patients, RIST with fludarabine and busulfan was associated with acceptable toxicities and a satisfactory antileukemia effect, regardless of the early chimerism status. C1 Univ Tokyo, Dept Hematol & Oncol, Grad Sch Med, Tokyo, Japan. Univ Tokyo, Sch Hlth Sci & Nursing, Dept Biostat Epidemiol & Prevent Hlth Sci, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Div Exploratory Res, Tokyo, Japan. Natl Canc Ctr, Hematopoiet Stem Cell Transplantat Unit, Tokyo, Japan. Tokyo Univ Hosp, Dept Cell Therapy & Tranplantat Med, Tokyo 113, Japan. Nagoya Univ, Sch Med, Dept HSCT Data Management, Nagoya, Aichi, Japan. Univ Michigan, Div Hematol Oncol, Ann Arbor, MI 48109 USA. Kanazawa Univ, Grad Sch Med, Dept Cellular Transplantat Biol, Kanazawa, Ishikawa 920, Japan. Toranomon Gen Hosp, Dept Hematol, Tokyo, Japan. Med Corp Kouryokai CPC Clin, Kagoshima, Japan. Osaka City Univ, Grad Sch Med, Dept Clin Hematol & Clin Diagnost, Osaka 558, Japan. Toyama Prefectrual Cent Hosp, Dept Internal Med, Toyama, Japan. RP Saito, AM (reprint author), Dana Farber Canc Inst, 44 Binney St,SM 275, Boston, MA 02115 USA. EM akiko_saito@dfci.harvard.edu NR 41 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2007 VL 82 IS 10 BP 873 EP 880 DI 10.1002/ajh.20977 PG 8 WC Hematology SC Hematology GA 215FU UT WOS:000249794500004 PM 17570513 ER PT J AU Grizzle, AJ Mahmood, MH Ko, Y Murphy, JE Armstrong, EP Skrepnek, GH Jones, WN Schepers, GP Nichol, WP Houranieh, A Dare, DC Hoey, CT Malone, DC AF Grizzle, Amy J. Mahmood, Maysaa H. Ko, Yu Murphy, John E. Armstrong, Edward P. Skrepnek, Grant H. Jones, William N. Schepers, Gregory P. Nichol, W. Paul Houranieh, Antoun Dare, Donna C. Hoey, Christophe T. Malone, Daniel C. TI Reasons provided by prescribers when overriding drug-drug interaction alerts SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PRIMARY-CARE; PREVENTION; EXPOSURE; AGENTS AB Objectives:To investigate prescribers' rationales for overriding drug-drug interaction (DDI) alerts and to determine whether these reasons were helpful to pharmacists as a part of prescription order verification. Study Design: An observational retrospective database analysis was conducted using override reasons derived from a computerized system at 6 Veterans Affairs medical centers. Methods: Data on DDI alerts (for interactions designated as "critical" and "significant") were obtained from ambulatory care pharmacy records from July 1, 2003, to June 30, 2004. Prescribers' reasons for overriding alerts were organized into 14 categories and were then rated as clinically useful or not to the pharmacist in the assessment of potential patient harm. Results: Of 291 890 overrides identified, 72% were for critical DDIs. Across the Veterans Affairs medical centers, only 20% of the override reasons for critical DDI alerts were rated as clinically useful for order verification. Despite a mandatory override reason for critical DDI alerts, 53% of the responses were "no reason provided! The top response categories for critical and significant DDI alerts were "no reason provided," "patient has been taking combination," and "patient being monitored." Conclusions When given the opportunity to provide a reason for overriding a DDI alert, prescribers rarely enter clinical justifications that are useful to order verification pharmacists. This brings into question how computerized physician order entry systems should be designed. C1 Univ Arizona, Coll Pharm, Ctr Hlth Outcomes & Pharmacoecon Res, Tucson, AZ 85721 USA. So Arizona VA Hlth Care Syst, Tucson, AZ USA. VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Pharm, Seattle, WA 98195 USA. VA Boston Healthcare Syst, Boston, MA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Grizzle, AJ (reprint author), Univ Arizona, Coll Pharm, Ctr Hlth Outcomes & Pharmacoecon Res, POB 210202, Tucson, AZ 85721 USA. EM grizzle@pharmacy.arizona.edu FU AHRQ HHS [2 U18 HS10385-04] NR 28 TC 45 Z9 46 U1 1 U2 2 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD OCT PY 2007 VL 13 IS 10 BP 573 EP 580 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 221OB UT WOS:000250236100005 PM 17927462 ER PT J AU Stein, PD Beemath, A Matta, F Weg, JG Yusen, RD Hales, CA Hull, RD Leeper, KV Sostman, HD Tapson, VF Buckley, JD Gottschalk, A Goodman, LR Wakefied, TW Woodard, PK AF Stein, Paul D. Beemath, Afzal Matta, Fadi Weg, John G. Yusen, Roger D. Hales, Charles A. Hull, Russell D. Leeper, Kenneth V., Jr. Sostman, H. Dirk Tapson, Victor F. Buckley, John D. Gottschalk, Alexander Goodman, Lawrence R. Wakefied, Thomas W. Woodard, Pamela K. TI Clinical characteristics of patients with acute pulmonary embolism: Data from PIOPED II SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE clinical diagnosis; deep venous thrombosis; pulmonary embolism; venous thromboembolism ID DIAGNOSIS; EMERGENCY; DISEASE; AUTOPSY AB BACKGROUND: Selection of patients for diagnostic tests for acute pulmonary embolism requires recognition of the possibility of pulmonary embolism on the basis of the clinical characteristics. Patients in the Prospective Investigation of Pulmonary Embolism Diagnosis II had a broad spectrum of severity, which permits an evaluation of the subtle characteristics of mild pulmonary embolism and the characteristics of severe pulmonary embolism. METHODS: Data are from the national collaborative study, Prospective Investigation of Pulmonary Embolism Diagnosis II. RESULTS: There may be dyspnea only on exertion. The onset of dyspnea is usually, but not always, rapid. Orthopnea may occur. In patients with pulmonary embolism in the main or lobar pulmonary arteries, dyspnea or tachypnea occurred in 92%, but the largest pulmonary embolism was in the segmental pulmonary arteries in only 65%. In general, signs and symptoms were similar in elderly and younger patients, but dyspnea or tachypnea was less frequent in elderly patients with no previous cardiopulmonary disease. Dyspnea may be absent even in patients with circulatory collapse. Patients with a low-probability objective clinical assessment sometimes had pulmonary embolism, even in proximal vessels. CONCLUSION: Symptoms may be mild, and generally recognized symptoms may be absent, particularly in patients with pulmonary embolism only in the segmental pulmonary branches, but they may be absent even with severe pulmonary embolism. A high or intermediate-probability objective clinical assessment suggests the need for diagnostic studies, but a low-probability objective clinical assessment does not exclude the diagnosis. Maintenance of a high level of suspicion is critical. (c) 2007 Elsevier Inc. All rights reserved. C1 St Joseph Mercy Oakland Hosp, Dept Res, Pontiac, MI USA. Wayne State Univ, Sch Med, Dept Med, Detroit, MI 48201 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Calgary, Dept Med, Calgary, AB, Canada. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Methodist Hosp, Houston, TX 77030 USA. Weill Cornell Med Coll, Off Dean, Houston, TX USA. Duke Univ, Dept Med, Durham, NC USA. Michigan State Univ, Dept Radiol, E Lansing, MI 48824 USA. Henry Ford Hosp, Dept Med, Detroit, MI 48202 USA. Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Washington Univ, Dept Radiol, St Louis, MO USA. RP Stein, PD (reprint author), 44405 Woodward Ave, Pontiac, MI 48341 USA. EM steinp@trinity-health.org FU NHLBI NIH HHS [U01 HL063942, HL063932, HL63899, HL63928, HL63931, HL63940, HL63941, HL63981, HL63982, HL67453, U01 HL063899, U01 HL063899-04, U01 HL063928, U01 HL063928-04, U01 HL063931, U01 HL063931-04, U01 HL063932, U01 HL063932-04, U01 HL063940, U01 HL063940-04, U01 HL063941, U01 HL063941-04, U01 HL063981, U01 HL063982, U01 HL063982-04, U01 HL067453, U01 HL067453-04] NR 21 TC 115 Z9 126 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2007 VL 120 IS 10 BP 871 EP 879 DI 10.1016/j.amjmed.2007.03.024 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 215HE UT WOS:000249798100012 PM 17904458 ER PT J AU Batcher, EL Tang, XC Singh, BN Singh, SN Reda, DJ Hershman, JM AF Batcher, Elizabeth L. Tang, X. Charlene Singh, Bramah N. Singh, Steven N. Reda, Domenic J. Hershman, Jerome M. CA SAFE-T Inves TI Thyroid function abnormalities during amiodarone therapy for persistent atrial fibrillation SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Amiodarone; hypothyroidism; Sotalol; thyroid ID CARDIOVASCULAR-DISEASE; INDUCED HYPOTHYROIDISM; INDUCED THYROTOXICOSIS; RISK-FACTOR; DYSFUNCTION; SOTALOL AB BACKGROUND: Many patients receiving amiodarone therapy are male. The long-term risk for amiodarone-induced thyroid dysfunction in these patients has not been systematically and prospectively investigated. The purpose of this study was to determine the extent of amiodarone-induced thyroid dysfunction in a large male cohort. METHODS: This is a substudy of a prospective randomized controlled trial (SAFE-Trial) in which amiodarone, sotalol, and placebo for persistent atrial fibrillation were evaluated. For the purpose of this substudy, sotalol and placebo groups were combined into a control group. Serial thyroid function tests were performed over 1-4.5 years. Of the 665 patients enrolled in the SAFE-Trial, 612 patients were included in this sub-study. RESULTS: Subclinical hypothyroidism, thyroid-stimulating hormone (TSH) level 4.5-10 mU/L, was seen among 25.8% of the amiodarone-treated patients and only 6.6% of controls (P < .0001). Overt hypothyroidism, TSH level > 10 mU/L, was seen among 5.0% of the amiodarone-treated patients, and only 0.3% of controls (P < .001). By 6 months, 93.8% of the patients who developed TSH elevations above 10 mU/L on amiodarone had been detected. There was a trend toward a greater proportion of hyperthyroidism, defined as a TSH < 0.35 mU/L, in the amiodarone group compared with the control group (5.3% vs 2.4%, P = .07). CONCLUSIONS: Hypothyroidism developed in 30.8% of older males treated with amiodarone and in only 6.9% of the controls. Hypothyroidism presented at an early stage of therapy. Hyperthyroidism occurred in 5.3% of amiodarone treated patients, and was a subclinical entity in all but 1 case. (c) 2007 Elsevier Inc. All rights reserved. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Dept Vet Affairs Med Ctr, Washington, DC USA. Vet Affairs Edward Hines Jr Hosp, Hines, IL USA. RP Batcher, EL (reprint author), Olive View UCLA Med Ctr, Dept Med, 14445 Olive View Dr, Sylmar, CA 91342 USA. EM batcherb@gmail.com NR 25 TC 27 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2007 VL 120 IS 10 BP 880 EP 885 DI 10.1016/j.amjmed.2007.04.022 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 215HE UT WOS:000249798100013 PM 17904459 ER PT J AU Li, WH Wu, CL Febbo, PG Olumi, AF AF Li, Wenhua Wu, Chin-Lee Febbo, Phillip G. Olumi, Aria F. TI Stromally expressed c-Jun regulates proliferation of prostate epithelial cells SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-I; ANDROGEN RECEPTOR; TUMOR PROGRESSION; GENE-EXPRESSION; P38 MAPK; CANCER; HYPERPLASIA; FIBROBLASTS; CARCINOMA; MICE AB Stromal-epithelial interactions play a critical role in development of benign prostatic hyperplasia. We have previously shown that stromal cells associated with prostatic carcinoma can potentiate proliferation and reduce cell death of prostatic epithelial cells. Genetic alterations in stromal cells affect stromal-epithelial interactions and modulate epithelial growth. The c-Jun proteins that are early transcription factor molecules have been shown to regulate stromal-epithelial interactions via paracrine signals. Moreover, the Jun-family member proteins have been shown to play an important role in proper development of the genito-urinary organs. In this study, we show that c-Jun protein in fibroblasts regulates production and paracrine signals of insulin-like growth factor-1 (IGF-1). c-jun(+/+) fibroblasts secrete higher levels of IGF-1 and stimulate benign prostatic hyperplasia-1 cellular proliferation. In addition, stromally produced IGF-1 up-regulates epithelial mitogen-activated protein kinase, Akt, and cyclin D protein levels while down-regulating the cyclin-dependent kinase inhibitor p27. These data suggest that stromally expressed c-Jun may promote prostatic epithelial proliferation through IGF-1 as a paracrine signal that, in turn, can promote prostate epithelial proliferation. identification of the signal transduction pathways between prostate epithelial cells and the surrounding stromal cells will improve our understanding of the normal and abnormal biology in prostatic diseases. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Genet, Durham, NC USA. RP Olumi, AF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol, Yawkey Bldg,Suite 7E,55 Fruit St, Boston, MA 02114 USA. EM aolumi@partners.org FU NIDDK NIH HHS [DK64062, K08 DK064062] NR 65 TC 29 Z9 31 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2007 VL 171 IS 4 BP 1189 EP 1198 DI 10.2353/ajpath.2007.070285 PG 10 WC Pathology SC Pathology GA 217TJ UT WOS:000249969900011 PM 17702894 ER PT J AU Spires-Jones, TL Meyer-Luehmann, M Osetek, JD Jones, PB Stern, EA Bacskai, BJ Hyman, BT AF Spires-Jones, Tara L. Meyer-Luehmann, Melanie Osetek, Jennifer D. Jones, Phillip B. Stern, Edward A. Bacskai, Brian J. Hyman, Bradley T. TI Impaired spine stability underlies plaque-related spine loss in an Alzheimer's disease mouse model SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CORTEX IN-VIVO; DENDRITIC SPINES; AMYLOID-BETA; MULTIPHOTON MICROSCOPY; TRANSGENIC MICE; NEURITIC ALTERATIONS; PLASTICITY; DEMENTIA; PROTEIN; ABNORMALITIES AB Dendritic spines, the site of most excitatory synapses in the brain, are lost in Alzheimer's disease and in related mouse models, undoubtedly contributing to cognitive dysfunction. We hypothesized that spine loss results from plaque-associated alterations of spine stability, causing an imbalance in spine formation and elimination. To investigate effects of plaques on spine stability in vivo, we observed cortical neurons using multiphoton microscopy in a mouse model of amyloid pathology before and after extensive plaque deposition. We also observed age-matched non-transgenic mice to study normal effects of aging on spine plasticity. We found that spine density and structural plasticity are maintained during normal aging. Tg2576 mice had normal spine density and plasticity before plaques appeared, but after amyloid pathology is established, severe disruptions were observed. in control animals, spine formation and elimination were equivalent over I hour of observation (similar to 5% of observed spines), resulting in stable spine density. However, in aged Tg2576 mice spine elimination increased, specifically in the immediate vicinity of plaques. Spine formation was unchanged, resulting in spine loss. These data show a small population of rapidly changing spines in adult and even elderly mouse cortex; further, in the vicinity of amyloid plaques, spine stability is markedly impaired leading to loss of synaptic structural integrity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Hyman, BT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,MassGen Inst Neurodegenerat Dis, 114 16th St, Charlestown, MA 02129 USA. EM bhyman@partners.org OI Jones, Phillip/0000-0003-0525-6323; Spires-Jones, Tara/0000-0003-2530-0598; Meyer-Luehmann, Melanie/0000-0003-3661-2220 FU NIA NIH HHS [AG08487, AG00277, R01 AG008487, T32 AG000277]; NIBIB NIH HHS [R01 EB000768] NR 52 TC 88 Z9 89 U1 1 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2007 VL 171 IS 4 BP 1304 EP 1311 DI 10.2353/ajpath.2007.070055 PG 8 WC Pathology SC Pathology GA 217TJ UT WOS:000249969900021 PM 17717139 ER PT J AU Spruill, LS Lowry, AS Stroud, RE Squires, CE Mains, IM Flack, EC Beck, C Ikonomidis, JS Crumbley, AJ McDermott, PJ Spinale, FG AF Spruill, Laura S. Lowry, Abigail S. Stroud, Robert E. Squires, Christina E. Mains, Ira M. Flack, English C. Beck, Christy Ikonomidis, John S. Crumbley, A. Jackson McDermott, Paul J. Spinale, Francis G. TI Membrane-type-1 matrix metalloproteinase transcription and translation in myocardial fibroblasts from patients with normal left ventricular function and from patients with cardiomyopathy SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE heart failure; extracellular matrix; proteases ID FAILING HUMAN HEART; CARDIAC FIBROBLASTS; EXTRACELLULAR-MATRIX; 1-MATRIX METALLOPROTEINASE; GENE-EXPRESSION; POSTTRANSCRIPTIONAL REGULATION; DILATED CARDIOMYOPATHY; IV COLLAGENASE; UP-REGULATION; CELL-SURFACE AB Past studies have identified that a unique type of matrix metalloproteinase, the membrane-type-1 MMP (MT1-MMP), is increased within the left ventricle (LV) of patients with dilated cardiomyopathy (DCM). However, the cellular and molecular basis for this induction of MT1-MMP with DCM is unknown. LV myocardial biopsies from nonfailing, reference normal patients (defined as LV ejection fraction >50%, elective coronary bypass surgery, no perfusion defect at biopsy site, n = 6) and DCM patients (LV ejection fraction <20%, at transplant, n = 5) were used to establish fibroblast cultures (FIBROS). Confluent LV FIBROS from culture passages 2-5 were measured with respect to MT1-MMP mRNA and protein levels and the distribution of the MT1-MMP mRNA pool in ribosomal fractions. Total MT1-MMP mRNA within DCM FIBROS increased by over 140%, and MT1-MMP protein increased by over 190% from reference normal FIBROS (both P < 0.05). MT1-MMP mRNA in monosome fractions decreased by over twofold in DCM FIBROS compared with reference normal (P < 0.05) and remained lower in polyribosomal fractions (i.e., 15.7 +/-5.2 vs. 1.4 +/-0.6% in polysomal fraction 6, P < 0.05). These differences in DCM MT1-MMP FIBROS transcription and translation persisted throughout passages 2-5. The unique findings from this study demonstrated that elevated steady-state MT1-MMP mRNA and protein levels occurred in DCM FIBROS despite a decline in translational deficiency. These phenotypic changes in DCM fibroblasts may provide the basis for developing cell specific pharmacological targets for control of MT1-MMP expression. C1 Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Surg, Div Cardiothorac Surg, Charleston, SC 29425 USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Ralph H Johnson Dept Vet Affairs Med Ctr, Rm 625,Thurmond Res Bldg,770 MUSC Complex,114 Dou, Charleston, SC 29425 USA. EM wilburnm@musc.edu FU NHLBI NIH HHS [P01 HL48788, R01 HL59165] NR 51 TC 17 Z9 17 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2007 VL 293 IS 4 BP C1362 EP C1373 DI 10.1152/ajpcell.00545.2006 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 218YR UT WOS:000250052400018 PM 17670887 ER PT J AU Meng, D Newburg, DS Young, C Baker, A Tonkonogy, SL Sartor, RB Walker, WA Nanthakumar, NN AF Meng, Di Newburg, David S. Young, Cheryl Baker, Amy Tonkonogy, Susan L. Sartor, R. Balfour Walker, W. Allan Nanthakumar, N. Nanda TI Bacterial symbionts induce a FUT2-dependent fucosylated niche on colonic epithelium via ERK and JNK signaling SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE bacterial colonization; fucosylation ID RAT SMALL-INTESTINE; EXPRESSION; MICE; MATURATION; DIVERSITY; COMMENSAL; CORTISONE; ECOSYSTEM; ONTOGENY; BINDING AB Bacterial symbionts induce a FUT2-dependent fucosylated niche on colonic epithelium via ERK and JNK signaling. Am J Physiol Gastrointest Liver Physiol 293: G780-G787, 2007. First published August 2, 2007; doi:10.1152/ajpgi.00010.2007.-The intestinal epithelium of the adult gut supports a complex, dynamic microbial ecosystem and expresses highly fucosylated glycans on its surface. Uncolonized gut contains little fucosylated glycan. The transition toward adult colonization, such as during recovery from germ-free status or from antibiotic treatment, increased expression of fucosylated epitopes in the colonic epithelium. This increase in fucosylation is accompanied by induction of fut2 mRNA expression and alpha 1,2/3-fucosyltransferase activity. Colonization stimulates ERK and JNK signal transduction pathways, resulting in activation of transcription factors ATF2 and c-Jun, respectively. This increases transcription of fut2 mRNA and expression of alpha 1,2/3-fucosyltransferase activity, resulting in a highly fucosylated intestinal mucosa characteristic of the adult mammalian gut. Blocking the ERK and JNK signaling cascade inhibits the ability of colonization to induce elevated fut2 mRNA and fucosyltransferase activity in the mature colon. Thus pioneer-mutualist symbiotic bacteria may utilize the ERK and JNK signaling cascade to induce the high degree of fucosylation characteristic of adult mammalian colon, and we speculate that this fucosylation facilitates colonization by adult microbiota. C1 Massachusetts Gen Hosp, Dev Gastroenterol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp Children, Harvard Med Sch, Harvard Clin Nutr Res Ctr, Pediat Gastroenterol & Nutr Unit,Dept Pediat, Boston, MA USA. No Carolina State Univ, Coll Vet Med, Dept Microbiol Pathol & Parasitol, Raleigh, NC USA. Univ No Carolina, Ctr Gastrointestinal Biol & Disease, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. RP Nanthakumar, NN (reprint author), Massachusetts Gen Hosp, Dev Gastroenterol Lab, 114 16th St,Rm 3650, Charlestown, MA 02129 USA. EM nanthaku@helix.mgh.harvard.edu FU FIC NIH HHS [D43 TW1265]; NCRR NIH HHS [RR018603]; NICHD NIH HHS [HD12437, HD13021, HD31852]; NIDDK NIH HHS [DK40561, DK33506, DK34987, DK53347, P30 DK040561, P30 DK040561-12] NR 27 TC 26 Z9 29 U1 2 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2007 VL 293 IS 4 BP G780 EP G787 DI 10.1152/ajpgi.00010.2007 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 218DC UT WOS:000249995200016 PM 17673542 ER PT J AU Roberts, JD Chiche, JD Kolpa, EM Bloch, DB Bloch, KD AF Roberts, Jesse D., Jr. Chiche, Jean-Daniel Kolpa, Emily M. Bloch, Donald B. Bloch, Kenneth D. TI cGMP-dependent protein kinase I interacts with TRIM39R, a novel Rpp21 domain-containing TRIM protein SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary; RING finger protein; RNase P ID SMOOTH-MUSCLE-CELLS; SITE-DIRECTED MUTAGENESIS; NITRIC-OXIDE SYNTHASE; NUCLEAR RNASE-P; CYCLIC-GMP; GENE-EXPRESSION; PULMONARY-HYPERTENSION; SUBSTRATE-SPECIFICITY; BINDING PROTEIN; RIBONUCLEASE-P AB Nitric oxide modulates vascular smooth muscle cell ( SMC) cytoskeletal kinetics and phenotype, in part, by stimulating cGMP-dependent protein kinase I (PKGI). To identify molecular targets of PKGI, an interaction trap screen in yeast was performed using a cDNA encoding the catalytic region of PKGI and a human lung cDNA library. We identified a cDNA that encodes a putative PKGI-interactor that is a novel variant of TRIM39, a member of the really interesting new gene ( RING) finger family of proteins. Although this TRIM39 variant encodes the NH2-terminal RING finger ( RF), B-box, and coiled-coil ( RBBC) domains of TRIM39, instead of a complete COOH-terminal B30.2 domain, this TRIM39 isoform contains the COOH-terminal portion of Rpp21, a component of RNase P. RT-PCR demonstrated that the TRIM39 variant, which we refer to as TRIM39R, is transcribed in the human fetal lung and in rat pulmonary artery SMC. Indirect immunofluorescence using an antibody generated against the conserved domains of TRIM39 and TRIM39R revealed the proteins in speckled intranuclear structures in human acute monocytic leukemia ( THP-1) and human epidermal carcinoma line ( HEp-2) cells. PKGI phosphorylated a typical PKGI/PKA phosphorylation domain in a conserved region of TRIM39 and TRIM39R. Additional studies demonstrated that PKGI interacts with both isoforms of TRIM39 in yeast cells and phosphorylates both isoforms of TRIM39 in human cell lines. Although PKGI has been observed to interact with proteins that regulate cytoskeletal function and gene expression, this investigation shows for the first time that PKGI interacts with tripartite motif ( TRIM) proteins, which, through diverse molecular pathways, are often observed to regulate important aspects of cellular homeostasis. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Gen Med Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA USA. Massachusetts Gen Hosp, Div Newborn Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Roberts, JD (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Gen Med Serv, 149 13th St, Charlestown, MA 02129 USA. EM roberts@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [HL-080316, HL-74352, R01 HL080316-02, HL-04237, HL-57172, R01 HL080316]; NIDDK NIH HHS [DK-051179] NR 79 TC 6 Z9 7 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 EI 1522-1504 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD OCT PY 2007 VL 293 IS 4 BP L903 EP L912 DI 10.1152/ajplung.00157.2007 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 218ZM UT WOS:000250054500008 PM 17601797 ER PT J AU Brukamp, K Jim, B Moeller, MJ Haase, VH AF Brukamp, Kirsten Jim, Belinda Moeller, Marcus J. Haase, Volker H. TI Hypoxia and podocyte-specific Vhlh deletion confer risk of glomerular disease SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE glomerulosclerosis; hypoxia-inducible factor; von Hippel-Lindau; apoptosis ID OBSTRUCTIVE SLEEP-APNEA; ENDOCRINE PANCREAS; TUMOR-SUPPRESSOR; CELL-DEATH; EXPRESSION; MOUSE; MICE; KIDNEY; GROWTH; APOPTOSIS AB Hypoxia is a potent regulator of a multitude of cellular processes, including metabolism and cell survival. The transcriptional response to oxygen deprivation is mainly mediated by hypoxia-inducible factors (HIFs), which are targeted for proteasomal degradation by the von Hippel-Lindau tumor suppressor protein (pVHL) under normoxia. Podocytes, as part of the glomerular filtration barrier, are prone to hypoxic injury during diseases affecting the glomerulus. VHL and HIF1 were functional in mature murine podocytes in vivo and in vitro, with HIF1 protein stabilization and target gene transcription under both hypoxia and VHL deficiency. Podocyte-specific Vhlh gene loss, mimicking podocyte hypoxia, in young mice of mixed background led to glomerulomegaly and occasional glomerulosclerosis, despite preserved glomerular development. In parallel, hypoxia effects on podocytes in cell culture included increased susceptibility to apoptosis, associated with nuclear translocation of apoptosis-inducing factor (AIF). Similarly, Vhlh gene inactivation in podocytes in vitro resulted in a significant survival disadvantage, particularly in conjunction with additional proapoptotic stimuli. Evaluation of the global transcriptional response to hypoxia in podocytes by microarray analysis revealed a typical upregulation of HIF target genes as well as the induction of genes relevant for stress response, cell-cell, and cell-extracellular matrix interaction. While the lack of a prominent phenotype in young mice with VHL-deficient podocytes is consistent with the absence of specific glomerular manifestations in human VHL disease, a low-oxygen environment of podocytes may contribute to the progression of glomerular disease by altering cellular metabolism and survival. C1 Univ Penn, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA. Rhein Westfal TH Aachen, Dept Internal Med, D-5100 Aachen, Germany. RP Brukamp, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Nephrol Div, 149 13th St 8th Floor, Boston, MA 02129 USA. RI Haase, Volker Hans/A-6758-2013; Moeller, Marcus/L-1836-2015 OI Haase, Volker Hans/0000-0002-7051-8994; FU NCI NIH HHS [R01-CA-100787, R01 CA100787]; NIDDK NIH HHS [K08 DK002668, P30-DK-50306] NR 38 TC 26 Z9 28 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2007 VL 293 IS 4 BP F1397 EP F1407 DI 10.1152/ajprenal.00133.2007 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 221BE UT WOS:000250201200050 PM 17609290 ER PT J AU Weintraub, D Hurtig, HI AF Weintraub, Daniel Hurtig, Howard I. TI Presentation and management of psychosis in Parkinson's disease and dementia with Lewy bodies SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DRUG-INDUCED PSYCHOSIS; DOPAMINERGIC-INDUCED HALLUCINATIONS; NURSING-HOME PLACEMENT; DOUBLE-BLIND; NEUROLEPTIC SENSITIVITY; VISUAL HALLUCINATIONS; COGNITIVE IMPAIRMENT; CONTROLLED-TRIAL; BODY DEMENTIA; RISK-FACTORS C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Parkinsons Dis Res & Mental Illness Res Educ & Cl, Philadelphia, PA USA. RP Weintraub, D (reprint author), Univ Penn, Dept Psychiat, 3535 Market St,Rm 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23 MH067894, K23 MH067894-04, K23MH067894] NR 58 TC 46 Z9 47 U1 1 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2007 VL 164 IS 10 BP 1491 EP 1498 DI 10.1176/appi.ajp.2007.07040715 PG 8 WC Psychiatry SC Psychiatry GA 218XP UT WOS:000250049600010 PM 17898337 ER PT J AU Zisook, S Lesser, I Stewart, JW Wisniewski, SR Balasubramani, GK Fava, M Gilmer, WS Dresselhaus, TR Thase, ME Nierenberg, AA Trivedi, MH Rush, AJ AF Zisook, Sidney Lesser, Ira Stewart, Jonathan W. Wisniewski, Stephen R. Balasubramani, G. K. Fava, Maurizio Gilmer, William S. Dresselhaus, Timothy R. Thase, Michael E. Nierenberg, Andrew A. Trivedi, Madhukar H. Rush, A. John TI Effect of age at onset on the course of major depressive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID STAR-ASTERISK-D; PSYCHIATRIC-DISORDERS; SOCIAL-CONSEQUENCES; ADULT-ONSET; OF-ONSET; PATTERNS; COMORBIDITY; INVENTORY; SCALE AB Objective: This report assesses whether age at onset defines a specific subgroup of major depressive disorder in 4,041 participants who entered the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Method: The study enrolled outpatients 18-75 years of age with nonpsychotic major depressive disorder from both primary care and psychiatric care practices. At study entry, participants estimated the age at which they experienced the onset of their first major depressive episode. This report divides the population into five age-at-onset groups: childhood onset (ages <12), adolescent onset (ages 12-17), early adult onset (ages 18-44), middle adult onset (ages 45-59), and late adult onset (ages >= 60). Results: No group clearly stood out as distinct from the others. Rather, the authors observed an apparent gradient, with earlier ages at onset associated with never being married, more impaired social and occupational function, poorer quality of life, greater medical and psychiatric comorbidity, a more negative view of life and the self, more lifetime depressive episodes and suicide attempts, and greater symptom severity and suicidal ideation in the index episode compared to those with later ages at onset of major depressive disorder. Conclusions: Although age at onset does not define distinct depressive subgroups, earlier onset is associated with multiple indicators of greater illness burden across a wide range of indicators. Age of onset was not associated with a difference in treatment response to the initial trial of citalopram. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. San Diego VA Med Ctr, San Diego, CA USA. Univ Calif Los Angeles, Med Ctr, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Los Angeles Biomed Res Inst, Los Angeles, CA USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Asher Depress Ctr, Chicago, IL 60611 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX 75230 USA. RP Zisook, S (reprint author), Univ Calif San Diego, Dept Psychiat, 9500 Gilman Dr,9116A, La Jolla, CA 92093 USA. EM szisook@ucsd.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 24 TC 140 Z9 146 U1 2 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2007 VL 164 IS 10 BP 1539 EP 1546 DI 10.1176/appi.ajp.2007.06101757 PG 8 WC Psychiatry SC Psychiatry GA 218XP UT WOS:000250049600018 PM 17898345 ER PT J AU Tohen, M Kryzhanovskaya, L Carlson, G DelBello, M Wozniak, J Kowatch, R Wagner, K Findling, R Lin, D Robertson-Plouch, C Xu, W Dittmann, RW Biederman, J AF Tohen, Mauricio Kryzhanovskaya, Ludmila Carlson, Gabrielle DelBello, Melissa Wozniak, Janet Kowatch, Robert Wagner, Karen Findling, Robert Lin, Daniel Robertson-Plouch, Carol Xu, Wen Dittmann, Ralf W. Biederman, Joseph TI Olanzapine versus placebo in the treatment of adolescents with bipolar mania SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATYPICAL ANTIPSYCHOTIC AGENTS; PROSPECTIVE FOLLOW-UP; DOUBLE-BLIND; WEIGHT-GAIN; DIVALPROEX SODIUM; LITHIUM TREATMENT; CONTROLLED-TRIAL; RATING-SCALE; CHILDREN; DISORDER AB Objective: The purpose of this study was to evaluate the efficacy and safety of olanzapine for the treatment of acute manic or mixed episodes associated with bipolar disorder in adolescents. Method: A 3-week multicenter, parallel, double-blind, randomized placebo-controlled trial was conducted at 24 sites in the United States and two sites in Puerto Rico. The participants were outpatient and inpatient male and female adolescents 13-17 years of age with an acute manic or mixed episode. Subjects received either olanzapine (2.5-20 mg/day [N=107]) or placebo (N=54). The mean change from baseline to endpoint in the Young Mania Rating Scale total score was the primary outcome measure. Results: The mean baseline-to-end point change in the Young Mania Rating Scale total score was significantly greater for patients receiving olanzapine relative to patients receiving placebo, and a greater proportion of olanzapine-treated patients met response and remission criteria (44.8% versus 18.5% and 35.2% versus 11.1%, respectively). The mean baseline-to-endpoint weight change was significantly greater for patients receiving olanzapine relative to patients receiving placebo (3.7 kg versus 0.3 kg), and the incidence of treatment-emergent weight gain >= 7% of baseline was higher for olanzapine-treated patients (41.9% versus 1.9%). The mean baseline-to-endpoint changes in prolactin, fasting glucose, fasting total cholesterol, uric acid, and the hepatic enzymes aspartate transaminase and alanine transaminase were significantly greater in patients treated with olanzapine relative to patients receiving placebo. Conclusions: Olanzapine was effective in the treatment of bipolar mania in adolescent patients. Patients treated with olanzapine, however, had significantly greater weight gain and increases in the levels of hepatic enzymes, prolactin, fasting glucose, fasting total cholesterol, and uric acid. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Harvard Univ, McLean Hosp, Sch Med, Belmont, MA 02178 USA. SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hamburg, Dept Child & Adolescent Psychosomat, Hamburg, Germany. RP Tohen, M (reprint author), Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM m.tohen@lilly.com NR 41 TC 139 Z9 140 U1 5 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2007 VL 164 IS 10 BP 1547 EP 1556 DI 10.1176/appi.ajp.2007.06111932 PG 10 WC Psychiatry SC Psychiatry GA 218XP UT WOS:000250049600019 PM 17898346 ER PT J AU Sergi, MJ Green, MF Widmark, C Reist, C Erhart, S Braff, DL Kee, KS Marder, SR Mintz, J AF Sergi, Mark J. Green, Michael F. Widmark, Clifford Reist, Christopher Erhart, Stephen Braff, David L. Kee, Kimmy S. Marder, Stephen R. Mintz, Jim TI Cognition and neurocognition: Effects of risperildone, olanzapine, and haloperldol SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SOCIAL COGNITION; ANTIPSYCHOTIC TREATMENT; EMOTION PERCEPTION; SCHIZOAFFECTIVE DISORDER; CHRONIC-SCHIZOPHRENIA; NEURAL BASIS; RISPERIDONE; HALOPERIDOL; DEFICITS; COMMUNICATION AB Objective: This study examined the short-term effects of first- and second-generation antipsychotic medications on social cognition and basic cognition. Method: One hundred patients with schizophrenia or schizoaffective disorder participated in an 8 week, double-blind study of risperidone, olanzapine, and haloperidol. Participants were administered multiple measures of social cognition, basic cognition, and clinical symptoms at baseline, the end of week 4, and the end of week 8. Seventy-three patients completed the baseline assessment and at least one other assessment. Data were analyzed with mixed-effects analyses of covariance. For data reduction, the social cognitive measures were clustered into a summary score, and-the cognitive measures were clustered into two summary scores: general cognitive ability and processing speed. (The effects on thinking of risperidone and olanzapine can be found at NCT00108368, www.clinicaltrials.gov.) Results: There were no treatment-related differences on any of the three summary scores. Social cognition did not show within-group changes over time either by itself or after control for the cognitive clusters. One cognitive score (general cognitive ability) increased during the study period for all three medication groups. Conclusions: The present study included a rather thorough assessment of social cognition and did not find any evidence of between-group or within-group effects of antipsychotic medication on social cognition. C1 Calif State Univ Northridge, Dept Psychol, Northridge, CA 91330 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA USA. Univ Calif Irvine, Sch Med, Dept Psychiat & Human Behav, Irvine, CA USA. VA Long Beach Healthcare Syst, Long Beach, CA USA. Univ Calif Los Angeles, Med Ctr, Dept Psychiat, Sylmar, CA USA. Univ Calif San Diego, Sch Med, Dept Psychiat, San Diego, CA 92103 USA. Calif State Univ, Psychol Program, Camarillo, CA USA. RP Sergi, MJ (reprint author), Calif State Univ Northridge, Dept Psychol, 18111 Nordhoff St, Northridge, CA 91330 USA. EM mark.sergi@csun.edu RI Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [MH042228] NR 47 TC 78 Z9 78 U1 1 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2007 VL 164 IS 10 BP 1585 EP 1592 DI 10.1176/appi.ajp.2007.06091515 PG 8 WC Psychiatry SC Psychiatry GA 218XP UT WOS:000250049600024 PM 17898351 ER PT J AU Buchanan, RW Javitt, DC Marder, SR Schooler, NR Gold, JM McMahon, RP Heresco-Levy, U Carpenter, WT AF Buchanan, Robert W. Javitt, Daniel C. Marder, Stephen R. Schooler, Nina R. Gold, James M. McMahon, Robert P. Heresco-Levy, Uriel Carpenter, William T. TI The Cognitive and Negative Symptoms in Schizophrenia, Trial (CONSIST): The efficacy of glutamatergic agents for negative symptoms and cognitive impairments SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HIGH-DOSE GLYCINE; CYCLOSERINE ADJUVANT THERAPY; N-METHYLGLYCINE SARCOSINE; PLACEBO-CONTROLLED TRIAL; TRANSPORTER-I INHIBITOR; D-SERINE; DEFICIT SYNDROME; ANTIPSYCHOTICS; NEUROLEPTICS; CLOZAPINE AB objective: Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known. Agents that act at the glycine site of the N-methyl-D-aspartic acid (NMDA) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments. Method: The Cognitive and Negative Symptoms in Schizophrenia Trial (CONSIST) was a 16-week double-blind, double-dummy, parallel group, randomized clinical trial of adjunctive glycine, D-cycloserine, or placebo conducted at four sites in the United States and one site in Israel. The participants were 157 inpatients and outpatients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospective criteria for moderate to severe negative symptoms without marked positive, depressive, or extrapyramidal symptoms. The primary outcome measures were the average "rate of change" of Scale for the Assessment of Negative Symptoms (SANS) total scores and change in the average cognitive domain z scores. Results: There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects. A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests. One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo. A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients. There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score. Conclusions: The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments. C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Zucker Hillside Hosp, Glen Oaks, NY USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Ezrath Nashim Herzog Mem Hosp, IL-91010 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Psychiat, IL-91010 Jerusalem, Israel. RP Carpenter, WT (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. EM wcarpent@mprc.umaryland.edu RI McMahon, Robert/C-5462-2009 FU NIMH NIH HHS [5 R01 MH59784, 5 R01 MH59687, 5 R01 MH59750, 5 R01 MH69807, P30 MH06850] NR 50 TC 210 Z9 213 U1 0 U2 9 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2007 VL 164 IS 10 BP 1593 EP 1602 DI 10.1176/appi.ajp.2007.06081358 PG 10 WC Psychiatry SC Psychiatry GA 218XP UT WOS:000250049600025 PM 17898352 ER PT J AU Thorndike, AN Regan, S Rigotti, NA AF Thorndike, Anne N. Regan, Susan Rigotti, Nancy A. TI The treatment of smoking by US physicians during ambulatory visits: 1994-2003 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID PRIMARY-CARE; TOBACCO-CESSATION; CLINICAL-PRACTICE; PATIENT SATISFACTION; UNITED-STATES; PREVENTION; SERVICES; TIME; SMOKERS AB Objectives. We sought to determine whether US physicians' practice patterns in treating tobacco use at ambulatory visits improved over the past decade with the appearance of national clinical practice guidelines, new smoking cessation medications, and public reporting of physician performance in counseling smokers. Methods. We compared data from the National Ambulatory Medical Care Survey, an annual survey of a random sample of office visits to US physicians, between 1994-1996 and 2001-2003. Results. Physicians identified patients' smoking status at 68% of visits in 2001-2003 versus 65% in 1994-1996 (adjusted odds ratio [AOR] = 1.16; 95% confidence interval [Cl]= 1.04, 1.30). Physicians counseled about smoking at 20% of smokers visits in 2001-2003 versus 22% in 1994-1996 (AOR=0.84; 95% Cl =0.71, 0.99). In both time periods, smoking cessation medication use was low (< 2% of smokers' visits) and visits with counseling for smoking were longer than those without such counseling (P <.005). Conclusions. In the past decade, there has been a small increase in physicians' rates of patients' smoking status identification and a small decrease in rates of counseling smokers. This lack of progress may reflect barriers in the US health care environment, including limited physician time to provide counseling. C1 Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Tobacco Res & Treatment Ctr, Boston, MA USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Div Gen Med, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM athorndike@partners.org OI Regan, Susan/0000-0003-0940-2017 FU NHLBI NIH HHS [K24 HL004440, K24-HL04440] NR 37 TC 79 Z9 80 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2007 VL 97 IS 10 BP 1878 EP 1883 DI 10.2105/AJPH.2006.092577 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 217GO UT WOS:000249936600030 PM 17761570 ER PT J AU Lokken, RP Gervais, DA Arellano, RS Tuncali, K Morrison, PR Tatli, S Mueller, PR Silverman, SG AF Lokken, R. Peter Gervais, Debra A. Arellano, Ronald S. Tuncali, Kemal Morrison, Paul R. Tatli, Servet Mueller, Peter R. Silverman, Stuart G. TI Inflammatory nodules mimic applicator track seeding after percutaneous ablation of renal tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cryoablation; percutaneous ablation; radiofrequency ablation; renal cell carcinoma; tumor seeding ID CELL CARCINOMA; RADIOFREQUENCY ABLATION; MASSES; CRYOABLATION; PATIENT AB OBJECTIVE. The objective of our study was to report the occurrence of benign inflammatory nodules that develop in or near applicator tracks after percutaneous radiofrequency ablation and cryoablation of renal tumors. CONCLUSION. Benign inflammatory nodules occur rarely after percutaneous ablation of renal tumors and may mimic tumor seeding of the applicator track. C1 Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Lokken, RP (reprint author), Brigham & Womens Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 75 Francis St, Boston, MA 02115 USA. EM rlokken@partners.org OI Lokken, R. Peter/0000-0003-1669-5188 FU NCRR NIH HHS [U41RR019703] NR 13 TC 31 Z9 31 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2007 VL 189 IS 4 BP 845 EP 848 DI 10.2214/AJR.07.2015 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212KS UT WOS:000249595800018 PM 17885054 ER PT J AU Donohoo, JH Anderson, MT Mayo-Smith, WW AF Donohoo, Jay H. Anderson, Maria T. Mayo-Smith, William W. TI Pacemaker reprogramming after radiofrequency ablation of a lung neoplasm SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chest; lung; pacemaker; percutaneous ablation; radiofrequency ablation C1 Rhode Isl Hosp, Dept Diagnost Imaging, Providence, RI 02903 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Dept Radiol, Boston, MA USA. Rhode Isl Hosp, Div Cardiol, Providence, RI USA. RP Mayo-Smith, WW (reprint author), Rhode Isl Hosp, Dept Diagnost Imaging, 593 Eddy St, Providence, RI 02903 USA. EM wmayo-smith@lifespan.org NR 7 TC 4 Z9 4 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2007 VL 189 IS 4 BP 890 EP 892 DI 10.2214/AJR.05.1399 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212KS UT WOS:000249595800027 PM 17885062 ER PT J AU Bredella, MA Torriani, M Hornicek, F Ouellette, HA Palmer, WE Williams, Z Fishman, AJ Plotkin, SR AF Bredella, Miriam A. Torriani, Martin Hornicek, Francis Ouellette, Hugue A. Palmer, William E. Williams, Ziv Fishman, Allan J. Plotkin, Scott R. TI Value of PET in the assessment of patients with neurofibromatosis type I SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE C-11 methionine PET; FDG PET; neurofibromatosis type 1; peripheral nerve sheath tumors; PET; radiotracers; soft-tissue tumors ID GASTROINTESTINAL STROMAL TUMORS; POSITRON-EMISSION-TOMOGRAPHY; NERVE SHEATH TUMORS; VON-RECKLINGHAUSENS-DISEASE; FDG-PET; SOFT-TISSUE; PLEXIFORM NEUROFIBROMAS; C-11-METHIONINE PET; BENIGN; MASSES AB OBJECTIVE. The objective of our study was to investigate the use of PET in the detection of malignant peripheral nerve sheath tumors (MPNSTs) in patients with neurofibromatosis type 1 (NF1). MATERIALS AND METHODS. Forty-five patients with NF1 who underwent wholebody PET for suspected MPNST based on clinical symptoms or radiologic examinations were ret-respectively evaluated. Ten patients underwent additional carbon-11 (C-11) methionine PET because of equivocal F-18-FDG PET findings or because of a discrepancy between the FDG PET and clinical findings. PET images were evaluated for the distribution and uptake pattern, and the standardized uptake values (SUVs) were obtained. Twenty-seven patients underwent biopsy or surgery of the detected lesions and 18 patients were followed up clinically and with repeat imaging studies. RESULTS. Fifty lesions were identified on FDG PET. There were eight false-positive results and one false-negative on FDG PET. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FDG PET in detecting MPNSTs in patients with NF1 were 95%, 72%, 71%, 95%, and 82%, respectively. Using C-11 methionine PET in combination with FDG PET reduced the number of false-positive results from eight to two, which increased the specificity from 72% to 91%. In five patients, C-11 methionine FDG PET contributed additional information about nontarget lesions that influenced treatment planning. CONCLUSION. FDG PET is a sensitive technique in the detection of MPNSTs in patients with NF1. The addition of C-11 methionine PET increases specificity in equivocal cases. PET may improve preoperative tumor staging by detecting metastases or second primary tumors, which often are present in patients with NF1. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, 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 NR 30 TC 52 Z9 53 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2007 VL 189 IS 4 BP 928 EP 935 DI 10.2214/AJR.07.2060 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212KS UT WOS:000249595800035 PM 17885067 ER PT J AU Dodd, JD Holmvang, G Hoffmann, U Ferencik, M Abbara, S Brady, TJ Cury, RC AF Dodd, Jonathan D. Holmvang, Godtfred Hoffmann, Udo Ferencik, Maros Abbara, Suhny Brady, Thomas J. Cury, Ricardo C. TI Quantification of left ventricular noncompaction and trabecular delayed hyperenhancement with cardiac MRI: Correlation with clinical severity SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE cardiomyopathy; left ventricle abnormality; left ventricular noncompaction; MRI; trabecular delayed hyperenhancement ID MAGNETIC-RESONANCE; NON-COMPACTION; IRREVERSIBLE INJURY; CARDIOMYOPATHY; CLASSIFICATION; ABNORMALITIES; ASSOCIATION; MYOCARDIUM; CARDIOLOGY; ADULTS AB OBJECTIVE. The purpose of this study was to investigate whether MRI can quantify the severity and extent of left ventricular noncompaction and detect trabecular delayed hyperenhancement and whether doing so can show a relationship with clinical stage of disease. MATERIALS AND METHODS. In a retrospective blinded study, nine patients with left ventricular noncompaction and 10 control subjects had cardiac MRI studies evaluated for the severity and extent of left ventricular noncompaction and the amount and degree of trabecular delayed hyperenhancement on a myocardial segment basis (16-segment model). Findings were correlated with parameters of clinical stage of disease. RESULTS. Fifty-seven (39%) myocardial segments showed left ventricular noncompaction whereas 22 (17%) showed trabecular delayed hyperenhancement. Significant differences among clinical severity groups were noted in the severity and extent of left ventricular noncompaction at the mid (p < 0.05 and p < 0.005, respectively) and apical levels (p < 0.003 and p < 0.001, respectively), severity of trabecular delayed hyperenhancement at the mid (P < 0.04) and apical levels (p < 0.02), and amount of trabecular delayed hyperenhancement at the apical level (p < 0.006). The extent of left ventricular noncompaction and the amount and degree of trabecular delayed hyperenhancement correlated significantly with ejection fraction (EF) (r = -0.47, -0.53, -0.53, respectively, p < 0.05). The degree of trabecular delayed hyperenhancement was an independent predictor of EF (R-2 = 0.30, p < 0.0001). Significant differences in the severity of trabecular delayed hyperenhancement were detected among patients with mild and those with moderate and severe clinical stage of disease (p < 0.0001). CONCLUSION. Cardiac MRI shows trabecular delayed hyperenhancement in left ventricular noncompaction. Evaluating the extent and severity of left ventricular noncompaction and trabecular delayed hyperenhancement may improve the ability of the clinician to predict the clinical stage of disease. