FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Greenberg, SM Eng, JA Ning, MM Rosand, J AF Greenberg, SM Eng, JA Ning, MM Rosand, J TI Microhemorrhages predict recurrent symptomatic hemorrhage and clinical decline following lobar hemorrhage SO STROKE LA English DT Meeting Abstract CT 29th International Stroke Conference CY FEB 05-07, 2004 CL SAN DIEGO, CALIFORNIA 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2004 VL 35 IS 1 BP 333 EP 333 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 758JH UT WOS:000187630500548 ER PT J AU Kerrigan, AJ Kaough, JE Wilson, BL Wilson, JB Bostick, R AF Kerrigan, AJ Kaough, JE Wilson, BL Wilson, JB Bostick, R TI Vocational rehabilitation of participants with severe substance use disorders in a VA Veterans Industries program SO SUBSTANCE USE & MISUSE LA English DT Article DE vocational rehabilitation; veterans industries; substance use; outcomes; work therapy ID ABUSE TREATMENT; WORK THERAPY AB There are approximately 100 Veterans Industries work therapy programs in the Veterans Health Administration (VHA) throughout the U.S. The majority of participants are veterans with severe substance use disorders and their length of stay ranges from 3 to 12 months. This study examines the Veterans Industries work therapy model at one site where veterans are referred from an addictions partial hospitalization treatment program. The study period was from 1996-97 and includes 80 patients. The characteristics of the participants are described. Barriers to employment are identified including unemployment rates, homelessness, drug of choice, age, and disability status. Outcome rates are reported including employment, abstinence, and housing support. C1 Dept Vet Affairs Med Ctr, Houston, TX USA. RP Kerrigan, AJ (reprint author), VA Med Ctr, Mental Hlth Care Line 116, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM kerrigan.anthonyj@med.va.gov NR 15 TC 2 Z9 2 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2004 VL 39 IS 13-14 BP 2513 EP 2523 DI 10.1081/LSUM-200034695 PG 11 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 910AO UT WOS:000227902000013 PM 15603012 ER PT J AU Kerrigan, AJ AF Kerrigan, AJ TI From work therapy to mainstream employment SO SUBSTANCE USE & MISUSE LA English DT Article C1 Dept Vet Affairs Med Ctr, Houston, TX USA. RP Kerrigan, AJ (reprint author), Dept Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2004 VL 39 IS 13-14 BP 2639 EP 2640 DI 10.1081/LSUM-200034700 PG 2 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 910AO UT WOS:000227902000025 PM 15603024 ER PT J AU Cooper, DKC AF Cooper, DKC TI The surgical anatomy of experimental and clinical thoracic organ transplantation SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article; Proceedings Paper CT 1st Symposium on Influenza and Cardiovascular Disease CY APR 26, 2003 CL Texas Heart Inst, Houston, TX HO Texas Heart Inst DE animal; cardiac surgical procedures/history; heart transplantation/methods; history of medicine/20th cent.; human; lung transplantation/methods ID LUNG-TRANSPLANTATION; HEART-TRANSPLANTATION; LOBAR TRANSPLANTATION; REGISTRY AB The experimental investigation of heart transplantation began almost 100 years ago, but it was not until the studies at Stanford Medical School in the late 1950s and early 1960s that clinical transplantation became a realistic possibility. Barnard performed the 1st human-to-human orthotopic heart transplantation in 1967 and followed this by introducing the technique of heterotopic heart transplantation in 1974. Reitz and colleagues at Stanford performed the 1st successful clinical transplantation of the heart and both lungs in 1981. Two years later at the Toronto General Hospital, successful single-lung transplantation was performed, followed by bilateral lung transplantation in 1986. Aspects of the surgical techniques of these various experimental and clinical procedures are discussed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Biol Res Ctr, Boston, MA USA. RP Cooper, DKC (reprint author), Univ Pittsburgh, Med Ctr, MUH, Thomas E Starzl Transplantat Inst, Room N761,3459 5th Ave, Pittsburgh, PA 15213 USA. EM cooperdk@upmc.edu NR 25 TC 5 Z9 10 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 2004 VL 31 IS 1 BP 61 EP 68 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 804FL UT WOS:000220284500012 PM 15061629 ER PT J AU Holliday, SL Saklad, AR Garcia-Cavasos, R Fischbach, M Padilla, PA McGlasson, D Brey, RL AF Holliday, SL Saklad, AR Garcia-Cavasos, R Fischbach, M Padilla, PA McGlasson, D Brey, RL TI Risk factors for cognitive dysfunction in SLE: San Antonio lupus study of neuropsychiatric disease SO THROMBOSIS RESEARCH LA English DT Meeting Abstract CT 11th International Congress on Antiphospholipid Antibodies CY NOV 14-18, 2004 CL Sydney, AUSTRALIA C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. UTHSCSA, San Antonio, TX USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2004 VL 114 IS 5-6 SI SI BP 629 EP 629 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 911OZ UT WOS:000228015200112 ER PT J AU Shin, M Yoshimoto, H Vacanti, JP AF Shin, M Yoshimoto, H Vacanti, JP TI In vivo bone tissue engineering using mesenchymal stem cells on a novel electrospun nanofibrous scaffold SO TISSUE ENGINEERING LA English DT Article ID FIBERS; POLYMER; CULTURE; FOAM AB The objective of this study was to assess bone formation from mesenchymal stem cells (MSCs) on a novel nanofibrous scaffold in a rat model. A highly porous, degradable poly(,E-caprolactone) (PCL) scaffold with an extracellular matrix-like topography was produced by electrostatic fiber spinning. MSCs derived from the bone marrow of neonatal rats were cultured, expanded, and seeded on the scaffolds. The cell-polymer constructs were cultured with osteogenic supplements in a rotating bioreactor for 4 weeks, and subsequently implanted in the omenta of rats for 4 weeks. The constructs were explanted and characterized by histology, immunohistochemistry, and scanning electron microscopy. The constructs maintained the size and shape of the original scaffolds. Morphologically, the constructs were rigid and had a bone-like appearance. Cells and extracellular matrix (ECM) formation were observed throughout the constructs. In addition, mineralization and type I collagen were also detected. This study establishes the ability to develop bone grafts on electrospun nanofibrous scaffolds in a well-vascularized site using MSCs. C1 Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Ctr Integrat Med & Innovat Technol, Boston, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Lab Tissue Engn & Organ Fabricat, Warren 1157,55 Fruit St, Boston, MA 02114 USA. EM vacanti@partners.org NR 28 TC 259 Z9 294 U1 6 U2 66 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN-FEB PY 2004 VL 10 IS 1-2 BP 33 EP 41 DI 10.1089/107632704322791673 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 775EW UT WOS:000189028600004 PM 15009928 ER PT J AU Nakagawa, K Abukawa, H Shin, MY Terai, H Troulis, MJ Vacanti, JP AF Nakagawa, K Abukawa, H Shin, MY Terai, H Troulis, MJ Vacanti, JP TI Osteoclastogenesis on tissue-engineered bone SO TISSUE ENGINEERING LA English DT Article ID BIODEGRADABLE POLYMER SCAFFOLDS; MESENCHYMAL STEM-CELLS; IN-VITRO; CULTURE; OSTEOBLASTS; MONOCYTES; ACTIN; CYCLE AB Bone remodeling plays an important role in bone function. To date, bone tissue-engineering research has focused primarily on bone formation from osteoblasts. This study demonstrates that osteoclastogenesis can occur on a mineralized polymer scaffold. Porcine bone marrow-derived mesenchymal stem cells (pMSCs) and hematopoietic cells were isolated from the bone marrow of Yucatan minipigs (n = 3) and cultured separately. pMSCs were differentiated into osteoblasts, seeded on porous poly(D,L-lactic-co-glycolic acid) foams, and cultured in a rotating oxygen-permeable bioreactor system. Once the cell-polymer constructs had started to mineralize, the hematopoietic cells were added and cocultured to include osteoclastogenesis. The cultured constructs were evaluated by histochemical and microscopic examination. Our results show that osteoblasts and osteoclasts were successfully differentiated from bone marrow on the scaffolds. This is the first demonstration of osteoclast formation on mineralized polymer surfaces. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren Bldg 1157,55 Fruit St, Boston, MA 02114 USA. EM jvacanti@partners.org NR 25 TC 32 Z9 32 U1 0 U2 4 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN-FEB PY 2004 VL 10 IS 1-2 BP 93 EP 100 DI 10.1089/107632704322791736 PG 8 WC Cell & Tissue Engineering SC Cell Biology GA 775EW UT WOS:000189028600010 PM 15009934 ER PT J AU Veilleux, NH Yannas, IV Spector, M AF Veilleux, NH Yannas, IV Spector, M TI Effect of passage number and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes in type I and II collagen-glycosaminoglycan matrices in vitro SO TISSUE ENGINEERING LA English DT Article ID DEDIFFERENTIATED CHONDROCYTES; EXTRACELLULAR-MATRIX; CARTILAGE REPAIR; MUSCLE ACTIN; TISSUE; SCAFFOLDS; DEFECTS; CULTURE; CELL; REGENERATION AB One tissue-engineering approach being investigated for the treatment of defects in articular cartilage involves the implantation of autologous chondrocyte-seeded absorbable scaffolds. The present study evaluated the effects of passage number (freshly isolated and passages 1 and 2) and collagen type on the proliferative, biosynthetic, and contractile activity of adult canine articular chondrocytes grown in type I and II collagen-glycosaminoglycan (GAG) matrices that were cross-linked by dehydrothermal/carbodiimide treatment. P0, P1, and P2 cells seeded in the type II matrices continued to proliferate over a 4-week period, but thereafter the P0 and P1 cells continued to increase in number and the P2 cells decreased. At 4 weeks the DNA contents of the type I and II matrices seeded with P1 and P2 cells were comparable, and higher than the values for matrices seeded with freshly isolated chondrocytes. The rates of protein and GAG synthesis by the P1 and P2 cells were comparable, and higher than the rates for the P0 chondrocytes, after 1 week, and the rates were generally higher in the type II than in the type I collagen scaffolds. Western blot analysis demonstrated the presence of newly synthesized type II collagen in type II matrices in which P1 and P2 cells were grown. The cross-linking treatment imparted a sufficient degree of mechanical stiffness to both types of matrices to resist cell-mediated contraction. This study demonstrated that adult articular chondrocytes expanded in number through two passages in monolayer culture can be expected to provide behavior comparable to or better than freshly isolated cells with respect to proliferation and biosynthesis through 4 weeks of culture in collagen-GAG matrices, and these cells retain the capability to synthesize type II collagen. The results of this investigation further commend the use of a type II collagen-GAG matrix, based on the higher biosynthetic rates of the cells grown in the matrices, for the preparation of chondrocyte-seeded scaffolds for articular cartilage tissue engineering. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Boston Healthcare Syst, Boston, MA USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. RP Spector, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Orthoped Surg, MRB 106,75 Francis St, Boston, MA 02115 USA. EM mspector@rics.bwh.harvard.edu FU NIDCR NIH HHS [5 T32 DE07311] NR 32 TC 51 Z9 53 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN-FEB PY 2004 VL 10 IS 1-2 BP 119 EP 127 DI 10.1089/107632704322791763 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 775EW UT WOS:000189028600013 PM 15009937 ER PT J AU Kamil, SH Rodrigruez, A Vacanti, CA Eavey, RD Vacanti, MP AF Kamil, SH Rodrigruez, A Vacanti, CA Eavey, RD Vacanti, MP TI Expansion of the number of human auricular chondrocytes: Recycling of culture media containing floating cells SO TISSUE ENGINEERING LA English DT Article ID TISSUE-ENGINEERED CARTILAGE; GROWTH-FACTOR-BETA; ARTICULAR CHONDROCYTES; VESICOURETERAL REFLUX; ELASTIC CARTILAGE; FLOW-CYTOMETRY; ALGINATE; RECONSTRUCTION; MICROTIA AB To grow a complete human size auricle by utilizing the principles of tissue engineering, a large number of chondrocytes is required for initial implantation. The number of chondrocytes can be increased by repeated passaging or by incubation with different growth factors, both of which can promote dedifferentiation. New methods of chondrocyte expansion over a relatively brief time period for potential practical application are required. In this study auricular chondrocytes were obtained from patients and cultured in vitro. Two groups of cells were created. Group A chondrocyte number was increased by repeated passaging. Group B cells were grown from floating culture medium and their number was increased both by passaging and by repeated recycling of the culture medium. Chondrocytes from both groups were implanted in nude mice for 8 weeks to generate tissue-engineered cartilage. Flow cytometry studies performed on both groups confirmed the presence of two distinct populations of structures as the source of chondrocytes from the recycled medium. Repeated recycling of the culture medium demonstrates a promising method to increase the number of chondrocytes in vitro for clinical application. C1 Univ Massachusetts, Sch Med, Dept Anesthesiol, Lab Tissue Engn, Worcester, MA 01655 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01605 USA. RP Vacanti, MP (reprint author), Univ Massachusetts, Sch Med, Dept Anesthesiol, Lab Tissue Engn, Worcester, MA 01655 USA. EM martin.vacanti@umassmed.edu NR 15 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN-FEB PY 2004 VL 10 IS 1-2 BP 139 EP 144 DI 10.1089/107632704322791781 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 775EW UT WOS:000189028600015 PM 15009939 ER PT J AU Yost, MJ Baicu, CF Stonerock, CE Goodwin, RL Price, RL Davis, JM Evans, H Watson, PD Gore, CM Sweet, J Creech, L Zile, MR Terracio, L AF Yost, MJ Baicu, CF Stonerock, CE Goodwin, RL Price, RL Davis, JM Evans, H Watson, PD Gore, CM Sweet, J Creech, L Zile, MR Terracio, L TI A novel tubular scaffold for cardiovascular tissue engineering SO TISSUE ENGINEERING LA English DT Article ID BIOENGINEERED CARDIAC GRAFTS; ARTIFICIAL SKIN; IN-VITRO; DESIGN; MUSCLE; ORIENTATION; MYOCARDIUM; CONSTRUCT; ADHESION; MATRIX AB We have developed a counter rotating cone extrusion device to produce the next generation of three-dimensional collagen scaffold for tissue engineering. The device can produce a continuously varying fibril angle from the lumen to the outside of a 5-mm-diameter collagen tube, similar to the pattern of heart muscle cells in the intact heart. Our scaffold is a novel, oriented, type I collagen, tubular scaffold. We selected collagen because we believe there are important signals from the collagen both geometrically and biochemically that elicit the in vivo-like phenotypic response from the cardiomyocytes. We have shown that cardiomyocytes can be cultured in these tubes and resemble an in vivo phenotype. This new model system will provide important information leading to the design and construction of a functional, biologically based assist device. C1 Univ S Carolina, Sch Med, Dept Surg, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Dept Anat & Dev Biol, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Dept Chem Engn, Columbia, SC 29208 USA. Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Univ S Carolina, Sch Med, Dept Pharmacol & Physiol, Columbia, SC USA. NYU, Coll Dent, New York, NY USA. RP Yost, MJ (reprint author), Univ S Carolina, Sch Med, Dept Surg, Columbia, SC 29208 USA. EM Yost@med.sc.edu FU NHLBI NIH HHS [HL072096, K25-HL67097] NR 24 TC 47 Z9 48 U1 1 U2 19 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JAN-FEB PY 2004 VL 10 IS 1-2 BP 273 EP 284 DI 10.1089/107632704322791916 PG 12 WC Cell & Tissue Engineering SC Cell Biology GA 775EW UT WOS:000189028600028 PM 15009952 ER PT J AU Knuefermann, P Vallejo, J Mann, DL AF Knuefermann, P Vallejo, J Mann, DL TI The role of innate immune responses in the heart in health and disease SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID TUMOR-NECROSIS-FACTOR; ISCHEMIA-REPERFUSION INJURY; TOLL-LIKE RECEPTOR-4; NF-KAPPA-B; LEUKEMIA-INHIBITORY FACTOR; ADULT FELINE MYOCARDIUM; FACTOR-ALPHA GENE; CARDIAC MYOCYTES; TRANSGENIC MICE; DILATED CARDIOMYOPATHY AB The ability of the myocardium to successfully adapt to environmental stress ultimately determines whether the heart will decompensate and fail, or whether it will maintain preserved function. Despite the importance of the myocardial response to environmental stress, very little is known with respect to the biochemical mechanisms that are responsible for mediating and integrating the stress response in the heart. The present review summarizes recent experimental material that suggests that the heart possesses a germ-line encoded "innate" stress response that is activated in response to diverse forms of tissue injury. The extant literature suggests that this innate stress response plays an important role in initiating and integrating homeostatic responses within the heart. Nonetheless, as will be discussed further herein, these inflammatory mediators all have the potential to produce cardiac decompensation when expressed at sufficiently high concentrations. (C) 2004, Elsevier Inc. C1 Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Houston Vet Adm Med Ctr, Houston, TX USA. RP Mann, DL (reprint author), Winters Ctr Heart Failure Res, MS 524,6565 Fannin, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL 42250-10/10, R01 HL 58081-01, R01 HL 61543-01] NR 48 TC 25 Z9 25 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 2004 VL 14 IS 1 BP 1 EP 7 AR PII S1050-1738(03)001677-1 DI 10.1016/j.tcm.2003.09.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 767GH UT WOS:000188431500001 PM 14720467 ER PT J AU Goldfeld, AE AF Goldfeld, AE TI Genetic susceptibility to pulmonary tuberculosis in Cambodia SO TUBERCULOSIS LA English DT Article; Proceedings Paper CT Symposium on Tuberculosis and Leprosy CY JUL 03-05, 2002 CL UNIV MALAYSIA SABAH, KOTA KINABALU, MALAYSIA HO UNIV MALAYSIA SABAH DE genetic susceptibility; HLA; candidate gene; polymorphisms; tuberculosis; Cambodia ID INTERFERON-GAMMA-RECEPTOR; NECROSIS-FACTOR-ALPHA; MYCOBACTERIUM-TUBERCULOSIS; CALMETTE-GUERIN; INFECTION; HLA; POLYMORPHISMS; ASSOCIATION; MICE; DEFICIENCY AB We. have studied the risk of progression to active pulmonary tuberculosis.(TB) among a population of Cambodian rural poor suffering from one of the highest global incidences of TB. Together with a community-based TB program, we have established a research partnership that has demonstrated the association of a particular HLA binding motif and progression to active pulmonary TB. We have also shown that candidate gene polymorphisms are ethnic specific and unique in Cambodia and are Likely markers for as yet unidentified disease susceptibility and resistance loci. We have also uncovered a high incidence of antigen-specific anergy to purified protein derivative among patients with active pulmonary TB and have correlated this with an expansion of immunosuppressive IL-10 producing T cells and other impaired T cell responses to mycobacterial antigens. These experiments tend, insight into TB susceptibility and the molecular mechanisms of antigen-specific anergy. Moreover, they demonstrate that a partnership between TB cure and scientific discovery is possible in even the most impoverished settings. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL59838] NR 38 TC 12 Z9 13 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2004 VL 84 IS 1-2 BP 76 EP 81 DI 10.1016/j.tube.2003.08.007 PG 6 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 766LV UT WOS:000188378600011 PM 14670348 ER PT B AU Welt, C AF Welt, C BE Filicori, M TI Are there practical benefits from measuring the inhibins? SO UPDATES IN INFERTILITY TREATMENT 2004 LA English DT Proceedings Paper CT Conference on Updates in Infertility Treatment CY JAN 22-24, 2004 CL Marco Isl, FL DE prognosis; infertility; assisted reproductive technology; sperm extraction ID FOLLICLE-STIMULATING-HORMONE; IN-VITRO FERTILIZATION; TESTICULAR SPERM EXTRACTION; GRANULOSA-LUTEAL CELLS; REGULAR MENSTRUAL CYCLES; SERUM INHIBIN; OVARIAN RESERVE; B LEVELS; NONOBSTRUCTIVE AZOOSPERMIA; DIMERIC INHIBIN AB The time, expense and emotional commitment involved in assisted reproductive technologies (ART) mandate the development of good prognostic markers of treatment success. Inhibin A and inhibin B, protein products of the granulosa and Sertoli cells, have been examined as markers because they reflect granulosa and Sertoli cell number and function and mirror the decrease in fertility and follicle number that occur during reproductive aging in women. Although initially promising, baseline day 3 inhibin B levels do not appear to predict pregnancy outcome during ART in the majority of studies. Inhibin B and inhibin A measured during stimulation testing are more Promising measurements of cycle outcome, but their relative value compared to traditional markers, age and FSH levels, needs further evaluation. Inhibin B levels measured during early ovarian hyperstimulation are the most favorable prognostic test for predicting the number of oocytes retrieved. In men, inhibin B measurements do not uniformly predict the success of testicular sperm extraction. Taken together, the data suggests that measurement of inhibin B may be most practical not for predicting the outcome of ART, but rather for early intervention during controlled ovarian stimulation in women. Large-scale, prospective studies are needed to validate these findings before inhibin B is put into widespread clinical use. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Welt, C (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, 55 Fruit St, Boston, MA 02114 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-088-8 PY 2004 BP 251 EP 263 PG 13 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BBR45 UT WOS:000227356900019 ER PT B AU Hall, JE AF Hall, JE BE Filicori, M TI Gonadotropin secretion in PCOS SO UPDATES IN INFERTILITY TREATMENT 2004 LA English DT Proceedings Paper CT Conference on Updates in Infertility Treatment CY JAN 22-24, 2004 CL Marco Isl, FL DE neuroendocrinology; polycystic ovarian syndrome; LH; FSH; obesity ID POLYCYSTIC-OVARY-SYNDROME; FOLLICLE-STIMULATING-HORMONE; SERUM INHIBIN-B; LUTEINIZING-HORMONE; PULSE-GENERATOR; MENSTRUAL-CYCLE; OVULATION INDUCTION; POSSIBLE MECHANISM; GENETIC VARIANT; GRANULOSA-CELLS AB Gonadotropin dysfunction characterized by an increased ratio of LH to FSH is commonly associated with polycystic ovarian syndrome (PCOS) and may be implicated in the pathophysiology of this disorder. However, the prevalence of gonadotropin abnormalities in PCOS is extremely variable, ranging from 35 to 90% in different studies. Two separate factors have been shown to impact on the LH/MH ratio in patients with PCOS. Exposure to endogenous progesterone in association with ovulation or exposure to a progestin results in a slowing of GnRH pulse frequency and a temporary decrease in mean LH and the LH/FSH ratio. In addition, mean LH, LH pulse amplitude and the LH/FSH ratio are profoundly affected by body mass index (BMI) with obese PCOS patients demonstrating values within the range of normal early follicular phase women. In contrast, LH pulse frequency is increased in comparison with normal women across the spectrum of BMI with no difference between lean and obese PCOS patients. As both increased LH and increased insulin are associated with ovarian hyperandrogenism, it is possible that the pathogenesis of PCOS is bimodal - due to high LH in lean patients and increased insulin levels in obese patients. However, the inverse relationship between BMI and LH is continuous across a wide spectrum of BMI suggesting that LH and obesity are not independent contributors to the PCOS phenotype, but are interrelated. Further studies are underway which explore the mechanism underlying the inverse relationship between LH and BMI in PCOS. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, 55 Fruit St, Boston, MA 02114 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-088-8 PY 2004 BP 441 EP 456 PG 16 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BBR45 UT WOS:000227356900032 ER PT J AU Bhayani, SB Pavlovich, CP Strup, SE Dahl, DM Landman, J Fabrizio, MD Sundaram, CP Kaouk, JH Su, LM AF Bhayani, SB Pavlovich, CP Strup, SE Dahl, DM Landman, J Fabrizio, MD Sundaram, CP Kaouk, JH Su, LM TI Laparoscopic radical prostatectomy: A multi-institutional study of conversion to open surgery SO UROLOGY LA English DT Article ID EXPERIENCE AB Objectives. To perform a multi-institutional review of the incidence and factors contributing to conversion from laparoscopic radical prostatectomy (LRP) to open radical retropubic prostatectomy (RRP) among eight surgeons. Methods. The medical records from all patients undergoing LRP at seven institutions were reviewed to assess the incidence of open conversion to RRP. The clinical, operative, pathologic, and functional outcomes of patients who required conversion were compiled and analyzed. Results. Of 670 operations, 13 (1.9%) were converted from LRP to RRP. The most common steps at which conversion occurred were the apical dissection (38%) and the posterior seminal vesicle dissection (31%). Failure to progress was the most common cause of conversion, followed by injury to adjacent structures and hypercarbia. Comorbidities associated with conversion were prior pelvic surgery and obesity (body mass index greater than 30). Six of the 13 conversions occurred in the surgeons' first 5 cases. Despite open conversion, patients were continent (no pads) (92%) and potent (44%) with at least 6 months of follow-up. Conclusions. Open conversion from LRP to RRP is an uncommon event, but is more likely to occur during a surgeon's early experience. Surgeons beginning their experience with LRP are advised to select their patients carefully to minimize the need for conversion to open surgery. Obese patients and those at risk of periprostatic adhesions should initially not be considered for LRP. Despite open conversion, the functional outcomes did not appear to be adversely affected. (C) 2004 Elsevier Inc. C1 Johns Hopkins Bayview Med Ctr, Dept Urol, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Brady Urol Inst, Baltimore, MD 21224 USA. Thomas Jefferson Univ, Dept Urol, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Univ Washington, Sch Med, Div Urol Surg, St Louis, MO USA. Eastern Virginia Med Sch, Divine Tidewater Urol, Norfolk, VA 23501 USA. Indiana Univ, Sch Med, Dept Urol, Indianapolis, IN USA. Cleveland Clin Fdn, Dept Urol, Cleveland, OH 44195 USA. RP Su, LM (reprint author), Johns Hopkins Bayview Med Ctr, Dept Urol, 4940 Eastern Ave,Room A345, Baltimore, MD 21224 USA. NR 7 TC 33 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JAN PY 2004 VL 63 IS 1 BP 99 EP 102 DI 10.1016/j.urology.2003.08.018 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 807YZ UT WOS:000220538100025 PM 14751358 ER PT J AU Yu, NR Eberhardt, RT Menzoian, JO Urick, CL Raffetto, JD AF Yu, NR Eberhardt, RT Menzoian, JO Urick, CL Raffetto, JD TI Vertebral artery dissection following intravascular catheter placement: a case report and review of the literature SO VASCULAR MEDICINE LA English DT Review DE arterial; catheter; dissection; iatrogenic; vertebral ID CHIROPRACTIC MANIPULATION; THERAPY; INJURY AB Vertebral artery dissections (VAD) are known to occur as a result of mechanical manipulations of the cervical region, traumatic injury, iatrogenic injury and are also known to arise spontaneously. We report a case of vertebral artery dissection following vertebral artery cannulation during a central line placement and review the literature. The patient underwent intravascular catheter placement that subsequently demonstrated arterial blood. Duplex ultrasound and computed tomographic (CT) scan confirmed vertebral artery cannulation. The catheter was removed at the bedside with pressure, and a subsequent duplex ultrasound scan revealed a vertebral artery dissection. There were no neurological sequelae. The patient was successfully anticoagulated with warfarin but died from unrelated complications. This case report describes the rare iatrogenic event of VAD and reviews its etiology, diagnosis, complications, and management. C1 Boston Med Ctr, Boston, MA USA. Boston VA Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Raffetto, JD (reprint author), VA Boston Hlth Care Syst, Dept Surg, 112,1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM joseph.raffetto@med.va.gov OI Eberhardt, Robert/0000-0002-5076-7416 NR 14 TC 7 Z9 9 U1 0 U2 2 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2004 VL 9 IS 3 BP 199 EP 203 DI 10.1191/1358863x04vm565cr PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 885VM UT WOS:000226185300007 PM 15675185 ER PT J AU Beckman, JA Mehta, RH Isselbacher, EM Bossone, E Cooper, JV Smith, DE Fang, JM Sechtem, U Pape, LA Myrmel, T Nienaber, CA Eagle, KA O'Gara, PT AF Beckman, JA Mehta, RH Isselbacher, EM Bossone, E Cooper, JV Smith, DE Fang, JM Sechtem, U Pape, LA Myrmel, T Nienaber, CA Eagle, KA O'Gara, PT TI Branch vessel complications are increased in aortic dissection patients with renal insufficiency SO VASCULAR MEDICINE LA English DT Article DE aortic dissection; kidney failure; mortality ID MANAGEMENT; SURGERY; DISEASE AB Morbidity and mortality from aortic dissection remain high despite advances in diagnosis and treatment. Simple markers to identify patients at high risk for non-aortic complications of dissection are lacking. We investigated the effect of renal insufficiency on the presentation, complications, and outcome of patients with acute aortic dissection. We evaluated 638 patients with type A and 365 patients with type B aortic dissection enrolled in the International Registry of Acute Aortic Dissection (IRAD) between January 1996 and December 2000. Chi-squared and Student's t testing were performed to identify the effect of renal insufficiency on patient presentation, management, and outcome. Patients with renal insufficiency more often required nitroprusside for blood pressure control (type A: 40.7% vs 31.1%, p = 0.049; type B: 66.7% vs 37.3, p = 0.0001) and had a greater risk of mesenteric ischemia (type A: 10.7% vs 1.4%, p < 0.0001; type B: 17.7% vs 3.0%, p < 0.0001). In conclusion, aortic dissection patients with renal insufficiency are at increased risk for drug-resistant hypertension and aortic branch vessel compromise. Routine measurement of serum creatinine provides a readily accessible clinical marker for important complications. Upon recognition, renal impairment indicates a need for close monitoring, aggressive blood pressure control, and evaluation of aortic branch vessel circulations. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CNR, Lecce, Italy. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Massachusetts Hosp, Worcester, MA USA. Tromsa Univ Hosp, Tromsa, Norway. Univ Rostock, Rostock, Germany. RP O'Gara, PT (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM pogara@partners.org OI Beckman, Joshua/0000-0001-8332-8439 FU NHLBI NIH HHS [K23 HL 04169] NR 14 TC 3 Z9 5 U1 0 U2 1 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1358-863X J9 VASC MED JI Vasc. Med. PY 2004 VL 9 IS 4 BP 267 EP 270 DI 10.1191/1358863x04vm561oa PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 889AL UT WOS:000226415800003 PM 15678618 ER PT S AU Scott, JA King, GL AF Scott, JA King, GL BE Kelly, F Meydani, M Packer, L TI Oxidative stress and antioxidant treatment in diabetes SO VITAMIN E AND HEALTH SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Vitamin E and Health CY MAY 22-24, 2004 CL Boston, MA SP Cognis Nutr & Hlth, BASF AG, NIH, NIDDK, Off Dietary Supplements, USDA, Natl Res Initiat, CSREES DE diabetic complications; oxidative stress; antioxidant treatment; vitamin E; PKC ID PROTEIN-KINASE-C; ACTIVATED SIGNALING PATHWAYS; NUTRITION EXAMINATION SURVEY; VITAMIN-E SUPPLEMENTATION; BETA-CELL DYSFUNCTION; 3RD NATIONAL-HEALTH; RETINAL BLOOD-FLOW; HIGH-RISK PATIENTS; ALPHA-LIPOIC ACID; INSULIN-RESISTANCE AB The many studies on oxidative stress, antioxidant treatment, and diabetic complications have shown that oxidative stress is increased and may accelerate the development of complications through the metabolism of excessive glucose and free fatty acids in diabetic and insulin-resistant states. However, the contribution of oxidative stress to diabetic complications may be tissue-specific, especially for microvascular disease that occurs only in diabetic patients but not in individuals with insulin resistance without diabetes, even though both groups suffer from oxidative stress. Although antioxidant treatments can show benefits in animal models of diabetes, negative evidence from large clinical trials suggests that new and more powerful antioxidants need to be studied to demonstrate whether antioxidants can be effective in treating complications. Furthermore, it appears that oxidative stress is only one factor contributing to diabetic complications; thus, antioxidant treatment would most likely be more effective if it were coupled with other treatments for diabetic complications. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu FU NIDDK NIH HHS [DK53105] NR 60 TC 109 Z9 114 U1 1 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-527-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1031 BP 204 EP 213 DI 10.1196/annals.1331.020 PG 10 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Nutrition & Dietetics; Physiology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Nutrition & Dietetics; Physiology GA BBW42 UT WOS:000228129200018 PM 15753146 ER PT S AU Gaziano, JM AF Gaziano, JM BE Kelly, F Meydani, M Packer, L TI Vitamin E and cardiovascular disease - Observational studies SO VITAMIN E AND HEALTH SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Vitamin E and Health CY MAY 22-24, 2004 CL Boston, MA SP Cognis Nutr & Hlth, BASF AG, NIH, NIDDK, Off Dietary Supplements, USDA, Natl Res Initiat, CSREES DE antioxidant; cardiovascular disease; vitamin E ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; ALPHA-TOCOPHEROL SUPPLEMENTATION; BETA-CAROTENE; MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; ANGINA-PECTORIS; E CONSUMPTION; FOAM CELLS; RISK AB Basic research suggests that oxidative stress may play an important role in many chronic diseases and provides plausible mechanisms by which natural antioxidants such as vitamin E may delay or prevent steps in atherogenesis. Dietary research has shown that those who consume higher amounts of fruits and vegetables have lower rates of heart disease and stroke, raising the possibility that antioxidants are protective. Results from large-scale human observational studies suggest that antioxidant consumption reduces the risk of developing cardiovascular disease (CVD). Both case-control and prospective cohort studies have carefully explored the relationship between vitamin E intake and plasma and tissue vitamin E levels and the risk of CVD. In many, but not all, of these studies vitamin E intake over an extended period was associated with decreased risk of cardiovascular events. Results from studies of blood levels are more limited and less consistent. This presentation summarizes data from the major observational studies. Overall, they support the possibility that vitamin E intake either from food or supplements may reduce risk of CVD; however, these studies have important limitations. For example, uncontrolled confounding can be similar in magnitude to the observed health effects, and antioxidant consumption may be merely a marker for a different cardioprotective factor (such as exercise or diet) that is responsible for these effects. In the search for small to moderate effects, randomized trials may be helpful, although to date, data from large-scale trials have been inconsistent. Several large-scale trials currently under way will help identify the potential benefits of vitamin E in the primary prevention of CVD and other chronic illness. Some are designed to test vitamin E alone as well as in combination with other antioxidant supplements because it is possible that antioxidants may be most effective if taken in particular combinations. Currently, the American Heart Association maintains that there are insufficient efficacy data from completed randomized trials to justify population-wide recommendations for use of vitamin E supplements in disease prevention. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Hlth Care Syst, Boston, MA USA. RP Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM jmgaziano@partners.org NR 46 TC 35 Z9 38 U1 0 U2 10 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-528-1; 1-57331-527-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2004 VL 1031 BP 280 EP 291 DI 10.1196/annals.1331.028 PG 12 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences; Nutrition & Dietetics; Physiology SC Biochemistry & Molecular Biology; Science & Technology - Other Topics; Nutrition & Dietetics; Physiology GA BBW42 UT WOS:000228129200026 PM 15753154 ER PT J AU Chen, WY Manson, JE AF Chen, WY Manson, JE TI The letrozole breast cancer trial: Clinical implications and remaining questions SO WOMENS HEALTH ISSUES LA English DT Editorial Material ID FIRST-LINE THERAPY; POSTMENOPAUSAL WOMEN; TAMOXIFEN; ANASTROZOLE; PREVENTION; EFFICACY; ESTROGEN C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Div Med Oncol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. RP Chen, WY (reprint author), Channing Labs, 3rd Floor,181 Longwood Ave, Boston, MA 02115 USA. EM wychen@partners.org NR 19 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2004 VL 14 IS 1 BP 7 EP 10 DI 10.1016/j.whi.2003.12.006 PG 4 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 801RT UT WOS:000220113700003 PM 15001182 ER PT J AU Philips, N Keller, T Gonzalez, S AF Philips, N Keller, T Gonzalez, S TI TGF beta-like regulation of matrix metalloproteinases by anti-transforming growth factor-beta, and anti-transforming growth factor-beta 1 antibodies in dermal fibroblasts: Implications for wound healing SO WOUND REPAIR AND REGENERATION LA English DT Article ID HUMAN SKIN FIBROBLASTS; EXPRESSION; FETAL; KERATINOCYTES; TGF-BETA-1; INVOLVEMENT; COLLAGENASE; INDUCTION; MIGRATION; INHIBITOR AB Transforming growth factor beta (TGF-beta) stimulates collagen and matrix metalloproteinase-2 expression and inhibits MMP-1 expression in dermal fibroblasts. Anti-TGF-beta antibodies have been proposed in the prevention of wound scars. The goal of this research was to investigate the regulation of matrix metalloproteinases-1 and -2 expression at the protein, mRNA, and transcriptional levels using an anti-TGF-beta antibody to TGF-beta 1, 2, 3, and 5 (all isoforms), and specifically by an anti-TGF-beta1 antibody. Both antibodies, though at doses lower than the recommended neutralization dose, stimulated the expression of TGF-beta, and exhibited TGF-beta-like regulation of the matrix metalloproteinases. The antibodies inhibited matrix metalloproteinase-1 protein, mRNA, and promoter activity. The protein levels of matrix metalloproteinase-2 were up-regulated to a greater extent than the matrix metalloproteinase-2 mRNA level by both antibodies. These effects of anti-TGF-beta and anti-TGF-beta1 antibodies on matrix metalloproteinase regulation were mimicked by exogenous TGF-beta1 but not rabbit or chicken IgG. We infer that the anti-TGF-beta1 isoform that forms part of the composition of the anti-TGF-beta antibody to all isoforms may be responsible for the feedback stimulation of TGF-beta and the resultant alterations in the expression of the matrix metalloproteinases by the anti-TGF-beta antibodies. C1 Georgian Court Coll, Dept Biol & Chem Biochem, Lakewood, NJ 08701 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Philips, N (reprint author), Georgian Court Coll, Dept Biol & Chem Biochem, 900 Lakewood Ave, Lakewood, NJ 08701 USA. EM Philips@georgian.edu NR 30 TC 21 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN PY 2004 VL 12 IS 1 BP 53 EP 59 DI 10.1111/j.1067-1927.2004.012111.x-1 PG 7 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 776WX UT WOS:000189143300009 PM 14974965 ER PT J AU Eckermann, JM Buhler, LH Zhu, A Dor, FJMF Awwad, M Cooper, DKC AF Eckermann, JM Buhler, LH Zhu, A Dor, FJMF Awwad, M Cooper, DKC TI Initial investigation of the potential of modified porcine erythrocytes for transfusion in primates SO XENOTRANSPLANTATION LA English DT Article DE alpha-galactosidase; blood transfusion; erythrocytes; Gal alpha 1; 3Gal; N-glycolylneuraminic acid; pig; red blood cells ID BEAN ALPHA-GALACTOSIDASE; N-GLYCOLYLNEURAMINIC ACID; NATURAL ANTIBODIES; ENDOTHELIAL-CELLS; EXPRESSION; DEPLETION; BABOONS; EPITOPES; ANTIGENS; THERAPY AB There is a shortage of human blood for transfusion. The possibility of using alpha-galactosidase-treated pig red blood cells (pRBCs) for transfusion into humans has been investigated. pRBCs were treated in vitro with alpha-galactosidase. In vitro binding of antibodies (Abs) in baboon or human sera to untreated/treated pRBCs was assessed by flow cytometry and serum cytotoxicity. In vivo clearance rates of (1) autologous baboon red blood cells (RBCs), (2) unmodified pRBCs, and (3) alpha-galactosidase-treated pRBCs were measured after transfusion into baboons receiving either no treatment or depletion of complement +/- depletion of anti-Galalpha1-3Gal (Gal) Ab or of macrophage phagocytes. In vitro binding of baboon or human Abs to treated pRBCs was absent or minimal compared with untreated pRBCs, and serum cytotoxicity was completely inhibited. In vivo autologous baboon RBCs survived for >16 days and unmodified pRBCs for <15 min in an untreated baboon. Treated pRBCs survived for 2 h in an untreated baboon, for 24 h in a complement-depleted baboon, and for 72 h when the baboon was depleted of both complement and anti-Gal Ab, or of complement and macrophage phagocytes. All baboons, however, became sensitized to Gal antigens. Failure to prolong the in vivo survival of treated pRBCs could be due to inadequate removal of Gal epitopes because sensitization to Gal developed, or could imply other, as yet unidentified, causes for RBC destruction. To fully assess the potential of pRBC transfusion in humans, more complete alpha-galactosidase treatment of pRBCs will be required. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Loma Linda Univ, Sch Med, Loma Linda, CA USA. RBC Biotechnol Inc, New York, NY USA. Immerge Biotherapeut Inc, Cambridge, MA USA. RP Buhler, LH (reprint author), Univ Hosp Geneva, Dept Surg, 24 Rue Micheli du Crest, CH-1211 Geneva 14, Switzerland. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1PO1 AI45897] NR 26 TC 11 Z9 16 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 18 EP 26 DI 10.1111/j.1399-3089.2004.00087.x PG 9 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000004 PM 14962289 ER PT J AU Baertschiger, RM Dor, FJMF Prabharasuth, D Kuwaki, K Cooper, DKC AF Baertschiger, RM Dor, FJMF Prabharasuth, D Kuwaki, K Cooper, DKC TI Absence of humoral and cellular alloreactivity in baboons sensitized to pig antigens SO XENOTRANSPLANTATION LA English DT Article DE alloantigens; baboon; cross-reactive antibodies; pig; xenoantigens; xenotransplantation ID HLA ANTIBODIES; ALLOTRANSPLANTATION; XENOGRAFTS; BLOCKADE; VIVO AB Aim: to study whether sensitization to pig antigens results in humoral and/or cellular sensitization to alloantigens in baboons, and thus increases the risks of organ allotransplantation after xenotransplantation. Serum from baboons that were naive (n = 4), sensitized to Galalpha1,3Gal (Gal) antigens (n = 2), or sensitized to Gal + non-Gal pig antigens (n = 2) were tested by flow cytometry for the presence of immunoglobulin G (IgG) and IgM antibodies that bind to pig or baboon peripheral blood mononuclear cells (PBMC). Two allosensitized baboons were used as positive controls. The same 10 sera were tested in a complement-mediated cytotoxicity assay to detect cytotoxic antibodies against pig, allo and self-PBMC. The T-cell responses of the same baboons to allogeneic and pig PBMC stimulators in mixed lymphocyte reaction (MLR) were studied. All baboon sera contained cytotoxic antibodies that bound to pig PBMC. Binding and cytotoxicity were higher in xenosensitized baboons, particularly in those sensitized to Gal + non-Gal antigens (P < 0.001). None of the naive or xenosensitized baboon sera bound to baboon PBMC. Serum from allosensitized baboons showed anti-baboon IgG and IgM binding, but there was no increase in binding to pig PBMC or in cytotoxicity to pig cells. The MLR response to pig stimulators in baboons sensitized to non-Gal pig antigens was greater than that of naive or Gal-sensitized baboons (P < 0.001), but there was no increase in the response to baboon cells. In baboons, no in vitro evidence that a previous pig xenograft might endanger the outcome of a subsequent allograft was documented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Univ Hosp Geneva, Dept Surg, Geneva, Switzerland. RP Cooper, DKC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1PO1 AI145897] NR 22 TC 21 Z9 21 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 27 EP 32 DI 10.1111/j.1399-3089.2004.00075.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000005 PM 14962290 ER PT J AU Matter-Reissmann, UB Sonntag, KC Gilli, UO Leguern, C Schneider, MKJ Seebach, JD AF Matter-Reissmann, UB Sonntag, KC Gilli, UO Leguern, C Schneider, MKJ Seebach, JD TI Human Fas-ligand expression on porcine endothelial cells does not protect against xenogeneic natural killer cytotoxicity SO XENOTRANSPLANTATION LA English DT Article DE adhesion; cytotoxicity; endothelial cells; Fas; Fas ligand; NK cells; xenotransplantation ID HUMAN NK CELLS; CONFER IMMUNE PRIVILEGE; ANTI-PIG CYTOTOXICITY; CD95 LIGAND; IN-VIVO; VASCULAR ENDOTHELIUM; CHEMOTACTIC ACTIVITY; ALLOGRAFT SURVIVAL; ISLET ALLOGRAFTS; GRAFT-REJECTION AB Several human leukocyte subsets including natural killer (NK) cells, cytotoxic T lymphocytes (CTL), and polymorphonuclear neutrophils (PMN) participate in cellular immune responses directed against vascularized pig-to-human xenografts. As these leukocytes express the death receptor Fas either constitutively (PMN) or upon activation (NK, CTL), we explored in vitro whether the transgenic expression of Fas ligand (FasL) on porcine endothelial cells (EC) is a valuable strategy to protect porcine xenografts. The porcine EC line 2A2 was stably transfected with human FasL (2A2-FasL) and interactions of 2A2-FasL with human leukocytes were analyzed using functional assays for apoptosis, cytotoxicity, chemotaxis, adhesion under shear stress, and transmigration. FasL expressed on porcine EC induced apoptosis in human NK and T cells, but did not protect porcine EC against killing mediated by human NK cells. 2A2-FasL released soluble FasL, which induced strong chemotaxis in human PMN. Adhesion under shear stress of PMN on 2A2-FasL cells was increased whereas transendothelial migration was decreased. In contrast, FasL had no effect on the adhesion of NK cells but increased their transmigration through porcine EC. Although FasL expression on porcine EC is able to induce apoptosis in human effector cells, it did not provide protection against xenogeneic cytotoxicity. The observed impact of FasL on adhesion and transendothelial migration provides evidence for novel biological functions of FasL. C1 Univ Zurich Hosp, Dept Internal Med, Lab Transplantat Immunol, CH-8091 Zurich, Switzerland. Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Seebach, JD (reprint author), Univ Zurich Hosp, Dept Internal Med, Lab Transplantat Immunol, Ramistr 100,C HOER 31, CH-8091 Zurich, Switzerland. FU NIAID NIH HHS [2R01AI33053] NR 54 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 43 EP 52 DI 10.1111/j.1399-3089.2004.00081.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000007 PM 14962292 ER PT J AU Knosalla, C Giovino, MA Harper, D Kaczmarek, E Gollackner, B Cooper, DKC Robson, SC AF Knosalla, C Giovino, MA Harper, D Kaczmarek, E Gollackner, B Cooper, DKC Robson, SC TI Relative effects of GAL(+) and GAL(low/-) porcine hematopoietic cells on primate platelet aggregation and endothelial cell activation: implications for the induction of mixed hematopoietic chimerism in the pig-to-primate model SO XENOTRANSPLANTATION LA English DT Article DE adhesion molecules; baboon; endothelial cell activation; Gal alpha 1,3Gal; hematopoietic cells; human; pig; platelets; thrombotic microangiopathy; xenotransplantation ID THROMBOTIC MICROANGIOPATHY; NONHUMAN-PRIMATES; XENOTRANSPLANTATION; TRANSPLANTATION; EXPRESSION; REGIMEN; GAL-ALPHA-1,3GAL; BABOONS AB Background: The induction of porcine hematopoietic cell chimerism in preconditioned baboons has been hampered by the development of thrombotic microangiopathy. As pigs that lack expression of Galalpha1,3 Gal (Gal) may become available in the near future, we have explored the effects of porcine hematopoietic cells that express low or no Gal (Gal(low/-)) on baboon platelet aggregation and on human umbilical vein endothelial cell (HUVEC) activation. Methods: Porcine mobilized peripheral blood progenitor cells (PBPC; Gal(+)) and bone marrow mononuclear cells (BM; Gal(+) or Gal(low/-)) were investigated for their potential to (i) induce aggregation of baboon platelets, and (ii) to activate endothelial cells as measured by increased expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin on HUVEC. alpha-Galactosidase-treated PBPC were also investigated for their effect on platelet aggregation. Results: Gal(+) PBPC and Gal(+) BM cells (10(7)) induced aggregation of baboon platelets by 42 and 31%, respectively, whereas Gal(low/-) BM cells did not induce any platelet aggregation. alpha-Galactosidase-treated PBPC induced less platelet aggregation than untreated PBPC. Gal(+) PBPC and Gal(+) BM cells (10(7)) increased expression of VCAM-1, ICAM-1 and E-selectin on HUVEC, whereas Gal(low/-) BM cells did not. Conclusions: In contrast to Gal(+) PBPC or BM, Gal(low/-) BM cells do not induce aggregation of baboon platelets or activate HUVEC. The induction of tolerance through mixed hematopoietic cell chimerism may be facilitated when alpha-galactosyltransferase-knockout pigs become available. C1 Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Immunobiol, Boston, MA 02215 USA. Immerge BioTherapeut, Charlestown, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Transplantat Biol Res Ctr, Massachusetts Gen Hosp, Sch Med, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [1PO1 AI45897] NR 20 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 72 EP 77 DI 10.1111/j.1399-3089.2004.00085.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000010 PM 14962295 ER PT J AU Harper, D Gollackner, B Xu, Y Calderhead, D Ryan, D Li, W Chang, J Wu, C Moran, K Latinne, D Bazin, H White-Scharf, ME Cooper, DKC Awwad, M AF Harper, D Gollackner, B Xu, Y Calderhead, D Ryan, D Li, W Chang, J Wu, C Moran, K Latinne, D Bazin, H White-Scharf, ME Cooper, DKC Awwad, M TI In vitro and in vivo investigation of a novel monoclonal antibody to plasma cells (W5 mAb) SO XENOTRANSPLANTATION LA English DT Article DE anti-plasma cell antibody; baboons; B cells; monoclonal antibody; plasma cells; xenotransplantation ID NONHUMAN PRIMATE; B-CELLS; DEPLETION; BABOONS; MOLECULES; REMOVAL AB Natural antibodies (Abs), predominately anti-Galalpha1-3Gal (Gal) Abs, in non-human primates and human beings present a major hurdle to successful pig-to-primate xenotransplantation. Attempts to inhibit anti-Gal Ab production in naive baboons using non-specific immunosuppressive or B cell-specific reagents have failed. A new rat monoclonal antibody (W5 mAb) has been generated, which binds to all B cells, including memory cells, and to the majority of plasma cells, but not to T cells. It has been tested in vitro and in vivo. By immunoprecipitation, W5 mAb bound a human leukocyte antigen class II (HLA-DR) determinant. Sorting splenic or bone marrow W5+ cells resulted in a highly enriched anti-Gal Ab and total immunoglobulin (Ig)-secretory population. In vivo studies in baboons demonstrated that W5 mAb was safe but, despite the concomitant administration of an anti-CD154 mAb to inhibit sensitization, anti-rat Abs were detected within 10 days and inhibited the effect of the W5 mAb. High levels of W5 mAb were able to completely deplete B cells in the blood, but not in lymphoid tissues. Enzyme-linked spot-forming assay (ELISPOT) demonstrated that only 50 to 60% of secreting cells (SC) were depleted in the bone marrow. No reduction in the serum levels of anti-Gal Ab was observed. W5 mAb did not cause complete inhibition of anti-Gal Ab production, probably as a result of its inability to completely deplete B and plasma cells from all lymphoid compartments. C1 Immerge BioTherapeut Inc, Cambridge, MA 02139 USA. Catholic Univ Louvain, Brussels, Belgium. BioTransplant Inc, Charlestown, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Awwad, M (reprint author), Immerge BioTherapeut Inc, 300 Technol Sq, Cambridge, MA 02139 USA. FU NIAID NIH HHS [1P01 AI45897] NR 17 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 78 EP 90 DI 10.1111/j.1399-3089.2004.00086.x PG 13 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000011 PM 14962296 ER PT J AU Dor, FJMF Cheng, J Alt, A Cooper, DKC Schuurman, HJ AF Dor, FJMF Cheng, J Alt, A Cooper, DKC Schuurman, HJ TI Gal alpha 1,3Gal expression on porcine pancreatic islets, testis, spleen, and thymus SO XENOTRANSPLANTATION LA English DT Article DE Gal alpha 1,3 Gal epitopes; pancreatic islets; pig; spleen; testis; thymus; xenotransplantation ID XENOANTIGEN; COMPLEMENT; ANTIBODIES; SURVIVAL; CELLS AB Galalpha1,3Gal (Gal) is the first target in antibody-mediated rejection of pig-to-non-human primate xenograft. Its expression may vary between organs and constituents of organs. Gal expression was studied in pancreas, testis, spleen and thymus of 22 pigs, with ages ranging from 1 to 22 months. The immunoperoxidase technique using the biotinylated lectin, Griffonia simplicifolia (IB4), was used. In the pancreas, neither endocrine (islet cells) nor exocrine cells expressed Gal. The Sertoli cells in the testis were negative. The spleen capsule and trabeculae did not stain for Gal, although both splenic T and B lymphocytes expressed Gal (B > T). Thymocytes were weakly positive, whereas thymic epithelial cells were negative for Gal. No age-related differences were seen in any tissues. Porcine islets of Langerhans, Sertoli cells, and the splenic and thymic structural frameworks did not express Gal, and therefore, should be relatively resistant to anti-Gal antibody-mediated rejection. The availability of pigs deficient in Gal as a source of islets may therefore not be beneficial in extending islet graft survival in non-human primate models. C1 Immerge Biotherapeut Inc, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Schuurman, HJ (reprint author), Immerge Biotherapeut Inc, 300 Technol Sq, Cambridge, MA 02139 USA. RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU NIAID NIH HHS [1PO1 AI145897] NR 18 TC 46 Z9 46 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JAN PY 2004 VL 11 IS 1 BP 101 EP 106 DI 10.1111/j.1399-3089.2004.00078.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 755MQ UT WOS:000187407000014 PM 14962299 ER PT B AU Brau, N Torriani, FJ Rodriguez-Torres, M Rockstroh, JK Lissen, E Lazzarin, A Carosi, G Sasadeusz, J Katlama, C Hadziyannis, SJ Connell, E Yetzer, E Dieterich, DT AF Brau, N Torriani, FJ Rodriguez-Torres, M Rockstroh, JK Lissen, E Lazzarin, A Carosi, G Sasadeusz, J Katlama, C Hadziyannis, SJ Connell, E Yetzer, E Dieterich, DT CA AIDS Pegasys Ribavirin Int coinfec GP MEDIMOND TI Safety of peginterferon alfa-2a (PEGASYS) 180 mcg weekly plus ribavirin (RBV) 800 mg daily in HIV/HCV coinfection compared to HCV monoinfection. SO XV INTERNATIONAL AIDS CONFERENCE: CLINICAL RESEARCH, TREATMENT, AND CARE LA English DT Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND C1 Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Brau, N (reprint author), Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY PY 2004 BP 109 EP 110 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA BBR13 UT WOS:000227337100022 ER PT J AU Glaser, V Raz, E AF Glaser, Vicki Raz, Erez TI An Interview with Erez Raz, Ph.D. SO ZEBRAFISH LA English DT Editorial Material C1 [Raz, Erez] Max Planck Inst Biophys Chem, D-37077 Gottingen, Germany. [Raz, Erez] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Raz, Erez] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2004 VL 1 IS 1 BP 9 EP 11 PG 3 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18CU UT WOS:000207983700003 ER PT J AU Payne-Ferreira, TL Tong, KW Yelick, PC AF Payne-Ferreira, Tracie L. Tong, Kevin W. Yelick, Pamela C. TI Maternal alk8 Promoter Fragment Directs Expression in Early Oocytes SO ZEBRAFISH LA English DT Article AB Zebrafish Alk8 is a novel type I TGF beta family member receptor that functions in Bmp signaling pathways to direct dorsoventral patterning of the early embryo. Both alk8 mRNA and protein is expressed in a variety of tissues, including teeth, eye, heart, blood, notochord, muscle, neural tissues, and neural crest cells (NCC's). Previous functional analyses, performed by microinjection of constitutively active (CA) and dominant negative (DN) alk8 mRNAs, revealed early developmental requirements for alk8. The alk8 gene is expressed ubiquitously as a maternal mRNA, and later exhibits more restricted zygotic gene expression. To identify regulatory elements directing the temporospatial expression of alk8, we characterized fluorescence in transgenic zebrafish lines containing alk8 promoter/green fluorescent protein (GFP) reporter constructs. This approach identified transgenic alk8(2.6):GFP lines that first expressed GFP in early stage 1A oocytes, and maintained GFP expression throughout the embryo only for the first 72 hours of development. Analysis of the nucleotide sequence of the 2.6 kb alk8 promoter element provides insight into the regulation of maternal alk8 gene expression. Significantly, the identified maternal alk8 promoter is one of only two maternal-specific promoter elements that have been described to date. C1 [Yelick, Pamela C.] Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org FU National Institute of Dental and Craniofacial Research (NICDR) [DE-5736, K22 DE014683, DE12024, DE12076] FX Supported by National Institute of Dental and Craniofacial Research (NICDR) grants DE-5736 and K22 DE014683 (TPF) and DE12024 and DE12076 (PCY). NR 43 TC 4 Z9 4 U1 2 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2004 VL 1 IS 1 BP 27 EP 39 DI 10.1089/154585404774101653 PG 13 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18CU UT WOS:000207983700006 PM 18248203 ER PT J AU Reuter, A Malaga-Trillo, E Binkle, U Rivera-Milla, E Beltre, R Zhou, Y Bastmeyer, M Stuermer, CAO AF Reuter, Alexander Malaga-Trillo, Edward Binkle, Ulrike Rivera-Milla, Eric Beltre, Rosanna Zhou, Yi Bastmeyer, Martin Stuermer, Claudia A. O. TI Evolutionary Analysis and Expression of Teleost Thy-1 SO ZEBRAFISH LA English DT Article AB Thy-1 is a developmentally regulated, immunoglobulin superfamily member (IgSF), glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein expressed most strongly in neurons and lymphocytes. Thy-1 is expressed in all vertebrates and has been implicated in a variety of processes, including axon regeneration and transmembrane signaling, but its specific function remains elusive. A Thy-1-like molecule in teleost fish was recently identified, with evidence for its role in lipid-raft based signal transduction linked to optic nerve regeneration. For a better characterization of Thy-1, the evolutionary relationships between novel fish homologues and other vertebrate Thy-1s were analyzed. Although the sequence similarity between fish and mammals is very low, there appeared conservation of gene structure and disrupted but recognizable synteny. In addition, the detailed expression analysis of teleost Thy-1 showed nervous system Thy-1 mainly in sensory systems. Strong Thy-1 expression was detected in the youngest retinal ganglion cells and in some neurons in deeper retinal layers, probably amacrine cells. From the olfactory bulbs, Thy-1-positive cells extended axons into the telencephalon. The vagal lobe stained intensively as well as facial and glossopharyngeal lobes and nerves. Outside the CNS, skin cells, blood vessels, kidney macrophages, swim bladder, spleen, gut-associated nerve fibers and the palatal organ were labeled. C1 [Reuter, Alexander; Malaga-Trillo, Edward; Binkle, Ulrike; Rivera-Milla, Eric; Bastmeyer, Martin; Stuermer, Claudia A. O.] Univ Konstanz, Dept Biol, D-78457 Constance, Germany. [Beltre, Rosanna; Zhou, Yi] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Beltre, Rosanna; Zhou, Yi] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Reuter, A (reprint author), Univ Konstanz, Dept Biol, D-78457 Constance, Germany. EM Alexander.Reuter@uni-konstanz.de RI Bastmeyer, Martin/H-9342-2013 FU Deutsche Forschungsgemeinschaft (DFG); Fonds der Chemischen Industrie (FCI) FX Supported by Deutsche Forschungsgemeinschaft (DFG) and Fonds der Chemischen Industrie (FCI). E.R-M. is a Deutscher Akademischer Austauschdienst (DAAD) fellow. NR 38 TC 3 Z9 3 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1545-8547 J9 ZEBRAFISH JI Zebrafish PY 2004 VL 1 IS 3 BP 191 EP 201 DI 10.1089/zeb.2004.1.191 PG 11 WC Developmental Biology; Zoology SC Developmental Biology; Zoology GA V18CW UT WOS:000207983900003 PM 18248231 ER PT J AU Shepard, JL Stern, HM Pfaff, KL Amatruda, JF AF Shepard, JL Stern, HM Pfaff, KL Amatruda, JF TI Analysis of the cell cycle in zebrafish embryos SO ZEBRAFISH: 2ND EDITION CELLULAR AND DEVELOPMENTAL BIOLOGY SE METHODS IN CELL BIOLOGY LA English DT Review ID DIFFERENT DEVELOPMENTAL-STAGES; DANIO-RERIO; HISTONE H3; MIDBLASTULA TRANSITION; EXPOSURE ROUTES; DNA-REPLICATION; GENETIC SCREENS; HUMAN-DISEASE; PHOSPHORYLATION; ACTIVATION C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Shepard, JL (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [5 H08 HL04082]; NICHD NIH HHS [1 R01 HD044930]; NIDDK NIH HHS [5 K08 DK 061849, 1R01 DK55381] NR 37 TC 39 Z9 39 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 76 BP 109 EP 125 PG 17 WC Cell Biology SC Cell Biology GA BBS32 UT WOS:000227571500007 PM 15602874 ER PT J AU Stewart, RA Look, AT Kanki, JP Henion, PD AF Stewart, RA Look, AT Kanki, JP Henion, PD TI Development of the peripheral sympathetic nervous system in zebrafish SO ZEBRAFISH: 2ND EDITION CELLULAR AND DEVELOPMENTAL BIOLOGY SE METHODS IN CELL BIOLOGY LA English DT Review ID DOPAMINE-BETA-HYDROXYLASE; NEURAL CREST DERIVATIVES; TYROSINE-HYDROXYLASE; GROWTH-FACTOR; CELL FATE; CATECHOLAMINERGIC NEURONS; NEUROTRANSMITTER IDENTITY; NORADRENERGIC NEURONS; EMBRYONIC-DEVELOPMENT; TRANSCRIPTION FACTORS C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Ohio State Univ, Ctr Mol Neurobiol, Columbus, OH 43210 USA. Ohio State Univ, Dept Neurosci, Columbus, OH 43210 USA. RP Stewart, RA (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. OI Stewart, Rodney/0000-0003-1220-1830 FU NCI NIH HHS [CA 104605]; NINDS NIH HHS [NS38115] NR 87 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 76 BP 237 EP + PG 26 WC Cell Biology SC Cell Biology GA BBS32 UT WOS:000227571500012 PM 15602879 ER PT J AU Albertson, RC Yelick, PC AF Albertson, RC Yelick, PC TI Morphogenesis of the jaw: Development beyond the embryo SO ZEBRAFISH: 2ND EDITION CELLULAR AND DEVELOPMENTAL BIOLOGY SE METHODS IN CELL BIOLOGY LA English DT Review ID ZEBRAFISH DANIO-RERIO; NEURAL CREST DEVELOPMENT; BRANCHIAL ARCH MUTANTS; ENDOTHELIN-B RECEPTOR; CRANIOFACIAL DEVELOPMENT; DELETION SYNDROME; BONE-DEVELOPMENT; PHARYNGEAL ARCH; AXIAL SKELETON; HEAD SKELETON C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Albertson, RC (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. NR 53 TC 14 Z9 14 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 76 BP 437 EP + PG 22 WC Cell Biology SC Cell Biology GA BBS32 UT WOS:000227571500019 PM 15602886 ER PT J AU Drummond, IA AF Drummond, IA TI Zebrafish kidney development SO ZEBRAFISH: 2ND EDITION CELLULAR AND DEVELOPMENTAL BIOLOGY SE METHODS IN CELL BIOLOGY LA English DT Review ID MICE LACKING GDNF; T-BOX GENES; SLIT DIAPHRAGM; INTRAFLAGELLAR TRANSPORT; CAENORHABDITIS-ELEGANS; DEVELOPING PRONEPHROS; RENAL DEVELOPMENT; PRIMARY CILIUM; RETINOIC ACID; TAIL MESODERM C1 Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. NR 123 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 76 BP 501 EP + PG 32 WC Cell Biology SC Cell Biology GA BBS32 UT WOS:000227571500023 PM 15602890 ER PT J AU Peterson, RT Fishman, MC AF Peterson, RT Fishman, MC TI Discovery and use of small molecules for probing biological processes in zebrafish SO ZEBRAFISH: 2ND EDITION CELLULAR AND DEVELOPMENTAL BIOLOGY SE METHODS IN CELL BIOLOGY LA English DT Review ID DIVERSITY-ORIENTED SYNTHESIS; DRUG DISCOVERY; TRIAZINE LIBRARY; DNA MICROARRAYS; DANIO-RERIO; IDENTIFICATION; GENE; MUTATION; TARGET; MODEL C1 Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Peterson, RT (reprint author), Massachusetts Gen Hosp, Dev Biol Lab, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 64 TC 42 Z9 45 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 76 BP 569 EP 591 PG 23 WC Cell Biology SC Cell Biology GA BBS32 UT WOS:000227571500026 PM 15602893 ER PT J AU Yi, Z AF Yi, Z TI Update of the expressed sequence tag (EST) and radiation hybrid panel projects SO ZEBRAFISH:2ND EDITION GENETICS GENOMICS AND INFORMATICS SE METHODS IN CELL BIOLOGY LA English DT Review ID ZEBRAFISH GENOME; MAP C1 Childrens Hosp Boston, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Yi, Z (reprint author), Childrens Hosp Boston, Div Hematol Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 77 BP 273 EP + PG 22 WC Cell Biology SC Cell Biology GA BBL01 UT WOS:000225969100015 ER PT J AU Hsu, K Look, AT Kanki, JP AF Hsu, K Look, AT Kanki, JP TI Lessons from transgenic zebrafish expressing the green fluorescent protein (GFP) in the myeloid lineage SO ZEBRAFISH:2ND EDITION GENETICS GENOMICS AND INFORMATICS SE METHODS IN CELL BIOLOGY LA English DT Review ID TRANSCRIPTION FACTOR PU.1; GENE-EXPRESSION; ETS ONCOGENE; DIFFERENTIATION; GATA-1; CELLS; FISH; ERYTHROPOIESIS; MACROPHAGES; LEUKEMIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. RP Hsu, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA006516, CA93152, CA96785] NR 30 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 77 BP 333 EP + PG 16 WC Cell Biology SC Cell Biology GA BBL01 UT WOS:000225969100018 PM 15602920 ER PT J AU Song, AH Zhou, Y AF Song, AH Zhou, Y TI Comparative genomics - An application for positional cloning of the weissherbst mutant SO ZEBRAFISH:2ND EDITION GENETICS GENOMICS AND INFORMATICS SE METHODS IN CELL BIOLOGY LA English DT Review C1 Childrens Hosp Boston, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Song, AH (reprint author), Childrens Hosp Boston, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 77 BP 459 EP + PG 17 WC Cell Biology SC Cell Biology GA BBL01 UT WOS:000225969100025 PM 15602927 ER PT J AU Berghmans, S Morris, JP Kanki, JP Look, AT AF Berghmans, S Morris, JP Kanki, JP Look, AT TI Zebrafish sperm cryopreservation SO ZEBRAFISH:2ND EDITION GENETICS GENOMICS AND INFORMATICS SE METHODS IN CELL BIOLOGY LA English DT Review ID FISH SPERMATOZOA; FLOW-CYTOMETRY; ANALYSIS CASA; FERTILIZATION; MEMBRANE; SEMEN; METHODOLOGY; QUALITY; STORAGE; FRESH C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Berghmans, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. OI Berghmans, Stephane/0000-0001-5414-8674 NR 39 TC 2 Z9 3 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X J9 METHOD CELL BIOL PY 2004 VL 77 BP 645 EP + PG 18 WC Cell Biology SC Cell Biology GA BBL01 UT WOS:000225969100034 PM 15602936 ER PT J AU Cramer, C Gao, Y Brunklaus, S Ratai, E AF Cramer, C Gao, Y Brunklaus, S Ratai, E TI Ion dynamics in mixed alkali borate glasses SO ZEITSCHRIFT FUR PHYSIKALISCHE CHEMIE-INTERNATIONAL JOURNAL OF RESEARCH IN PHYSICAL CHEMISTRY & CHEMICAL PHYSICS LA English DT Editorial Material DE conductivity; ion dynamics; mixed alkali effect; borate glasses ID DEPENDENT CONDUCTIVITIES; SOLID ELECTROLYTES; AC CONDUCTIVITY; CATION GLASSES; BETA-ALUMINA; RELAXATION; TRANSPORT; SPECTRA; SYSTEMS; SODIUM AB Frequency-dependent conductivities are a valuable tool for studying the ion dynamics on different time scales, the latter being determined by the inverse of the experimental frequency. Therefore, wide range conductivity spectra probe the transition from elementary steps of the ionic movement to macroscopic transport. We have studied the ion dynamics in mixed alkali borate glasses where we have systematically varied the total and the relative ion concentration. The glass system under investigation is y [x Li2O (.) (1 - x) Na2O] (.) (1 - y) B2O3 with x = 0.0, 0.2, 0.4, 0.6, 0.8, 1.0 and y = 0. 1, 0.2, 0.3. The conductivity spectra can be formally divided into a low-frequency and a high-frequency regime. In the low-frequency regime the conductivities of all glasses show a transition from their dc values into a dispersive regime where the conductivity is found to increase continuously with frequency, tending towards a linear frequency dependence at sufficiently low temperatures. The conductivity spectra can be described by the MIGRATION concept developed by Funke. We discuss the spectral shape of the conductivity spectra and its implications for the ion transport. In addition, we report on a new mixed alkali effect occurring in the high-frequency regime of the ac conductivity. From our results we conclude that apart from a low-frequency contribution to the conductivity which is linked to ion hopping sequencess, there is an additional contribution involving localized motions of both the mobile ions and the glassy network. C1 Univ Munster, Inst Chem Phys, D-48149 Munster, Germany. Univ Munster, Sonderforsch Bereich 458, D-48149 Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, NMR Ctr, Charlestown, MA 02129 USA. RP Cramer, C (reprint author), Univ Munster, Inst Chem Phys, Corrensstr 30, D-48149 Munster, Germany. EM CramerC@uni-muenster.de NR 36 TC 7 Z9 7 U1 2 U2 3 PU R OLDENBOURG VERLAG PI MUNICH PA LEKTORAT MINT, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0942-9352 J9 Z PHYS CHEM JI Z. Phys. Chemie-Int. J. Res. Phys. Chem. Chem. Phys. PY 2004 VL 218 IS 12 BP 1413 EP 1428 DI 10.1524/zpch.218.12.1413.53830 PG 16 WC Chemistry, Physical SC Chemistry GA 880YT UT WOS:000225827500006 ER PT J AU McQueen, MB Bertram, L Rimm, EB Blacker, D Santangelo, SL AF McQueen, MB Bertram, L Rimm, EB Blacker, D Santangelo, SL TI A QTL genome scan of the metabolic syndrome and its component traits SO BMC GENETICS LA English DT Article; Proceedings Paper CT 13th Genetic Analysis Workshop CY NOV 11-14, 2002 CL NEW ORLEANS, LOUISIANA ID DIABETES-SUSCEPTIBILITY GENES; INSULIN-RESISTANCE SYNDROME; LINKAGE ANALYSIS; RISK-FACTORS; WIDE SCAN; PHENOTYPES; LOCUS; CHROMOSOME-17; PEDIGREES; SEARCH AB Background: Because high blood pressure, altered lipid levels, obesity, and diabetes so frequently occur together, they are sometimes collectively referred to as the metabolic syndrome. While there have been many studies of each metabolic syndrome trait separately, few studies have attempted to analyze them combined, i.e., as one composite variable, in quantitative trait linkage or association analysis. We used genotype and phenotype data from the Framingham Heart Study to perform a full-genome scan for quantitative trait loci underlying the metabolic syndrome. Results: Heritability estimates for all of the covariate-adjusted and age- and gender-standardized individual traits, and the composite metabolic syndrome trait, were all fairly high (0.39-0.62), and the composite trait was among the highest at 0.61. The composite trait yielded no regions with suggestive linkage by Lander and Kruglyak's criteria, although there were several noteworthy regions for individual traits, some of which were also observed for the composite variable. Conclusion: Despite its high heritability, the composite metabolic syndrome trait variable did not increase the power to detect or localize linkage peaks in this sample. However, this strategy and related methods of combining correlated individual traits deserve further investigation, particularly in settings with complex causal pathways. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Genet & Aging Unit, Charlestown, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Charlestown, MA USA. RP McQueen, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM mmcqueen@hsph.harvard.edu; bertram@helix.mgh.harvard.edu; erimm@hsph.harvard.edu; blacker@psych.mgh.harvard.edu; ssantangelo@psych.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NCI NIH HHS [CA-84719, P50 CA084719]; NICHD NIH HHS [R01 HD060726]; NIMH NIH HHS [R01 MH060009, R01MH59632, R01MH60009, T32 MH017119, T32 MH17119]; PHS HHS [U10 13Y11309] NR 19 TC 39 Z9 39 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD DEC 31 PY 2003 VL 4 SU 1 AR S96 DI 10.1186/1471-2156-4-S1-S96 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 765ZL UT WOS:000188320900096 PM 14975164 ER PT J AU Yun, SH Tearney, GJ Bouma, BE Park, BH de Boer, JF AF Yun, SH Tearney, GJ Bouma, BE Park, BH de Boer, JF TI High-speed spectral-domain optical coherence tomography at 1.3 mu m wavelength SO OPTICS EXPRESS LA English DT Article ID REFLECTOMETRY; INTERFEROMETRY AB We demonstrate a high-speed spectral domain optical coherence tomography (SD-OCT) system capable of acquiring individual axial scans in 24.4 mus at a rate of 19,000 axial scans per second, using an InGaAs line scan camera and broadband light source centered at 1.31 mum. Sensitivity of >105 dB over a 2-mm depth range was obtained with a free-space axial resolution of 12-14 mum, in agreement with our signal-to-noise ratio predictions. Images of human tissue obtained in vivo with SD-OCT show similar penetration depths to those obtained with state-of-the-art time domain OCT despite the ten-fold higher image acquisition speed. These results demonstrate the potential of 1.3 mum SD-OCT for high-speed and high-sensitivity imaging in patients. (C) 2003 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yun, SH (reprint author), Harvard Univ, Sch Med, 50 Blossom St,BAR-718, Boston, MA 02114 USA. EM syun@bics.bwh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 FU NCI NIH HHS [R01 CA103769-02, R01 CA103769]; NCRR NIH HHS [R01 RR019768, R01 RR019768-02] NR 18 TC 261 Z9 266 U1 2 U2 20 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 29 PY 2003 VL 11 IS 26 BP 3598 EP 3604 DI 10.1364/OE.11.003598 PG 7 WC Optics SC Optics GA 758FL UT WOS:000187623000011 PM 19471496 ER PT J AU Towbin, H Bair, KW DeCaprio, JA Eck, MJ Kim, S Kinder, FR Morollo, A Mueller, DR Schindler, P Song, HK van Oostrum, J Versace, RW Voshol, H Wood, J Zabludoff, S Phillips, PE AF Towbin, H Bair, KW DeCaprio, JA Eck, MJ Kim, S Kinder, FR Morollo, A Mueller, DR Schindler, P Song, HK van Oostrum, J Versace, RW Voshol, H Wood, J Zabludoff, S Phillips, PE TI Proteomics-based target identification - Bengamides as a new class of methionine aminopeptidase inhibitors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMOBILIZED PH GRADIENTS; PROTEIN P(67); SACCHAROMYCES-CEREVISIAE; SELECTIVE-INHIBITION; 67-KDA POLYPEPTIDE; IN-VIVO; FUMAGILLIN; ANGIOGENESIS; OVALICIN; ISOFORMS AB LAF389 is a synthetic analogue of bengamides, a class of marine natural products that produce inhibitory effects on tumor growth in vitro and in vivo. A proteomics-based approach has been used to identify signaling pathways affected by bengamides. LAF389 treatment of cells resulted in altered mobility of a subset of proteins on two-dimensional gel electrophoresis. Detailed analysis of one of the proteins, 14-3-3gamma, showed that bengamide treatment resulted in retention of the amino-terminal methionine, suggesting that bengamides directly or indirectly inhibited methionine aminopeptidases (MetAps). Both known MetAps are inhibited by LAF389. Short interfering RNA suppression of MetAp2 also altered amino-terminal processing of 14-3-3gamma. A high resolution structure of human MetAp2 co-crystallized with a bengamide shows that the compound binds in a manner that mimics peptide substrates. Additionally, the structure reveals that three key hydroxyl groups on the inhibitor coordinate the di-cobalt center in the enzyme active site. C1 Novartis Pharma AG, CH-4036 Basel, Switzerland. Novartis Pharmaceut, E Hanover, NJ 07936 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Towbin, H (reprint author), Novartis Pharma AG, Lichstr 35, CH-4036 Basel, Switzerland. RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 NR 37 TC 101 Z9 105 U1 0 U2 9 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 DEC 26 PY 2003 VL 278 IS 52 BP 52964 EP 52971 DI 10.1074/jbc.M309039200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756LX UT WOS:000187480700119 PM 14534293 ER PT J AU Rahemtullah, A Misdraji, J Pitman, MB AF Rahemtullah, A Misdraji, J Pitman, MB TI Adenosquamous carcinoma of the pancreas - Cytologic features in 14 cases SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, DC SP US & Canadian Acad Pathol DE adenosquamous carcinoma; squamous cell carcinoma; fine-needle aspiration biopsy; pancreas; pancreatic neoplasms ID SQUAMOUS-CELL CARCINOMA; FINE-NEEDLE ASPIRATION; COMPUTED-TOMOGRAPHY; DIAGNOSIS; TUMORS; BIOPSY AB BACKGROUND. Adenosquamous carcinoma (ASCa) is a rare subtype of ductal adenocarcinoma of the pancreas with what to the authors' knowledge are limited cytologic descriptions. In the current study, the authors describe their experience with the fine-aspiration biopsy (FNAB) diagnosis of ASCa and characterize cytologic features in 14 cases. METHODS. Fourteen cases of ASCa were identified from pathology case files. Cytologic material was examined for cellularity, grade, tumor cell necrosis, and specific features of glandular and squamous differentiation. RESULTS. The 10 females and 4 males had an average age of 70 years. Nine patients (64%) were reported to have Stage IV disease at the time of presentation. All tumors were high grade, with moderate to high cellularity. Tumor cell necrosis was noted in 12. Nine of the 14 cases (64%) demonstrated predominantly squamous differentiation with keratinization. Seven of these nine contained at least focal intracellular mucin or honeycombed glandular sheets. Two of the nine had rare cytoplasmic vacuoles as the only evidence of glandular differentiation. Five cases (36%) were predominantly glandular. All but one of these five cases contained atypical to malignant keratinized cells. One of the five cases lacked keratinization but had tumor cells with dense cytoplasm; the diagnosis of ASCa was confirmed on histology. In 13 patients for whom follow-up was known, 12 had died of disease (mean, 5.6 months) and 1was alive at 13 months of follow-up. CONCLUSIONS. A specific diagnosis of ASCa is possible when aspirates show evidence of both squamous and glandular differentiation, although one component often predominates and features of dual differentiation may be focal. A purely squamous tumor should raise the suspicion of a metastasis, but also may represent undersampling of an ASCa. (C) 2003 American Cancer Society. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Cytopathol Lab, Boston, MA 02114 USA. RP Rahemtullah, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,James Homer Wright Pathol Labs, Warren 219,55 Fruit St, Boston, MA 02114 USA. EM arahemtullah@partners.org NR 28 TC 28 Z9 30 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2003 VL 99 IS 6 BP 372 EP 378 DI 10.1002/cncr.11855 PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 755LK UT WOS:000187404200009 PM 14681946 ER PT J AU Gold, BD Westra, SJ Harris, NL Winter, HS Doody, DP Graeme-Cook, FM Griffiths, E Pasternack, MS Basgoz, N Barron, RF AF Gold, BD Westra, SJ Harris, NL Winter, HS Doody, DP Graeme-Cook, FM Griffiths, E Pasternack, MS Basgoz, N Barron, RF TI Case 40-2003: A 14-month-old boy with recurrent abdominal distention and diarrhea - Tuberculous enterocolitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; INTESTINAL TUBERCULOSIS; ENDOSCOPIC BIOPSY; CHILDREN; SARCOIDOSIS; INFECTIONS; VASCULITIS; FEATURES; SPECTRUM C1 Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Mt Auburn Hosp, Cambridge, MA USA. RP Gold, BD (reprint author), Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. NR 43 TC 3 Z9 3 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 25 PY 2003 VL 349 IS 26 BP 2541 EP 2549 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 757BT UT WOS:000187529500011 PM 14695415 ER PT J AU Misra, A Haudek, SB Knuefermann, P Vallejo, JG Chen, ZJ Michael, LH Sivasubramanian, N Olson, EN Entman, ML Mann, DL AF Misra, A Haudek, SB Knuefermann, P Vallejo, JG Chen, ZJ Michael, LH Sivasubramanian, N Olson, EN Entman, ML Mann, DL TI Nuclear factor-kappa B protects the adult cardiac myocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarction SO CIRCULATION LA English DT Article DE myocytes; apoptosis; myocardial infarction ID OVEREXPRESSION; HEART AB Background-Previous studies have shown that tumor necrosis factor (TNF) confers cytoprotective responses in cardiac myocytes. However, the mechanisms for the cytoprotective effects of TNF remain unknown. Given that TNF signals through nuclear factor kappaB (NF-kappaB) and given that NF-kappaB mediates cytoprotective responses, we asked whether NF-kappaB activation conferred cytoprotective responses in acute myocardial ischemia/infarction. Methods and Results-We examined infarct size and the prevalence of apoptosis in transgenic mice harboring cardiac-restricted expression of a mutated IkappaBalpha protein (IkappaBalphaDeltaN) that prevents nuclear translocation of NF-kappaB in cardiac myocytes. Triphenyltetrazolium chloride staining showed that infarct size was approximate to50% greater (P<0.02) in the IκBα&UDelta;N mice compared with littermate controls at 24 hours. The prevalence of cardiac myocyte apoptosis was significantly greater (P<0.008) in the IkappaBalphaDeltaN mice compared with the littermate control mice 3 and 6 hours after left anterior descending occlusion. To explore the mechanism for these findings, we examined protein levels of c-IAP1, c-IAP2, and Bcl-2 as well as manganese superoxide dismutase and c-Jun NH2-terminal kinase activity. These studies showed that protein levels of c-IAP1 and Bcl-2 were significantly lower in the IkappaBalphaDeltaN mice, whereas there was no change in c-IAP2 levels, manganese superoxide dismutase, or c-Jun NH2-terminal kinase activity. Conclusions-Transgenic mice with a defect in activation of NF-kappaB have increased susceptibility to tissue injury after acute left anterior descending occlusion. These studies suggest that the cytoprotective effects of NF-kappaB are mediated, at least in part, by Bcl-2 or c-IAP1. C1 Houston Vet Adm Med Ctr, Med Care Serv Line, Winters Ctr Heart Failure Res, Houston, TX 77030 USA. Baylor Coll Med, Methodist Hosp, DeBakey Heart Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX USA. RP Mann, DL (reprint author), Houston Vet Adm Med Ctr, Med Care Serv Line, Winters Ctr Heart Failure Res, 6565 Fannin,MS 524, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-42250-10/10, P50 HL-O6H, R01 HL-58081-01, R01 HL-61543-01]; NIGMS NIH HHS [R01 GM-59203-03] NR 9 TC 87 Z9 92 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 23 PY 2003 VL 108 IS 25 BP 3075 EP 3078 DI 10.1161/01.CIR.0000108929.93074.0B PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 756ZA UT WOS:000187514600019 PM 14676146 ER PT J AU Kolodgie, FD Petrov, A Virmani, R Narula, N Verjans, JW Weber, DK Hartung, D Steinmetz, N Vanderheyden, JL Vannan, MA Gold, HK Reutelingsperger, CPM Hofstra, L Narula, J AF Kolodgie, FD Petrov, A Virmani, R Narula, N Verjans, JW Weber, DK Hartung, D Steinmetz, N Vanderheyden, JL Vannan, MA Gold, HK Reutelingsperger, CPM Hofstra, L Narula, J TI Targeting of apoptotic macrophages and experimental atheroma with radiolabeled annexin V - A technique with potential for noninvasive imaging of vulnerable plaque SO CIRCULATION LA English DT Article DE apoptosis; atherosclerosis; imaging; nuclear medicine ID SMOOTH-MUSCLE-CELLS; SUDDEN CORONARY DEATH; ATHEROSCLEROTIC LESIONS; PHOSPHATIDYLSERINE; EXPOSURE; SURFACE; EXPRESSION; ACTIVATION; BINDING; RABBIT AB Background - Apoptosis is common in advanced human atheroma and contributes to plaque instability. Because annexin V has a high affinity for exposed phosphatidylserine on apoptotic cells, radiolabeled annexin V may be used for noninvasive detection of apoptosis in atherosclerotic lesions. Methods and Results - Atherosclerotic plaques were produced in 5 rabbits by deendothelialization of the infradiaphragmatic aorta followed by 12 weeks of cholesterol diet; 5 controls were studied without manipulation. Animals were injected with human recombinant annexin V labeled with technetium-99m before imaging. Aortas were explanted for ex vivo imaging, macroautoradiography, and histological characterization of plaque. Radiolabeled annexin V cleared rapidly from the circulation (T-1/2, alpha 9 and beta 46 minutes). There was intense uptake of radiolabel within lesions by 2 hours; no uptake was seen in controls. The results were confirmed in the ex vivo imaging of the explanted aorta. Quantitative annexin uptake was 9.3-fold higher in lesion versus nonlesion areas; the lesion-to-blood ratio was 3.0 +/- 0.37. Annexin uptake paralleled lesion severity and macrophage burden; no correlation was observed with smooth muscle cells. DNA fragmentation staining of apoptotic nuclei was increased in advanced lesions with evolving necrotic cores, predominantly in macrophages; the uptake of radiolabel correlated with the apoptotic index. Conclusions - Because annexin V clears rapidly from blood and targets apoptotic macrophage population, it should constitute an attractive imaging agent for the noninvasive detection of unstable atherosclerotic plaques. C1 Armed Forces Inst Pathol, Washington, DC 20306 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. Theseus Imaging, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Limburg, Cardiovasc Res Inst, NL-6200 MD Maastricht, Netherlands. RP Narula, J (reprint author), Univ Calif Irvine, 101 City Dr,Bldg 53,Route 81,Room 100, Orange, CA 92868 USA. FU NHLBI NIH HHS [1 R01 HL68657-01] NR 21 TC 163 Z9 180 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 DEC 23 PY 2003 VL 108 IS 25 BP 3134 EP 3139 DI 10.1161/01.CIR.0000105761.00573.50 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 756ZA UT WOS:000187514600029 PM 14676140 ER PT J AU Barbie, TU Barbie, DA MacLaughlin, DT Maheswaran, S Donahoe, PK AF Barbie, TU Barbie, DA MacLaughlin, DT Maheswaran, S Donahoe, PK TI Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN OVARIAN-CANCER; IN-VIVO; CYCLE ARREST; P16 GENE; RETINOBLASTOMA PROTEIN; RECOMBINANT ADENOVIRUS; CARCINOMA CELLS; NUDE-MICE; P16(INK4A); APOPTOSIS AB In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin. Because the uterine cervix is derived from the same Mullerian duct precursor as the epithelium of the ovary, we tested the hypothesis that cervical cancer cells might also respond to MIS. A number of cervical cancer cell lines express the MIS type 11 receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter. As in the ovarian cancer cell line OVCAR8, suppression of growth of the C33A cervical cancer cell line by MIS is associated with induction of the p16 tumor suppressor protein. However, in contrast to OVCAR8 cells, induction of p130 and p107 appears to play an important role in the inhibition of growth of C33A cells by MIS. Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. FU NCI NIH HHS [CA 17393, R01 CA017393]; NICHD NIH HHS [HD 32112, R01 HD032112] NR 48 TC 38 Z9 44 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 23 PY 2003 VL 100 IS 26 BP 15601 EP 15606 DI 10.1073/pnas.2636900100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 757GL UT WOS:000187554600058 PM 14671316 ER PT J AU Fackler, MJ McVeigh, M Evron, E Garrett, E Mehrotra, J Polyak, K Sukumar, S Argani, P AF Fackler, MJ McVeigh, M Evron, E Garrett, E Mehrotra, J Polyak, K Sukumar, S Argani, P TI DNA methylation of RASSF1A, Hin-1, RAR-beta, cyclin D2 and twist in in situ and invasive lobular breast carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE methylation; breast cancer; lobular; ductal; DCIS; LCIS ID TUMOR-SUPPRESSOR GENE; ACID RECEPTOR-BETA; FREQUENT EPIGENETIC INACTIVATION; CANCER CELLS; PROMOTER HYPERMETHYLATION; E-CADHERIN; ESTROGEN-RECEPTOR; CPG ISLAND; RETINOID RECEPTORS; SERIAL ANALYSIS AB Little is known about epigenetic silencing of genes by promoter hypermethylation in lobular breast cancers. The promoter methylation status of 5 cancer-related genes (RASSF1A, HIN-1, RAR-beta, Cyclin D2 and Twist) was evaluated in 2 types of lobular cancers, in situ (LCIS) and invasive lobular carcinomas (ILC) (n = 32), and compared to ductal in situ (DCIS) and invasive (IDC) breast cancers (n = 71). By using methylation-specific PCR (MSP), 100% of ILC and 69% of LCIS cases were found to have 1 or more hypermethylated genes among the panel of 5 genes (compared to 100% 1 DC and 95% of DCIS). Two or more hypermethylated genes were detected per tumor in 79% of invasive and 61% of in situ lobular carcinomas compared to 81% of IDC and 77% of DCIS. By contrast, DNA from nearly all normal reduction mammoplasty tissues (n = 8) was unmethylated for the 5 genes. The methylation profiles of lobular vs. ductal carcinomas with respect to RASSF1A, Cyclin D2, RARbeta, and Hin-1 genes were similar, suggesting that gene silencing by promoter hypermethylation is likely to be important in both groups of diseases. Distinctly different, Twist was hypermethylated less often in ILC (16%, 3/19 cases) than in IDC (56%, 15/27 cases) (p = 0.01). These results suggest that these 2 types of tumors share many common methylation patterns and some molecular differences. Additional studies might lend further understanding into the etiology and clinical behavior of this tumor type. (C) 2003 Wiley-Liss, Inc. C1 Sidney Kimmel Comprehens Canc Ctr, Breast Canc Program, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Div Biostat, Baltimore, MD USA. Sidney Kimmel Comprehens Canc Ctr, Dept Pathol, Baltimore, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Argani, P (reprint author), Johns Hopkins Hosp, Dept Pathol, Weinberg Bldg,Room 2242,401 N Broadway, Baltimore, MD 21231 USA. FU NCI NIH HHS [P50 CA 88843, P50 CA 89393] NR 50 TC 181 Z9 188 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 20 PY 2003 VL 107 IS 6 BP 970 EP 975 DI 10.1002/ijc.11508 PG 6 WC Oncology SC Oncology GA 744GJ UT WOS:000186619300014 PM 14601057 ER PT J AU Bithell, A Alberta, J Hornby, F Stiles, CD Williams, BP AF Bithell, A Alberta, J Hornby, F Stiles, CD Williams, BP TI Expression of the guanine nucleotide exchange factor, mr-gef, is regulated during the differentiation of specific subsets of telencephalic neurons SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE development and regeneration; cell differentiation and migration; telencephalon; neuronal differentiation; GEF; GABAergic; PDGF; ganglionic eminence ID DEVELOPING CEREBRAL-CORTEX; CENTRAL-NERVOUS-SYSTEM; ZONE PROGENITOR CELLS; INSULINOMA GENE-RIG; DLX GENES; MAMMALIAN TELENCEPHALON; GANGLIONIC EMINENCES; SUBVENTRICULAR ZONE; RAS SUPERFAMILY; GROWTH-FACTOR AB We have performed a screen combining subtractive hybridization with PCR to isolate genes that are regulated when neuroepithelial (NE) cells differentiate into neurons. From this screen, we have isolated a number of known genes that have not previously been associated with neurogenesis, together with several novel genes. Here we report that one of these genes, encoding a guanine nucleotide exchange factor (GEF), is regulated during the differentiation of distinct neuronal populations. We have cloned both rat and mouse GEF genes and shown that they are orthologs of the human gene, MR-GEF, which encodes a GEE that specifically activates the small GTPase, Rap1. We have therefore named the rat gene rat mr gef (rmr-gef) and the mouse gene mouse mr-gef (mmr-gef). Here, we will collectively refer to these two rodent genes as mr-gef Expression studies show that mr-gef is expressed by young neurons of the developing rodent CNS but not by progenitor cells in the ventricular zone (VZ). The expression pattern of mr-gef during early telencephalic neurogenesis is strikingly similar to that of GABA and the LIM homeobox gene Lhx6, a transcription factor expressed by GABAergic interneurons generated in the ventral telencephalon, some of which migrate into the cortex during development. These observations suggest that mr-gef encodes a protein that is part of a signaling pathway involved in telencephalic neurogenesis-1 particularly in the development of GABAergic interneurons. (C) 2003 Elsevier B.V. All fights reserved. C1 Inst Psychiat, Dept Psychol Med, Sect Expt Neuropathol & Psychiat, London SE5 8AF, England. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Williams, BP (reprint author), Inst Psychiat, Dept Psychol Med, Sect Expt Neuropathol & Psychiat, P052,De Crespigny Pk, London SE5 8AF, England. OI Bithell, Angela/0000-0002-0294-078X NR 67 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD DEC 19 PY 2003 VL 146 IS 1-2 BP 107 EP 118 DI 10.1016/j.devbrainres.2003.09.017 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 753EC UT WOS:000187218300012 ER PT J AU Fanning, PJ Emkey, G Smith, RJ Grodzinsky, AJ Szasz, N Trippel, SB AF Fanning, PJ Emkey, G Smith, RJ Grodzinsky, AJ Szasz, N Trippel, SB TI Mechanical regulation of mitogen-activated protein kinase signaling in articular cartilage SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR-I; MATRIX SYNTHESIS; DYNAMIC COMPRESSION; INTERSTITIAL FLUID; GENE-EXPRESSION; CHONDROCYTES; AGGRECAN; EXPLANTS; CELLS; INTERLEUKIN-1 AB Articular chondrocytes respond to mechanical forces by alterations in gene expression, proliferative status, and metabolic functions. Little is known concerning the cell signaling systems that receive, transduce, and convey mechanical information to the chondrocyte interior. Here, we show that ex vivo cartilage compression stimulates the phosphorylation of ERK1/ 2, p38 MAPK, and SAPK/ ERK kinase- 1 ( SEK1) of the JNK pathway. Mechanical compression induced a phased phosphorylation of ERK consisting of a rapid induction of ERK1/ 2 phosphorylation at 10 min, a rapid decay, and a sustained level of ERK2 phosphorylation that persisted for at least 24 h. Mechanical compression also induced the phosphorylation of p38 MAPK in strictly a transient fashion, with maximal phosphorylation occurring at 10 min. Mechanical compression stimulated SEK1 phosphorylation, with a maximum at the relatively delayed time point of 1 h and with a higher amplitude than ERK1/ 2 and p38 MAPK phosphorylation. These data demonstrate that mechanical compression alone activates MAPK signaling in intact cartilage. In addition, these data demonstrate distinct temporal patterns of MAPK signaling in response to mechanical loading and to the anabolic insulin- like growth factor- I. Finally, the data indicate that compression coactivates distinct signaling pathways that may help define the nature of mechanotransduction in cartilage. C1 Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Trippel, SB (reprint author), Indiana Univ, Sch Med, Dept Orthoped Surg, 541 Clin Dr, Indianapolis, IN 46202 USA. FU NIAMS NIH HHS [AR33236, AR45749] NR 52 TC 90 Z9 94 U1 0 U2 8 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 DEC 19 PY 2003 VL 278 IS 51 BP 50940 EP 50948 DI 10.1074/jbc.M305107200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 752ZM UT WOS:000187206300015 PM 12952976 ER PT J AU Hoshiya, Y Gupta, V Kawakubo, H Brachtel, E Carey, JL Sasur, L Scott, A Donahoe, PK Maheswaran, S AF Hoshiya, Y Gupta, V Kawakubo, H Brachtel, E Carey, JL Sasur, L Scott, A Donahoe, PK Maheswaran, S TI Mullerian inhibiting substance promotes interferon gamma-induced gene expression and apoptosis in breast cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REGULATORY FACTOR-I; BILIARY GLYCOPROTEIN CD66A; KAPPA-B; ADHESION MOLECULE; TRANSCRIPTIONAL ACTIVATION; EPITHELIAL-CELLS; IL-12/PULSE IL-2; IRF FAMILY; IFN-GAMMA; LONG ARM AB This report demonstrates that in addition to interferons and cytokines, members of the TGFbeta superfamily such as Mullerian inhibiting substance (MIS) and activin A also regulate IRF-1 expression. MIS induced IRF-1 expression in the mammary glands of mice in vivo and in breast cancer cells in vitro and stimulation of IRF-1 by MIS was dependent on activation of the NFkappaB pathway. In the rat mammary gland, IRF-1 expression gradually decreased during pregnancy and lactation but increased at involution. In breast cancer, the IRF-1 protein was absent in 13% of tumors tested compared with matched normal glands. Consistent with its growth suppressive activity, expression of IRF-1 in breast cancer cells induced apoptosis. Treatment of breast cancer cells with MIS and interferon gamma (IFN-gamma) co-stimulated IRF-1 and CEACAM1 expression and synergistic induction of CEACAM1 by a combination of MIS and IFN-gamma was impaired by antisense IRF-1 expression. Furthermore, a combination of IFN-gamma and MIS inhibited the growth of breast cancer cells to a greater extent than either one alone. Both reagents alone significantly decreased the fraction of cells in the S-phase of the cell cycle, an effect not enhanced when they were used in combination. However, MIS promoted IFN-gamma-induced apoptosis demonstrating a functional interaction between these two classes of signaling molecules in regulation of breast cancer cell growth. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, WRN 1024,55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA89138-01A1, CA17393]; NICHD NIH HHS [HD32112] NR 60 TC 20 Z9 22 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 19 PY 2003 VL 278 IS 51 BP 51703 EP 51712 DI 10.1074/jbc.M307626200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 752ZM UT WOS:000187206300105 PM 14532292 ER PT J AU Badgaiyan, RD Schacter, DL Alpert, NM AF Badgaiyan, RD Schacter, DL Alpert, NM TI Priming of new associations: a PET study SO NEUROREPORT LA English DT Article DE amnesia; associative priming; extrastriate cortex; hippocampus; left prefrontal cortex; medial temporal lobe ID POSITRON-EMISSION-TOMOGRAPHY; INFERIOR PREFRONTAL CORTEX; IMPLICIT MEMORY; EXPLICIT MEMORY; MODALITIES; PERSPECTIVES; SPECIFICITY; HIPPOCAMPUS; ACTIVATION; RETRIEVAL AB Cognitive properties of associative priming are different from those of the non-associative priming. We examined areas associated with associative priming to understand its cortical processing. After subjects had studied pairs of unrelated words, they were shown one of the studied words and a 3-letter word-stem that could be completed using either the word that was paired with the presented studied word (same context), or with a different word (different context). As compared to the fixation, both conditions elicited increased activations in the left prefrontal and decreased activation in the extrastriate cortex. Medial temporal lobe was activated only in the same-context condition. This finding helps to understand why associative priming is impaired in some amnesic patients. (C) 2003 Lippincott Williams Wilkins. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, PET Imaging Lab, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St,William James Hall,Rm 875, Cambridge, MA 02138 USA. EM rajendra@wjh.harvard.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NCI NIH HHS [T32CA09362]; NIMH NIH HHS [MH57915, MH60941] NR 23 TC 10 Z9 10 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 19 PY 2003 VL 14 IS 18 BP 2475 EP 2479 DI 10.1097/01.wnr.00000093757.78398.b9 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 772LP UT WOS:000188843800036 PM 14663213 ER PT J AU Gibbs, RA Belmont, JW Hardenbol, P Willis, TD Yu, FL Yang, HM Ch'ang, LY Huang, W Liu, B Shen, Y Tam, PKH Tsui, LC Waye, MMY Wong, JTF Zeng, CQ Zhang, QR Chee, MS Galver, LM Kruglyak, S Murray, SS Oliphant, AR Montpetit, A Hudson, TJ Chagnon, F Ferretti, V Leboeuf, M Phillips, MS Verner, A Kwok, PY Duan, SH Lind, DL Miller, RD Rice, JP Saccone, NL Taillon-Miller, P Xiao, M Nakamura, Y Sekine, A Sorimachi, K Tanaka, T Tanaka, Y Tsunoda, T Yoshino, E Bentley, DR Deloukas, P Hunt, S Powell, D Altshuler, D Gabriel, SB Qiu, RZ Ken, A Dunston, GM Kato, K Niikawa, N Knoppers, BM Foster, MW Clayton, EW Wang, VO Watkin, J Gibbs, RA Belmont, JW Sodergren, E Weinstock, GM Wilson, RK Fulton, LL Rogers, J Birren, BW Han, H Wang, HG Godbout, M Wallenburg, JC L'Archeveque, P Bellemare, G Todani, K Fujita, T Tanaka, S Holden, AL Lai, EH Collins, FS Brooks, LD McEwen, JE Guyer, MS Jordan, E Peterson, JL Spiegel, J Sung, LM Zacharia, LF Kennedy, K Dunn, MG Seabrook, R Shillito, M Skene, B Stewart, JG Valle, DL Clayton, EW Jorde, LB Belmont, JW Chakravarti, A Cho, MK Duster, T Foster, MW Jasperse, M Knoppers, BM Kwok, PY Licinio, J Long, JC Marshall, PA Ossorio, PN Wang, VO Rotimi, CN Royal, CDM Spallone, P Terry, SF Lander, ES Lai, EH Nickerson, DA Abecasis, GR Altshuler, D Bentley, DR Boehnke, M Cardon, LR Daly, MJ Deloukas, P Douglas, JA Gabriel, SB Hudson, RR Hudson, TJ Kruglyak, L Kwok, PY Nakamura, Y Nussbaum, RL Royal, CDM Schaffner, SF Sherry, ST Stein, LD Tanaka, T AF Gibbs, RA Belmont, JW Hardenbol, P Willis, TD Yu, FL Yang, HM Ch'ang, LY Huang, W Liu, B Shen, Y Tam, PKH Tsui, LC Waye, MMY Wong, JTF Zeng, CQ Zhang, QR Chee, MS Galver, LM Kruglyak, S Murray, SS Oliphant, AR Montpetit, A Hudson, TJ Chagnon, F Ferretti, V Leboeuf, M Phillips, MS Verner, A Kwok, PY Duan, SH Lind, DL Miller, RD Rice, JP Saccone, NL Taillon-Miller, P Xiao, M Nakamura, Y Sekine, A Sorimachi, K Tanaka, T Tanaka, Y Tsunoda, T Yoshino, E Bentley, DR Deloukas, P Hunt, S Powell, D Altshuler, D Gabriel, SB Qiu, RZ Ken, A Dunston, GM Kato, K Niikawa, N Knoppers, BM Foster, MW Clayton, EW Wang, VO Watkin, J Gibbs, RA Belmont, JW Sodergren, E Weinstock, GM Wilson, RK Fulton, LL Rogers, J Birren, BW Han, H Wang, HG Godbout, M Wallenburg, JC L'Archeveque, P Bellemare, G Todani, K Fujita, T Tanaka, S Holden, AL Lai, EH Collins, FS Brooks, LD McEwen, JE Guyer, MS Jordan, E Peterson, JL Spiegel, J Sung, LM Zacharia, LF Kennedy, K Dunn, MG Seabrook, R Shillito, M Skene, B Stewart, JG Valle, DL Clayton, EW Jorde, LB Belmont, JW Chakravarti, A Cho, MK Duster, T Foster, MW Jasperse, M Knoppers, BM Kwok, PY Licinio, J Long, JC Marshall, PA Ossorio, PN Wang, VO Rotimi, CN Royal, CDM Spallone, P Terry, SF Lander, ES Lai, EH Nickerson, DA Abecasis, GR Altshuler, D Bentley, DR Boehnke, M Cardon, LR Daly, MJ Deloukas, P Douglas, JA Gabriel, SB Hudson, RR Hudson, TJ Kruglyak, L Kwok, PY Nakamura, Y Nussbaum, RL Royal, CDM Schaffner, SF Sherry, ST Stein, LD Tanaka, T CA Int HapMap Consortium TI The International HapMap Project SO NATURE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LINKAGE-DISEQUILIBRIUM; HUMAN GENOME; ESTIMATING RECOMBINATION; SEQUENCE VARIATION; GENETIC-VARIATION; CROHNS-DISEASE; SUSCEPTIBILITY; DIVERSITY; COMPLEX C1 Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA. ParAllele Biosci, San Francisco, CA 94080 USA. Chinese Acad Sci, Beijing Genom Inst, Beijing 100300, Peoples R China. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. Chinese Natl Human Genome Ctr Shanghai, Shanghai 201203, Peoples R China. Chinese Natl Human Genome Ctr Beijing, Beijing Econ & Technol Dev Zone, Beijing 100176, Peoples R China. Univ Hong Kong, Genome Res Ctr, Pokfulam, Hong Kong, Peoples R China. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Chinese Univ Hong Kong, Dept Biochem, Shatin, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Dept Biochem, Knowloon, Hong Kong, Peoples R China. Illumina, San Diego, CA 92121 USA. McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. RIKEN, SNP Res Ctr, Tsurumi Ku, Kanagawa 2300045, Japan. RIKEN, Technol Transfer & Res Coordinat Div, Wako, Saitama 35101, Japan. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Whitehead Inst MIT, Ctr Genome Res, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beijing Normal Univ, Beijing 100875, Peoples R China. Hlth Sci Univ Hokkaido, Ezuko Inst Dev Disabil, Kumamoto 575, Japan. Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 3908621, Japan. 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, 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. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA. Univ Oxford, Dept Stat, Oxford OX1 3TG, England. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. NIH, NHGRI, Bethesda, MD 20892 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Chinese Acad Social Sci, Ctr Appl Eth, Beijing 100054, Peoples R China. Genet Interest Grp, London N1 3QP, England. Kyoto Univ, Inst Res Human, Sakyo Ku, Kyoto 6068501, Japan. Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 8528523, Japan. Univ Montreal, Publ Law Res Ctr, CRDP, Montreal, PQ H3C 3J7, Canada. 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. Whitehead Inst MIT, Ctr Genome Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. Chinese Acad Sci, Beijing 100864, Peoples R China. Chinese Minist Sci & Technol, Beijing 100862, 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, Japan. Hiraka & Associates, Minato Ku, Tokyo 1050001, Japan. SNP Consortium, Deerfield, IL 60015 USA. GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. NIH, NHGRI, Bethesda, MD 20892 USA. Fdn Natl Inst Hlth, Bethesda, MD 20892 USA. NIH, Off Technol Transfer, Rockville, MD 20852 USA. Univ Maryland, Sch Law, Baltimore, MD 21201 USA. Exchange House, London EC2A 2HS, England. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Stanford Ctr Biomed Eth, Palo Alto, CA 94304 USA. NYU, Dept Sociol, New York, NY 10003 USA. Univ Calif Berkeley, Dept Sociol, Berkeley, CA 94720 USA. Univ New Mexico, Hlth Sci Ctr, Gallup, NM 87301 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Wisconsin, Sch Law, Madison, WI 53706 USA. Univ London London Sch Econ & Polit Sci, London WC2A 2AE, England. Genet Alliance, Washington, DC 20008 USA. Univ Washington, Dept Genome Sci, Washington, DC 98125 USA. Univ Chicago, Dept Ecol & Evolut, Chicago, IL 60637 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. NIH, NHGRI, Bethesda, MD 20892 USA. RP Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, 1 Baylor Plaza, Houston, TX 77030 USA. EM drb@sanger.ac.uk; fost1848@msmailhub.oulan.ou.edu RI Tam, Paul/C-4405-2009; Abecasis, Goncalo/B-7840-2010; Altshuler, David/A-4476-2009; Tsui, Lap-chee/A-1081-2010; Schaffner, Stephen/D-1189-2011; Deloukas, Panos/B-2922-2013; Kwok, Pui-Yan/F-7725-2014; Tsunoda, Tatsuhiko/K-2061-2014; Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tanaka, Toshihiro/J-9310-2014; Licinio, Julio/L-4244-2013; OI Altshuler, David/0000-0002-7250-4107; Deloukas, Panos/0000-0001-9251-070X; Kwok, Pui-Yan/0000-0002-5087-3059; Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tanaka, Toshihiro/0000-0001-6201-9784; Licinio, Julio/0000-0001-6905-5884; Cunningham, Fiona/0000-0002-7445-2419; Thorisson, Gudmundur/0000-0001-5635-1860; Belmont, John/0000-0001-7409-3578; Abecasis, Goncalo/0000-0003-1509-1825; Adebamowo, Clement/0000-0002-6571-2880 NR 68 TC 3294 Z9 3391 U1 19 U2 198 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD DEC 18 PY 2003 VL 426 IS 6968 BP 789 EP 796 DI 10.1038/nature02168 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 754QM UT WOS:000187342000046 ER PT J AU Huynh, KD Lee, JT AF Huynh, KD Lee, JT TI Inheritance of a pre-inactivated paternal X chromosome in early mouse embryos SO NATURE LA English DT Article ID XIST RNA ACCUMULATION; GENE-EXPRESSION; SPERMATOGENESIS; MAMMALS; STAGE; CELLS; MICE AB In mammals, dosage compensation ensures equal X-chromosome expression between males (XY) and females (XX) by transcriptionally silencing one X chromosome in XX embryos(1). In the prevailing view, the XX zygote inherits two active X chromosomes, one each from the mother and father, and X inactivation does not occur until after implantation(2-6). Here, we report evidence to the contrary in mice. We find that one X chromosome is already silent at zygotic gene activation (2-cell stage). This X chromosome is paternal in origin and exhibits a gradient of silencing. Genes close to the X-inactivation centre show the greatest degree of inactivation, whereas more distal genes show variable inactivation and can partially escape silencing. After implantation, imprinted silencing in extraembryonic tissues becomes globalized and more complete on a gene-by-gene basis. These results argue that the XX embryo is in fact dosage compensated at conception along much of the X chromosome. We propose that imprinted X inactivation results from inheritance of a pre-inactivated X chromosome from the paternal germ line. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. NR 30 TC 252 Z9 259 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 18 PY 2003 VL 426 IS 6968 BP 857 EP 862 DI 10.1038/nature02222 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 754QM UT WOS:000187342000063 PM 14661031 ER PT J AU Leissring, MA Farris, W Chang, AY Walsh, DM Wu, XN Sun, XY Frosch, MP Selkoe, DJ AF Leissring, MA Farris, W Chang, AY Walsh, DM Wu, XN Sun, XY Frosch, MP Selkoe, DJ TI Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death SO NEURON LA English DT Article ID INSULIN-DEGRADING ENZYME; BRAIN A-BETA; ALZHEIMERS-DISEASE; MOUSE MODEL; PRECURSOR PROTEIN; IN-VIVO; PEPTIDE; DEGRADATION; EXPRESSION; ANTIBODIES AB Converging evidence suggests that the accumulation of cerebral amyloid p-protein (Abeta) in Alzheimer's disease (AD) reflects an imbalance between the production and degradation of this self-aggregating peptide. Upregulation of proteases that degrade Abeta thus represents a novel therapeutic approach to lowering steady-state Abeta levels, but the consequences of sustained upregulation in vivo have not been studied. Here we show that transgenic overexpression of insulin-degrading enzyme (IDE) or neprilysin (NEP) in neurons significantly reduces brain Abeta levels, retards or completely prevents amyloid plaque formation and its associated cytopathology, and rescues the premature lethality present in amyloid precursor protein (APP) transgenic mice. Our findings demonstrate that chronic upregulation of Abeta-degrading proteases represents an efficacious therapeutic approach to combating Alzheimer-type pathology in vivo. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Selkoe, DJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis,Dept Neurol, Boston, MA 02115 USA. FU NIA NIH HHS [AG12749] NR 41 TC 436 Z9 458 U1 3 U2 28 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 18 PY 2003 VL 40 IS 6 BP 1087 EP 1093 DI 10.1016/S0896-6273(03)00787-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 756UZ UT WOS:000187503400008 PM 14687544 ER PT J AU Heney, NM Lawner, BE Young, RH Gomery, P Ongaro, TJ AF Heney, NM Lawner, BE Young, RH Gomery, P Ongaro, TJ TI A 33-year-old woman with gross hematuria - Inflammatory pseudotumor of the urinary bladder SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TRANSITIONAL-CELL CARCINOMA; PROLIFERATIONS; LEIOMYOSARCOMA; CHILDREN; SARCOMA; ADULTS C1 Massachusetts Gen Hosp, Urol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Urol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Heney, NM (reprint author), Massachusetts Gen Hosp, Urol Serv, Boston, MA 02114 USA. NR 19 TC 5 Z9 5 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 18 PY 2003 VL 349 IS 25 BP 2442 EP 2447 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 754PJ UT WOS:000187326200012 PM 14681511 ER PT J AU Blumenthal, D AF Blumenthal, D TI Health policy report: Academic-industrial relationships in the life sciences SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONFLICTS-OF-INTEREST; UNIVERSITY; FACULTY C1 Massachusetts Gen Hosp Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA USA. RP Blumenthal, D (reprint author), Massachusetts Gen Hosp Partners Hlth Care Syst, Inst Hlth Policy, Boston, MA USA. NR 45 TC 68 Z9 68 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 18 PY 2003 VL 349 IS 25 BP 2452 EP 2459 DI 10.1056/NEJMhpr035460 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 754PJ UT WOS:000187326200014 PM 14681513 ER PT J AU Castiglione-Gertsch, M O'Neill, A Price, KN Goldhirsch, A Coates, AS Colleoni, M Nasi, ML Bonetti, M Gelber, RD AF Castiglione-Gertsch, M O'Neill, A Price, KN Goldhirsch, A Coates, AS Colleoni, M Nasi, ML Bonetti, M Gelber, RD CA IBCSG TI Adjuvant chemotherapy followed by goserelin versus either modality alone for premenopausal lymph node-negative breast cancer: A randomized trial SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DISEASE-FREE SURVIVAL; CLINICAL-TRIAL; TAMOXIFEN; ESTROGEN; RECEPTOR; FLUOROURACIL; METHOTREXATE; THERAPY; WOMEN; CYCLOPHOSPHAMIDE AB Background: Although chemotherapy and ovarian function suppression are both effective adjuvant therapies for patients with early-stage breast cancer, little is known of the efficacy of their sequential combination. In an International Breast Cancer Study Group (IBCSG) randomized clinical trial (Trial VIII) for pre- and perimenopausal women with lymph node-negative breast cancer, we compared sequential chemotherapy followed by the gonadotropin-releasing hormone agonist goserelin with each modality alone. Methods: From March 1990 through October 1999, 1063 patients stratified by estrogen receptor (ER) status and radiotherapy plan were randomly assigned to receive goserelin for 24 months (n = 346), six courses of "classical" CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy (n = 360), or six courses of classical CMF followed by 18 months of goserelin (CMF --> goserelin; n = 357). A fourth arm (no adjuvant treatment) with 46 patients was discontinued in 1992. Tumors were classified as ER-negative (30%), ER-positive (68%), or ER status unknown (3%). Twenty percent of patients were aged 39 years or younger. The median follow-up was 7 years. The primary outcome was disease-free survival (DFS). Results: Patients with ER-negative tumors achieved better disease-free survival if they received CMF (5-year DFS for CMF = 84%, 95% confidence interval [CI] = 77% to 91%; 5-year DFS for CMF --> goserelin = 88%, 95% CI = 82 % to 94 %) than if they received goserelin alone (5-year DFS = 73%, 95% CI = 64% to 81%). By contrast, for patients with ER-positive disease, chemotherapy alone and goserelin alone provided similar outcomes (5-year DFS for both treatment groups = 81%, 95% CI = 76% to 87%), whereas sequential therapy (5-year DFS = 86%, 95% CI = 82% to 91%) provided a statistically nonsignificant improvement compared with either modality alone, primarily because of the results among younger women. Conclusions: Premenopausal women with ER-negative (i.e., endocrine nonresponsive), lymph node-negative breast cancer should receive adjuvant chemotherapy. For patients with ER-positive (i.e., endocrine responsive) disease, the combination of chemotherapy with ovarian function suppression or other endocrine agents, and the use of endocrine therapy alone should be studied. C1 IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. European Inst Oncol, IBCSG Sci Comm, Milan, Italy. Oncol Inst So Switzerland, Bellinzona, Switzerland. Univ Sydney, IBCSG Sci Comm, Sydney, NSW 2006, Australia. Canc Council Australia, Sydney, NSW, Australia. RP Castiglione-Gertsch, M (reprint author), IBCSG Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM monica.castiglione@siak.ch OI Bonetti, Marco/0000-0003-2304-4180 NR 57 TC 162 Z9 168 U1 0 U2 2 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-. Natl. Cancer Inst. PD DEC 17 PY 2003 VL 95 IS 24 BP 1833 EP 1846 DI 10.1093/jnci/djg119 PG 14 WC Oncology SC Oncology GA 754GX UT WOS:000187308700008 ER PT J AU Braunwald, E AF Braunwald, E TI Cardiology: The past, the present, and the future SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-College-of-Cardiology CY MAR 31, 2003 CL CHICAGO, ILLINOIS SP Amer Coll Cardiol ID ANGIOTENSIN-CONVERTING-ENZYME; CLINICAL-PRACTICE GUIDELINES; VENTRICULAR ASSIST DEVICE; MYOCARDIAL-INFARCTION; AUTOMATIC DEFIBRILLATOR; POSTMENOPAUSAL WOMEN; DOSE REQUIREMENT; AMERICAN-COLLEGE; HEART-FAILURE; RISK C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. NR 51 TC 24 Z9 24 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 DEC 17 PY 2003 VL 42 IS 12 BP 2031 EP 2041 DI 10.1016/j.jacc.2003.08.025 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 753ER UT WOS:000187219600001 PM 14680723 ER PT J AU Bijsterveld, NR Peters, RJG Murphy, SA Bernink, PJLM Tijssen, JGP Cohen, M AF Bijsterveld, NR Peters, RJG Murphy, SA Bernink, PJLM Tijssen, JGP Cohen, M CA TIMI 11B ESSENCE Study Grp TI Recurrent cardiac ischemic events early after discontinuation of short-term heparin treatment in acute coronary syndromes - Results from the thrombolysis in myocardial infarction (TIMI) 11B and efficacy and safety of subcutaneous enoxaparin in non-Q-wave coronary events (ESSENCE) studies SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID MOLECULAR-WEIGHT HEPARIN; UNSTABLE ANGINA; UNFRACTIONATED HEPARIN; ARTERY-DISEASE; THROMBIN GENERATION; ST-ELEVATION; RANDOMIZED-TRIAL; REBOUND ISCHEMIA; REACTIVATION; INHIBITOR AB OBJECTIVES The aim of this study was to determine whether discontinuation of low-molecular-weight heparin (LMWH) treatment results in a clustering of cardiac ischemic events as previously observed after cessation of unfractionated heparin (UFH) in acute coronary syndrome (ACS) patients. BACKGROUND Clinical trials in patients with ACS have shown early recurrent ischemic events after discontinuation of UFH treatment. We analyzed whether LMWE cessation also results in early ischemic recurrence events and if continuation of a fixed-dose LMWH prevents this complication. METHODS The combined incidence of death, myocardial infarction, or urgent revascularization in the first seven days after discontinuation of UFH (n = 3,012), short-term enoxaparin 1 mg/kg subcutaneously twice a day (n = 2,011), and short-term enoxaparin followed by prolonged enoxaparin 60 mg subcutaneously twice a day (n = 1,075) was analyzed from the combined Thrombolysis In Myocardial Infarction (TIMI) 11B/Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE) database in a per patient analysis. RESULTS The cessation of both UFH and short-term enoxaparin resulted in a similar clustering of recurrent ischemic events on the first day, with an incidence of the primary end point of 2.8% in both groups. Of all recurrent events in the first week after cessation, 40% occurred in the first 24 h. The continuation of a fixed-dose enoxaparin treatment prevented this early excess, with a first day incidence of 0.4% (p < 0.0001). The TIMI risk score characteristics predicted the incidence of early rebound ischemic events. CONCLUSIONS There is significant clustering of recurrent ischemic events within 24 h after cessation of both short-term UFH and enoxaparin treatment, and patients should be carefully monitored during that period. This early rebound may be prevented by continuation of a fixed dose of enoxaparin. (J Am Coll Cardiol 2003-,42:2083-9) (C) 2003 by the American College of Cardiology Foundation. C1 Acad Med Ctr, Dept Cardiol, NL-1100 DD Amsterdam, Netherlands. Beth Israel Med Ctr, Dept Cardiol, Newark, NJ USA. Martini Hosp, Dept Cardiol, Groningen, Netherlands. TIMI Data Coordinating Ctr, Boston, MA USA. RP Peters, RJG (reprint author), Acad Med Ctr, Dept Cardiol, Room F3-236,Meibergdreef 9,POB 22660, NL-1100 DD Amsterdam, Netherlands. NR 24 TC 17 Z9 18 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 DEC 17 PY 2003 VL 42 IS 12 BP 2083 EP 2089 DI 10.1016/j.jacc.2003.05.014 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 753ER UT WOS:000187219600009 PM 14680731 ER PT J AU Mably, JD Mohideen, MAPK Burns, CG Chen, JN Fishman, MC AF Mably, JD Mohideen, MAPK Burns, CG Chen, JN Fishman, MC TI Heart of glass regulates the concentric growth of the heart in zebrafish SO CURRENT BIOLOGY LA English DT Article ID DANIO-RERIO; CARDIOVASCULAR-SYSTEM; GENE CLOCHE; MUTATION; PROTEIN; IDENTIFICATION; TRANSCRIPTION; GASTRULATION; PREDICTION; INDUCTION AB Background: Patterned growth of vertebrate organs is essential for normal physiological function, but the underlying pathways that govern organotypic growth are not clearly understood. Heart function is critically dependent upon the concentric thickening of the ventricular wall generated by the addition of cells to the myocardium along the axis from the endocardium (inside) to the outside of the chamber. In heart of glass mutant embryos, the number of cells in the myocardium is normal, but they are not added in the concentric direction. As a consequence, the chambers are huge and dysfunctional, and the myocardium remains a single layer. Results: To begin to define the factors controlling the concentric growth of cells in the myocardium, we used positional cloning to identify the heart of glass (heg) gene. heg encodes a protein of previously undescribed function, expressed in the endocardial layer of the heart. By alternative splicing, three distinct isoforms are generated, one of which is predicted to be transmembrane and two other secreted. By selective morpholino perturbation, we demonstrate that the transmembrane form is critical for the normal pattern of growth. Conclusions: heart of glass encodes a previously uncharacterized endocardial signal that is vital for patterning concentric growth of the heart. Growth of the heart requires addition of myocardial cells along the endocardial-to-myocardial axis. This axis of patterning is driven by heg, a novel transmembrane protein expressed in the endocardium. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02129 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Novartis Inst Biomed Res, Cambridge, MA 02139 USA. RP Fishman, MC (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St, Boston, MA 02129 USA. OI Chen, Jau-Nian/0000-0001-8807-3607 FU NHLBI NIH HHS [T32 HL007208, 5R01 HL 49579, 5R01 HL 63206-04]; NIDDK NIH HHS [5R01 DK 55383] NR 50 TC 138 Z9 139 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 16 PY 2003 VL 13 IS 24 BP 2138 EP 2147 DI 10.1016/j.cub.2003.11.055 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 756GB UT WOS:000187456500020 PM 14680629 ER PT J AU Hadjikhani, N de Gelder, B AF Hadjikhani, N de Gelder, B TI Seeing fearful body expressions activates the fusiform cortex and amygdala SO CURRENT BIOLOGY LA English DT Article ID EMOTIONAL FACIAL EXPRESSIONS; IMPAIRED RECOGNITION; PARKINSONS-DISEASE; BIOLOGICAL MOTION; VISUAL-CORTEX; PERCEPTION; FACES; SENSITIVITY; DEPRESSION; SYSTEMS AB Darwin's evolutionary approach to organisms' emotional states attributes a prominent role to expressions of emotion in whole-body actions. Researchers in social psychology [1, 2] and human development [3] have long emphasized the fact that emotional states are expressed through body movement, but cognitive neuroscientists have almost exclusively considered isolated facial expressions (for review, see [4]). Here we used high-field fMRI to determine the underlying neural mechanisms of perception of body expression of emotion. Subjects were presented with short blocks of body expressions of fear alternating with short blocks of emotionally neutral meaningful body gestures. All images had internal facial features blurred out to avoid confounds due to a face or facial expression. We show that exposure to body expressions of fear, as opposed to neutral body postures, activates the fusiform gyrus and the amygdala. The fact that these two areas have previously been associated with the processing of faces and facial expressions [5-8] suggests synergies between facial and body-action expressions of emotion. Our findings open a new area of investigation of the role of body expressions of emotion in adaptive behavior as well as the relation between processes of emotion recognition in the face and in the body. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. RP Hadjikhani, N (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RI Hadjikhani, Nouchine/C-2018-2008; Frank, David/E-8213-2012 OI Hadjikhani, Nouchine/0000-0003-4075-3106; FU NCRR NIH HHS [P41 RR 14075]; NINDS NIH HHS [R01 NS 44824-01] NR 38 TC 146 Z9 150 U1 2 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 16 PY 2003 VL 13 IS 24 BP 2201 EP 2205 DI 10.1016/j.cub.2003.11.049 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 756GB UT WOS:000187456500029 PM 14680638 ER PT J AU Van Remmen, H Ikeno, Y Hamilton, M Pahlavani, M Wolf, N Thorpe, SR Alderson, NL Baynes, JW Epstein, CJ Huang, TT Nelson, J Strong, R Richardson, A AF Van Remmen, H Ikeno, Y Hamilton, M Pahlavani, M Wolf, N Thorpe, SR Alderson, NL Baynes, JW Epstein, CJ Huang, TT Nelson, J Strong, R Richardson, A TI Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging SO PHYSIOLOGICAL GENOMICS LA English DT Article DE oxidative damage; mitochondria ID MANGANESE SUPEROXIDE-DISMUTASE; MITOCHONDRIAL TARGETING SEQUENCE; AGE-RELATED CATARACT; DIETARY RESTRICTION; OXIDATIVE DAMAGE; CALORIC RESTRICTION; TRANSGENIC MICE; KNOCKOUT MICE; C57BL/6 MICE; SPAN AB Mice heterozygous for the Sod2 gene (Sod2(+/)- mice) have been used to study the phenotype of life- long reduced Mn- superoxide dismutase ( MnSOD) activity. The Sod2(+/-) mice have reduced MnSOD activity ( similar to 50%) in all tissues throughout life. The Sod2(+/-) mice have increased oxidative damage as demonstrated by significantly elevated levels of 8- oxo- 2- deoxyguanosine ( 8oxodG) in nuclear DNA in all tissues of Sod2(+/-) mice studied. The levels of 8oxodG in nuclear DNA increased with age in all tissues of Sod2(+/-) and wild- type ( WT) mice, and at 26 mo of age, the levels of 8oxodG in nuclear DNA were significantly higher ( from 15% in heart to over 60% in liver) in the Sod2(+/-) mice compared with WT mice. The level of 8oxodG was also higher in mitochondrial DNA isolated from liver and brain in Sod2(+/-) mice compared with WT mice. The increased oxidative damage to DNA in the Sod2(+/-) mice is associated with a 100% increase in tumor incidence ( the number of mice with tumors) in old Sod2(+/-) mice compared with the old WT mice. However, the life spans ( mean and maximum survival) of the Sod2(+/-) and WT mice were identical. In addition, biomarkers of aging, such as cataract formation, immune response, and formation of glycoxidation products carboxymethyl lysine and pentosidine in skin collagen changed with age to the same extent in both WT and Sod2(+/-) mice. Thus life- long reduction of MnSOD activity leads to increased levels of oxidative damage to DNA and increased cancer incidence but does not appear to affect aging. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Barshop Ctr Longev Studies, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Res Serv, San Antonio, TX 78284 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Richardson, A (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,MSC 7762, San Antonio, TX 78229 USA. FU NEI NIH HHS [R01-EY-11733]; NIA NIH HHS [R01-AG-015908, 1P30-AG-13319, P01-AG-020591, P01-AG-19316, R01-AG-16998]; NIDDK NIH HHS [R01-DK-19971] NR 50 TC 419 Z9 432 U1 2 U2 15 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC 16 PY 2003 VL 16 IS 1 BP 29 EP 37 DI 10.1152/physiolgenomics.00122.2003 PG 9 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 754PW UT WOS:000187327300005 PM 14679299 ER PT J AU Achenbach, S Nomayo, A Couturier, G Ropers, D Pohle, K Schlundt, C Schmermund, A Matarazzo, TJ Hoffmann, U Daniel, WG Killip, T AF Achenbach, S Nomayo, A Couturier, G Ropers, D Pohle, K Schlundt, C Schmermund, A Matarazzo, TJ Hoffmann, U Daniel, WG Killip, T TI Relation between coronary calcium and 10-year risk scores in primary prevention patients SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; HEART-DISEASE; ARTERY-DISEASE; EVENTS; ADULTS; PREDICTION; AGE AB d=In 380 patients, coronary calcifications were quantified by electron beam tomography and compared with the predicted 10-year cardiovascular event risk determined by the Framingham equation, Adult Treatment Panel III tables' and the PROCAM algorithm. The correlation between the amount of calcium and the predicted cardiac event risk was low (correlation coefficient range 0.19 to 0.28). The assessment of coronary calcium may thus potentially yield information that is additive. to the analysis of traditional risk factors. (C) 2003 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, CIMIT Vulnerable Plaque Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, Erlangen, Germany. Beth Israel Hosp, Continuum Heart Inst, New York, NY USA. Univ Essen Gesamthsch, Dept Cardiol, Essen, Germany. RP Achenbach, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, CIMIT Vulnerable Plaque Program, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 19 TC 20 Z9 20 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2003 VL 92 IS 12 BP 1471 EP 1475 DI 10.1016/j.amjcard.2003.08.064 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 753ZD UT WOS:000187277500023 PM 14675591 ER PT J AU Kanaya, AM Vittinghoff, E Shlipak, MG Resnick, HE Visser, M Grady, D Barrett-Connor, E AF Kanaya, AM Vittinghoff, E Shlipak, MG Resnick, HE Visser, M Grady, D Barrett-Connor, E TI Association of total and central obesity with mortality in postmenopausal women with coronary heart disease SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body composition; body mass index; body weight; coronary disease; mortality; obesity ID BODY-MASS INDEX; CARDIOVASCULAR RISK-FACTORS; ESTROGEN PLUS PROGESTIN; ALL-CAUSE MORTALITY; FOLLOW-UP; FAT DISTRIBUTION; WEIGHT CHANGE; ESTROGEN/PROGESTIN REPLACEMENT; WAIST CIRCUMFERENCE; VISCERAL ADIPOSITY AB Overweight and abdominal obesity increase mortality risk, although the risk may be mediated by traditional cardiac risk factors. The authors assessed the association of baseline measures, change in overall body weight and abdominal obesity (waist circumference), and weight and waist circumference cycling with total mortality among postmenopausal women with known heart disease. They used data from 2,739 US women who participated in the Heart and Estrogen/progestin Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women died. In adjusted Cox models that included either baseline waist circumference or body mass index (BMI), each was associated with mortality. However, after further adjustment for diabetes, hypertension, and lipoproteins, these associations disappeared. In models including both waist circumference and BMI, larger waist circumference (hazard ratio = 1.40 per standard deviation, 95% confidence interval: 1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio = 0.81 per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with decreased risk of total mortality, independent of cardiac risk factors. Weight and waist circumference cycling were not associated with mortality. Results show that both BMI and waist circumference are associated with mortality among postmenopausal women with established heart disease, but waist circumference may be more important than BMI, and their effects may be largely mediated by other cardiac risk factors. C1 Womens Hlth Clin Res Ctr, San Francisco, CA 94115 USA. Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. MedStar Res Inst, Washington, DC USA. VU Univ Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. RP Kanaya, AM (reprint author), Womens Hlth Clin Res Ctr, 1635 Divisadero St,Suite 600, San Francisco, CA 94115 USA. FU NIAMS NIH HHS [5 K12 AR47659] NR 57 TC 67 Z9 68 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2003 VL 158 IS 12 BP 1161 EP 1170 DI 10.1093/aje/kwg271 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 753DK UT WOS:000187216600006 PM 14652301 ER PT J AU Fan, VS Bryson, CL Curtis, JR Fihn, SD Bridevaux, PO McDonell, MB Au, DH AF Fan, VS Bryson, CL Curtis, JR Fihn, SD Bridevaux, PO McDonell, MB Au, DH TI Inhaled corticosteroids in chronic obstructive pulmonary disease and risk of death and hospitalization - Time-dependent analysis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE antiinflammatory agents; steroidal/therapeutic use; proportional hazards models; treatment outcome ID QUALITY-OF-LIFE; VETERANS-AFFAIRS; FLUTICASONE PROPIONATE; PHARMACY RECORDS; MORTALITY; VALIDATION; BUDESONIDE; DISTANCE; MODERATE; SURVIVAL AB Observational studies of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD) have shown improved survival whereas randomized trials have not. It has been suggested that this difference may be due to immortal time bias. To investigate this further, we performed a prospective cohort study of patients with COPD, using time-dependent methods to determine whether use of inhaled corticosteroids more than 80% of the time reduced the risk of all-cause mortality and COPD exacerbations. Of 8,033 patients, 2,686 (33%) received inhaled corticosteroids. We did not find a significant reduction in mortality for average inhaled steroid use at either low (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.69-1.33) or medium/high dose (HR, 0.86; 95% CI, 0.67-1.10). Similarly, recent inhaled corticosteroid use was not associated with a reduction in mortality at low (HR, 0.80; 95% CI, 0.60-1.07) or medium/high doses (HR, 0.88; 95% CI, 0.71-1.09). There was no association between inhaled corticosteroid use and hospitalizations or exacerbations due to COPD. Patients using medium/high-dose inhaled corticosteroids did not have a significantly lower risk of COPD hospitalizations (HR, 0.85; 95% CI, 0.64-1.13) or COPD exacerbations (HR, 1.13; 95% CI, 0.94-1.36). In a time-dependent study of outpatients with COPD, adherence to inhaled corticosteroid use was not associated with a decreased risk of mortality or exacerbations. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA USA. RP Fan, VS (reprint author), Hlth Serv Res & Dev 152, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 29 TC 53 Z9 55 U1 1 U2 1 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 DEC 15 PY 2003 VL 168 IS 12 BP 1488 EP 1494 DI 10.1164/rccm.200301-019OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 753DB UT WOS:000187215700020 PM 14525798 ER PT J AU Shao, L Kasanov, J Hornicek, FJ Morii, T Fondren, G Weissbach, L AF Shao, L Kasanov, J Hornicek, FJ Morii, T Fondren, G Weissbach, L TI Ecteinascidin-743 drug resistance in sarcoma cells: transcriptional and cellular alterations SO BIOCHEMICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the American-Association-for-Cancer-Research CY APR 06-10, 2002 CL SAN FRANCISCO, CALIFORNIA SP Amer Assoc Canc Res DE ecteinascidin-743; chondrosarcoma; drug resistance; chemotherapy; collagen; extracellular matrix ID GROWTH-FACTOR-BETA; MATRIX GENE-EXPRESSION; ASCORBIC-ACID 2-PHOSPHATE; HEPATIC STELLATE CELLS; FOCAL ADHESION KINASE; BREAST-CANCER CELLS; HUMAN CHONDROSARCOMA; EXTRACELLULAR-MATRIX; MULTIDRUG-RESISTANCE; I COLLAGEN AB A human chondrosarcoma cell line, CS-1, was treated successively with increasing concentrations of the marine chemotherapeutic Ecteinascidin-743 (ET-743), yielding a variant cell line displaying a significant degree of resistance to the cytotoxic action of this drug. Various experiments were performed to discern molecular aberrations between the parent and resistant cell line, and also identify potential molecular markers indicative of drug resistance. Although no significant differences in the levels of membrane transporters such as P-glycoprotein or multidrug resistance protein 1 (MRP1) were detected, the cell migratory ability of the ET-743-resistant cell variant was reduced, as was its attachment capability to gelatin-coated cell culture dishes. Staining of the actin-containing cytoskeleton with fluorescent-labeled phalloidin revealed marked differences in the cytoskeleton architecture between the parent and ET-743-resistant CS-1 cell lines. Comparison of serum-free conditioned medium from both cell lines showed conspicuous differences in the levels of several proteins, including a quartet of high molecular weight proteins (greater than or equal to140 kDa). The protein sequences of two of these high molecular weight proteins, present at significantly higher concentrations in conditioned medium obtained from the parent cell line, corresponded to subunits of types I and IV collagen. Analysis of type I collagen alpha1 chain mRNA revealed a significantly lower level in the ET-743-resistant CS-1 cell line. Thus, prolonged exposure to ET-743 may cause changes in cell function through cytoskeleton rearrangement and/or modulation of collagen levels. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopead Res Labs, Boston, MA 02114 USA. RP Weissbach, L (reprint author), Harvard Univ, Sch Med, GRJ 1124,55 Fruit St, Boston, MA 02114 USA. NR 97 TC 22 Z9 24 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 15 PY 2003 VL 66 IS 12 BP 2381 EP 2395 DI 10.1016/j.bcp.2003.08.033 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 749KL UT WOS:000186919000012 PM 14637196 ER PT J AU Smoller, JW Rosenbaum, JF Biederman, J Kennedy, J Dai, D Racette, SR Laird, NM Kagan, J Snidman, N Hirshfeld-Becker, D Tsuang, MT Sklar, PB Slaugenhaupt, SA AF Smoller, JW Rosenbaum, JF Biederman, J Kennedy, J Dai, D Racette, SR Laird, NM Kagan, J Snidman, N Hirshfeld-Becker, D Tsuang, MT Sklar, PB Slaugenhaupt, SA TI Association of a genetic marker at the corticotropin-releasing hormone locus with behavioral inhibition SO BIOLOGICAL PSYCHIATRY LA English DT Article DE genetic; CRH; behavioral inhibition; temperament; anxiety; anxiety disorders ID TRANSMISSION/DISEQUILIBRIUM TEST; FEARFUL TEMPERAMENT; ANXIETY DISORDERS; SOCIAL ANXIETY; BRAIN ACTIVITY; CHILDHOOD; CHILDREN; LINKAGE; TESTS; DISEQUILIBRIUM AB Background: Behavioral inhibition to the unfamiliar (BI), a heritable temperamental profile involving an avoidant response to novel situations, may be an intermediate phenotype in the development of anxiety disorders. Corticotropin-releasing hormone (CRH) is a key mediator of the stress response through its effects on the hypothalamic-pituitary-adrenal axis and limbic brain systems. Transgenic mice overexpressing CRH exhibit BI-like behaviors, implicating this gene in the development of the phenotype. Methods: We genotyped a marker tightly linked to the CRH locus in 85 families of children who underwent laboratory-based behavioral assessments of BI and performed family-based association analyses. Results: We observed an association between an allele of the CRH-linked locus and BI (p = .015). Among offspring of parents with panic disorder, this association was particularly marked (p = .0009). We further demonstrate linkage disequilibrium between this marker and single nucleotide polymorphisms encompassing the CRH gene. Conclusions: These results are consistent with the possibility that variants in the CRH gene are associated with anxiety proneness. C1 Harvard Univ, Sch Publ Hlth, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Harvard Inst Human Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Mol Neurogenet Unit, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Brockton W Roxbury Vet Affairs Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, 15 Parkman St,WAC-812, Boston, MA 02114 USA. FU NIMH NIH HHS [K-08 MH01770-02] NR 36 TC 83 Z9 88 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2003 VL 54 IS 12 BP 1376 EP 1381 DI 10.1016/S0006-3223(03)00598-5 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 753UW UT WOS:000187249800010 PM 14675801 ER PT J AU Davies, FE Dring, AM Li, C Rawstron, AC Shammas, MA O'Connor, SM Fenton, JAL Hideshima, T Chauhan, D Tai, IT Robinson, E Auclair, D Rees, K Gonzalez, D Ashcroft, AJ Dasgupta, R Mitsiades, C Mitsiades, N Chen, LB Wong, WH Munshi, NC Morgan, GJ Anderson, KC AF Davies, FE Dring, AM Li, C Rawstron, AC Shammas, MA O'Connor, SM Fenton, JAL Hideshima, T Chauhan, D Tai, IT Robinson, E Auclair, D Rees, K Gonzalez, D Ashcroft, AJ Dasgupta, R Mitsiades, C Mitsiades, N Chen, LB Wong, WH Munshi, NC Morgan, GJ Anderson, KC TI Insights into the multistep transformation of MGUS to myeloma using microarray expression analysis SO BLOOD LA English DT Article ID PLASMA-CELL DIFFERENTIATION; TRANSCRIPTION FACTOR XBP-1; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; OLIGONUCLEOTIDE ARRAYS; MONOCLONAL GAMMOPATHY; GENES; TRANSLOCATIONS; IDENTIFICATION; LYMPHOMA AB To define specific pathways important in the multistep transformation process of normal plasma cells (PCs) to monoclonal gammopathy of uncertain significance (MGUS) and multiple myeloma (MM), we have applied microarray analysis to PCs from 5 healthy donors (N), 7 patients with MGUS, and 24 patients with newly diagnosed MM. Unsupervised hierarchical clustering using 125 genes with a large variation across all samples defined 2 groups: N and MGUS/MM. Supervised analysis identified 263 genes differentially expressed between N and MGUS and 380 genes differentially expressed between N and MM, 197 of which were also differentially regulated between N and MGUS. Only 74 genes were differentially expressed between MGUS and MM samples, indicating that the differences between MGUS and MM are smaller than those between N and MM or N and MGUS. Differentially expressed genes included oncogenes/tumor-suppressor genes (LAF4, RB1, and disabled homolog 2), cell-signaling genes (RAS family members, B-cell signaling and NF-kappaB genes), DNA-binding and transcription-factor genes (XBP1, zinc finger proteins, forkhead box, and ring finger proteins), and developmental genes (WNT and SHH pathways). Understanding the molecular pathogenesis of MM by gene expression profiling has demonstrated sequential genetic changes from N to malignant PCs and highlighted important pathways involved in the transformation of MGUS to MM. C1 Univ Leeds, Sch Med, Acad Unit Heamatol & Oncol, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. RP Davies, FE (reprint author), Univ Leeds, Sch Med, Acad