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Cardiac MR PET CT Program, Boston, MA 02114 USA. St Vincents Univ Hosp, Dept Radiol, Dublin, Ireland. Massachusetts Gen Hosp, Harvard Med Sch, Div Cardiol, Boston, MA 02114 USA. RP Dodd, JD (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. NR 18 TC 35 Z9 40 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2007 VL 189 IS 4 BP 974 EP 980 DI 10.2214/AJR.07.2364 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 212KS UT WOS:000249595800043 PM 17885073 ER PT J AU Rusby, JE Brachtel, EF Taghian, A Michaelson, JS Koerner, FC Smith, BL AF Rusby, Jennifer E. Brachtel, Elena F. Taghian, Alphonse Michaelson, James S. Koerner, Frederick C. Smith, Barbara L. TI Microscopic anatomy within the nipple: implications for nipple-sparing mastectomy SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAY 02-06, 2007 CL Phoenix, AZ SP Amer Soc Breast Surg DE anatomy; duct; microvessel density; nipple-sparing mastectomy ID SUBCUTANEOUS MASTECTOMY; BREAST-CANCER; RADIOTHERAPY ELIOT; AREOLA COMPLEX; FOLLOW-UP; RECONSTRUCTION; COMPLICATIONS; CARCINOMA AB Background: Precise anatomical relationships between ducts and vasculature within the nipple remain unknown. This study investigated nipple microvessels and their position relative to ducts. Methods: Nipple and duct bundle cross-sectional areas were measured in 48 specimens. Vessels located within the central duct bundle or within a peripheral rim were counted in 7 non-irradiated and 5 irradiated nipples. Results: Mean nipple diameter was 11.1 mm and duct bundle diameter 5.2 mm. A 2-mm and a 3-mm peripheral rim of nipple tissue would result in complete duct excision in 96% and 87% of sections,, respectively. Twenty-nine percent of vessels are located in the duct bundle. A 2-mm rim contains 50%; a 3-mm rim contains 66%. Similar proportions were seen in irradiated nipples. Conclusions: This study describes a strategy to balance duct removal with vascular preservation. Ducts can be excised leaving a rim of nipple tissue that contains a large proportion of microvessels. (c) 2007 Excerpta Medica Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Smith, BL (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 9A, Fruit St, Boston, MA 02114 USA. EM blsmith1@partners.org NR 26 TC 21 Z9 24 U1 0 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2007 VL 194 IS 4 BP 433 EP 437 DI 10.1016/j.amjsurg.2007.06.019 PG 5 WC Surgery SC Surgery GA 217FE UT WOS:000249933000003 PM 17826051 ER PT J AU Castillo, CFD Warshaw, AL AF Castillo, Carlos Fernandez-del Warshaw, Andrew. L. TI Surgical pioneers of the pancreas SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE pancreas; pioneer; surgery; history AB State-of-the-art pancreatic surgery is the result of multiple innovations in imaging, pharmacology, endoscopy, and surgical technology, but the initial driving force that brought this discipline to its current level was the boldness and creativity of a group of surgical pioneers. From the many individuals who participated in this process, a group of 11 surgeons was selected, and brief descriptions of their contributions are given. (C) 2007 Excerpta Medica Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 5 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2007 VL 194 IS 4A SU S BP S2 EP S5 DI 10.1016/j.amjsurg.2007.05.033 PG 4 WC Surgery SC Surgery GA 219KR UT WOS:000250084000002 ER PT J AU Koreishi, A Lauivers, GY Misdraji, J AF Koreishi, Aashiyana Lauivers, Gregory Y. Misdraji, Joseph TI Pneumatosis intestinalis - A challenging biopsy diagnosis SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pneumatosis intestinalis; giant cells; PI; granuloma; pseudolipomatosis; mucosal biopsy; diagnosis ID ACTIVE CYTOMEGALOVIRAL INFECTION; CYSTOIDES-INTESTINALIS; SPONTANEOUS PNEUMOTHORAX; UNREPORTED COMPLICATION; PLEURAL EOSINOPHILIA; LUNG TRANSPLANTATION; MUCOSAL CHANGES; BOWEL; FEATURES; AIDS AB Background: Pneumatosis intestinalis is characterized by the accumulation of gas in the gastrointestinal wall. The histopathologic diagnosis is easily made on resection specimens in which the presence of submucosal or subserosal empty spaces lined by histiocytes and giant cells presents little diagnostic dilemma. In biopsy material, though, the diagnosis is more challenging, as giant cells and histiocytes can be interpreted as granulomatous inflammation indicative of other conditions such as infection or Crohn disease. Design: Nine gastrointestinal biopsies diagnosed as pneumatosis intestinalis from 7 patients were reviewed. Clinical history, radiologic features, and endoscopic findings were obtained from patient records. Results: Five patients presented with blood in the stool (one also with diarrhea) and 2 patients were diagnosed after screening colonoscopies. The endoscopist frequently described polyps or raised mucosal folds (6 cases). In all biopsies submucosal cystic spaces lined by giant cells could be observed. The cysts were intact (2 biopsies), partially intact (5 biopsies), or collapsed (5 biopsies), with 3 biopsies showing 2 cyst architectural conformations. The arrangement of the giant cells lining a rounded or clefilike space was the most helpful feature in distinguishing pneumatosis intestinalis from granulomatous colitis. Additional useful features included the recognition of "pseudolipomatosis" (n = 4) and the presence of round empty spaces in the submucosa resembling fat (n = 3). Nonspecific findings included variable inflammation, eosinophilia, mild gland disarray, vascular ectasia and edema, and mild melanosis coli. Two cases were initially given a diagnosis of granulomatous inflammation. One patient with acquired immunodeficiency syndrome and positive cytomegalovirus antigenemia assay had ischemic colitis on the biopsy and another had a subsequent resection with ischemic colitis. A third patient was treated for cytomegalovirus colitis. None had a history of or developed Crohn disease. Conclusions: Pneumatosis intestinalis remains a challenging diagnosis on biopsy material, particularly because endoscopy usually does not suggest that diagnosis. The presence of giant cells in the submucosa, variable inflammation, and crypt disarray can be easily confused with Crohn disease. Attention to the arrangement of the giant cells lining intact, partial, or collapsed cysts is crucial to making the correct diagnosis. Although nonspecific by itself. pseudolipomatosis may also indicate the presence of gas within the tissue and suggest the diagnosis. C1 Harvard Univ, Sch Med, James Homer Wright Pathol Labs, Boston, MA USA. RP Koreishi, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 105F, Boston, MA 02114 USA. EM jmisdraji@partners.org NR 28 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1469 EP 1475 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400002 PM 17895747 ER PT J AU Staats, PN Clement, PB Young, RH AF Staats, Paul N. Clement, Philip B. Young, Robert H. TI Primary endometrioid adenocarcinoma of the vagina - A clinicopathologic study of 18 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE vagina; endometrioid carcinoma; adenocarcinoma; endometriosis ID TAMOXIFEN THERAPY; BREAST-CANCER; PELVIC ENDOMETRIOSIS; PROBLEMATIC ASPECTS; UTERINE CORPUS; CARCINOMA; OVARIAN; HYPERPLASIA; MALIGNANCY; PATHOLOGY AB Vaginal adenocarcinoma is the second most common primary cancer of the vagina, yet there has been very little study of most subtypes other than clear cell carcinoma. We reviewed 18 cases of primary vaginal endometrioid adenocarcinoma, in our experience the second most common subtype. The patients ranged from 45 to 81 years of age (mean 60). Most presented with vaginal bleeding, and had had a prior hysterectomy. Five had a history of unopposed estrogen therapy but none had a history of intrauterine diethylstilbestrol exposure. The tumors were at the vaginal apex in 10 cases, in the posterior wall in 3, the lateral wall in 3, and the anterior wall in 1. On microscopic examination, each of the tumors had a pure or predominant component of typical endometrioid adenocarcinoma. There was squamous metaplasia in 4 cases, mucinous metaplasia in 4, and prominent nonvillous papillae in 2. The tumors were grade I of 3 in 4 cases, grade 2 in 13, and grade 3 in 1. Eleven cases were FIGO stage 1, 5 stage 11, and 2 stage IV. Vaginal endometriosis was identified in 14 cases, and is important in indicating a primary vaginal tumor, rather than secondary spread from the endometrium. Other subtypes of adenocarcinoma (such as serous when the tumor has a papillary pattern) and atypical forms of endometriosis, including polypoid endometriosis, are the most common other differential diagnostic considerations. The prognosis seems to be good in low-stage patients, with I I patients alive and well and 2 alive with recurrent disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Univ British Columbia, Vancouver Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Hlth Sci Ctr, Vancouver, BC V5Z 1M9, Canada. RP Staats, PN (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM pstaats@partners.org NR 60 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1490 EP 1501 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400004 PM 17895749 ER PT J AU Hristov, AC Young, RH Vang, R Yemelyanova, AV Seidinan, JD Ronnett, BM AF Hristov, Alexandra C. Young, Robert H. Vang, Russell Yemelyanova, Anna V. Seidinan, Jeffrey D. Ronnett, Brigitte M. TI Ovarian metastases of appendiceal tumors with goblet cell carcinoidlike and signet ring cell patterns - A report of 30 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE appendix; ovary; metastases; adenocarcinoma; goblet cell carcinoid tumor; signet ring cell carcinoma ID BILATERAL KRUKENBERG TUMORS; CLINICOPATHOLOGICAL ANALYSIS; VERMIFORM APPENDIX; MUCINOUS ADENOCARCINOMA; PSEUDOMYXOMA-PERITONEI; EPITHELIAL NEOPLASMS; CARCINOMA; EMPHASIS; CYSTADENOCARCINOMA; PROGNOSIS AB Synchronous and metachronous ovarian and appendiceal mucinous tumors are often the subject of diagnostic consultations in gynecologic pathology practices to address whether the tumors are independent neoplasms or related as primary and metastasis. Those with goblet cell carcinoidlike patterns have not been extensively evaluated in a large series. Clinicopathologic features of 30 cases were examined. All patients presented with signs or symptoms related to a pelvic/ adnexal or abdominal mass. The ovarian tumors were bilateral in 25 of 28 cases with data on both ovaries and were typically large (mean/median: 14cm, range: 4.5 to 24.0cm). The appendices were often firm or thickened but usually did not have a discrete measurable tumor and were not notably enlarged, microscopically, transmural invasion was present in all of them. The ovarian and appendiceal tumors exhibited a variety of patterns of differentiation, including signet ring cell and glandular, with all displaying some goblet cell carcinoidlike patterns (nests, islands, cords, or cryptlike tubules with goblet cells); teratomatous elements were not identified in any ovarian tumors. Chromogranin was expressed in 7 of 19 ovarian tumors (mean/median: 6.3%/0%; range: 0% to 20%) and synaptophysin was expressed in 4 of 18 of these (mean/median: 7.8%/0% range: 0% to 90%). Chromogranin was expressed in 6 of 16 appendiceal tumors (mean/median: 11.9%/0%;, range: 0% to 70%) and synaptophysin was expressed in 6 of 15 of these (mean/median: l6.7%/0%; range: 0% to 90%). Follow-up was available for 25 patients: 17 died of disease at intervals ranging from 4 to 47 months (mean/median: 18/16) and 8 were alive with disease at I to 25 months (mean/median: 11/10); median survival was 19 months and the 1-year and 2-year survival rates were 63% and 34%, respectively. The clinicopathologic features of these ovarian tumors indicate they should be labeled as metastatic appendiceal adenocarcinomas rather than as goblet cell carcinoid tumors both to reflect their behavior and help distinguish them from the rare true primary ovarian goblet cell carcinoid tumors. As the ovarian tumors have appreciable components of signet ring cells they qualify as Krukenberg tumors. In cases in which the primary tumor is not already evident, their "goblet cell carcinoidlike" patterns should direct attention to the appendix as a possible source. C1 Johns Hopkins Univ, Sch Med & Hosp, Dept Pathol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med & Hosp, Dept Gynecol & Obstet, Baltimore, MD USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA USA. Washington Hosp Ctr, Dept Pathol, Washington, DC 20010 USA. RP Hristov, AC (reprint author), Johns Hopkins Univ Hosp, Dept Pathol, Weinberg Bldg,Room 2242,401 N Broadway, Baltimore, MD 21231 USA. EM bronnett@jhmi.edu NR 43 TC 36 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1502 EP 1511 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400005 PM 17895750 ER PT J AU Hansel, DE Epstein, JI Berbescu, E Fine, SW Young, RH Cheville, JC AF Hansel, Donna E. Epstein, Jonathan I. Berbescu, Ema Fine, Samson W. Young, Robert H. Cheville, John C. TI Renal carcinoid tumor: A clinicopathologic study of 21 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE kidney; cancer; carcinoid; neuroendocrine; metastasis ID HORSESHOE KIDNEY; CELL-CARCINOMA; ASSOCIATION; TERATOMA AB Renal carcinoid tumors are exceedingly rare tumors that have been primarily documented as case reports in the literature. In this study, we report a series of 21 renal carcinoid tumors, with emphasis on histopathologic features and clinical outcomes. Patient age ranged from 27 to 78 years (average 52 y). The majority of specimens consisted of radical nephrectomies with or without associated lymph node dissection. Nine tumors were present in the left kidney and 10 were present in the right; location was not available for 2 specimens. No anatomic region of the kidney appeared to be preferentially involved. Twenty tumors were unifocal and ranged in size from 2.6 to 17cm (average 6.4cm), and I tumor presented as 2 nodules measuring 1 and 2.8cm. Four patients had a documented history of a horseshoe kidney. Two patients had a history of renal calculi and 1 patient had a history of urothelial carcinoma 8 years prior. Presenting symptoms and clinical findings included back or flank pain (n = 6/9), enlarging abdominal mass or fullness (n = 2/9), hematuria (n = 2/9), and anemia (n = 1/9). Twelve patients had concurrent metastases at the time of initial surgery to sites including lymph nodes (n = 11/12), liver (n = 5/12), bone (n = 1/12), and lung (n = 1/12). One additional patient developed subsequent metastases to the liver within 6 months of surgery. Examination of the specimens identified carcinoid tumor with a variety of patterns including tightly packed cords and trabeculae with minimal stroma (n = 17/21), trabecular growth with prominent stroma (n = 4/21), focal solid nests (n = 4/21), focal glandlike lumina (n = 4/21). The border between tumor and normal kidney was sharply defined in most cases (n = 16/21), although focal infiltration was noted in 5/21 cases. Extracapsular extension was documented in 11/21 (52%) cases. Calcifications were present in 5/21 cases. Mitotic activity, measured as mitoses per 10 high-power fields, ranged from 0 to 2 in most cases, with I case demonstrating up to 4 mitotic figures per single high-power field. Necrosis was absent in all cases. Immunostains were frequently positive for synaptophysin (n = 18/20), chromogranin (n = 13/20), Cam5.2 (n = 14/16), subset of cases (n = 3/18) and CK20 was positive in I case. TTF-1 and WT-1 were negative in all cases examined. Clinical follow-up was available on 15 patients and ranged from 3 months to I I years. One patient died of disease at 8 months after surgery and I patient died without disease at I I years after surgery. Of the remaining patients, 7 patients were alive without disease and 6 patients were alive with disease. Additional metastases developed in 4 patients and included metastases to the liver and bone. C1 Cleveland Clin, Div Pathol, Cleveland, OH 44195 USA. Cleveland Clin, Lab Med, Cleveland, OH 44195 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Urol, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Oncol, Baltimore, MD 21287 USA. Mayo Clin, Dept Urol, Rochester, MN USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Mayo Clin, Dept Med Oncol, Rochester, MN USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Hansel, DE (reprint author), Cleveland Clin, Div Pathol, 9500 Euclid Ave,Desk L25, Cleveland, OH 44195 USA. EM hanseld@ccf.org NR 25 TC 38 Z9 48 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1539 EP 1544 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400010 PM 17895755 ER PT J AU Deshpande, V Nielsen, GP Rosenthal, DI Rosenberg, AE AF Deshpande, Vikram Nielsen, GunnIaligur Petur Rosenthal, Daniel I. Rosenberg, Andrew E. TI Intraosseous Benign Notochord Cell Tumors (BNCT): Further evidence supporting a relationship to chordoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chordoma; benign notochordal cells tumor ID CLASSIC CHORDOMAS; REST; DISTINCT; ENTITY; LESION AB Background: Previous studies have documented the existence of intraosseous benign notochordal cell tumors (BNCTs) within the axial skeleton. Evidence suggests that they may be associated with the development of chordomas. To further investigate the relationship between BNCT and classic chordoma, we reviewed a large series of resected sacral/coccygeal chordomas in an attempt to identify the presence of coexisting BNCTs. Design: Eighty-two sacrectomy/coccygectomy specimens performed for chordoma were identified. Available hematoxylin and eosin slides were reviewed to identify BNCTs and assess their relationship with the coexisting chordoma. BNCTs were defined, in accordance with prior descriptions, as cohesive aggregates of large cells that appeared adipocytelike because of their vacuolated cytoplasm. The cells exhibited only minimal nuclear atypia and lacked lobulation and myxoid stroma. Results: We identified 6 BNCTs, each was adjacent to but separate from the sacral chordoma. There were 5 females and 1 male, and the mean age was 58 years. Five lesions arose in the sacrum. One lesion arose in the coccyx, and involved 2 contiguous vertebral levels. The BNCTs ranged in size from I to 20 mm with a mean size of 6.1 mm. The lesions were exclusively composed of adipocytelike nuclei without significant nuclear atypia or myxoid stroma. Three lesions contained sclerotic bony trabeculae and intralesional hernatopoietic elements were identified in 1 case. In all cases the chordoma was of the conventional type and were morphologically different from the BNCT. Conclusions: BNCTs were identified in 7.3% of sacral/coccygeal resections performed for primary chordoma. We speculate that this finding provides further evidence that BNCT is the precursor lesion for chordoma. Additional investigations are needed to further understand this relationship. C1 Massachusetts Gen Hosp, Dept Pathol, WRN2, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN2, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 9 TC 32 Z9 36 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1573 EP 1577 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400015 PM 17895760 ER PT J AU Cornell, LD Chicano, SL Deshpande, V Collins, AB Selig, MK Lawers, GY Barisoni, L Colvin, RB AF Cornell, Lynn D. Chicano, Sonia L. Deshpande, Vikram Collins, A. Bernard Selig, Martin K. Lawers, Gregory Y. Barisoni, Laura Colvin, Robert B. TI Pseuclotumors due to IgG4 immune-complex tubulointerstitial nephritis associated with autoimmune pancreatocentric disease SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol DE immune complex; tubulointerstitial nephritis; autoimmune pancreatitis; kidney ID CHRONIC-PANCREATITIS; SCLEROSING PANCREATITIS; SJOGRENS-SYNDROME; EXTRAPANCREATIC LESIONS; INTERSTITIAL NEPHRITIS; STEROID-THERAPY; FEATURES; INVOLVEMENT; CHOLANGITIS; DEPOSITS AB Autoimmune pancreatitis (AIP) is a mass-forming chronic fibroinflammatory condition centered on the pancreatobiliary system and characterized by predominant immunoglobulin G4 (IgG4)-positive plasma cells. Recent reports have brought to light the multiorgan involvement of this disease. We describe a series of 5 cases of tubulointerstitial nephritis (TIN) associated with AIP and characterize the clinical, pathologic, ultrastructural, and immunopathologic features of TIN. The specimens consisted of 4 biopsies and I nephrectomy. The average patient age was 64 years (range 45 to 78) and the male to female ratio was 4:1. All had histologic and/or clinical and radiographic evidence of AIP, mass-forming sclerosing cholangitis, or both. The clinical impression in 4 patients was a renal mass or vasculitis. Two patients had renal insufficiency. Histologic preparations revealed a dense tubulointerstitial lymphoplasmacytic infiltrate. Eosinophils were often numerous. Tubulitis and tubular injury were present, along with tubular atrophy with focally thickened tubular basement membranes (TBMs). The histologic appearance ranged from a cellular, inflammatory pattern without tubular atrophy to a striking expansive interstitial fibrosis with tubular destruction. The nephrectomy specimen demonstrated a masslike nodular pattern of inflammation with normal renal tissue elsewhere. Glomeruli were uninvolved. By immunohistochemistry or immunofluorescence, numerous plasma cells in the infiltrate were positive for IgG4. TBM granular IgG deposits, predominantly of the IgG4 subclass, were detected in 4 of 5 cases by either immunofluorescence or immunohistochemistry. By electron microscopy, corresponding amorphous electron-dense deposits were present in the TBM in these cases. This type of TIN, typically characterized by a masslike lesion consisting of a lymphoplasmacytic infiltrate with eosinophils and prominent IgG4-positive plasma cells and immune-complex deposits in the TBM, may be part of a systemic IgG4-related disease, which we term "IgG4-associated immune complex Multiorgan Autoimmune Disease" (IMAD). C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NYU, Sch Med, New York, NY USA. RP Cornell, LD (reprint author), Massachusetts Gen Hosp, Dept Pathol, Thier 8,55 Fruit St, Boston, MA 02114 USA. EM cornell@alum.mit.edu NR 49 TC 114 Z9 126 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2007 VL 31 IS 10 BP 1586 EP 1597 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 217TE UT WOS:000249969400017 PM 17895762 ER PT J AU Christ, F Aretz, HT AF Christ, F. Aretz, H. T. TI Introduction to the topic: Learning institutions for the welfare of the patient - A necessity! SO ANAESTHESIST LA German DT Editorial Material C1 Klinikum Univ Munich, Anasthesiol Klin, Munich, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Christ, F (reprint author), Klinikum Univ Munich, Anasthesiol Klin, Munich, Germany. EM Frank.Christ@med.uni-muenchen.de NR 3 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0003-2417 J9 ANAESTHESIST JI Anaesthesist PD OCT PY 2007 VL 56 IS 10 BP 981 EP 982 DI 10.1007/s00101-007-1275-9 PG 2 WC Anesthesiology SC Anesthesiology GA 223XI UT WOS:000250408700001 PM 17926011 ER PT J AU Spohr, F Busch, CJ Peich, C Motsch, J Gebhard, MM Kuebler, WM Bloch, KD Weimann, J AF Spoehr, Fabian Busch, Cornelius J. Peich, Christian Motsch, Johann Gebhard, Martha M. Kuebler, Wolfgang M. Bloch, Kenneth D. Weimann, Jorg TI 4-aminopyridine restores impaired hypoxic pulmonary vasoconstriction in endotoxemic mice SO ANESTHESIOLOGY LA English DT Article ID GATED K+ CHANNELS; RESPIRATORY-DISTRESS-SYNDROME; INHALED NITRIC-OXIDE; SMOOTH-MUSCLE-CELLS; PRESSURE-FLOW RELATIONSHIPS; POTASSIUM CHANNEL; PROBABLE IMPLICATIONS; CONTROVERSIAL ISSUES; ARTERY MYOCYTES; MOLECULAR-BASIS AB Background: Hypoxic pulmonary vasoconstriction (HPV) is impaired during inflammatory lung processes such as pneumonia or the acute respiratory distress syndrome. Voltage-gated potassium channels play a central role in mediating HPV. The aim of this study was to determine whether 4-aminopyridine (4-AP), a known voltage-gated potassium channel inhibitor, may restore HPV in sepsis. Methods: The effects of 0.01, 0.1, and 1.0 mm 4-AP on HPV responsiveness were assessed in isolated lungs of untreated mice and of mice 18 h after lipopolysaccharide injection (20 mg/kg intraperitoneal Escherichia coli 0111:B4 lipopolysaccharide). HPV was quantified as the increase in perfusion pressure in response to hypoxic ventilation in percent of baseline perfusion pressure. Intrinsic pulmonary vascular resistance (R-0) and pulmonary vascular distensibility (alpha) were determined by nonlinear regression analysis of pulmonary vascular pressure-flow curves generated during normoxic and hypoxic ventilation, respectively. Results: HPV was impaired in lungs isolated from lipopolysaccharide-challenged mice. Addition of 4-AP to the perfusate did not alter HPV responsiveness in untreated mice but dose dependently restored HPV in endotoxemic mice. Analysis of pulmonary vascular pressure-flow curves revealed that 4-AP (1) counteracted the observed lipopolysaccharide-induced changes in a and R, under normoxic conditions and (2) augmented the hypoxia-induced increase in R. in lungs of endotoxemic mice. Conclusions: This study demonstrates that lipopolysaccharide-induced pulmonary vascular hyporesponsiveness to hypoxia can be restored by 4-AP in murine endotoxemia and, thus, may be a new therapeutic approach to treat patients with hypoxemia due to impaired HPV. C1 Vrije Univ Amsterdam Med Ctr, Dept Anesthesiol, NL-1007 MB Amsterdam, Netherlands. Univ Heidelberg, Dept Anaesthesiol, Heidelberg, Germany. Univ Heidelberg, Dept Expt Surg, D-6900 Heidelberg, Germany. Charite Univ Med Berlin, Inst Physiol, Berlin, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Boston, MA 02115 USA. RP Weimann, J (reprint author), Vrije Univ Amsterdam Med Ctr, Dept Anesthesiol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM j.weimann@vumc.nl FU NHLBI NIH HHS [HL 74352] NR 49 TC 10 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2007 VL 107 IS 4 BP 597 EP 604 PG 8 WC Anesthesiology SC Anesthesiology GA 216JJ UT WOS:000249874000014 PM 17893456 ER PT J AU Eikermann, M Fassbender, P Malhotra, A Takahashi, M Kubo, S Jordan, AS Gautam, S White, DP Chamberlin, NL AF Eikermann, Matthias Fassbender, Philipp Malhotra, Atul Takahashi, Masaya Kubo, Shigeto Jordan, Amy S. Gautam, Shiva White, David P. Chamberlin, Nancy L. TI Unwarranted administration of acetylcholinesterase inhibitors can impair genioglossus and diaphragm muscle function SO ANESTHESIOLOGY LA English DT Article ID RESIDUAL NEUROMUSCULAR BLOCK; UPPER AIRWAY PATENCY; ADDUCTOR POLLICIS; NEOSTIGMINE; REVERSAL; RECOVERY; VECURONIUM; GLYCOPYRROLATE; TRANSMISSION; STIMULATION AB Background: It is standard practice to administer a cholinesterase inhibitor (e.g., neostigmine) at the end of a surgical case to reverse suspected effects of neuromuscular blocking agents regardless of whether such residual effects are present. The authors hypothesized that cholinesterase inhibition when given the in absence of neuromuscular blockade (NB) would decrease upper airway dilatory muscle activity and consequently upper airway volume. Methods: The authors measured genioglossus and diaphragm electromyograms during spontaneous ventilation in anesthetized, tracheostomized rats before and after administration of neostigmine (0.03, 0.06, or 0.12 mg/kg), after recovery of the train-of-four ratio (quadriceps femoris muscle) to unity after NB (n = 18). For comparison, the authors made the same measurements in rats that had no previous NB (n = 27). In intact anesthetized rats, the authors measured upper airway volume and end-expiratory lung volume by magnetic resonance imaging before and after 0.12 mg/kg neostigmine (n = 9). Results: Neostigmine treatment in rats that had fully recovered from NB based on the train-of-four ratio caused dose-dependent decreases in genioglossus electromyogram. (to 70.3 +/-7.6, 49.2 +/- 3.2, and 39.7 +/- 2.3% of control, respectively), decreases in diaphragm electromyograrn (to 103.1 +/- 6.5, 83.1 +/- 4.7, and 68.7 +/- 7.3% of control), and decreases in minute ventilation to a nadir value of 79.6 +/- 6% of preneostigmine baseline. Genioglossus electromyogram effects were the same when neostigmine was given with no previous NB. Neostigmine caused a decrease in upper airway volume to 83 +/- 3% of control, whereas end-expiratory lung volume remained constant. Conclusions: The cholinesterase inhibitor neostigmine markedly impairs upper airway dilator volume, genioglossus muscle function, diaphragmatic function, and breathing when given after recovery from vecuronium-induced neuromuscular block. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Klinikum Essen, Klin Anasthesie & Intens Med, Essen, Germany. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Eikermann, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM meikermann@partners.org OI Jordan, Amy/0000-0001-8561-9766 FU NHLBI NIH HHS [R01 HL073146-03, R01-HL73146, R01 HL073146, P50 HL 60292, P50 HL060292]; NIA NIH HHS [K23 AG024837, K23 AG024837-01] NR 38 TC 46 Z9 48 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD OCT PY 2007 VL 107 IS 4 BP 621 EP 629 PG 9 WC Anesthesiology SC Anesthesiology GA 216JJ UT WOS:000249874000017 PM 17893459 ER PT J AU Sonnen, JA Larson, EB Crane, PK Haneuse, S Li, G Schellenberg, GD Craft, S Leverenz, JB Montine, TJ AF Sonnen, Joshua A. Larson, Eric B. Crane, Paul K. Haneuse, Sebasuen Li, Ge Schellenberg, Gerald D. Craft, Suzanne Leverenz, James B. Montine, Thomas J. TI Pathological correlates of dementia in a longitudinal, population-based sample of aging SO ANNALS OF NEUROLOGY LA English DT Article ID VASCULAR COGNITIVE IMPAIRMENT; ALZHEIMER-DISEASE PATHOLOGY; CEREBROVASCULAR PATHOLOGY; NEUROFIBRILLARY PATHOLOGY; CEREBRAL INFARCTIONS; LEWY BODIES; DIAGNOSIS; NEUROPATHOLOGY; PURIFICATION; PREVALENCE AB Objective: Previously published community- or population-based studies of brain aging and dementia with autopsy were restricted to a single sex, a single ethnic group, Roman Catholic clergy, or focused pathological assessments. Our goal was to determine the independent pathological correlates associated with dementia in a typical US population. Methods: We evaluated autopsy data from the Adult Changes in Thought study, an ongoing longitudinal, population-based study of brain aging and dementia. Analyses were based on data collected from about 3,400 people 65 years or older who were cognitively intact at the time of enrollment in the Group Health Cooperative in King County, Washington. Alt consecutive autopsies (n = 221; 20% of deaths) from this cohort were evaluated and analyzed by weighted multivariate analysis to account for potential participation bias. Results: After adjusting for age, sex, education, and APOE, independent correlates of dementia (relative risk, 95% confidence interval; overall p value) included Braak stage (V/VI vs 0/I/II: 5.89, 1.62-17.60; p < 0.05), number of cerebral microinfarcts in standardized sections (> 2 vs none: 4.80, 1.91-10.26; p < 0.001), and neocortical Lewy bodies (any vs none: 5.08, 1.37-18.96; P < 0.05). Estimates of adjusted population attributable risk for these three processes were 45% for Braak stage, 33% for microinfarcts, and 10% for neocortical Lewy bodies. Interpretation: Our results underscore the therapeutic imperative for Alzheimer's and Lewy body diseases, and provide evidence to support the immediate use of strategies that target cerebral microinfarcts as a means to partially prevent or delay the onset of dementia. C1 Univ Washington, Dept Pathol, Seattle, WA 98104 USA. Univ Washington, Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Mental Illness, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Geriatr, Seattle, WA USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Parkinsons Res, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Educ, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Clin Ctr, Seattle, WA USA. RP Sonnen, JA (reprint author), Univ Washington, Dept Pathol, 325 9th Ave,Box 359791, Seattle, WA 98104 USA. EM jsonnen@u.washington.edu RI Crane, Paul/C-8623-2014; Sonnen, 37382016/H-3738-2016; OI Sonnen, 37382016/0000-0001-9267-8705; Crane, Paul/0000-0003-4278-7465 FU NIA NIH HHS [AG000258, R01 AG023801, AG023801, AG06781]; NINDS NIH HHS [NS48595] NR 47 TC 215 Z9 218 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD OCT PY 2007 VL 62 IS 4 BP 406 EP 413 DI 10.1002/ana.21208 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 227WU UT WOS:000250689300012 PM 17879383 ER PT J AU Iaiza, E De Pauli, F Ermacora, P Follador, A Cardellino, G Fasola, G Ramoni, M Sonis, S Aprile, G AF Iaiza, Emiliana De Pauli, Federica Ermacora, Paola Follador, Alessandro Cardellino, Giovanni Fasola, Gianpiero Ramoni, Marco Sonis, Stephen Aprile, Giuseppe TI Comparison of toxicity frequencies between Italian and American patients being treated with chemotherapy for colorectal cancer (CRC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th National Congress of Medical Oncology CY OCT 12-15, 2007 CL Palermo, ITALY C1 [Iaiza, Emiliana; De Pauli, Federica; Ermacora, Paola; Follador, Alessandro; Cardellino, Giovanni; Fasola, Gianpiero; Aprile, Giuseppe] Univ Hosp, Dept Oncol, Udine, Italy. [Sonis, Stephen; Aprile, Giuseppe] BWH, Boston, MA USA. [Ramoni, Marco] Harvard Univ, Sch Med, Boston, MA USA. [Sonis, Stephen; Aprile, Giuseppe] Dana Faber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2007 VL 18 SU 11 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 264WX UT WOS:000253322200042 ER PT J AU Aprile, G Ramoni, M Keefe, D Sonis, S AF Aprile, Giuseppe Ramoni, Marco Keefe, Dorothy Sonis, Stephen TI Acute toxicities in colorectal cancer (CRC) patients undergoing chemotherapy (CT): Clustering and cycle-to-cycle prediction by means of Bayesian analysis SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th National Congress of Medical Oncology CY OCT 12-15, 2007 CL Palermo, ITALY C1 [Aprile, Giuseppe; Sonis, Stephen] Brigham & Womens Hosp, Div Oral Med, Boston, MA 02115 USA. [Aprile, Giuseppe; Sonis, Stephen] Dana Faber Canc Inst, Boston, MA 02115 USA. [Aprile, Giuseppe] Univ Hosp, Dept Oncol, Udine, Italy. [Ramoni, Marco] Harvard Univ, Sch Med, Dept Informat, Boston, MA USA. [Keefe, Dorothy] Royal Adelaide Hosp, Dept Med, Adelaide, SA 5000, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2007 VL 18 SU 11 BP 12 EP 12 PG 1 WC Oncology SC Oncology GA 264WX UT WOS:000253322200044 ER PT J AU Cappuzzo, F Finocchiaro, G Janne, PA Franklin, WA Bencardino, K Crino, L Roncalli, M Carnaghi, C Varella-Garcia, M Santoro, A AF Cappuzzo, Federico Finocchiaro, Giovanna Jaenne, Pasi A. Franklin, Wilbur A. Bencardino, Katia Crino, Lucio Roncalli, Massimo Carnaghi, Carlo Varella-Garcia, Marileila Santoro, Armando TI Comprehensive assessment of molecular markers predicting response to cetuximab therapy in colorectal cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th National Congress of Medical Oncology CY OCT 12-15, 2007 CL Palermo, ITALY C1 Dana Farber Canc Inst, Ist Clin Humaitas IRCCS Rozzano, Boston, MA 02115 USA. Colorado Canc Ctr, Aurora, CO USA. Monteluce Policlin, Perugia, Italy. Policlin San Matteo, I-27100 Pavia, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2007 VL 18 SU 11 BP 18 EP 18 PG 1 WC Oncology SC Oncology GA 264WX UT WOS:000253322200071 ER PT J AU Neri, P Calimeri, T Propato, M Rossi, M Pietragalla, A Ventura, M Cucinotto, I Bulotta, A Eramo, O Di Martino, MT Munshi, NC Anderson, KC Tagliaferri, P Tassone, P AF Neri, P. Calimeri, T. Propato, M. Rossi, M. Pietragalla, A. Ventura, M. Cucinotto, I Bulotta, A. Eramo, O. Di Martino, M. T. Munshi, N. C. Anderson, K. C. Tagliaferri, P. Tassone, P. TI In vitro and in vivo activity of valproic acid in myeloma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th National Congress of Medical Oncology CY OCT 12-15, 2007 CL Palermo, ITALY C1 [Neri, P.; Calimeri, T.; Propato, M.; Rossi, M.; Pietragalla, A.; Ventura, M.; Cucinotto, I; Bulotta, A.; Eramo, O.; Tagliaferri, P.; Tassone, P.] Magna Graecia Univ Catanzaro, Med Oncol Unit, I-88100 Catanzaro, Italy. [Neri, P.; Munshi, N. C.; Tassone, P.] Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2007 VL 18 SU 11 BP 86 EP 86 PG 1 WC Oncology SC Oncology GA 264WX UT WOS:000253322200361 ER PT J AU Li, PMMC Somdas, MA Eddington, DK Nadol, JB AF Li, Peter M. M. C. Somdas, Mehmet A. Eddington, Donald K. Nadol, Joseph B., Jr. TI Analysis of intracochlear new bone and fibrous tissue formation in human subjects with cochlear implants SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE bone; cochlear implant; computer-assisted three-dimensional imaging; fibrous tissue; histopathology ID LABYRINTHITIS OSSIFICANS; INSERTION TRAUMA; TEMPORAL BONE; ELECTRODES; HEARING; HISTOPATHOLOGY; PRESERVATION; PERFORMANCE; POSITION AB Objectives: In this study we aimed to evaluate new bone and new fibrous tissue formation in the inner ear following cochlear implantation. Methods: Twelve temporal bones from patients who underwent cochlear implantation during life were prepared for histologic study. The specimens were reconstructed by both 2-dimensional and 3-dimensional methods. These reconstructions were used to calculate the total volume and distribution of new bone and new fibrous tissue in the cochlea, the number of spiral ganglion cells, and other histopathologic parameters. Clinical data, including the last-recorded word recognition scores, were obtained from the patients' medical records. Results: New bone and new fibrous tissue were found in all 12 specimens, particularly at the site of cochleostomy. There was a significant correlation between overall damage to the lateral cochlear wall and the total volume of intracochlear new tissue (Spearman rho = .853; p = .0004). The total volume of new tissue did not correlate with word recognition scores or spiral ganglion cell counts. Conclusions: These preliminary results suggest that the degree of damage to the lateral cochlear wall may play an important role in influencing the amount of new tissue formation following cochlear implantation. Intracochlear new tissue does not appear to be an important determinant of performance as measured by word recognition scores or the total number of remaining spiral ganglion cells. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA 02114 USA. MIT, Elect Res Lab, Boston, MA USA. RP Nadol, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [5 R01 DC000152] NR 21 TC 40 Z9 41 U1 2 U2 8 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2007 VL 116 IS 10 BP 731 EP 738 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 221OC UT WOS:000250236200004 PM 17987778 ER PT J AU Pawlik, TM Gleisner, AL Bauer, TW Adams, RB Reddy, SK Clary, BM Martin, RC Scoggins, CR Tanabe, KK Michaelson, JS Kooby, DA Staley, CA Schulick, RD Vauthey, JN Abdalla, EK Curley, SA Choti, MA Elias, D AF Pawlik, Timothy M. Gleisner, Ana Luiza Bauer, Todd W. Adams, Reid B. Reddy, Srinevas K. Clary, Bryan M. Martin, Robert C. Scoggins, Charles R. Tanabe, Kenneth K. Michaelson, James S. Kooby, David A. Staley, Charles A. Schulick, Richard D. Vauthey, Jean-Nicolas Abdalla, Eddie K. Curley, Steven A. Choti, Michael A. Elias, Dominque TI Liver-directed surgery for metastatic squamous cell carcinoma to the liver: Results of a multi-center analysis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Cancer Symposium of the Society-of-Surgical-Oncology CY MAR 15-18, 2007 CL Washington, DC SP Soc Surg Oncol DE squamous cell carcinoma; hepatic resection; prognosis ID POSITRON-EMISSION-TOMOGRAPHY; HEPATIC RESECTION; ESOPHAGEAL-CARCINOMA; DISTANT METASTASES; NONNEUROENDOCRINE METASTASES; COLORECTAL METASTASES; NONCOLORECTAL PRIMARY; SURGICAL RESECTION; RADIATION-THERAPY; CANCER AB Background: The role of hepatic resection for metastatic squamous cell carcinoma (SCC) remains unknown. The current study evaluates the role of hepatic resection in patients with metastatic SCC to the liver. Methods: Between 1988 and 2006, 52 patients underwent hepatic resection of metastatic SCC at eight major cancer centers. Clinicopathologic factors were analyzed with regard to disease-free survival (DFS) and overall survival (OS). Results: Primary SCC site was anal (n = 27), head/neck (n = 12), lung (n = 4), esophagus (n = 2), and other (n = 7). Treatment of primary SCC was chemotherapy +/- radiotherapy alone (n = 29), chemotherapy +/- radiotherapy + surgery (n = 15), or surgery alone (n = 8). Forty-seven patients underwent resection alone, 2 resection + radiofrequency ablation (RFA), and 3 RFA only. At last follow-up, 33 (63.5%) patients had recurred. The median time to recurrence was 9.8 months, and 5-year DFS was 18.6%. Factors associated with reduced DFS were liver tumor size > 5 cm (hazard ratio (HR) = 2.02) and positive surgical margin (HR = 2.33). The overall median survival after hepatic resection was 22.3 months and 5-year actuarial OS was 20.5%. Risk factors associated with worse overall survival included synchronous disease (HR = 4.09), hepatic metastasis > 5 cm (HR = 1.71) and positive surgical resection margin (HR = 1.83). Conclusions: The majority of patients will recur following hepatic resection of SCC. Long-term survival, however, can be achieved following surgical resection of SCC liver metastasis, especially in patients who present with limited metachronous disease amenable to margin negative resection. C1 Johns Hopkins Sch Med, Dept Surg, Baltimore, MD 21205 USA. Univ Virginia, Med Ctr, Dept Surg, Charlottesville, VA USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Univ Louisville, Med Ctr, Dept Surg, Louisville, KY 40292 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg, Houston, TX 77030 USA. Inst Gustave Roussy, Dept Surg, F-94800 Villejuif, France. RP Pawlik, TM (reprint author), Johns Hopkins Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM tpawlik1@jhmi.edu NR 45 TC 20 Z9 20 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2007 VL 14 IS 10 BP 2807 EP 2816 DI 10.1245/s10434-007-9467-8 PG 10 WC Oncology; Surgery SC Oncology; Surgery GA 212RY UT WOS:000249615700019 PM 17551795 ER PT J AU Ellis, MW Griffith, ME Dooley, DP McLean, JC Jorgensen, JH Patterson, JE Davis, KA Hawley, JS Regules, JA Rivard, RG Gray, PJ Ceremuga, JM DeJoseph, MA Hospenthal, DR AF Ellis, Michael W. Griffith, Matthew E. Dooley, David P. McLean, Joseph C. Jorgensen, James H. Patterson, Jan E. Davis, Kepler A. Hawley, Joshua S. Regules, Jason A. Rivard, Robert G. Gray, Paula J. Ceremuga, Julia M. DeJoseph, Mary A. Hospenthal, Duane R. TI Targeted intranasal mupirocin to prevent colonization and infection by community-associated methicillin-resistant Staphylococcus aureus strains in soldiers: A cluster randomized controlled trial SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; PANTON-VALENTINE LEUKOCIDIN; NASAL CARRIAGE; ANTERIOR NARES; HEALTHY-ADULTS; UNITED-STATES; PROPHYLAXIS; EMERGENCE; PREVALENCE; OINTMENT AB Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that primarily manifests as uncomplicated skin and soft tissue infections. We conducted a cluster randomized, double-blind, placebo-controlled trial to determine whether targeted intranasal mupirocin therapy in CAMRSA-colonized soldiers could prevent infection in the treated individual and prevent new colonization and infection within their study groups. We screened 3,447 soldiers comprising 14 training classes for CA-MRSA colonization from January to December 2005. Each training class was randomized to either the mupirocin or placebo study group, and the participants identified as CA-MRSA colonized were treated with either mupirocin or placebo. All participants underwent repeat screening after 8 to 10 weeks and were monitored for 16 weeks for development of infection. Of 3,447 participants screened, 134 (3.9%) were initially colonized with CAMRSA. Five of 65 (7.7%; 95% confidence interval [95% CI], 4.0% to 11.4%) placebo-treated participants and 7 of 66 (10.6%; 95% CI, 7.9% to 13.3%) mupirocin-treated participants developed infections; the difference in the infection rate of the placebo- and mupirocin -treated groups was -2.9% (95% CI, -7.5% to 1.7%). Of those not initially colonized with CA-MRSA, 63 of 1,459 (4.3%; 95% CI, 2.7% to 5.9%) of the placebo group and 56 of 1,607 (3.5%; 95% CI, 2.6% to 5.2%) of the mupirocin group developed infections; the difference in the infection rate of the placebo and mupirocin groups was 0.8% (95% CI, -1.0% to 2.7%). Of 3,447 participants, 3,066 (89%) were available for the second sampling and completed follow-up. New CA-MRSA colonization occurred in 24 of 1,459 (1.6%; 95% CI, 0.05% to 2.8%) of the placebo group participants and 23 of 1,607 (1.4%; 95% CI, 0.05% to 2.3%) of the mupirocin group participants; the difference in the infection rate of the placebo and mupirocin groups was 0.2% (95% CI, -1.3% to 1.7%). Despite CA-MRSA eradication in colonized participants, this study showed no decrease in infections in either the mupirocin -treated individuals or within their study group. Furthermore, CA-MRSA eradication did not prevent new colonization within the study group. C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX USA. DD Eisenhower Army Med Ctr, Dept Med Infect Dis, Ft Gordon, GA USA. Brooke Army Med Ctr, Dept Med Infect Dis, Ft Sam Houston, TX 78234 USA. Brooke Army Med Ctr, Dept Prevent Med, Ft Sam Houston, TX 78234 USA. Brooke Army Med Ctr, Pathol & Area Lab Serv, Ft Sam Houston, TX 78234 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, San Antonio, TX USA. RP Ellis, MW (reprint author), Brooke Army Med Ctr, Infect Dis Serv, MCHE MDI, 3581 Roger Brooke, Ft Sam Houston, TX 78234 USA. EM michael.w.ellis@us.army.mil NR 53 TC 80 Z9 82 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2007 VL 51 IS 10 BP 3591 EP 3598 DI 10.1128/AAC.01086-06 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 215FX UT WOS:000249794800017 PM 17682105 ER PT J AU Peng, LF Kim, SS Matchacheep, S Lei, XG Su, S Lin, WY Runguphan, W Choe, WH Sakamoto, N Ikeda, M Kato, N Beeler, AB Porco, JA Schreiber, SL Chung, RT AF Peng, Lee F. Kim, Sun Suk Matchacheep, Sirinya Lei, Xiaoguang Su, Shun Lin, Wenyu Runguphan, Weerawat Choe, Won-Hyeok Sakamoto, Naoya Ikeda, Masanori Kato, Nobuyuki Beeler, Aaron B. Porco, John A., Jr. Schreiber, Stuart L. Chung, Raymond T. TI Identification of novel epoxide inhibitors of hepatitis C virus replication using a high-throughput screen SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SMALL MOLECULES; CELL-CULTURE; LIBRARY; DIVERSITY AB Using our high-throughput hepatitis C replicon assay to screen a library of over 8,000 novel diversity-oriented synthesis (DOS) compounds, we identified several novel compounds that regulate hepatitis C virus (HCV) replication, including two libraries of epoxides that inhibit HCV replication (best 50% effective concentration, < 0.5 mu M). We then synthesized an analog of these compounds with optimized activity. C1 Massachusetts Gen Hosp, GI Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Broad Inst Harvard, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Gachon Univ Gil Med Ctr, Dept Gastroenterol & Hepatol, Inchon 405760, South Korea. Boston Univ, Dept Chem, Boston, MA 02215 USA. Boston Univ, Ctr Chem Methodol & Library Dev CMLD BU, Boston, MA 02215 USA. Tokyo Med & Dent Univ, Dept Gastroenterol & Hepatol, Tokyo, Japan. Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Biol Mol, Okayama, Japan. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, Dept Med, GRJ 825A,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org RI IKEDA, Masanori/B-2279-2011; Sakamoto, Naoya/G-2734-2012 FU NCI NIH HHS [N01 CO12400, N01CO12400]; NIDDK NIH HHS [K08 DK088951, 5 T32 DK07191-31, T32 DK007191]; NIGMS NIH HHS [P50 GM067041]; NINDS NIH HHS [NS050854-01, R03 NS050854] NR 19 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2007 VL 51 IS 10 BP 3756 EP 3759 DI 10.1128/AAC.00233-07 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 215FX UT WOS:000249794800042 PM 17682098 ER PT J AU Zuo, R AF Zuo, Rongjun TI Biofilms: strategies for metal corrosion inhibition employing microorganisms SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE bacterial biofilm; corrosion control ID SULFATE-REDUCING BACTERIA; AXENIC AEROBIC BIOFILMS; MICROBIOLOGICALLY INFLUENCED CORROSION; ESCHERICHIA-COLI BIOFILMS; CARBON-STEEL CORROSION; MILD-STEEL; REGENERATIVE BIOFILMS; PROTECTIVE-COATINGS; DIFFERENT MEDIA; SAE-1018 STEEL AB Corrosion causes dramatic economic loss. Currently widely used corrosion control strategies have disadvantages of being expensive, subject to environmental restrictions, and sometimes inefficient. Studies show that microbial corrosion inhibition is actually a common phenomenon. The present review summarizes recent progress in this novel strategy: corrosion control using beneficial bacteria biofilms. The possible mechanisms may involve: (1) removal of corrosive agents (such as oxygen) by bacterial physiological activities (e.g., aerobic respiration), (2) growth inhibition of corrosion-causing bacteria by antimicrobials generated within biofilms [e.g., sulfate-reducing bacteria (SRB) corrosion inhibition by gramicidin S-producing Bacillus brevis biofilm], (3) generation of protective layer by biofilms (e.g., Bacillus licheniformis biofilm produces on aluminum surface a sticky protective layer of gamma-polyglutamate). Successful utilization of this novel strategy relies on advances in study at the interface of corrosion engineering and biofilm biology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. RP Zuo, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med Surg Serv, Boston, MA 02115 USA. EM zuorongjun@gmail.com NR 57 TC 68 Z9 75 U1 5 U2 57 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD OCT PY 2007 VL 76 IS 6 BP 1245 EP 1253 DI 10.1007/s00253-007-1130-6 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 212SE UT WOS:000249616300003 PM 17701408 ER PT J AU Philips, N Keller, T Hendrix, C Hamilton, S Arena, R Tuason, M Gonzalez, S AF Philips, Neena Keller, Thomas Hendrix, Cynthia Hamilton, Shannon Arena, Rosemarie Tuason, Marvin Gonzalez, Salvador TI Regulation of the extracellular matrix remodeling by lutein in dermal fibroblasts, melanoma cells, and ultraviolet radiation exposed fibroblasts SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE lutein; ultraviolet radiation; extracellular matrix; melanoma; fibroblasts ID HUMAN SKIN FIBROBLASTS; GROWTH-FACTOR-BETA; LIPID-PEROXIDATION; POLYPODIUM-LEUCOTOMOS; BREAST-CANCER; MACULAR DEGENERATION; UVA IRRADIATION; EXPRESSION; COLLAGENASE; CAROTENOIDS AB With aging and cancer there is increased expression or activity of matrix metalloproteinases (MMPs) that degrade and remodel the structural extracellular matrix (ECM). In addition, exposure of skin to ultraviolet (UV) radiation (photoaging) leads to loss of cell viability, membrane damage, and deposition of excessive elastotic material. Lutein has antioxidant, anti-inflammatory, photoprotective, and anti-carcinogenic properties. The goal of this research was to investigate lutein's anti-aging and anti-carcinogenic effects via the regulation of the extracellular matrix remodeling. To this purpose, the effects of lutein on the expression of MMPs and their inhibitors (TIMPs, tissue inhibitors of metalloproteinases) in dermal fibroblasts (intrinsic aging) and melanoma cells were examined. Further, for lutein's photoprotective effects, the regulation of cell viability, membrane integrity, and elastin expression in the non-irradiated, and UVA or UVB radiation exposed fibroblasts were analyzed. Lutein significantly inhibited MMP-1 expression, transcriptionally, and MMP-2 protein levels in dermal fibroblasts, without altering TIMPs expression. It significantly inhibited MMP-1 expression in melanoma cells while stimulating TIMP-2. Lutein did not alter fibroblast or melanoma cell viability or membrane integrity. In ultraviolet radiation exposed fibroblasts, lutein improved cell viability, membrane integrity and inhibited elastin expression, though more significantly in the UVB exposed fibroblasts. In summary, the mechanism to lutein's anti-aging and anti-carcinogenic effects include the inhibition of MMP to TIMP ratio in dermal fibroblasts and melanoma cells, and the inhibition of cell loss, membrane damage and elastin expression in ultraviolet radiation exposed fibroblasts. C1 Univ Coll, Teaneck, NJ 07666 USA. Georgian Court Univ, Sch Sci & Math, Lakewood, NJ USA. Fairleigh Dickinson Univ, Sch Nat Sci, Teaneck, NJ USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Philips, N (reprint author), Univ Coll, H-DH4-03,1000 River Rd, Teaneck, NJ 07666 USA. EM nphilips@fdu.edu NR 56 TC 19 Z9 21 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD OCT PY 2007 VL 299 IS 8 BP 373 EP 379 DI 10.1007/s00403-007-0779-0 PG 7 WC Dermatology SC Dermatology GA 208CE UT WOS:000249296600003 PM 17710425 ER PT J AU Smoller, JW Pollack, MH Wassertheil-Smoller, S Jackson, RD Oberman, A Wong, ND Sheps, D AF Smoller, Jordan W. Pollack, Mark H. Wassertheil-Smoller, Sylvia Jackson, Rebecca D. Oberman, Albert Wong, Nathan D. Sheps, David TI Panic attacks and risk of incident cardiovascular events among postmenopausal women in the women's health initiative observational study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORONARY-HEART-DISEASE; ARTERY-DISEASE; DEPRESSIVE SYMPTOMS; PHOBIC ANXIETY; RATE-VARIABILITY; CHEST-PAIN; DISORDER; MORTALITY; TRIAL; ISCHEMIA AB Context: Previous studies have documented an association of depression and phobic anxiety with cardiovascular morbidity and mortality, but little is known about the cardiovascular sequelae of panic anxiety. Objective: To determine whether panic attacks are associated with risk of cardiovascular morbidity and mortality in postmenopausal women. Design: Prospective cohort survey. Setting: Ten clinical centers of the 40- center Women's Health Initiative. Participants: A total of 3369 community- dwelling, generally healthy postmenopausal women ( aged 51- 83 years) enrolled between 1997 and 2000 in the Myocardial Ischemia and Migraine Study who completed a questionnaire about occurrence of panic attacks in the previous 6 months. Main Outcome Measures: Cardiovascular/ cerebrovascular outcomes ( fatal and nonfatal myocardial infarction and stroke) and all- cause mortality were ascertained after a mean of 5.3 years of follow- up. Results: A 6- month history of full- blown panic attacks, endorsed by 10% of postmenopausal women in this cohort, was associated with both coronary heart disease ( hazard ratio, 4.20; 95% confidence interval, 1.76- 9.99) and the combined end point of coronary heart disease or stroke ( hazard ratio, 3.08; 95% confidence interval, 1.60- 5.94) after controlling for multiple potential confounders. The hazard ratio for all- cause mortality, excluding those with a history of cardiovascular/ cerebrovascular events, was 1.75 ( 95% confidence interval, 1.04- 2.94). Conclusion: Panic attacks are relatively common among postmenopausal women and appear to be an independent risk factor for cardiovascular morbidity and mortality in older women. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Albert Einstein Coll Med, Dept Epidemiol, New York, NY USA. Albert Einstein Coll Med, Sch Med, New York, NY USA. Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Univ Calif Irvine, Dept Med, Heart Dis Prevent Program, Irvine, CA 92717 USA. Univ Florida, Div Cardiovasc Med, Gainesville, FL 32611 USA. Malcolm Randall Vet Affairs Med Ctr, Gainesville, FL USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Simches Res Bldg,185 Cambridge St,Ste 2200, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 37 TC 104 Z9 107 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2007 VL 64 IS 10 BP 1153 EP 1160 DI 10.1001/archpsyc.64.10.1153 PG 8 WC Psychiatry SC Psychiatry GA 215YI UT WOS:000249844500006 PM 17909127 ER PT J AU Johnson, SC Ries, ML Hess, TM Carlsson, CM Gleason, CE Alexander, AL Rowley, HA Asthana, S Sager, MA AF Johnson, Sterling C. Ries, Michele L. Hess, Timothy M. Carlsson, Cynthia M. Gleason, Carey E. Alexander, Andrew L. Rowley, Howard A. Asthana, Sanjay Sager, Mark A. TI Effect of Alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID MILD COGNITIVE IMPAIRMENT; CORTICAL MIDLINE STRUCTURES; E EPSILON-4 CARRIERS; PREFRONTAL CORTEX; APOLIPOPROTEIN-E; OLDER-ADULTS; HIPPOCAMPAL ACTIVATION; MACAQUE MONKEY; FAMILIAL RISK; FMRI EVIDENCE AB Context: Asymptomatic middle- aged adult children of patients with Alzheimer disease ( AD) recently were found to exhibit functional magnetic resonance imaging ( fMRI) deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is yet unknown. This study examines the neural substrates of self- appraisal ( SA) in persons at risk for AD. Accurate appraisal of deficits is a problem for many patients with AD, and prior fMRI studies of healthy young adults indicate that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during SA tasks. Objective: To determine whether parental family history of AD ( hereafter referred to as FH) or presence of the epsilon 4 allele of the apolipoprotein E gene ( APOE4) exerts independent effects on brain function during SA. Design: Cross- sectional factorial design in which APOE4 status ( present vs absent) was one factor and FH was the other. All participants received cognitive testing, geno-typing, and an fMRI task that required subjective SA decisions regarding trait adjective words in comparison with semantic decisions about the same words. Setting: An academic medical center with a research-dedicated 3.0- T MR imaging facility. Participants: Cognitively normal middle- aged adults ( n= 110), 51 with an FH and 59 without an FH. Main Outcome Measure: Blood oxygen - dependent contrast measured using T2*- weighted echo- planar imaging. Results: Parental family history of AD and APOE4 status interacted in the posterior cingulate and left superior and medial frontal regions. There were main effects of FH ( FH negative > FH positive) in the left hippocampus and ventral posterior cingulate. There were no main effects of APOE genotype. Conclusions: Our results suggest that FH may affect brain function during subjective SA in regions commonly affected by AD. Although the participants in this study were asymptomatic and middle- aged, the findings suggest that there may be subtle alterations in brain function attributable to AD risk factors. C1 William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Sch Med & Publ Hlth, Madison, WI USA. Univ Wisconsin, Dept Med Phys, Sch Med & Publ Hlth, Madison, WI 53706 USA. Univ Wisconsin, Dept Radiol, Sch Med & Publ Hlth, Madison, WI 53706 USA. RP Johnson, SC (reprint author), William S Middleton Mem Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, 2500 Overlook Terr 11G, Madison, WI 53705 USA. EM scj@medicine.wisc.edu FU NIA NIH HHS [R01 AG021155-04, R01 AG 21155, R01 AG021155, R01 AG021155-01A2, R01 AG021155-02, R01 AG021155-03, R01 AG021155-05] NR 68 TC 23 Z9 23 U1 6 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2007 VL 64 IS 10 BP 1163 EP 1171 DI 10.1001/archpsyc.64.10.1163 PG 9 WC Psychiatry SC Psychiatry GA 215YI UT WOS:000249844500007 PM 17909128 ER PT J AU Keogh, IJ Troulis, MJ Monroy, AA Eavey, RD Kaban, LB AF Keogh, Ivan J. Troulis, Maria J. Monroy, Angelo A. Eavey, Roland D. Kaban, L. B. TI Isolated microtia as a marker for unsuspected hemifacial microsomia SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID MALFORMATIONS; MODEL; ISOTRETINOIN; EMBRYOPATHY; ANOMALIES; ANOTIA; MOUSE AB Objective: To determine the proportion of hemifacial microsorma (HFM) in patients with unilateral or bilateral "isolated" microtia. Design: Prospective cohort clinical study. Setting: University-affiliated, tertiary referral clinic for patients with microtia. Patients: One hundred consecutive patients with isolated microtia. Interventions: All the patients underwent a clinical examination and audiologic evaluation. The OMENS classification system was used to grade the severity of craniofacial features: orbital deformity, mandibular hypoplasia, ear deformity, nerve (cranial nerve VII) involvement, and soft-tissue deficiency. Each anatomical abnormality was graded from 0 (normal) to 3 (most severe) (score range, 0-15). Main outcome Measures: The OMENS scores, percentage of patients with isolated microtia and undiagnosed HFM, and isolated microtia as an early clinical marker for HFM. Results: Forty patients (40%) with microtia were determined to have HFM (31 unilateral and 9 bilateral). Mean patient age was 9.2 years (range, 6 weeks to 41 years), with male predominance (27 males and 13 females). The OMENS scores were less than 5 in 24 patients and 6 to 10 in 16 patients. Thirty patients had cranial nerve deficits, and 37 had mandibular asymmetry. Thirty-seven patients demonstrated conductive hearing loss, and I had sensorineural hearing loss. Conclusions: Isolated microtia served as an early clinical marker for asymmetrical facial growth in 40% of the patients. Isolated microtia and HFM could represent a spectrum of expression of the same developmental phenomenon. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Otolaryngol, Pediat Otolaryngol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Boston, MA USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Dept Genet, Boston, MA USA. Royal Coll Surgeons Ireland, Dublin, Ireland. Univ Coll Hosp Galway, Dept Otolaryngol, Galway, Ireland. RP Keogh, IJ (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Otolaryngol, Pediat Otolaryngol Serv, Boston, MA 02114 USA. EM ivankeogh@oceanfree.net RI KEOGH, IVAN/M-2704-2016 OI KEOGH, IVAN/0000-0001-6358-6377 NR 22 TC 15 Z9 16 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2007 VL 133 IS 10 BP 997 EP 1001 DI 10.1001/archotol.133.10.997 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 218XN UT WOS:000250049400005 PM 17938322 ER PT J AU Nguyen, HT Faquin, WC Weinstein, HJ Cunningham, MJ AF Nguyen, Hien T. Faquin, William C. Weinstein, Howard J. Cunningham, Michael J. TI Pathology quiz case 2 - Follicular lymphoma (FL), grade 3, pediatric type SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID CHILDHOOD C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Nguyen, HT (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2007 VL 133 IS 10 BP 1063 EP + DI 10.1001/archotol.133.10.1063 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 218XN UT WOS:000250049400019 PM 17938336 ER PT J AU Perrin, JM Romm, D Bloom, SR Homer, CJ Kuhlthau, KA Cooley, C Duncan, P Roberts, R Sloyer, P Wells, N Newacheck, P AF Perrin, James M. Romm, Diane Bloom, Sheila R. Homer, Charles J. Kuhlthau, Karen A. Cooley, Carl Duncan, Paula Roberts, Richard Sloyer, Phyllis Wells, Nora Newacheck, Paul TI A family-centered, community-based system of services for children and youth with special health care needs SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PREVALENCE AB Objective: To present a conceptual definition of a family-centered system of services for children and youth with special health care needs (CYSHCN). Previous work by the Maternal and Child Health Bureau to define CYSHCN has had widespread program effects. This article similarly seeks to provide a definition of a system of services. Design: Comprehensive literature review of systems of services and consensus panel organized to review and refine the definition. Setting: Policy research group and advisors at multiple sites. Participants: Policy researchers, content experts on CYSHCN, family representatives, and state program directors. Outcome: Definition of a system of services for CYSHCN. Results: This article defines a system of services for CYSHCN as a family-centered network of community-based services designed to promote the healthy development and well-being of these children and their families. The definition can guide discussion among policy makers, practitioners, state programs, researchers, and families for implementing the "community-based systems of services" contained in Title V of the Social Security Act. Critical characteristics of a system include coordination of child and family services, effective communication among providers and the family, family partnership in care provision, and flexibility. Conclusions: This definition provides a conceptual model that can help measurement development and assessment of how well systems work and achieve their goals. Currently available performance objectives for the provision of care for CYSHCN and national surveys of child health could be modified to assess systems of services in general. C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Initiat Child Healthcare Qual, Boston, MA USA. Crotched Mt Rehabil Ctr, Greenfield, NH USA. Univ Vermont, Dept Pediat, Burlington, VT USA. Utah State Univ, Early Intervent Res Inst, Logan, UT 84322 USA. Florida Dept Hlth, Childrens Med Serv, Tallahassee, FL USA. Family Voices, Boston, MA USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. RP Perrin, JM (reprint author), MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, 50 Staniford St,Ste 901, Boston, MA 02114 USA. EM jperrin@partners.org FU PHS HHS [U53MC04473] NR 16 TC 32 Z9 35 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 2007 VL 161 IS 10 BP 933 EP 936 DI 10.1001/archpedi.161.10.933 PG 4 WC Pediatrics SC Pediatrics GA 215YH UT WOS:000249844400002 PM 17909135 ER PT J AU Fisher, LB Miles, IW Austin, B Camargo, CA Colditz, GA AF Fisher, Laurie B. Miles, Isa Williams Austin, Bryn Camargo, Carlos A., Jr. Colditz, Graham A. TI Predictors of initiation of alcohol use among US adolescents - Findings from a prospective cohort study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID STUDENTS AGES 18-24; COLLEGE-STUDENTS; SUBSTANCE USE; DRUG-USE; EXPECTANCY QUESTIONNAIRE; YOUNG ADOLESCENTS; RISK BEHAVIOR; PERCEIVED COMPETENCES; UNINTENTIONAL INJURY; ADVERTISING EXPOSURE AB Objective: To identify precursors of adolescent alcohol initiation and binge drinking. Design: Prospective cohort study. Setting: Self-report questionnaires. Participants: A total of 5511 Growing Up Today Study participants aged 11 to 18 years in 1998. Main Exposures: Individual, family, and social factors. Main Outcome Measures: First whole drink of alcohol and binge drinking. Results: Between 1998 and 1999, 611 girls (19%) and 384 boys (17%) initiated alcohol use. Older age, later maturational stage, smoking, adults drinking in the home, underage sibling drinking, peer drinking, possession of or willingness to use alcohol promotional items, and positive attitudes toward alcohol were associated with an increased likelihood of alcohol initiation. Girls who ate family dinner at home every day were less likely to initiate alcohol use than girls who ate family dinner only on some days or never ( odds ratio, 0.66; 95% confidence interval, 0.50-0.87). Girls with higher social self-esteem and boys with higher athletic self-esteem were more likely to initiate alcohol use than those with lower self-esteem. Among teens who initiated alcohol use, 149 girls (24%) and 112 boys (29%) further engaged in binge drinking. Among girls, positive attitudes toward alcohol, underage sibling drinking, and possession of or willingness to use alcohol promotional items were associated with binge drinking; among boys, positive attitudes toward alcohol and older age were associated with binge drinking. Conclusions: Eating family dinner at home every day may delay alcohol uptake among some adolescents. Alcohol promotional items appear to encourage underage alcohol initiation and binge drinking; this may warrant marketing restrictions on the alcohol industry. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Publ Hlth, Dept Epidemiol & Hlth Policy,Div Adolescent & You, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Publ Hlth, Div Adolescent & Young Adult Med,Dept Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Barnes Jewish Hosp, St Louis, MO 63110 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. RP Fisher, LB (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM laurie.fisher@channing.harvard.edu RI Price, Katie/H-1931-2012; Brower, Susan/C-7090-2009; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU PHS HHS [6T71-MC00009-15-01] NR 77 TC 76 Z9 79 U1 9 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD OCT PY 2007 VL 161 IS 10 BP 959 EP 966 DI 10.1001/archpedi.161.10.959 PG 8 WC Pediatrics SC Pediatrics GA 215YH UT WOS:000249844400006 PM 17909139 ER PT J AU Wilde, MC Castriotta, RJ Lai, JM Atanasov, S Masel, BE Kuna, ST AF Wilde, Mark C. Castriotta, Richard J. Lai, Jenny M. Atanasov, Strahil Masel, Brent E. Kuna, Samuel T. TI Cognitive impairment in patients with traumatic brain injury and obstructive sleep apnea SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the International-Neuropsychological-Society CY FEB 01-04, 2006 CL Boston, MA SP Int Neuropsychol Soc DE brain injuries; hypersomnia; neuropsychology; rehabilitation; sleep apnea; obstructive; sleep disorders; trauma ID PSYCHOMOTOR VIGILANCE PERFORMANCE; MILD HEAD-INJURY; DAYTIME SLEEPINESS; ADULTS; DISORDERS; RECOVERY; NIGHT AB Objective: To examine the impact of comorbid obstructive sleep apnea (OSA) on the cognitive functioning of traumatic brain injury (TBI) patients. Design: A case-control study. Neuropsychologic test performances of TBI patients with OSA were compared with those who did not have OSA. The diagnosis of OSA was based on standard criteria using nocturnal polysomnography. Setting: Three academic medical centers with level I trauma centers, accredited sleep disorders centers, and rehabilitation medicine programs. Participants: Thirty-five TBI patients who were part of a project that assessed the effect of sleep disorders in a larger sample of consecutively recruited TBI patients. There were 19 patients with TBI and OSA. They were compared with 16 TBI patients without OSA who were comparable in terms of age, education, severity of injury (when available), time postinjury, and Glasgow Coma Scale scores (when available). Interventions: Not applicable. Main Outcome Measures: The Psychomotor Vigilance Test, Rey Complex Figure Test, Rey Auditory Verbal Learning Test, digit span test from the Wechsler Memory Scale-Revised, and finger-tapping test. Results: The TBI patients with OSA performed significantly worse than the non-sleep disordered TBI patients on verbal and visual delayed-recall measures. The groups performed comparably on motor, visual construction, and attention tests. The TBI patients with OSA made more attention lapses (reaction times >= 500ms), but showed comparable fastest and slowest reaction times on a measure of sustained attention. Conclusions: OSA is associated with more impairment of sustained attention and memory in TBI patients. It is possible that early identification and treatment of OSA may improve cognitive, and thus potentially functional, outcomes of TBI patients with this disease. C1 Univ Texas Hlth Ctr, Houston, TX USA. Mem Hermann Hosp Sleep Disorders Ctr, Houston, TX USA. Univ Texas, Med Branch, Galveston, TX USA. Transit Learning Ctr, Galveston, TX USA. Univ Penn, Sch Med, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. RP Castriotta, RJ (reprint author), Univ Texas, Hlth Sci Ctr, Div Pulm & Crit Care & Sleep Med, 6431 Fannin St, Houston, TX 77030 USA. EM Richard.J.Castriotta@uth.tmc.edu RI Castriotta, Richard/B-1158-2009; Sanguansri, Luz/B-6630-2011; OI Sanguansri, Luz/0000-0003-1908-7604; Castriotta, Richard/0000-0003-3502-4558 NR 30 TC 51 Z9 53 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD OCT PY 2007 VL 88 IS 10 BP 1284 EP 1288 DI 10.1016/j.apmr.2007.07.012 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 220MT UT WOS:000250161500009 PM 17908570 ER PT J AU Miller, E Lasser, KE Becker, AE AF Miller, E. Lasser, K. E. Becker, A. E. TI Breast and cervical cancer screening for women with mental illness: patient and provider perspectives on improving linkages between primary care and mental health SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE mammography; cervical cancer screening; mental health; women's health; preventive care ID PREVENTIVE MEDICAL-SERVICES; PSYCHIATRIC-PATIENTS; MAMMOGRAPHY RATES; INCOME WOMEN; BARRIERS; DISORDERS; RISK AB Objective: Previous research suggests that women with mental illness may be at increased risk for breast and cervical cancer. This qualitative study of patients and primary care and mental health providers explored challenges to accessing and providing breast and cervical cancer screening for women with mental illness. Method: Key informant patient and provider participants were recruited from a community health setting and teaching hospital. Narrative data from 1) interviews with women in a community primary care setting (n = 16); 2) telephone interviews with women with mental illness (n = 16); and 3) focus groups with primary care providers (n = 9) and mental health providers (n = 26) were collected. Results: Patient, provider, and system factors that may contribute to suboptimal cancer screening among women with mental illness were identified. Communication between primary care and mental health providers was noted as a key area for intervention to enhance screening. Barriers to and possibilities for a more proactive role for mental health providers were also considered. Conclusions: Both patient and provider study participants emphasized the need to address communication gaps between primary care and mental health providers and to promote the active collaboration of mental health providers in preventive cancer screening for women with mental illness. C1 Univ Calif Davis, Sch Med, Ctr Reduciing Hlth Dispar, Davis, CA USA. Cambridge Hlth Alliance, Dept Med, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Cambridge, MA 02138 USA. RP Miller, E (reprint author), CTSC, Ctr Reduciing Hlth Dispar, UC Davis Med Ctr, 2921 Stockton Blvd Suite 1400, Sacramento, CA 95817 USA. EM elizabeth.miller@ucdmc.ucdavis.edu RI Miller, Elizabeth/E-7939-2012; OI Lasser, Karen/0000-0003-3777-6075 NR 18 TC 24 Z9 25 U1 1 U2 6 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD OCT PY 2007 VL 10 IS 5 BP 189 EP 197 DI 10.1007/s00737-007-0198-4 PG 9 WC Psychiatry SC Psychiatry GA 215AA UT WOS:000249778300002 PM 17680330 ER PT J AU Huang, AL Silver, AE Shvenke, E Schopfer, DW Jahangir, E Titas, MA Shpilman, A Menzoian, JO Watkins, MT Raffetto, JD Gibbons, G Woodson, J Shaw, PM Dhadly, M Eberhardt, RT Keaney, JF Gokce, N Vita, JA AF Huang, Alex L. Silver, Annemarie E. Shvenke, Elena Schopfer, David W. Jahangir, Eiman Titas, Megan A. Shpilman, Alex Menzoian, James O. Watkins, Michael T. Raffetto, Joseph D. Gibbons, Gary Woodson, Jonathan Shaw, Palma M. Dhadly, Mandeep Eberhardt, Robert T. Keaney, John F., Jr. Gokce, Noyan Vita, Joseph A. TI Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE endothelium; cardiovascular risk; surrogate markers; reactive hyperemia; flow-mediated dilation ID FLOW-MEDIATED DILATION; OXIDE-DEPENDENT VASODILATION; STAGE RENAL-DISEASE; ENDOTHELIAL DYSFUNCTION; NITRIC-OXIDE; BRACHIAL-ARTERY; HUMAN FOREARM; SHEAR-STRESS; RISK; RESISTANCE AB Objective-Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. Methods and Results-We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66 +/- 11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death ( 15), myocardial infarction ( 18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75 +/- 39 versus 95 +/- 50 cm/s, P +/- 0.009). Patients with an event also had lower flow-mediated dilation (4.5 +/- 3.0 versus 6.9 +/- 4.6%, P +/- 0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P = 0.018) and lower flow- mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P = 0.001) both predicted cardiovascular events while adjusting for other risk factors. Conclusions-Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow- mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow- mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity. C1 Boston Univ, Med Ctr, Cardiol Sect, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Cardiol Sect, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Univ Connecticut, Ctr Hlth, Dept Surg, Farmington, CT USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02118 USA. RP Vita, JA (reprint author), Boston Univ, Med Ctr, Cardiol Sect, Evans Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM jvita@bu.edu RI Jahangir, Eiman/P-1053-2015; OI Jahangir, Eiman/0000-0001-6944-5321; Vita, Joseph/0000-0001-5607-1797; Eberhardt, Robert/0000-0002-5076-7416 FU NHLBI NIH HHS [R01 HL083269-03, HL 083269, HL083781, HL55993, HL60886, HL75795, K12 HL083781, K12 HL083781-01, K12 HL083781-02, P01 HL060886, P01 HL081587, P01 HL081587-010005, P01 HL081587-020005, P01 HL081587-030005, P01 HL081587-040005, P50 HL055993, P50 HL083801, P50 HL083801-01, P50 HL083801-010001, P50 HL083801-017464, P50 HL083801-02, P50 HL083801-020001, P50 HL083801-03, P50 HL083801-030001, R01 HL075795, R01 HL075795-01, R01 HL075795-02, R01 HL075795-03, R01 HL075795-05, R01 HL083269, R01 HL083269-01A1, R01 HL083269-02, T32 HL 07224, T32 HL007224] NR 31 TC 120 Z9 122 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2007 VL 27 IS 10 BP 2113 EP 2119 DI 10.1161/ATVBAHA.107.147322 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 212HO UT WOS:000249587000007 PM 17717291 ER PT J AU Todd, DJ Kagan, A Chibnik, LB Kay, J AF Todd, Derrick J. Kagan, Anna Chibnik, Lori B. Kay, Jonathan TI Cutaneous changes of nephrogenic systemic fibrosis - Predictor of early mortality and association with gadolinium exposure SO ARTHRITIS AND RHEUMATISM LA English DT Article ID RENAL-DIALYSIS PATIENTS; DERMOPATHY; SCLEROMYXEDEMA; SURGERY; SKIN; INSUFFICIENCY; INVOLVEMENT; DISEASE AB Objective. Nephrogenic systemic fibrosis (NSF) is a rapidly progressive, debilitating condition that causes cutaneous and visceral fibrosis in patients with renal failure. Little is known about its prevalence or etiology. The aim of this study was to. establish the prevalence of NSF and associated risk factors. Methods. Two cohorts of patients were recruited from 6 outpatient hemodialysis centers and examined for cutaneous changes of NSF, which were defined using a scoring system based on hyperpigmentation, hardening, and tethering of skin on the extremities. Demographic data were gathered, mortality was followed up prospectively for 24 months, and gadolinium exposure was ascertained for a subgroup of patients in the second cohort. Results. Examination reproducibility was 97% in cohort 1. In cohort 2, 25 (13%) of 186 patients demonstrated cutaneous changes of NSF. Twenty-four-month mortality following examination was 48% and 20% in patients with and those without cutaneous changes of NSF, respectively (adjusted hazard ratio 2.9, 95% confidence interval [95% CI] 1.4-5.9). Cutaneous changes of NSF were observed in 16 (30%) of 54 patients with prior exposure to gadopentetate dimeglumine contrast during imaging studies. Exposure to gadolinium-containing contrast was associated with an increased risk of developing cutaneous changes of NSF (odds ratio 14.7, 95% CI 1.9-117.0) compared with nonexposed patients. Conclusion. In patients receiving hemodialysis, NSF is an underrecognized disorder that is associated with increased mortality. Exposure to gadolinium-containing contrast material appears to be a significant risk factor for the development of NSF. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Kay, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Yawkey 2-174,55 Fruit St, Boston, MA 02114 USA. EM jkay@partners.org OI Kay, Jonathan/0000-0002-8970-4260 NR 28 TC 123 Z9 127 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2007 VL 56 IS 10 BP 3433 EP 3441 DI 10.1002/art.22925 PG 9 WC Rheumatology SC Rheumatology GA 221ZB UT WOS:000250264800032 PM 17907148 ER PT J AU Ozbaydar, M Elhassan, B Warner, JJP AF Ozbaydar, Mehmet Elhassan, Bassem Warner, Jon J. P. TI The use of anchors in shoulder surgery: A shift from metallic to bioabsorbable anchors SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Review DE anchor; arthroscopy; bioabsorbable ID ROTATOR CUFF REPAIR; SUTURE ANCHORS; BIODEGRADABLE POLYMERS; STABILIZATION; FAILURE; INTERFACE; STRENGTH; TACKS AB With major advances in arthroscopy, suture anchors became the primary devices used to assist in fixing soft tissues to bone. Metallic anchors were first produced and used in soft tissue fixation around the shoulder. However, their use resulted in some reported complications, including articular surface damage from migrating implants and distortion and artifact production in postoperative magnetic resonance imaging. Bioabsorbable anchors were developed to avoid these problems. Their newer versions were proven to have pulling-out strength equal to that of metallic anchors, with a reported lower complication rate. This had led to a major shift away from metallic anchors toward bioabsorbable anchors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Div Shoulder Surg, Boston, MA 02114 USA. RP Elhassan, B (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Div Shoulder Surg, 55 Fruit St, Boston, MA 02114 USA. EM belhassan@partners.org RI Ozbaydar, Mehmet/D-7391-2016 NR 32 TC 24 Z9 25 U1 1 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2007 VL 23 IS 10 BP 1124 EP 1126 DI 10.1016/j.arthro.2007.05.011 PG 3 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 225DY UT WOS:000250498500015 PM 17916480 ER PT J AU Saam, T Yuan, C Chu, BC Takaya, N Underhill, H Cai, JM Tran, N Polissar, NL Neradilek, B Jarvik, GP Isaac, C Garden, GA Maravilla, KR Hashimoto, B Hatsukami, TS AF Saam, Tobias Yuan, Chun Chu, Baocheng Takaya, Norihide Underhill, Hunter Cai, Jianming Tran, Nam Polissar, Nayak L. Neradilek, Blazej Jarvik, Gail P. Isaac, Carol Garden, Gwenn A. Maravilla, Kenneth R. Hashimoto, Beverly Hatsukami, Thomas S. TI Predictors of carotid atherosclerotic plaque progression as measured by noninvasive magnetic resonance imaging SO ATHEROSCLEROSIS LA English DT Article DE Magnetic resonance imaging; Carotid arteries; Atherosclerosis; Plaque; Progression AB The purpose of this in vivo MRI study was to quantify changes in atherosclerotic plaque morphology prospectively and to identify factors that may alter the rate of progression in plaque burden. Sixty-eight asymptomatic subjects with >= 50% stenosis, underwent serial carotid MRI examinations over an 18-month period. Clinical risk factors for atherosclerosis, and medications were documented prospectively. The wall and total vessel areas, matched across time-points, were measured from cross-sectional images. The normalized wall index (NWI = wall area/total vessel area), as a marker of disease severity, was documented at baseline and at 18 months. Multiple regression analysis was used to correlate risk factors and morphological features of the plaque with the rate of progression/regression. On average, the wall area increased by 2.2% per year (P = 0.001). Multiple regression analysis demonstrated that statin therapy (P = 0.01) and a normalized wall index >0.64 (P = 0.001) were associated with a significantly reduced rate of progression in mean wall area. All other documented risk factors were not significantly associated with changes in wall area. Findings from this study suggest that increased normalized wall index and the use of statin therapy are associated with reduced rates of plaque progression amongst individuals with advanced, asymptomatic carotid atherosclerosis. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 [Hatsukami, Thomas S.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Saam, Tobias; Yuan, Chun; Chu, Baocheng; Takaya, Norihide; Underhill, Hunter; Cai, Jianming; Maravilla, Kenneth R.] Univ Washington, Dept Radiol, Seattle, WA USA. [Saam, Tobias] Univ Munich, Dept Clin Radiol, Munich, Germany. [Takaya, Norihide] Juntendo Univ, Sch Med, Dept Cardiol, Tokyo 113, Japan. [Tran, Nam; Isaac, Carol; Hatsukami, Thomas S.] Univ Washington, Dept Surg, Seattle, WA 98195 USA. [Polissar, Nayak L.; Neradilek, Blazej] Mt Whisper Light Stat Consulting, Seattle, WA USA. [Jarvik, Gail P.] Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA. [Garden, Gwenn A.] Univ Washington, Dept Neurol, Seattle, WA 98195 USA. [Hashimoto, Beverly] Virginia Mason Med Ctr, Dept Radiol, Seattle, WA 98101 USA. RP Hatsukami, TS (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM tomhat@u.washington.edu RI Jarvik, Gail/N-6476-2014 OI Jarvik, Gail/0000-0002-6710-8708 FU NHLBI NIH HHS [R01 HL074366, R01 HL67406, R01 HL067406-06, P01 HL072262-050002, R01 HL073401-04, R01 HL061851, R01 HL074366-04, R01 HL61851, R01 HL061851-04, R01 HL067406, R01 HL073401, P01 HL072262] NR 18 TC 57 Z9 60 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2007 VL 194 IS 2 BP E34 EP E42 DI 10.1016/j.atherosclerosis.2006.08.016 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V26XU UT WOS:000208579100005 PM 16978632 ER PT J AU Eddy, KT Tanofsky-Kraff, M Thompson-Brenner, H Herzog, DB Brown, TA Ludwig, DS AF Eddy, Kamryn T. Tanofsky-Kraff, Marian Thompson-Brenner, Heather Herzog, David B. Brown, Timothy A. Ludwig, David S. TI Eating disorder pathology among overweight treatment-seeking youth: Clinical correlates and cross-sectional risk modeling SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE pediatric overweight; eating disorder; binge eating; structural equation modeling; risk modeling ID OBESE CHILDREN; APPEARANCE QUESTIONNAIRE; SOCIOCULTURAL ATTITUDES; CHILDHOOD OBESITY; ADOLESCENT GIRLS; PUBERTAL CHANGES; UNITED-STATES; SELF-REPORT; BODY-FAT; PSYCHOPATHOLOGY AB Preliminary research suggests that pediatric overweight is associated with increased eating disorder pathology, however, little is known about which overweight youth are most vulnerable to eating disorder pathology. We therefore investigated 122 overweight treatment-seeking youth to describe eating disorder pathology and mental health correlates, and to identify psychopathological constructs that may place overweight youth at increased risk for eating disorder pathology. Youth participated in a comprehensive assessment of eating disorders, mood and anxiety disorders, general psychopathology, and risk variables involving semi-structured clinical interviews and self- and parent-report questionnaires prior to the initiation of weight-loss treatment. Ten youth met criteria for an eating disorder, and over one-third endorsed recent binge eating. Eating disorder pathology was associated with depressive and anxious symptoms (p's<0.001). Structural equation modeling indicated increased negative affect, teasing experience, and thin-ideal internalization, and decreased perfectionism were associated with increased eating disorder pathology. Findings corroborate earlier work indicating that eating disorder pathology is elevated and clinically significant in overweight treatment-seeking youth, bolstering the need for mental health assessment of such individuals. Cross-sectional modeling proposed key variables that relate to eating disorder pathology in overweight treatment-seeking youth, which following prospective replication, may inform the development of effective interventions for overweight and eating disorders. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Chicago Hosp, Dept Psychiat, Chicago, IL 60637 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Med & clin Psychol, Bethesda, MD 20814 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Eddy, KT (reprint author), Univ Chicago Hosp, Dept Psychiat, MC 3077,5841 S Maryland Ave, Chicago, IL 60637 USA. EM kamryn@bu.edu FU NIDDK NIH HHS [P30 DK040561-12, P30 DK040561]; NIMH NIH HHS [F31MH071019] NR 58 TC 63 Z9 63 U1 2 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 EI 1873-622X J9 BEHAV RES THER JI Behav. Res. Ther. PD OCT PY 2007 VL 45 IS 10 BP 2360 EP 2371 DI 10.1016/j.brat.2007.03.017 PG 12 WC Psychology, Clinical SC Psychology GA 218TU UT WOS:000250038600010 PM 17509523 ER PT J AU Kiepiela, P Smith, AN Rosenberg, E AF Kiepiela, P. Smith, A. N. Rosenberg, E. TI Retraction notice to "Laboratory markers associated with progression of HIV infection [vol 19, pg 243, 2005]" SO BEST PRACTICE & RESEARCH IN CLINICAL OBSTETRICS & GYNAECOLOGY LA English DT Correction C1 Univ Kwazulu Natal, Sch Med, HIV Pathogenesis Programme, DDMRI, ZA-4013 Durban, South Africa. Harvard Univ, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Kiepiela, P (reprint author), Univ Kwazulu Natal, Sch Med, HIV Pathogenesis Programme, DDMRI, 719 Umbilo Rd, ZA-4013 Durban, South Africa. NR 1 TC 0 Z9 0 U1 1 U2 5 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6934 J9 BEST PRACT RES CL OB JI Best Pract. Res. Clin. Obstet. Gynaecol. PD OCT PY 2007 VL 21 IS 5 BP 883 EP 883 DI 10.1016/j.bpobgyn.2007.07.011 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 230YD UT WOS:000250911400012 PM 18061996 ER PT J AU Jarrett, ME Kohen, R Cain, KC Burr, RL Poppe, A Navaja, GP Heitkemper, MM AF Jarrett, Monica E. Kohen, Ruth Cain, Kevin C. Burr, Robert L. Poppe, Ann Navaja, Grace P. Heitkemper, Margaret M. TI Relationship of SERT Polymorphisms to depressive and anxiety symptoms in irritable bowel syndrome SO BIOLOGICAL RESEARCH FOR NURSING LA English DT Article DE irritable bowel syndrome; serotonin transporter; protein (SERT); 5-HTTLPR; STin2 VNTR; depression; anxiety; adult ID SEROTONIN TRANSPORTER GENE; AFFECTIVE-DISORDERS; PROMOTER POLYMORPHISM; DOUBLE-BLIND; MAJOR DEPRESSION; 5-HTT GENE; ASSOCIATION; METAANALYSIS; WOMEN; SUSCEPTIBILITY AB This study investigates the association of psychological symptoms with the distribution of two serotonin transporter gene (SERT) polymorphisms, located in the promoter region (5-HTTLPR) and in intron 2 (STin2 VNTR), in patients with irritable bowel syndrome (IBS). Participants, 21 men and 117 women, were assessed for mental health history and current psychological distress. A blood sample was used for genotyping. Participants who were homozygous for the short allele of 5-HTTLPR or carried a STin2.9 VNTR allele were significantly more likely to have a history of depression. Participants did not differ by genotype in their history of anxiety or suicidal ideation nor in their current levels of depression, anxiety, or general psychological distress. The results support a biopsychosocial model of IBS in which SERT genotype modifies the risk for depressive episodes. Long term, practitioners may individualize treatment of patients with IBS using genotype as one of the factors. C1 Univ Washington, Dept Biobehav & Nursing Hlth Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriat Res Educat & Clin Ctr, Seattle, WA USA. RP Jarrett, ME (reprint author), Univ Washington, Dept Biobehav & Nursing Hlth Syst, Seattle, WA 98195 USA. EM jarrett@u.washington.edu FU NINR NIH HHS [NR04142, P30 NR04001] NR 42 TC 44 Z9 48 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1099-8004 J9 BIOL RES NURS JI Biol. Res. Nurs. PD OCT PY 2007 VL 9 IS 2 BP 161 EP 169 DI 10.1177/1099800407307822 PG 9 WC Nursing SC Nursing GA 216XU UT WOS:000249913100007 PM 17909168 ER PT J AU Koreth, J AF Koreth, John TI Multiple myeloma in a 50-year-old with an HLA-identical sibling SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID STEM-CELL TRANSPLANTATION; THALIDOMIDE; THERAPY; CHEMOTHERAPY; SINGLE C1 Childrens Hosp, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Koreth, J (reprint author), Childrens Hosp, Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. NR 13 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2007 VL 13 IS 10 BP 1247 EP 1248 DI 10.1016/j.bbmt.2007.08.042 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 219RX UT WOS:000250103400016 PM 17889363 ER PT J AU Kaneko-Tarui, T Zhang, L Austin, KJ Henkes, LE Johnson, J Hansen, TR Pru, JK AF Kaneko-Tarui, Tomoko Zhang, Ling Austin, Kathleen J. Henkes, Luiz E. Johnson, Joshua Hansen, Thomas R. Pru, James K. TI Maternal and embryonic control of uterine sphingolipid-metabolizing enzymes during murine embryo implantation SO BIOLOGY OF REPRODUCTION LA English DT Article DE ceramide; decidua; decidualization; implantation; pregnancy; sphingolipid; sphingosine-1-phosphate; uterus ID RECURRENT PREGNANCY LOSS; SPHINGOSINE 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; RECEPTOR; ANGIOGENESIS; TROPHOBLAST; KINASE; CELLS; DECIDUALIZATION; TRAFFICKING AB During early gestation in invasively implanting species, the uterine stromal compartment undergoes dramatic remodeling, defined by the differentiation of stromal fibroblast cells into decidual cells. Lipid signaling molecules from a number of pathways are well-established functional components of this decidualization reaction. Because of a correlation in the events that transpire in the uterus during early implantation with known functions of bioactive sphingolipid metabolites established from studies in other organ systems, we hypothesized that uterine sphingolipid metabolism would change during implantation. By a combination of Northern blot, Western blot, and immunohistochemical analyses, we establish that enzymes at each of the major catalytic steps in the sphingolipid cascade become transcriptionally up-regulated in the uterus during decidualization. Each of the enzymes analyzed was up-regulated from Days of Pregnancy (DOP) 4.5-7.5. When comparing embryo-induced decidualization (decidual) with mechanically induced decidualization (deciduomal), sphingomyelin phosphodiesterase 1 (Smpd1) mRNA and sphingosine kinase I (SPHK1) protein were shown to be dually regulated in the endometrium by both maternal and embryonic factors. As measured by the diacyl glycerol kinase assay, ceramide levels rose in parallel with Smpd1 gene expression, suggesting that elevated transcription of sphingolipid enzymes results in heightened catalytic activity of the pathway. Altogether, these findings place sphingolipids on a growing list of lipid signaling molecules that become increasingly present at the maternal-embryonic interface. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Dept Obstet Gynecol & R B, Boston, MA 02114 USA. Colorado State Univ, Dept Biomed Sci, Ft Collins, CO 80523 USA. RP Pru, JK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Vincent Ctr Reprod Biol Vincent Obstet & G S, Res Bldg, Room 931, 55 Fruit St, Boston, MA 02114 USA. EM jpru@partners.org RI Kaneko-Tarui, Tomoko/E-3319-2010 FU NICHD NIH HHS [HD 032475]; NIEHS NIH HHS [ES012070] NR 46 TC 10 Z9 10 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 2007 VL 77 IS 4 BP 658 EP 665 DI 10.1095/biolreprod.107.061044 PG 8 WC Reproductive Biology SC Reproductive Biology GA 214VQ UT WOS:000249766700008 PM 17582011 ER PT J AU Aidlen, JT Nazarey, PP Kinane, TB Donahoe, PK Schnitzer, JJ Kling, DE AF Aidlen, Jeremy T. Nazarey, Pradeep P. Kinane, T. Bernard Donahoe, Patricia K. Schnitzer, Jay J. Kling, David E. TI Retinoic acid-mediated differentiation protects against nitrofen-induced apoptosis SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE apoptosis; nitrofen; differentiation; birth defects; retinoic acid; differentiation; Bcl-2; p27 (kip1); embryonic stem cell ID CONGENITAL DIAPHRAGMATIC-HERNIA; EMBRYONIC CARCINOMA-CELLS; NEURAL DIFFERENTIATION; STEM-CELLS; VITAMIN-A; BCL-2 FAMILY; LUNG GROWTH; FETAL RATS; DEATH; EXPRESSION AB Nitrofen is a diphenyl ether that induces a spectrum of birth defects subsequent to administration to pregnant rodents, in which the molecular etiology of these defects are poorly characterized. Because previous reports showed that nitrofen induced apoptosis in undifferentiated P19 teratocarcinoma cells, we hypothesized that undifferentiated fetal cells have greater susceptibility to nitrofen-induced apoptosis than their differentiated derivatives. METHODS: To investigate this hypothesis, cell lines including P19 and F9 were differentiated with retinoic acid into neuronal and endodermal derivatives respectively. Apoptosis was characterized by caspase-3 cleavage and Terminal transferase dUTP nick end labeling (TUNEL) assays. RESULTS: Both differentiated cell-types had reduced nitrofen-induced caspase-3 cleavage and DNA fragmentation compared with the naive controls, strongly suggesting that differentiation of these cells protects against nitrofen-induced apoptosis. In addition, resistance to apoptotic induction was proportional to the expression levels of the differentiation marker, p27 (kip1) while direct proportionality was not observed for the antiapoptotic protein Bcl-2. CONCLUSIONS: These studies show that nitrofen may induce its associated birth defects via a mechanism involving apoptosis of undifferentiated fetal cells. Birth Defects Res (Part B) 80:406-416, 2007. (c) 2007 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Pediat Surg Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. RP Kling, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat,Pediat Surg Labs, CPZN6100,185 Cambridge St, Boston, MA 02114 USA. EM dkling@partners.org FU NHLBI NIH HHS [HL062615, HL069684]; NICHD NIH HHS [P01 HD039942] NR 74 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD OCT PY 2007 VL 80 IS 5 BP 406 EP 416 DI 10.1002/bdrb.20131 PG 11 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 226TW UT WOS:000250612400005 PM 17896343 ER PT J AU Cserti, CM Dzik, WH AF Cserti, Christine M. Dzik, Walter H. TI The ABO blood group system and Plasmodium falciparum malaria SO BLOOD LA English DT Review ID VON-WILLEBRAND-FACTOR; ENDOTHELIAL-CELL ACTIVATION; GROUP-A ANTIGEN; CEREBRAL MALARIA; INFECTED ERYTHROCYTES; NITRIC-OXIDE; ROSETTING ANTIBODIES; CHONDROITIN SULFATE; NATURAL-SELECTION; PROMOTER REGION AB In the century since the discovery of the ABO blood groups, numerous associations between ABO groups and disease have been noted. However, the selection pressures defining the ABO distributions remain uncertain. We review published information on Plasmodium falciparum infection and ABO blood groups. DNA sequence information dates the emergence and development of the group 0 allele to a period of evolution before human migration out of Africa, concomitant with P falciparum's activity. The current geographic distribution of group 0 is also consistent with a selection pressure by P falciparum in favor of group 0 individuals in malaria-endemic regions. We critically review clinical reports of ABO and P falciparum infection, documenting a correlation between disease severity and ABO group. Finally, we review published data on the pathogenesis of P falciparum infection, and propose a biologic model to summarize the role of ABO blood groups in cytoadherence biology. Such ABO-related mechanisms also point to a new hypothesis to account for selection of the Le(a-b-) phenotype. Taken together, a broad range of available evidence suggests that the origin, distribution, and relative proportion of ABO blood groups in humans may have been directly influenced by selective genetic pressure from P falciparum infection. C1 Univ Toronto, Toronto Gen Hosp, Hlth Network, Blood Transfus Lab, Toronto, ON M5G 2C4, Canada. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Cserti, CM (reprint author), Univ Toronto, Toronto Gen Hosp, Hlth Network, Blood Transfus Lab, 200 Elizabeth St,3EC-306, Toronto, ON M5G 2C4, Canada. EM christine.cserti@uhn.on.ca NR 108 TC 96 Z9 106 U1 2 U2 25 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2007 VL 110 IS 7 BP 2250 EP 2258 DI 10.1182/blood-2007-03-077602 PG 9 WC Hematology SC Hematology GA 215ID UT WOS:000249800900018 PM 17502454 ER PT J AU Zhu, JQ Carman, CV Kim, M Shimaoka, M Springer, TA Luo, BH AF Zhu, Jieqing Carman, Christopher V. Kim, Minsoo Shimaoka, Motomu Springer, Timothy A. Luo, Bing-Hao TI Requirement of alpha and beta subunit transmembrane helix separation for integrin outside-in signaling SO BLOOD LA English DT Article ID MURINE MONOCLONAL-ANTIBODY; CYTOPLASMIC DOMAINS; GLYCOPROTEIN-IIIA; LIVING CELLS; BINDING; AFFINITY; ACTIVATION; ALPHA(IIB)BETA(3); ADHESION; LIGAND AB Adhesion to extracellular ligands through integrins regulates cell shape, migration, growth, and survival. How integrins transmit signals in the outside-to-in direction remains unknown. Whereas in resting integrins the alpha and beta subunit transmembrane domains are associated, ligand binding promotes dissociation and separation of these domains. Here we address whether such separation is required for outside-in signaling. By introduction of an intersubunit disulfide bond, we generated mutant integrin alpha IIb beta 3 with blocked transmembrane separation that binds ligand, mediates adhesion, adopts an extended conformation after ligand binding, and forms anti body-induced macroclusters on the cell surface similarly to wild type. However, the mutant integrin exhibits a profound defect in adhesion-induced outside-in signaling as measured by cell spreading, actin stress-fiber and focal adhesion formation, and focal adhesion kinase activation. This defect was rescued by reduction of the disulfide bond. Our results demonstrate that the separation of transmembrane domains is required for integrin outside-in signal transduction. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Brown Univ, Sch Med, Rhode Isl Hosp, Div Surg Res, Providence, RI 02912 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA USA. RP Luo, BH (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM luo@lsu.edu RI Carman, Christopher/L-8108-2016 OI Carman, Christopher/0000-0001-7358-2548 FU NHLBI NIH HHS [HL48675, P01 HL048675, R01 HL087088, R01 HL087088-01A1] NR 44 TC 71 Z9 77 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2007 VL 110 IS 7 BP 2475 EP 2483 DI 10.1182/blood-2007-03-080077 PG 9 WC Hematology SC Hematology GA 215ID UT WOS:000249800900045 PM 17615290 ER PT J AU Hatjiharissi, E Xu, LA Santos, DD Hunter, ZR Ciccarelli, BT Verselis, S Modica, M Cao, Y Manning, RJ Leleu, X Dimmock, EA Kortsaris, A Mitsiades, C Anderson, KC Fox, EA Treon, SP AF Hatjiharissi, Evdoxia Xu, Lian Santos, Daniel Ditzel Hunter, Zachary R. Ciccarelli, Bryan T. Verselis, Sigitas Modica, Michael Cao, Yang Manning, Robert J. Leleu, Xavier Dimmock, Elizabeth A. Kortsaris, Alexandros Mitsiades, Constantine Anderson, Kenneth C. Fox, Edward A. Treon, Steven P. TI Increased natural killer cell expression of CD16, augmented binding and ADCC activity to rituximab among individuals expressing the Fc gamma RIIIa-158 V/V and V/F polymorphism SO BLOOD LA English DT Article ID FC-GAMMA-RIIIA; ANTI-CD20 MONOCLONAL-ANTIBODY; NON-HODGKINS-LYMPHOMA; CLINICAL-RESPONSE; PREDICT RESPONSE; HUMAN-IGG AB The presence of valine (V) at position 158 of Fc-gamma Rllla (CD16) is known to improve clinical response to rituximab in indolent non-Hodgkin lymphoma (NHL). Little is known about the basic mechanisms for this observation. We examined natural killer (NK) cells from healthy donors representing the Fc gamma Rllla-158 polymorphic subgroups (V/V, V/F, and F/F) for gene transcript and cell surface CD16 expression, rituximab binding, and rituximab-dependent NK cell-mediated cytotoxicity. We observed higher levels of Fc gamma Rllla transcripts among individuals with the Fc gamma Rllla-158 V/V versus V/F or F/F genotype (P < .001); increased cell surface CD16 expression by quantitative flow cytometry on NK cells from individuals expressing at least one valine at Fc gamma Rllla-158 versus F/F (P = .029); as well as augmented rituximab binding and rituximab-mediated, anti body-dependent cellular cytotoxicity (ADCC). These results suggest that individuals expressing at least one valine at Fc gamma Rllla-158 might, in part, have better clinical outcomes due to increased CD16 expression, rituximab binding, and rituximab-mediated ADCC. C1 Dana Farber Canc Inst, Bing Canc Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Democritus Univ Thrace, Sch Med, Alexandroupolis, Greece. Dana Farber Canc Inst, Mol Diagnost Lab, Boston, MA USA. Dana Farber Canc Inst, Jerome Lipper Multiploe Myeloma Ctr, Boston, MA USA. RP Treon, SP (reprint author), Dana Farber Canc Inst, Bing Canc Waldenstroms Macroglobulinemia, M548,44 Binney St, Boston, MA 02115 USA. EM steven_treon@dfci.harvard.edu RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 FU NCI NIH HHS [K23 CA087977-03, K23 CA087977] NR 16 TC 110 Z9 116 U1 3 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2007 VL 110 IS 7 BP 2561 EP 2564 DI 10.1182/blood-2007-01-070656 PG 4 WC Hematology SC Hematology GA 215ID UT WOS:000249800900055 PM 17475906 ER PT J AU Fasseu, M Aplan, PD Chopin, M Boissel, N Bories, JC Soulier, J von Boehmer, H Sigaux, F Regnault, A AF Fasseu, Magali Aplan, Peter D. Chopin, Martine Boissel, Nicolas Bories, Jean-Christophe Soulier, Jean von Boehmer, Harald Sigaux, Francois Regnault, Armelle TI p(16INK4A) tumor suppressor gene expression and CD3(epsilon) deficiency but not pre-TCR deficiency inhibit TAL1-linked T-lineage leukemogenesis SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DOUBLE-TRANSGENIC MICE; CELL LEUKEMIA; THYMOCYTE DIFFERENTIATION; RECOMBINASE ACTIVITY; MOLECULAR-GENETICS; ACTIVATED LCK; MUTANT MICE; ALPHA-CHAIN; NOTCH1 AB Inactivation of the CDKN2 genes that encode the p16(INK4A) and p14(ARF) proteins occurs in the majority of human T-cell acute lymphoblastic leukemias (T-ALLs). Ectopic expression of TAL1 and LMO1 genes is linked to the development of T-ALL in humans. In TAL1xLMO1 mice, leukemia develops in 100% of mice at 5 months. To identify the molecular events crucial to leukemic transformation, we produced several mouse models. We report here that expression of P16(INK4A) in developing TAL1xLMO1 thymocytes blocks leukemogenesis in the majority of the mice, and the leukemias that eventually develop show P16(INK4A) loss of expression. Events related to the T-cell receptor 0 selection process are thought to be important for leukemic transformation. We show here that the absence of the pT alpha. chain only slightly delays the appearance of TAL1xLMO1-induced T-ALL, which indicates a minor role of the pT alpha chain. We also show that the CD3 epsilon-mediated signal transduction pathway is essential for this transformation process, since the TAL1xLMO1xCD3 epsilon-deficient mice do not develop T-ALL for up to 1 year. C1 Hop St Louis, Inst Hematol, INSERM U462, F-75010 Paris, France. NCI, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD USA. Hop St Louis, Inst Hematopl, INSERM, U662, Paris, France. Hop St Louis, Inst Hematol, EA 3963, INSERM, Paris, France. Dana Farber Canc Inst, Boston, MA USA. RP Regnault, A (reprint author), Hop St Louis, Inst Hematol, INSERM U462, 1 Ave Claude Vellefaux, F-75010 Paris, France. EM armelle.regnault@wanadoo.fr RI REGNAULT, Armelle/G-4142-2011; Aplan, Peter/K-9064-2016 OI REGNAULT, Armelle/0000-0001-7286-9491; FU Intramural NIH HHS NR 62 TC 9 Z9 9 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 OCT 1 PY 2007 VL 110 IS 7 BP 2610 EP 2619 DI 10.1182/blood-2007-01-066209 PG 10 WC Hematology SC Hematology GA 215ID UT WOS:000249800900062 PM 17507663 ER PT J AU Paffett-Lugassy, N Hsia, N Fraenkel, PG Paw, B Leshinsky, I Barut, B Bahary, N Caro, J Handin, R Zon, LI AF Paffett-Lugassy, Noelle Hsia, Nelson Fraenkel, Paula G. Paw, Barry Leshinsky, Irene Barut, Bruce Bahary, Nathan Caro, Jaime Handin, Robert Zon, Leonard I. TI Functional conservation of erythropoietin signaling in zebrafish SO BLOOD LA English DT Article ID ERYTHROID COLONY FORMATION; TYROSINE KINASE JAK2; IN-VIVO; MYELOPROLIFERATIVE-DISORDERS; STAT5A(-/-)5B(-/-) MICE; POLYCYTHEMIA-VERA; ENDOTHELIAL-CELLS; TRANSGENIC MICE; MESSENGER-RNA; SWISS-MODEL AB Erythropoietin (Epo) and its cognate receptor (EpoR) are required for maintaining adequate levels of circulating erythrocytes during embryogenesis and adulthood. Here, we report the functional characterization of the zebrafish epo and epor genes. The expression of epo and epor was evaluated by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and whole-mount in situ hybridization, revealing marked parallels between zebrafish and mammalian gene expression patterns. Examination of the hypochromic mutant, weissherbst, and adult hypoxia-treated hearts indicate that zebrafish epo expression is induced by anemia and hypoxia. Overexpression of epo mRNA resulted in severe polycythemia, characterized by a striking increase in the number of cells expressing scl, c-myb, gata1, ikaros, epor, and beta e1-globin, suggesting that both the erythroid progenitor and mature erythrocyte compartments respond to epo. Morpholino-mediated knockdown of the epor caused a slight decrease in primitive and complete block of definitive erythropoiesis. Abrogation of STAT5 blocked the erythropoietic expansion by epo mRNA, consistent with a requirement for STAT5 in epo signaling. Together, the characterization of zebrafish epo and epor demonstrates the conservation of an ancient program that ensures proper red blood cell numbers during normal homeostasis and under hypoxic conditions. C1 Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Stem Cell Program, Boston, MA 02115 USA. Howard Hughes Med Inst, Dana Farber Canc Inst, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Hematol, Boston, MA USA. Thomas Jefferson Univ, Jefferson Med Coll, Div Hematol, Dept Med, Philadelphia, PA USA. Univ Pittsburgh, Sch Med, Div Oncol, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Oncol, Dept Med, Pittsburgh, PA 15260 USA. RP Zon, LI (reprint author), Childrens Hosp, 1 Blackfan Circle,Karp 7, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NHLBI NIH HHS [R01 HL048801, R01 HL48801-13]; NIDDK NIH HHS [K08 DK061685, K08 DK061685-01, K08 DK061685-02, K08 DK061685-03, K08 DK061685-04, K08 DK061685-04S1, K08 DK061685-05] NR 63 TC 61 Z9 66 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2007 VL 110 IS 7 BP 2718 EP 2726 DI 10.1182/blood-2006-04-016535 PG 9 WC Hematology SC Hematology GA 215ID UT WOS:000249800900074 PM 17579187 ER PT J AU Patterson, EK Watson, PH Hodsman, AB Hendy, GN Canaff, L Bringhurst, FR Poschwatta, CH Fraher, LJ AF Patterson, Eric K. Watson, Patricia H. Hodsman, Anthony B. Hendy, Geoffrey N. Canaff, Lucie Bringhurst, F. Richard Poschwatta, Clare H. Fraher, Laurence J. TI Expression of PTH1R constructs in LLC-PK1 cells: Protein nuclear targeting is mediated by the PTH1R NLS SO BONE LA English DT Article DE parathyroid hormone receptor; nuclear localization sequence; nuclear trafficking; G protein-coupled receptors ID HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; KINASE-C; PHOSPHORYLATION SITES; PTH/PTHRP RECEPTOR; LOCALIZATION; RAT; BINDING; 14-3-3-ISOFORMS; INTERNALIZATION AB This study demonstrates that the PTH1R NLS can target a fusion protein to the nucleus, and that this is blocked by sequences downstream of the NLS. GFP fused to the NLS showed a significant increase in nuclear targeting compared to GFP alone or GFP fused to a peptide of the same length. In previous studies, we demonstrated that the type I PTH/PTHrP receptor (PTH1R) localizes to the nucleus of cells within rat liver, kidney, uterus, ovary and gut. Similarly, nuclear localization of the PTH1R was observed in the cultured osteoblast-like cells MC3T3-E1, UMR106, ROS 17/2.8 and SaOS-2. We have identified a putative bipartite nuclear localization signal (NLS), from residues 471-488 in the protein sequence of the PTH1R. In this study, several PTH1R constructs were made in the Enhanced Green Fluorescent Protein (EGFP) expression vector (Clontech), transiently transfected into LLC-PK1 Clone 46 cells, and the resultant fusion protein expression followed by fluorescence microscopy. This particular clone of LLC-PK1 shows no biochemical response in vitro to parathyroid hormone. Constructs included the entire PTH1R sequence (PTH1R-GFP), the putative NLS fused to the C-terminus of GFP (GFP-NLS) or the NLS through to the C-terminus of the PTH1R fused to GFP (GFP-NLSCT). Deconvolution fluorescence microscopy of cells transfected with PTH1R-GFP showed abundant fluorescent signal throughout the cells with distinctly fluorescing plasma membranes. These cells also exhibited an increase in cANIP production in response to (0-10(-8) M) hPTH (1-34), with an increase in cAMP from 11 fmol/mu g of protein to 101 fmol/mu g. In contrast, cells transfected with the GFP-NLS construct showed significant nuclear sequestration of fluorescence as compared to GFP alone, GFP-NLSCT, or a short amino acid sequence fused to GFP (GFP-FFVAIYCFCNGEVQAEI). These results indicate that the NLS at residues 471-488 of the mature rat PTH1R is functional and plays a role in targeting the PTH1R the nucleus, also the addition of GFP to the C-terminus of the PTH1R still allows cAMP generation which will be useful for further studies. (C) 2007 Elsevier Inc. All rights reserved. C1 St Josephs Hlth Care, Lawson Hlth Res Inst, London, ON N6A 4V2, Canada. Univ Western Ontario, Dept Biochem, London, ON N6A 4V2, Canada. Univ Western Ontario, Dept Med, London, ON N6A 4V2, Canada. McGill Univ, Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. RP Fraher, LJ (reprint author), St Josephs Hlth Care, Lawson Hlth Res Inst, Room E4-158,268 Grosvenor St, London, ON N6A 4V2, Canada. EM lfraher@lri.sjhc.london.on.ca OI Patterson, Eric/0000-0003-3697-3042 NR 39 TC 4 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 8756-3282 J9 BONE JI Bone PD OCT PY 2007 VL 41 IS 4 BP 603 EP 610 DI 10.1016/j.bone.2007.04.201 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 215IC UT WOS:000249800800014 PM 17627912 ER PT J AU Xu, LH Fang, JP Huang, WG Xu, HG Weng, WJ Kao, GS Le, Y AF Xu, L. H. Fang, J. P. Huang, W. G. Xu, H. G. Weng, W. J. Kao, G. S. Le, Y. TI Marrow graft rejection by repeated transfusions of allogeneic donor spleen cells SO BONE MARROW TRANSPLANTATION LA English DT Article DE sensitized recipient; rejection; spleen cells; murine ID BONE-MARROW; PRETRANSPLANT LYMPHOCYTOTOXINS; APLASTIC-ANEMIA; HUMORAL THEORY; T-CELLS; TRANSPLANTATION; ANTIBODY; RECIPIENTS; ALLOIMMUNIZATION; CYTOTOXICITY AB Many hematological diseases require long-term transfusion support, which causes production of donor-reactive antibodies in sensitized recipients. Sensitized patients are at an increased risk for graft rejection when they undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we established a highly sensitized murine model to investigate the mechanism of donor graft rejection. After BALB/c mice were repeatedly transfused with allogeneic spleen cells from C57BL/6 mice, there was a significant increase in complement-dependent cytotoxicity in the serum of sensitized mice. For transplantation, 1 x 10(7) bone marrow cells (BMCs) from C57BL/6 mice were injected into lethally irradiated recipient BALB/c mice. Sensitized mice died between 12 and 15 days post-transplantation, while non-sensitized mice remained alive after 28 days. The hematopoietic recovery rate declined over time in sensitized recipients. The homing trace assay showed a rapid disappearance of donor BMCs in the spleen and bone marrow of sensitized recipients. In addition, the recipient cells and antibodies in the sensitized serum were capable of inducing high level of cell- and complement-mediated cytotoxicity to the donor graft. Our finding may explain the impaired hematopoietic stem cell homing and poor hematopoietic engraftment observed in highly sensitized allo-HSCT patients. C1 Zhongshan Univ, Affiliated Hosp 2, Dept Pediat, Guangzhou 510120, Guangdong, Peoples R China. Zhongshan Univ, Dept Expt Anim Ctr, Guangzhou, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA. RP Fang, JP (reprint author), Zhongshan Univ, Affiliated Hosp 2, Dept Pediat, 107 Yan Jiang Rd W, Guangzhou 510120, Guangdong, Peoples R China. EM jpfang2005@163.com NR 26 TC 4 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD OCT PY 2007 VL 40 IS 7 BP 691 EP 698 DI 10.1038/sj.bmt.1705791 PG 8 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 211XD UT WOS:000249555700011 PM 17660838 ER PT J AU Petit, JH Gluck, C Kiger, WS Henry, DL Karasiewicz, C Talcott, JA Berg, S Holupka, EJ Kaplan, ID AF Petit, Joshua H. Gluck, Clifford Kiger, W. S., III Henry, D. Laury Karasiewicz, Carol Talcott, James A. Berg, Solomon Holupka, Edward J. Kaplan, Irving D. TI Androgen deprivation-mediated cytoreduction before interstitial brachytherapy for prostate cancer does not abrogate the elevated risk of urinary morbidity associated with larger initial prostate volume SO BRACHYTHERAPY LA English DT Article DE androgen deprivation; brachytherapy; morbidity; prostate cancer ID QUALITY-OF-LIFE; SEED IMPLANTATION; RETENTION; CATHETERIZATION AB PURPOSE: We examined whether prostate volume reduction after a short course of androgen deprivation (AD) lowered the risks of acute and chronic urinary morbidity related to radioactive seed implantation for low-risk prostate cancer. METHODS AND MATERIALS: Eighty-one patients received AD for cytoreduction before interstitial brachytherapy alone. Urinary morbidity was carefully assessed for all patients during a median followup of 53 (range, 23-78) months after treatment. Outcomes were then compared with those of a control group of 81 patients who were matched 1: 1 based on identical prostate volume measured at the time of radioactive seed implant, but who had not received AD. RESULTS: Despite effective cytoreduction (median, 30% prostate volume reduction) with AD, prolonged catheterization was required significantly more often for patients who had received AD when compared with the control group of patients who were implanted at identical prostate volumes but who had not received AD (27% vs. 9%, p = 0.02). This finding remained statistically significant on multivariate analysis (p = 0.04). Surgical intervention (9% vs. 4%, p = 0.09) and subsequent urinary incontinence (4% vs. 1%, p = 0.16) were also more frequent among patients who had received AD when compared with implant volume-matched controls. CONCLUSIONS: Patients who achieved smaller prostate volumes through the use of AD maintained a significantly elevated risk (threefold) for urinary complications, commensurate with their initially large prostate volume, when compared with a control group of patients who were implanted at identical prostate volumes but who-had not received AD. Therefore, patients presenting with larger prostate glands that would warrant a short course of AD before implant should be counseled accordingly when discussing options for local therapy. (c) 2007 American Brachytherapy Society. All rights reserved. C1 [Petit, Joshua H.; Kiger, W. S., III; Henry, D. Laury; Karasiewicz, Carol; Holupka, Edward J.; Kaplan, Irving D.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, Boston, MA 02215 USA. [Gluck, Clifford; Berg, Solomon] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Urol, Boston, MA 02215 USA. [Talcott, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA 02215 USA. RP Petit, JH (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Radiat Oncol, 330 Brookline Ave, Boston, MA 02215 USA. EM jpetit@partners.org NR 14 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1538-4721 J9 BRACHYTHERAPY JI Brachytherapy PD OCT-DEC PY 2007 VL 6 IS 4 BP 267 EP 271 DI 10.1016/j.brachy.2007.08.007 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 248CR UT WOS:000252129500006 PM 17959423 ER PT J AU Caplan, D Stanczak, L Waters, G AF Caplan, David Stanczak, Louise Waters, Gloria TI Syntactic and thematic constraint effects on BOLD signal correlates of comprehension of relative clauses SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID WORKING-MEMORY C1 [Caplan, David] Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. [Stanczak, Louise; Waters, Gloria] Boston Univ, Sargent Coll, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. EM dcaplan@partners.org NR 7 TC 0 Z9 0 U1 2 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2007 VL 103 IS 1-2 BP 8 EP 9 DI 10.1016/j.bandl.2007.07.004 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 227MF UT WOS:000250660100002 ER PT J AU Brownell, H Lundgren, K Cayer-Meade, C Nichols, M Caddick, K Spitzer, J AF Brownell, Hiram Lundgren, Kristine Cayer-Meade, Carol Nichols, Michelle Caddick, Kathryn Spitzer, Jacque TI Assessing quality of metaphor interpretation by right hemisphere damaged patients SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 [Brownell, Hiram; Lundgren, Kristine; Cayer-Meade, Carol; Nichols, Michelle; Spitzer, Jacque] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. [Brownell, Hiram; Lundgren, Kristine; Cayer-Meade, Carol; Nichols, Michelle; Spitzer, Jacque] VA Boston Healthcare Syst, Boston, MA USA. [Brownell, Hiram; Caddick, Kathryn] Boston Coll, Dept Psychol, Boston, MA USA. EM hiram.brownell@bc.edu NR 9 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2007 VL 103 IS 1-2 BP 197 EP 198 DI 10.1016/j.bandl.2007.07.113 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 227MF UT WOS:000250660100096 ER PT J AU Lundgren, K Brownell, H Cayer-Meade, C Spitzer, J AF Lundgren, Kristine Brownell, Hiram Cayer-Meade, Carol Spitzer, Jacque TI Training theory of mind following right hemisphere damage: A pilot study SO BRAIN AND LANGUAGE LA English DT Meeting Abstract ID AUTISM C1 [Lundgren, Kristine; Brownell, Hiram; Cayer-Meade, Carol; Spitzer, Jacque] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02130 USA. [Lundgren, Kristine; Brownell, Hiram; Cayer-Meade, Carol; Spitzer, Jacque] VA Boston Healthcare Syst, Boston, MA USA. [Brownell, Hiram] Boston Coll, Dept Psychol, Boston, MA 02467 USA. EM klundgre@bu.edu NR 6 TC 4 Z9 4 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2007 VL 103 IS 1-2 BP 209 EP 210 DI 10.1016/j.bandl.2007.07.119 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 227MF UT WOS:000250660100102 ER PT J AU Katz, WF Garst, DM Carter, GS McNeil, MR Fossett, TR Doyle, PJ Szuminsky, NJ AF Katz, William F. Garst, Diane M. Carter, Gregory S. McNeil, Malcolm R. Fossett, Tepanta R. Doyle, Patrick J. Szuminsky, Neil J. TI Treatment of an individual with aphasia and apraxia of speech using EMA visually-augmented feedback SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 [Katz, William F.] Univ Texas, Callier Ctr Commun Disorders, Dallas, TX 75235 USA. [Katz, William F.; Garst, Diane M.; Carter, Gregory S.] Dallas Vet Adm Med Ctr, Dallas, TX USA. [McNeil, Malcolm R.; Fossett, Tepanta R.; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [McNeil, Malcolm R.; Fossett, Tepanta R.; Doyle, Patrick J.; Szuminsky, Neil J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. EM wkatz@utdallas.edu NR 3 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2007 VL 103 IS 1-2 BP 213 EP 214 DI 10.1016/j.bandl.2007.07.121 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 227MF UT WOS:000250660100104 ER PT J AU McNeil, MR Fossett, TRD Katz, WF Garst, D Carter, G Szuminsky, N Doyle, PJ AF McNeil, Malcolm R. Fossett, Tepanta R. D. Katz, William F. Garst, Diane Carter, Gregory Szuminsky, Nell Doyle, Patrick J. TI Effects of on-line kinematic feedback treatment for apraxia of speech SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 [McNeil, Malcolm R.; Fossett, Tepanta R. D.; Doyle, Patrick J.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. [McNeil, Malcolm R.; Fossett, Tepanta R. D.; Szuminsky, Nell; Doyle, Patrick J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Katz, William F.; Garst, Diane] Univ Texas, Callier Ctr Commun Disorders, Dallas, TX 75235 USA. [Carter, Gregory] Dallas Vet Adm Med Ctr, Dallas, TX USA. EM mcneil@pitt.edu NR 3 TC 3 Z9 3 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT-NOV PY 2007 VL 103 IS 1-2 BP 223 EP 225 DI 10.1016/j.bandl.2007.07.025 PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 227MF UT WOS:000250660100109 ER PT J AU Breitkreutz, I Raab, MS Vallet, S Hideshima, T Raje, N Chauhan, D Munshi, NC Richardson, PG Anderson, KC AF Breitkreutz, Iris Raab, Marc S. Vallet, Sonia Hideshima, Teru Raje, Noopur Chauhan, Dharminder Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI Targeting MEK1/2 blocks osteoclast differentiation, function and cytokine secretion in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; osteoclasts; bone disease; myeloma therapy; new drug development ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; BONE-MARROW MICROENVIRONMENT; AZD6244 ARRY-142886; ALPHA(V)BETA(3) INTEGRIN; OSTEOLYTIC LESIONS; RECEPTOR ACTIVATOR; ZOLEDRONIC ACID; GENE-EXPRESSION; KEY REGULATOR; CELL-GROWTH AB Osteolytic bone disease in multiple myeloma (MM) is associated with upregulation of osteoclast (OCL) activity and constitutive inhibition of osteoblast function. The extracellular signal-regulated kinase 1/2 (ERK1/2) pathway mediates OCL differentiation and maturation. We hypothesized that inhibition of ERK1/2 could prevent OCL differentiation and downregulate OCL function. It was found that AZD6244, a mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitor, blocked OCL differentiation and formation in a dose-dependent manner, evidenced by decreased alpha V beta 3-integrin expression and tartrate-resistant acid phosphatase positive (TRAP+) cells. Functional dentine disc cultures showed inhibition of OCL-induced bone resorption by AZD6244. Major MM growth and survival factors produced by OCLs including B-cell activation factor (BAFF) and a proliferation-inducing ligand (APRIL), as well as macrophage inflammatory protein (MIP-1 alpha), which mediates OCL differentiation and MM, were also significantly inhibited by AZD6244. In addition to ERK inhibition, NFATc1 (nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1) and c-fos were both downregulated, suggesting that AZD6244 targets a later stage of OCL differentiation. These results indicate that AZD6244 inhibits OCL differentiation, formation and bone resorption, thereby abrogating paracrine MM cell survival in the bone marrow microenvironment. The present study therefore provides a preclinical rationale for the evaluation of AZD6244 as a potential new therapy for patients with MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU PHS HHS [P01 78378, R01 50947] NR 47 TC 28 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2007 VL 139 IS 1 BP 55 EP 63 DI 10.1111/j.1365-2141.2007.06747.x PG 9 WC Hematology SC Hematology GA 209WN UT WOS:000249418800007 PM 17854307 ER PT J AU Lutskiy, MI Shcherbina, A Bachli, ET Cooley, J Remold-O'Donnell, E AF Lutskiy, Maxim I. Shcherbina, Anna Bachli, Eric T. Cooley, Jessica Remold-O'Donnell, Eileen TI WASP localizes to the membrane skeleton of platelets SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE Wiskott-Aldrich syndrome; platelets; WASP; membrane skeleton; integrin outside-in signalling ID WISKOTT-ALDRICH-SYNDROME; GLYCOPROTEIN-IIB-IIIA; SYNDROME PROTEIN WASP; ARP2/3 COMPLEX; N-WASP; ACTIN POLYMERIZATION; CYTOSKELETON; ACTIVATION; PHOSPHORYLATION; ASSOCIATION AB Patients with Wiskott-Aldrich syndrome (WAS), an X-linked blood cell disease, suffer from severe thrombocytopenia due to accelerated loss of defective platelets. The affected gene encodes WASP, an actin regulatory protein thought to reside in the cytoplasm of resting leucocytes. In contrast, this study showed that, for platelets, one-quarter of WASP molecules fractionate in the detergent-insoluble high speed pellet characterized as the membrane skeleton, the scaffold structure that underlies the lipid bilayer and stabilizes the surface membrane. Following treatment of platelets with thrombin and stirring, which induces cytoarchitectural remodelling, WASP and other membrane skeletal components sedimented at lower g force and partitioned in the low-speed pellet. Thrombin and stirring also induced WASP tyrosine phosphorylation, a rapid activating reaction, and proteolytic inactivation by cysteine protease calpain. Both the alteration of the sedimentation profile and the proteolytic inactivation were specific for the membrane skeletal pool of WASP and were abrogated in alpha IIb beta 3 integrin-deficient platelets and in normal platelets treated with an integrin antagonist. The findings demonstrate that WASP is a component of the resting platelet membrane skeleton and participates in membrane skeletal rearrangements downstream of integrin outside-in signalling. The possible implications for the platelet defect in WAS are discussed. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, Boston, MA 02115 USA. Fed Res Ctr Paediat Haematol Oncol & Immunol, Moscow, Russia. RP Remold-O'Donnell, E (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pediat, 800 Huntington Ave, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL059561, HL081407, HL59561, R21 HL081407]; NIAID NIH HHS [AI39574, R01 AI039574] NR 35 TC 6 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2007 VL 139 IS 1 BP 98 EP 105 DI 10.1111/j.1365-2141.2007.06745.x PG 8 WC Hematology SC Hematology GA 209WN UT WOS:000249418800013 PM 17854313 ER PT J AU Gupta, R Soupir, CP Johari, V Hasserjian, RP AF Gupta, Raavi Soupir, Chad P. Johari, Vandita Hasserjian, Robert P. TI Myelodysplastic syndrome with isolated deletion of chromosome 20q: an indolent disease with minimal morphological dysplasia and frequent thrombocytopenic presentation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplastic syndromes; thrombocytopenia; cytogenetics; histopathology; idiopathic thrombocytopenic purpura ID PROGNOSIS; PURPURA AB The present study analysed the clinicopathological features of nine myelodysplastic syndrome (MDS) patients in which del(20q) was the sole cytogenetic abnormality and a control group of 17 adult patients with idiopathic thrombocytopenic purpura (ITP). Seven of nine del(20q) patients were thrombocytopenic and six of nine were mildly anaemic at presentation. There was no significant morphological dysplasia identified in the del(20q) group as compared with the ITP group. These results indicate that MDS with del(20q) commonly presents with thrombocytopenia and has minimal morphological dysplasia. Cytogenetic analysis on adult patients undergoing bone marrow sampling for thrombocytopenia may help avoid misdiagnosis of MDS with del(20q) as ITP. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Columbia Univ, Med Ctr, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Baystate Med Ctr, Springfield, MA USA. Tufts Univ, Sch Med, Springfield, MA 01199 USA. RP Hasserjian, RP (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 244,55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org NR 9 TC 32 Z9 35 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2007 VL 139 IS 2 BP 265 EP 268 DI 10.1111/j.1365-2141.2007.06776.x PG 4 WC Hematology SC Hematology GA 214OG UT WOS:000249747400010 PM 17764468 ER PT J AU Steinman, MA Baron, RB Marlow, B AF Steinman, Michael A. Baron, Robert B. Marlow, Bernard TI Is continuing medical education a drug-promotion tool? SO CANADIAN FAMILY PHYSICIAN LA English DT Editorial Material ID PHYSICIANS; INDUSTRY; COMPANIES; SALE C1 Coll Family Physicians Canada, Mississauga, ON L4W 5A4, Canada. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. RP Steinman, MA (reprint author), Coll Family Physicians Canada, 2630 Skymark Ave, Mississauga, ON L4W 5A4, Canada. EM mike.steinman@ucsf.edu NR 16 TC 12 Z9 12 U1 0 U2 0 PU COLL FAMILY PHYSICIANS CANADA PI MISSISSAUGA PA 2630 SKYMARK AVE, MISSISSAUGA, ONTARIO L4W 5A4, CANADA SN 0008-350X J9 CAN FAM PHYSICIAN JI Can. Fam. Phys. PD OCT PY 2007 VL 53 BP 1650 EP 1653 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 226JG UT WOS:000250584700005 PM 17934022 ER PT J AU Nguyen, PL D'Amico, AV Lee, AK Suh, WW AF Nguyen, Paul L. D'Amico, Anthony V. Lee, Andrew K. Suh, W. Warren TI Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure - A systematic review of the literature SO CANCER LA English DT Review DE salvage therapy; prostatectomy; brachytherapy; cryosurgery; local neoplasm recurrence; prostate cancer; prostate-specific antigen ID PREOPERATIVE PSA VELOCITY; EXTERNAL-BEAM RADIATION; NEOADJUVANT ANDROGEN ABLATION; SURROGATE END-POINT; RADICAL PROSTATECTOMY; FOLLOW-UP; CRYOSURGICAL ABLATION; PRETREATMENT NOMOGRAM; RADIOTHERAPY FAILURE; RECURRENT AB Among men who experience prostate-specific antigen (PSA) failure after external beam radiation or brachytherapy (RT), many will harbor occult micrometastases; however, a significant minority will have a true local-only failure and, thus, potentially may benefit from a salvage local therapy. Those most likely to have a local-only failure initially have low-risk disease (PSA <10 ng/mL, Gleason score <= 6, clinical T1c or T2a tumor status), pretreatment PSA velocity <2.0 ng/mL per year at the time of initial presentation, interval to PSA failure >3 years, PSA doubling time >12 months, negative bone scan and pelvic imaging, and positive rebiopsy. In addition, men with presalvage PSA levels >10 ng/mL, presalvage T3/T4 disease, or presalvage Gleason scores >= 7 on a rebiopsy sample without significant RT effects are unlikely to be cured by salvage local therapy. Based on a review of all series of post-RT salvage prostatectomy, cryosurgery, and brachytherapy published in English since 1990, morbidity can be substantial. Although urinary incontinence appeared to be greater after salvage prostatectomy (41%) or cryosurgery (36%) than after brachytherapy (6%), patients who received salvage brachytherapy faced a 17% risk of grade 3 or 4 genitourinary complications and a fistula risk that averaged 3.4% across all series. From this review, the authors concluded that prospective randomized studies are needed to determine the relative efficacy of the 3 major local salvage modalities and that additional research is needed to identify, factors associated with an increased risk of significant complications to improve patient selection and to augment the benefit/risk ratio associated with attempts to cure local-only recurrences after radiation therapy. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St, Boston, MA 02115 USA. EM pnguyen@lroc.harvard.edu NR 87 TC 118 Z9 120 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2007 VL 110 IS 7 BP 1417 EP 1428 DI 10.1002/cncr.22941 PG 12 WC Oncology SC Oncology GA 211HG UT WOS:000249514300002 PM 17694553 ER PT J AU Nguyen, PL Chen, MH D'Amico, AV Tempany, CM Steele, GS Albert, M Cormack, RA Carr-Locke, DL Bleday, R Suh, WW AF Nguyen, Paul L. Chen, Ming-Hui D'Amico, Anthony V. Tempany, Clare M. Steele, Graerne S. Albert, Michele Cormack, Robert A. Carr-Locke, David L. Bleday, Ronald Suh, W. Warren TI Magnetic resonance image-guided salvage brachytherapy after radiation in select men who initially presented with favorable-risk prostate cancer - A prospective phase 2 study SO CANCER LA English DT Article DE salvage therapy; brachytherapy; magnetic resonance imaging; local neoplasm recurrence; prostate cancer; prostate-specific antigen ID EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; FOLLOW-UP; INTERSTITIAL BRACHYTHERAPY; ANDROGEN DEPRIVATION; RADIOTHERAPY FAILURE; PSA VELOCITY; THERAPY; ANTIGEN; RECURRENCE AB BACKGROUND. The authors prospectively evaluated the late gastrointestinal (GO and genitourinary (GU) toxicity and prostate-specific antigen (PSA) control of magnetic resonance imaging (MRI)-guided brachytherapy used as salvage for radiation therapy (RT) failure. METHODS. From October 2000 to October 2005, 25 men with a rising PSA level and biopsy-proven, intraprostatic cancer at least 2 years after initial RT (external beam in 13 men and brachytherapy in 12 men) who had favorable clinical features (Gleason score <= 7, PSA <10 ng/mL, negative pelvic and bone imaging studies), received MRI-guided salvage brachytherapy to a minimum peripheral dose of 137 gray on a phase 1/2 protocol. Estimates of toxicity and cancer control were calculated using the Kaplan-Meier method. RESULTS. The median follow-up was 47 months. The 4-year estimate of grade 3 or 4 GI or GU toxicity was 30%, and 13% of patients required a colostomy and/or urostomy to repair a fistula. An interval <4.5 years between RT courses was associated with both outcomes with a hazard ratio of 12 (95% confidence interval [95% CI], 1.4-100; P = .02) for grade 3 or 4 toxicity and 25 (95% CI, 1.1-529; P = .04) for colostomy and/or urostomy. PSA control (nadir +2 definition) was 70% at 4 years. CONCLUSIONS. The current results indicated that MRI-guided salvage brachytherapy in men who are selected based on presenting characteristics and postfailure PSA kinetics can achieve high PSA control rates, although complications requiring surgical intervention may occur in 10% to 15% of patients. Prospective randomized studies are needed to characterize the relative cancer control and toxicity after all forms of salvage local therapy. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Colorectal Surg, Boston, MA 02115 USA. RP Nguyen, PL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. EM pnguyen@lroc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 FU NCI NIH HHS [R01 CA111288, R25 CA089017]; NCRR NIH HHS [RR019703] NR 51 TC 62 Z9 62 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 OCT 1 PY 2007 VL 110 IS 7 BP 1485 EP 1492 DI 10.1002/cncr.22934 PG 8 WC Oncology SC Oncology GA 211HG UT WOS:000249514300010 PM 17701957 ER PT J AU Deininger, MWN Cortes, J Paquette, R Park, B Hochhaus, A Baccarani, M Stone, R Fischer, T Kantarjian, H Niederwieser, D Gambacorti-Passerini, C So, C Gathmann, I Goldman, JM Smith, D Druker, BJ Guilhot, F AF Deininger, Michael W. N. Cortes, Jorge Paquette, Ron Park, Byung Hochhaus, Andreas Baccarani, Michele Stone, Richard Fischer, Thomas Kantarjian, Hagop Niederwieser, Dietger Gambacorti-Passerini, Carlo So, Charlene Gathmann, Insa Goldman, John M. Smith, Douglas Druker, Brian J. Guilhot, Francois TI The prognosis for patients with chronic myeloid leukemia who have clonal cytogenetic abnormalities in Philadelphia chromosome-negative cells SO CANCER LA English DT Article DE chronic myeloid leukemia; cytogenetic abnormalities; Philadelphia chromosome; BCR-ABL; imatinib ID CHRONIC MYELOGENOUS LEUKEMIA; IMATINIB MESYLATE THERAPY; INTERFERON-ALPHA; CHRONIC-PHASE; CML PATIENTS; FOLLOW-UP; PH-CELLS; EMERGENCE; HEMATOPOIESIS; ABERRATIONS AB BACKGROUND. Clonal cytogenetic abnormalities (CCA) were detected in Philadelphia chromosome (Ph)-negative cells in some patients with chronic myeloid leukemia (CML) who attained a cytogenetic response to imatinib mesylate. In some patients, CCA/Ph-negative status was associated with myelodysplasia or acute myeloid leukemia. The objective of the current study was to determine the prognostic impact of CCA/Ph-negative cells. METHODS. The authors compared the pretherapeutic risk factors (Kruskall-Wallis test), exposure to cytotoxic drugs (chi-square test), and overall and progression-free survival (Kaplan-Meyer and logistic regression analysis, respectively) of 515 patients with mostly chronic-phase CML who were treated with imatinib mesylate after failure of interferon-alpha according to whether they attained a major cytogenetic response (MCR) (n = 324 patients), an MCR with CCA/Ph-negative status (n = 30 patients), or no MCR (n = 161 patients). RESULTS. CCA/Ph-negative status most frequently involved chromosomes Y, 8, and 7. No significant differences in pretherapeutic risk factors were detected between patients who attained an MCR with and without CCA/Ph-negative cells, except that exposure to alkylating agents was more frequent in patients with CCA/Ph-negative cells, and overall and progression-free survival were identical. With a median follow-up of 51 months, only 2 patients developed myelodysplastic syndromes (MDS). CONCLUSIONS. The overall prognosis for patients who had CML with CCA/Ph-negative status was good and was driven by the CML response to imatinib mesylate. Isolated CCA/Ph-negative cells in the absence of morphologic evidence of MDS do not justify a change in therapy. C1 Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Med Oncol, Portland, OR 97239 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Calif Los Angeles, Div Hematol Oncol, Los Angeles, CA USA. Univ Heidelberg, Fac Med, D-6800 Mannheim, Germany. Univ Bologna, S Orsola M Malpighi Hosp, Dept Hematol & Oncol L & A Seragnoli, Bologna, Italy. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Mainz, Dept Med 3, D-6500 Mainz, Germany. Univ Leipzig, Dept Hematol & Oncol, D-7010 Leipzig, Germany. Univ Milan, Dept Internal Med, Monza, Italy. McGill Univ, Dept Hematol, Montreal, PQ, Canada. Novartis Pharmaceut, Dept Biostat, Basel, Switzerland. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Kimmel Comprehens Canc Ctr, Div Hematol Malignancies, Baltimore, MD USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Univ Miletrie Hosp, Clin Res Ctr, Dept Oncol Hematol & Cell Therapy, Poitiers, France. Novartis Pharmaceut, Clin Dev, Basel, Switzerland. RP Deininger, MWN (reprint author), Oregon Hlth & Sci Univ, Inst Canc, Div Hematol & Med Oncol, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deininge@ohsu.edu OI GAMBACORTI PASSERINI, CARLO/0000-0001-6058-515X; Hochhaus, Andreas/0000-0003-0626-0834; /0000-0003-3516-7516 NR 27 TC 69 Z9 70 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 OCT 1 PY 2007 VL 110 IS 7 BP 1509 EP 1519 DI 10.1002/cncr.22936 PG 11 WC Oncology SC Oncology GA 211HG UT WOS:000249514300013 PM 17702093 ER PT J AU Lee, BH Tothova, Z Levine, RL Anderson, K Buza-Vidas, N Cullen, DE McDowell, EP Adelsperger, J Frhling, S Huntly, BJP Beran, M Jacobsen, SE Gilliland, DG AF Lee, Benjamin H. Tothova, Zuzana Levine, Ross L. Anderson, Kristina Buza-Vidas, Natalija Cullen, Dana E. McDowell, Elizabeth P. Adelsperger, Jennifer Frhling, Stefan Huntly, Brian J. P. Beran, Miloslav Jacobsen, Sten Eirik Gilliland, D. Gary TI FLT3 mutations confer enhanced proliferation and survival properties to multipotent progenitors in a murine model of chronic myelomonocytic leukemia SO CANCER CELL LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; CHRONIC MYELOPROLIFERATIVE DISORDERS; MARROW TRANSPLANT MODEL; LYMPHOMA CELL-LINES; TYROSINE KINASE; BONE-MARROW; ACTIVATING MUTATION; PROGNOSTIC-FACTORS; CONSTITUTIVE ACTIVATION AB Despite their known transforming properties, the effects of leukemogenic FLT3-ITD mutations on hematopoietic stem and multipotent progenitor cells and on hematopoietic differentiation are not well understood. We report a mouse model harboring an ITD in the murine Flt3 locus that develops myeloproliferative disease resembling CMML and further identified FLT3-ITD mutations in a subset of human CMML. These findings correlated with an increase in number, cell cycling, and survival of multipotent stem and progenitor cells in an ITD dose-dependent manner in animals that exhibited alterations within their myeloid progenitor compartments and a block in normal B cell development. This model provides insights into the consequences of constitutive signaling by an oncogenic tyrosine kinase on hematopoietic progenitor quiescence, function, and cell fate. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Lund Univ, Lund Stem Cell Ctr, Hematopoiet Stem Cell Lab, S-22184 Lund, Sweden. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. RP Lee, BH (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. EM bhlee@partners.org; ggilliland@rics.bwh.harvard.edu RI huntly, brian/E-6725-2014; OI huntly, brian/0000-0003-0312-161X; Jacobsen, Sten Eirik Waelgaard/0000-0002-1362-3659 FU Howard Hughes Medical Institute [HHMI_GILLILAND_D]; Medical Research Council [G116/187]; NCI NIH HHS [CA105423, CA113434, CA66996, K08 CA113434, K08 CA113434-01A1, K08 CA113434-02, P01 CA066996, P01 CA066996-100001, U01 CA105423]; PHS HHS [HHMI_GILLILAND_D] NR 60 TC 92 Z9 95 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD OCT PY 2007 VL 12 IS 4 BP 367 EP 380 DI 10.1016/j.ccr.2007.08.031 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 223ID UT WOS:000250362600010 PM 17936561 ER PT J AU Meyerhardt, JA Clark, JW Supko, JG Eder, JP Ogino, S Stewart, CF D'Amato, F Dancey, J Enzinger, PC Zhu, AX Ryan, DP Earle, CC Mayer, RJ Michelini, A Kinsella, K Fuchs, CS AF Meyerhardt, Jeffrey A. Clark, Jeffrey W. Supko, Jeffrey G. Eder, Joseph P. Ogino, Shuji Stewart, Clinton F. D'Amato, Ferdinando Dancey, Janet Enzinger, Peter C. Zhu, Andrew X. Ryan, David P. Earle, Craig C. Mayer, Robert J. Michelini, Ann Kinsella, Kate Fuchs, Charles S. TI Phase I study of gefitinib, irinotecan, 5-fluorouracil and leucovorin in patients with metastatic colorectal cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; PREVIOUSLY TREATED PATIENTS; CELL LUNG-CANCER; SOLID TUMORS; TRIAL; FLUOROURACIL; IRESSA; THERAPY; MALIGNANCIES AB Purpose To determine the maximum tolerated doses (MTD), toxicities, efficacy, and pharmacokinetics (PK) of gefitinib combined with irinotecan, 5-fluorouracil (5-FU) and leucovorin (IFL) in patients with previously untreated advanced colorectal cancer. Experimental Design Starting doses were gefitinib 250 mg/day orally without interruption, irinotecan 100 mg/m(2) stop as a 90 min intravenous (i.v.) infusion, 5-FU 400 mg/m(2) stop bolus i.v. and leucovorin 20 mg/m(2) stop i.v. on days 1 and 8 of a 21-day cycle. Dose escalations involved increasing gefitinib to 500 mg then increasing irinotecan to 125 mg/m(2) stop and 5-FU to 500 mg/m(2) stop. Results Twenty-four patients received therapy. The starting doses proved to be the MTD, as attempts to increase the dose of either gefitinib or the chemotherapeutic agents resulted in dose-limiting toxicities. Gastrointestinal effects and bone marrow suppression were the principal toxicities; however, only 1/17 (6%) patients treated with the MTD had severe (grades 3-4) diarrhea and severe neutropenia occurred in only two (12%) patients. Partial responses occurred in 10/17 patients receiving the MTD and another five had stable disease. Median progression-free and overall survivals were 12.2 and 26.6 months, respectively. In ten patients treated with the MTD, the steady-state PK of gefitinib was not affected by IFL nor did gefitinib appear to influence the PK of either irinotecan or 5-FU. Conclusions Gefitinib can be safely combined with an intermittent weekly schedule of IFL. Evidence of promising activity should encourage further clinical evaluation of epidermal growth factor receptor tyrosine kinase inhibitors, such as gefitinib, combined with multiagent chemotherapy for metastatic colorectal cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. NCI, Div Canc Treatment, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Meyerhardt, JA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM jmeyerhardt@partners.org FU NCI NIH HHS [2 P30CA0516, U01 CA62490] NR 52 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2007 VL 60 IS 5 BP 661 EP 670 DI 10.1007/s00280-006-0411-6 PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 201EJ UT WOS:000248814000005 PM 17216531 ER PT J AU Michaud, DS Wolpin, B Giovannucci, E Liu, S Cochrane, B Manson, JE Pollak, MN Ma, J Fuchs, CS AF Michaud, Dominique S. Wolpin, Brian Giovannucci, Ed Liu, Simin Cochrane, Barbara Manson, JoAnn E. Pollak, Michael N. Ma, Jing Fuchs, Charles S. TI Prediagnostic plasma c-pepticle and pancreatic cancer risk in men and women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PHYSICAL-ACTIVITY; COLON-CANCER; MALE SMOKERS; GLUCOSE; OBESITY; INSULIN; MORTALITY; HEALTH; ANTHROPOMETRY; PREVENTION AB Background: Hyperinsulinemia and insulin resistance have been proposed as underlying mechanisms for the increase in pancreatic cancer among long-standing diabetics and obese individuals. An association between serum insulin levels and pancreatic cancer risk was reported in a recent study, but the population was composed of heavy smokers and their findings may not be generalizable to nonsmokers. Methods: Pancreatic cancer cases and matched controls were obtained from four large-scale prospective cohorts to examine the association between prediagnostic plasma levels of C-peptide and insulin and pancreatic cancer. One hundred ninety-seven pancreatic cancer cases were diagnosed during a maximum of 20 years of follow-up, after excluding cases diagnosed within 2 years of blood collection or with baseline diabetes. We estimated OR and confidence intervals (0) using conditional logistic regression with adjustment for pancreatic cancer risk factors. Results: Prediagnostic plasma C-peptide was positively associated with pancreatic cancer risk (OR, 1.52; 95% CI, 0.87-2.64, highest compared with the lowest quartile, P-trend = 0-005). The association was not modified by body mass index or physical activity but seemed to be slightly stronger among never smokers than ever smokers. Fasting C-peptide and insulin were not related to pancreatic cancer; however, we observed a strong linear association for nonfasting C-peptide and pancreatic cancer (OR, 4.24; 95% CI, 1.30-13.8, highest versus lowest quartile, P-trend < 0-001). Conclusions: Based on our finding of a strong positive association with nonfasting C-peptide levels, we propose that insulin levels in the postprandial state may be the relevant exposure for pancreatic carcinogenesis; however, other studies will need to examine this possibility. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. McGill Univ, Jewish Gen Hosp, Dept Med, Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. McGill Univ, Jewish Gen Hosp, Dept Oncol, Lady Davis Res Inst, Montreal, PQ H3T 1E2, Canada. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Michaud, DS (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Kresge 920,677 Huntington Ave, Boston, MA 02115 USA. EM dmichaud@hsph.harvard.edu RI Pollak, Michael/G-9094-2011; Liu, Simin/I-3689-2014; Michaud, Dominique/I-5231-2014 OI Pollak, Michael/0000-0003-3047-0604; Liu, Simin/0000-0003-2098-3844; FU NCI NIH HHS [CA90598, CA42182, CA55075, CA86102, CA87969, CA95589, R01 CA124908, T32 CA009172]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 33 TC 56 Z9 59 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2007 VL 16 IS 10 BP 2101 EP 2109 DI 10.1158/1055-9965.EPI-07-0182 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 222HC UT WOS:000250285900027 PM 17905943 ER PT J AU Manne, SL Chung, DC Weinberg, DS Vig, HS Catts, Z Cabral, MK Shannon, K Meropol, NJ AF Manne, Sharon L. Chung, Daniel C. Weinberg, David S. Vig, Hetal S. Catts, Zohra Cabral, Melissa Klein Shannon, Kristen Meropol, Neal J. TI Knowledge and attitudes about Microsatellite instability testing among high-risk individuals diagnosed with colorectal cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HEALTH BELIEF MODEL; BREAST-CANCER; LYNCH-SYNDROME; SELF-EFFICACY; PSYCHOLOGICAL IMPACT; DECISION-MAKING; OVARIAN-CANCER; YOUNG-WOMEN; POPULATION; ADHERENCE AB For individuals meeting Bethesda criteria for hereditary nonpolyposis colorectal cancer syndrome, the microsatellite instability (MSI) test is recommended as a screening evaluation before proceeding to genetic testing. The MSI test is new to the medical setting, but will be increasingly used to screen patients at high risk for hereditary nonpolyposis colorectal cancer. The main goals of this study were to examine knowledge about and exposure to the MSI test among individuals considering the test, to evaluate perceived benefits and barriers to undergoing the MSI test, and to identify the demographic, medical, and psychosocial correlates of the perceived benefits and barriers to undergoing the test. One hundred and twenty-five patients completed a survey after being offered the test, but prior to making the decision whether to pursue MSI testing. Results indicated low levels of knowledge about and previous exposure to the MSI test. Participants held positive attitudes about the potential benefits of the test and perceived few barriers to undergoing the test. Motivations were similar to those cited by individuals considering other genetic tests. Participants with non-metastatic disease, with lower perceived risk for cancer recurrence, and who reported more self-efficacy endorsed more benefits from the test. Higher levels of cancer-specific psychological distress were associated with more perceived barriers to having the test. These findings suggest that individuals considering the MSI test know very little about it but hold positive attitudes about the test's utility. More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test. C1 Fox Chase Canc Ctr, Div Populat Med Sci, Philadelphia, PA 19111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA USA. Helen F Graham Canc Ctr, Newark, DE USA. RP Manne, SL (reprint author), Fox Chase Canc Ctr, Div Populat Med Sci, 333 Cottoman Ave,P1100, Philadelphia, PA 19111 USA. EM Sharon.Manne@fccc.edu FU NCI NIH HHS [CA 109332] NR 42 TC 17 Z9 17 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2007 VL 16 IS 10 BP 2110 EP 2117 DI 10.1158/1055-9965.EPI-07-0412 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 222HC UT WOS:000250285900028 PM 17932359 ER PT J AU Corsten, MF Miranda, R Kasmieh, R Krichevsky, AM Weissleder, R Shah, K AF Corsten, Maarten F. Miranda, Rafael Kasmieh, Randa Krichevsky, Anna M. Weissleder, Ralph Shah, Khalid TI MicroRNA-21 knockdown disrupts glioma growth In vivo and displays synergistic cytotoxicity with neural precursor cell-delivered S-TRAIL in human gliomas SO CANCER RESEARCH LA English DT Article ID GLIOBLASTOMA-MULTIFORME; TUMOR-REGRESSION; APOPTOSIS; EXPRESSION; OLIGONUCLEOTIDES; INHIBITION; THERAPY; LIGAND; CANCER; MIGRATION AB Despite the development of new glioma therapies that allow for tumor-targeted in situ delivery of cytotoxic drugs, tumor resistance to apoptosis remains a key impediment to effective treatment. Mounting evidence indicates that microRNAs (miRNA) might play a fundamental role in tumorigenesis, controlling cell proliferation and apoptosis. In gliomas, microRNA-21 (miR-21) levels have been reported to be elevated and their knockdown is associated with increased apoptotic activity. We hypothesized that suppression of miR-21 might sensitize gliomas for cytotoxic tumor therapy. With the use of locked nucleic acid (LNA)-antimiR-21 oligonucleotides, bimodal imaging vectors, and neural precursor cells (NPC) expressing a secretable variant of the cytotoxic agent tumor necrosis factor-related apoptosis inducing ligand (S-TRAIL), we show that the combined suppression of miR-21 and NPC-S-TRAIL leads to a synergistic increase in caspase activity and significantly decreased cell viability in human glioma cells in vitro. This phenomenon persists in vivo, as we observed complete eradication of LNA-antimiR-21-treated gliomas subjected to the presence of NIPC-S-TRAIL in the murine brain. Our results reveal the efficacy of miR-21 antagonism in murine glioma models and implicate miR-21 as a target for therapeutic intervention. Furthermore, our findings provide the basis for developing combination therapies using miRNA modulation and cytotoxic tumor therapies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. RP Shah, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA 02129 USA. EM kshah@helix.mgh.harvard.edu RI leng, xianwei/F-9073-2011 FU NCI NIH HHS [P01 CA69246, P50 CA86355, R21 CA116141] NR 36 TC 270 Z9 292 U1 7 U2 35 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2007 VL 67 IS 19 BP 8994 EP 9000 DI 10.1158/0008-5472.CAN-07-1045 PG 7 WC Oncology SC Oncology GA 217NV UT WOS:000249955500005 PM 17908999 ER PT J AU Janeway, KA Liegl, B Harlow, A Le, C Perez-Atayde, A Kozakewich, H Corless, CL Heinrich, NC Fletcher, JA AF Janeway, Katherine A. Liegl, Bernadette Harlow, Amy Le, Claudia Perez-Atayde, Antonio Kozakewich, Harry Corless, Christopher L. Heinrich, Nflchael C. Fletcher, Jonathan A. TI Pediatric KIT-wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors SO CANCER RESEARCH LA English DT Article ID OF-THE-LITERATURE; 12-YEAR-OLD GIRL; YOUNG-ADULTS; CHILDREN; IMATINIB; STOMACH; DEREGULATION; MUTATIONS; BIOLOGY; PDGFRA AB Fewer than 15% of gastrointestinal stromal tumors (GIST) in pediatric patients harbor JUT or platelet-derived growl factor receptor alpha (PDGFRA) mutations in contrast to a mutation rate of 80% in adult GISTs. However, some therapeutic inhibitors of KIT have efficacy in pediatric GIST, suggesting that KIT may, nevertheless, play an important role in oncogenesis. In adult GIST, characteristic cytogenetic changes occur during progression to malignancy. A better understanding of mechanisms of genetic progression and KIT and PDGFRA transforming roles in pediatric GIST might facilitate treatment advances. KIT and PDGFRA mutation analysis was done in 27 pediatric GISTs. The activation status of KIT, PDGFRA, and downstream signaling intermediates was defined, and chromosomal aberrations were determined by single nucleotide polymorphism assays. Mutations in KIT or PDGFRA were identified in 11% of pediatric GISTs. KIT and the signaling intermediates AKT and mitogen-activated protein kinase were activated in pediatric GISTs. In particular, most pediatric KIT-wild-type GISTs displayed levels of KIT activation similar to levels in adult JUT-mutant GISTs. Pediatric JUT-wild-type GISTs lacked the typical cytogenetic deletions seen in adult JUT-mutant GISTs. Notably, most pediatric KIT-wild-type GISTs progress to malignancy without acquiring large-scale chromosomal aberrations, which is a phenomenon not reported previously in malignant solid tumors. KIT activation levels in pediatric JUT-wild-type GISTs are comparable with those in KIT-mutant GISTs. Therapies that inhibit KIT activation, or crucial KIT signaling intermediates, should be explored in pediatric KIT-wild-type GIST. C1 Childrens Hosp, Dept Med, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Med Univ, Dept Pathol, Graz, Austria. Oregon Hlth & Sci Univ, Dept Med, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Dev & Cell Biol, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Janeway, KA (reprint author), Dana Farber Canc Inst, Dept Pediat, 44 Britney St, Boston, MA 02115 USA. EM katherine.janeway@childrens.harvard.edu FU NCI NIH HHS [1P50CA12703-01]; NHLBI NIH HHS [5732HL007574.25] NR 25 TC 80 Z9 88 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2007 VL 67 IS 19 BP 9084 EP 9088 DI 10.1158/0008-5472.CAN-07-1938 PG 5 WC Oncology SC Oncology GA 217NV UT WOS:000249955500018 PM 17909012 ER PT J AU Varghese, S Rabkin, SD Nielsen, GP MacGarvey, U Liu, RB Martuza, RL AF Varghese, Susan Rabkin, Samuel D. Nielsen, G. Petur MacGarvey, Usha Liu, Renbin Martuza, Robert L. TI Systemic therapy of spontaneous prostate cancer in transgenic mice with oncolytic herpes simplex viruses SO CANCER RESEARCH LA English DT Article ID EXPRESSING INTERLEUKIN-12; REPLICATION-COMPETENT; BETA-GALACTOSIDASE; BREAST-CANCER; VECTOR G207; MOUSE; MODEL; TUMOR; EFFICACY; GLIOMA AB Oncolytic viruses are an innovative therapeutic strategy for cancer, wherein viral replication and cytotoxicity are selective for tumor cells. Here we show the efficacy of systemically administered oncolytic viruses for the treatment of spontaneously arising tumors, specifically the use of oncolytic herpes simplex viruses(HSV) administered i.v. to treat spontaneously developing primary and metastatic prostate cancer in the transgenic TRAMP mouse, which recapitulates human prostate cancer progression. Four administrations of systemically delivered NV1023 virus, an HSV-1/HSV-2 oncolytic recombinant, to TRAMP mice at 12 or IS weeks of age (presence of prostate adenocarcinoma or metastatic disease, respectively) inhibited primary tumor growth and metastases to lymph nodes. Expression of interleukin 12 (IL-12) from NV1042 virus, a derivative of NV1023, was additionally effective, significantly reducing the frequency of development of prostate cancer and lung metastases, even when the mice were treated after the onset of metastasis at 18 weeks of age. NVI042-infected cells, as detected by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining for Lac Z expressed by the virus, were present in prostate tumors I week after the final virus injection and viral DNA was detected at 2 weeks after final virus injection by real-time PCR in primary and metastatic tumors but not in liver or blood. No toxicity was observed in any of the treated mice. The efficacy of the IL-12-expressing NV1042 virus in this aggressive prostate cancer model using a clinically relevant treatment paradigm merits its consideration for clinical studies. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. RP Martuza, RL (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, WHT-502,55 Fruit St, Boston, MA 02114 USA. EM rmartuza@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [1R01CA102139-0141]; NINDS NIH HHS [P30 NS045776] NR 48 TC 25 Z9 27 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2007 VL 67 IS 19 BP 9371 EP 9379 DI 10.1158/0008-5472.CAN-07-0674 PG 9 WC Oncology SC Oncology GA 217NV UT WOS:000249955500052 PM 17909046 ER PT J AU Fulci, G Dmitrieva, N Gianni, D Fontana, EJ Pan, XG Lu, YH Kaufman, CS Kaur, B Lawler, SE Lee, RJ Marsh, CB Brat, DJ Rooijen, N Rachamimov, AS Hochberg, FH Weissleder, R Martuza, RL Chiocca, EA AF Fulci, Giulia Dmitrieva, Nina Gianni, Davide Fontana, Elisabeth J. Pan, Xiaogang Lu, Yanhui Kaufman, Claire S. Kaur, Balveen Lawler, Sean E. Lee, Robert J. Marsh, Clay B. Brat, Daniel J. van Rooijen, Nico Rachamimov, Anat Stemmer Hochberg, Fred H. Weissleder, Ralph Martuza, Robert L. Chiocca, E. Antonio TI Depletion of peripheral macrophages and brain microglia increases brain tumor titers of oncolytic viruses SO CANCER RESEARCH LA English DT Article ID HERPES-SIMPLEX-VIRUS; CELL-BASED DELIVERY; PHASE-I TRIAL; PERIVASCULAR MACROPHAGES; GLIOBLASTOMA-MULTIFORME; GLIOMA VIROTHERAPY; MALIGNANT GLIOMA; GM-CSF; THERAPY; MUTANT AB Clinical trials have proven oncolytic virotherapy to be safe but not effective. We have shown that oncolytic viruses (OV) injected into intracranial gliomas established in rodents are rapidly cleared, and this is associated with up-regulation of markers (CD68 and CD163) of cells of monocytic lineage (monocytes/microglia/macrophages). However, it is unclear whether these cells directly impede intratumoral persistence of OV through phagocytosis and whether they infiltrate the tumor from the blood or the brain parenchyma. To investigate this, we depleted phagocytes with clodronate liposomes (CL) in vivo through systemic delivery and ex vivo in brain slice models with gliomas. Interestingly, systemic CL depleted over 80% of peripheral CD163(+) macrophages in animal spleen and peripheral blood, thereby decreasing intratumoral infiltration of these cells, but CD68(+) cells were unchanged. Intratumoral viral titers increased 5-fold. In contrast, ex vivo CL depleted only CD68(+) cells from brain slices, and intratumoral. viral titers increased 10-fold. These data indicate that phagocytosis by both peripheral CD163(+) and brain-resident CD68(+) cells infiltrating tumor directly affects viral clearance from tumor. Thus, improved therapeutic efficacy may require modulation of these innate immune cells. In support of this new therapeutic paradigm, we observed intratumoral up-regulation of CD68(+) and CD163(+) cells following treatment with OV in a patient with glioblastoma. C1 Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Neurosurg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Neurosurg Serv, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging, Charlestown, MA USA. Ohio State Univ, Ctr Med, Dept Internal Med, Columbus, OH USA. Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH USA. Ohio State Univ, James Canc Hosp, Solove Res Inst, Dept Neurol Surg,Dardinger Lab Neurooncol & Neuro, Columbus, OH USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA USA. Vrije Univ Amsterdam, Dept Cell Biol & Immunol, Amsterdam, Netherlands. RP Fulci, G (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, Brain Tumor Res Ctr, Neurosurg Serv, Simches Res Bldg CRPZN 3800,185 Cambridge St, Boston, MA 02114 USA. EM gfulci@partners.org; EA.Chiocca@osumc.edu RI kaur, Balveen/E-3355-2011 FU NCI NIH HHS [P01 CA069246, CA095673, P01 CA069246-04, P01 CA069246-06, P01 CA69246, R01 CA085139, R01 CA095673, R01 CA85139]; NHLBI NIH HHS [R01 HL063800, R01 HL63800]; NINDS NIH HHS [NS41571, R01 NS041571] NR 50 TC 86 Z9 87 U1 1 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 OCT 1 PY 2007 VL 67 IS 19 BP 9398 EP 9406 DI 10.1158/0008-5472.CAN-07-1063 PG 9 WC Oncology SC Oncology GA 217NV UT WOS:000249955500055 PM 17909049 ER PT J AU Zhang, XP Zhang, L Yang, HM Huang, X Otu, H Libermann, TA DeWolf, WC Khosravi-Far, R Olumi, AF AF Zhang, Xiaoping Zhang, Liang Yang, Hongmei Huang, Xu Otu, Hasan Libermann, Towia A. DeWolf, William C. Khosravi-Far, Roya Olumi, Aria F. TI c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; RECEPTOR-INDUCED APOPTOSIS; DEATH DOMAIN; TRANSCRIPTION FACTORS; MEDIATED APOPTOSIS; EXPRESSION; PATHWAYS; FAMILY; AP-1 AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo-2L promotes apoptosis in cancer cells while sparing normal cells. Although many cancers are sensitive to TRAIL-induced apoptosis, some evade the proapoptotic effects of TRAIL. Therefore, differentiating molecular mechanisms that distinguish between TRAIL-sensitive and TRAIL-resistant tumors are essential for effective cancer therapies. Here, we show that c-Fos functions as a proapoptotic agent by repressing the antiapoptotic molecule c-FLIP(L). c-Fos binds the c-FLIP(L) promoter, represses its transcriptional activity, and reduces c-FLIP(L) mRNA and protein levels. Therefore, c-Fos is a key regulator of e-FLIP(L), and activation of c-Fos determines whether a cancer cell will undergo cell death after TRAM treatment. Strategies to activate c-Fos or inhibit c-FLIP(L) may potentiate TRAIL-based proapoptotic therapies. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Urol Surg, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Genom, Boston, MA USA. RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St,Yawkey Bldg,Suite 7E, Boston, MA 02114 USA. EM aolumi@partners.org RI Libermann, Towia/F-9866-2010; OI Libermann, Towia/0000-0002-4006-8179; Otu, Hasan/0000-0002-9253-8152 FU NHLBI NIH HHS [1 R01 HL080192, R01 HL080192, R01 HL080192-07]; NIDDK NIH HHS [K08 DK064062, DK64062] NR 45 TC 50 Z9 51 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2007 VL 67 IS 19 BP 9425 EP 9434 DI 10.1158/0008-5472.CAN-07-1310 PG 10 WC Oncology SC Oncology GA 217NV UT WOS:000249955500058 PM 17909052 ER PT J AU Nimmegeers, S Sips, P Buys, E Brouckaert, P Van de Voorde, J AF Nimmegeers, Sofie Sips, Patrick Buys, Emmanuel Brouckaert, Peter Van de Voorde, Johan TI Functional role of the soluble guanylyl cyclase alpha(1) subunit in vascular smooth muscle relaxation SO CARDIOVASCULAR RESEARCH LA English DT Article; Proceedings Paper CT 2nd International Conference of cGMP Ceneratore, Effectore and Therapeutic Implications CY JUN 10-12, 2005 CL Potsdam, GERMANY DE arteries; nitric oxide; endothelial function; second messengers; vasoconstriction/dilatation ID RAT MESENTERIC-ARTERY; NITRIC-OXIDE SYNTHASE; K+ CHANNELS; BAY 41-2272; CYCLIC-GMP; NO; ACTIVATION; CELLS; STIMULATORS; INVOLVEMENT AB Objective: Soluble guanylyl cyclase (sGC), the predominant receptor for nitric oxide (NO), exists in 2 active isofon-nS (alpha(2)beta(1) and alpha(1)beta(1)). In vascular tissue sGC alpha(1)beta(1), is believed to be the most important. The aim of our study was to investigate the functional importance of the sGC alpha(1)-subunit in vasorelaxation. Methods: Aortic and femoral artery segments from male and/or female sGC alpha(-/-)(1) mice and wild-type littermates were mounted in a small-vessel myograph for isometric tension recording. This was supplemented with biochemical measurements of the cGMP concentration and sGC enzyme activity. Results: The functional importance of sGC alpha(1)beta(1) was demonstrated by the significantly decreased relaxing effects of acetylcholine (ACh), sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), NO gas, YC-1, BAY 41-2272 and T-1032 in the sGC alpha(-/-)(1) mice of both genders. Moreover, the basal and SNP-stimulated cGMP levels and basal sGC activity were significantly lower in the sGC alpha(-/-)(1) mice. However, the relaxing effects of NO, BAY 41-2272 and YC-1 seen in blood vessels from sGC alpha(-/-)(1) mice indicate a role for an sGC alpha(1) independent mechanism. The increase in sGC activity after addition of BAY 41-2272 and the inhibition of the ACh-, SNP-, SNAP- and NO gas-induced response by the sGC inhibitor IH-[1,2,4]oxadiazolo[4,3-a]quinoxalin-l-one (ODQ) in the sGC alpha(-/-)(1) mice are observations suggesting that the sGC alpha(2)beta(1) isoform is also functionally active. However, the insignificant increase in cGMP in response to SNP and the non-upregulated sGC alpha(2) expression level in the sGCu alpha(-/-)(1) mice suggest rather the involvement of (an) sGC-independent mechanism(s). Conclusions: We conclude that sGCu alpha(1)beta(1) is involved in the vasorelaxation induced by NO-dependent and NO-independent sGC activators in both genders. However, the remaining relaxation seen in the sGC alpha(-/-)(1) mice suggests that besides sGC alpha(1)beta(1) also the minor isoform sGC alpha(2)beta(1) and/or (an) sGC-independent mechanism(s) play(s) a substantial role. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Dept Physiol & Physiopathol, Ghent 9000, Belgium. Univ Ghent, Dept Physiol & Physiopathol, Ghent, Belgium. Univ Ghent VIB, Dept Mol Biomed Res, Ghent, Belgium. Univ Ghent, Dept Mol Biol, Ghent, Belgium. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Van de Voorde, J (reprint author), Dept Physiol & Physiopathol, DePintelaan 185, Ghent 9000, Belgium. EM johan.vandevoorde@UGent.be OI Sips, Patrick/0000-0001-9241-5980 NR 33 TC 34 Z9 36 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD OCT 1 PY 2007 VL 76 IS 1 BP 149 EP 159 DI 10.1016/j.cardiores.2007.06.002 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 218OV UT WOS:000250025700018 PM 17610859 ER PT J AU Campbell, LL Polyak, K AF Campbell, Lauren L. Polyak, Kornelia TI Breast tumor heterogeneity SO CELL CYCLE LA English DT Article DE breast cancer; tumor heterogeneity; cancer stem cells; clonal evolution ID CANCER STEM-CELLS; IN-VITRO PROPAGATION; ADULT HUMAN BREAST; CLONAL EVOLUTION; INTRATUMORAL HETEROGENEITY; POPULATION ANALYSES; PROGENITOR CELLS; SOLID TUMORS; OLD IDEA; PROGRESSION AB Breast tumors are composed of a variety of cell types with distinct morphologies and behaviors. It is not clear how this tumor heterogeneity comes about. Two popular concepts that attempt to explain this are the cancer stem cell hypothesis and the clonal evolution model. Each of these ideas has been investigated for some time, leading to the accumulation of numerous findings that are used to support one or the other. Although the two views share some similarities, they are fundamentally different notions with very different clinical implications. Analysis of the research backing each concept, along with a review of the results of our recent study investigating putative breast cancer stem cells, suggests how the cancer stem cell hypothesis and the clonal evolution model may be involved in generating breast tumor heterogeneity. An understanding of this process will allow the development of more effective ways to treat and prevent breast cancer. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binny St D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu FU NCI NIH HHS [CA89393, CA94074] NR 78 TC 200 Z9 209 U1 4 U2 26 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 1 PY 2007 VL 6 IS 19 BP 2332 EP 2338 PG 7 WC Cell Biology SC Cell Biology GA 233IX UT WOS:000251085700004 PM 17786053 ER PT J AU Schild, S Tamayo, R Nelson, EJ Qadri, F Calderwood, SB Camilli, A AF Schild, Stefan Tamayo, Rita Nelson, Eric J. Qadri, Firclausi Calderwood, Stephen B. Camilli, Andrew TI Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment SO CELL HOST & MICROBE LA English DT Article ID RHODOBACTER-CAPSULATUS; TRANSPORT-SYSTEMS; MOLECULAR-CLONING; CHITIN CATABOLISM; BIOFILM FORMATION; IN-VITRO; DI-GMP; EXPRESSION; VIRULENCE; BACTERIA AB The facultative pathogen Vibrio cholerae can exist in both the human small bowel and in aquatic environments. While investigation of the infection process has revealed many factors important for pathogenesis, little is known regarding transmission of this or other water-borne pathogens. Using a temporally controlled reporter of transcription, we focus on bacterial gene expression during the late stage of infection and identify a unique class of V. cholerae genes specific to this stage. Mutational analysis revealed limited roles for these genes in infection. However, using a host-to-environment transition assay, we detected roles for six of ten genes examined for the ability of V. cholerae to persist within cholera stool and/or aquatic environments. Furthermore, passage through the intestinal tract was necessary to observe this phenotype. Thus, V. cholerae genes expressed prior to exiting the host intestinal tract are advantageous for subsequent life in aquatic environments. C1 Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol Microbiol, Boston, MA 02111 USA. Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. RP Camilli, A (reprint author), Tufts Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol Microbiol, Boston, MA 02111 USA. EM andrew.camilli@tufts.edu OI Schild, Stefan/0000-0001-7842-0177 FU NIAID NIH HHS [R01 AI055058-01, R01 AI055058-02, AI55058, R01 AI055058, R01 AI055058-03, R01 AI055058-04, R01 AI055058-05]; NIDDK NIH HHS [P30 DK034928, P30 DK34928] NR 45 TC 83 Z9 87 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD OCT PY 2007 VL 2 IS 4 BP 264 EP 277 DI 10.1016/j.chom.2007.09.004 PG 14 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 223IC UT WOS:000250362500009 PM 18005744 ER PT J AU Hyun, I Hochedlinger, K Jaenisch, R Yamanaka, S AF Hyun, Insoo Hochedlinger, Konrad Jaenisch, Rudolf Yamanaka, Shinya TI New Advances in iPS Cell Research Do Not Obviate the Need for Human Embryonic Stem Cells SO CELL STEM CELL LA English DT Editorial Material ID FIBROBLASTS C1 Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Kyoto Univ, Inst Frontier Med Sci, Dept Stem Cell Biol, Kyoto 6068507, Japan. Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama 3320012, Japan. RP Hyun, I (reprint author), Case Western Reserve Univ, Sch Med, Dept Bioeth, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM insoo.hyun@case.edu NR 7 TC 62 Z9 63 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD OCT PY 2007 VL 1 IS 4 BP 367 EP 368 DI 10.1016/j.stem.2007.09.006 PG 2 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XU UT WOS:000251055300007 PM 18371375 ER PT J AU Lengner, CJ Camargo, FD Hochedlinger, K Welstead, GG Zaidi, S Gokhale, S Scholer, HR Tomilin, A Jaenisch, R AF Lengner, Christopher J. Camargo, Fernando D. Hochedlinger, Konrad Welstead, G. Grant Zaidi, Sarnir Gokhale, Surnita Scholer, Hans R. Tomilin, Alexey Jaenisch, Rudolf TI Oct4 expression is not required for mouse somatic stem cell self-renewal SO CELL STEM CELL LA English DT Article ID MARROW STROMAL CELLS; BONE-MARROW; PROGENITOR CELLS; IN-VITRO; PERIPHERAL-BLOOD; PORCINE SKIN; GERM-CELLS; DIFFERENTIATION; PROLIFERATION; PLURIPOTENCY AB The Pou domain containing transcription factor Oct4 is a well-established regulator of pluripotency in the inner cell mass of the mammalian blastocyst as well as in embryonic stem cells. While it has been shown that the Oct4 gene is inactivated through a series of epigenetic modifications following implantation, recent studies have detected Oct4 activity in a variety of somatic stem cells and tumor cells. Based on these observations it has been suggested that Oct4 may also function in maintaining self-renewal of somatic stem cells and, in addition, may promote tumor formation. We employed a genetic approach to determine whether Oct4 is important for maintaining pluripotency in the stem cell compartments of several somatic tissues, including the intestinal epithelium, bone marrow (hematopoietic and mesenchymal lineages), hair follicle, brain, and liver. Oct4 gene ablation in these tissues revealed no abnormalities in homeostasis or regenerative capacity. We conclude that Oct4 is dispensable for both self-renewal and maintenance of somatic stem cells in the adult mammal. C1 MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Stem Cell Inst, Ctr Regenerat Med, Boston, MA 02114 USA. Max Planck Inst Mol Biomed, Dept Cell & Dev Biol, D-48149 Munster, Germany. Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. RP Jaenisch, R (reprint author), MIT, Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. EM jaenisch@wi.mit.edu RI Tomilin, Alexey/C-3361-2014; OI Tomilin, Alexey/0000-0002-1137-7167; Lengner, Christopher/0000-0002-0574-5189; Scholer, Hans/0000-0003-2643-5136 FU NCI NIH HHS [F32 CA119647-01, F32 CA119647, F32-CA119647, R01 CA087869, R01-CA087869, R37 CA084198, R37-CA084198]; NICHD NIH HHS [R01-HD0445022] NR 62 TC 234 Z9 247 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD OCT PY 2007 VL 1 IS 4 BP 403 EP 415 DI 10.1016/j.stem.2007.07.020 PG 13 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XU UT WOS:000251055300010 PM 18159219 ER PT J AU Arinobu, Y Mizuno, SI Chong, Y Shigematsu, H Lino, T Iwasaki, H Graf, T Mayfield, R Chan, S Kastner, P Akashi, K AF Arinobu, Yojiro Mizuno, Shin-ichi Chong, Yong Shigematsu, Hirokazu Lino, Tadafumi Iwasaki, Hiromi Graf, Thomas Mayfield, Robin Chan, Susan Kastner, Philippe Akashi, Koichi TI Reciprocal activation of GATA-1 and PU.1 marks initial specification of hematopoietic stem cells into myeloerythroid and myelolymphoid lineages SO CELL STEM CELL LA English DT Article ID SELF-RENEWAL CAPACITY; BONE-MARROW; TRANSCRIPTION FACTORS; COMMITTED PROGENITORS; RAG1 LOCUS; COMMITMENT; EXPRESSION; DIFFERENTIATION; IDENTIFICATION; BLOOD AB A hierarchical hematopoietic development with myeloid versus lymphoid bifurcation has been proposed downstream of the multipotent progenitor (MPP) stage, based on prospective isolation of progenitors capable of generating only myeloerythroid cells (common myeloid progenitor, CMP) or only lymphocytes (common lymphoid progenitor, CLP). By utilizing GATA-1 and PU.1 transcription factor reporters, here we identified progenitor populations that are precursors for either CMPs or CLPs. Two independent populations expressing either GATA-1 or PU.1 resided within the CD34(+)Sca-1(+)c-Kit(+) MPP fraction. The GATA-1(+) MPP displayed potent myeloerythroid potential without giving rise to lymphocytes, whereas the PU.l(+) MPP showed granulocyte/monocyte/lymphoid-restricted progenitor activity without megakaryocyte/erythroid differentiation. Furthermore, GATA-1+ and PU.1(+) MPPs possessed huge expansion potential and differentiated into the original CMPS and CLPs, respectively. Thus, the reciprocal activation of GATA-1 and PU.1 primarily organizes the hematopoietic lineage fate decision to form the earliest hematopoietic branchpoint that comprises isolatable myeloerythroid and myelo-lymphoid progenitor populations. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10461 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Univ Strasbourg 1, F-67000 Strasbourg, France. Inst Genet & Biol Mol & Cellulaire, INSERM, U596, CNRS,UMR 7104, Illkirch Graffenstaden, France. RP Akashi, K (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM koichi_akashi@dfci.harvard.edu RI Graf, Thomas/B-4252-2015 OI Graf, Thomas/0000-0003-2774-4117 FU NCI NIH HHS [CA072009]; NIDDK NIH HHS [DK050654, DK061320] NR 47 TC 161 Z9 163 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1934-5909 J9 CELL STEM CELL JI Cell Stem Cell PD OCT PY 2007 VL 1 IS 4 BP 416 EP 427 DI 10.1016/j.stem.2007.07.004 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA 232XU UT WOS:000251055300011 PM 18371378 ER PT J AU Choi, IJ Fujimoto, S Yamauchi, K Graham, DY Yamaoka, Y AF Choi, Il Ju Fujimoto, Saori Yamauchi, Kazuyoshi Graham, David Y. Yamaoka, Yoshio TI Helicobacter pylori environmental interactions: effect of acidic conditions on H-pylori-induced gastric mucosal interleukin-8 production SO CELLULAR MICROBIOLOGY LA English DT Article ID FACTOR-KAPPA-B; ENDOTHELIAL GROWTH-FACTOR; IL-8 GENE-EXPRESSION; EPITHELIAL-CELLS; LOW-PH; CLINICAL PRESENTATION; PROMOTER ACTIVATION; MESSENGER-RNA; SURFACE PH; CANCER AB To explore the interactions between the host, environment and bacterium responsible for the different manifestations of Helicobacter pylori infection, we examined the effect of acidic conditions on H. pylori-induced interleukin (IL)-8 expression. AGS gastric epithelial cells were exposed to acidic pH and infected with H. pylori [wild-type strain, its isogenic cag pathogenicity island (PAI) mutant or its oipA mutant]. Exposure of AGS cells to acidic pH alone did not enhance IL-8 production. However, following exposure to acidic conditions, H. pylori infection resulted in marked enhancement of IL-8 production which was independent of the presence of the cag PAI and OipA, indicating that H. pylori and acidic conditions act synergistically to induce gastric mucosal IL-8 production. In neutral pH environments H. pylori-induced IL-8 induction involved the NF-kappa B pathways, the extracellular signal-regulated kinase (ERK)-> c-Fos/c-Jun -> activating protein (AP-1) pathways, JNK -> c-Jun -> AP-1 pathways and the p38 pathways. At acidic pH H. pylori-induced augmentation of IL-8 production involved markedly upregulated the NF-kappa B pathways and the ERK -> c-Fos -> AP-1 pathways. In contrast, activation of the JNK -> c-Jun -> AP-1 pathways and p38 pathways were pH independent. These results might explain the clinical studies in which patients with duodenal ulcers had higher levels of IL-8 in the antral gastric mucosa than patients with simple H. pylori gastritis. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med Gastroenterol, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIDDK NIH HHS [R01 DK062813-05, DK62813, R01 DK062813, P30 DK056338, R01 DK062813-03, DK56338] NR 34 TC 13 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD OCT PY 2007 VL 9 IS 10 BP 2457 EP 2469 DI 10.1111/j.1462-5822.2007.00973.x PG 13 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 206ZP UT WOS:000249221700013 PM 17517062 ER PT J AU Ng, CY Weiss, MJ Boskovic, S Kawai, T Benichou, G Madsen, JC Wain, JC Allan, JS AF Ng, Choo Y. Weiss, Matthew J. Boskovic, Svjetlan Kawai, Tatsuo Benichou, Gilles Madsen, Joren C. Wain, John C. Allan, James S. TI Induction of mixed chimerism and transplantation tolerance in a non-human primate lung allograft model: Early results SO CHEST LA English DT Meeting Abstract CT CHEST 2007 Conference CY OCT 20-25, 2007 CL Chicago, IL SP Amer Coll Chest Phys C1 [Ng, Choo Y.; Weiss, Matthew J.; Boskovic, Svjetlan; Kawai, Tatsuo; Benichou, Gilles; Madsen, Joren C.; Wain, John C.; Allan, James S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2007 VL 132 IS 4 SU S BP 598S EP 598S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 222FY UT WOS:000250282700602 ER PT J AU Shapiro, S Waxman, A Schilz, R Strootman, D Rollins, K Feldman, BJ AF Shapiro, Shelley Waxman, Aaron Schilz, Robert Strootman, Deb Rollins, Kristan Feldman, B. Jeremy TI Multicenter experience with the rapid transition to intravenous treprostinil from epoprostenol in pulmonary arterial hypertension SO CHEST LA English DT Meeting Abstract CT CHEST 2007 Conference CY OCT 20-25, 2007 CL Chicago, IL SP Amer Coll Chest Phys C1 [Shapiro, Shelley; Waxman, Aaron; Schilz, Robert; Strootman, Deb; Rollins, Kristan; Feldman, B. Jeremy] W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2007 VL 132 IS 4 SU S BP 635S EP 635S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 222FY UT WOS:000250282700730 ER PT J AU Creaney, J van Bruggen, I Hof, M Segal, A Musk, AW de Klerk, N Horick, N Skates, SJ Robinson, BWS AF Creaney, Jenette van Bruggen, Ivonne Hof, Michelle Segal, Amanda Musk, Arthur W. de Klerk, Nick Horick, Nora Skates, Steven J. Robinson, Bruce W. S. TI Combined CA125 and mesothelin levels for the diagnosis of malignant mesothelioma SO CHEST LA English DT Article DE CA125; malignant mesothelioma; mesothelin; SMRP; tumor markers ID SERUM CA-125 LEVELS; PERITONEAL MESOTHELIOMA; OVARIAN-CARCINOMA; CANCER; MARKERS; ANTIGEN; EXPRESSION; FAMILY AB Background: Malignant mesothelioma is an aggressive, uniformly fatal tumor. Serum markers would be useful for the diagnosis of this disease. One potential marker is mesothelin. The purpose of this study was to study the mesothelin biomarker in a large patient cohort and to determine if another biomarker, CA125, improves on the sensitivity of mesothelin in the diagnosis of mesothelioma. Methods: Serum levels of mesothelin and CA125 were determined by commercially available assays in 117 samples obtained at diagnosis from patients with pleural malignant mesothelioma, 33 healthy, asbestos-exposed individuals, 53 patients with asbestos-related lung or pleural disease, and 30 patients presenting with benign pleural effusions. Cross-validated sensitivities were determined, and receiver operator characteristic curves were generated to compare the diagnostic accuracy of the biomarkers. Results: CA125 had a cross-validated sensitivity of 27% for mesothelioma patients at a specificity of 95% relative to asbestos-exposed individuals, or 50% relative to individuals with benign pleural effusions. Mesothelin had a cross-validated sensitivity of 52% for mesothelioma. patients, at a sensitivity of 95% relative to individuals with benign lung or pleural disease. CA125 and mesothelin levels were discordant in > 50% of mesothelioma patients. Combining the data from the two biomarkers using a logistic regression model did not improve sensitivity for detecting mesothelioma above that of the mesothelin marker alone. Conclusion: Combining mesothelin and CA125 data does not improve the sensitivity of mesothelioma. diagnosis over mesothelin alone. The use of both markers potentially increases the number of patients who can be monitored. C1 Univ Western Australia, Natl Res Ctr Asbestos Related Dis, Inst Med Res, Nedlands, WA 6009, Australia. Queen Elizabeth II Med Ctr, Perth, WA, Australia. Telethon Inst Child Hlth Res, Subiaco, WA, Australia. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. RP Creaney, J (reprint author), Sir Charles Gairdner Hosp, Natl Res Ctr Asbestos Related Dis, Verdun St, Nedlands, WA 6009, Australia. EM creaneyj@cyllene.uwa.edu.au RI Robinson, Bruce/N-1900-2014; de Klerk, Nicholas/D-8388-2016 OI de Klerk, Nicholas/0000-0001-9223-0767 NR 26 TC 56 Z9 59 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2007 VL 132 IS 4 BP 1239 EP 1246 DI 10.1378/chest.07-0013 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 221UY UT WOS:000250254000024 PM 17646232 ER PT J AU Dunn, IF Agarwalla, PK Papanastassiou, AM Butler, WE Smith, ER AF Dunn, Ian F. Agarwalla, Pankaj K. Papanastassiou, Alexander M. Butler, William E. Smith, Edward R. TI Multiple pilocytic astrocytomas of the cerebellum in a 17-year-old patient with neurofibromatosis type I SO CHILDS NERVOUS SYSTEM LA English DT Article DE neurofibromatosis I; multiple pilocytic astrocytomas; brain tumor; pediatric ID BRAIN-STEM; TUMORS AB Objective Approximately 10% of patients with neurofibromatosis I (NFI) patients will have central nervous system (CNS) tumors. The most common of these are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. While isolated pilocytic astrocytomas in NFI are well described, the appearance of multiple pilocytic astrocytomas in an individual patient is less common. The most frequent combination in NFI patients with more than one pilocytic astrocytoma is optic tract/hypothalamic and brainstem. Other combinations are exceedingly rare; multiple pilocytic astrocytomas have only been reported once in the cerebral hemispheres in a patient with NFI. This report presents the first documented case, to our knowledge, of multiple pilocytic astrocytomas in the cerebellum of a patient with NF1. Methods Case report. Conclusion The finding of multiple cerebellar pilocytic astrocytomas in a patient with NF1 is important because it expands the spectrum of presentations for patients with NF1 and also highlights specific diagnostic and therapeutic challenges faced by the treating physicians. The genetic and molecular basis of NF1 is reviewed. Strategies of diagnosis and treatment outlined here are relevant to both patients with NF1 and all patients with multiple posterior fossa tumors. C1 Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. RP Smith, ER (reprint author), Childrens Hosp, Dept Neurosurg, 300 Longwood Ave, Boston, MA 02115 USA. EM edward.smith@childrens.harvard.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0256-7040 J9 CHILD NERV SYST JI Childs Nerv. Syst. PD OCT PY 2007 VL 23 IS 10 BP 1191 EP 1194 DI 10.1007/s00381-007-0343-4 PG 4 WC Clinical Neurology; Pediatrics; Surgery SC Neurosciences & Neurology; Pediatrics; Surgery GA 208CO UT WOS:000249297600016 PM 17457593 ER PT J AU Sokolowska, M Borowiec, M Ptasinska, A Cieslak, M Shelhamer, JH Kowalski, ML Pawliczak, R AF Sokolowska, M. Borowiec, M. Ptasinska, A. Cieslak, M. Shelhamer, J. H. Kowalski, M. L. Pawliczak, R. TI 85-kDa cytosolic phospholipase A(2) group IV alpha gene promoter polymorphisms in patients with severe asthma: a gene expression and case-control study SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE airway inflammation; cytosolic phospholipase A(2); gene expression; microsatellites; severe asthma ID CYCLOOXYGENASE-2; INTERLEUKIN-8; CELLS AB Cytosolic phospholipase A(2) (cPLA(2)) group IVa is a critical enzyme involved in the liberation of arachidonic acid from cellular membranes. cPLA2 (-/-) mice have reduced allergen- induced bronchoconstriction and bronchial hyperresponsiveness. The goal of this study was to investigate polymorphisms of the (CA)(n) and (T)(n) microsatellites and surrounding regions in the cPLA(2)alpha gene promoter. We analysed the cPLA(2) promoter regions containing (CA) n and (T) (n) repeats in 87 patients with severe asthma and in 48 control subjects by bidirectional sequencing. Functional studies were performed utilizing reporter genes derived from subjects with varying numbers of these repeats, and on constructs with a series of deletions. We found that the (CA) n and (T) (n) regions are polymorphic and that constructs with CA or T repeats or CA and T repeats deleted revealed, respectively, a 41.8 +/- 7%, 22.3 +/- 5% and 100 +/- 20% increase in reporter gene activity. A lower number of CA or T repeats caused higher cPLA(2) promoter luciferase activity. The group of shorter alleles of the (CA) (n) microsatellite region ( n = 12 - 18) (P-cor = 0 . 00006), and the group of shorter alleles of ( T) (n) repeats region ( n = 17 - 38) (P-cor = 0 . 0039) occurred significantly more often in patients with severe asthma. We also found novel SNPs in positions - 292 C > G, - 185 A > C, - 180 T > C and - 165 A > C. Two of them were associated with the severe asthma phenotype: - 180T allele (P-cor = 0 . 03996) and - 185 A allele (P-cor = 0 . 03966). These results demonstrate that (CA)(n) and (T)(n) repeats may have an influence on cPLA(2) transcription which might play a role in severe asthma pathogenesis. C1 Med Univ Lodz, Dept Immunopathol, Chair Immunol, Lodz, Poland. Harvard Univ, Joslin Diabet Ctr, Boston, MA 02115 USA. Natl Inst Hlth, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD USA. Med Univ Lodz, Chair Immunol, Dept Rheumatol Immunol & Allergy, Lodz, Poland. RP Pawliczak, R (reprint author), Med Univ Lodz, Dept Immunopathol, Chair Immunol, Lodz, Poland. EM rafal.pawliczak@csk.umed.lodz.pl RI Borowiec, Maciej/S-9220-2016; Pawliczak, Rafal/S-9649-2016; OI Pawliczak, Rafal/0000-0001-6784-453X NR 21 TC 10 Z9 10 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD OCT PY 2007 VL 150 IS 1 BP 124 EP 131 DI 10.1111/j.1365-2249.2007.03459.x PG 8 WC Immunology SC Immunology GA 207UB UT WOS:000249275500015 PM 17672871 ER PT J AU Tolaney, SM Colson, YL Gill, RR Schulte, S Duggan, MM Shulman, LN Winer, EP AF Tolaney, Sara M. Colson, Yolanda L. Gill, Ritu R. Schulte, Stephanie Duggan, Margaret M. Shulman, Lawrence N. Winer, Eric P. TI Sarcoidosis mimicking metastatic breast cancer SO CLINICAL BREAST CANCER LA English DT Article DE invasive ductal carcinoma; invasive lobular carcinoma; nonnecrotizing granulomas; paclitaxel ID POSITRON-EMISSION-TOMOGRAPHY; FOLLOW-UP; MALIGNANCY; ASSOCIATION; THERAPY; NEOPLASMS; LESIONS; TUMORS; RISK AB The clinical and radiographic aspects of sarcoidosis and malignancy might mimic one another, making the distinction between the two difficult in some cases. Although there have been many theories on the link between sarcoidosis and malignancy, the association remains unproven. An unfortunate consequence of the presence of both entities in the same patient is the risk of misdiagnosis and incorrect treatment. We describe 3 patients who presented with locally advanced breast cancer and who were found to have pulmonary findings for metastatic disease that were proven upon biopsy to be consistent with sarcoidosis. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Thorac Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Surg Oncol, Boston, MA 02115 USA. RP Tolaney, SM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 220, Boston, MA 02115 USA. EM stolaney@partners.org NR 30 TC 10 Z9 10 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1526-8209 J9 CLIN BREAST CANCER JI Clin. Breast Cancer PD OCT PY 2007 VL 7 IS 10 BP 804 EP 810 DI 10.3816/CBC.2007.n.044 PG 7 WC Oncology SC Oncology GA 227ZG UT WOS:000250696000012 PM 18021484 ER PT J AU Germain, D Frank, DA AF Germain, Doris Frank, David A. TI Targeting the cytoplasmic and nuclear functions of signal transducers and activators of transcription 3 for cancer therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID POTENT ANTITUMOR-ACTIVITY; GROWTH-FACTOR RECEPTOR; NON-HODGKINS-LYMPHOMA; CYCLIN D1 EXPRESSION; BREAST-CANCER; SUPPRESSES GROWTH; MULTIPLE-MYELOMA; STAT3 ACTIVATION; IN-VIVO; TYROSINE PHOSPHORYLATION AB Signal transducers and activators of transcription (STAT) are a highly conserved family of transcription factors that are activated by phosphorylation in the cytoplasm, after which they translocate to the nucleus to regulate gene expression. Among the seven STATs, STAT3 is of particular interest due to its constitutive phosphorylation in a large proportion of human cancers and its ability to induce neoplastic transformation. Inhibition of STAT3 can reverse tumor growth in experimental systems while having few effects in normal cells. These findings have implicated STAT3 as a potentially important target for therapeutic intervention. In addition to its welldescribed role as a transcription factor, STAT3 has been found recently to have important effects in the cytoplasm, Collectively, these functions of STAT3 directly contribute to tumorigenesis, invasion, and metastasis. Given the potential importance of STAT3 as a target for cancer therapy, molecules have been developed that can block STAT3 function at a variety of steps. These drugs show promise as anticancer agents in model systems of a variety of common human cancers. Thus, elucidating the functions of STAT3 and developing agents to inhibit this protein remain important scientific and clinical challenges. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Mt Sinai Sch Med, Div Hematol & Oncol, Dept Med, New York, NY USA. RP Frank, DA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM david.frank@dfci.harvard.edu NR 61 TC 146 Z9 155 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5665 EP 5669 DI 10.1158/1078-0432.CCR-06-2491 PG 5 WC Oncology SC Oncology GA 218CN UT WOS:000249993700003 PM 17908954 ER PT J AU Mizukami, Y Kohgo, Y Chung, DC AF Mizukami, Yusuke Kohgo, Yutaka Chung, Daniel C. TI Hypoxia inducible factor-1-independent pathways in tumor angiogenesis SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; KAPPA-B ACTIVATION; COLON-CANCER CELLS; TRANSCRIPTION FACTOR; PROSTAGLANDIN E-2; UP-REGULATION; C-MYC; COLORECTAL-CANCER; VEGF EXPRESSION AB Among the factors that can stimulate angiogenesis, vascular endothelial growth factor has emerged as one of the most important, and inhibition of vascular endothelial growth factor has recently shown efficacy in the treatment of advanced colorectal cancer. Hypoxia develops within solid tumors and is one of the most potent stimuli of vascular endothelial growth factor expression. This effect is mediated primarily by hypoxia inducible factor-1 (HIF-1), often considered a master regulator of angiogenesis in hypoxia. Consequently, inhibition of HIF-1 has been proposed as a strategy to block tumor angiogenesis therapeutically. However, accumulating evidence indicates that HIF-independent pathways can also control angiogenesis. This review highlights some of the key signaling pathways independent of HIF-1 that can stimulate angiogenesis in hypoxia. Understanding the full spectrum of molecular pathways that control tumor angiogenesis is critical for the optimal design of targeted therapies. C1 Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, Asahikawa, Hokkaido 078, Japan. Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Med,Gastrointestinal Unit, Boston, MA 02115 USA. RP Mizukami, Y (reprint author), Asahikawa Med Coll, Div Gastroenterol & Hematol Oncol, Dept Med, 2-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078, Japan. EM mizu@asahikawa-med.ac.jp NR 55 TC 115 Z9 121 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5670 EP 5674 DI 10.1158/1078-0432.CCR-07-0111 PG 5 WC Oncology SC Oncology GA 218CN UT WOS:000249993700004 PM 17908955 ER PT J AU Mathew, P Thall, PF Bucana, CD Oh, WK Morris, MJ Jones, DM Johnson, MM Wen, S Pagliaro, LC Tannir, NM Tu, SM Meluch, AA Smith, L Cohen, L Kim, SJ Troncoso, P Fidler, IJ Logothetis, C AF Mathew, Paul Thall, Peter F. Bucana, Corazon D. Oh, William K. Morris, Michael J. Jones, Donnah M. Johnson, Marcella M. Wen, Sijin Pagliaro, Lance C. Tannir, Nizar M. Tu, Shi-Ming Meluch, Anthony A. Smith, Lon Cohen, Lorenzo Kim, Sun-Jin Troncoso, Patricia Fidler, Isaiah J. Logothetis, ChristopherJ. TI Platelet-derived growth factor receptor inhibition and chemotherapy for castration-resistant prostate cancer with bone metastases SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 18th European-Organisation-for-the-Research-and-Treatment-of-Cancer/National- Cancer-Institute/American-Association-for-Cancer-Research CY NOV 07-10, 2006 CL Prague, CZECH REPUBLIC SP Natl Canc Inst, Amer Assoc Canc Res, European Org Res & Treatment Canc ID PHASE-II TRIAL; PROGNOSTIC FACTORS; PERFORATION; IMATINIB; THERAPY; DRUGS; CELLS AB Purpose: To further assess preclinical and early clinical evidence that imatinib mesylate, a platelet derived growth factor receptor (PDGFR) inhibitor, modulates taxane activity in prostate cancer and bone metastases, a randomized study was conducted. Experimental Design: Men with progressive castration -resistant prostate cancer with bone metastases (n = 144) were planned for equal randomization to i.v. 30 Mg/m(2) clocetaxel on days 1, 8,15, and 22 every 42 days with 600 mg imatinib daily or placebo, for an improvement in median progression-free survival from 4.5 to 7.5 months (two-sided alpha = 0.05 and beta = 0.20). Secondary end points included differential toxicity and bone turnover markers, tumor phosphorylated PDGFR (p-PDGFR) expression, and modulation of p-PDGFR in peripheral blood leukocytes. Results: Accrual was halted early because of adverse gastrointestinal events. Among 116 evaluable men (57 clocetaxel + imatinib; 59 clocetaxel + placebo), respective median times to progression were 4.2 months (95% confidence interval, 3.1-7.5) and 4.2 months (95% confidence interval, 3.0-6.8; P = 0.58, log-rank test). Excess grade 3 toxicities (n = 23) in the clocetaxel + imatinib group were principally fatigue and gastrointestinal. Tumor p-PDGFR expression was observed in 12 of 14 (86%) evaluable bone specimens. In peripheral blood leukocytes, p-PDGFR reduction was more likely in clocetaxel + imatinib- treated patients compared with docetaxel + placebo (P < 0.0001), as were reductions in urine N-telopepticles (P = 0.004) but not serum bone-specific alkaline phosphatase (P = 0.099). Conclusions: These clinical and translational results question the value of PDGFR inhibition with taxane chemotherapy in prostate cancer bone metastases and are at variance with the preclinical studies. This discordance requires explanation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Behav Sci, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Canc Biol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Quantitat Sci, Houston, TX 77030 USA. Dana Farber Canc Inst, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Med, Genitourinary Oncol Serv, New York, NY 10021 USA. Sarah Cannon Canc Ctr, Nashville, TN USA. RP Mathew, P (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Unit 1374, 1155 Herman P Pressler, Houston, TX 77030 USA. EM pmathew@mdanderson.org RI Oh, William/B-9163-2012; OI Oh, William/0000-0001-5113-8147; Morris, Michael J./0000-0002-9454-0096 FU NCI NIH HHS [5-P50 CA090270-06] NR 34 TC 66 Z9 66 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5816 EP 5824 DI 10.1158/1078-0432.CCR-07-1269 PG 9 WC Oncology SC Oncology GA 218CN UT WOS:000249993700023 PM 17908974 ER PT J AU Huang, CY Beer, TM Higano, CS True, LD Vessella, R Lange, P Garzotto, M Nelson, PS AF Huang, Chung-Ying Beer, Tomasz M. Higano, Celestia S. True, Lawrence D. Vessella, Robert Lange, Paulh. Garzotto, Mark Nelson, Peter S. TI Molecular alterations in prostate carcinomas that associate with in vivo exposure to chemotherapy: Identification of a cytoprotective mechanism involving growth differentiation factor 15 SO CLINICAL CANCER RESEARCH LA English DT Article ID MACROPHAGE INHIBITORY CYTOKINE-1; GENE-EXPRESSION; NEOADJUVANT DOCETAXEL; BREAST-CANCER; PACLITAXEL RESISTANCE; RADICAL PROSTATECTOMY; MITOXANTRONE; CDNA; PREDNISONE; DIAGNOSIS AB Purpose: To identify molecular alterations associating with in vivo exposure of prostate carcinoma to chemotherapy and assess functional roles modulating tumor response and resistance. Experimental Design: Patients with high-risk localized prostate cancer (tumor-nodemetastasis >= T-2b or prostate-specific antigen 15 ng/mL or Gleason glacle. >= 4+3) were enrolled into a phase II clinical trial of neoadjuvant chemotherapy with clocetaxel and mitoxantrone followed by prostatectomy. Pretreatment prostate tissue was acquired by needle biopsy and posttreatment tissue was acquired by prostatectomy. Prostate epithelium was captured by microdissection, and transcript levels were quantitated by cDNA microarray hybridization. Gene expression changes associated with chemotherapy were determined by a random variance t test. Several were verified by quantitative reverse transcription PCR. In vitro analyses determining the influence of growth differentiation factor 15 (GDF15) on chemotherapy resistance were done. Results: Gene expression changes after chemotherapy were measured in 31 patients who completed four cycles of neoadjuvant chemotherapy. After excluding genes shown previ6usly to be influenced by the radical prostatectomy procedure, we identified 51 genes with significant transcript level alterations following chemotherapy. This group included several cytokines, including GDF15, chemokine (C-X-C motif) ligand 10, and interleukin receptor 1 p, Overexpression of GDF15 or exposure of prostate cancer cell lines to exogenous recombinant GDF15 conferred resistance to clocetaxel and mitoxantrone. Conclusions: Consistent molecular alterations were identified in prostate cancer cells exposed to clocetaxel and mitoxantrone chemotherapy. These alterations include transcripts encoding cytokines known to be regulated through the nuclear factor-kappa B pathway. Chemotherapy- induced cytokines and growth factors, such as GDF15, contribute to tumor cell therapy resistance and may serve as targets to improve responses. C1 Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Seattle, WA 98105 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Med, Inst Canc, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Urol, Inst Canc, Portland, OR 97201 USA. Portland VA Med Ctr, Urol Sect, Portland, OR USA. RP Nelson, PS (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Mailstop D4-100,1100 Fairview Ave, Seattle, WA 98105 USA. EM pnelson@fhcrc.org FU NCI NIH HHS [CA97186, P01 CA098912, R01 CA119125] NR 30 TC 40 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5825 EP 5833 DI 10.1158/1078-0432.CCR-07-1037 PG 9 WC Oncology SC Oncology GA 218CN UT WOS:000249993700024 PM 17908975 ER PT J AU Liu, TC Wakimoto, H Martuza, RL Rabkin, SD AF Liu, Ta-Chiang Wakimoto, Hiroaki Martuza, Robert L. Rabkin, Samuel D. TI Herpes simplex virus Us3(-) mutant as oncolytic strategy and synergizes with phosphatidylinositol 3-kinase-akt-targeting molecular therapeutics SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE U(S)3; PHASE-I; FUTURE-DIRECTIONS; BLOCKS APOPTOSIS; CANCER; TYPE-2; GENE; PATHWAY; HERPES-SIMPLEX-VIRUS-1; REPLICATION AB Purpose: Oncolytic herpes simplex virus (HSV) vectors have shown safety in clinical trials, but efficacy remains unsatisfactory. Novel HSV vectors that possess tumor selectivity with enhanced potency are therefore needed. The gene product of HSV Us3 protects virus-infected cells from apoptosis, a cellular pathway frequently dysfunctional in tumors. We hypothesized that Us3 mutants, whose replication would be inhibited by apoptosis in normal cells, would be selective for tumor cells. Experimental Design: HSV mutants G207 (ribonucleotide reductase-/gamma 34.5(-)), R7041 (Us3(-)), and R7306 (Us3 revertant) were tested in normal and tumor cells for viral replication, antitumoral potency, apoptosis induction, and Akt activation. Safety and biodistribution after systemic administration and antitumoral efficacy after intratumoral (i.t.) or i.v. administration were examined. Results: Us3 deletion results in up to 3-log replication inhibition in normal cells, which correlates with enhanced apoptosis induction. In contrast, R7041 replicates very well in tumor cells, showing 1 to 2 log greater yield than G207. In vivo, R7041 shows no signs of toxicity after systemic delivery in both immunocompetent and immunodeficient mice and shows preferential and prolonged replication in tumors compared with normal tissues. R7041 displays significant antitumoral efficacy after i.t. or i.v. administration. An additional feature of Us3 mutants is enhanced Akt activation compared with wild-type infection, which sensitizes cells to phosphatidylinositol 3-kinase-Akt inhibitors (LY294002, Akt inhibitor IV), shown by synergistic antitumoral activity in vitro and enhanced efficacy in vivo. Conclusions: Us3 deletion confers enhanced tumor selectivity and antitumoral potency on herpes simplex virus-1 and provides for a novel mechanism of combination therapy with phosphaticlylinositol 3-kinase-Akt-targeting molecular therapeutics. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Res Ctr,Mol Neurosurg Lab, Boston, MA 02114 USA. RP Liu, TC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Brain Tumor Res Ctr,Mol Neurosurg Lab, CPZN-3800 Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM tachiangliu@yahoo.com RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [CA102139]; NINDS NIH HHS [NS32677] NR 38 TC 19 Z9 20 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5897 EP 5902 DI 10.1158/1078-0432.CCR-07-1013 PG 6 WC Oncology SC Oncology GA 218CN UT WOS:000249993700034 PM 17908985 ER PT J AU Neri, P Kumar, S Fulciniti, MT Vallet, S Chhetri, S Mukherjee, S Tai, YT Chauhan, D Tassone, P Venuta, S Munshi, NC Hideshima, T Anderson, KC Raje, N AF Neri, Paola Kumar, Shaji Fulciniti, Maria Teresa Vallet, Sonia Chhetri, Shweta Mukherjee, Sidhartha Tai, YuTzu Chauhan, Dharminder Tassone, Pierfrancesco Venuta, Salvatore Munshi, Nikhil C. Hideshima, Teru Anderson, Kenneth C. Raje, Noopur TI Neutralizing B-cell-activating factor antibody improves survival and inhibits osteoclastogenesis in a severe combined Immunodeficient human multiple myeloma model SO CLINICAL CANCER RESEARCH LA English DT Article ID NECROSIS-FACTOR FAMILY; IN-VIVO MODEL; NF-KAPPA-B; BONE-MARROW; DRUG-RESISTANCE; LYMPHOCYTE STIMULATOR; AUTOIMMUNE-DISEASE; TNF RECEPTOR; BAFF-R; GROWTH AB Purpose: B-cell - activating factor (BAFF) is a tumor necrosis factor superfamily member critical for the maintenance and homeostasis of normal B-cell development. It has been implicated in conferring a survival advantage to B-cell malignancies, including multiple myeloma (MM). Experimental Design: Here, we validate the role of BAFF in the in vivo pathogenesis of MM examining BAFF and its receptors in the context of patient MM cells and show activity of antiBAFF antibody in a severe combined immunodeficient model of human MM. Results: Gene microarrays and flow cytometry studies showed increased transcripts and the presence of all three receptors for BAFF in CD138(+) patient MM cells, as well as an increase in plasma BAFF levels in 51 MM patients. Functional studies show that recombinant BAFF protects MM cells against dexa methasone-induced apoptosis accompanied by an increase in survival proteins belonging to the BCL family. These in vitro studies led to the evaluation of a clinical grade-neutralizing antibody to BAFF in a severe combined immunodeficient human MM model. Anti-BAFF - treated animals showed decreased soluble human interleukin 6 receptor levels, a surrogate marker of viable tumor, suggesting direct anti-MM activity. This translated into a survival advantage of 16 days (P < 0.05), a decrease in tartrate-resistant acid phosphatase-positive osteoclasts, and a reduction in radiologically evident lytic lesions in anti-BAFF-treated animals. Conclusions: Our data show a role for BAFF as a survival factor in W Importantly, the in vivo antitumor activity of neutralizing anti-BAFF antibody provide the preclinical rationale for its evaluation in the treatment of MM. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Hlthcare Syst, Boston, MA USA. Magna Graecia Univ Catanzaro, Ctr Canc, Catanzaro, Italy. RP Raje, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, PO Box 218,55 Fruit St, Boston, MA 02114 USA. EM nraje@partners.org FU PHS HHS [P50-100707, P01-78378, R01-50947] NR 48 TC 71 Z9 73 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2007 VL 13 IS 19 BP 5903 EP 5909 DI 10.1158/1078-0432.CCR-07-0753 PG 7 WC Oncology SC Oncology GA 218CN UT WOS:000249993700035 PM 17908986 ER PT J AU Ray, IB Fendelander, L Singh, JP AF Ray, Indranill Basu Fendelander, Lahn Singh, Jagmeet P. TI Cardiac resynchronization therapy and its potential proarrhythmic effect SO CLINICAL CARDIOLOGY LA English DT Article DE cardiac resynchronization; proarrhythmia; pacemakers; implantable devices; defibrillators; heart failure; sudden cardiac death ID BIVENTRICULAR PACING DECREASES; SYMPTOMATIC HEART-FAILURE; VENTRICULAR-TACHYCARDIA; TRANSMURAL DISPERSION; EJECTION FRACTION; CONDUCTION DELAY; RATE-VARIABILITY; QT INTERVAL; REPOLARIZATION; DEFIBRILLATOR AB Cardiac resynchronization therapy (CRT) has become an established adjunctive treatment to optimal pharmacologic therapy in patients with advanced chronic heart failure (CHF), diminished left ventricular (LV) function and intraventricular conduction delay. Although CRT has been shown to improve ventricular hemodynamics, quality of life and exercise capacity, there is some evidence that it may rarely potentiate ventricular arrhythmias. As CRT is considered for an expanded population of CHF patients, and left-sided pacing is considered as an option for pacemaker-indicated patients (potentially without defibrillator backup), the effect of these pacing modalities on the incidence of ventricular tachyarrhythmia must be systematically studied and mechanistically understood. Strategies to prospectively predict the proarrhythmic potential of LV epicardial pacing need to be developed, and therapy accordingly individualized. This review attempts to summarize the current information on proarrhythmia in resynchronization therapy. C1 Harvard Thorndike Electrophysiol Inst, Dept Med, Beth Israel Deaconess Med Ctr, Guidant Corp, St Paul, MN USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Med, Cardiac Arrythmia Serv, Boston, MA USA. RP Singh, JP (reprint author), Massachusetts Gen Hosp, Cardiac Arrythmia Serv Heart Ctr, 55 Fruit St,Gray-Bigelow 109, Boston, MA 02114 USA. EM jsingh@partners.org RI Basu Ray, Indranill/D-3794-2011 NR 38 TC 11 Z9 12 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD OCT PY 2007 VL 30 IS 10 BP 498 EP 502 DI 10.1002/clc.17 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 222US UT WOS:000250323500003 PM 17823906 ER PT J AU Michael, P Rumsfeld, JS Peterson, PN Masoudi, FA Strunk, A Ross, C Lyons, EE Smith, SS Lauer, MS Magid, DJ AF Michael, P. Rumsfeld, John S. Peterson, Pamela N. Masoudi, Frederick A. Strunk, Adam Ross, Colleen Lyons, Ella E. Smith, S. Scott Lauer, Michael S. Magid, David J. TI Chest pain on exercise treadmill test predicts future cardiac Hospitalizations SO CLINICAL CARDIOLOGY LA English DT Article DE treadmill testing; epidemiology; morbidity ID CORONARY-ARTERY DISEASE; MYOCARDIAL-INFARCTION; MORTALITY; ISCHEMIA; DEATH; MEN; PROGNOSIS; SILENT; SCORE AB Background: Patients often have chest pain during exercise treadmill testing (ETT). However, the evidence supporting chest pain as an independent adverse prognostic factor during ETT has been inconsistent. The objective of this study was to determine the importance of chest pain during ETT in predicting future nonfatal cardiac hospitalizations. Methods: This was a prospective cohort study of all patients undergoing ETT between July 2001 and June 2004 in a large managed care organization. The primary outcome of interest was nonfatal cardiac hospitalizations including myocardial infarction and unstable angina. Multivariable Cox proportional hazards regression assessed the independent association between chest pain during ETT and subsequent nonfatal cardiac hospitalizations, adjusting patient, clinical and other treadmill variables. Results: Of the 8,459 patients undergoing ETT, 697 (8.2%) patients had chest pain during the test. Patients with chest pain during ETT had more nonfatal cardiac hospitalizations compared to patients without chest pain (11.9% vs. 2.6%; p < 0.0001). In multivariable Cox regression analysis, patients with chest pain during ETT remained at significantly increased risk of nonfatal cardiac hospitalizations (HR 3.44; 95% CI 2.60-4.56). The association between chest pain and adverse outcomes was consistent among prespecified subgroups including patients without ST-segment changes and with good functional capacity on ETT. Conclusions: Chest pain during ETT, even without ECG changes, predicts subsequent cardiac hospitalizations. Future studies should evaluate whether aggressive management of such patients can prevent subsequent hospitalizations. C1 Denver VA Med Ctr, Denver, CO USA. Univ Colorado Hllt Sci Ctr, Denver, CO USA. Dencer Hlth Med Ctr, Denver, CO USA. Clin Res Unit, Denver, CO USA. Internal Med, Kaiser Permanente Colorado, Denver, CO USA. Cleveland Clin Fdn, Cleveland, OH USA. RP Michael, P (reprint author), 1055 Clermont St,111b, Denver, CO 80220 USA. EM Michael.ho@uchsc.edu RI Lauer, Michael/L-9656-2013 OI Lauer, Michael/0000-0002-9217-8177 NR 17 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD OCT PY 2007 VL 30 IS 10 BP 505 EP 510 DI 10.1002/clc.20139 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 222US UT WOS:000250323500004 ER PT J AU Scirica, BM Morrow, DA Cannon, CP de Lemos, JA Murphy, S Sabatine, MS Wiviott, SD Rifai, N McCabe, CH Braunwald, E AF Scirica, Benjamin M. Morrow, David A. Cannon, Christopher P. de Lemos, James A. Murphy, Sabina Sabatine, Marc S. Wiviott, Stephen D. Rifai, Nader McCabe, Carolyn H. Braunwald, Eugene CA Study Grp TI Clinical application of C-reactive protein across the spectrum of acute coronary syndromes SO CLINICAL CHEMISTRY LA English DT Article ID ACUTE-MYOCARDIAL-INFARCTION; LONG-TERM MORTALITY; UNSTABLE ANGINA; RISK STRATIFICATION; ARTERY-DISEASE; TROPONIN-I; CARDIOVASCULAR-DISEASE; CONSECUTIVE PATIENTS; NATRIURETIC PEPTIDE; HEART-FAILURE AB Background: High-sensitivity C-reactive protein (hsCRP) is associated with adverse cardiovascular outcomes in acute coronary syndromes (ACS). The ability to formulate recommendations regarding clinical use of hsCRP is limited by a paucity of data regarding several key issues. The purpose of this study was to evaluate hsCRP across the spectrum of ACS. Methods: hsCRP was measured on admission in 3225 patients with ACS. hsCRP concentrations were compared in patients who suffered an adverse cardiac outcome within 10 months of study entry and in patients who had no adverse event. Because of heterogeneity in the relationship between hsCRP and clinical outcomes, evaluation was limited to patients from whom samples were collected within 48 h of symptom onset. Results: Patients in the highest quartile of hsCRP compared to those in the lowest quartile were at increased risk of death at 30 days [adjusted hazard ratio (adjHR) 4.6, P <0.0011 and 10 months (adjHR 3.9, P <0.001). In patients with unstable angina/non-ST-elevation myocardial infarction (STEMI), hsCRP >3 mg/L was associated with increased 10-month mortality (adjHR 2.3, P = 0.002), whereas in STEMI a relationship with mortality was seen at hsCRP >10 mg/L (adjHR 3.0, P = 0.008). Increased concentrations of hsCRP were strongly associated with the development of heart failure at 30 days (adjHR 8.2, P = 0.001) and 10 months (adjHR 2.6, P 0.014). Conclusion: Increased baseline concentrations of hsCRP are strongly associated with mortality and heart failure across the ACS spectrum. hsCRP measurement should be performed early after presentation and index diagnosis-specific cutpoints should be used. (c) 2007 American Association for Clinical Chemistry C1 Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, Boston, MA 02461 USA. RP Scirica, BM (reprint author), Brigham & Womens Hosp, Dept Med, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02461 USA. EM bscirica@partners.org NR 32 TC 51 Z9 62 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2007 VL 53 IS 10 BP 1800 EP 1807 DI 10.1373/clinchem.2007.087957 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 216LJ UT WOS:000249879200011 PM 17717132 ER PT J AU Welzel, TM Graubard, BI El-Serag, HB Shaib, YH Hsing, AW Davila, JA McGlynn, KA AF Welzelt, Tania M. Graubard, Barry I. El-Serag, Hashem B. Shaib, Yasser H. Hsing, Ann W. Davila, Jessica A. McGlynn, Katherine A. TI Risk factors for intrahepatic and extrahepatic Cholangiocarcinoma in the United States: A population-based case-control study SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID PRIMARY SCLEROSING CHOLANGITIS; HEPATITIS-C-VIRUS; FATTY LIVER-DISEASE; HEPATOCELLULAR-CARCINOMA; HELICOBACTER-PYLORI; NATURAL-HISTORY; STEM-CELLS; STEATOSIS; HEPATOLITHIASIS; CIRRHOSIS AB Background & Aims: Intrahepatic and extrahepatic cholangiocarcinomas are rare and highly malignant cancers of the bile duct. Although the incidence of extrahepatic cholangiocarcinoma (ECC) has remained constant, the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the United States. Because the etiology of both tumors is poorly understood, a population-based case-control study was conducted to examine the association of ECC and ICC with preexisting medical conditions. Methods: Medical conditions among 535 ICC patients, 549 ECC patients (diagnosed 1993-1999), and 102,782 cancer-free controls were identified by using the Surveillance, Epidemiology and End Results-Medicare databases. Logistic regression analysis was used to calculate adjusted odds ratios. Results: In addition to established risk factors (choledochal cysts, cholangitis, inflammatory bowel disease), several other conditions were significantly associated with ECC and ICC: biliary cirrhosis (ECC, ICC: P <.001), cholelithiasis (ECC, ICC: P <.001), alcoholic liver disease (ECC, P <.001; ICC, P =.01), nonspecific cirrhosis (ECC, ICC: P <.001), diabetes (ECC, ICC: P <.001), thyrotoxicosis (ECC, P =.006; ICC, P =.04), and chronic pancreatitis (ECC, ICC: P <.001). Conditions only associated with ICC were obesity (ECC, P =.71; ICC, P =.01), chronic nonalcoholic liver disease (ECC, P =.08; ICC, P =.02), HCV infection (ECC, P =.67; ICC, P =.01), and smoking (ECC, P =.07; ICC, P =.04). Conclusions: Several novel associations with ECC and ICC were identified. HCV infection, chronic nonalcoholic liver disease, and obesity, all of which are increasing in incidence, and smoking were associated only with ICC, suggesting that these conditions might explain the divergent incidence trends of the tumors. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Michael E Debakey Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Michael E Debakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Welzel, TM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,EPS Suite 550,MSC-7234, Bethesda, MD 20892 USA. EM weizelt@mall.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 53 TC 201 Z9 211 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2007 VL 5 IS 10 BP 1221 EP 1228 DI 10.1016/j.cgh.2007.05-020 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223IN UT WOS:000250363600019 PM 17689296 ER PT J AU Wheat, LJ Freifeld, AG Kleiman, MB Baddley, JW McKinsey, DS Loyd, JE Kauffman, CA AF Wheat, L. Joseph Freifeld, Alison G. Kleiman, Martin B. Baddley, John W. McKinsey, David S. Loyd, James E. Kauffman, Carol A. TI Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the infectious diseases society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; CHRONIC PULMONARY HISTOPLASMOSIS; AMPHOTERICIN-B; MEDIASTINAL FIBROSIS; TRANSPLANT RECIPIENTS; ITRACONAZOLE THERAPY; FUNGAL-INFECTIONS; CEREBRAL HISTOPLASMOSIS; FLUCONAZOLE THERAPY AB Evidence-based guidelines for the management of patients with histoplasmosis were prepared by an Expert Panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 30: 688-95). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. Since 2000, several new antifungal agents have become available, and clinical trials and case series have increased our understanding of the management of histoplasmosis. Advances in immunosuppressive treatment for inflammatory disorders have created new questions about the approach to prevention and treatment of histoplasmosis. New information, based on publications from the period 1999-2006, are incorporated into this guideline document. In addition, the panel added recommendations for management of histoplasmosis in children for those aspects that differ from aspects in adults. C1 MiraVista Diagnosit MiraBella Technol, Indianapolis, IN 46241 USA. Indiana Univ, Sch Med, Indianapolis, IN 46241 USA. Univ Nebraska Med Ctr, Omaha, NE USA. Univ Alabama, Birmingham, AL 35487 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Michigan, Sch Med, Vet Affairs Med Ctr, Ann Arbor, MI USA. RP Wheat, LJ (reprint author), MiraVista Diagnosit MiraBella Technol, 4444 Decatur Blvd,Ste 300, Indianapolis, IN 46241 USA. EM jwheat@miravistalabs.com NR 105 TC 314 Z9 333 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 1 PY 2007 VL 45 IS 7 BP 807 EP 825 DI 10.1086/521259 PG 19 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 207FV UT WOS:000249237900001 PM 17806045 ER PT J AU Sheehy, N Israel, DA AF Sheehy, Niall Israel, David A. TI Acute varicella infection mimics recurrent Hodgkin's disease on F-18 FDG PET/CT SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE positron-emission tomography; chickenpox; varicella; fluorodeoxyglucose; Hodgkin disease ID POSITRON-EMISSION-TOMOGRAPHY; LYMPHOMA AB We report a case where acute varicella infection, chickenpox, mimics the findings of recurrent Hodgkin disease on F-18 FDG PET/CT. A 28-year-old man with a history of Hodgkin disease in remission had fatigue, pyrexia, and a raised ESR. His F-18 FDG PET/CT, performed to exclude lymphoma recurrence, demonstrated FDG-avid lymphadenopathy and increased FDG uptake in his spleen. A day later he developed the generalized rash of acute varicella infection. This was managed with valacyclovir. Repeat F-18 FDG PET/CT done I month later showed no evidence of FDG-avid disease. In this patient the stimulation of an immune response by the acute viral infection mimics recurrent lymphoma. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sheehy, N (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM nsheehy@partners.org NR 8 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2007 VL 32 IS 10 BP 820 EP 821 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216MT UT WOS:000249882800017 PM 17885370 ER PT J AU Sheehy, N Israel, DA AF Sheehy, N. Israel, D. A. TI Findings on (18)FDG-PET imaging in statin-induced rhabdomyolysis SO CLINICAL RADIOLOGY LA English DT Article C1 Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. RP Sheehy, N (reprint author), Dana Farber Canc Inst, Dept Radiol, 44 Binney St, Boston, MA 02115 USA. EM nsheehy@partners.org NR 5 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD OCT PY 2007 VL 62 IS 10 BP 1012 EP 1014 DI 10.1016/j.crad.2007.04.010 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 215BU UT WOS:000249784100015 PM 17765468 ER PT J AU Chen, NC Brand, JC Brown, CH AF Chen, Neal C. Brand, Jeff C., Jr. Brown, Charles H. TI Biomechanics of intratunnel anterior cruciate ligament graft fixation SO CLINICS IN SPORTS MEDICINE LA English DT Article ID INTERFERENCE SCREW FIXATION; HAMSTRING TENDON GRAFTS; SOFT-TISSUE GRAFTS; BONE-MINERAL DENSITY; PATELLAR TENDON; INSERTION TORQUE; PULLOUT STRENGTH; TIBIAL TUNNEL; FOLLOW-UP; ABSORBABLE INTERFERENCE AB Interference screw fixation of bone-patellar tendon-bone grafts now is considered the standard against which all ACL graft-fixation techniques are compared, but mechanical fixation of the ACL graft in the bone tunnels is the weak link in the early postoperative period. This article discusses some of the limitations of in vitro biomechanical studies and reviews variables that influence the tensile properties of intratunnel fixation methods for bone-tendon-bone and soft tissue grafts. C1 Alexandria Orthopaed & Sports Med Assoc, Alexandria, MN 56308 USA. Combined Harvard Orthopaed Residency Progam, Boston, MA USA. Massachusetts Gen Hosp, Hand & Upper Extrem Serv, Boston, MA 02114 USA. Hosp Special Surg, Sports Med & Shoulder Serv, New York, NY 10021 USA. Abu Dhabi Knee & Sports Med Ctr, Abu Dhabi 43330, U Arab Emirates. RP Brand, JC (reprint author), Alexandria Orthopaed & Sports Med Assoc, 1500 Irving, Alexandria, MN 56308 USA. EM bjbrand@info-link.net NR 72 TC 11 Z9 13 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 0278-5919 J9 CLIN SPORT MED JI Clin. Sports Med. PD OCT PY 2007 VL 26 IS 4 BP 695 EP + DI 10.1016/j.csm.2007.06.009 PG 21 WC Sport Sciences SC Sport Sciences GA 231SZ UT WOS:000250970600014 PM 17920961 ER PT J AU Oster, TJ Anderson, A Filley, CM Wortzel, HS Arciniegas, DB AF Oster, Timothy J. Anderson, Alan Filley, Christopher M. Wortzel, Hal S. Arciniegas, David B. TI Quetiapine for mania due to traumatic brain injury SO CNS SPECTRUMS LA English DT Article ID ATYPICAL ANTIPSYCHOTIC TREATMENT; PLACEBO-CONTROLLED TRIALS; BIPOLAR DISORDER; HEAD-INJURY; RANDOMIZED-TRIAL; VALPROATE; SCHIZOPHRENIA; CARBAMAZEPINE; HALOPERIDOL; RISPERIDONE AB Secondary mania develops in as many as 9% of persons with traumatic brain injuries. The treatment of posttraumatic mania is not well defined, and agents traditionally used for the treatment of idiopathic manic episodes may not be well suited for use among individuals wit h traumatic brain injuries. Atypical antipsychotics are indicated for the treatment of idiopathic bipolar disorder, and have been used for other purposes among individuals with posttraumatic neu ro psychiatric disturbances. This article offers the first description of the treatment of posttraumatic mania using the atypical antipsychotic quetiapine. Beneficial effects of this agent on posttraumatic mania, cognitive impairments, and functional disability in the subacute post-injury period are described. Possible mechanisms of action are discussed and the need for additional investigation of quetiapine for posttraumatic mania is highlighted. C1 Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Denver, CO 80262 USA. HealthONE Spalding Rehabil Hosp, Brain Injury Rehabil Unit, Aurora, CO USA. Univ Colorado, Sch Med, Dept Neurol, Behav Neurol Sect, Boulder, CO 80309 USA. Denver Vet Affairs Med Ctr, VISN MIRECC 19, Denver, CO USA. RP Arciniegas, DB (reprint author), Univ Colorado, Sch Med, Dept Psychiat, Neurobehav Disorders Program, Campus Box C268-25,4200 E 9th Ave, Denver, CO 80262 USA. EM David.Arciniegas@UCHSC.edu RI Arciniegas, David/A-3792-2009 NR 59 TC 10 Z9 10 U1 0 U2 1 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2007 VL 12 IS 10 BP 764 EP 769 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223HE UT WOS:000250359900010 PM 17934381 ER PT J AU Li, MW Biggers, JD Toner, M Griffey, SM Lloyd, KCK AF Li, Ming-Wen Biggers, John D. Toner, Mehmet Griffey, Stephen M. Lloyd, K. C. Kent TI Phenotypic analysis of C57BL/6j and FVB/NJ mice generated using evaporatively dried spermatozoa SO COMPARATIVE MEDICINE LA English DT Article ID IN-VITRO FERTILIZATION; INTRACYTOPLASMIC SPERM INJECTION; LONG-TERM PRESERVATION; MOUSE SPERMATOZOA; CRYOPRESERVED SPERMATOZOA; INTRACELLULAR TREHALOSE; MAMMALIAN-CELLS; ABILITY; TEMPERATURE; INTEGRITY AB Combination of evaporative drying and frozen storage at -80 degrees C has been used successfully to preserve hybrid 136132171 mouse spermatozoa. To determine whether this method can be applied equally well to inbred mice, spermatozoa of C57BL/6J and FVB/ NJ mice were evaporatively dried and stored for 1 mo at -80 degrees C before being used for intracytoplasmic sperm injection (ICSI) to produce live offspring. After weaning, 1 male and 1 female mouse from each litter were randomly selected at 8 wk of age for natural mating to produce live offspring. Results showed that spermatozoa from both inbred strains that had been evaporatively dried and subsequently stored at -80 degrees C could be used successfully to derive live, healthy, and reproductively sound offspring by ICSI. No significant differences were found in embryo transfer rate (number of pups born/number of embryos transferred), litter size, weaning rate, body weight, number of pathologic lesions, and amount of contamination by pathogens of mice produced by ICSI using evaporatively dried spermatozoa compared with mice produced by natural mating or by ICSI using fresh (that is, nonpreserved) spermatozoa. Progeny produced by mating mice generated from ICSI using evaporatively dried spermatozoa were normal. Therefore, spermatozoa from inbred mouse strains C57BL/6J and FVB/NJ can be preserved successfully after evaporative drying and frozen storage at -80 degrees C. C1 Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. Univ Calif Davis, Sch Vet Med, Comparat Pathol Lab, Davis, CA 95616 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA USA. Shriners Hosp Children, Boston, MA USA. RP Lloyd, KCK (reprint author), Univ Calif Davis, Sch Vet Med, Ctr Comparat Med, Davis, CA 95616 USA. EM kclloyd@ucdavis.edu FU NCRR NIH HHS [U42 RR14905, R24 RR018934] NR 29 TC 3 Z9 3 U1 1 U2 5 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD OCT PY 2007 VL 57 IS 5 BP 469 EP 475 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 223JV UT WOS:000250367200005 PM 17974129 ER PT J AU Cai, WL AF Cai, Wenli TI 3D planar reformation of vascular central axis surface with biconvex slab SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS LA English DT Article DE computed tomographic angiography (CTA); vessel visualizations; curved multi-planar reformation ID CT ANGIOGRAPHY; EXTRACTION; ALGORITHM AB Curved multi-planar reformation (curved MPR) is one of the commonly used vascular visualization methods in clinics. It re-samples and visualizes the vascular central axis surface (WAS), which is a curved surface passing through the vascular central axis (VCA) or vessel centerline. The rotation of the WAS along the VCA generates a set of 2D images. In this paper, we introduce a 3D curved MPR method, WAS planar reformation (VPR) by a convex hull, called a biconvex slab. The entire vessel is enclosed within a biconvex slab and rendered in one image by volume rendering, such as MIP or X-ray. The method is applied to computed tomographic angiography (CTA) data sets. The resulting image is clear and free from obstruction by bones and other adjacent organs. (c) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, Boston, MA 02114 USA. RP Cai, WL (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiol, 25 New Chardon St 400C, Boston, MA 02114 USA. EM Cai.Wenli@mgh.harvard.edu NR 13 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 0895-6111 J9 COMPUT MED IMAG GRAP JI Comput. Med. Imaging Graph. PD OCT PY 2007 VL 31 IS 7 BP 570 EP 576 DI 10.1016/j.compmedimag.2007.06.007 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 216FL UT WOS:000249863800011 PM 17706399 ER PT J AU Kocaturk, T Pineda, R Green, LK Azar, DT AF Kocaturk, Tolga Pineda, Roberto, II Green, Laura K. Azar, Dimitri T. TI Post-LASIK epithelial dendritic defect associated with Alternaria SO CORNEA LA English DT Article DE Alternaria; interface inflammation; laser in situ keratomileusis ID IN-SITU KERATOMILEUSIS; KERATITIS; KERATOMYCOSIS; AIR AB Purpose: To report a case of a dendritic epithelia] defect with interface inflammation associated with Alternaria sp. after laser in situ keratomileusis (LASIK) surgery. Methods: A case report of a 46-year-old woman who presented with a dendritic epithelial defect and interface inflammation after LASIK surgery. Results: After an apparent post-LASIK herpes simplex keratitis with related interface inflammation failed to respond to medical therapy, cornea culture results were positive for Alternaria fungal sp. 2 weeks and 6 days after presentation. Viral cultures and polymerase chain reaction were negative for herpes simplex virus. Six months after penetrating keratoplasty (and I year after LASIK), the patient underwent a cataract extraction OD. Best-corrected visual acuity 18 months after the original LASIK procedure was 20/25 OD. Conclusions: Alternaria keratitis may present with a dendritic epithelial defect with interface inflammation mimicking herpes simplex virus. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Adnan Menderes Univ, Sch Med, Dept Ophthalmol, Aydin, Turkey. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago Eye Ctr, Eay & Ear Infirm, Chicago, IL USA. RP Pineda, R (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM Roberto_Pineda@MEEI.HARVARD.EDU NR 11 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD OCT PY 2007 VL 26 IS 9 BP 1144 EP 1146 PG 3 WC Ophthalmology SC Ophthalmology GA 215GN UT WOS:000249796400029 PM 17893555 ER PT J AU Pineda, R Kocaturk, T Bhui, RD AF Pineda, Roberto, II Kocaturk, Tolga Bhui, Ravinder Dennis TI Visual outcome and rehabilitation in a case of bilateral Acanthamoeba sclerokeratitis SO CORNEA LA English DT Article DE Acanthamoeba sclerokeratitis; infectious keratitis; Acanthamoeba keratitis ID KERATITIS AB Purpose: To report a rare and complicated case of bilateral Acanthamoeba sclerokeratitis (ASK). Methods: Case report of a 42-year-old patient who was referred to the Massachusetts Eye and Ear Infirmary 7 months after a history of culture-confirmed bilateral Acanthamoeba polyphaga sclerokeratitis. At the time of referral to the MEEI, he was noted to have iris neovascularization and chronic mydriasis in both eyes. The anterior chambers were shallow, and there were mature cortical cataracts that obscured the posterior pole in both eyes. His visual acuity in both eyes was limited to hand motions. Results: The patient underwent sequential cataract extraction, penetrating keratoplasty (PK), and yttrium argon garnet laser capsulotomy of the right eye over a span of 3 months. This treatment substantially improved the vision in his right eye to 20/400. Cataract extraction surgery and a PK have been scheduled for this patient's left eye in the near future. Conclusions: Some patients with ASK and apparently poor visual prognosis can achieve substantial visual improvement after anterior-segment surgery. This report describes the management and outcome of only the second reported case of bilateral ASK in the world. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Adnan Menderes Univ, Sch Med, Dept Ophthalmol, Aydin, Turkey. Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. RP Pineda, R (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM Roberto_Pineda@MEEI.HARVARD.EDU NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD OCT PY 2007 VL 26 IS 9 BP 1150 EP 1152 PG 3 WC Ophthalmology SC Ophthalmology GA 215GN UT WOS:000249796400031 PM 17893557 ER PT J AU Calfee, CS Eisner, MD Ware, LB Thompson, BT Parsons, PE Wheeler, AP Korpak, A Matthay, MA AF Calfee, Carolyn S. Eisner, Mark D. Ware, Lorraine B. Thompson, B. Taylor Parsons, Polly E. Wheeler, Arthur P. Korpak, Anna Matthay, Michael A. CA Natl heart, lung, blood inst acute TI Trauma-associated lung injury differs clinically and biologically from acute lung injury due to other clinical disorders SO CRITICAL CARE MEDICINE LA English DT Article DE respiratory distress syndrome; adult multiple trauma; biological markers ID RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; HUMAN-ENDOTHELIAL-CELLS; PULMONARY-EDEMA FLUID; VON-WILLEBRAND-FACTOR; VONWILLEBRAND-FACTOR; CONTROLLED-TRIAL; FACTOR ANTIGEN; RISK; MORTALITY AB Objective: Patients with trauma-associated acute lung injury have better outcomes than patients with other clinical risks for lung injury, but the mechanisms behind these improved outcomes are unclear. We sought to compare the clinical and biological features of patients with trauma-associated lung injury with those of patients with other risks for lung injury and to determine whether the improved outcomes of trauma patients reflect their baseline health status or less severe lung injury, or both. Design, Setting, and Patients: Analysis of clinical and biological data from 1,451 patients enrolled in two large randomized, controlled trials of ventilator management in acute lung injury. Measurements and Main Results: Compared with patients with other clinical risks for lung injury, trauma patients were younger and generally less acutely and chronically ill. Even after adjusting for these baseline differences, trauma patients had significantly lower plasma levels of intercellular adhesion molecule-1, von Willebrand factor antigen, surfactant protein-D, and soluble tumor necrosis factor receptor-1, which are biomarkers of lung epithelial and endothelial injury previously found to be prognostic in acute lung injury. In contrast, markers of acute inflammation, except for interleukin-6, and disordered coagulation were similar in trauma and nontrauma patients. Trauma-associated lung injury patients had a significantly lower odds of death at 90 days, even after adjusting for baseline clinical factors including age, gender, ethnicity, comorbidities, and severity of illness (odds ratio, 0.44; 95% confidence interval, 0.24-0.82; p = .01). Conclusions: Patients with trauma-associated lung injury are less acutely and chronically ill than other lung injury patients; however, these baseline clinical differences do not adequately explain their improved outcomes. Instead, the better outcomes of the trauma population may be explained, in part, by less severe lung epithelial and endothelial injury. C1 Univ Calif San Francisco, Div Pulm & Crit Care, Dept Med, San Francisco, CA 94143 USA. Cardiovasc Res Inst, San Francisco, CA USA. Vanderbilt Univ, Dept Med, Div Allergy Pulm & Crit Care, Nashville, TN USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Med Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. Univ Vermont, Dept Med, Div Pulm & Crit Care Med, Burlington, VT USA. RP Calfee, CS (reprint author), Univ Calif San Francisco, Div Pulm & Crit Care, Dept Med, 505 Parnassus Ave, San Francisco, CA 94143 USA. EM carolyn.caffee@ucsf.edu FU NHLBI NIH HHS [R37 HL051856-14, R37 HL051856] NR 39 TC 87 Z9 90 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2007 VL 35 IS 10 BP 2243 EP 2250 DI 10.1097/01.CCM.0000280434.33451.87 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 217HH UT WOS:000249938500001 PM 17944012 ER PT J AU Villar, J Perez-Mendez, L Flores, C Maca-Meyer, N Espinosa, E Muriel, A Sanguesa, R Blanco, J Muros, M Kacmarek, RM AF Villar, Jesus Perez-Mendez, Lina Flores, Carlos Maca-Meyer, Nicole Espinosa, Elena Muriel, Arturo Sanguesa, Ruben Blanco, Jesus Muros, Mercedes Kacmarek, Robert M. CA GRECIA GEN-SEP Grps TI A CXCL2 polymorphism is associated with better outcomes in patients with severe sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE sepsis; CXCL2; macrophage inflammatory protein-2; polymorphism; genetic association study; acute respiratory distress ID KAPPA-B ACTIVATION; MACROPHAGE INFLAMMATORY PROTEIN-2; RESPIRATORY-DISTRESS-SYNDROME; PROMOTER POLYMORPHISM; SEPTIC SHOCK; POPULATION; SUSCEPTIBILITY; EPIDEMIOLOGY; ANGIOGENESIS; DEFINITIONS AB Objective: Several studies have implicated the CXCL2 chemokine as a mediator in the development of sepsis. We hypothesized that a tandem repeat polymorphism (AC)n in the CXCL2 gene, previously associated with susceptibility to severe sepsis, contributes to morbidity and mortality in severe sepsis. Design: Prospective, observational, genetic study of septic patients. Setting: A network of Spanish postsurgical and critical care units. Patients. A total of 183 critically ill patients fulfilling the International Sepsis Criteria for severe sepsis. Interventions: None. Measurements and Main Results: Patients were classified into three groups according to the presence of compound 24 +/- 1 (AC) repeat genotypes: homozygote 24 +/- 1 carriers (HC group), heterozygote 24 +/- 1 carriers (HTC), and non 24 +/- 1 carriers (NC group). Mortality, development of acute respiratory distress syndrome, and number of failing organs were determined for each group. Overall mortality was 46.4%. HC patients had a lower mortality (39.9%) than HTC (52.2%) and NC (72.7%) patients (trend test p = .018). This difference remained significant when using a multiple logistic regression analysis (p = .035). The presence of population stratification was ruled out, since 20 independent genomic control markers demonstrated homogeneity among groups. An exploratory analysis of the effect of acute respiratory distress syndrome on mortality showed a relative risk of 2.60 in the HC group (p = .0004), while in the nonhomozygote carriers (NHC) group the relative risk was 3.34 (p = .0001). Conclusions: Our data suggest that a tandem repeat polymorphism (AC)n at position -665 in the CXCL2 gene may be an independent predictor of mortality for severe sepsis. Additional studies are needed to confirm these results. C1 Hosp Univ Dr Negrin, MODERN, Las Palmas Gran Canaria, Spain. St Michaels Hosp, Keenan Res Ctr, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada. Hosp Univ NS Candelaria, Div Clin Genet & Epidemiol, Tenerife, Spain. Hosp Univ NS Candelaria, Div Human Genet, Tenerife, Spain. Hosp Univ NS Candelaria, Dept Anesthesia, Tenerife, Spain. Hosp Univ NS Candelaria, Dept Clin Biochem, Tenerife, Spain. Univ Chicago, Div Pulm & Crit Care, Dept Med, Chicago, IL 60637 USA. Hosp Univ Rio Hortega, Intens Care Unit, Valladolid, Spain. Harvard Univ, Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02115 USA. RP Villar, J (reprint author), Hosp Univ Dr Negrin, MODERN, Las Palmas Gran Canaria, Spain. EM jesus.villar54@gmail.com NR 37 TC 19 Z9 20 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2007 VL 35 IS 10 BP 2292 EP 2297 DI 10.1097/01.CCM.0000284511.73556.59 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 217HH UT WOS:000249938500009 PM 17944017 ER PT J AU Pumbwe, L Skilbeck, CA Wexler, HM AF Pumbwe, Lilian Skilbeck, Christopher A. Wexler, Hannah M. TI Impact of anatomic site on growth, efflux-pump expression, cell structure, and stress responsiveness of Bacteroides fragilis SO CURRENT MICROBIOLOGY LA English DT Article DE adaptation; colonization; membrane proteins; regulation ID OUTER-MEMBRANE VESICLES; ELECTRON MICROSCOPY; BILE-SALTS; RESISTANCE; GINGIVALIS AB This study investigated whether B. fragilis from various human sites acquired stable traits enabling it to express certain efflux pumps (EPs), adopt a particular cell structure, and tolerate certain stressors. Isolates from blood, abscess, and stool (n = 11 each) were investigated. Bacteria from various sites portrayed different ultrastructres and EP expression. Blood isolates were tolerant to nutrient limitation and stool isolates to NaCl and bile salt stress. Stressors significantly increased EP expression. These data demonstrate that (1) B. fragilis acquires stable traits from various in vivo microenvironments; (2) that EPs are involved in stress responsiveness; and (3) that EP expression is tightly controlled and site dependent. C1 Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Pumbwe, L (reprint author), Univ Calif Los Angeles, Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA 90095 USA. EM lilskil@ucla.edu NR 21 TC 2 Z9 2 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD OCT PY 2007 VL 55 IS 4 BP 362 EP 365 DI 10.1007/s00284-007-0278-8 PG 4 WC Microbiology SC Microbiology GA 212UC UT WOS:000249621300016 PM 17882508 ER PT J AU Culley, DJ Xie, ZC Crosby, G AF Culley, Deborah J. Xie, Zhongcong Crosby, Gregory TI General anesthetic-induced neurotoxicity: an emerging problem for the young and old? SO CURRENT OPINION IN ANESTHESIOLOGY LA English DT Article DE aging; Alzheimer's disease; anesthesia; brain; neurotoxicity; postoperative cognitive dysfunction AB Purpose of review A growing body of evidence from cells, rodents, and sub-human primates suggests that general anesthetics can be neurotoxic to the developing and senescent brain. We review this evidence and put the studies into perspective for the practicing clinician. Recent findings Studies indicate that a variety of general anesthetics, which act primarily as gamma-amino-butyric acid receptor modulators and N-methyl-D-aspartic acid glutamate receptor antagonists, produce apoptotic neurodegeneration in the developing rodent and nonhuman primate brain. Vulnerability to this neurotoxicity is greatest during the period of synaptogenesis and presumably reflects disruption of the normal balance between excitation and inhibition during a critical period of brain development. Moreover, in the rodent, the neurodegeneration is associated with cognitive impairment into adulthood. Recent data also reveal that general anesthesia produces enduring cognitive impairment in aged but not young rodents and that halothane and isoflurane increase the generation and toxicity of amyloid beta, a protein strongly implicated in the pathogenesis of Alzheimer's disease. The meaning of these experimental results for human surgical patients is unclear, however, because human studies are lacking. Summary General anesthetics produce neurotoxicity and enduring cognitive impairment in young and aged animals but it is premature to change clinical practice because the issue has not been adequately studied in humans. C1 [Culley, Deborah J.; Crosby, Gregory] Harvard Univ, Brigham & Womens Hosp, Dept Anesthesia, Sch Med, Boston, MA 02115 USA. [Xie, Zhongcong] Harvard Univ, Sch Med, Dept Anesthesia, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Crosby, G (reprint author), Brigham & Womens Hosp, Lab Aging Neurosci, Dept Anesthesiol Perioperat & Pain Med, 75 Francis St, Boston, MA 02115 USA. EM gcrosby@zeus.bwh.harvard.edu FU National Institutes of Health (Bethesda, Maryland, USA) [KO8 GM077057, K12 AG 000294, K08NS048140, P60 AG008812, R01 AG20253] FX This work was supported by National Institutes of Health (Bethesda, Maryland, USA) grants KO8 GM077057 to D.J.C.; K12 AG 000294, K08NS048140, and P60 AG008812 to Z.X.; and R01 AG20253 to G.C. NR 57 TC 40 Z9 43 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0952-7907 EI 1473-6500 J9 CURR OPIN ANESTHESIO JI Curr. Opin. Anesthesiol. PD OCT PY 2007 VL 20 IS 5 BP 408 EP 413 PG 6 WC Anesthesiology SC Anesthesiology GA V42SF UT WOS:000209632800003 PM 17873593 ER PT J AU Arnaout, MA Goodman, SL Xiong, JP AF Arnaout, M. Amin Goodman, Simon L. Xiong, Jian-Ping TI Structure and mechanics of integrin-based cell adhesion SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID PHOSPHATIDYLINOSITOL PHOSPHATE KINASE; MEDIATES RAP1-INDUCED ADHESION; BETA CYTOPLASMIC DOMAIN; CD11B A-DOMAIN; I-LIKE DOMAIN; CRYSTAL-STRUCTURE; ALPHA-ACTININ; LIGAND-BINDING; MIGRATING CELLS; FOCAL ADHESIONS AB Integrins are alpha/beta heterodimeric adhesion glycoprotein receptors that regulate a wide variety of dynamic cellular processes such as cell migration, phagocytosis, and growth and development. X-ray crystallography of the integrin ectodomain revealed its modular architecture and defined its metal-dependent interaction with extracellular ligands. This interaction is regulated from inside the cell (inside-out activation), through the short cytoplasmic alpha and beta integrin tails, which also mediate biochemical and mechanical signals transmitted to the cytoskeleton by the ligand-occupied integrins, effecting major changes in cell shape, behavior, and fate. Recent advances in the structural elucidation of integrins and integrin-binding cytoskeleton proteins are the subjects of this review. C1 Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Struct Biol Program, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Merck Serono KGaA, Therapeut Area Oncol, D-64271 Darmstadt, Germany. RP Arnaout, MA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Leukocyte Biol & Inflammat Program, Struct Biol Program, 149 13th St, Charlestown, MA 02129 USA. EM arnaout@receptor.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL070219-05, R01 HL070219]; NIDDK NIH HHS [R01 DK048549, R01 DK048549-22, R01 DK074447, R01 DK074447-03] NR 110 TC 217 Z9 223 U1 5 U2 34 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2007 VL 19 IS 5 BP 495 EP 507 DI 10.1016/j.ceb.2007.08.002 PG 13 WC Cell Biology SC Cell Biology GA 234KY UT WOS:000251164200002 PM 17928215 ER PT J AU Streblow, DN Orloff, SL Nelson, JA AF Streblow, Daniel N. Orloff, Susan L. Nelson, Jay A. TI Acceleration of allograft failure by cytomegalovirus SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID MUSCLE-CELL MIGRATION; TRANSPLANT VASCULAR SCLEROSIS; SOLID-ORGAN TRANSPLANTATION; REPLACE PREEMPTIVE THERAPY; PDGF BETA-RECEPTOR; CHRONIC REJECTION; RENAL-TRANSPLANTATION; RAT CYTOMEGALOVIRUS; HEART-TRANSPLANTATION; EXTRACELLULAR-MATRIX AB A number of human herpesviruses are important opportunistic pathogens that have been associated with increased morbidity and mortality in transplant recipients including human cytomegalovirus (HCMV), HHV6, HHV7, HHV8 as well as HSV-1, VZV. However, HCMV has been linked both epidemiologically and through the use of animal models to the acceleration of acute and chronic allograft rejection. This review will cover the pathophysiology, epidemiology, and mechanisms of CMV-associated disease in the setting of transplantation. C1 OHSU, MMI, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. OHSU, Dept Surg, Portland, OR USA. OHSU, Vaccine & Gene Therapy Inst, Beaverton, OR 97006 USA. RP Nelson, JA (reprint author), OHSU, MMI, Portland, OR USA. EM nelsonj@ohsu.edu FU NHLBI NIH HHS [R01 HL065754, HL71695, R01 HL071695, HL65754, R01 HL083194, HL083194, HL 66238-01, R01 HL066238]; NIAID NIH HHS [AI21640, R01 AI021640] NR 64 TC 68 Z9 70 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2007 VL 19 IS 5 BP 577 EP 582 DI 10.1016/j.coi.2007.07.012 PG 6 WC Immunology SC Immunology GA 224RR UT WOS:000250464600016 PM 17716883 ER PT J AU Ruas, JL Lendahl, U Poellinger, L AF Ruas, Jorge L. Lendahl, Urban Poellinger, Lorenz TI Modular of vascular gene expression by hypoxia SO CURRENT OPINION IN LIPIDOLOGY LA English DT Review DE atherosclerosis; diabetes; gene regulation; hypoxia; signal transduction ID INDUCIBLE FACTOR 1-ALPHA; TRANSCRIPTIONAL ACTIVITY; INTRAPLAQUE HEMORRHAGE; SIGNAL-TRANSDUCTION; HIF-1-ALPHA; CELLS; RECRUITMENT; HIF-1; HYDROXYLATION; ANGIOGENESIS AB Hypoxia-inducible factor and Notch transcription factors represent potentially attractive targets for regulation of angiogenesis and possibly inflammation. In view of the pleiotropic effects of these transcription factors, however, successful targeting of these signaling pathways will require the development of gene specific (and possibly tissue-specific) modulators and extensive validation in relevant model systems. C1 Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Poellinger, L (reprint author), Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. EM lorenz.poellinger@ki.se NR 39 TC 23 Z9 29 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-9672 J9 CURR OPIN LIPIDOL JI Curr. Opin. Lipidology PD OCT PY 2007 VL 18 IS 5 BP 508 EP 514 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Peripheral Vascular Disease SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 217UW UT WOS:000249973800004 PM 17885420 ER PT J AU Jeyaretna, DS Kuroda, T AF Jeyaretna, Deva S. Kuroda, Toshihiko TI Recent advances in the development of oncolytic HSV-1 vectors: 'Arming' of HSV-1 vectors and application of bacterial artificial chromosome SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Review DE bacterial artificial chromosome; gene therapy; oncolytic HSV; site-specific recombinase; therapeutic transgene; transcriptional targeting ID HERPES-SIMPLEX-VIRUS; POSITRON-EMISSION-TOMOGRAPHY; YEAST CYTOSINE DEAMINASE; SQUAMOUS-CELL CARCINOMA; LONG-TERM SURVIVAL; BRAIN-TUMORS; IONIZING-RADIATION; PROTEIN-KINASE; RIBONUCLEOTIDE REDUCTASE; GENE-THERAPY AB HSV-1 was one of the first oncolytic viruses to have been investigated for its therapeutic potential against cancer. Among the dozens of oncolytic HSV-1 vectors that have so far been reported, some carry transgenes, including interleukins, anti-angiogenic peptides, and prodrug-converting enzymes. 'Arming' of HSV-1 with therapeutic transgenes such as these is expected to enhance its efficacy. HSV-1 is a 152-kb double-stranded DNA virus, and the generation of armed HSV usually takes several months to achieve by conventional homologous recombination methods. Recently, bacterial artificial chromosome (BAC)-based systems termed 'HSVQuik' and 'Flip-Flop HSV-BAC' were developed to enable the fast generation of recombinant HSV-1 vectors within weeks by using site-specific recombinases. These systems provide powerful tools for screening potential transgenes that might greatly enhance the efficacy of HSV-1 vectors. This review discusses the current state of research into the development of oncolytic HSV-1 vectors, and highlights the promise that armed oncolytic HSV-1 vectors might hold for the future. C1 Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, Boston, MA 02114 USA. RP Kuroda, T (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Surg Oncol, 55 Fruit St,WRN 401, Boston, MA 02114 USA. EM kuroda@helix.mgh.harvard.edu NR 125 TC 11 Z9 12 U1 0 U2 1 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2007 VL 9 IS 5 BP 447 EP 466 PG 20 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 219OC UT WOS:000250093500005 PM 17932809 ER PT J AU Klig, JE O'Malley, PJ AF Klig, Jean E. O'Malley, Patricia J. TI Pediatric office emergencies SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE emergency medical services for children; pediatric office emergency; prehospital care ID MEDICAL-SERVICES; PRACTICING PEDIATRICIANS; MANAGE EMERGENCIES; PREPAREDNESS; CHILDREN; PHYSICIAN; PRACTITIONER; PROGRAM; IMPACT AB Purpose of review An emergency in the office setting can be problematic without adequate staff, support, tools, and protocols. Though many emergencies are not immediately life-threatening, one risks the 'worst case scenario' occurring if not adequately prepared. Pediatric patients are prone to respiratory distress and compromise in many emergencies, and can rapidly decompensate without adequate support. A review of the history of emergency medical services for children and the framework for office emergency preparedness offers insight into current challenges for primary care providers. Recent findings Research has demonstrated that many primary care offices and clinics are ill prepared to handle common pediatric emergencies. Reliance on the Emergency Medical Services system is insufficient to assure optimal outcomes, especially given variations in the equipment, training, and experience of Emergency Medical Services providers in the care of children, and in remote areas where access may be delayed. Preparation and practice for office emergencies through 'mock code' exercises can increase practitioner confidence and reduce anxiety to perform life-saving care. Summary Better outcomes for off ice emergencies can result from staff training, availability of appropriate equipment and medications, maintenance of skills via formal and informal practice, and pathways for expeditious transfer to a definitive care facility. C1 Med Ctr, Dept Pediat Emergency Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Klig, JE (reprint author), Med Ctr, Dept Pediat Emergency Med, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM jean.klig@bmc.org NR 45 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD OCT PY 2007 VL 19 IS 5 BP 591 EP 596 PG 6 WC Pediatrics SC Pediatrics GA 217HG UT WOS:000249938400012 PM 17885481 ER PT J AU Del Barrio, MG Taveira-Marques, R Muroyama, Y Yuk, DI Li, SG Wines-Samuelson, M Shen, J Smith, HK Xiang, MQ Rowitch, D Richardson, WD AF Del Barrio, Marta G. Taveira-Marques, Raquel Muroyama, Yuko Yuk, Dong-In Li, Shengguo Wines-Samuelson, Mary Shen, Jie Smith, Hazel K. Xiang, Mengqing Rowitch, David Richardson, William D. TI A regulatory network involving Foxn4, Mash1 and delta-like 4/Notch1 generates V2a and V2b spinal interneurons from a common progenitor pool SO DEVELOPMENT LA English DT Article DE Notch1; delta-like 4; Foxn4; gata; Scl (Tal1); Chx10; spinal cord; neurogenesis; chick; mouse; V2 interneurons; Mash1 (Ascl1) ID CENTRAL-NERVOUS-SYSTEM; NEURAL-TUBE; TRANSCRIPTION FACTORS; HOMEODOMAIN PROTEIN; LOCOMOTOR CIRCUITS; NEURONAL FATE; CELL IDENTITY; CORD; NOTCH; SPECIFICATION AB In the developing central nervous system, cellular diversity depends in part on organising signals that establish regionally restricted progenitor domains, each of which produces distinct types of differentiated neurons. However, the mechanisms of neuronal subtype specification within each progenitor domain remain poorly understood. The p2 progenitor domain in the ventral spinal cord gives rise to two interneuron ( IN) subtypes, V2a and V2b, which integrate into local neuronal networks that control motor activity and locomotion. Foxn4, a forkhead transcription factor, is expressed in the common progenitors of V2a and V2b INs and is required directly for V2b but not for V2a development. We show here in experiments conducted using mouse and chick that Foxn4 induces expression of delta- like 4 ( DII4) and Mash1 ( Ascl1). DII4 then signals through Notch1 to subdivide the p2 progenitor pool. Foxn4, Mash1 and activated Notch1 trigger the genetic cascade leading to V2b INs, whereas the complementary set of progenitors, without active Notch1, generates V2a INs. Thus, Foxn4 plays a dual role in V2 IN development: ( 1) by initiating Notch- Delta signalling, it introduces the asymmetry required for development of V2a and V2b INs from their common progenitors; ( 2) it simultaneously activates the V2b genetic programme. C1 UCL, Wolfson Inst Biomed Res, London WC1E 6BT, England. UCL, Dept Biol, London WC1E 6BT, England. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis,Program Neurosci, Boston, MA 02115 USA. RP Richardson, WD (reprint author), UCL, Wolfson Inst Biomed Res, Gower St, London WC1E 6BT, England. EM w.richardson@ucl.ac.uk RI Richardson, William/C-1762-2008; Messier, Claude/A-2322-2008; OI Richardson, William/0000-0001-7261-2485; Messier, Claude/0000-0002-4791-1763; Muroyama, Yuko/0000-0002-6697-2123 FU NEI NIH HHS [EY015777]; NINDS NIH HHS [R01 NS042818, R01 NS047572]; Wellcome Trust NR 39 TC 62 Z9 64 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 1 PY 2007 VL 134 IS 19 BP 3427 EP 3436 DI 10.1242/dev.005868 PG 10 WC Developmental Biology SC Developmental Biology GA 215MJ UT WOS:000249812400005 PM 17728344 ER PT J AU Wu, XW Li, SH Chrostek-Grashoff, A Czuchra, A Meyer, H Yurchenco, PD Brakebusch, C AF Wu, Xunwei Li, Shaohua Chrostek-Grashoff, Anna Czuchra, Aleksandra Meyer, Hannelore Yurchenco, Peter D. Brakebusch, Cord TI Cdc42 is crucial for the establishment of epithelial polarity during early mammalian development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Cdc42; epithelial polarity; embryoid bodies ID EMBRYONIC STEM-CELLS; MDCK CELLS; ENDODERM DIFFERENTIATION; BASEMENT-MEMBRANES; RHO-GTPASES; COMPLEX; TIGHT; RAC; POLARIZATION; LAMININ AB To study the role of Cdc42 in the establishment of epithelial polarity during mammalian development, we generated murine Cdc42-null embryonic stem cells and analyzed peri-implantation development using embryoid bodies (EBs). Mutant Ells developed endoderm and underlying basement membrane, but exhibited defects of cell polarity, cell-cell junctions, survival, and cavitation. These defects corresponded to a decreased phosphorylation and membrane localization of aPKC, a reduced phosphorylation of GSK3 beta, and a diminished activity of Rac1. However, neither Rac1 nor the kinase function of GSK3 beta seem to contribute to cell polarization and cell-cell contacts. In contrast, EBs expressing dominant-negative (dn) PKC zeta mimicked well the phenotype of Cdc42-null EBs, suggesting a major role of aPKC in mediating cell polarization downstream. of Cdc42. Finally, aggregation experiments with endodermal cell lines suggested that Cdc42 might affect formation of adherens and tight junctions by PKC zeta-dependent regulation of the protein levels of p120 catenin and E-cadherin. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Harvard Med Sch, Charlestown, MA 02129 USA. Univ Med & Dent New Jersey, Dept Surg, New Brunswick, NJ 08903 USA. Univ Copenhagen, Inst Mol Pathol, Copenhagen, Denmark. Robert Wood Johnson Med Sch, Dept Pathol & Lab Med, Piscataway, NJ USA. Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. RP Brakebusch, C (reprint author), Univ Copenhagen, BRIC, Ole Maaloes Vej 5, DK-2200 Copenhagen, Denmark. EM cord.brakebusch@bric.dk FU NIDDK NIH HHS [R01 DK36425] NR 38 TC 47 Z9 47 U1 2 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD OCT PY 2007 VL 236 IS 10 BP 2767 EP 2778 DI 10.1002/dvdy.21309 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 220YB UT WOS:000250192100005 PM 17849438 ER PT J AU Wikstrom, JD Katzman, SM Mohamed, H Twig, G Graf, SA Heart, E Molina, AJA Corkey, BE de Vargas, LM Danial, NN Collins, S Shirihai, OS AF Wikstrom, Jakob D. Katzman, Shana M. Mohamed, Hibo Twig, Gilad Graf, Solomon A. Heart, Emma Molina, Anthony J. A. Corkey, Barbara E. de Vargas, Lina Moitoso Danial, Nika N. Collins, Sheila Shirihai, Orian S. TI beta-cell mitochondria exhibit membrane potential heterogeneity that can be altered by stimulatory or toxic fuel levels SO DIABETES LA English DT Article ID UNCOUPLING PROTEIN-2; INSULIN-SECRETION; GLUCOSE; ISLET; GLUCOKINASE; METABOLISM; EXPRESSION; APOPTOSIS; MICE; GENE AB OBJECTIVE-beta-Cell response to glucose is characterized by mitochondrial membrane potential (Delta psi) hyperpolarization and the production of metabolites that serve as insulin secretory signals. We have previously shown that glucose-induced mitochondrial hyperpolarization accompanies the concentration-dependent increase in insulin secretion within a wide range of glucose concentrations. This observation represents the integrated response of a large number of mitochondria within each individual cell. However, it is currently unclear whether all mitochondria within a single beta-cell represent a metabolically homogenous population and whether fuel or other stimuli can recruit or silence sizable subpopulations of mitochondria. This study offers insight into the different metabolic states of P-cell mitochondria. RESULTS-We show that mitochondria display a wide heterogeneity in Delta psi and a millivolt range that is considerably larger than the change in millivolts induced by fuel challenge. Increasing glucose concentration recruits mitochondria into higher levels of homogeneity, while an in vitro diabetes model results in increased Delta psi heterogeneity. Exploration of the mechanism behind heterogeneity revealed that temporary changes in Delta psi of individual mitochondria, ATP-hydrolyzing mitochondria, and uncoupling protein 2 are not significant contributors to Delta psi heterogeneity. We identified BAD, a proapoptotic BCL-2 family member previously implicated in mitochondrial recruitment of glucokinase, as a significant factor influencing the level of heterogeneity. CONCLUSIONS-We suggest that mitochondrial Delta psi heterogeneity in beta-cells reflects a metabolic reservoir recruited by an increased level of fuels and therefore may serve as a therapeutic target. C1 Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Boston Univ, Obes Res Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Hamner Inst Hlth Sci, Div Translat Biol, Endocrine Biol Program, Res Triangle Pk, NC USA. RP Shirihai, OS (reprint author), Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, 136 Harrison Ave, Boston, MA 02111 USA. EM orian.shirihai@tufts.edu OI Wikstrom, Jakob/0000-0002-4287-1774; Corkey, Barbara/0000-0002-5467-1630 FU NCRR NIH HHS [P41 RR001395]; NHLBI NIH HHS [5R01HL071629]; NIDDK NIH HHS [1R01DK074778, 1R21DK070303, 22RO1DK35914]; NINDS NIH HHS [P30 NS047243] NR 45 TC 57 Z9 59 U1 0 U2 6 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2007 VL 56 IS 10 BP 2569 EP 2578 DI 10.2337/db06-0757 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 218UQ UT WOS:000250040900020 PM 17686943 ER PT J AU Weissberg-Benchell, J Wolpert, H Anderson, BJ AF Weissberg-Benchell, Jill Wolpert, Howard Anderson, Barbara J. TI Transitioning from pediatric to adult care - A new approach to the post-adolescent young person with type 1 diabetes SO DIABETES CARE LA English DT Editorial Material ID HEALTH BELIEF MODEL; ASSOCIATION COHORT; INTENSIVE THERAPY; EATING HABITS; SWEDEN DISS; SELF-CARE; MORTALITY; MELLITUS; SERVICES; PEOPLE C1 Childrens Mem Hosp, Dept Child & Adolescent Psychiat, Chicago, IL 60614 USA. Joslin Diabet Ctr, Boston, MA USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX USA. RP Weissberg-Benchell, J (reprint author), Childrens Mem Hosp, Dept Child & Adolescent Psychiat, 2300 Childrens Plaza,Box 10, Chicago, IL 60614 USA. EM jwbenchell@childrensmemorial.org NR 59 TC 104 Z9 105 U1 1 U2 12 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2007 VL 30 IS 10 BP 2441 EP 2446 DI 10.2337/dc07-1249 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221JN UT WOS:000250223400003 PM 17666466 ER PT J AU Herman, WH Ma, Y Uwaifo, G Haffner, S Kahn, SE Horton, ES Lachin, JM Montez, MG Brenneman, T Barrett-Connor, E AF Herman, William H. MA, Yong Uwaifo, Gabriel Haffner, Steven Kahn, Steven E. Horton, Edward S. Lachin, John M. Montez, Maria G. Brenneman, Tina Barrett-Connor, Elizabeth CA Diabet Prevention Program Res Grp TI Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the diabetes prevention program SO DIABETES CARE LA English DT Article ID QUALITY-OF-CARE; GLYCATED HEMOGLOBIN; GLYCOSYLATED HEMOGLOBIN; NONDIABETIC SUBJECTS; MANAGED CARE; ADULTS; GLYCEMIA; HEALTH; VARIABILITY; HBA(1C) AB OBJECTIVE - We sought to examine racial and ethnic differences in At C in individuals with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - We studied 3,819 individuals aged >= 25 years with IGT who were found to be eligible to participant in the Diabetes Prevention Program. AIC was compared among five racial and ethnic groups before and after adjustment for factors that differed among groups or might affect glycemia including age, sex, education, marital status, blood pressure, adiposity (BMI and waist circumference), hematocrit, fasting and post-glucose load glucose levels, glucose area under the curve (AUC), beta-cell function, and insulin resistance. RESULTS - Mean +/- SD AIC was 5.91 +/- 0.50%. Among whites, AIC was 5.80 +/- 0.44%, among Hispanics 5.89 +/- 0.46%, among Asian 5.96 +/- 0.45%, among American Indians 5.96 +/- 0.46%, and among blacks 6.19 +/- 0.59%. Age, sex, systolic blood pressure, diastolic blood pressure, BMI, fasting glucose, glucose AUC, corrected insulin response, and insulin resistance were eachindependent predictors of AIC. Adjusting for these and other factors, mean AIC levels were 5.78% forwhites, 5.93% for Hispanics, 6.00% forAsians, 6.12% for American Indians, and 6.18% for blacks (P < 0.001). CONCLUSIONS - AIC levels are higher among U.S. racial and ethnic minority groups with IGT after adjustment for factors likely to affect glycemia. Among patients with IGT, AlC may not be valid for assessing and comparing glycemic control across racial and ethnic groups or as an indicator of health care disparities. C1 George Washington Univ, Diabet Prevent Program Coordinat Ctr, Ctr Biostat, Rockville, MD 20852 USA. Univ Michigan, Dept Internal Med & Epidemiol, Hlth Syst, Ann Arbor, MI USA. Medstar Res Inst, Washington, DC USA. Univ Texas, Hlth Sci Ctr, Dept Med Clin Epidemiol, San Antonio, TX USA. Univ Washington, VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Joslin Diabet Ctr, Sect Clin Res, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Diabet Prevent Program, San Antonio, TX USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA USA. RP Herman, WH (reprint author), George Washington Univ, Diabet Prevent Program Coordinat Ctr, Ctr Biostat, 6110 Executive Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu RI Uwaifo, Gabriel/M-2361-2016; OI Uwaifo, Gabriel/0000-0002-6962-9304; Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 27 TC 244 Z9 255 U1 4 U2 13 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 EI 1935-5548 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2007 VL 30 IS 10 BP 2453 EP 2457 DI 10.2337/dc06-2003 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221JN UT WOS:000250223400005 PM 17536077 ER PT J AU Meigs, JB Larson, MG Fox, CS Keaney, JF Vasan, RS Benjamin, EJ AF Meigs, James B. Larson, Martin G. Fox, Caroline S. Keaney, John F., Jr. Vasan, Ramachandran S. Benjamin, Emelia J. TI Association of oxidative stress, insulin resistance, and diabetes risk phenotypes - The framingham offspring study SO DIABETES CARE LA English DT Article ID ACTIVATED SIGNALING PATHWAYS; ENDOTHELIAL DYSFUNCTION; METABOLIC SYNDROME; LIPID-PEROXIDATION; GLUCOSE; MARKERS; OBESITY; MYELOPEROXIDASE; MELLITUS; DISEASE AB OBJECTIVE - Systemic oxidative stress causes insulin resistance in rodents. We tested the hypothesis that oxidative stress and insulin resistance are associated in humans. RESEARCH DESIGN AND METHODS - We used cross-sectional data from 2,002 nondiabetic subjects of the community-based Framingham Offspring Study. We measured insulin resistance with the homeostasis model and defined categorical insulin resistance as oxidative stress using the ratio of urine 8-epi-prostaglandin F-2 alpha (8-epi-PGF(2 alpha)) to creatinine and used age- and sex-adjusted regression models to test the association of oxidative stress with insulin resistance in individuals without diabetes and among subgroups at elevated risk of diabetes. RESULTS - Across 8-epi-PGF(2 alpha)/creatinine tertiles, the prevalence of insulin resistance increased (18.0 and 29.4% for the first, second, and third tertiles, respectively; P < 0.0001), as did mean levels of HOMA-IR (3.28,3.83, and 4.06 units; P < 0.0001). The insulin resistanceoxidative stress association was attenuated by additional adjustment for BMI (P = 0.06 across tertiles for insulin resistance prevalence; P = 0.004 for mean HOMA-IR). Twenty-six percent of participants were obese (BMI :30 kg/m(2)), 39% had metabolic syndrome (according to the Adult Treatment Panel III definition), and 37% had impaired fasting glucose (IFG) (fasting glucose 5.6-6.9 mmol/l). Among 528 obese participants, respectively, insulin resistance prevalence was 41.3, 60.6, and 54.2% across 8-epi-PGF(2 alpha)/creatinine tertiles (P = 0.005); among 781 subjects with metabolic syndrome, insulin resistance prevalence was 41.3, 56.7, and 51.7% (P = 0.0025); and among 749 subjects with IFG, insulin resistance prevalence was 39.6, 47.2, and 51.6% (P = 0.04). CONCLUSIONS - Systemic oxidative stress is associated with insulin resistance in individuals at average or elevated risk of diabetes even after accounting for BMI. C1 Harvard Med Sch, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. Boston Univ, Dept Math & Stat, Boston, MA USA. Natl Heart Lung Blood Inst, Framingham Heart Study, Framingham, MA USA. Harvard Med Sch, Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA. Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA USA. Whitaker Cardiovasc Inst, Evans Dept Med, Boston, MA USA. Boston Univ, Sch Med, Prevent Med Sect, Boston, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24-HL-04334, HL076784, HL64753, HL71039, N01 HV 28178, N01-HC-25195]; NIA NIH HHS [AG028321] NR 47 TC 96 Z9 117 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2007 VL 30 IS 10 BP 2529 EP 2535 DI 10.2337/dc07-0817 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221JN UT WOS:000250223400022 PM 17586736 ER PT J AU Wallace, TM Utzschneider, KM Tong, J Carr, DB Zraika, S Bankson, DD Knopp, RH Kahn, SE AF Wallace, Tara M. Utzschneider, Kristina M. Tong, Jenny Carr, Darcy B. Zraika, Sakeneh Bankson, Daniel D. Knopp, Robert H. Kahn, Steven E. TI Relationship of liver enzymes to insulin sensitivity and Intraw-abdominal fat SO DIABETES CARE LA English DT Article ID GAMMA-GLUTAMYL-TRANSFERASE; C-REACTIVE PROTEIN; MIDDLE-AGED MEN; ALANINE AMINOTRANSFERASE; METABOLIC SYNDROME; HEPATIC STEATOSIS; SUBCUTANEOUS FAT; UNITED-STATES; RESISTANCE; RISK AB OBJECTIVE - The purpose of this study was to determine the relationship between plasma liver enzyme concentrations, insulin sensitivity, and intra-abdominal fat (IAF) distribution. RESEARCH DESIGN AND METHODS - Plasma gamma-glutamyl transferase (GGT), aspartate transaminase (AST), alanine transaminase (ALT) levels, insulin sensitivity (insulin sensitivity index [S,]), IAF area, and subcutaneous fat (SCF) area were measured in 177 nondiabetic subjects (75 men and 102 women, aged 31-75 years) with no history of liver disease. On the basis of BMI (< or >= 27.5 kg/m(2)) and S-1 (< or >= 7.0 X 10(-5) min/pmol) subjects were divided into lean insulin sensitive (LIS, n = 53), lean insulin resistant (LIR, n = 60), and obese insulin resistant (OIR, n = 56) groups. RESULTS- Levels of all three liver enzymes were higher in men than in women (P < 0.0001 for each). In men, GGT levels were higher in insulin-resistant than in insulin-sensitive subjects (P < 0.01). In women, GGT levels were higher in the OIR than in the LIS group (P < 0.01) but no different in the LIR group. There was no difference in ALT and AST levels among the LIS, LIR, and OIR groups. GGT was associated with SI (r = -0.26, P < 0.0001), IAF area (r = 0.22, P < 0.01), waist-to-hip ratio (WHR) (r = 0.25, P = 0.001), BMI (r = 0.17, P < 0.05), and SCF area (r = 0.16, P < 0.05) after adjustments for age and sex. In men, only S, (r = -0.29, P < 0.05) remained independently correlated with GGT in multiple regression analysis. In women, IAF area (r = 0.29, P < 0.01) and WHR (r = 0.29, P < 0.01) were independently associated with GGT, but S, was not. CONCLUSIONS- in nondiabetic men GGT but not AST or ALT levels, are inversely related to insulin sensitivity independent of IAF area. However in women, GGT is related to measures of central body fat rather than to insulin sensitivity. C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Kahn, SE (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM skahn@u.washington.edu FU NCRR NIH HHS [RR-37, RR-16066]; NHLBI NIH HHS [HL-07028, HL-30086]; NIDDK NIH HHS [DK-35747, DK-35816, DK-02654, DK-17047] NR 35 TC 27 Z9 27 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2007 VL 30 IS 10 BP 2673 EP 2678 DI 10.2337/dc06-1758 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221JN UT WOS:000250223400053 PM 17666458 ER PT J AU Laybutt, DR Hawkins, YC Lock, J Lebet, J Sharma, A Bonner-Weir, S Weir, GC AF Laybutt, D. R. Hawkins, Y. C. Lock, J. Lebet, J. Sharma, A. Bonner-Weir, S. Weir, G. C. TI Influence of diabetes on the loss of beta cell differentiation after islet transplantation in rats SO DIABETOLOGIA LA English DT Article DE diabetes; differentiation; gene expression; glucotoxicity; insulin secretion; islets; pancreatic beta cells; transplantation ID INSULIN-SECRETION; CHRONIC HYPERGLYCEMIA; GLUCOSE-TOLERANCE; GLUT2 EXPRESSION; KIDNEY CAPSULE; FOLLOW-UP; MELLITUS; MICE; MASS; ANGIOGENESIS AB Aims/hypothesis Hyperglycaemia can impair beta cell function after islet transplantation. Appropriate glucose-induced insulin secretion is dependent on a unique expression pattern of genes. Here we examined the effects of diabetes on gene expression in transplanted islets. Materials and methods Streptozotocin-induced diabetic or control non-diabetic Lewis rats were transplanted under the kidney capsule with an insufficient number (2,000) of syngeneic islets to normalise blood glucose levels in diabetic rats. Eighteen days after transplantation, islet grafts were retrieved and RT-PCR used to assess expression of selected genes critical for beta cell function. Islet grafts from diabetic rats transplanted with a sufficient number of islets (3,000) to normalise hyperglycaemia were used to assess the effects of correcting blood glucose levels. Additionally, gene expression of transplanted islets from non-diabetic rats was compared with freshly isolated islets. Results In islet grafts from diabetic rats, mRNA levels of several transcription factors important for the maintenance of beta cell differentiation were reduced (pancreatic and duodenal homeobox 1 [Pdx1], neurogenic differentiation 1 [Neurod1], NK6 transcription factor related, locus 1 [Nkx6.1], paired box gene 6 [Pax6]), as were genes implicated in beta cell function (Glut2 [also known as solute carrier family 2 [facilitated glucose transporter], member 2 [Slc2a2], glucokinase, insulin, islet amyloid polypeptide [Iapp]). Conversely, mRNA levels of lactate dehydrogenase, which is normally suppressed in beta cells, were increased. The majority of the changes in gene expression were normalised after correction of hyperglycaemia, indicating that the severe loss of beta cell differentiation correlates with continuous exposure to diabetes. Even islet grafts from non-diabetic rats showed a few alterations in beta cell gene expression in comparison with fresh islets. Conclusion/interpretation Chronic hyperglycaemia contributes to the deterioration of beta cell differentiation after islet transplantation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplant & Cell Biol,Res Div, Boston, MA 02215 USA. St Vincents Hosp, Garvan Inst Med Res, Diabet & Obes Res Program, Sydney, NSW 2010, Australia. RP Laybutt, DR (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplant & Cell Biol,Res Div, 1 Joslin Pl, Boston, MA 02215 USA. EM Gordon.Weir@joslin.harvard.edu FU NIDDK NIH HHS [U19DK6125, DK50657, P01 DK53087, DK36836] NR 30 TC 34 Z9 34 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2007 VL 50 IS 10 BP 2117 EP 2125 DI 10.1007/s00125-007-0749-2 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208DI UT WOS:000249299600013 PM 17641871 ER PT J AU Barth, JL Yu, Y Song, W Lu, K Dashti, A Huang, Y Argraves, WS Lyons, TJ AF Barth, J. L. Yu, Y. Song, W. Lu, K. Dashti, A. Huang, Y. Argraves, W. S. Lyons, T. J. TI Oxidised, glycated LDL selectively influences tissue inhibitor of metalloproteinase-3 gene expression and protein production in human retinal capillary pericytes SO DIABETOLOGIA LA English DT Article DE diabetic retinopathy; gene array; glycation; lipoprotein; metalloproteinase; oxidation ID SMOOTH-MUSCLE-CELLS; VASCULAR ENDOTHELIAL-CELLS; EARLY DIABETIC-RETINOPATHY; LOW-DENSITY-LIPOPROTEIN; MATRIX METALLOPROTEINASES; MACULAR DEGENERATION; DCCT/EDIC COHORT; TIMP-3; GROWTH; INFLAMMATION AB Aims/hypothesis Matrix metalloproteinases (MMPs) and their natural inhibitors, tissue inhibitor of metalloproteinases (TIMPs), regulate important biological processes including the homeostasis of the extracellular matrix, proteolysis of cell surface proteins, proteinase zymogen activation, angiogenesis and inflammation. Studies have shown that their balance is altered in retinal microvascular tissues in diabetes. Since LDLs modified by oxidation/glycation are implicated in the pathogenesis of diabetic vascular complications, we examined the effects of modified LDL on the gene expression and protein production of MMPs and TIMPs in retinal pericytes. Methods Quiescent human retinal pericytes were exposed to native LDL (N-LDL), glycated LDL (G-LDL) and heavily oxidised and glycated LDL (HOG-LDL) for 24 h. We studied the expression of the genes encoding MMPs and TIMPs mRNAs by analysis of microarray data and quantitative PCR, and protein levels by immunoblotting and ELISA. Results Microarray analysis showed that MMP1, MMP2, MMP11, MMP14 and MMP25 and TIMP1, TIMP2, TIMP3 and TIMP4 were expressed in pericytes. Of these, only TIMP3 mRNA showed altered regulation, being expressed at significantly lower levels in response to HOG- vs N-LDL. Quantitative PCR and immunoblotting of cell/matrix proteins confirmed the reduction in TIMP3 mRNA and protein in response to HOG-LDL. In contrast to cellular TIMP3 protein, analysis of secreted TIMP1, TIMP2, MMP1 and collagenase activity indicated no changes in their production in response to modified LDL. Combined treatment with N- and HOG-LDL restored TIMP3 mRNA expression to a level comparable with that after N-LDL alone. Conclusion/interpretation Among the genes encoding for MMPs and TIMPs expressed in retinal pericytes, TIMP3 is uniquely regulated by HOG-LDL. Reduced TIMP3 expression might contribute to microvascular abnormalities in diabetic retinopathy. C1 Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK 73104 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. VA Med Ctr, Oklahoma City, OK USA. RP Lyons, TJ (reprint author), Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, WP1345, Oklahoma City, OK 73104 USA. EM timothy-lyons@ouhsc.edu FU NCI NIH HHS [CA095841, R24 CA095841]; NCRR NIH HHS [M01 RR-14467, P20RR016434, P20 RR016434]; NHLBI NIH HHS [R01 HL061873, HL61873] NR 49 TC 23 Z9 23 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2007 VL 50 IS 10 BP 2200 EP 2208 DI 10.1007/s00125-007-0768-z PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 208DI UT WOS:000249299600023 PM 17676308 ER PT J AU Li, J Baxter, RM Weiner, L Goetinck, PF Calautti, E Brissette, JL AF Li, Jian Baxter, Ruth M. Weiner, Lorin Goetinck, Paul F. Calautti, Enzo Brissette, Janice L. TI Foxn1 promotes keratinocyte differentiation by regulating the activity of protein kinase C SO DIFFERENTIATION LA English DT Article DE keratinocyte; epidermis; terminal differentiation; Foxn1; protein kinase C ID EPITHELIAL TERMINAL DIFFERENTIATION; CYCLOSPORINE-A; HAIR-GROWTH; NUDE GENE; MOUSE SKIN; IN-VITRO; EXPRESSION; MICE; ACTIVATION; CALCIUM AB The transcription factor Foxn1 (the product of the nude locus) promotes the terminal differentiation of epithelial cells in the epidermis and hair follicles. Activated early in terminal differentiation, Foxn1 can modulate the timing or order of trait acquisition, as it induces early features of epidermal differentiation while suppressing late features. Here, we identify protein kinase C (PKC) as a key target of Foxn1 in keratinocyte differentiation control. Foxn1 has broad negative effects on the PKC family, as the loss of Foxn1 function leads to higher levels of total, primed, and activated PKC. Phosphorylated PKC substrates (the mediators of PKC function) rise when Foxn1 is inactivated and fall when Foxn1 is overproduced, suggesting that Foxn1 antagonizes PKC's effects. When PKC inhibitors are applied to nude (Foxn1 null) keratinocytes, nude defects are normalized or suppressed, as the inhibitors prevent nude cells from underproducing early differentiation markers and overproducing late markers. Taken together, the results suggest that Foxn1 acts as a restraint or brake on PKC signaling and that without this brake PKC disrupts differentiation. The results further suggest that Foxn1 modulates stage-specific markers by modulating PKC activity, providing control over the timing of steps in the differentiation program. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Brissette, JL (reprint author), Univ Turin, Ctr Mol Biotechnol, Dulbecco Telethon Inst, Via Nizza 52, I-10126 Turin, Italy. EM jbrissette@partners.org OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NIAMS NIH HHS [AR045284]; NICHD NIH HHS [HD037490]; Telethon [TCP06001]; Fondazione Telethon NR 44 TC 7 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD OCT PY 2007 VL 75 IS 8 BP 694 EP 701 DI 10.1111/j.1432-0436.2007.00176.x PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 217NF UT WOS:000249953900003 PM 17459087 ER PT J AU Carraro, A Hsu, WM Miller, ML Kulig, KM Neville, C Borenstein, J Bonner, K Orrick, B Weinberg, E Swart, E Morgan, K Kaazempur-Mofrad, M Umberto, C Joseph, V AF Carraro, A. Hsu, W. -M. Miller, M. L. Kulig, K. M. Neville, C. Borenstein, J. Bonner, K. Orrick, B. Weinberg, E. Swart, E. Morgan, K. Kaazempur-Mofrad, M. Umberto, Cillo Joseph, Vacanti TI Liver assist device as bridge for liver transplant in hepatic failure: A first in vivo step of tissue engineering development SO DIGESTIVE AND LIVER DISEASE LA English DT Meeting Abstract C1 [Carraro, A.; Umberto, Cillo] Univ Padua, Hepatobiliary & Liver Transplant Unit, I-35100 Padua, Italy. [Carraro, A.; Hsu, W. -M.; Miller, M. L.; Kulig, K. M.; Neville, C.; Borenstein, J.; Orrick, B.; Morgan, K.; Joseph, Vacanti] Massachusetts Gen Hosp, Ctr Regenerat Med, Dept Surg, Boston, MA 02114 USA. [Hsu, W. -M.; Bonner, K.; Orrick, B.] Natl Taiwan Univ Hosp, Dept Surg, Taipei, Taiwan. [Weinberg, E.; Swart, E.] MIT, Dept Engn Mech & Biol Engn, Cambridge, MA 02139 USA. [Kaazempur-Mofrad, M.] Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PACINI EDITORE PI PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE OSPEDALETTO, 56121 PISA, ITALY SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD OCT PY 2007 VL 39 IS 10 BP A35 EP A35 DI 10.1016/j.dld.2007.07.017 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 230GH UT WOS:000250863800035 ER PT J AU Zickmund, SL Brown, KE Bielefeldt, K AF Zickmund, Susan L. Brown, Kyle E. Bielefeldt, Klaus TI A systematic review of provider knowledge of hepatitis C: Is it enough for a complex disease? SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE hepatitis C; provider; knowledge; attitude; stigmatization; barriers ID PRIMARY-CARE PHYSICIANS; CROSS-SECTIONAL SURVEY; INFECTED PATIENTS; GENERAL-PRACTICE; NATIONAL-SURVEY; UNITED-STATES; MANAGEMENT; VIRUS; EXPERIENCES; RESIDENTS AB As studies indicate that patients with hepatitis C face poor provider knowledge and even stigmatization, we conducted a systematic review of provider knowledge about and attitudes toward hepatitis C. We searched Medline for original studies between 1990 and 2005. Articles were abstracted to define target population, recruitment strategies, study design, and key findings. Twenty-six publications performed in nine countries were identified. Whereas studies demonstrated an understanding of the nature of hepatitis C, significant knowledge deficits existed related to natural history, diagnostic approaches, and treatment. The relevance of simple measures, such as vaccinations against hepatitis A and B, was underappreciated. While providers were aware of risk factors for the disease, there were substantial misperceptions, with 5%-20% of providers considering casual contact as a risk for disease acquisition. We conclude that while healthcare providers understand the nature of hepatitis C, important knowledge gaps persist, which may constitute barriers to appropriate therapy. C1 Univ Pittsburgh, Sch Med, Dept Med, VA Pittsburgh Healthcare Syst,Ctr Hlth Equ Res &, Pittsburgh, PA 15240 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City Vet Adm Med Ctr, Iowa City, IA USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol, Pittsburgh, PA USA. RP Zickmund, SL (reprint author), Univ Pittsburgh, Sch Med, Dept Med, VA Pittsburgh Healthcare Syst,Ctr Hlth Equ Res &, 151C-U Univ Dr C, Pittsburgh, PA 15240 USA. EM Susan.Zickmund@med.va.gov NR 48 TC 25 Z9 27 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2007 VL 52 IS 10 BP 2550 EP 2556 DI 10.1007/s10620-007-9753-0 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208DN UT WOS:000249300100014 PM 17406823 ER PT J AU Leung, FW Go, VLW Scremin, OU Obenaus, A Tuck, ML Golub, MS Eggena, P Leung, JW AF Leung, Felix W. Go, Vay Liang W. Scremin, Oscar U. Obenaus, Andre Tuck, Michael L. Golub, Michael S. Eggena, Peter Leung, Joseph W. TI Pilot studies to demonstrate that intestinal mucosal afferent nerves are functionally linked to visceral adipose tissue SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE capsaicin; capsaicin-sensitive afferent nerves; pulse Doppler flowmetry; hydrogen gas clearance; laser Doppler flowmetry; adipose tissue blood flow; mesenteric artery blood flow ID HYDROGEN GAS CLEARANCE; CAPSAICIN-DESENSITIZED RATS; LASER DOPPLER FLOWMETRY; BLOOD-FLOW MEASUREMENTS; ULCER MARGIN HYPEREMIA; REFLECTANCE SPECTROPHOTOMETRY; MESENTERIC HYPEREMIA; GLUCOSE-TOLERANCE; FAT ACCUMULATION; BODY-FAT AB Dietary capsaicin reduces rodent visceral fat weight. We tested the hypothesis that intact intestinal mucosal afferent nerve function is necessary for fat deposition in visceral adipose tissue sites. Rats were treated daily for 2 weeks with intragastric ( chronic treatment) vehicle or capsaicin. Superior mesenteric artery blood flow and mesenteric and inguinal fat blood flow were measured before and after capsaicin was administered into the duodenum ( acute treatment). Fat from all sites was dissected and weighed. Chronic capsaicin significantly attenuated acute capsaicin-induced mesenteric hyperemia but did not abolish the reflex wiping of the eye exposed to capsaicin, indicating that functional ablation was limited to the intestinal mucosal afferent nerves. The associated vasoconstriction in adipose tissue was inhibited at the visceral ( mesenteric) site and maintained but attenuated at the subcutaneous ( inguinal) site. The onset of vasoconstriction was instantaneous, indicating a reflex mechanism. There was a redistribution of fat from visceral to subcutaneous sites, reflected by a decrease and an increase in the percentage of body fat in the visceral and subcutaneous sites, respectively. These pilot studies reveal for the first time that normal intestinal mucosal afferent nerve function is necessary for the physiologic accumulation of fat in visceral adipose tissue sites. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Div Gastroenterol 111G, Sepulveda, CA 91343 USA. Sepulveda Ambulatory Care Ctr & Nursing Home, Res & Med Serv, Sepulveda, CA 91343 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Loma Linda Univ, Dept Radiat Med, Loma Linda, CA 92350 USA. Univ Calif Davis, Sacramento, CA 95655 USA. No Calif Healthcare Syst, Sacramento Vet Affairs Med Ctr, Sacramento, CA 95655 USA. RP Leung, FW (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr & Nursing Home, Div Gastroenterol 111G, 16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@va.gov FU NCI NIH HHS [1 P01 CA42710] NR 50 TC 7 Z9 7 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2007 VL 52 IS 10 BP 2695 EP 2702 DI 10.1007/s10620-006-9645-8 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208DN UT WOS:000249300100036 PM 17393331 ER PT J AU Lu, M Malladi, V Agha, A Abudayyeh, S Han, C Siepman, N Graham, DY AF Lu, Maggie Malladi, Vikram Agha, Aamer Abudayyeh, Suhaib Han, Cong Siepman, Nancy Graham, David Y. TI Failures in a proton pump inhibitor therapeutic substitution program: Lessons learned SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE proton pump inhibitor; lansoprazole; rabeprazole; therapeutic substitution; gastroesophageal reflux disease; clinical trial ID GASTROESOPHAGEAL-REFLUX DISEASE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RHEUMATOID-ARTHRITIS; INTERCHANGE PROGRAM; OMEPRAZOLE; LANSOPRAZOLE; NONRESPONDERS; RESPONDERS; RESPONSES; SYMPTOMS AB The pathogenesis of patient dissatisfaction following involuntary therapeutic substitutions involving proton pump inhibitors (PPIs) is poorly understood. The aim of this study was to describe the patient population experiencing therapeutic failure and investigate whether failure was related to individual differences in response to the different PPIs. Treatment failures in a lansoprazole-rabeprazole therapeutic substitution program were compared to switch successes. A subgroup was randomized in a double-blind, double-dummy, crossover study to four 2-week periods of lansoprazole-rabeprazole-lansoprazole-rabeprazole or vice versa. Measures included overall rating of gastrointestinal reflux disease (GERD) symptoms for the past week as well as the frequency and distress scales of the GERD Symptom Assessment Scale. One hundred fifteen nonresponders were compared with 54 successful responders. Nonresponders consisted primarily of patients with GERD (74%, vs. 44% of responders; P = 0.005) who had undergone upper gastrointestinal endoscopy ( 50%, vs. 31% of responders; P = 0.02). Twelve patients completed the randomized treatment study. The interrater kappa coefficient for responder status was estimated to be 0.80 for lansoprazole and 0.21 for rabeprazole. The majority of PPI nonresponders had a clinical diagnosis of GERD and were receiving >= 40 mg of rabeprazole daily. This pilot study provides new insights into the design of subsequent studies of nonresponders in PPI therapeutic substitution programs. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Room 3A-320 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu FU NIDDK NIH HHS [DK56338] NR 19 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2007 VL 52 IS 10 BP 2813 EP 2820 DI 10.1007/s10620-007-9811-7 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 208DN UT WOS:000249300100053 PM 17393309 ER PT J AU Kazantsev, AG AF Kazantsev, Aleksey G. TI Cellular pathways leading to neuronal dysfunction and degeneration SO DRUG NEWS & PERSPECTIVES LA English DT Review ID ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE; NEURODEGENERATIVE DISEASES; MITOCHONDRIAL DYSFUNCTION; ALPHA-SYNUCLEIN; POSTTRANSLATIONAL MODIFICATIONS; PROTEIN DEACETYLASES; MOLECULAR-MECHANISMS; HISTONE ACETYLATION AB There is no cure for devastating neurodegenerative disorders such as Alzheimer's, Parkinson's, Huntington's diseases or amyotrophic lateral sclerosis, which cause longterm suffering and ultimately death. Slowly progressing neurodegenerative diseases affect the lives of many thousands of patients and their families. These disorders are characterized by pathological changes in disease-specific areas of the brain. In each disease, these pathological processes lead to dysfunction and degeneration in distinct subsets of neurons. Research on neurodegenerative disorders has revealed a complex picture of cellular pathology involving abnormalities in biochemical processes, gene regulation, responses to external stimuli, etc. However, despite the differences in the clinical manifestations and selective neuronal vulnerability, on cellular and molecular levels the underlying pathological processes appear similar across different diseases, suggesting common pathways of neurodegeneration. Elucidation of the precise neurodegenerative mechanism(s) is essential for development of effective and safe therapy for these lethal human disorders. (c) 2007 Prous Science. All rights reserved. C1 [Kazantsev, Aleksey G.] Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA USA. [Kazantsev, Aleksey G.] Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Drug Discovery Lab, Charlestown, MA USA. RP Kazantsev, AG (reprint author), Harvard Univ, Sch Med, Dept Neurol, Charlestown, MA USA. EM akazantsev@partners.org NR 106 TC 11 Z9 11 U1 1 U2 3 PU PROUS SCIENCE, SA-THOMSON REUTERS PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD OCT PY 2007 VL 20 IS 8 BP 501 EP 509 DI 10.1358/dnp.2007.20.8.1157616 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 249MS UT WOS:000252233300003 PM 18080037 ER PT J AU Nicosia, MA Robbins, J AF Nicosia, Mark A. Robbins, JoAnne TI The usefulness of the line spread test as a measure of liquid consistency SO DYSPHAGIA LA English DT Article DE deglutition; deglutition disorders; dysphagia; viscosity; thickened liquids ID VISCOSITY; FOODS AB Although dietary modification is a common treatment strategy used to manage dysphagic patients who aspirate thin liquids, there are no standard definitions for thickened liquid preparation. This lack of standardization leads to variability in practice and points to the need for a simple tool for clinicians to assess thickened liquid consistency. The current study analyzed the utility of the Line Spread Test (LST) in this regard. Twenty-six liquids (10 powder-thickened "nectar" juices, 10 powder-thickened "honey" juices, and 6 barium mixtures) were assessed using both a viscometer for objective measurement of viscosity and the LST. Whereas the LST was able to separate the juices into nectar and honey categories, it was not able to separate barium mixtures into these categories nor compare barium to juices. Furthermore, the LST was not predictive of viscosity. Thus, the results of the current study suggest that the LST may be useful in the broad categorization of fluids into therapeutically significant groupings but that it cannot be used more specifically to measure fluid viscosity. Further studies of this and other tools are necessary to identify inexpensive practical tools for quantification of thickened liquid consistency. C1 William S Middleton Mem Vet Adm Med Ctr, GRECC, Madison, WI 53705 USA. Univ Wisconsin, Inst Aging, Madison, WI 53706 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Commun Sci & Disorders Res Grp Invest, Rockville, MD USA. RP Robbins, J (reprint author), William S Middleton Mem Vet Adm Med Ctr, GRECC, 2500 Overlook Terrace,11G, Madison, WI 53705 USA. EM jrobbin2@wisc.edu FU NIA NIH HHS [T32 AG00213]; NIDCD NIH HHS [U01 DC03206]; NINDS NIH HHS [R01 NS24427] NR 24 TC 12 Z9 12 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2007 VL 22 IS 4 BP 306 EP 311 DI 10.1007/s00455-007-9086-3 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 219VN UT WOS:000250116400004 PM 17581694 ER PT J AU Felton, SM Gaige, TA Benner, T Reese, TG Wedeen, VJ Gilbert, RJ AF Felton, Samuel M. Gaige, T. A. Benner, T. Reese, T. G. Wedeen, V. J. Gilbert, R. J. TI Association of lingual myoarchitecture with local mechanics during the propulsive phase of swallowing determined by magnetic resonance imaging SO DYSPHAGIA LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, NMR Ctr, Dept Radiol, Charlestown, MA USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD OCT PY 2007 VL 22 IS 4 BP 365 EP 365 PG 1 WC Otorhinolaryngology SC Otorhinolaryngology GA 219VN UT WOS:000250116400030 ER PT J AU Bagby, S Xue, H Kupfer, P Lin, B DuPriest, E Roulliet, J AF Bagby, S. Xue, H. Kupfer, P. Lin, B. DuPriest, E. Roulliet, J. TI Maternal protein restriction in microswine: food restriction from weaning to prevent excess intake corrects vascular dysfunction in juvenile offspring SO EARLY HUMAN DEVELOPMENT LA English DT Meeting Abstract C1 [Bagby, S.; Kupfer, P.; Lin, B.; DuPriest, E.; Roulliet, J.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Bagby, S.; Xue, H.; Kupfer, P.; Lin, B.; DuPriest, E.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD OCT PY 2007 VL 83 SU 1 BP S87 EP S87 DI 10.1016/S0378-3782(07)70187-1 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 232YS UT WOS:000251058200188 ER PT J AU Lapatto, R Pallais, JC Zhang, DS Chan, YM Mahan, A Cerrato, F Le, WW Hoffman, GE Seminara, SB AF Lapatto, Risto Pallais, J. Carl Zhang, Dongsheng Chan, Yee-Ming Mahan, Amy Cerrato, Felecia Le, Wei Wei Hoffman, Gloria E. Seminara, Stephanie B. TI Kiss1(-/-) mice exhibit more variable hypogonadism than Gpr54(-/-) mice SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FOLLICLE-STIMULATING-HORMONE; METASTASIS-SUPPRESSOR GENE; PERSISTENT VAGINAL CORNIFICATION; HYPOGONADOTROPIC HYPOGONADISM; TARGETED DISRUPTION; KISS-1; MOUSE; IMMUNOREACTIVITY; KISSPEPTINS AB The G protein-coupled receptor Gpr54 and its ligand metastin (derived from the Kiss1 gene product kisspeptin) are key gatekeepers of sexual maturation. Gpr54 knockout mice demonstrate hypogonadotropic hypogonadism, but until recently, the phenotype of Kiss1 knockout mice was unknown. This report describes the reproductive phenotypes of mice carrying targeted deletions of Kiss1 or Gpr54 on the same genetic background. Both Kiss1 and Gpr54 knockout mice are viable but infertile and have abnormal sexual maturation; the majority of males lack preputial separation, and females have delayed vaginal opening and absence of estrous cycling. Kiss1 and Gpr54 knockout males have significantly smaller testes compared with controls. Gpr54 knockout females have smaller ovaries and uteri than wild-type females. However, Kiss1 knockout females demonstrate two distinct phenotypes: half have markedly reduced gonadal weights similar to those of Gpr54 knockout mice, whereas half exhibit persistent vaginal cornification and have gonadal weights comparable with those of wild-type females. FSH levels in both Kiss1 and Gpr54 knockout males and females are significantly lower than in controls. When injected with mouse metastin 43-52, a Gpr54 agonist, Gpr54 knockout mice fail to increase gonadotropins, whereas Kiss1 knockout mice respond with increased gonadotropin levels. In summary, both Kiss1 and Gpr54 knockout mice have abnormal sexual maturation consistent with hypogonadotropic hypogonadism, although Kiss1 knockout mice appear to be less severely affected than their receptor counterparts. Kiss1 knockout females demonstrate a bimodal phenotypic variability, with some animals having higher gonadal weight, larger vaginal opening, and persistent vaginal cornification. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Univ Helsinki, Hosp Children & Adolescents, FIN-00029 Helsinki, Finland. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21209 USA. RP Lapatto, R (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Barlett Hall Extens,55 Fruit St, Boston, MA 02114 USA. EM rlapatto@partners.org FU NICHD NIH HHS [U54 HD028138, U54 HD 028138, U54 HD 28934] NR 32 TC 269 Z9 278 U1 0 U2 15 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2007 VL 148 IS 10 BP 4927 EP 4936 DI 10.1210/en.2007-0078 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 211LP UT WOS:000249525600048 PM 17595229 ER PT J AU Fong, DG Ryou, M Pai, RD Tavakkolizadeh, A Rattner, DW Thompson, CC AF Fong, D. G. Ryou, M. Pai, R. D. Tavakkolizadeh, A. Rattner, D. W. Thompson, C. C. TI Transcolonic ventral wall hernia mesh fixation in a porcine model SO ENDOSCOPY LA English DT Article ID NOTES SURVIVAL; REPAIR AB Background and study aims: A natural orifice transluminal endoscopic surgery (NOTES) approach to ventral wall hernia repair may represent a potentially less invasive alternative to current transabdominal surgical techniques. We aimed to investigate the feasibility of using transcolonic NOTES to deliver hernia repair mesh into the peritoneal cavity, as well as the ability to manipulate composite mesh and secure it to the abdominal wall. Methods: Five pigs weighing 20 to 25 kg were used in this feasibility study involving two acute and three survival experiments. A prototype mesh delivery system was used to transfer 1.5-2-cm x 2.5-3-cm pieces of composite hernia mesh into the peritoneal cavity. Neodymium magnets on a prototype control arm were used to help position the mesh by magnetically engaging previously placed endoscopic clips. Transfascial fixation of the mesh with 3-0 monofilament sutures was achieved using a 19-gauge hollow needle, pusher wire, and a suture tag system. Results: Composite hernia mesh was successfully transferred and secured in 5/5 attempts. All three survival animals thrived for 14 days prior to elective sacrifice. At necropsy, the mesh sites were found to be well peritonealized without adhesions. Suture placement through the posterior fascia was confirmed in 10/12 sutures. Of these, four sutures were within the abdominal musculature, and two sutures were through the anterior fascia (transfascial). Conclusions: Transcolonic delivery, transcutaneous magnetic manipulation, and fixation of composite hernia mesh are technically feasible in a porcine model with animal survival. An effective suturing method that allows consistent anchoring through the anterior fascia would be preferred and may require the development of novel devices. C1 Brigham & Womens Hosp, Div Gastroenterol, Therapeut Endoscopy Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. RP Thompson, CC (reprint author), Brigham & Womens Hosp, Div Gastroenterol, Therapeut Endoscopy Grp, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org NR 9 TC 51 Z9 54 U1 1 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2007 VL 39 IS 10 BP 865 EP 869 DI 10.1055/s-2007-966916 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 228HE UT WOS:000250719700004 PM 17968801 ER PT J AU Ryou, M Fong, DG Pai, RD Tavakkolizadeh, A Rattner, DW Thompson, CC AF Ryou, M. Fong, D. G. Pai, R. D. Tavakkolizadeh, A. Rattner, D. W. Thompson, C. C. TI Dual-port distal pancreatectomy using a prototype endoscope and endoscopic stapler: a natural orifice transluminal endoscopic surgery (NOTES) survival study in a porcine model SO ENDOSCOPY LA English DT Article ID TRANSVAGINAL HYDROLAPAROSCOPY; LAPAROSCOPIC PNEUMODISSECTION; CLOSURE; PERFORATIONS; PANCREAS; PROGRESS AB Background and study alms: Natural orifice transluminal endoscopic surgery (NOTES) is a potentially less invasive alternative to laparoscopic surgery that may be applicable to distal pancreatectomy. We aimed to demonstrate the technical feasibility of a NOTES distal pancreatectomy in an in vivo porcine model via a combined transvaginal-transcolonic approach. Material and methods: The procedure was performed in. five female Yorkshire pigs weighing approximately 30 kg each. A prototype endoscope ("R-scope"), advanced into the peritoneal cavity through an anterior colotomy, and a computer-assisted linear stapler, introduced transvaginally, were used in dissection and resection of the distal pancreas. Prone positioning was used to enhance retroperitoneal exposure. Pneumodissection was used for blunt dissection. The colotomies were closed with endoloops. Necropsies were done immediately after the procedure in the first three animals, and after 2 weeks' survival in the final two animals. Results: Distal pancreatectomy was successful in all five animals. Prone positioning was critically important for proper exposure of retroperitoneal and pelvic structures. Pneumodissection was effective for blunt dissection, and both the linear stapler and R-scope functioned smoothly. Transvaginal and transcolonic access provided similar intraperitoneal views, and the dual-lumen approach enhanced triangulation. Both survival animals thrived postoperatively. Necropsies revealed clean staple lines; closed transcolonic and transvaginal incisions; and absence of infection, hemorrhage, or fluid collections. Conclusions: NOTES distal pancreatectomy is technically feasible in the porcine model. The transvaginal approach provides a vantage point very similar to that of the transcolonic route and holds promise as a NOTES access site, either singly or as part of a dual-lumen approach. The endoscopic linear stapler and R-scope both advance NOTES capabilities. The novel concepts of fully prone positioning, pneumodissection, and endoloop colotomy closures are introduced. Considering anatomical differences and that healthy animals were used, transferring this technique to patients with pancreatic disease might be difficult and further modifications would likely be needed. C1 Harvard Univ, Brigham & Womens Hosp, Div Gastroenterol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Gen Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gen Surg, Boston, MA USA. RP Thompson, CC (reprint author), Harvard Univ, Brigham & Womens Hosp, Div Gastroenterol, Sch Med, 75 Francis St, Boston, MA 02115 USA. EM ccthompson@partners.org NR 27 TC 70 Z9 74 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2007 VL 39 IS 10 BP 881 EP 887 DI 10.1055/s-2007-966908 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 228HE UT WOS:000250719700007 PM 17968804 ER PT J AU Rossetti, AO Logroscino, G Milligan, TA Michaelides, C Replansky, S Bromfield, EB AF Rossetti, Andrea O. Logroscino, G. Milligan, T. A. Michaelides, C. Replansky, S. Bromfield, E. B. TI Status epilepticus clinical prognostic score: Validation and application SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Rossetti, Andrea O.] CHU Vaudois, CH-1011 Lausanne, Switzerland. [Logroscino, G.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Milligan, T. A.; Replansky, S.; Bromfield, E. B.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Michaelides, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI LOGROSCINO, GIANCARLO/K-5148-2016 OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 6 EP 6 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900012 ER PT J AU Spitz, M Anderson, CA Wortzel, HS Maa, EH Strom, LS AF Spitz, Mark Anderson, C. A. Wortzel, H. S. Maa, E. H. Strom, L. S. TI Disrobing in epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Spitz, Mark; Anderson, C. A.; Wortzel, H. S.; Maa, E. H.; Strom, L. S.] Univ Colorado, Ctr Hlth Sci, Denver, CO 80309 USA. [Anderson, C. A.; Wortzel, H. S.] Denver Vet Affairs Med Ctr, MIRECC, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 17 EP 17 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900041 ER PT J AU Thibert, RL Conant, KD Braun, EK Bruno, PL Nespeca, MP Said, RR Thiele, EA AF Thibert, Ronald L. Conant, K. D. Braun, E. K. Bruno, P. L. Nespeca, M. P. Said, R. R. Thiele, E. A. TI Epilepsy in Angelman syndrome SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 30-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Thibert, Ronald L.; Conant, K. D.; Bruno, P. L.; Thiele, E. A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Braun, E. K.] Angelman Syndrome Fdn, Aurora, CO USA. [Nespeca, M. P.] Univ Calif San Diego, San Diego, CA 92103 USA. [Said, R. R.] Univ Texas SW Med Ctr, Comprehens Epilepsy Program, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 EI 1528-1167 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 72 EP 72 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900197 ER PT J AU Bruno, PL Conant, KD Thibert, RL Braun, EK Said, RR Nespeca, MP Thiele, EA AF Bruno, Patricia L. Conant, K. D. Thibert, R. L. Braun, E. K. Said, R. R. Nespeca, M. P. Thiele, E. A. TI Treatment of epilepsy in Angelman Syndrome SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Bruno, Patricia L.; Conant, K. D.; Thibert, R. L.; Thiele, E. A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Braun, E. K.] Angelman Syndrome Fdn, Aurora, IL USA. [Nespeca, M. P.] Univ Calif San Diego, Div Pediat Neurol, San Diego, CA 92103 USA. [Said, R. R.] Univ Texas SW Med Ctr Dallas, Comprehens Epilepsy Program, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 74 EP 75 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900204 ER PT J AU Conant, KD Thibert, RL Braun, EK Thiele, EA AF Conant, Kerry D. Thibert, R. L. Braun, E. K. Thiele, E. A. TI Sleep disturbances and epilepsy in Angelman Syndrome SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Conant, Kerry D.; Thibert, R. L.; Thiele, E. A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. [Braun, E. K.] Angelman Syndrome, Aurora, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 76 EP 77 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900209 ER PT J AU Pfeifer, H Thiele, EA AF Pfeifer, Heidi Thiele, E. A. TI Initiating and maintaining the ketogenic diet in breastfed infants SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Pfeifer, Heidi; Thiele, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 94 EP 94 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900257 ER PT J AU Lyczkowski, D Pfeifer, HH Thiele, EA AF Lyczkowski, David Pfeifer, H. H. Thiele, E. A. TI The low glycemic index dietary treatment for epilepsy in tuberous sclerosis complex SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Lyczkowski, David; Pfeifer, H. H.; Thiele, E. A.] Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 101 EP 101 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900277 ER PT J AU Paolini, JL Muzykewicz, DA Major, P Numis, A Pulsifer, M Thiele, EA AF Paolini, Jan L. Muzykewicz, D. A. Major, P. Numis, A. Pulsifer, M. Thiele, E. A. TI Epilepsy and autism in tuberous sclerosis complex SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Paolini, Jan L.; Muzykewicz, D. A.; Major, P.; Numis, A.; Pulsifer, M.; Thiele, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 116 EP 117 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900321 ER PT J AU Major, P Thiele, EA AF Major, Philippe Thiele, E. A. TI Vagal nerve stimulation (VNS) for refractory epilepsy in tuberous sclerosis complex SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Major, Philippe; Thiele, E. A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 145 EP 146 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900401 ER PT J AU Tanaka, N von Pechmann, D Wakeman, DG Liu, H Madsen, JR Bourgeois, BF Cole, AJ Hamalainen, MS Stufflebeam, SM AF Tanaka, Naoaki von Pechmann, D. Wakeman, D. G. Liu, H. Madsen, J. R. Bourgeois, B. F. Cole, A. J. Haemaelaeinen, M. S. Stufflebeam, S. M. TI Ictal magnetoencephalographic study in patients with intractable epilepsy using dynamic statistical parametric mapping (DSPM) SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Tanaka, Naoaki; von Pechmann, D.; Wakeman, D. G.; Liu, H.; Haemaelaeinen, M. S.; Stufflebeam, S. M.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Madsen, J. R.] Childrens Hosp, Dept Neurosurg, Boston, MA USA. [Bourgeois, B. F.] Childrens Hosp, Dept Neurol, Boston, MA USA. [Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 209 EP 209 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900561 ER PT J AU Kobayashi, E Grova, C Tanaka, N Lina, JM Hamalainen, M Stufflebeam, S AF Kobayashi, Eliane Grova, C. Tanaka, N. Lina, J. M. Haemaelaeinen, M. Stufflebeam, S. TI Contribution of distributed source analyses of MEG signal to the understanding of epileptic networks in focal cortical dysplasia (FCD) SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Kobayashi, Eliane; Grova, C.] Montreal Neurol Hosp & Inst, Montreal, PQ, Canada. [Grova, C.; Lina, J. M.] Univ Montreal, Dept Psychol, Ctr Rech & Neuropsychol, MEG Lab, Montreal, PQ, Canada. [Tanaka, N.; Haemaelaeinen, M.; Stufflebeam, S.] Harvard Univ, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, MEG Lab, Boston, MA 02115 USA. [Lina, J. M.] Ecole Technol Super, Montreal, PQ, Canada. RI Hamalainen, Matti/C-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 210 EP 210 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900562 ER PT J AU Swiercz, W Sabolek, HR Staley, KJ AF Swiercz, Waldemar Sabolek, H. R. Staley, K. J. TI A computer model of ca3 epileptiform activity exacerbated by loss of function in excitatory connections SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Swiercz, Waldemar; Sabolek, H. R.; Staley, K. J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Swiercz, Waldemar; Sabolek, H. R.; Staley, K. J.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 240 EP 240 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900647 ER PT J AU Sabolek, H Swiercz, WB Dzhala, VI Staley, KJ AF Sabolek, Helen Swiercz, W. B. Dzhala, V. I. Staley, K. J. TI Using calcium imaging to investigate "Cerebral Fibrillation" as a mechanism of epileptiform activity following loss of function in excitatory pathways SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Sabolek, Helen; Swiercz, W. B.; Dzhala, V. I.; Staley, K. J.] Massachusetts Gen Hosp, Charlestown, MA USA. [Sabolek, Helen; Swiercz, W. B.; Dzhala, V. I.; Staley, K. J.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 242 EP 243 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900653 ER PT J AU Moussally, J Zheng, Y Cole, AJ AF Moussally, Jon Zheng, Y. Cole, A. J. TI Intravenous levetiracetam in the rat pilocarpine-induced status epilepticus model: behavioral, physiological and histological studies SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. [Moussally, Jon] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Moussally, Jon; Zheng, Y.; Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Res Lab, Boston, MA 02114 USA. [Zheng, Y.; Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 293 EP 293 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900791 ER PT J AU Lee, CL Antalffy, B Frost, JD Hrachovy, RA Swann, JW AF Lee, Chong L. Antalffy, B. Frost, J. D., Jr. Hrachovy, R. A. Swann, J. W. TI Persistent focal neocortical abnormalities in the TTX model of infantile spasms SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Lee, Chong L.; Swann, J. W.] Cain Fdn Labs, Baylor Coll Med, Houston, TX 77030 USA. [Lee, Chong L.; Antalffy, B.; Frost, J. D., Jr.; Hrachovy, R. A.; Swann, J. W.] Baylor Coll Med, Houston, TX 77030 USA. [Hrachovy, R. A.] Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 295 EP 295 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900797 ER PT J AU Gopal, AA Meng, NF Melinosky, C Bromfield, E Cole, AJ Devinsky, O Doyle, W Eskandar, E Madsen, JR Ulbert, I Halgren, E Cash, SS AF Gopal, Abilash A. Meng, N. F. Melinosky, C. Bromfield, E. Cole, A. J. Devinsky, O. Doyle, W. Eskandar, E. Madsen, J. R. Ulbert, I. Halgren, E. Cash, S. S. TI Preictal increases in multi-unit firing inpatients with intractable focal epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Gopal, Abilash A.; Meng, N. F.; Melinosky, C.; Cole, A. J.; Eskandar, E.; Cash, S. S.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gopal, Abilash A.] Tufts Univ, Sch Med, Boston, MA 02111 USA. [Bromfield, E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Devinsky, O.; Doyle, W.] NYU, New York, NY USA. [Madsen, J. R.] Childrens Hosp, Boston, MA 02115 USA. [Ulbert, I.] Hungarian Acad Sci, Inst Psychol, Budapest, Hungary. [Halgren, E.] Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 309 EP 310 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900833 ER PT J AU Michaelides, C Kumar, J Costello, D Cole, AJ AF Michaelides, Costas Kumar, J. Costello, D. Cole, A. J. TI Tiagabine-induced reversible encephalopathy. A case series SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Michaelides, Costas; Kumar, J.; Costello, D.; Cole, A. J.] Massachusetts Gen Hosp, Epilepsy Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 314 EP 316 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900849 ER PT J AU Pugh, MJV VanCott, A Knoefel, JE Cramer, JA Berlowitz, DR AF Pugh, Mary Jo V. VanCott, A. Knoefel, J. E. Cramer, J. A. Berlowitz, D. R. TI Potential drug interactions among older veterans newly treated for epilepsy: A common event SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Pugh, Mary Jo V.] S Texas Vet Hlth Care Syst, VERDICT 11C6, San Antonio, TX USA. [Pugh, Mary Jo V.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78285 USA. [VanCott, A.] VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. [VanCott, A.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Knoefel, J. E.] VA New Mexico Hlth Care Syst, Albuquerque, NM USA. [Berlowitz, D. R.] Boston Univ, Sch Publ Hlth, Hlth Serv Res & Policy, Boston, MA 02215 USA. [Berlowitz, D. R.] Bedford VA Hosp, CHQOER, Bedford, MA USA. [Cramer, J. A.] Yale Univ, New Haven, CT 06520 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 326 EP 326 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900877 ER PT J AU Maa, E Bainbridge, J Spitz, MC Staley, KJ AF Maa, Edward Bainbridge, J. Spitz, M. C. Staley, K. J. TI Oral bumetanide add-on therapy in refractory temporal lobe epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Maa, Edward; Bainbridge, J.; Spitz, M. C.] Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. [Staley, K. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 330 EP 331 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900889 ER PT J AU Herzog, AG Blum, AS Farina, EL Maestri, X Garcia, E Selvitelli, M Krishnamurthy, K Hoch, DB Replansky, S Dworetzky, B Bromfield, EB AF Herzog, Andrew G. Blum, A. S. Farina, E. L. Maestri, X. Garcia, E. Selvitelli, M. Krishnamurthy, K. Hoch, D. B. Replansky, S. Dworetzky, B. Bromfield, E. B. TI Variation of serum valproate and lamotrigine levels in relation to menstrual cycle phase and oral contraceptive use: An interim analysis SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Herzog, Andrew G.; Farina, E. L.; Selvitelli, M.; Krishnamurthy, K.] Beth Israel Deaconess Med Ctr, Harvard Neuroendocrine Unit, Boston, MA USA. [Blum, A. S.; Maestri, X.] Rhode Isl Hosp, Dept Neurol, Providence, RI USA. [Garcia, E.] Newton Wellesley Hosp, Dept Neurol, Newton, MA USA. [Hoch, D. B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Replansky, S.; Dworetzky, B.; Bromfield, E. B.] Brigham & Womens Hosp, Dept Neurol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 362 EP 362 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900976 ER PT J AU Cole, AJ Hammer, A Vuong, A VanLandingham, KX AF Cole, Andrew J. Hammer, A. Vuong, A. VanLandingham, K. X. TI Lamotrigine as adjunctive therapy in subjects with primary generalized tonic-clonic seizures with and without generalized spike and wave SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Cole, Andrew J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Hammer, A.; Vuong, A.; VanLandingham, K. X.] GlaxoSmithKline Inc, Res & Dev, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 370 EP 370 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917900997 ER PT J AU Zhao, S Aviles, ER Fujikawa, DG AF Zhao, Shuangping Aviles, E. R., Jr. Fujikawa, D. G. TI Translocation to neuronal nuclei of mitochondrial and lysosomal death-promoting proteins within the first 60 minutes of generalized seizures SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Zhao, Shuangping; Aviles, E. R., Jr.; Fujikawa, D. G.] VA Greater LA Healthcare Syst, North Hills, CA USA. [Fujikawa, D. G.] Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 387 EP 387 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901044 ER PT J AU Tallent, M Huberfeld, G Swiercz, WB Shao, LR AF Tallent, Melanie Huberfeld, Gilles Swiercz, Waldemar B. Shao, Li-Rong TI The transition from interictal to ictal bursting: An update SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Tallent, Melanie] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. [Huberfeld, Gilles] Univ Paris 06, Fac Med Pitie Salpetriere, Epilepsy Unit, INSERM U739, Paris, France. [Swiercz, Waldemar B.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. [Shao, Li-Rong] Univ Utah, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 408 EP 408 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901095 ER PT J AU Deuffic-Burban, S Losina, E Wang, B Gabillard, D Messou, E Divi, N Freedberg, KA Anglaret, X Yazdanpanah, Y AF Deuffic-Burban, Sylvie Losina, Elena Wang, Bingxia Gabillard, Delphine Messou, Eugene Divi, Nomita Freedberg, Kenneth A. Anglaret, Xavier Yazdanpanah, Yazdan TI Estimates of opportunistic infection incidence or death within specific CD4 strata in HIV-infected patients in Abidjan, Cote d'Ivoire: impact of alternative methods of CD4 count modelling SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE CD4 cell count; highly active antiretroviral therapy; opportunistic infections; sub-Saharan Africa; time-dependent variable ID ACTIVE ANTIRETROVIRAL THERAPY; COTRIMOXAZOLE PROPHYLAXIS; VIRAL LOAD; HIV-1-INFECTED ADULTS; BACTERIAL DISEASES; CHRONIC MORTALITY; RANDOMIZED-TRIAL; MORBIDITY; AFRICA; COHORT AB CD4 lymphocyte count is an important surrogate marker of HIV disease progression, but it is often unavailable at the time of clinical events. We analysed data from the Cotrame cohort (1999-2004) and the Trivacan Structured Treatment Interruption trial (2002-2005) to estimate the incidence of opportunistic infections and death within specific CD4 strata in HIV-infected patients receiving highly active antiretroviral therapy (HAART) in sub-Saharan Africa. We used three methods of CD4 modelling: the first assumed that CD4 cell count remained constant until the next measurement; the second assumed that it changed immediately to the level of the subsequent measurement; and the third assumed that it followed a linear function between two consecutive CD4 measurements. The cohort used in this analysis consisted of 981 patients. The incidence rates of opportunistic infections were highest in the lower CD4 strata and decreased in the higher CD4 count strata. The incidence rates of mild opportunistic infections and severe bacterial infections, however, remained high in the highest CD4 stratum. Although all confidence intervals overlapped among the three methods, the incidence rate estimates showed differences of up to 74% in the lowest CD4 stratum. Different methods of estimating CD4 counts at the time of clinical events led to minor differences in incidence rates, except in the CD4 stratum < 50 cells/mm(3), where the follow-up time was shorter. All of the models indicate that the overall incidence of opportunistic infections under HAART in sub-Saharan Africa is high. This suggests that prophylaxis against opportunistic infections may be needed even for patients receiving HAART. C1 CRESGE LEM, CNRS, UMR 8179, F-59046 Lille, France. CHRU Lille, Hop Swynghedauw, INSERM, U795,CTRS, Lille, France. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Univ Bordeaux 2, INSERM, U593, F-33076 Bordeaux, France. Programme PACCI, Abidjan, Cote Ivoire. Ctr Hosp Tourcoing, Serv Malad Infect & Voyageur, F-59208 Tourcoing, France. Fac Med Lille, EA 2694, F-59045 Lille, France. RP Deuffic-Burban, S (reprint author), CRESGE LEM, CNRS, UMR 8179, 41 Rue Port, F-59046 Lille, France. EM sylvie.burban@libertysurf.fr RI Anglaret, Xavier/F-7333-2013 FU NIAID NIH HHS [K23 AI0794, AI058736, K23 AI001794, K23 AI001794-05, K24 AI062476, K24 AI062476-01, K25 AI050436, K25 AI050436-05, K25 AI50436, P30 AI042851, P30 AI042851-05, P30 AI42851, R01 AI058736, R01 AI058736-01A1] NR 21 TC 11 Z9 14 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD OCT PY 2007 VL 22 IS 10 BP 737 EP 744 DI 10.1007/s10654-007-9175-5 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 213DY UT WOS:000249647500009 PM 17828437 ER PT J AU Gastinne, T Leleu, X Duhamel, A Moreau, AS Franck, G Andrieux, J Lai, JL Coiteux, V Yakoub-Agha, I Bauters, F Harousseau, JL Zandecki, M Facon, T AF Gastinne, Thomas Leleu, Xavier Duhamel, Alain Moreau, Anne-Sophie Franck, Genevieve Andrieux, Joris Lai, Jean-Luc Coiteux, Valerie Yakoub-Agha, Ibrahim Bauters, Francis Harousseau, Jean-Luc Zandecki, Marc Facon, Thierry CA Intergroupe Francophone du Myelome TI Plasma cell growth fraction using Ki-67 antigen expression identifies a subgroup of multiple myeloma patients displaying short survival within the ISS stage I SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE multiple myeloma; proliferation index; Ki-67; International Staging System; prognostic factor ID MONOCLONAL-ANTIBODY KI-67; PATHOLOGICAL BONE-MARROW; HIGH-DOSE THERAPY; PROLIFERATIVE ACTIVITY; PROGNOSTIC-FACTORS; CHROMOSOME-13 ABNORMALITIES; RANDOMIZED TRIAL; LYMPHOID-TISSUE; BETA-2-MICROGLOBULIN; TRANSPLANTATION AB The current most powerful prognostic model in Multiple Myeloma (MM) combines beta-2 microglobulin (b2m) with albumin, corresponding to the International Staging System (ISS). However, the prognosis of patients within the ISS stage I (high albumin and low b2m) may vary. Ki-67 is a nuclear protein associated with cell proliferation. We retrospectively evaluated the percentage of bone marrow plasma cells expressing Ki-67 antigen (Ki-67 index) in a series of 174 untreated MM patients at diagnosis. Median survival was 51, 41 and 20 months respectively, and median Ki-67 index was 3.0%, 6.1% and 6.5% in ISS stages I, II, and III respectively. Independently of ISS, Ki-67 index >= 4% was highly predictive of adverse prognosis. Ki-67 index correlated with markers of intrinsic malignancy and with markers of tumour burden. Within ISS stage I, median survival was of 31 months (RR of death 2.65) in patients with Ki-67 index >= 4%. Eventually, the combination of Ki-67 with b2m produced an efficient prognostic model, which appeared most effective in our series when compared with b2m and KI-67 with chromosome 13 deletion models. In this series, we demonstrated that a proliferation marker provides clear-cut additional survival prognostic information to b2m into the ISS model. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CHU Nantes, Serv Hematol Clin, F-44035 Nantes 01, France. Harvard Univ, Sch Med, Boston, MA USA. CHRU, Serv Malad Sang, Lille, France. CHRU, Serv Biostat, Lille, France. CHU Angers, Hematol Lab, Angers, France. CHU Angers, UPRES EA 3863 Anal Determinants Reponse I, Angers, France. CHRU, Serv Genet Med, Lille, France. RP Gastinne, T (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Duhamel, Alain/B-8624-2011; FACON, THIERRY/M-9736-2014; Duhamel, Alain/A-4899-2013 OI FACON, THIERRY/0000-0001-7705-8460; NR 37 TC 11 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD OCT PY 2007 VL 79 IS 4 BP 297 EP 304 DI 10.1111/j.1600-0609.2007.00915.x PG 8 WC Hematology SC Hematology GA 210AC UT WOS:000249428100005 PM 17692103 ER PT J AU Shields, DC Costello, DJ Gale, JT Hoch, DB Eskandar, EN AF Shields, D. C. Costello, D. J. Gale, J. T. Hoch, D. B. Eskandar, E. N. TI Stereotactic cortical resection in non-lesional extra-temporal partial epilepsy SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE epilepsy surgery; epileptogenic zone; extra-temporal epilepsy; non-lesional epilepsy; partial seizure AB The presentation and treatment of a patient with extra-temporal non-lesional partial epilepsy is discussed herein. His clinical semiology was consistent with supplementary motor area seizures; however, MR imaging did not demonstrate a lesion. A region of stable cortical glucose hypermetabolism in the left frontal region was noted with 2-fluoro-2-deoxy-D-glucose (FDG)-PET. This was consistent with the frequent interictal discharges evident over the left fronto-temporal region and the stereotypic high amplitude ictal discharges arising with highest amplitude from the left frontal region. Epileptiform activity evident on an intracranial 64-point subdural recording grid placed over the left dorsolateral frontal cortex confirmed a distribution concordant with FDG-PET findings. The subsequent resection was guided by the PET and EEG findings rather than structural MR imaging, and a limited cortical resection led to an immediate and substantial reduction in seizure frequency. C1 Wang Ambulatory Care Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA USA. RP Eskandar, EN (reprint author), Wang Ambulatory Care Ctr, 331,15 Parkman St, Boston, MA 02114 USA. EM eeskandar@partners.org OI Hoch, Daniel/0000-0002-4294-024X NR 6 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD OCT PY 2007 VL 14 IS 10 BP 1186 EP 1188 DI 10.1111/j.1468-1331.2007.01920.x PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 213IU UT WOS:000249660900028 PM 17708755 ER PT J AU He, W Yasuda, T Spooner, A Fischman, A AF He, W. Yasuda, T. Spooner, A. Fischman, A. TI Importance of follow-up of normal stress myocardial perfusion studies in a sub-group of patients with MPHR < 75% SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Meeting Abstract CT 20th Annual Congress of the European-Association-of-Nuclear-Medicine CY 2007 CL Copenhagen, DENMARK SP European Assoc Nucl Med C1 [He, W.; Yasuda, T.; Spooner, A.; Fischman, A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2007 VL 34 SU 2 BP S182 EP S182 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 264JP UT WOS:000253283900298 ER PT J AU Biederman, J AF Biederman, J. TI Neurobiological overview of attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S606 EP S606 DI 10.1016/S0924-977X(07)70960-4 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231901368 ER PT J AU Biederman, J AF Biederman, J. TI Volumetric MRI in adults with ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER C1 [Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S192 EP S192 DI 10.1016/S0924-977X(07)70214-6 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900051 ER PT J AU Busner, J Targum, SD Miller, DS AF Busner, J. Targum, S. D. Miller, D. S. TI Effect of comorbidities and adverse events on clinical global impressions ratings SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 Penn State Univ, Coll Med, Wayne, NJ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. [Miller, D. S.] United BioSource Corp, Training & Educ Grp, Wayne, NJ USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S584 EP S584 DI 10.1016/S0924-977X(07)70911-2 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231901319 ER PT J AU Meyer-Luhmann, M Hyman, BT Jucker, M AF Meyer-Luehmann, M. Hyman, B. T. Jucker, M. TI Exploring the early pathogenesis in Alzheimer's disease: insights from transgenic mouse models SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Meyer-Luehmann, M.; Hyman, B. T.] Massachusetts Gen Hosp, Charlestown, MA USA. [Jucker, M.] Abt Zellbiol Neurol Erkrankungen, Hertie Inst Klin Hirnforsch, Tubingen, Germany. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S205 EP S205 DI 10.1016/S0924-977X(07)70249-3 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900086 ER PT J AU Parikh, R Sonawalla, S Sharma, S Farabaugh, A Yeung, A Safren, S Fava, M AF Parikh, R. Sonawalla, S. Sharma, S. Farabaugh, A. Yeung, A. Safren, S. Fava, M. TI Cross cultural aspects of depression among college students SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Parikh, R.; Sharma, S.] Jaslok Hosp & Res Ctr, Bombay, Maharashtra, India. [Sonawalla, S.; Farabaugh, A.; Yeung, A.; Safren, S.; Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S327 EP S328 DI 10.1016/S0924-977X(07)70469-8 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900306 ER PT J AU Sonawalla, S Farabaugh, A Yeung, A Mischoulon, D Alpert, J Fava, M AF Sonawalla, S. Farabaugh, A. Yeung, A. Mischoulon, D. Alpert, J. Fava, M. TI Sleep disturbance and suicidal ideation among college students SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 20th Congress of the European-College-of-Neuropsychopharmacology CY OCT 13-17, 2007 CL Vienna, AUSTRIA SP European Coll Neuropsychopharmacol C1 [Sonawalla, S.; Farabaugh, A.; Yeung, A.; Mischoulon, D.; Alpert, J.; Fava, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2007 VL 17 SU 4 BP S330 EP S330 DI 10.1016/S0924-977X(07)70474-1 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 235KE UT WOS:000251231900311 ER PT J AU Papakostas, GI Fava, M AF Papakostas, George I. Fava, Maurizio TI A meta-analysis of clinical trials comparing the serotonin (5HT)-2 receptor antagonists trazodone and nefazodone with selective serotonin reuptake inhibitors for the treatment of major depressive disorder SO EUROPEAN PSYCHIATRY LA English DT Article DE 5HT2; SSRI; trazodone; nefazodone; depression ID DOUBLE-BLIND; PROLONGED-RELEASE; OUTPATIENTS; FLUOXETINE; EFFICACY; SLEEP; PAROXETINE; SERTRALINE; TOLERABILITY; MULTICENTER AB Objective. - To compare response rates among patients with major depressive disorder (MDD) treated with either a serotonin-2 (5HT2-) receptor antagonist or a selective serotonin reuptake inhibitor (SSRI). Methods. - Medline and PubMed were searched for double-blind, randomized clinical trials comparing either trazodone or nefazodone with an SSRI for the treatment of MDD. Data from 9 reports involving a total 988 patients were identified and combined using a random-effects model. Results. - Patients randomized to treatment with a 5HT2 antagonist were as likely to experience clinical response as patients randomized to treatment with an SSRI (RR = 1.002, 95% CI: 0.85-1.17, P = 0.978). Pooled response rates for trazodone/nefazodone and the SSRIs were 61.1% and 61.7%, respectively. There was also no difference in overall discontinuation rates (P = 0.334), discontinuation due to adverse events (P - 0.676). or discontinuation due to inefficacy (P = 0.289) between the two groups. Conclusions. - These results suggest that the 5HT2-receptor antagonists trazodone and nefazodone and the SSRIs do not differ with respect to their overall efficacy and tolerability in the treatment of MDD. Although the sample size was relatively large and conveyed sufficient statistical power to test for differences in the overall sample, depression is a heterogeneous condition and differences may exist between treatments in particular subgroups of patients. (c) 2007 Elsevier Masson SAS. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Depress Clin & Res Program,Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM gpapakostas@partners.org RI Papakostas, George/I-6905-2013 OI Papakostas, George/0000-0002-2465-5103 FU NIMH NIH HHS [K23 MH069629] NR 33 TC 15 Z9 15 U1 0 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0924-9338 J9 EUR PSYCHIAT JI Eur. Psychiat. PD OCT PY 2007 VL 22 IS 7 BP 444 EP 447 DI 10.1016/j.eurpsy.2007.01.1220 PG 4 WC Psychiatry SC Psychiatry GA 230WN UT WOS:000250907100005 PM 17418537 ER PT J AU Podar, K Raab, MS Chauhan, D Anderson, KC AF Podar, Klaus Raab, Marc S. Chauhan, Dharminder Anderson, Kenneth C. TI The therapeutic role of targeting protein kinase C in solid and hematologic malignancies SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE activators; inhibitors; protein kinase C; tumorigenesis ID MULTIPLE-MYELOMA CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ENDOTHELIAL GROWTH-FACTOR; LUNG-CANCER CELLS; NON-HODGKINS-LYMPHOMA; PHASE-II TRIAL; ANTISENSE OLIGONUCLEOTIDE INHIBITOR; VIVO PHOSPHORYLATION SITES; SELECTIVE SMALL-MOLECULE; LINDAU GENE-PRODUCT AB The protein kinase C (PKC) family, the most prominent target of tumor-promoting phorbol esters, is functionally linked to cell differentiation, growth, survival, migration and tumorigenesis and so mediates tumor cell proliferation, survival, multidrug resistance, invasion, metastasis and tumor angiogenesis. Therefore, targeting PKC isozymes may represent an attractive target for novel anticancer therapies. Recent preclinical and clinical studies using the macrocyclic bisindolylmaleimide enzastaurin or the N-benzylstaurosporine midostaurin demonstrate promising activity of PKC inhibitors in a variety of tumors, including diffuse large B-cell lymphoma, multiple myeloma and Waldenstroem's macroglobulinemia. However, our knowledge of PKCs in tumorigenesis is still only partial and each PKC isoform may contribute to tumorigenesis in a distinct way. Specifically, PKC isoforms have vastly different roles, which vary depending on expression levels of organ and tissue distribution, cell type, intracellular localization, protein-protein and lipid-protein interactions and the biologic environment. Although PKC activation generally positively affects tumor cell growth, motility, invasion and metastasis, recent reports show that many PKCs can also have negative effects. Therefore, it is necessary to further dissect the relative contribution of PKC isozymes in the development and progression of specific tumors in order to identify therapeutic opportunities, using either PKC inhibitors or PKC activators. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Podar, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM klaus_podar@dfci.harvard.edu FU NCI NIH HHS [R0-1 CA 50945, IP50 CA100707]; PHS HHS [P0-1 78378] NR 193 TC 45 Z9 47 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD OCT PY 2007 VL 16 IS 10 BP 1693 EP 1707 DI 10.1517/13543784.16.10.1693 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 225VD UT WOS:000250545400017 PM 17922632 ER PT J AU Wu, M Goss, PE AF Wu, Melinda Goss, Paul E. TI Update on the use of letrozole in breast cancer SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE adjuvant breast cancer treatment; aromatase inhibitors; letrozole ID NONSTEROIDAL AROMATASE INHIBITOR; QUALITY-OF-LIFE; PHASE-II TRIAL; EXTENDED ADJUVANT THERAPY; POSTMENOPAUSAL WOMEN; RANDOMIZED-TRIAL; ENDOCRINE THERAPY; DOUBLE-BLIND; COST-EFFECTIVENESS; ESTROGEN-RECEPTOR AB Endocrine therapy is the mainstay of adjuvant treatment for hormone-receptor-positive early breast cancer. Letrozole is a potent third-generation aromatase inhibitor that suppresses plasma estrogen levels to near-undetectable levels in postmenopausal women. The results of well-controlled clinical trials have demonstrated the efficacy of letrozole over the gold-standard treatment, tamoxifen, in the neoadjuvant and upfront adjuvant settings and over placebo in the extended adjuvant setting (i.e., following 5 years of adjuvant tamoxifen). Important benefits in disease-free survival and especially distant disease-free survival have been demonstrated, in both low- and high-risk subgroups of patients (e.g., node-positive disease, prior chemotherapy). Both the efficacy and safety of letrozole for the adjuvant treatment of breast cancer are reviewed. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Director Breast Canc Res, 55 Fruit St,Lawrence House 302, Boston, MA 02114 USA. RP Goss, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Sch Med,Director Breast Canc Res, 55 Fruit St,Lawrence House 302, Boston, MA 02114 USA. EM pgoss@partners.org NR 91 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1465-6566 EI 1744-7666 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD OCT PY 2007 VL 8 IS 14 BP 2329 EP 2345 DI 10.1517/14656566.8.14.2329 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 223KE UT WOS:000250368100011 PM 17927487 ER PT J AU Muller, FL Jang, YM Liu, YH Van Remmen, H AF Muller, Florian L. Jang, Youngmok Liu, Yuhong Van Remmen, Holly TI Does superoxide-induced mitochondrial dysfunction lead to muscle atrophy? SO FREE RADICAL RESEARCH LA English DT Meeting Abstract CT European Meeting of the Society-for-Free-Radical-Research-Europe (SFRR-Europe) CY OCT 10-13, 2007 CL Vilamoura, PORTUGAL SP Soc Free Rad Res Europe, Portuguese Grp Free Rad, Spanish Grp Free Rad C1 [Muller, Florian L.; Jang, Youngmok; Liu, Yuhong; Van Remmen, Holly] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1071-5762 J9 FREE RADICAL RES JI Free Radic. Res. PD OCT PY 2007 VL 41 SU 1 BP S11 EP S11 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 250JP UT WOS:000252296300022 ER PT J AU Nguyen, DD Maillard, MH Cotta-De-Almeida, V Mizoguch, E Klein, C Fuss, I Nagler, C Mizoguch, A Bhan, AK Snapper, SB AF Nguyen, Deanna D. Maillard, Michel H. Cotta-De-Almeida, Vinicius Mizoguch, Emiko Klein, Christoph Fuss, Ivan Nagler, Cathryn Mizoguch, Atsushi Bhan, Atul K. Snapper, Scott B. TI Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein SO GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; REGULATORY T-CELLS; ULCERATIVE-COLITIS; INTESTINAL INFLAMMATION; OXAZOLONE COLITIS; MURINE MODEL; IFN-GAMMA; IN-VITRO; INNATE; ANTIGEN AB Background & Aims: Controversy exists as to whether patients with inflammatory bowel disease have an underlying immunodeficiency. We have focused on a murine model of the Wiskott-Aldrich syndrome, an immunodeficiency in which autoimmunity can manifest in the form of an inflammatory bowel disease-like illness. Wiskott-Aldrich syndrome protein (WASP) deficiency in mice results in similar clinical features. Herein, we characterized the colitis in WASP-deficient mice. Methods: WASP-deficient mice were followed clinically and histologically. Immunologic studies were performed to determine the pathogenic cell population(s), the predominant cytokine expression pattern, and the role of cytokine(s) in colitis pathogenesis. Results: All WASP-deficient mice develop colitis by 6 months of age. Lymphocytes are required for disease induction, and CD4(+) T cells from WASP-deficient mice are sufficient to induce disease in lymphocyte-deficient hosts. Lamina propria preparations from WASP-deficient mice demonstrated elevations in interferon-gamma, interleukin (IL)-4, and IL-13 levels but decreased IL-6 and no difference in IL-17 expression in comparison with vvild-type controls. Treatment with neutralizing antibody to IL-4, but not to interferon-gamma, abrogated colitis development. However, mice deficient in both WASP and IL-4 showed no difference in histologic colitis scores at 24 weeks of age compared with WASP-deficient mice. Conclusions: These results demonstrate a critical role for lymphocytes and a relative T helper 2 cytokine predominance in the colitis associated with WASP-deficient mice. This is the only model of colitis with elevated T helper 2 cytokines and aberrant natural regulatory T cell function and is unique in having a human disease counterpart with similar defects. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Lausanne Med Sch, Dept Med, Div Gastroenterol & Hepatol, Lausanne, Switzerland. Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Rio De Janeiro, Brazil. Hannover Med Sch, Dept Pediat Hematol Oncol, D-3000 Hannover, Germany. NIH, Mucosal Immun Sect, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Immunopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Snapper, SB (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St,Jackson 825C, Boston, MA 02114 USA. EM ssnapper@hms.harvard.edu RI Cotta-de-Almeida, Vinicius/G-3939-2012 FU NHLBI NIH HHS [HL59561, P01 HL059561-10, P01 HL059561]; NIAID NIH HHS [R56 AI050950, R01 AI081807, AI50950, R01 AI050950, R01 AI050950-03]; NIDDK NIH HHS [DK74454, T32DK007191, T32 DK007191, R03 DK074454, P30 DK043351, DK64351, DK64289, DK55678, DK47677, K08 DK064289, R01 DK064351, R01 DK055678, R01 DK047677, P30 DK043351-17] NR 43 TC 40 Z9 40 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2007 VL 133 IS 4 BP 1188 EP 1197 DI 10.1053/j.gastro.2007.07.010 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218SW UT WOS:000250036200016 PM 17764675 ER PT J AU Marro, S Barisani, D Chiabrando, D Fagoonee, S Muckenthaler, MU Stolte, J Meneverv, R Haile, D Silengo, L Altruda, F Tolosano, E AF Marro, Samuele Barisani, Donatella Chiabrando, Deborah Fagoonee, Sharmila Muckenthaler, Martina U. Stolte, Jens Meneverv, Raffaella Haile, David Silengo, Lorenzo Altruda, Fiorella Tolosano, Emanuela TI Lack of haptoglobin affects iron transport across duodenum by modulating ferroportin expression SO GASTROENTEROLOGY LA English DT Article ID HEMOGLOBIN SCAVENGER RECEPTOR; PLASMA-PROTEIN; LIVER-CELLS; HEPCIDIN; HEMOCHROMATOSIS; METABOLISM; MICE; RAT; CIRCULATION; ABSORPTION AB Background & Aims: Haptoglobin is an acute phase protein responsible for the recovery of free hemoglobin from plasma. Haptoglobin-mill mice were previously shown to have an altered heme-iron distribution, thus reproducing what occurs in humans in cases of congenital or acquired anhaptoglobinemia. Here, we report the analysis of iron homeostasis in haptoglobin-mill mice. Methods: Iron absorption was measured in tied-off duodenal segments. Iron stores were evaluated on tissue homogenates and sections. The expression of molecules involved in iron homeostasis was analyzed at the protein and messenger RNA levels both in mice and in murine RAW264.7 macrophages stimulated in vitro with hemoglobin. Results: Analysis of intestinal iron transport reveals that haptoglobin-null mice export significantly more iron from the duodenal mucosa to plasma compared with control counterparts. Increased iron export from the duodenum correlates with increased duodenal expression of ferroportin, both at the protein and messenger RNA levels, whereas hepatic hepcidin expression remains unchanged. Up-regulation of the ferroportin transcript, but not of the protein, also occurs in haptoglobin-null spleen macrophages, which accumulate free hemoglobin-derived iron. Finally, we demonstrate that hemoglobin induces ferroportin expression in RAW264.7 cells. Conclusions: Taking together these data, we suggest that haptoglobin, by controlling plasma levels of hemoglobin, participates in the regulation of ferroportin expression, thus contributing to the regulation of iron transfer from duodenal mucosa to plasma. C1 Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, I-10126 Turin, Italy. Univ Milano Bicocca, Dept Expt Med, Milan, Italy. Univ Heidelberg, Dept Pediat Oncol Hematol & Immunol, Heidelberg, Germany. EMBL, Genom Core Facil, Heidelberg, Germany. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Tolosano, E (reprint author), Univ Turin, Ctr Mol Biotechnol, Dept Genet Biol & Biochem, I-10126 Turin, Italy. EM emanuela.tolosano@unito.it RI Marro, Samuele/I-4493-2014; Tolosano, Emanuela/A-4684-2015 OI Marro, Samuele/0000-0002-9326-6945; Tolosano, Emanuela/0000-0002-1622-2340 FU Telethon [GGP04181] NR 35 TC 17 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2007 VL 133 IS 4 BP 1261 EP 1271 DI 10.1053/j.gastro.2007.07.004 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 218SW UT WOS:000250036200023 PM 17919498 ER PT J AU Mino-Kenudson, M Hull, MJ Brown, I Muzikansky, A Srivastava, A Glickman, J Park, DY Zuckerberg, L Misdraji, J Odze, RD Lauwers, GY AF Mino-Kenudson, Mari Hull, Mindy J. Brown, Ian Muzikansky, Alona Srivastava, Amitabh Glickman, Jonathan Park, Do-Youn Zuckerberg, Lawrence Misdraji, Joseph Odze, Robert D. Lauwers, Gregory Y. TI EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than mucosal biopsy SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/107th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2006 CL Los Angeles, CA SP Amer Gastroenterol Assoc ID HIGH-GRADE DYSPLASIA; OPTICAL COHERENCE TOMOGRAPHY; EARLY ADENOCARCINOMA; EPITHELIAL NEOPLASMS; ENDOSCOPIC BIOPSY; TUMOR INVASION; RESECTION; CANCER; ESOPHAGECTOMY; CARCINOMA AB Background: EMR of Barrett's esophagus (BE)-related superficial neoplasms represents an efficacious staging modality it also allows for better pathologic grading compared with mucosal biopsy specimens. However, the interobserver variation in the interpretation of EMR specimens has not been tested. Objective: To evaluate consistency in the diagnosis of BE-related neoplasia on EMR specimens. Design: Nine pathologists reviewed 25 esophageal EMR specimens and corresponding biopsy specimens independently Each pathologist classified the cases as either non-neoplastic BE, low-grade dysplasia, high-grade dysplasia, intramucosal adenocarcinoma, or invasive adenocarcinoma. interobserver concordance for both specimens from EMRs and biopsies was measured by intraclass correlation and Kendall's coefficient of concordance. The proportion of agreement was also calculated for each specimen and compared for EMR and biopsy by using the Wilcoxon signed rank test. Setting: Teaching hospitals. Patients: Twenty-five patients who underwent EMR for BE-related neoplasia. Results: The intraclass correlation and the Kendall's coefficient for the 25 biopsy specimens was 0.938 (95% CI 0.880-0.965) and 0.677, respectively; for the 25 EMRs, these were significantly improved, at 0.977 (95% CI 0.957-0.987) and 0.831, respectively In addition, the proportion of agreement for EMR specimens was significantly better compared with biopsy specimens (P = .015). Conclusions: Interobserver agreement of BE-related neoplasia on EMR specimens is significantly higher compared with biopsy specimens. The results may relate to the larger tissue sampling compared with biopsy specimens and the ability to evaluate mucosal landmarks, such as double muscularis mucosae. Thus, we suggest that EMRs, in addition to being a staging and therapeutic procedure, improve diagnostic consistency. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03766 USA. Dartmouth Coll Sch Med, Lebanon, NH USA. Sullivan Nicolaides Lab, Dept Pathol, Taringa, Qld, Australia. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, WRN 2,55 Fruit St, Boston, MA 02114 USA. RI Srivastava, Amitabh/A-9386-2009; Brown, Ian/R-7763-2016 OI Brown, Ian/0000-0001-6329-2547 NR 42 TC 55 Z9 55 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2007 VL 66 IS 4 BP 660 EP 666 DI 10.1016/j.gie.2007.02.063 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 220OO UT WOS:000250166200004 PM 17905005 ER PT J AU Olson, JS Lieberman, DA Sonnenberg, A AF Olson, Jeffrey S. Lieberman, David A. Sonnenberg, Amnon TI Practice patterns in the management of patients with esophageal strictures and rings SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL REFLUX DISEASE; SINGLE DILATION; NATURAL-HISTORY; SCHATZKIS RING; COMPLICATIONS; DILATATION; BALLOON; STENOSES; THERAPY AB Background: Only few data exist on the epidemiology and management of esophageal strictures and rings. Objective: To study the epidemiology and management of esophageal strictures and rings. Design: Case-control study Setting: Endoscopic data repository of U.S. gastroenterology practices from 1998 to 2003 (Clinical Outcomes Research Initiative). Patients: Case subjects included 7287 patients with strictures and 4993 patients with rings. The control group consisted of 124,120 patients without endoscopic evidence of esophageal stenosis. Interventions: Esophageal dilation. Main Outcome Measurements: Patient demographics, types and diameters of esophageal dilators, frequency of repeat dilations. Results: Strictures displayed a male predominance, and rings displayed a small female predominance. Compared with the control population, strictures and rings both occurred most frequently in elderly white patients. Dysphagia and reflux were the most common indications for dilation in both conditions. Compared with strictures, rings were treated more often with larger dilators and rubber bougies. One-year rates of repeat dilation for strictures and rings were 13% and 4%, respectively. The mean interval length between repeat dilations was 82 days for Strictures and 184 days for rings. Limitations: Only a limited amount of information about individual patients was retrievable from the electronic database. Conclusions: The variations in the demographic characteristics and the treatment practice allude to differences in the Underlying pathophysiology of these 2 benign obstructing lesions of the esophagus. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-G1,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU NIDDK NIH HHS [U01-DK057132-06A1] NR 26 TC 8 Z9 8 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2007 VL 66 IS 4 BP 670 EP 675 DI 10.1016/j.gie.2007.02.031 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 220OO UT WOS:000250166200006 PM 17905007 ER PT J AU Spiegel, BMR Esrailian, E Eisen, G AF Spiegel, Brennan M. R. Esrailian, Eric Eisen, Glenn TI The budget impact of endoscopic screening for esophageal varices in cirrhosis SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; PROTON PUMP INHIBITORS; UPPER GI ENDOSCOPY; TERM-FOLLOW-UP; PRIMARY PROPHYLAXIS; PORTAL-HYPERTENSION; COST-EFFECTIVENESS; CAPSULE ENDOSCOPY; NATURAL-HISTORY; GASTROINTESTINAL ENDOSCOPY AB Background: The cost-effectiveness of screening for esophageal varices in cirrhosis remains uncertain. Previous analyses found that screening with upper endoscopy (EGD) may not be cost effective versus empiric beta-blocker (BB) therapy. However, these models were conducted before advances in variceal screening, including capsule endoscopy (CE), and they did not measure the budget impact (vs cost-effectiveness) of variceal screening. Objective: To compare the managed care budget impact of variceal screening strategies. Design: Budget impact model. Setting: Hypothetical managed care organization with 1 million covered lives. Patients: Patients with compensated cirrhosis. Interventions: Compared 5 strategies: (1) empiric BB, (2) screening EGD followed by BB if varices present (EGD -> BB), (3) EGD followed by endoscopic band ligation if varices present (EGD -> EBL), (4) CE followed by BB if varices present (CE -> BB), and (5) CE followed by EBL if varices present (CE -> EBL). Main Outcome Measurement: Per-member per-month cost. Results: BB was the least expensive, and CE -> EBL was the most expensive. Substituting CE -> BB in lieu of BB cost each member an additional $0.20 per month to subsidize. Compared with CE -> BB, both EGD-based strategies were more expensive. However, CE was not viable in managed care organizations capable of reducing the cost of endoscopy below $410, unless the cost of CE was reduced in lockstep. Limitations: Data on CE remain limited. Conclusions: Screening for varices may have an acceptable budget impact but is highly sensitive to local costs of EGD and CE. In managed care organizations willing to subsidize EBL for variceal prophylaxis, it is inefficient to screen with CE compared with EGD. C1 Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Div Gastroenterol, Los Angeles, CA 90073 USA. CURE Digest Dis Res Ctr, Los Angeles, CA USA. Oregon Hlth & Sci Univ, Div Gastroenterol, Portland, OR 97201 USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, VA Greater Los Angeles Healthcare Syst, David Geffen Sch Med, VA Ctr Outcomes Res & Educ,Div Gastroenterol, 11301 Wilshire Blvd,Bldg 115 Rm 215, Los Angeles, CA 90073 USA. FU NCI NIH HHS [U01 CA89389-01]; NIDDK NIH HHS [T32 DK07180-30, R33 DK61778-01, 2P30 DK041301-17] NR 86 TC 24 Z9 24 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2007 VL 66 IS 4 BP 679 EP 692 DI 10.1016/j.gie.2007.02.048 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 220OO UT WOS:000250166200008 PM 17905009 ER PT J AU Matthes, K Yusuf, TE Willingham, FF Mino-Kenudson, M Rattner, DW Brugge, WR AF Matthes, Kai Yusuf, Tony E. Willingham, Field F. Mino-Kenudson, Mari Rattner, David W. Brugge, William R. TI Feasibility of endoscopic transgastric distal pancreatectomy in a porcine animal model SO GASTROINTESTINAL ENDOSCOPY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/107th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2006 CL Los Angeles, CA SP Amer Gastroenterol Assoc ID ORGAN RESECTION; ANASTOMOSIS; EXPERIENCE; SURVIVAL; SURGERY; COST AB Background: In contrast to laparoscopic tubal ligation, oophorectomy, and appendectomy, laparoscopic distal pancreatectomy is associated with a morbidity rate of more than 50% and a mortality rate of more than 3%. Objective: To develop a minimally invasive, transgastric endoscopic technique for distal pancreatectomy in a nonsurvival series in swine. Design: Experimental study. Setting: Animal trial at a tertiary-care academic hospital. Subjects: Six healthy Yorkshire swine under general anesthesia. Interventions: A double-channel gastroscope was introduced into the stomach, and a gastric incision was created by using a triple-lumen, 4-mm, cutting-wire needle knife. The peritoneal cavity was accessed. An Endoloop was placed endoscopically around the distal aspect of the pancreas, and the tail of the pancreas was transected by using a diathermic snare. One to 3 hemoclips were placed across the pancreatic duct. The pancreatic specimen was retrieved, and the gastrotomy was closed encloscopically with metal clips. The animals were euthanized after the procedure. The abdominal cavity was examined grossly, and the resected pancreas was examined histologically. Main Outcome and Measurements: Feasibility of endoscopic transgastric distal pancreatectomy and rate of complications. Results: The pancreatic tail was successfully resected via a transgastric endoscopic approach in all animals. The procedure took an average (standard deviation) of 77.3 +/- 18.9 minutes. There was I complication, an episode of bleeding from a splenic laceration, which resulted in the loss of 250 mL of blood. Limitations: Nonsurvival series, animal study. Conclusions: Transgastric endoscopic distal pancreatectomy is technically feasible and can be performed in the porcine animal model. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,GI Endoscopy Unit, Dept Med,Div Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Gastrointestinal Pathol Serv, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Brugge, WR (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,GI Endoscopy Unit, Dept Med,Div Gastroenterol, 55 Fruit St,Blake 4, Boston, MA 02114 USA. OI Willingham, Field/0000-0002-7071-3001 NR 16 TC 33 Z9 35 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2007 VL 66 IS 4 BP 762 EP 766 DI 10.1016/j.gie.2007.02.042 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 220OO UT WOS:000250166200021 PM 17905020 ER PT J AU Pham, L Purcell, P Morse, L Stashenko, P Battaglino, RA AF Pham, L. Purcell, P. Morse, L. Stashenko, P. Battaglino, R. A. TI Expression analysis of nha-oc/NHA2: A novel gene selectively expressed in SO GENE EXPRESSION PATTERNS LA English DT Article DE osteoclast specific; cation proton exchanger; bone resorption ID OSTEOCLAST DIFFERENTIATION AB Bone resorption by osteoclasts is required for normal bone remodeling and reshaping of growing bones. Excessive resorption is an important pathologic, feature of many diseases, including osteoporosis, arthritis, and periodontitis [Abu-Amer, Y. (2005). Advances in osteoclast differentiation and function. Curr. Drug Targets. Immune. Endocr. Metabol. Disord. 5, 347-355]. On the other hand, deficient resorption leads to osteopetrosis which is characterized by increased bone mass and may lead to bone deformities or in severe cases to death [Blair, H.C., Athanasou, N.A. 2004. Recent advances in osteoclast biology and pathological bone ddresorption. Histol. Histo-pathol. 19, 189-199; Del Fattore, A., Peruzzi, B., Rucci, N., Recchia, L, Cappariello, A., Longo, M., Fortunati, D., Ballanti, P., lacobini, M., Luciani, M., Devito, R., Pinto, R., Caniglia, M., Lanino, E., Messina, C., Cesaro, S., Letizia, C., Bianchini, G., Fryssira, H., Grabowski, P., Shaw, N., Bishop, N., Hughes, D., Kapur, R.P., Datta, H.K., Taranta, A., Fornari, R., Migliaccio, S., and Teti, A. 2006. Clinical, genetic, and cellular analysis of 49 osteopetrotic patients: implications for diagnosis and treatment. J. Med. Genet. 43, 315-325]. Recently, we identified a gene, nha-oc/NHA2, which is strongly up regulated during RANKL-induced osteoclast differentiation in vitro and in vivo. nha-oc/NHA2 encodes a novel cation/proton exchanger that is strongly expressed in osteoclasts. The purpose of this work was to further validate the restricted expression of nha-oc/NHA2 in osteoclasts by in situ hybridization. Our results showed that nha-oc is expressed predominantly in bone. In the head, expression was found in the supraoccipitale bone, calvarium, mandible, and maxilla. Furthermore, nha-oc positive cells co-express the osteoclast markers TRAP and cathepsin k, confirming nha-oc/NHA2 osteoclast localization. However, only a subset of cathepsin k-expressing cells is positive for nha-oc/NHA2, suggesting that nha-oc is expressed by terminally differentiated osteoclasts. (c) 2007 Elsevier B.V. All rights reserved. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Sch Med, Dept Phys Med & Rehabil, Boston, MA USA. Spaulding Rehabil Hosp, Boston, MA USA. RP Battaglino, RA (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM rbattaglino@forsyth.org RI battaglino, ricardo/D-2892-2015; Morse, Leslie/C-9442-2015 OI Morse, Leslie/0000-0002-7426-6341 FU NIDCR NIH HHS [DE-007378-18, R01 DE007378-16A1, R01 DE007378] NR 10 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD OCT PY 2007 VL 7 IS 8 BP 846 EP 851 DI 10.1016/j.modgep.2007.07.002 PG 6 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 234VP UT WOS:000251192600003 PM 17698421 ER PT J AU Han, M Rivera, MN Batten, JM Haber, DA Dal Cin, P Iafrate, AJ AF Han, Moonjoo Rivera, Miguel N. Batten, Julie M. Haber, Daniel A. Dal Cin, Paola Iafrate, A. John TI Wilms' tumor with an apparently balanced translocation t(X; 18) resulting in deletion of the WTX gene SO GENES CHROMOSOMES & CANCER LA English DT Article ID HETEROZYGOSITY; KIDNEY; LOCUS AB The recent description of a new X chromosome tumor suppressor gene, WTX, that is commonly inactivated in Wilms' tumor prompted us to examine the possible involvement of WTX in a case of Wilms' tumor containing an apparently balanced reciprocal translocation between chromosomes X and 18 (t(X; 18)(q 11;p 11)). Fluorescence in situ hybridization (FISH) analysis of paraffin tumor sections indeed revealed a deletion of the WTX locus at Xq 11. High-resolution array comparative genomic hybridization (array CGH) analysis of tumor DNA revealed a 1.5 Mb chromosome deletion encompassing the WTX gene at Xq 11. No loss of genetic material was detected on chromosome 18. Interestingly, unlike most tumors with acquired chromosomal translocations, where a new fusion oncogene or promoter-oncogene fusion is created and drives tumor growth, the t(X; 18) in this tumor appears to drive tumorigenesis via deletion of a tumor suppressor. This case demonstrates the importance of array CGH and FISH as adjuncts in tumor cytogenetics and in identifying pathogenic microdeletions in "balanced" translocations that are not truly balanced. (c) 2007 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Diagnost Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Harvard Univ, Sch Med, Dept Pathol, Cytogenet Lab,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Iafrate, AJ (reprint author), Massachusetts Gen Hosp, Dept Pathol, Mol Diagnost Lab, 55 Fruit St, Boston, MA 02114 USA. EM aiaftate@partners.org NR 23 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2007 VL 46 IS 10 BP 909 EP 913 DI 10.1002/gcc.20476 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 206OG UT WOS:000249192200004 PM 17620295 ER PT J AU Kim, N Dempsey, CM Kuan, CJ Zoval, JV O'Rourke, E Ruvkun, G Madou, MJ Sze, JY AF Kim, Nahui Dempsey, Catherine M. Kuan, Chih-Jen Zoval, Jim V. O'Rourke, Eyleen Ruvkun, Gary Madou, Marc J. Sze, Ji Y. TI Gravity force transduced by the MEC-4/MEC-10 DEG/ENaC channel modulates DAF-16/FoxO activity in Caenorhabditis elegans SO GENETICS LA English DT Article ID C-ELEGANS; LIFE-SPAN; SIGNALING PATHWAY; NERVOUS-SYSTEM; PROTEIN DAF-16; GENES; NEURONS; LONGEVITY; TOUCH; MECHANOSENSATION AB The gravity response is an array of behavioral and physiological plasticity elicited by changes in ambient mechanical force and is an evolutionarily ancient adaptive mechanism. We show in Caenorhabditis elegans that the force of hypergravity is translated into biological signaling via a genetic pathway involving three factors: the degenerin/epithelial Na+ channel (DEG/ENaC) class of mechanosensory channels of touch receptor neurons, the neurotransmitter serotonin, and the FoxO transcription factor DAF-16 known to regulate development, energy metabolism, stress responses, and aging. After worms were exposed to hypergravity for 3 hr, their muscular and neuronal functions were preserved, but they exhibited DAF-16::GFP nuclear accumulation in cells throughout the body and accumulated excess fat. Mutations in MEC-4/MEC-10 DEG/ENaC or its partners MEC-6, MEC-7, and MEC-9 blocked DAF-16::GFP nuclear accumulation induced by hypergravity but did not affect DAF-16 response to other stresses. We show that exogenous serotonin and the antidepressant fluoxetine can attenuate DAF-16:: GFP nuclear accumulation in WTanimals exposed to hypergravity. These results reveal a novel physiological role of the mechanosensory channel, showing that the perception of mechanical stress controls FoxO signaling pathways and that inactivation of DEG/ENaC may decouple mechanical loading and physiological responses. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. Univ Calif Irvine, Dept Mech & Aerosp Engn, Irvine, CA 92697 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sze, JY (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, 202 Golding Bldg,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jsze@aecom.yu.edu RI Madou, Marc/E-5869-2013 OI Madou, Marc/0000-0003-4847-3117 NR 62 TC 15 Z9 27 U1 0 U2 7 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2007 VL 177 IS 2 BP 835 EP 845 DI 10.1534/genetics.107.076901 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 227LI UT WOS:000250657800015 PM 17720915 ER PT J AU He, HS Wang, J Liu, T Liu, XS Li, TT Wang, YF Qian, ZW Zheng, HX Zhu, XP Wu, T Shi, B Deng, W Zhou, W Skogerbo, G Chen, RS AF He, Housheng Wang, Jie Liu, Tao Liu, X. Shirley Li, Tiantian Wang, Yunfei Qian, Zuwei Zheng, Haixia Zhu, Xiaopeng Wu, Tao Shi, Baochen Deng, Wei Zhou, Wei Skogerbo, Geir Chen, Runsheng TI Mapping the C-elegans noncoding transcriptome with a whole-genome tiling microarray SO GENOME RESEARCH LA English DT Article ID CAENORHABDITIS-ELEGANS; GENE-EXPRESSION; RNAS; RESOLUTION; SEQUENCES; ARRAYS; DNA; IDENTIFICATION; NEMATODES; BRIGGSAE AB The number of annotated protein coding genes in the genome of Caenorhabditis elegans is similar to that of other animals, but the extent of its non- protein- coding transcriptome remains unknown. Expression profiling on whole- genome tiling microarrays applied to a mixed- stage C. elegans population verified the expression of 71% of all annotated exons. Only a small fraction ( 11%) of the polyadenylated transcription is non- annotated and appears to consist of similar to 3200 missed or alternative exons and 7800 small transcripts of unknown function ( TUFs). Almost half ( 44%) of the detected transcriptional output is non- polyadenylated and probably not protein coding, and of this, 70% overlaps the boundaries of protein- coding genes in a complex manner. Specific analysis of small non- polyadenylated transcripts verified 97% of all annotated small ncRNAs and suggested that the transcriptome contains similar to 1200 small (< 500 nt) unannotated noncoding loci. After combining overlapping transcripts, we estimate that at least 70% of the total C. elegans genome is transcribed. C1 Chinese Acad Sci, Inst Biophys, Bioinformat Lab, Beijing 100101, Peoples R China. Chinese Acad Sci, Inst Biophys, Natl Lab Biomacromol, Beijing 100101, Peoples R China. Chinese Acad Sci, Grad Sch, Beijing 100080, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Chinese Acad Sci, Inst Comp Technol, Key Lab Intelligent Informat Proc, Bioinformat Res Grp, Beijing 100080, Peoples R China. Chinese Natl Human Genome Ctr, Beijing 100176, Peoples R China. RP Zhu, XP (reprint author), Chinese Acad Sci, Inst Biophys, Bioinformat Lab, Beijing 100101, Peoples R China. EM crs@sun5.ibp.ac.cn RI Liu, Tao/G-3585-2010; Wang, Jie/F-9747-2011; He, Housheng/G-9614-2011; Deng, Wei/I-1280-2012; Wu, Tao/A-1063-2013; Zhu, Xiaopeng/A-6755-2011; OI Liu, Tao/0000-0002-8818-8313; Wu, Tao/0000-0002-9859-4534; Zhu, Xiaopeng/0000-0003-2007-9820; Liu, Tao/0000-0003-0446-9001 FU NHGRI NIH HHS [R01 HG004069, R01 HG004069-02] NR 31 TC 44 Z9 51 U1 1 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2007 VL 17 IS 10 BP 1471 EP 1477 DI 10.1101/gr.661807 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 216HN UT WOS:000249869200008 PM 17785534 ER PT J AU Moye, J Butz, SW Marson, DC Wood, E AF Moye, Jennifer Butz, Steven W. Marson, Daniel C. Wood, Erica CA ABA-APA Capacity Assessment Older Adults Working Grp TI A conceptual model and assessment template for capacity evaluation in adult guardianship SO GERONTOLOGIST LA English DT Article DE capacity; competency; dementia; guardianship ID OLDER-ADULTS; COMPETENCE; CONSENT; ETHNICITY; DEMENTIA; DISEASE AB Purpose: We develop a conceptual model and associated assessment template that is usable across state jurisdictions for evaluating the independent-living capacity of older adults in guardianship proceedings. Design and Methods: We used an iterative process in which legal provisions for guardianship and prevailing clinical practices for capacity assessment were integrated, through expert group consensus and external review by legal and health care professionals, to form a conceptual model and template. Results: The model and template provide a structure for conducting and documenting a capacity evaluation in guardianship by using six assessment domains of interest to the courts: (a) medical condition, (b) cognition, (c) functional abilities, (d) values, (e) risk of harm and level of supervision needed, and (f) means to enhance capacity. The template also addresses the participation of the person in the guardianship hearing, confidentiality and privilege issues, and certification by the examiner. An online version of the template can be adapted to address specific jurisdictional requirements. Implications: A conceptual model and evaluation template provide a useful cross-jurisdictional format for conducting and documenting capacity assessments of older adults in guardianship proceedings. The template may be particularly useful to clinicians for providing courts with information to support limited guardianship orders. C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Alabama, Dept Neurol, Birmingham, AL USA. Univ Alabama, Alzheimers Disease Res Ctr, Birmingham, AL USA. Amer Bar Assoc, Commission Law & Aging, Washington, DC USA. RP Moye, J (reprint author), VA Med Ctr, 940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 33 TC 18 Z9 18 U1 0 U2 9 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2007 VL 47 IS 5 BP 591 EP 603 PG 13 WC Gerontology SC Geriatrics & Gerontology GA 272EN UT WOS:000253842800003 PM 17989401 ER PT J AU Moye, J Wood, S Edelstein, B Armesto, JC Bower, EH Harrison, JA Wood, E AF Moye, Jennifer Wood, Stacey Edelstein, Barry Armesto, Jorge C. Bower, Emily H. Harrison, Julie A. Wood, Erica TI Clinical evidence in guardianship of older adults is inadequate: Findings from a tri-state study SO GERONTOLOGIST LA English DT Article ID COUNTY AB Purpose: This preliminary study compared clinical evaluations for guardianship in three states with varying levels of statutory reform. Design and Methods: Case files for 298 cases of adult guardianship were reviewed in Massachusetts, Pennsylvania, and Colorado, three states with varying degrees of statutory reform. The quality and content of the written clinical evidence for guardianship and the hearing outcome were recorded. Results: The quality of the written clinical evidence for guardianship was best in Colorado, the state with the most progressive statutory reform, earning a grade of B in our ratings, and worst in Massachusetts, a state with minimal reform, earning a grade of D - with nearly two thirds of the written evidence illegible. Information on specific functional deficits was frequently missing and conclusory statements were common. Information about the individual's key values and preferences was almost never provided, and individuals were rarely present at the hearing. Limited orders were used for 34% of the cases in Colorado, associated with more complete clinical testimony, but such orders were used in only 1 case in either Massachusetts or Pennsylvania. Implications: In this study, states with progressive statutes that promote functional assessment are associated with increased quality of clinical testimony and use of limited orders. A continuing dialogue between clinical and legal professionals is needed to advance reform in guardianship, and thereby provide for the needs and protect the rights of adults who face guardianship proceedings. C1 VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Colorado, Dept Psychol, Colorado Springs, CO USA. W Virginia Univ, Dept Psychol, Morgantown, WV USA. Amer Bar Assoc, Commission Law & Aging, Washington, DC USA. RP Moye, J (reprint author), Vet Adm Med Ctr, 940 Belmont St, Brockton, MA 02301 USA. EM jennifer.moye@va.gov RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X FU NIMH NIH HHS [R29 MH057104] NR 18 TC 15 Z9 15 U1 0 U2 8 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2007 VL 47 IS 5 BP 604 EP 612 PG 9 WC Gerontology SC Geriatrics & Gerontology GA 272EN UT WOS:000253842800004 PM 17989402 ER PT J AU Bernards, A Settleman, J AF Bernards, Andre Settleman, Jeffrey TI GEFs in growth factor signaling SO GROWTH FACTORS LA English DT Article DE growth factors; guanine nucleotide exchange factor; signal transduction; Ras superfamily; GTPase regulation ID GUANINE-NUCLEOTIDE-EXCHANGE; CAUSE NOONAN-SYNDROME; FACIO-CUTANEOUS SYNDROME; MUTATIONS CAUSE NOONAN; OF-FUNCTION MUTATIONS; GERMLINE MUTATIONS; RAS ACTIVATION; FACTOR DOMAINS; PROTEIN; UBIQUITIN AB Evolutionary conserved members of the Ras superfamily of small GTP-binding proteins function as binary molecular switches to control diverse biological processes. In the context of cellular signaling, these include functions in exocytic and endocytic trafficking, as well as roles in signal relay downstream of various cell surface receptors. We previously reviewed roles played by the large family of GTPase, activating proteins in these processes. In this companion review, we highlight recent findings relating to the regulation of another major class of Ras superfamily regulatory proteins, the guanine nucleotide exchange factors. C1 Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA. [Settleman, Jeffrey] Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Harvard Univ, Sch Med, Bldg 149,13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu NR 64 TC 12 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0897-7194 J9 GROWTH FACTORS JI Growth Factors PD OCT PY 2007 VL 25 IS 5 BP 355 EP 361 DI 10.1080/08977190701830375 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 264UV UT WOS:000253316800007 PM 18236214 ER PT J AU Yurkovetsky, Z Ta'asan, S Skates, S Rand, A Lomakin, A Linkov, F Marrangoni, A Velikokhatnaya, L Winans, M Gorelik, E Maxwell, GL Lu, K Lokshin, A AF Yurkovetsky, Zoya Ta'asan, Shlomo Skates, Steve Rand, Alex Lomakin, Aleksey Linkov, Faina Marrangoni, Adele Velikokhatnaya, Lyudmila Winans, Matthew Gorelik, Elieser Maxwell, G. Larry Lu, Karen Lokshin, Anna TI Development of multimarker panel for early detection of endometrial cancer. High diagnostic power of prolactin SO GYNECOLOGIC ONCOLOGY LA English DT Article DE endometrial cancer; cancer markers; early detection; multiplex profiling; prolactin ID STAGE OVARIAN-CANCER; SERUM CA-125 LEVELS; GYNECOLOGIC CANCER; PERIPHERAL-BLOOD; TUMOR-MARKERS; AMYLOID-A; CARCINOMA; IMMUNE; RESPONSES; CELLS AB Objective. Endometrial carcinoma is the most common gynecologic cancer. Although the prognosis for endometrial cancer is generally good, cancers identified at late stages are associated with high levels of morbidity and mortality. Therefore, prevention and early detection may further reduce the burden of this challenging disease. Methods. A panel of 64 serum biomarkers was analyzed in sera of patients with stages I-III endometrial cancer and age-matched healthy women, utilizing a multiplex xMAP(TM) bead-based immunoassay. For multivariate analysis, four different statistical classification methods were used: logistic regression (LR), separating hyperplane (SHP), k nearest neighbors (KNN), and classification tree (CART). For each of these classifiers, a diagnostic model was created based on the cross-validation set consisting of sera from 115 patients with endometrial cancer and 135 healthy women. Results. Our data have demonstrated that patients with endometrial cancer have significantly different expression patterns of several serum biomarkers as compared to healthy controls. Prolactin was the strongest discriminative biomarker for endometrial cancer providing 98.3% sensitivity and 98.0% specificity alone. Our results have revealed that serum concentration of cancer antigens, including CA 125, CA 15-3, and CEA are higher in patients will Stage III endometrial cancer as compared to those with Stage I. In addition, we have shown that the expression of CA 125, AFP, and ACTH is elevated in women with tumor grade 3 vs. grade 1. Furthermore, five-biomarker panel (prolactin, GH, Eotaxin, E-selectin, and TSH) identified in this study was able to discriminate endometrial cancer from ovarian and breast cancers with high sensitivity and specificity. Conclusions. The ability of prolactin to accurately discriminate between cancer and control groups indicates that this biomarker could potentially be used for development of btood-based test for the early detection of endometrial cancer in high-risk populations. Combining the information on multiple serum markers using flexible statistical methods allows for achieving high cancer selectivity. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. Carnegie Mellon Univ, Dept Math Sci, Pittsburgh, PA 15213 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. MIT, Dept Phys, Cambridge, MA 02139 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. Walter Reed Army Med Ctr, US Mil Canc Inst, Gynecol Dis Ctr, Washington, DC 20307 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Lokshin, A (reprint author), Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, 5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM lokshina@pitt.edu RI Ta'asan, Shlomo/B-8366-2017 OI Ta'asan, Shlomo/0000-0002-6085-7124 FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [R03 CA136019, R01 CA098642, R01 CA098642-03, R01 CA098642-01A1, R01 CA098642-04, U01 CA117452, U01 CA117452-01, R01 CA108990, R01 CA108990-02, R01 CA108990-01A1, R03 CA136019-01, R01 CA108990-04, U01 CA117452-03, R01 CA098642-02, U01 CA117452-04S1, U01 CA117452-02, U01 CA117452-04, R01 CA108990-03] NR 50 TC 53 Z9 55 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2007 VL 107 IS 1 BP 58 EP 65 DI 10.1016/j.ygyno.2007.05.041 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 220YG UT WOS:000250192600010 PM 17659325 ER PT J AU Larocca, A Rossi, D Pregno, P Masini, L Rus, C Magarotto, V D'Agostino, F Falco, P Gay, F Gugliotta, L Gaidano, G Iacobetti, M Mitsiades, C Richardson, PG Anderson, KC Boccadoro, M Palumbo, A AF Larocca, A. Rossi, D. Pregno, P. Masini, L. Rus, C. Magarotto, V D'Agostino, F. Falco, P. Gay, F. Gugliotta, L. Gaidano, G. Iacobetti, M. Mitsiades, C. Richardson, P. G. Anderson, K. C. Boccadoro, M. Palumbo, A. TI A multicenter phase I/II trial on combination of Melphalan, Prednisone, Thalidomide and Defibrotide in advanced stage Multiple Myeloma patients SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 41st Congress of the Italian-Society-of-Hematology CY OCT 14-17, 2007 CL Bologna, ITALY SP Italian Soc Hematol C1 [Larocca, A.; Rus, C.; Magarotto, V; D'Agostino, F.; Falco, P.; Gay, F.; Boccadoro, M.; Palumbo, A.] Univ Turin, Osped Molinette, Azienda Osped S Giovanni Battista, Div Ematol, Turin, Italy. [Rossi, D.; Gaidano, G.] Univ Piemonte Orientale, Dipartimento Oncol, Dipartimento Sci Med & IRCAD, Div Ematol, Novara, Italy. [Pregno, P.] Azienda Osped San Giovanni Battista, Turin, Italy. [Masini, L.; Gugliotta, L.] Arcispedale Santa Maria Nuova, Reggio Emilia, Italy. [Mitsiades, C.; Richardson, P. G.; Anderson, K. C.] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myelomoa Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2007 VL 92 SU 3 BP 138 EP 139 PG 2 WC Hematology SC Hematology GA 224TZ UT WOS:000250470701103 ER PT J AU Aspinall, MG Hamermesh, RG AF Aspinall, Mara G. Hamermesh, Richard G. TI Realizing the promise of personalized medicine SO HARVARD BUSINESS REVIEW LA English DT Article AB Scientific advances have begun to give doctors the power to customize therapy for individuals. However, adoption of this approach has progressed slowly and unevenly because the trial-and-error treatment model still governs how the health care system develops, regulates, pays for, and delivers therapies. Aspinall, the president of Genzyme Genetics, and Hamermesh, chair of a Harvard Business School initiative to improve leadership in health care organizations, discuss the barriers to personalized medicine and suggest ways to overcome them. The blockbuster model for developing drugs, the authors point out, is still what most major pharmaceutical companies, follow, even though its days are numbered. What the industry must embrace in its place is a business model based on a larger portfolio of targeted - and therefore more effective and profitable treatments, not a limited palette of one-size-fits-all drugs. The current regulatory environment overemphasizes large-scale clinical trials of broad-based therapies. Instead, the focus should be on enrolling subpopulations, based on diagnostic testing, in trials of targeted drug treatments and on monitoring and assessing effectiveness after drugs are approved. A dysfunctional payment system complicates matters by rewarding providers for performance of procedures rather than for accurate diagnosis and effective prevention. Aspinall and Hamermesh call for coordinating regulation and reimbursement so that incentives are provided for the right outcomes, Finally, the authors urge changing physicians' habits through education about genomics, diagnostic testing, and targeted therapies. They say that medical schools and physician organizations must become committed advocates of personalized medicine so that patients and the medical industry can get all the benefits it offers. C1 Genzyme Corp, Westborough, MA 01581 USA. Dana Farber Canc Inst, Boston, MA USA. RP Aspinall, MG (reprint author), Genzyme Corp, Westborough, MA 01581 USA. EM mara.aspinall@genzyme.com; rhamermesh@hbs.edu NR 0 TC 58 Z9 61 U1 1 U2 30 PU HARVARD BUSINESS SCHOOL PUBLISHING CORPORATION PI WATERTOWN PA 300 NORTH BEACON STREET, WATERTOWN, MA 02472 USA SN 0017-8012 J9 HARVARD BUS REV JI Harv. Bus. Rev. PD OCT PY 2007 VL 85 IS 10 BP 108 EP + PG 11 WC Business; Management SC Business & Economics GA 213QL UT WOS:000249682100020 PM 17972499 ER PT J AU Allensworth-Davies, D Leigh, J Pukstas, K Geron, SM Hardt, E Brandeis, G Engle, RL Parker, VA AF Allensworth-Davies, Donald Leigh, Jennifer Pukstas, Kim Geron, Scott Miyake Hardt, Eric Brandeis, Gary Engle, Ryann L. Parker, Victoria A. TI Country of origin and racio-ethnicity: Are there differences in perceived organizational cultural competency and job satisfaction among nursing assistants in long-term care? SO HEALTH CARE MANAGEMENT REVIEW LA English DT Article; Proceedings Paper CT 59th Annual Scientific Meeting of the Gerontological-Society-of-America CY NOV 16-20, 2006 CL Dallas, TX SP Gerontol Soc Amer DE cultural competence; cultural diversity; long-term care; job satisfaction ID DISCRIMINATION; PROFESSIONALS; PERCEPTIONS; MANAGEMENT; DIVERSITY AB Background: Long-term care facilities nationwide are finding it difficult to train and retain sufficient numbers of nursing assistants, resulting in a dire staffing situation. Researchers, managers, and practitioners alike have been trying to determine the correlates of job satisfaction to address this increasingly untenable situation. One factor that has received little empirical attention in the long-term care literature is cultural competence. Cultural competence is defined as a set of skills, attitudes, behaviors, and policies that enable organizations and staff to work effectively in cross-cultural situations. Purpose: To examine organizational cultural competence as perceived by nursing assistants and determine if this was related to differences in job satisfaction across countries of origin and racio-ethnic groups. C1 Boston Univ, Sch Publ Hlth, Data Coordinatong Ctr, Boston, MA 02215 USA. Newton Wellesley Eating Disorders & Behav Med, Newton, MA USA. Boston Univ, Sch Social Work, Inst Geriatr Social Work, Boston, MA 02215 USA. Boston Med Ctr, Geriatr Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Ctr Org Leadership & Management Res, Boston, MA USA. RP Allensworth-Davies, D (reprint author), Boston Univ, Sch Publ Hlth, Data Coordinatong Ctr, Boston, MA 02215 USA. EM ddavies7@bu.edu NR 30 TC 4 Z9 4 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0361-6274 J9 HEALTH CARE MANAGE R JI Health Care Manage. Rev. PD OCT-DEC PY 2007 VL 32 IS 4 BP 321 EP 329 PG 9 WC Health Policy & Services SC Health Care Sciences & Services GA 225CY UT WOS:000250495900004 PM 18075441 ER PT J AU Kerr, EA Hofer, TP Hayward, RA Adams, JL Hogan, MM McGlynn, EA Asch, SM AF Kerr, Eve A. Hofer, Timothy P. Hayward, Rodney A. Adams, John L. Hogan, Mary M. McGlynn, Elizabeth A. Asch, Steven M. TI Quality by Any Other Name?: A Comparison of Three Profiling Systems for Assessing Health Care Quality SO HEALTH SERVICES RESEARCH LA English DT Article DE Quality of care; performance profiling; quality monitoring ID OF-CARE; HOSPITAL-CARE; POOR QUALITY; PHYSICIAN; EXPLICIT; CRITERIA AB Objective. Many performance measurement systems are designed to identify differences in the quality provided by health plans or facilities. However, we know little about whether different methods of performance measurement provide similar answers about the quality of care of health care organizations. To examine this question, we used three different measurement approaches to assess quality of care delivered in veteran affairs (VA) facilities. Data Sources/Study Setting. Medical records for 621 patients at 26 facilities in two VA regions. Study Design. We examined agreements in quality conclusions using: focused explicit (38 measures for six conditions/prevention), global explicit (372 measures for 26 conditions/prevention), and structured implicit review physician-rated care (a single global rating of care for three chronic conditions and overall acute, chronic and preventive care). Trained nurse abstractors and physicians reviewed all medical records. Correlations between scores from the three systems were adjusted for measurement error in each using multilevel regression models. Results. Intercorrelations of scores were generally moderate to high across all three systems, and rose with adjustment for measurement error. Site-level correlations for prevention and diabetes care were particularly high. For example, adjusted for measurement error at the site level, prevention quality was correlated at 0.89 between the implicit and global systems, 0.67 between implicit and focused, and 0.73 between global and focused systems. Conclusions. We found moderate to high agreement in quality scores across the three profiling systems for most clinical areas, indicating that all three were measuring a similar construct called "quality." Adjusting for measurement error substantially enhanced out ability to identify this underlying construct. C1 [Kerr, Eve A.; Hofer, Timothy P.; Hayward, Rodney A.; Hogan, Mary M.] Vet Affairs Ann Arbor Healthcare Syst, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. [Kerr, Eve A.; Hofer, Timothy P.; Hayward, Rodney A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Adams, John L.; McGlynn, Elizabeth A.; Asch, Steven M.] Rand Corp, Santa Monica, CA USA. [Asch, Steven M.] Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Asch, Steven M.] Univ Calif Los Angeles, Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Kerr, EA (reprint author), Vet Affairs Ann Arbor Healthcare Syst, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. RI Kerr, Eve/I-3330-2013 FU Department of Veterans Affairs Health Services Research and Development Service [IIR#98-103]; NIDDK of the National Institutes of Health [P60DK-20572] FX This study was supported by the Department of Veterans Affairs Health Services Research and Development Service (IIR#98-103). Additional support was provided by the Michigan Diabetes Research and Training Center Grant P60DK-20572 from the NIDDK of the National Institutes of Health. NR 30 TC 14 Z9 14 U1 2 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2007 VL 42 IS 5 BP 2070 EP 2087 DI 10.1111/j.1475-6773.2007.00730.x PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 210AL UT WOS:000249429000017 PM 17850534 ER PT J AU Parker, MA Corliss, DA Gray, B Anderson, JK Bobbin, RP Snyder, EY Cotanche, DA AF Parker, Mark A. Corliss, Deborah A. Gray, Brianna Anderson, Julia K. Bobbin, Richard P. Snyder, Evan Y. Cotanche, Douglas A. TI Neural stem cells injected into the sound-damaged cochlea migrate throughout the cochlea and express markers of hair cells, supporting cells, and spiral ganglion cells SO HEARING RESEARCH LA English DT Article DE stem cell; hearing loss; spiral ganglion; hair cell ID INNER-EAR; ACOUSTIC TRAUMA; MOUSE COCHLEA; GENE-THERAPY; GUINEA-PIGS; NEURONS; REPLACEMENT; TRANSPLANTATION; REGENERATION; REPAIR AB Most cases of hearing loss are caused by the death or dysfunction of one of the many cochlear cell types. We examined whether cells from a neural stem cell line could replace cochlear cell types lost after exposure to intense noise. For this purpose, we transplanted a clonal stem cell line into the scala tympani of sound damaged mice and guinea pigs. Utilizing morphological, protein expression and genetic criteria, stem cells were found with characteristics of both neural tissues (satellite, spiral ganglion, and Schwann cells) and cells of the organ of Corti (hair cells, supporting cells). Additionally, noise-exposed, stem cell-injected animals exhibited a small but significant increase in the number of satellite cells and Type I spiral ganglion neurons compared to non-injected noise-exposed animals. These results indicate that cells of this neural stem cell line migrate from the scala tympani to Rosenthal's canal and the organ of Corti. Moreover, they suggest that cells of this neural stem cell line may derive some information needed from the microenvironment of the cochlea to differentiate into replacement cells in the cochlea. (C) 2007 Elsevier B.V. All rights reserved. C1 Emerson Coll, Dept Commun Sci & Disorders, Boston, MA 02116 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. LSU Hlth Sci Ctr, Dept Otolaryngol, Kresge Hearing Res Labs, New Orleans, LA USA. Burnham Inst, La Jolla, CA 92037 USA. Hlth Sci & Technol Program, Boston, MA USA. RP Parker, MA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM Mark_Parker@meei.harvard.edu OI Cotanche, Douglas/0000-0001-7972-0446 FU NIDCD NIH HHS [F32 DC005866, F32 DC005866-03, F32 DC05866-02, R01 DC001689-14, R01 DC001689-15, R01 DC001689-16A1] NR 44 TC 44 Z9 58 U1 2 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 2007 VL 232 IS 1-2 BP 29 EP 43 DI 10.1016/j.heares.2007.06.007 PG 15 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 223JA UT WOS:000250364900003 PM 17659854 ER PT J AU Canellos, GP AF Canellos, George P. TI Relapsed and refractory Hodgkin's lymphoma: New avenues? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID STEM-CELL TRANSPLANTATION; TERM-FOLLOW-UP; HIGH-DOSE CHEMOTHERAPY; ANTI-CD30 MONOCLONAL-ANTIBODY; FIELD RADIATION-THERAPY; CLINICAL STAGE-I; SALVAGE THERAPY; PROGNOSTIC-FACTORS; PHASE-I; COMBINATION CHEMOTHERAPY AB Relapse or progression following therapy for Hodgkin's lymphoma occurs in 10% to 60% of patients depending on initial clinical stage. Patterns of failure in advanced disease determine prognosis of salvage therapy. Progression or early relapse after less than 12 months requires intensive salvage therapy. Only late, isolated, asymptomatic relapse, which occurs in less than 25% of those relapsing from systemic therapy, can be treated with conventional-dose chemotherapy with or without radiation. Overall about 40% to 50% of relapses from advanced disease can be salvaged with higher percentages for patients relapsing from early stage disease. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Canellos, GP (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM george_canellos@dfci.harvard.edu NR 70 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2007 VL 21 IS 5 BP 929 EP + DI 10.1016/j.hoc.2007.06.012 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 225CU UT WOS:000250495500012 PM 17908629 ER PT J AU Decker, NK Bloch, KD Shah, V AF Decker, Ningling K. Bloch, Kenneth D. Shah, Vijay TI The protein kinase G-vasodilator stimulated phosphoprotein pathway disrupts hepatic stellate cell driven angiogenesis by disrupting focal adhesion formation SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Mayo Clin, Gastroenterol Res Unit, Rochester, MN USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 73 BP 266A EP 266A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400074 ER PT J AU Schiodt, FV Chung, RT Michael, SL Hay, JE Martin, P Lee, WM AF Schiodt, Frank V. Chung, Raymond T. Michael, Schilky L. Hay, J. Eileen Martin, Paul Lee, William M. TI Older age is not associated with worse outcomes in acute liver failure SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Rigshosp, Dept Hepatol A, DK-2100 Copenhagen, Denmark. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Weill Cornell Med Ctr, New York, NY USA. Mayo Clin, Rochester, MN USA. Mt Sinai Sch Med, New York, NY USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 92 BP 274A EP 275A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400093 ER PT J AU Delgado-Borrego, A Christofe, M Healey, D Ludwig, DA Jonas, MM Chung, RT AF Delgado-Borrego, Aymin Christofe, Marielle Healey, David Ludwig, David A. Jonas, Maureen M. Chung, Raymond T. TI Overweight is associated with diminished antiviral response in HCV-infected children SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Miami, Miami, FL 33152 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 98 BP 277A EP 277A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400099 ER PT J AU Di Bisceglie, AM Shiffman, ML Everson, GT Lindsay, KL Everhart, JE Wright, EC Lee, WM Lok, AS Bonkovsky, H Morgan, TR Dienstag, JL Ghany, M Morishima, C Snow, KK AF Di Bisceglie, Adrian M. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Everhart, James E. Wright, Elizabeth C. Lee, William M. Lok, Anna S. Bonkovsky, Herbert Morgan, Timothy R. Dienstag, Jules L. Ghany, Marc Morishima, Chihiro Snow, Kristin K. TI Prolonged antiviral therapy with peginterferon to prevent complications of advanced liver disease associated with hepatitis C: Results of the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. NIDDKD, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Off Director, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Div Digest & Liver Dis, Dallas, TX 75230 USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Calif Irvine, Gastroenterol Serv, Irvine, CA USA. VA Long Beach Healthcare Syst, Irvine, CA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIDDKD, Liver Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Washington, Dept Lab Med, Div Virol, Seattle, WA 98195 USA. New England Res Inst, Watertown, MA 02172 USA. RI Lok, Anna /B-8292-2009 NR 0 TC 23 Z9 23 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA LB1 BP 290A EP 290A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400128 ER PT J AU Goessling, W North, TE Lord, AM Lee, S Puder, M Moon, RT Zon, LI AF Goessling, Wolfram North, Trista E. Lord, Allegra M. Lee, Sang Puder, Mark Moon, Randall T. Zon, Leonard I. TI Prostaglandin E2 modulates wnt-mediated control of liver development and regeneration in zebrafish SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Childrens Hosp, Stem Cell Program, HHMI, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Washington, Dept Pharmacol, HHMI, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 192 BP 323A EP 323A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400198 ER PT J AU Lieber, CS Leo, MA Wang, XL Ponomarenko, A DeCarli, LM AF Lieber, Charles S. Leo, Maria A. Wang, Xiaolei Ponomarenko, Anatoly DeCarli, Leonore M. TI Effect of chronic alcohol consumption on nuclear gene regulators of mitochondrial function SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 James J Peters VA Med Ctr, Bronx, NY USA. Mt Sinai Hosp, Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 203 BP 327A EP 328A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400209 ER PT J AU Butt, AA Skanderson, M McGinnis, KA Kwoh, CK Justice, AC AF Butt, Adeel A. Skanderson, Melissa McGinnis, Kathleen A. Kwoh, C. K. Justice, Amy C. TI Real-life rates of treatment completion for HCV SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 281 BP 364A EP 364A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400287 ER PT J AU Lindsay, KL Morishima, C Wright, EC Dienstag, JL Shiffman, ML Everson, GT Lok, AS Bonkovsky, HL Lee, WM Morgan, TR Ghany, M AF Lindsay, Karen L. Morishima, Chihiro Wright, Elizabeth C. Dienstag, Jules L. Shiffman, Mitchell L. Everson, Gregory T. Lok, Anna S. Bonkovsky, Herbert L. Lee, William M. Morgan, Timothy R. Ghany, Marc TI Systemic factors associated with virologic nonresponse to peginterferon/ribavirin retreatment of chronic hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 USC Keck Sch Med, Dept Med Gastroenterol, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Colorado, Denver, CO 80202 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Connecticut, Farmington, CT USA. Univ Texas, Dallas, TX 75230 USA. Univ Calif Irvine, Irvine, CA USA. NIDDK, NIH, Bethesda, MD USA. RI Lok, Anna /B-8292-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 320 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400326 ER PT J AU Nakamoto, N Kaplan, D Li, Y Cole-Clough, J Shoked, A Kaminski, M Price, DA Wherry, EJ Freeman, G Chang, KM AF Nakamoto, Nobuhiro Kaplan, David Li, Yun Cole-Clough, Jennifer Shoked, Abraham Kaminski, Mary Price, David A. Wherry, E. John Freeman, Gordon Chang, Kyong-Mi TI Lack of functional restoration by PD1/PD-L1 blockade in intrahepatic HCV-specific CD8 T cells from chronically HCV-infected patients SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Univ Penn, Wistar Inst, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Oxford, Weatherall Inst Mol Med, Oxford OX1 2JD, England. RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 467 BP 446A EP 446A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400473 ER PT J AU Lin, WY Weinberg, E Kim, KA Peng, LF Kim, SS Brockman, M Lopez-Marra, H De Sa Borges, CB Hyppolite, G Shao, RX Chung, RT AF Lin, Wenyu Weinberg, Ethan Kim, Kyung Ah Peng, Lee F. Kim, Sun Suk Brockman, Mark Lopez-Marra, Hernan De Sa Borges, Carolina Bastos Hyppolite, Guibenson Shao, Run-Xuan Chung, Raymond T. TI Hiv and GP120 enhance HCV replication and upregulate TGF-beta 1 SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 469 BP 447A EP 447A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400475 ER PT J AU Shao, RX Kato, N Otsuka, M Yamada, N Chang, JH Muroyama, R Kawabe, T Omata, M AF Shao, Run-Xuan Kato, Naoyo Otsuka, Motoyuki Yamada, Nooyuki Chang, Jin-Hai Muroyama, Ryosuke Kawabe, Takao Omata, Masao TI Hepatitis C virus NS5A binding to nucleosome assembly protein 1 (NAP 1) accelerated HCV replication SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Tokyo, Sch Med, Tokyo 106, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Ajinomoto Co Inc, Inst Life Sci, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 486 BP 454A EP 454A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400492 ER PT J AU Kuntzen, T Berical, A Lennon, N Heckerman, D Timm, J Adams, S zur Wiesch, JCS Carlson, J Ybung, S Kim, AY Kadie, C Lauer, GM Marincola, FM Chung, RT Bihl, FK Cerny, A Brander, C Spengler, U Birren, BW Walker, BD Lake-Bakaar, G Daar, ES Jacobson, IM Gomperts, ED Edlin, BR Donfield, SM Talal, A Marion, TN Henn, MR Allen, TM AF Kuntzen, Thomas Berical, Andrew Lennon, Niall Heckerman, David Timm, Joerg Adams, Sharon Schulze zur Wiesch, Julian C. Carlson, Jonathan Ybung, Sarah Kim, Arthur Y. Kadie, Carl Lauer, Georg M. Marincola, Francesco M. Chung, Raymond T. Bihl, Florian K. Cerny, Andreas Brander, Christian Spengler, Ulrich Birren, Bruce W. Walker, Bruce D. Lake-Bakaar, Gerond Daar, Eric S. Jacobson, Ira M. Gomperts, Edward D. Edlin, Brian R. Donfield, Sharyne M. Talal, Andrew Marion, Tony N. Henn, Matthew R. Allen, Todd M. TI HLA class I associated sequence polymorphisms in HCV reveal reproducible patterns of immune escape - Towards a comprehensive map of key residues for vaccine design SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr,Dept Infect Dis, Charlestown, MA 02139 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA USA. Microsoft Res, Redmond, WA USA. Essen Univ Hosp, Dept Virol, Essen, Germany. Natl Inst Hlth, Clin Ctr, HLA Lab, Bethesda, MD USA. Univ Klinikum Hamburg Eppendorf, Med Klin 1, Hamburg, 02115, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. Clin Moncucco, Swiss HCV Cohort Study, Lugano, Switzerland. Univ Bonn Hosp, Dept Internal Med 1, Bonn, 38163, Germany. Univ Tennessee, Ctr Hlth Sci, Hepatitis C Cooperat, Memphis, TN 10021 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 90024 USA. Univ Calif Los Angeles, Med Ctr, Div HIV Med, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Div Infect Dis, Los Angeles Biomed Res Inst Harbor, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA USA. Rho Inc, Dept Biostat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 487 BP 455A EP 455A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400493 ER PT J AU Ryan, JC Monto, A Lehil, M Kim, M Tracy, D George, S Kennedy, AP Wright, TL Currie, S AF Ryan, James C. Monto, Alexander Lehil, Mandeep Kim, Michael Tracy, Daniel George, Sally Kennedy, Alan P. Wright, Teresa L. Currie, Sue TI Hepatitis C resolution correlates with patterned KIR receptor expression on killer lymphocytes SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, GI Div, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 488 BP 455A EP 455A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400494 ER PT J AU Newell, P Villanueva, A Chiang, D Peix, J Alsinet, C Van Laarhoven, S Thung, SN Fiel, MI Yea, S Roayaie, S Schwartz, M Kahn, M Friedman, SL Llovet, JM AF Newell, Pippa Villanueva, Augusto Chiang, Derek Peix, Judit Alsinet, Clara Van Laarhoven, Stijn Thung, Swan N. Fiel, Maria Isabel Yea, Steven Roayaie, Sasan Schwartz, Myron Kahn, Michael Friedman, Scott L. Llovet, Josep M. TI Activation of the Wnt/B-catenin pathway in hepatocellular carcinoma, and in vitro growth inhibition with a novel small molecule ICG-001 SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Mt Sinai Sch Med, New York, NY USA. Hosp Clin Barcelona, Liver Unit, Barcelona, Spain. Univ So Calif, Ctr Stem Cell & Regenerat Med, Los Angeles, CA USA. MIT, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 641 BP 523A EP 523A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400647 ER PT J AU Chiang, D Villanueva, A Peix, J Newell, P Wurmbach, E Donovan, D Beroukhim, R Getz, G Roayaie, S Schwartz, M Waxman, S Bruix, J Mazzaferro, V Friedman, SL Loda, M Ligon, A Meyerson, M Llovel, JM AF Chiang, Derek Villanueva, Augusto Peix, Judit Newell, Philippa Wurmbach, Elisa Donovan, Diana Beroukhim, Rameen Getz, Gad Roayaie, Sasan Schwartz, Myron Waxman, Samuel Bruix, Jordi Mazzaferro, Vincenzo Friedman, Scott L. Loda, Massimo Ligon, Azra Meyerson, Matthew Llovel, Josep M. TI Integrative genomic classification of hepatitis C virus positive hepatocellular carcinomas SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Dana Farber Canc Inst, Dept Med Oncol, Cambridge, MA USA. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Cambridge, MA USA. MIT & Harvard, Broad Inst, Canc Program, Cambridge, MA USA. Mt Sinai Sch Med, Surg Oncol & Pathol Dept, Div Liver Dis, New York, NY USA. Hosp Clin Barcelona, IDIBAPS, BCLC Grp, Liver Unit, Barcelona, Spain. IRCCS, Ist Nazl Tumori, Madison, WI USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 657 BP 530A EP 530A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400663 ER PT J AU Currie, S Shen, H Brau, N Anand, BS Aytaman, A Chang, KM Cheung, RCM Morgan, TR Pedrosa, M Schmidt, WN Monto, A McQuaid, R Wright, TL Bini, EJ AF Currie, Sue Shen, Hui Brau, Norbert Anand, Bhupinderjit S. Aytaman, Ayse Chang, Kyong-Mi Cheung, Ramsey Chi-Man Morgan, Timothy R. Pedrosa, Marcos Schmidt, Warren N. Monto, Alexander McQuaid, Rosemary Wright, Teresa L. Bini, Edmund J. TI Does gender matter? A prospective evaluation of risk factors for HCV infection and treatment candidacy in women SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, GI Div, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Div Gastroenterol, San Francisco, CA USA. New York VA Harbor Hlth Care Syst, New York, NY USA. Houston VAMC, GI Div, Houston, TX USA. Brooklyn VAMC, GI Div, Brooklyn, NY USA. Bronx VAMC, Bronx, NY USA. Philadelphia VAMC, GI Div, Philadelphia, PA USA. Palo Alto VAMC, Palo Alto, CA USA. Long Beach VAMC, GI Div, Long Beach, CA USA. Boston VAMC, GI Div, Boston, MA USA. Iowa City VAMC, GI ID Div, Iowa City, IA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 890 BP 632A EP 632A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401153 ER PT J AU Loggi, E Bihl, FK Fortini, C Cursaro, C Grandini, E Micco, L Gramenzi, A Bernardi, M Brander, C Andreone, P AF Loggi, Elisabetta Bihl, Florian K. Fortini, Cinzia Cursaro, Carmela Grandini, Elena Micco, Lorenzo Gramenzi, Annagiulia Bernardi, Mauro Brander, Christian Andreone, Pietro TI Restoration of HBV-specific T cell responses in lamivudine long term responder SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Bologna, Dept Internal Med, Bologna, Italy. Univ Hosp Geneva, Div Gastroenterol & Hepatol, Geneva, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 977 BP 672A EP 673A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401240 ER PT J AU Yanagisawa, K Wong, R Lin, W Baden, R Iken, K Lemon, SM Chung, RT Golden-Mason, L Rosen, HR Koziel, MJ Exley, MA AF Yanagisawa, Kazuhiko Wong, Roujie Lin, Wenyu Baden, Rachel Iken, Khadija Lemon, Stanley M. Chung, Raymond T. Golden-Mason, Lucy Rosen, Hugo R. Koziel, Margaret J. Exley, Mark A. TI Expression of hepatitis C virus proteins is sufficient to induce recognition by resident hepatic and invariant CD1D-restricted T cells SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Colorado Hlth Sci Univ, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1025 BP 694A EP 694A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401288 ER PT J AU zur Wiesch, JCS Kasprowicz, V Kim, AY Longworth, S Nolan, B Kuntzen, T McGovern, B Lewis-Ximenes, L Chung, RT Kwok, W Walker, BD Lauer, GM AF zur Wiesch, Julian C. Schulze Kasprowicz, Victoria Kim, Arthur Y. Longworth, Steve Nolan, Brian Kuntzen, Thomas McGovern, Barbara Lewis-Ximenes, Lia Chung, Raymond T. Kwok, William Walker, Bruce D. Lauer, Georg M. TI Detection of CD4+ T cell responses in patients with acute HCV infection irrespective of clinical outcome SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Klinikum Hamburg Eppendorf, Med Klin 1, Hamburg, Germany. Massachusetts Gen Hosp, Partners Aids Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Benaroya Res Inst, Seattle, WA USA. Lemuel Shattuck Hosp, Boston, MA USA. Inst Oswaldo Cruz, Rio De Janeiro, MA, Brazil. Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1029 BP 696A EP 696A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401292 ER PT J AU Shah, N Zheng, H Misdraji, J Chung, RT AF Shah, Nirali Zheng, Hui Misdraji, Joseph Chung, Raymond T. TI Beneficial effect of angiotensin-blocking agents on liver fibrosis in patients with hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1047 BP 703A EP 704A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401310 ER PT J AU Nevzorova, Y Tschaharganeh, DF Sicinski, P Trautwein, C Liedtke, C AF Nevzorova, Yulia Tschaharganeh, Darjus F. Sicinski, Peter Trautwein, Christian Liedtke, Christian TI Differential functions of cyclin El and E2 for cell cycle control and endoreplication during liver regeneration in mice SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Hosp Aachen, Dept Med 3, Aachen, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1241 BP 788A EP 788A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401504 ER PT J AU Schiff, ER Everson, GT Tsai, N Bzowei, NH Gish, RG McHutchison, JG Jacobson, IM Tong, MJ Jensen, DM Lauer, GM Cruickshank, S Ferraro, J Haller, A Duke, R Rodell, T Apelian, D AF Schiff, Eugene R. Everson, Gregory T. Tsai, Naoky Bzowei, Nathalie H. Gish, Robert G. McHutchison, John G. Jacobson, Ira M. Tong, Myron J. Jensen, Donald M. Lauer, Georg M. Cruickshank, Scott Ferraro, John Haller, Aurelia Duke, Richard Rodell, Timothy Apelian, David TI HCV-specific cellular immunity, RNA reductions, and normalization of ALT in chronic HCV subjects after treatment with Gl-5005, a yeast-based immunotherapy targeting NS3 and Core: A randomized, double-blind, placebo controlled phase 1B study SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 GlobeImmune, Clin Dev & Regulatory Affairs, Louisville, CO USA. Univ Miami, Liver Res Ctr, Miami, FL 33152 USA. Huntington Med Res Inst, Pasadena, CA USA. Univ Colorado, Sch Med, Hlth Sci Ctr, Denver, CO 80202 USA. Cornell Univ, Weill Med Coll, New York, NY USA. Univ Chicago, Chicago, IL 60637 USA. Calif Pacific Med Ctr, Dept Transplantat, San Francisco, CA USA. Univ Hawaii, Dept Med, Honolulu, HI 96822 USA. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Scott Cruickshank & Associates Inc, Santa Barbara, CA USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1304 BP 816A EP 816A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401567 ER PT J AU Rodriguez-Torres, M Sulkowski, M Chung, RT Hamzeh, F Jensen, DM AF Rodriguez-Torres, Maribel Sulkowski, Mark Chung, Raymond T. Hamzeh, Fayez Jensen, Donald M. TI Association of pre-treatment and on-treatment factors with rapid virologic response in HCV genotype 1 infected patients treated with pegIFA alpha-2a/RBV SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Fdn Gastroenterol Diego, Santurce, PR 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 60637 USA. Roche Labs, Nutley, NJ USA. Univ Chicago, Chicago, IL USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1305 BP 817A EP 817A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401568 ER PT J AU Kim, KA Lin, W Weinberg, E Borges, CB Tai, AW Kamegaya, Y Chung, RT AF Kim, Kyung Ah Lin, Wenyu Weinberg, Ethan Borges, Carolina B. Tai, Andrew W. Kamegaya, Yoshitaka Chung, Raymond T. TI Hepatic SOCS3 expression is strongly associated with non-response to IFN treatment in chronic HCV SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1334 BP 831A EP 832A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401597 ER PT J AU Peng, LF Kim, SS Lin, W Sakamoto, N Kato, N Ikeda, M Schreiber, S Baines, RT AF Peng, Lee F. Kim, Sun-Suk Lin, Wenyu Sakamoto, Naoya Kato, Noboyuki Ikeda, Masanori Schreiber, Stuart Baines, Richard T. TI Identification of modulators of HCV replication using a high- throughput screen SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 1379 BP 852A EP 852A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401642 ER EF