Unit Heamatol & Oncol, Algernon Firth Bldg, Leeds LS2 9JT, W Yorkshire, England. RI Tai, Isabella/E-8035-2012; Tang, Macy/B-9798-2014; OI Rawstron, Andy/0000-0003-0798-9790 FU NCI NIH HHS [CA78373, CA96470]; NHGRI NIH HHS [HG02341]; PHS HHS [50947] NR 27 TC 155 Z9 156 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 DEC 15 PY 2003 VL 102 IS 13 BP 4504 EP 4511 DI 10.1182/blood-2003-01-0016 PG 8 WC Hematology SC Hematology GA 751ZT UT WOS:000187122000048 PM 12947006 ER PT J AU Li, AH Zhou, JB Zuckerman, D Rue, M Dalton, V Lyons, C Silverman, LB Sallan, SE Gribben, JG AF Li, AH Zhou, JB Zuckerman, D Rue, M Dalton, V Lyons, C Silverman, LB Sallan, SE Gribben, JG TI Sequence analysis of clonal immunoglobulin and T-cell receptor gene rearrangements in children with acute lymphoblastic leukemia at diagnosis and at relapse: implications for pathogenesis and for the clinical utility of PCR-based methods of minimal residual disease detection SO BLOOD LA English DT Article ID POLYMERASE-CHAIN-REACTION; IG HEAVY-CHAIN; B-PRECURSOR; JUNCTIONAL DIVERSITY; FLOW-CYTOMETRY; BONE-MARROW; CHILDHOOD; EVOLUTION; QUANTIFICATION; HETEROGENEITY AB Immunoglobulin (Ig) and T-cell receptor (TCR) gene rearrangements provide clonal markers useful for diagnosis and measurement of minimal residual disease (MRD) in acute lymphoblastic leukemia (ALL). We analyzed the sequences of Ig and TCR gene rearrangements obtained at presentation and relapse in 41 children with ALL to study clonal stability, which has important implications for monitoring MRD, during the course of the disease. In 42%, all original Ig and/or TCR sequences were conserved. In 24%, one original sequence was preserved but the other lost, and in 14% the original sequences were conserved with new sequences identified at relapse. In 20% only new sequences were found at relapse. Using primers designed from the novel relapse sequences, the relapse clone could be identified as subdominant clones in the diagnostic sample in 8 of 14 patients. Alteration of these clonal gene rearrangements is a common feature in childhood ALL. MRD detection should include multiple gene targets to minimize false-negative samples or, include also multicolor flow cytometry. In some cases the leukemic progenitor cell might arise earlier in lineage before D(H)J(H) recombination but retain the capacity to further differentiate into cells capable of altering the pattern of Ig and/or TCR rearrangements. C1 Dana Farber Canc Inst, Dept Med Oncol Biostat & Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Hematol Oncol,Dept Med, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Rue, Montserrat/B-5663-2009 OI Rue, Montserrat/0000-0002-7862-9365 FU NCI NIH HHS [P01CA68484] NR 50 TC 45 Z9 47 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2003 VL 102 IS 13 BP 4520 EP 4526 DI 10.1182/blood-2003-05-1455 PG 7 WC Hematology SC Hematology GA 751ZT UT WOS:000187122000050 PM 12946997 ER PT J AU Hirano, N Butler, MO von Bergwelt-Baildon, MS Maecker, B Schultze, JL O'Connor, KC Schur, PH Kojima, S Guinan, EC Nadler, LM AF Hirano, N Butler, MO von Bergwelt-Baildon, MS Maecker, B Schultze, JL O'Connor, KC Schur, PH Kojima, S Guinan, EC Nadler, LM TI Autoantibodies frequently detected in patients with aplastic anemia SO BLOOD LA English DT Article ID HUMAN TUMOR-ANTIGENS; BONE-MARROW FAILURE; T-CELL RECOGNITION; H-Y-ANTIGEN; GENE-EXPRESSION; INTERFERON-GAMMA; ANTITHYMOCYTE GLOBULIN; STEM/PROGENITOR CELLS; LYMPHOCYTES-T; IDENTIFICATION AB Although accumulating evidence strongly suggests that aplastic anemia (AA) is a T cell-mediated autoimmune disease, no target antigens have yet been described for AA. In autoimmune diseases, target autoantigens frequently induce not only cellular T-cell responses but also humoral B-cell responses. We hypothesized that the presence of antigen-specific autoantibodies could be used as a "surrogate marker" for the identification of target T-cell autoantigens in AA patients. We screened a human fetal liver library for serologic reactivity against hematopoietic stem/progenitor cell antigens and isolated 32 genes. In 7 of 18 AA patients, an immunoglobulin G (IgG) antibody response was detected to one of the genes, kinectin, which is expressed in all hematopoietic cell lineages tested including CD34(+) cells. No response to kinectin was detected in healthy volunteers, multiply transfused non-AA patients, or patients with other autoimmune diseases. Epitope mapping of IgG autoantibodies against kinectin revealed that the responses to several of the epitopes were shared by different AA patients. Moreover, CD8(+) cytotoxic T cells raised against kinectin-derived peptides suppressed the colony formation of granulocyte macrophage colony-forming units (CFU-GMs) in an HLA class I-restricted fashion. These results suggest that kinectin may be a candidate autoantigen that is involved in the pathophysiology of AA. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Lab Mol Immunol, Ctr Neurol Dis, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Nagoya Univ, Dept Pediat, Nagoya, Aichi, Japan. RP Hirano, N (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Kojima, Seiji/I-1601-2012; Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 FU NCI NIH HHS [K08-CA-87720, P01-CA-66996, P01-CA-78378]; NHLBI NIH HHS [P50-HL-54785]; NIAID NIH HHS [P01-AI-41584] NR 50 TC 66 Z9 81 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2003 VL 102 IS 13 BP 4567 EP 4575 DI 10.1182/blood-2002-11-3409 PG 9 WC Hematology SC Hematology GA 751ZT UT WOS:000187122000057 PM 12947009 ER PT J AU Oh, WK Halabi, S Kelly, WK Werner, C Godley, PA Vogelzang, NJ Small, EJ AF Oh, WK Halabi, S Kelly, WK Werner, C Godley, PA Vogelzang, NJ Small, EJ CA Cncr Leukemia Grp B TI A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma - Cancer and leukemia group B 99813 SO CANCER LA English DT Article DE hormone-refractory disease; progressive disease; chemotherapy; growth factor ID ONCOLOGY-GROUP; TRIAL; CHEMOTHERAPY; MITOXANTRONE; PHOSPHATE; HYDROCORTISONE; COMBINATION; PREDNISONE; GUIDELINES; MANAGEMENT AB BACKGROUND. The authors determined the safety and efficacy of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor (G-CSF) support in patients with hormone-refractory prostate carcinoma. METHODS. in the current multicenter, cooperative group study, patients with advanced prostate carcinoma whose disease progressed despite androgen deprivation therapy were treated with a combination of oral estramustine(240 mg three times per day for 5 days), 70 mg/m(2) of docetaxel, and carboplatin at a dose of (area under the curve) 5. G-CSF was used to minimize the neutropenia associated with this regimen. Each cycle was repeated every 21 days. RESULTS. Forty patients were treated with a median of 7 cycles of therapy. Of the 34 evaluable patients with elevated pretreatment prostate-specific antigen (PSA) levels, 23 (68%) had a greater than or equal to 50% decline in PSA and 20 (59%) had a greater than or equal to 75% decline. Twenty-one patients had measurable disease, with 1 complete response (5%) and 10 partial responses (47%), for an overall measurable response rate of 52% (95% confidence interval [95% CI], 30-74%). The most common Grade 3 or Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria) included neutropenia in 23% of patients, thrombocytopenia in 13%, and fatigue in 13%. Febrile neutropenia occurred in 1 patient (3%). The overall median time to disease progression was 8.1 months (95% CI, 6-10 months) and the overall survival period was 19 months (95% CI, 13-26 months). CONCLUSIONS. The combination of estramustine, docetaxel, and carboplatin with G-CSF support was found to have significant clinical activity with an acceptable toxicity profile in patients with progressive hormone-refractory prostate carcinoma. (C) 2003 American Cancer Society. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. CALGB Stat Off, Durham, NC USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Univ N Carolina, Div Hematol Oncol, Chapel Hill, NC USA. Univ Chicago, Med Ctr, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St,D1230, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU NCI NIH HHS [CA60138, CA04326, CA32291, CA33601, CA41287, CA47559, CA77440, CA77651, CA77658] NR 26 TC 60 Z9 61 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 DEC 15 PY 2003 VL 98 IS 12 BP 2592 EP 2598 DI 10.1002/cncr.11829 PG 7 WC Oncology SC Oncology GA 750UZ UT WOS:000187018000008 PM 14669278 ER PT J AU Chavez-Reyes, A Parant, JM Amelse, LL Luna, RMD Korsmeyer, SJ Lozano, G AF Chavez-Reyes, A Parant, JM Amelse, LL Luna, RMD Korsmeyer, SJ Lozano, G TI Switching mechanisms of cell death in mdm2- and mdm4-null mice by deletion of p53 downstream targets SO CANCER RESEARCH LA English DT Article ID HUMAN-MALIGNANT GLIOMAS; TUMOR-SUPPRESSOR P53; WILD-TYPE P53; IN-VIVO; EMBRYONIC LETHALITY; CYCLE ARREST; MDM2-DEFICIENT MICE; POTENTIAL MEDIATOR; GENE AMPLIFICATION; MDM2 GENE AB The p53 tumor suppressor ensures maintenance of genome integrity by initiating either apoptosis or cell cycle arrest in response to DNA damage. Deletion of either mdm2 or mdm4 genes, which encode p53 inhibitors, results in embryonic lethality. The lethal phenotypes are rescued in the absence of p53, which indicates that increased activity of p53 is the cause of lethality in the mdm2- and mdm4-null embryos. Here we show that mdm2-null embryos die because of apoptosis initiated at 3.5 days postcoitum (dpc). Partial rescue of mdm2-null embryos by deletion of bax allows survival to 6.5 dpc and alters the mechanism of death from apoptosis to cell cycle arrest, indicating that bax is a critical component of the p53 pathway in early embryogenesis. The death of mdm4-null embryos is due to p53-initiated cell cycle arrest at 7.5 dpc. Deletion of p21(p21(waf1/cip1)), a p53 downstream target partially responsible for cell cycle arrest, does not rescue this phenotype; however, deletion of p21 alters the mechanism of cell death from lack of proliferation to apoptosis. Thus, in both examples, deletion of a p53 downstream target gene allows p53 to redirect its efforts, highlighting a high degree of plasticity in p53 function. C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Univ Autonoma Nuevo Leon, Sch Biol Sci, Dept Microbiol & Immunol, Monterrey, Mexico. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Lozano, G (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA47296, CA16672] NR 53 TC 50 Z9 54 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2003 VL 63 IS 24 BP 8664 EP 8669 PG 6 WC Oncology SC Oncology GA 757UR UT WOS:000187580300016 PM 14695178 ER PT J AU Abdollahi, A Lipson, KE Sckell, A Zieher, H Klenke, F Poerschke, D Roth, A Han, XH Krix, M Bischof, M Hahnfeldt, P Grone, HJ Debus, J Hlatky, L Huber, PE AF Abdollahi, A Lipson, KE Sckell, A Zieher, H Klenke, F Poerschke, D Roth, A Han, XH Krix, M Bischof, M Hahnfeldt, P Grone, HJ Debus, J Hlatky, L Huber, PE TI Combined therapy with direct and indirect angiogenesis inhibition results in enhanced antiangiogenic and antitumor effects SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECOMBINANT HUMAN ENDOSTATIN; CELL LUNG-CANCER; ADVANCED SOLID TUMORS; PHASE-I; FACTOR RECEPTOR; CLINICAL-TRIAL; CARCINOMA; COMBINATION; ANGIOSTATIN AB The multifaceted nature of the angiogenic process in malignant neoplasms suggests that protocols that combine antiangiogenic agents may be more effective than single-agent therapies. However it is unclear which combination of agents would be most efficacious and will have the highest degree of synergistic activity while maintaining low overall toxicity. Here we investigate the concept of combining a "direct" angiogenesis inhibitor (endostatin) with an "indirect" antiangiogenic compound [SU5416, a vascular endothelial growth factor receptor 2 (VEGFR2) receptor tyrosine kinase (RTK) inhibitor]. These angiogenic agents were more effective in combination than when used alone in vitro (endothelial cell proliferation, survival, migration/invasion, and tube formation tests) and in vivo. The combination of SU5416 and low-dose endostatin further reduced tumor growth versus monotherapy in human prostate (M), lung (A459), and glioma (U87) xenograft models, and reduced functional microvessel density, tumor microcirculation, and blood perfusion as detected by intravital microscopy and contrast-enhanced Doppler ultrasound. One plausible explanation for the efficacious combination could be that, whereas SU5416 specifically inhibits vascular endothelial growth factor signaling, low-dose endostatin is able to inhibit a broader spectrum of diverse angiogenic pathways directly in the endothelium. The direct antiangiogenic agent might be able to suppress alternative angiogenic pathways up-regulated by the tumor in response to the indirect, specific pathway inhibition. For future clinical evaluation of the concept, a variety of agents with similar mechanistic properties could be tested. C1 German Canc Res Ctr, Dept Radiat Oncol, D-69120 Heidelberg, Germany. German Canc Res Ctr, Dept Radiol, D-69120 Heidelberg, Germany. German Canc Res Ctr, Dept Pathol, D-69120 Heidelberg, Germany. SUGEN Inc, San Francisco, CA USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Heidelberg, Sch Med, Dept Orthoped, Heidelberg, Germany. Univ Heidelberg, Sch Med, Dept Radiat Oncol, Heidelberg, Germany. RP Huber, PE (reprint author), German Canc Res Ctr, Dept Radiat Oncol, 280 Neuenheimer Feld, D-69120 Heidelberg, Germany. OI Sckell, Axel/0000-0002-9992-0784 NR 48 TC 113 Z9 118 U1 0 U2 5 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 DEC 15 PY 2003 VL 63 IS 24 BP 8890 EP 8898 PG 9 WC Oncology SC Oncology GA 757UR UT WOS:000187580300044 PM 14695206 ER PT J AU Nasraway, SA Shorr, AF Kuter, DJ O'Grady, N Le, VH Cammarata, SK AF Nasraway, SA Shorr, AF Kuter, DJ O'Grady, N Le, VH Cammarata, SK TI Linezolid does not increase the risk of thrombocytopenia in patients with nosocomial pneumonia: Comparative analysis of linezolid and vancomycin use SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE-UNIT; DRUG-INDUCED THROMBOCYTOPENIA; CRITICALLY ILL PATIENTS; DOUBLE-BLIND; MULTICENTER; EXPERIENCE AB Reports from uncontrolled studies suggest that linezolid is associated with rates of thrombocytopenia higher than those reported in clinical studies. We assessed the risk of thrombocytopenia in 686 patients with nosocomial pneumonia who received linezolid or vancomycin for greater than or equal to 5 days in 2 randomized, double- blind studies and for whom follow- up platelet counts had been measured. New- onset thrombocytopenia ( platelet count of < 150 x 10(9) platelets/ L) occurred in 19 ( 6.4%) of 295 linezolid recipients and 22 ( 7.7%) of 285 vancomycin recipients with baseline platelet counts of &GE; 150 x 10(9) platelets/ L; severe thrombocytopenia (platelet count of < 50 x 10(9) platelets/ L) occurred in only 1 patient in each group. Platelet counts decreased to less than the baseline level in 4 ( 6.6%) of 61 linezolid recipients and 5 ( 11.1%) of 45 vancomycin recipients who had baseline counts of < 150 x 10(9) platelets/ L. No patient had a decrease to < 20 x 10(9) platelets/ L. There were no statistically significant differences between groups in these or any other platelet assessments. Clinically significant thrombocytopenia was uncommon in our analysis, and linezolid was not associated with a greater risk of thrombocytopenia in seriously ill patients than was vancomycin. C1 Tufts Univ, Tufts New England Med Ctr, Sch Med, Dept Surg,Div Surg Crit Care, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Massachusetts Gen Hosp Canc Ctr,Hematol Div, Boston, MA USA. Walter Reed Army Med Ctr, Pulm & Crit Care Med Serv, Washington, DC 20307 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Pharmacia, Clin Biostat, Peapack, NJ USA. Pharmacia, Infect Dis Clin Res, Peapack, NJ USA. RP Nasraway, SA (reprint author), Tufts Univ, Tufts New England Med Ctr, Sch Med, Dept Surg,Div Surg Crit Care, 750 Washington St,NEMC Box 4630, Boston, MA 02111 USA. NR 23 TC 47 Z9 55 U1 0 U2 0 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 DEC 15 PY 2003 VL 37 IS 12 BP 1609 EP 1616 DI 10.1086/379327 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300015 PM 14689341 ER PT J AU Mortensen, EM Kapoor, WN Chang, CCH Fine, MJ AF Mortensen, EM Kapoor, WN Chang, CCH Fine, MJ TI Assessment of mortality after long-term follow-up of patients with community-acquired pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID NATIONAL DEATH INDEX; OLD MANS FRIEND; UNITED-STATES; PROGNOSIS; VALIDATION; RESIDUALS; OUTCOMES; SURVIVAL; COHORT; CARE AB Although studies have assessed short- term mortality among patients with community- acquired pneumonia, there is limited data on prognosis and risk factors that affect long- term mortality. The mortality among patients enrolled at 4 sites of the Pneumonia Patient Outcome Research Team cohort study who survived at least 90 days after presentation to the hospital was compared with that among age- matched control subjects. Overall, 1419 of 1555 patients survived for >90 days, with a mean follow- up period of 5.9 years. There was significantly higher long- term mortality among patients with pneumonia than among age- matched controls. Factors significantly associated with long- term mortality were age ( stratified by decade), do- not- resuscitate status, poor nutritional status, pleural effusion, glucocorticoid use, nursing home residence, high school graduation level or less, male sex, preexisting comorbid illnesses, and the lack of feverishness. This study demonstrates that there is significantly higher long- term mortality among patients with pneumonia than among age- matched controls and that long- term mortality largely is not affected by acute physiologic derangements. C1 Univ Pittsburgh, Dept Med, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Vet Affairs Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Mortensen, EM (reprint author), UTHSCSA, ALMD, VERDICT, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. OI Mortensen, Eric/0000-0002-3880-5563 FU AHRQ HHS [F32 HS00135, R01HSO6468] NR 32 TC 86 Z9 88 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 DEC 15 PY 2003 VL 37 IS 12 BP 1617 EP 1624 DI 10.1086/379712 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300016 PM 14689342 ER PT J AU Gandhi, RT Wurcel, A Rosenberg, ES Johnston, MN Hellmann, N Bates, M Hirsch, MS Walker, BD AF Gandhi, RT Wurcel, A Rosenberg, ES Johnston, MN Hellmann, N Bates, M Hirsch, MS Walker, BD TI Progressive reversion of human immunodeficiency virus type 1 resistance mutations in vivo after transmission of a multiply drug-resistant virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-1; FITNESS; SUSCEPTIBILITY; TRANSCRIPTASE; INFECTION; THERAPY; VITRO; INTERRUPTION; MORTALITY; GENOTYPE AB Evolution and transmission of multiply drug- resistant human immunodeficiency virus type 1 ( HIV- 1) may limit therapeutic options as global treatment efforts expand. However, the stability of these mutants in the absence of drug selection pressure is not known. We performed a longitudinal analysis of plasma virus from a person who acquired HIV- 1 that contained multiple reverse transcriptase ( RT) and protease ( PR) mutations. In the absence of therapy, 5 of 12 drug resistance mutations reverted in a stepwise fashion to wild type over the course of 52 weeks. Reversion of the M184V mutation alone did not change viral replicative capacity ( RC), but it led to enhanced resistance to zidovudine and tenofovir. However, reversions of a second RT mutation and 3 PR mutations were associated with an increase in viral RC, and this was temporally correlated with a marked decrease in CD4 cell number. This study demonstrates the gradual stepwise back- mutation of certain drug resistance mutations in vivo in the absence of ongoing drug selection pressure. Moreover, it suggests that, despite initially impaired viral fitness, a transmitted HIV- 1 isolate with multiple drug resistance mutations can evolve to develop increased RC and significant pathogenicity. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partner AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Div Aids, Sch Med, Boston, MA USA. ViroLogic, San Francisco, CA USA. RP Gandhi, RT (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, GRJ 504,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 93 Z9 95 U1 1 U2 3 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 DEC 15 PY 2003 VL 37 IS 12 BP 1693 EP 1698 DI 10.1086/379773 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300027 PM 14689353 ER PT J AU Pincus, JM Crosby, SS Losina, E King, ER LaBelle, C Freedberg, KA AF Pincus, JM Crosby, SS Losina, E King, ER LaBelle, C Freedberg, KA TI Acute human immunodeficiency virus infection in patients presenting to an urban urgent care center SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PRIMARY HIV-INFECTION; ANTIRETROVIRAL THERAPY; TYPE-1 INFECTION; DIAGNOSIS; MONONUCLEOSIS; ILLNESS; ROUTINE; CANCER; MODEL; TIME AB Acute infection with human immunodeficiency virus ( HIV) is often accompanied by a flu- like illness, and early identification and treatment may help control the infection and prevent transmission. We enrolled patients who presented to an urban urgent care center with any symptoms of a viral illness and any recent potential risk for HIV infection, and we tested them for acute HIV infection using enzyme- linked immunosorbent and RNA assays. Of 499 patients enrolled over a 1- year period, acute HIV infection was diagnosed in 5 ( 1.0%; 95% confidence interval [ CI], 0.1% - 1.9%), and chronic HIV infection was diagnosed in 6 ( 1.2%; 95% CI, 0.2% - 2.2%). There were no false- positive results of the RNA assay. No signs or symptoms reliably distinguished patients with acute HIV infection from those who were HIV uninfected. Given the importance of this diagnosis, testing for acute HIV infection using RNA and antibody assays should be offered to all patients in similar settings with viral symptoms and any risk factors for HIV infection. C1 Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med,Boston Med Ctr, Boston, MA 02118 USA. Boston Univ, Infect Dis Clin, Boston Med Ctr, Sch Med,Sect Community Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA USA. RP Pincus, JM (reprint author), Boston Univ, Infect Dis Clin, Boston Med Ctr, Sch Med,Sect Community Med, 1 Boston Med Ctr Pl,Dowling 1, Boston, MA 02118 USA. FU NIAID NIH HHS [K25 AI050436, K25 AI50436, P30 AI042851, P30 AI42851, R01 AI-42006, R01 AI042006, U 01 AI52403, U01 AI052403] NR 41 TC 45 Z9 45 U1 0 U2 0 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 DEC 15 PY 2003 VL 37 IS 12 BP 1699 EP 1704 DI 10.1086/379772 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VJ UT WOS:000186949300028 PM 14689354 ER PT J AU Metzger, DS Navaline, H AF Metzger, DS Navaline, H TI Human immunodeficiency virus prevention and the potential of drug abuse treatment SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on Bloodborne and Sexually Transmitted Infections among Intravenous Drug Users and Their Partners in the Western Hemisphere CY DEC 17-19, 2001 CL BUENOS AIRES, ARGENTINA SP Ctr AIDS & Other Med Consequences Drug Abuse, NIDA, NIH, US Dept HHS, Pan Amer Hlth Org, WHO Americas, Reg Off ID METHADONE-MAINTENANCE TREATMENT; OUT-OF-TREATMENT; RISK-REDUCTION; HIV SEROCONVERSION; FOLLOW-UP; USERS; AIDS; BEHAVIORS; INJECTORS AB Since first recognition of the scope of the acquired immunodeficiency syndrome epidemic among the drug-using community, substance abuse treatment has been viewed as playing an important role in preventing new infections. In the past 20 years, many studies have documented significantly lower rates of drug use, drug-related risk behaviors, and human immunodeficiency virus (HIV) infections among drug users who remain in treatment programs. There is also growing evidence that drug detoxification alone is insufficient to provide protection from HIV infection. These findings have important implications for users of cocaine and noninjection drugs, as well as heroin injectors. Despite strong evidence of effectiveness and widespread support for the important public health role of drug treatment, its impact has been compromised by limited availability and acceptability. The available data clearly establish drug abuse treatment as HIV prevention, yet without expansion of existing treatment programs and the continued development of treatments for addiction to cocaine and other widely used stimulants, its public health potential cannot be realized. C1 Univ Penn, Ctr Studies Addict, HIV Prevent Res Div, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Metzger, DS (reprint author), Univ Penn, Ctr Studies Addict, HIV Prevent Res Div, Vet Affairs Med Ctr, 3535 Market St,Rm 4001, Philadelphia, PA 19104 USA. NR 37 TC 37 Z9 39 U1 1 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2003 VL 37 SU 5 BP S451 EP S456 DI 10.1086/377548 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 749VL UT WOS:000186949600022 PM 14648463 ER PT J AU Aguirre, AJ Bardeesy, N Sinha, M Lopez, L Tuveson, DA Horner, J Redston, MS DePinho, RA AF Aguirre, AJ Bardeesy, N Sinha, M Lopez, L Tuveson, DA Horner, J Redston, MS DePinho, RA TI Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma SO GENES & DEVELOPMENT LA English DT Article DE pancreatic cancer; Ink4a/Arf; PanIN; metastasis; mouse model ID TUMOR-SUPPRESSOR GENE; EPIDERMAL-GROWTH-FACTOR; CELL-CYCLE ARREST; K-RAS MUTATIONS; TRANSGENIC MICE; INTRAEPITHELIAL NEOPLASIA; FACTOR RECEPTOR; IN-VIVO; TELOMERE DYSFUNCTION; ACINAR-CELLS AB Pancreatic ductal adenocarcinoma ranks among the most lethal of human malignancies. Here, we assess the cooperative interactions of two signature mutations in mice engineered to sustain pancreas-specific Cre-mediated activation of a mutant Kras allele (Kras(G12D)) and deletion of a conditional Ink4a/Arf tumor suppressor allele. The phenotypic impact of Kras(G12D) alone was limited primarily to the development of focal premalignant ductal lesions, termed pancreatic intraepithelial neoplasias (PanINs), whereas the sole inactivation of Ink4a/Arf failed to produce any neoplastic lesions in the pancreas. In combination, Kras(G12D) expression and Ink4a/Arf deficiency resulted in an earlier appearance, of PanIN lesions and these neoplasms progressed rapidly to highly invasive and metastatic cancers, resulting in death in all cases by 11 weeks. The evolution of these tumors bears striking resemblance to the human disease, possessing a proliferative stromal component and ductal lesions with a propensity to advance to a poorly differentiated state. These findings in the mouse provide experimental support for the widely accepted model of human pancreatic adenocarcinoma in which activated KRAS serves to initiate PanIN lesions, and the INK4A/ARF tumor suppressors function to constrain the malignant conversion of these PanIN lesions into lethal ductal adenocarcinoma. This faithful mouse model may permit the systematic analysis of genetic lesions implicated in the human disease and serve as a platform for the identification of early disease markers and for the efficient testing of novel therapies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Penn, Dept Med, Philadelphia, PA 19103 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19103 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19103 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 82 TC 497 Z9 510 U1 7 U2 31 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 DEC 15 PY 2003 VL 17 IS 24 BP 3112 EP 3126 DI 10.1101/gad.1158703 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 760GJ UT WOS:000187803000013 PM 14681207 ER PT J AU Qin, ZH Wang, YM Kegel, KB Kazantsev, A Apostol, BL Thompson, LM Yoder, J Aronin, N DiFiglia, M AF Qin, ZH Wang, YM Kegel, KB Kazantsev, A Apostol, BL Thompson, LM Yoder, J Aronin, N DiFiglia, M TI Autophagy regulates the processing of amino terminal huntingtin fragments SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; ISOLATED RAT HEPATOCYTES; CELL-DEATH; MUTANT HUNTINGTIN; CATHEPSIN-D; INTRACELLULAR PROTEIN; ALZHEIMERS-DISEASE; POLYGLUTAMINE TRACT; PARKINSONS-DISEASE; CASPASE CLEAVAGE AB The N-terminus of mutant huntingtin (htt) has a polyglutamine expansion and forms neuronal aggregates in the brain of Huntington's disease (HD) patients. Htt expression in vitro activates autophagy, but it is unclear whether autophagic/lysosomal pathways process htt, especially N-terminal htt fragments. We explored the role of autophagy in htt processing in three cell lines, clonal striatal cells, PC12 cells and rodent embryonic cells lacking cathepsin D. Blocking autophagy raised levels of exogenously expressed htt1-287 or 1-969, reduced cell viability and increased the number of cells bearing mutant htt aggregates. Stimulating autophagy promoted htt degradation, including breakdown of caspase cleaved N-terminal htt fragments. Htt expression increased levels of the lysosomal enzyme cathepsin D by an autophagy-dependent pathway. Cells without cathepsin D accumulated more N-terminal htt fragments and cells with cathepsin D were more efficient in degrading wt htt than mutant htt in vitro. These results suggest that autophagy plays a critical role in the degradation of N-terminal htt. Altered processing of mutant htt by autophagy and cathepsin D may contribute to HD pathogenesis. C1 Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. Univ Massachusetts, Med Ctr, Dept Med & Cell Biol, Worcester, MA 01655 USA. RP DiFiglia, M (reprint author), Massachusetts Gen Hosp, Lab Cellular Neurobiol, 16th St,Bldg 114,Rm 2125, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS13579, NS16367, NS38194] NR 66 TC 175 Z9 183 U1 2 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2003 VL 12 IS 24 BP 3231 EP 3244 DI 10.1093/hmg/ddg346 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 753GT UT WOS:000187224200004 PM 14570716 ER PT J AU Earle, CC Emanuel, EJ AF Earle, CC Emanuel, EJ TI Patterns of care studies: Creating "An environment of watchful concern" SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID QUALITY C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 12 TC 5 Z9 5 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 DEC 15 PY 2003 VL 21 IS 24 BP 4479 EP 4480 DI 10.1200/JCO.2003.09.979 PG 2 WC Oncology SC Oncology GA 755VN UT WOS:000187432300004 PM 14597747 ER PT J AU Nichols, KE Heath, JA Friedman, D Biegel, JA Ganguly, A Mauch, P Diller, L AF Nichols, KE Heath, JA Friedman, D Biegel, JA Ganguly, A Mauch, P Diller, L TI TP53, BRCA1, and BRCA2 tumor suppressor genes are not commonly mutated in survivors of Hodgkin's disease with second primary neoplasms SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTIPLE PRIMARY CANCERS; 2ND MALIGNANT NEOPLASMS; STRAND BREAK REPAIR; POLYMORPHIC VARIANTS; GERMLINE MUTATIONS; P53 MUTATIONS; RISK-FACTORS; FAMILIES; CONTRIBUTE; POPULATION AB Purpose: Despite recognition that second malignant neoplasms (SMNs) contribute significantly to mortality after the successful treatment of Hodgkin's disease (HD), little is known about the molecular events leading to secondary tumors. Factors contributing to second cancer risk include the carcinogenic effects of ionizing radiation and chemotherapy, in combination with possible host susceptibility. To clarify whether host genetic factors contribute to secondary tumorigenesis, we performed mutational analyses of the TP53, BRCA1, and BRCA2 tumor suppressor genes in a cohort of 44 HD patients developing one or more SMN. Patients and Methods: Family cancer histories and constitution 31 DNA samples were obtained from 44 HD patients with SMNs identified. Using DNA-based sequencing, we evaluated the TP53 gene in all 44 patients. Nineteen female patients developing one or more secondary breast cancer were also analyzed for mutations in the BRCA1 and BRCA2 breast cancer-susceptibility genes. Results: Nineteen patients (43%) had more than one SMN, and 12 patients (27%) had a positive family history of cancer. One of 44 patients tested for TP53 harbored a novel homozygous germline abnormality. One of 19 patients tested for BRCA2 carried a previously described heterozygous inactivating mutation. We identified no germline BRCA 1 mutations. Conclusion: Despite features suggestive of genetic predisposition, the TP53, BRCA1, and BRCA2 genes were not frequently mutated in this cohort of HD patients developing SMNs. Larger studies of these genes or investigations of other genes involved in cellular DNA damage response pathways may identify host genetic factors that contribute to secondary tumorigenesis. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Dept Pediat Oncol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Human Genet, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. Childrens Hosp & Med Ctr, Dept Pediat Hematol Oncol, Seattle, WA 98105 USA. RP Diller, L (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. NR 41 TC 16 Z9 19 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 DEC 15 PY 2003 VL 21 IS 24 BP 4505 EP 4509 DI 10.1200/JCO.2003.12.042 PG 5 WC Oncology SC Oncology GA 755VN UT WOS:000187432300009 PM 14673037 ER PT J AU Crivellari, D Price, K Gelber, RD Castiglione-Gertsch, M Rudenstam, CM Lindtner, J Fey, MF Senn, HJ Coates, AS Collins, J Goldhirsch, A AF Crivellari, D Price, K Gelber, RD Castiglione-Gertsch, M Rudenstam, CM Lindtner, J Fey, MF Senn, HJ Coates, AS Collins, J Goldhirsch, A TI Adjuvant endocrine therapy compared with no systemic therapy for elderly women with early breast cancer: 21-year results of international breast cancer study group trial IV SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FIRST-LINE THERAPY; RANDOMIZED TRIAL; POSTMENOPAUSAL WOMEN; ARTERIAL THROMBOSIS; TAMOXIFEN TREATMENT; COMPETING CAUSES; CLINICAL-TRIAL; PHASE-III; CHEMOTHERAPY; ANASTROZOLE AB Purpose: Increasing numbers of older women are affected by early breast cancer, because of prolonged life expectancy and the increasing incidence of breast cancer with age, The role of adjuvant therapy for this population is still a matter of debate. We reviewed the long-term outcome of a mature trial comparing endocrine treatment versus no adjuvant therapy in older women with node-positive breast cancer. Patients and Methods: From 1978 to 1981, 349 women 66 to 80 years of age with pathologically involved lymph nodes after total mastectomy and axillary clearance were randomly assigned to receive 12 months of adjuvant tamoxifen plus low-dose prednisone (p+T) or no adjuvant therapy. Three hundred twenty patients were eligible. Results: At 21 years' median follow-up, 1 year of p+T significantly prolonged disease-free survival (DFS; P =.003) and overall survival (P =.05; 15-year DFS, 10% +/- 3% v 19% +/- 3%; hazard ratio, 0.71; 95% Cl, 0.58 to 0.86). When comparing competing causes of failure (breast cancer recurrence and deaths before breast cancer recurrence), p+T was far superior in controlling, breast cancer recurrence (P =.0003), but the improvement was seen mainly in soft tissue sites. Conversely, patients in the p+T group were more likely to die before a breast cancer recurrence (P =.03). Conclusion: This trial demonstrates that significant treatment benefits continue to be observed in older patients treated for 1 year with p+T. Despite issues relating to competing causes of failure, older breast cancer patients can benefit from treatment and should be considered for trials of adjuvant systemic therapy. (C) 2003 by American Society of Clinical Oncology. C1 Ctr Riferimento Oncol, I-33081 Aviano, Italy. European Inst Oncol, Milan, Italy. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. Int Breast Canc Study Grp, Coordinating Ct, Bern, Switzerland. Inst Med Oncol, Bern, Switzerland. Kantonsspital, Orthopad Chirurg Klin, CH-9007 St Gallen, Switzerland. Oncol Inst So Switzerland, Lugano, Switzerland. Sahlgrens Univ Hosp, W Swedish Breast Canc Study Grp, S-41345 Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Royal Melbourne Hosp, Dept Surg, Melbourne, Vic, Australia. RP Crivellari, D (reprint author), Ctr Riferimento Oncol, Via Pedemontana Occidentale 12, I-33081 Aviano, Italy. FU NCI NIH HHS [CA-75362] NR 37 TC 49 Z9 51 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 DEC 15 PY 2003 VL 21 IS 24 BP 4517 EP 4523 DI 10.1200/JCO.2003.03.559 PG 7 WC Oncology SC Oncology GA 755VN UT WOS:000187432300011 PM 14673038 ER PT J AU Keating, NL Landrum, MB Ayanian, JZ Winer, EP Guadagnoli, E AF Keating, NL Landrum, MB Ayanian, JZ Winer, EP Guadagnoli, E TI Consultation with a medical oncologist before surgery and type of surgery among elderly women with early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LYMPH-NODE DISSECTION; CONSERVING SURGERY; OLDER WOMEN; AXILLARY DISSECTION; CLAIMS DATA; LINKED MEDICARE; CARCINOMA; CARE; PATIENT; PATTERNS AB Purpose: Prior studies have documented variation in breast cancer treatment and care that does not follow guideline recommendations, particularly for elderly women. We assessed whether consultation with a medical oncologist before surgery was associated with use of definitive surgery, axillary node dissection, and type of surgery. Methods: We conducted a retrospective cohort study of a population-based sample of 9,630 women aged : 66 years diagnosed with breast cancer during 1995 to 1996. We measured the adjusted proportion visiting a medical oncologist before surgery, identified factors associated with such visits, and assessed the association between visits with a medical oncologist and use of definitive surgery (mastectomy or breast-conserving surgery with radiation v breast-conserving surgery without radiation); axillary dissection; and breast-conserving surgery versus mastectomy among women undergoing definitive surgery. Results: Nineteen percent of women visited a medical oncologist before surgery; these women were younger, more often had larger or more poorly differentiated cancers, had more comorbid illnesses, and were treated more often at a teaching hospital (all P <.05). Women who saw a medical oncologist before surgery were more likely than others to undergo definitive surgery (adjusted odds ratio [OR], 1.28; 95% Cl, 1.05 to 1.56) and axillary dissection (adjusted OR, 1.44; 95% Cl, 1.19 to 1.73), but less likely to undergo breast-conserving surgery among women undergoing definitive surgery (OR, 0.84; 95% Cl, 0.75 to 0.95). Conclusion: Elderly women who consulted with a medical oncologist before surgery were more likely to receive guideline-recommended care. Additional research is needed allow a better understanding of the quality and content of discussions that elderly women have with various providers about breast-conserving surgery and mastectomy. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Keating, NL (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. NR 52 TC 43 Z9 44 U1 1 U2 5 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 DEC 15 PY 2003 VL 21 IS 24 BP 4532 EP 4539 DI 10.1200/JCO.2003.05.131 PG 8 WC Oncology SC Oncology GA 755VN UT WOS:000187432300013 PM 14673040 ER PT J AU Day, CL Walker, BD AF Day, CL Walker, BD TI Progress in defining CD4 helper cell responses in chronic viral infections SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID VIRUS-SPECIFIC CD4(+); ACUTE HEPATITIS-C; T-CELLS; HIV-1 INFECTION; ANTIRETROVIRAL THERAPY; CD8-T-CELL MEMORY; TYPE-1 INFECTION; CD4-T-CELL HELP; DEFICIENT MICE; IMMUNE EVASION C1 Univ Oxford, Nuffield Dept Med, Oxford OX1 35Y, England. Massachusetts Gen Hosp, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02114 USA. RP Walker, BD (reprint author), Partners AIDS Res Ctr, 149 13th St,5th Fl, Charlestown, MA 02129 USA. RI Day, Cheryl/J-9844-2012 NR 45 TC 50 Z9 52 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 15 PY 2003 VL 198 IS 12 BP 1773 EP 1777 DI 10.1084/jem.20031947 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 756CZ UT WOS:000187449400002 PM 14676292 ER PT J AU Hillinger, S Yang, SK Zhu, L Huang, M Duckett, R Atianzar, K Batra, RK Strieter, RM Dubinett, SM Sharma, S AF Hillinger, S Yang, SK Zhu, L Huang, M Duckett, R Atianzar, K Batra, RK Strieter, RM Dubinett, SM Sharma, S TI EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MODIFIED DENDRITIC CELLS; ANGIOGENESIS IN-VIVO; GROWTH-FACTOR-BETA; X-C-CHEMOKINE; T-CELL; INTERFERON-GAMMA; MURINE TUMORS; INTRATUMORAL INJECTION; LYMPHOID ORGANS; CXC CHEMOKINES AB The antitumor efficacy of EBV-induced molecule I ligand CC chemokine (ELC/CCL19) was evaluated in a murine lung cancer model. The ability of ELC/CCL19 to chemoattract both dendritic cells and T lymphocytes formed the rationale for this study. Compared with diluent-treated tumor-bearing mice, intratumoral injection of recombinant ELC/CCL19 led to significant systemic reduction in tumor volumes (p < 0.01). ELC/CCL19-treated mice exhibited an increased influx of CD4 and CD8 T cell subsets as well as dendritic cells at the tumor sites. These cell infiltrates were accompanied by increases in IFN-gamma, MIG/CXCL9, IP-10/ CXCL10, GM-CSF, and IL-12 but a concomitant decrease in the immunosuppressive molecules PGE(2) and TGFbeta. Transfer of T lymphocytes from ELC/CCL19 treated tumor-bearing mice conferred the antitumor therapeutic efficacy of ELC/CCL19 to naive mice. ELC/CCL19 treated tumor-bearing mice showed enhanced frequency of tumor specific T lymphocytes secreting IFN-gamma. In vivo depletion of IFN-gamma, MIG/CXCL9, or IP-10/CXCL10 significantly reduced the antitumor efficacy of ELC/CCL19. These findings provide a strong rationale for further evaluation of ELC/CCL19 in tumor immunity and its use in cancer immunotherapy. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Mol Gene Med Lab, Los Angeles, CA 90073 USA. RP Sharma, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Pulm & Crit Care Med, Jonsson Comprehens Canc Ctr, 37-131 Ctr Hlth Sci,10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA78654, CA71818, CA90388]; PHS HHS [1P50] NR 52 TC 46 Z9 49 U1 1 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6457 EP 6465 PG 9 WC Immunology SC Immunology GA 753JF UT WOS:000187227700023 PM 14662845 ER PT J AU Kretschmer, K Jungebloud, A Stopkowicz, J Kleinke, T Hoffmann, R Weiss, S AF Kretschmer, K Jungebloud, A Stopkowicz, J Kleinke, T Hoffmann, R Weiss, S TI The selection of marginal zone B cells differs from that of B-1a cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSGENIC MICE; GENE-EXPRESSION; LYMPHOCYTES-B; POSITIVE SELECTION; BONE-MARROW; REPERTOIRE; POPULATION; ANTIGEN; ORIGINS; ABSENCE AB Transgenic (Tg) L2 mice expressing high levels of the lambda2 (315) L chain contain only B cell populations involved in the first line of defense, i.e., B-1 and marginal zone (MZ) B cells. The strongly oligoclonal IgH chain repertoire of Tg B-la cells in such mice was attributed to strong positive selection by autoantigens. In this study, we show that the MZ B cells of L2 mice correspond very closely to MZ B cells of normal mice, as revealed by surface marker expression and gene expression profiling. We demonstrate that the IgH chain repertoire of these Tg MZ B cells is extremely heterogeneous. This is in sharp contrast to the oligoclonality found in B-1a cells of the same mice, which was attributed to strong positive selection mediated by autoantigens. Therefore, the strong positive selection of the IgH chain repertoire in L2 mice is B-1a specific. Thus, our data demonstrate that despite common functional properties, MZ B and B-1a cells exhibit striking differences in their selection and/or maintenance requirements. C1 German Res Ctr, Mol Immunol Gesell Biotechnol Forsch, Braunschweig, Germany. Basel Inst Immunol, Basel, Switzerland. RP Kretschmer, K (reprint author), Harvard Univ, Sch Med, Dept Canc Biol & AIDS, Dana Farber Canc Inst, 44 Binney St,Smith 736, Boston, MA 02115 USA. RI Kretschmer, Karsten/E-8174-2010 NR 37 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6495 EP 6501 PG 7 WC Immunology SC Immunology GA 753JF UT WOS:000187227700027 PM 14662849 ER PT J AU Frenkel, D Huang, ZH Maron, R Koldzic, DN Hancock, WW Moskowitz, MA Weiner, HL AF Frenkel, D Huang, ZH Maron, R Koldzic, DN Hancock, WW Moskowitz, MA Weiner, HL TI Nasal vaccination with myelin oligodendrocyte glycoprotein reduces stroke size by inducing IL-10-producing CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; GROWTH-FACTOR-BETA; NITRIC-OXIDE SYNTHASE; BASIC-PROTEIN; ORAL TOLERANCE; AUTOIMMUNE ENCEPHALOMYELITIS; ARTERY OCCLUSION; DENDRITIC CELLS; NERVOUS-SYSTEM; BRAIN-INJURY AB Inflammation plays an important role in ischemic stroke and in humans IL-10 may have a beneficial effect in stroke. We mucosally administered myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide to C57BL/6 mice before middle cerebral artery occlusion (MCAO) to induce an anti-inflammatory T cell response directed at CNS myelin. Nasal and oral administration of MOG(35-35) peptide decreased ischemic infarct size at 24 and 72 h after MCAO surgery. Nasal MOG(35-55) peptide was most efficacious and reduced infarct size by 70% at 24 h and by 50% at 72 h (p less than or equal to 0.0001 vs control) and also improved behavior score. Immunohistochemistry demonstrated increased IL-10 and reduced IFN-gamma in the area surrounding the ischemic infarct following nasal treatment. Nasal MOG did not reduce infarct size in IL-10-deficient mice. Adoptive transfer of CD4(+) T cells to untreated mice from nasally tolerized mice before MCAO surgery decreased stroke size (p < 0.001 vs control), whereas, CD4(+) T cells from nasally tolerized IL-10-deficient mice had no effect. Our results demonstrate that IL-10-secreting CD4(+) T cells induced by nasal MOG reduce injury following stroke. In addition, we observed a dramatic reduction of CD11b(+) cells in nasal MOG-treated animals. CD11b(+) cells may contribute to secondary infarct expansion by enhancing NO synthesis that may be reduced by elevated IL-10 levels. Modulation of cerebral inflammation by nasal vaccination with myelin Ags that increase IL-10 in the brain may improve outcome after stroke and enhance mechanisms of recovery. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke & Neurovasc Regulat Lab, Boston, MA 02115 USA. RP Weiner, HL (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Ctr Neurol Dis, 77 Francis St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI43458]; NINDS NIH HHS [NS38037] NR 37 TC 94 Z9 101 U1 1 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 DEC 15 PY 2003 VL 171 IS 12 BP 6549 EP 6555 PG 7 WC Immunology SC Immunology GA 753JF UT WOS:000187227700034 PM 14662856 ER PT J AU Christen, U McGavern, DB Luster, AD von Herrath, MG Oldstone, MBA AF Christen, U McGavern, DB Luster, AD von Herrath, MG Oldstone, MBA TI Among CXCR3 chemokines, IFN-gamma-inducible protein of 10 kDa (CXC chemokine ligand (CXCL) 10) but not monokine induced by IFN-gamma (CXCL9) imprints a pattern for the subsequent development of autoimmune disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; INDUCED DEMYELINATING DISEASE; DEPENDENT DIABETES-MELLITUS; T-CELL IMMUNITY; BETA-CELLS; TRANSGENIC MODEL; VIRAL-INFECTION; TOLERANCE INDUCTION; VIRUS-INFECTION; CUTTING EDGE AB Infection of the pancreas with lymphocytic choriomeningitis virus results in rapid and differential expression among CXCR3 chemokines. IFN-gamma-inducible protein of 10 kDa (IP-10), in contrast with monokine induced by IFN-gamma and IFN-inducible T cell-alpha chemoattractant, is strongly expressed within 24 h postinfection. Blocking of IP-10, but not monokine induced by IFN-gamma, aborts severity of Ag-specific injury of pancreatic beta cells and abrogates type 1 diabetes. Mechanistically, IP-10 blockade impedes the expansion of peripheral Ag-specific T cells and hinders their migration into the pancreas. IP-10 expression was restricted to viruses infecting the pancreas and that are capable of causing diabetes. Hence, virus-induced organ-specific autoimmune diseases may be dependent on virus tropism and its ability to alter the local milieu by selectively inducing chemokines that prepare the infected tissue for the subsequent destruction by the adaptive immune response. C1 La Jolla Inst Allergy & Immunol, Dept Dev Immunol, San Diego, CA 92121 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02129 USA. RP Christen, U (reprint author), La Jolla Inst Allergy & Immunol, Dept Dev Immunol, DI-3,10355 Sci Ctr Dr, San Diego, CA 92121 USA. RI Christen, Urs/A-7338-2009 FU NIA NIH HHS [AG00080]; NIAID NIH HHS [AI41439]; NIDDK NIH HHS [R29DK51091]; PHS HHS [R01A69212] NR 43 TC 120 Z9 124 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6838 EP 6845 PG 8 WC Immunology SC Immunology GA 753JF UT WOS:000187227700068 PM 14662890 ER PT J AU Lee, I Wang, LQ Wells, AD Ye, QR Han, RX Dorf, ME Kuziel, WA Rollins, BJ Chen, LP Hancock, WW AF Lee, I Wang, LQ Wells, AD Ye, QR Han, RX Dorf, ME Kuziel, WA Rollins, BJ Chen, LP Hancock, WW TI Blocking the monocyte chemoattractant protein-1/CCR2 chemokine pathway induces permanent survival of islet allografts through a programmed death-1 ligand-1-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-CELL-ACTIVATION; PANCREATIC-ISLETS; ENDOTHELIAL-CELLS; PD-1 PATHWAY; MICE LACKING; RECEPTOR 2; B7 FAMILY; NOD MICE; EXPRESSION AB Islet allografts are subject to rapid rejection through host cellular immune responses involving mononuclear cell recruitment and tissue injury. Interruption of leukocyte recruitment through chemokine receptor targeting is of therapeutic benefit in various experimental models, but little is known about the contribution of chemokine pathways to islet allograft rejection. We found that marine islets produce monocyte chemoattractant protein-1 (MCP-1; CCL2) in vitro and that islet allograft rejection was associated with intragraft expression of MCP-1 and its receptor, CCR2. We therefore investigated whether MCP-1 and CCR2 are required for the rejection of fully MHC-disparate islet allografts. Wild-type mice treated with blocking anti-MCP-1 mAb plus a brief, subtherapeutic course of rapamycin had long-term islet allograft survival, in contrast to the effect of treatment with either mAb or rapamycin alone. CCR2(-/-) mice treated with rapamycin also maintained islet allografts long-term. Both MCP/CCR2-and rapamycin-sensitive signals were required for maximal proliferation of alloreactive T cells, suggesting that MCP-1/CCR2 induce rejection by promoting alloreactive T cell clonal expansion and homing and migration. Prolonged islet allograft survival achieved by blockade of the MCP-1/CCR2 pathway plus rapamycin therapy was accompanied by a mononuclear cell infiltrate expressing the inhibitory receptor, programmed death-1 (PD-1), and its ligand (PD-L1, B7-H1), and prolongation of islet allograft survival was abrogated by anti-PD-L1 mAb therapy. These data show that the blockade of MCP-1 binding to CCR2 in conjunction with subtherapeutic immunosuppression can have profound effects on islet allograft survival and implicate the expression of the PD-1/PD-L1 pathway in the regulation of physiologic responses in vivo. C1 Childrens Hosp Philadelphia, Abramson Res Ctr 916E, Dept Pathol & Lab Med, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Biesecker Pediat Liver Ctr, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Texas, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. Univ Texas, Inst Cellular & Mol Biol, Austin, TX 78712 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Dept Immunol, Rochester, MN 55095 USA. RP Hancock, WW (reprint author), Childrens Hosp Philadelphia, Abramson Res Ctr 916E, Dept Pathol & Lab Med, Joseph Stokes Jr Res Inst, 3615 Civic Ctr Blvd, Philadelphia, PA 19104 USA. FU NIAID NIH HHS [AI40152]; NIDDK NIH HHS [DK063591] NR 48 TC 78 Z9 84 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6929 EP 6935 PG 7 WC Immunology SC Immunology GA 753JF UT WOS:000187227700078 PM 14662900 ER PT J AU Martin-Orozco, N Chen, ZB Poirot, L Hyatt, E Chen, A Kanagawa, O Sharpe, A Mathis, D Benoist, C AF Martin-Orozco, N Chen, ZB Poirot, L Hyatt, E Chen, A Kanagawa, O Sharpe, A Mathis, D Benoist, C TI Paradoxical dampening of anti-islet self-reactivity but promotion of diabetes by OX40 ligand SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; DIABETOGENIC T-CELLS; DENDRITIC CELLS; IN-VIVO; B-CELL; GENETIC-CONTROL; OX-40 LIGAND; LYMPH-NODES; MICE; EXPRESSION AB Costimulatory signals received by diabetogenic T cells during priming by or upon secondary encounter with autoantigen are decisive in determining the outcome of autoimmune attack. The OX40-OX40 ligand (OX40L) costimulatory pathway is known to influence T cell responses, prompting us to examine its role in autoimmune diabetes. A null allele at OX40L completely prevented diabetes development in nonobese diabetic mice and strongly reduced its incidence in a TCR transgenic model (BDC2.5). However, somewhat paradoxically, the initial activation of T cells responsive to islet beta cell Ag was slightly faster and more efficient in the absence of OX40L, with an increased degree of cell proliferation and survival in the deficient hosts. Activated T cell migration into and retention within the islets was also slightly accelerated. When challenged in vitro, splenocytes from BDC2.5.OX40L(o/o) mice showed no altered reactivity to exogenously added peptide, no bias to the Th1 or Th2 phenotype, and no alteration in T cell survival. Thus, the OX40/OX40L axis has the paradoxical effect of dampening the early activation and migration of autoimmune T cells, but sustains the long-term progression to autoimmune destruction. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Div Immunol Res, Boston, MA 02215 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Ctr Immunol, St Louis, MO 63110 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. RI Martin Orozco, Natalia/E-4794-2010 FU NIAID NIH HHS [1 P01 AI3967]; NIDDK NIH HHS [2 P30 DK36836-17] NR 41 TC 26 Z9 27 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6954 EP 6960 PG 7 WC Immunology SC Immunology GA 753JF UT WOS:000187227700081 PM 14662903 ER PT J AU Feeney, ME Draenert, R Roosevelt, KA Pelton, SI McIntosh, K Burchett, SK Mao, C Walker, BD Goulder, PJR AF Feeney, ME Draenert, R Roosevelt, KA Pelton, SI McIntosh, K Burchett, SK Mao, C Walker, BD Goulder, PJR TI Reconstitution of virus-specific CD4 proliferative responses in pediatric HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL RESPONSES; ACTIVE ANTIRETROVIRAL THERAPY; IMMUNE-RESPONSES; HIV-1-INFECTED CHILDREN; LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; COMBINATION THERAPY; VIRAL REPLICATION; CD8-T-CELL MEMORY AB Gag-specific CD4 proliferative responses correlate inversely with HIV-1 RNA levels in infected adults, and robust responses are characteristic of long-term nonprogressive infection. However, strong responses are seldom detected in adult subjects with progressive infection and are not generally reconstituted on highly active antiretroviral therapy (HAART). To date, the role of HIV-1-specific Th responses in children has not been thoroughly examined. We characterized Gag-specific CD4 responses among 35 perinatally infected subjects, including 2 children who spontaneously control viremia without antiretroviral therapy, 21 children with viral loads (VL) of <400 on HAART, and 12 viremic children. Gag-specific Th activity was assessed by lymphoproliferative assay, and responses were mapped using overlapping Gag peptides in an IFN-gamma ELISPOT. Robust proliferative responses were detected in the children exhibiting spontaneous control of viremia, and mapping of targeted Gag regions in one such subject identified multiple epitopes. Among children greater than or equal to5 years old, 14 of 17 subjects with VL of <400 on HAART demonstrated a significant p24 proliferative response (median p24 stimulation index, 20), in contrast with only 1 of 9 viremic children (median p24 stimulation index, 2.0; p = 0.0008). However, no subject younger than 5 years of age possessed a significant response, even when viremia was fully suppressed. When compared with adults with VL of <400 on HAART, Th responses among children with VL of <400 were both more frequent (p = 0.009) and of greater magnitude (p = 0.002). These data suggest that children may have a greater intrinsic capacity to reconstitute HIV-1-specific immunity than adults, and may be excellent candidates for immune-based therapies. C1 Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. Boston Med Ctr, Boston, MA 02118 USA. RP Goulder, PJR (reprint author), Partners AIDS Res Ctr, 5th Floor,149 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [K30 HL04095]; NIAID NIH HHS [AI46995, AI52078, AI28568] NR 52 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2003 VL 171 IS 12 BP 6968 EP 6975 PG 8 WC Immunology SC Immunology GA 753JF UT WOS:000187227700083 PM 14662905 ER PT J AU Taylor, NS Ge, ZM Shen, ZL Dewhirst, FE Fox, JG AF Taylor, NS Ge, ZM Shen, ZL Dewhirst, FE Fox, JG TI Cytolethal distending toxin: A potential virulence factor for Helicobacter cinaedi SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting of the European-Helicobacter-Pylori-Study-group CY SEP 11-14, 2002 CL ATHENS, GREECE SP European Helicobacter Pylori Study Grp ID CAMPYLOBACTER-CINAEDI; SP-NOV; CDTB; IDENTIFICATION; CELLULITIS; BACTEREMIA; DISEASE; CELLS; MICE AB Although Helicobacter cinaedi is the most commonly reported enterohepatic helicobacter in humans, there are no reports of virulence factors, and little is known about how it infects and causes disease. In this study, H. cinaedi isolates from humans and animals were examined for production of cytolethal distending toxin (Cdt). Cdt causes distention in cells and arrest in the G2/M phase of cell division. It is encoded by three genes: cdtA, cdtB, and cdtC. cdtB is the most conserved. All isolates except the American Type Culture Collection strain (identified as H. fennelliae) demonstrated Cdt activity and had a cdtB polymerase chain-reaction product homologous with known cdtB. Deduced amino acid sequences of cdtB showed a high (93%-99%) degree of similarity among the H. cinaedi isolates. H. cinaedi shares the production of Cdt with other enteric pathogens, including enterohepatic Helicobacter species. This is the first report of a putative virulence factor in H. cinaedi. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA USA. RP Taylor, NS (reprint author), MIT, Div Comparat Med, 16-869,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM nstaylor@mit.edu FU NCI NIH HHS [R01 CA67529]; PHS HHS [R01 A150952] NR 19 TC 36 Z9 36 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2003 VL 188 IS 12 BP 1892 EP 1897 DI 10.1086/379837 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 762QB UT WOS:000187992700015 PM 14673770 ER PT J AU Ross, AJ Tilman, C Yao, H MacLaughlin, D Capel, B AF Ross, AJ Tilman, C Yao, H MacLaughlin, D Capel, B TI AMH induces mesonephric cell migration in XX gonads SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st International Workshop on Anti-Mullerian Hormone/Mullerian Inhibiting Substance CY OCT 07-08, 2002 CL Aix En Provence, FRANCE DE AMH; testis; mesonephros; migration ID MULLERIAN-INHIBITING SUBSTANCE; SEXUAL DEVELOPMENT; TESTIS DIFFERENTIATION; DETERMINING GENE; SOX9 EXPRESSION; SERTOLI-CELLS; HORMONE GENE; FETAL TESTIS; IN-VIVO; MOUSE AB Migration of mesonephric cells into XY gonads is a critical early event in testis cord formation. Based on the fact that anti-Mullerian hormone (AMH) can induce testis cord formation in XX gonads, we investigated whether AMH plays a role in the induction of cell migration. Addition of recombinant AMH induced mesonephric migration into XX gonads in culture. AMH-treated XX gonads displayed increased vascular development and altered morphology of the coelomic epithelium, both features of normal testis differentiation. AMH did not induce markers of Sertoli or Leydig cell differentiation. We examined early testis development in Amh-deficient mice, but found no abnormalities, suggesting that any function AMH may have in vivo is redundant. Other transforming growth factor (TGF-P) family proteins, bone morphogenetic proteins (BMP2 and BMP4) show similar inductive effects on XX gonads in culture. Although neither BMP2 nor BMP4 is expressed in embryonic XY gonads, our findings suggest that a TGF-P signalling pathway endogenous to the XY gonad may be involved in regulation of mesonephric cell migration. The factors involved in this process remain to be identified. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Duke Univ, Med Ctr, Dept Cell Biol, Box 3709,340 Nanaline Duke,Res Dr, Durham, NC 27710 USA. EM b.capel@cellbio.duke.edu RI Yao, Humphrey Hung-Chang/B-4795-2010 OI Yao, Humphrey Hung-Chang/0000-0003-2944-8469 FU NICHD NIH HHS [HD39963-04, F32 HD041317, R37 HD039963, HD41317-02, R01 HD039963] NR 37 TC 36 Z9 37 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC 15 PY 2003 VL 211 IS 1-2 BP 1 EP 7 DI 10.1016/j.mce.2003.09.021 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 754WF UT WOS:000187354900002 PM 14656469 ER PT J AU Donahoe, PK Clarke, T Teixeira, J Maheswaran, S MacLaughlin, DT AF Donahoe, PK Clarke, T Teixeira, J Maheswaran, S MacLaughlin, DT TI Enhanced purification and production of Mullerian inhibiting substance for therapeutic applications SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st International Workshop on Anti-Mullerian Hormone/Mullerian Inhibiting Substance CY OCT 07-08, 2002 CL AIX PROVENCE, FRANCE DE Mullerian inhibiting substance; tumor growth; tobacco recombinant ovarian cancer ID HUMAN OVARIAN-CANCER; II RECEPTOR; IN-VIVO; DEVELOPMENTAL EXPRESSION; SEXUAL DEVELOPMENT; DUCT REGRESSION; CELL-GROWTH; PATHWAY; MANAGEMENT; HORMONE AB It is almost 60 years since Prof. Alfred Jost reported the seminal observations regarding Mullerian inhibiting substance (MIS). His experiments clearly showed that a testicular product other than testosterone, a Mullerian inhibitor, was responsible for Mullerian duct regression. Twenty-five years later Dr. Picon established an organ culture assay which paved the way for the initial studies into the biochemistry and biology of Mullerian inhibiting substance, also known as Anti-Mullerian hormone (AMH), undertaken first in Dr. Nathalie Josso's Laboratory in Paris then in our own laboratory in Boston. Purification of MIS led to cloning the human gene and production of recombinant human (rhMIS). MIS is a 140kDa glycoprotein homodimer which is activated by a biosynthetic protease, cleaving MIS into an aminoterminus (110 kDa) and a carboxyterminus (25 kDa). The latter domain is sufficient for biological activities. MIS functions by interacting with two receptors; a type II binds the hormone and at type I that initiates downstream signaling. The MIS type II receptor has been cloned and functionally confirmed as distinct from that of other members of the TGFbeta superfamily. MIS can employ a number of type I receptors (ALK2, ALK3, ALK6) and BMP receptor specific SMADS 1, 5, and 8 in various tissue specific contexts. Cell lines derived from human ovarian, breast, and prostate tumors, and from rodent Leydig cell tumors, which respond to MIS in growth inhibition assays, all express the MIS type II receptor. A variety of signal transduction pathways are associated with the grown inhibition mediated by MIS. For example, breast and prostate cancer cell lines use a MIS-mediated NFkappaB pathway leading to G1 arrest and apoptosis. The ovarian cancer cell lines employ a pathway which enhances p16, modulates the E2Fs, and induces apoptosis. These signal transduction events can establish new rational treatment strategies to complement the growth inhibitory effects mediated by MIS. These combination strategies are being tested in vitro, and where appropriate will be tested in vivo using the highly purified MIS preparations, prior to use in early human clinical trials. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Donahoe, PK (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Warren 11,55 Fruit St, Boston, MA 02114 USA. OI Teixeira, Jose/0000-0002-6438-5064 NR 32 TC 17 Z9 20 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC 15 PY 2003 VL 211 IS 1-2 BP 37 EP 41 DI 10.1016/j.mce.2003.09.009 PG 5 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 754WF UT WOS:000187354900007 PM 14656474 ER PT J AU Hoshiya, Y Gupta, V Segev, DL Hoshiya, M Carey, JL Sasur, LM Tran, TT Ha, TU Maheswaran, S AF Hoshiya, Y Gupta, V Segev, DL Hoshiya, M Carey, JL Sasur, LM Tran, TT Ha, TU Maheswaran, S TI Mullerian inhibiting substance induces NF kappa B signaling in breast and prostate cancer cells SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st International Workshop on Anti-Mullerian Hormone/Mullerian Inhibiting Substance CY OCT 07-08, 2002 CL AIX PROVENCE, FRANCE DE MIS; MIS type II receptor; NF kappa B; IEX-1; breast; prostate ID RESPONSE GENE; II RECEPTOR; IN-VIVO; HORMONE; EXPRESSION; PATHWAY; GROWTH; DUCT; ALK2 AB The MIS type II receptor is expressed at high levels in the Mullerian duct and in Sertoli cells and granulosa cells of the embryonic and adult gonads. The presence of MIS type II and type I receptors in tissues and cell lines derived from breast and prostate suggests that the prostate and mammary glands may be additional targets for MIS action. In both breast and prostate cancer cells, MIS activated NFkappaB DNA binding activity and induced IEX-1, an immediate early gene which regulates cell growth and apoptosis. Exposure of cells to MIS inhibited growth by increasing the fraction of cells in the G1 phase of the cell cycle and by inducing apoptosis. These results suggest that MIS may be a putative mediator of growth regulatory signals in the breast and prostate. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Maheswaran, S (reprint author), Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. FU NCI NIH HHS [CA89138-01A1] NR 23 TC 32 Z9 34 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC 15 PY 2003 VL 211 IS 1-2 BP 43 EP 49 DI 10.1016/j.mce.2003.09.010 PG 7 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 754WF UT WOS:000187354900008 PM 14656475 ER PT J AU Fynn-Thompson, E Cheng, H Teixeira, J AF Fynn-Thompson, E Cheng, H Teixeira, J TI Inhibition of steroidogenesis in Leydig cells by Mullerian-inhibiting substance SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 1st International Workshop on Anti-Mullerian Hormone/Mullerian Inhibiting Substance CY OCT 07-08, 2002 CL Aix En Provence, FRANCE DE Mullerian-inhibiting substance; anti-Mullerian hormone; steroidogenesis; Leydig cells ID II RECEPTOR; SEXUAL DEVELOPMENT; HORMONE-RECEPTOR; TRANSGENIC MICE; MOUSE OVARY; IN-VIVO; DIFFERENTIATION; EXPRESSION; GROWTH; GENE AB Mullerian-inhibiting substance (MIS), a member of the transforming growth factor-beta family of cytokines that signal through a heteromeric complex of single-transmembrane serine/threonine kinase receptors, is required for Mullerian duct regression and normal reproductive tract development in the male embryo. However, the continued expression of MIS at high levels in males until puberty and its induction in females after birth suggested other roles for MIS. Additionally, Leydig cell development and steroidogenic capacity and ovarian follicle recruitment were abnormal in MIS-knockout or MIS-overexpressing mice. We have shown that MIS inhibits the cAMP-induced expression of cytochrome P450 C17alpha-hydroxylase/C17-20 lyase (Cyp17) mRNA both in vitro and in vivo. Our current efforts are to understand the molecular mechanisms regulating both MIS type II receptor (MISRII) expression and its signaling in rodent Leydig cell lines. MISRII expression in R2C cells requires both steroidogenic factor-1 and an unknown protein to bind to its proximal promoter in the context of 1.6 kb 5'-flanking DNA. When bound by MIS, signaling by the receptor in MA-10 cells blocks the protein kinase A-mediated induction of Cyp17 expression by a cAMP regulatory element-binding protein independent mechanism. We continue to investigate the molecular mechanisms of MISRII expression and possible interactions between MIS-regulated SMAD activation and cAMP signaling. These studies will provide a better understanding of the role played by MIS during postnatal life. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Pediat Surg Res Labs, 32 Fruit St, Boston, MA 02114 USA. EM teixeira@helix.mgh.harvard.edu OI Teixeira, Jose/0000-0002-6438-5064 FU NCI NIH HHS [R29 CA079459, R29 CA079459-04, R29-CA79459]; NICHD NIH HHS [U54-HD28138] NR 29 TC 23 Z9 26 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD DEC 15 PY 2003 VL 211 IS 1-2 BP 99 EP 104 DI 10.1016/j.mce.2003.09.015 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 754WF UT WOS:000187354900015 PM 14656482 ER PT J AU Wang, XW Seed, B AF Wang, XW Seed, B TI A PCR primer bank for quantitative gene expression analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN GENOME; OLIGONUCLEOTIDE; MOUSE; MICROARRAYS; SELECTION; SEQUENCE; DESIGN; PROBES; TIME AB Although gene expression profiling by microarray analysis is a useful tool for assessing global levels of transcriptional activity, variability associated with the data sets usually requires that observed differences be validated by some other method, such as real-time quantitative polymerase chain reaction (real-time PCR). However, non-specific amplification of non-target genes is frequently observed in the latter, confounding the analysis in similar to40% of real-time PCR attempts when primer-specific labels are not used. Here we present an experimentally validated algorithm for the identification of transcript-specific PCR primers on age nomic scale that can be applied to real-time PCR with sequence-independent detection methods. An online database, PrimerBank, has been created for researchers to retrieve primer information for their genes of interest. PrimerBank currently contains 147 404 primers encompassing most known human and mouse genes. The primer design algorithm has been tested by conventional and real-time PCR for a subset of 112 primer pairs with a success rate of 98.2%. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Seed, B (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, 50 Blossom St, Boston, MA 02114 USA. EM seed@molbio.mgh.harvard.edu FU NHLBI NIH HHS [U01 HL66678, U01 HL066678] NR 38 TC 377 Z9 381 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 15 PY 2003 VL 31 IS 24 AR e154 DI 10.1093/nar/gng154 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 758PH UT WOS:000187659000028 PM 14654707 ER PT J AU White, BR Pierce, MC Nassif, N Cense, B Park, BH Tearney, GJ Bouma, BE Chen, TC de Boer, JF AF White, BR Pierce, MC Nassif, N Cense, B Park, BH Tearney, GJ Bouma, BE Chen, TC de Boer, JF TI In vivo dynamic human retinal blood flow imaging using ultra-high-speed spectral domain optical Doppler tomography SO OPTICS EXPRESS LA English DT Article ID COHERENCE TOMOGRAPHY; REAL-TIME; HUMAN SKIN; CIRCULATION AB An ultra- high- speed spectral domain optical Doppler tomography ( SD- ODT) system is used to acquire images of blood flow in a human retina in vivo, at 29,000 depth profiles ( A- lines) per second and with data acquisition over 99% of the measurement time. The phase stability of the system is examined and image processing algorithms are presented that allow accurate determination of bi- directional Doppler shifts. Movies are presented of human retinal flow acquired at 29 frames per second with 1000 A- lines per frame over a time period of 3.28 seconds, showing accurate determination of vessel boundaries and time- dependent bi- directional flow dynamics in artery- vein pairs. The ultra- high- speed SD- ODT system allows visualization of the pulsatile nature of retinal blood flow, detects blood flow within the choroid and retinal capillaries, and provides information on the cardiac cycle. In summary, accurate video rate imaging of retinal blood flow dynamics is demonstrated at ocular exposure levels below 600 muW. (C) 2003 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, 50 Blossom St,BAR 724, Boston, MA 02114 USA. EM deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 23 TC 327 Z9 329 U1 3 U2 32 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD DEC 15 PY 2003 VL 11 IS 25 BP 3490 EP 3497 DI 10.1364/OE.11.003490 PG 8 WC Optics SC Optics GA 754PE UT WOS:000187324900021 PM 19471483 ER PT J AU Shen, KZ Zhu, ZT Munhall, A Johnson, SW AF Shen, KZ Zhu, ZT Munhall, A Johnson, SW TI Synaptic plasticity in rat subthalamic nucleus induced by high-frequency stimulation SO SYNAPSE LA English DT Article DE short-term potentiation; long-term potentiation; long-term depression; EPSC ID LONG-TERM POTENTIATION; ADVANCED PARKINSONS-DISEASE; DEEP BRAIN-STIMULATION; IN-VITRO; SUBSTANTIA-NIGRA; DOPAMINE NEURONS; GLOBUS-PALLIDUS; DEPRESSION; TRANSMISSION; HIPPOCAMPUS AB The technique of deep brain stimulation (DBS) has become a preferred surgical choice for the treatment of advanced Parkinson's disease. The subthalamic nucleus (STN) is presently the most promising target for such DBS. In this study, whole-cell patch-clamp recordings were made from 46 STN neurons in rat brain slices to examine the effect of high-frequency stimulation (HIPS) of the STN on glutamatergic synaptic transmission in STN neurons. HFS, consisting of trains of stimuli at a frequency of 100 Hz for 1 min, produced three types of synaptic plasticity in 17 STN neurons. First, HIPS of the STN induced short-term potentiation (STP) of evoked postsynaptic current (EPSC) amplitude in four neurons. STP was associated with a reduction in the EPSC paired-pulse ratio, suggesting a presynaptic site of action. Second, HFS of the STN generated long-term potentiation (LTP) of EPSC amplitude in eight neurons. Although the EPSC paired-pulse ratio was reduced transiently in the first 2 min following HIPS, ratios measured 6-20 min after HFS were unchanged from control. This suggests that LTP is maintained by a postsynaptic mechanism. Third, HFS produced long-term depression (LTD) of EPSC amplitude in five STN neurons. LTD was associated with a significant increase in EPSC paired-pulse ratios, indicating a presynaptic site of action. These results suggest that HIPS can produce long-term changes in the efficacy of synaptic transmission in the STN. HFS-induced synaptic plasticity might be one mechanism underlying the effectiveness of DBS in the STN as a treatment of advanced Parkinson's disease. (C) 2003 Wiley-Liss, Inc. C1 Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. Vet Adm Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NINDS NIH HHS [NS 38175] NR 40 TC 68 Z9 70 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 15 PY 2003 VL 50 IS 4 BP 314 EP 319 DI 10.1002/syn.10274 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 739ZF UT WOS:000186375900006 PM 14556236 ER PT J AU Hertl, M Cosimi, AB AF Hertl, M Cosimi, AB TI Live-donor liver transplantation for acute-on-chronic hepatitis B liver failure. Transplantation 2003; 76 : 1174. Chi-Leung Liu, Sheung-Tat Fan, Chung-Mau Lo, William Ignace Wei, Boon-Hun Yong, Ching-Lung Lai, and John Wong SO TRANSPLANTATION LA English DT Editorial Material ID RIGHT LOBE; GRAFTS C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, Boston, MA 02114 USA. RP Hertl, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Unit, 55 Fruit St,Blake 655, Boston, MA 02114 USA. NR 9 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2003 VL 76 IS 11 BP 1539 EP 1540 DI 10.1097/00007890-200312150-00002 PG 2 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 755HM UT WOS:000187397500002 PM 14705620 ER PT J AU Sharland, A Lee, JH Saidman, S Waneck, GL AF Sharland, A Lee, JH Saidman, S Waneck, GL TI CD8-interaction mutant HLA-Cw3 molecules protect porcine cells from human natural killer cell-mediated antibody-dependent cellular cytotoxicity without stimulating cytotoxic T lymphocytes SO TRANSPLANTATION LA English DT Article ID HUMAN NK CELLS; AORTIC ENDOTHELIAL-CELLS; HLA-G EXPRESSION; CLASS-I; XENOTRANSPLANTATION; TRANSPLANTATION; RECEPTORS; SWINE; PIGS; CD8 AB Background. CD56(+) human natural killer (NK) cells are the principal anti-pig cytotoxic effectors in vitro. Expression of certain human leukocyte antigen (HLA) class I molecules in porcine cells can inhibit NK cell-mediated natural cytotoxicity in serum-free medium, but had not been shown to inhibit antibody-dependent cellular cytotoxicity (ADCC) by CD16(+) NK cells in the presence of human xenoreactive immunoglobulin G. Moreover, expression of HLA molecules might amplify the previously weak CD8(+) cytotoxic T-lymphocyte (CTL) response against porcine cells. Methods. A novel porcine B-lymphoblastoid cell line (13271) was stably transfected with HLA-Cw*0304 gene constructs encoding wild-type (wt) Cw3 or genetically modified Cw3 unable to interact with CD8 (Cw3-D227K). The Cw3 transfectants were used in limiting dilution assays to estimate the CTL precursor frequency in CD56-depleted human peripheral blood mononuclear cells (PBMC) obtained from eight unrelated donors. The 13271 transfectants were also used as targets for clonal and polyclonal NK cells in the presence and absence of human serum, to measure inhibition of ADCC. Results. Expression of Cw3-wt in 13271 cells significantly increased the human CTL response compared with the empty-vector control transfectant, whereas no significant increase resulted from expression of CD8-interaction mutant Cw3-D227K molecules. The Cw3-D227K mutant was indistinguishable from Cw3-wt in its ability to inhibit both natural cytotoxicity and ADCC mediated by human NK clones that have the appropriate CD158b inhibitory receptor. Conclusions. Transgenic expression of HLA molecules in pig cells will likely amplify the CD8(+) CTL response against the xenograft. Disruption of HLA-CD8 interaction could minimize this amplification without compromising NK-cell inhibition. C1 Massachusetts Gen Hosp, Dept Surg, Lab Mol & Cellular Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Histocompatabil Lab, Boston, MA 02114 USA. RP Waneck, GL (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. RI Sharland, Alexandra/G-1493-2011 FU NIAID NIH HHS [AI43440] NR 30 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2003 VL 76 IS 11 BP 1615 EP 1622 DI 10.1097/01.TP.0000086342.60603.C2 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 755HM UT WOS:000187397500017 PM 14702534 ER PT J AU Baden, LR Katz, JT Fishman, JA Koziol, C DelVecchio, A Doran, M Rubin, RH AF Baden, LR Katz, JT Fishman, JA Koziol, C DelVecchio, A Doran, M Rubin, RH TI Salvage therapy with voriconazole for invasive fungal infections in patients failing or intolerant to standard antifungal therapy SO TRANSPLANTATION LA English DT Article ID CELL TRANSPLANT RECIPIENTS; AMPHOTERICIN-B; IMMUNOCOMPROMISED PATIENTS; ASPERGILLOSIS; ITRACONAZOLE; SAFETY; EPIDEMIOLOGY; EFFICACY AB Background. Invasive fungal infections (IFI), particularly those caused by Aspergillus and other angioinvasive molds, are associated with an excessive mortality despite therapy. Methods. Voriconazole was prescribed on a compassionate basis to patients with IFI who were intolerant to or who had progressed despite standard therapy. Outcome was determined by protocol-based criteria as established by the consensus definitions (complete response [CR], partial response [PR], stable disease, failure, and intolerance). Results. Forty-five patients were enrolled in a compassionate release program (29 [64%] because of failure of response to standard therapy), between 1998 and 2002. Of the 45 patients enrolled, 35 (78%) had invasive Aspergillus, 3 (7%) had Fusarium, and 2 (4%) had Scedosporium infections. Underlying illnesses were as follows: 13 (29%) solid-organ transplant (SOT), 11 (24%) BMT, and 7 (13%) hematologic malignancy. Site of infection was as follows: 26 (58%) pulmonary, 9 (20%) disseminated, 5 (11%) central nervous system (CNS), and 3 (7%) sinus. Overall response rates were as follows: 9 (20%) CR, 17 (38%) PR, 15 (33%) failure, and 4 (9%) intolerant. Seven of the eight (88%) patients with sinus or CNS disease demonstrated stabilization of the IFI. The median duration of voriconazole therapy was 79 days with 9 (20%) patients receiving over 1 year of therapy. Nine thousand one hundred twenty-eight days of therapy were given with only four serious adverse events in two cases considered possibly or probably drug related. Conclusions. In this population of severely immunocompromised patients with life-threatening IFI who have failed or were intolerant to standard antifungal therapy, voriconazole demonstrated substantial efficacy and an acceptable level of toxicity. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Baden, LR (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Div Infect Dis, 75 Francis St,PBB-A4, Boston, MA 02215 USA. NR 26 TC 48 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2003 VL 76 IS 11 BP 1632 EP 1637 DI 10.1097/01.TP.0000089109.42239.75 PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 755HM UT WOS:000187397500022 PM 14702539 ER PT J AU Bez, A Corsini, E Curti, D Biggiogera, M Colombo, A Nicosia, RF Pagano, SF Parati, EA AF Bez, A Corsini, E Curti, D Biggiogera, M Colombo, A Nicosia, RF Pagano, SF Parati, EA TI Neurosphere and neurosphere-forming cells: morphological and ultrastructural characterization SO BRAIN RESEARCH LA English DT Article DE neurosphere; neurosphere-forming cells; characterization ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; ADULT-MOUSE BRAIN; IN-VIVO; GROWTH-FACTOR; BONE-MARROW; SPINAL-CORD; NEURONS; CNS; ASTROCYTES AB Despite recent advances in our understanding of neural stem cell (NSQ biology, the free-floating structures generated by these cells in vitro, the "neurospheres", have not been fully characterized. To fill this gap, we examined neurospheres and neurosphere-derived NSCs by confocal microscopy, electron microscopy (EM) and cytofluorimetry. Here, we show that neurospheres and neurosphere-forming cells are morphologically and functionally heterogeneous. Confocal microscopy reveals differences in cell size, viability, cytoplasmic content and in the presence and distribution of active mitochondria. By electron microscopy, neurospheres appear as complex structures in which biological events such as mitosis, apoptosis and even phagocytosis are influenced by NSCs localization within the architecture of the neurosphere. NSCs derived from neurospheres are not synchronized and are represented in all phases of the cell cycle. Cytofluorimetric studies demonstrate NSCs' heterogeneity in cell size by forward scatter (FSC) analysis, and in cytoplasmic granularity by side scatter (SSC) profiling. These findings may contribute to our understanding of the morphogenesis of the neurospheres, particularly as this process relates to the high environmental adaptability of the NSCs and the reported existence of different subpopulations of neural stem cells. (C) 2003 Elsevier B.V All rights reserved. C1 Natl Neurol Inst C Besta, Dept Neurobiol & Neurorestorat Therapies, Neurobiol Lab, I-20133 Milan, Italy. Univ Pavia, Dept Physiol Sci & Cellular & Mol Pharmacol, I-27100 Pavia, Italy. Univ Pavia, Dept Biol Anim, I-27100 Pavia, Italy. ICP, Inst Obstet & Gynaecol L Mangiagalli, Milan, Italy. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. RP Parati, EA (reprint author), Natl Neurol Inst C Besta, Dept Neurobiol & Neurorestorat Therapies, Neurobiol Lab, Via Celoria 11, I-20133 Milan, Italy. RI Parati, Eugenio/G-8765-2011 NR 45 TC 150 Z9 160 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2003 VL 993 IS 1-2 BP 18 EP 29 DI 10.1016/j.brainres.2003.08.061 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 753UR UT WOS:000187249400003 PM 14642827 ER PT J AU Blevins, JE Eakin, TJ Murphy, JA Schwartz, MW Baskin, DG AF Blevins, JE Eakin, TJ Murphy, JA Schwartz, MW Baskin, DG TI Oxytocin innervation of caudal brainstem nuclei activated by cholecystokinin SO BRAIN RESEARCH LA English DT Article DE brainstem; adiposity; satiety; food intake ID C-FOS EXPRESSION; CORTICOTROPIN-RELEASING-FACTOR; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; DORSAL VAGAL COMPLEX; AGOUTI-RELATED PROTEIN; CCK-A RECEPTORS; FOOD-INTAKE; RAT-BRAIN; SOLITARY TRACT AB The integration of 'long-term' adiposity signaling with the 'short-term' meal-related signal cholecystokinin (CCK) is proposed to involve descending hypothalamic projections to areas of the caudal brainstem (CBS) that regulate the amount of food consumed during a single meal. One such projection extends from cell bodies in the hypothalamic paraventricular nucleus (PVN) to the nucleus tractus solitarius (NTS), where cells that respond to peripheral CCK are concentrated. Candidate neuronal cell types that may comprise this PVN-NTS projection includes those expressing corticotropin-releasing hormone (CRH) or oxytocin. We therefore sought to determine whether oxytocin or CRH axons are preferentially located in close anatomical proximity to neurons of the NTS that are activated by peripheral administration of CCK, as determined by immunocytochemical staining for Fos protein. Rats received injections of either an anorexic dose of CCK (8 nmol/kg, i.p.) or vehicle and were perfused 2 h later with 4% paraformaldehyde. Immunocytochemistry was performed on cryostat sections (14 Inn) of caudal brainstem, using a polyclonal antibody to Fos protein and either a monoclonal antibody to oxytocin or a polyclonal antibody to CRH. As expected, CCK administration significantly increased the numbers of Fos-positive neurons by 489% (p < 0.0 1) and 400% (p < 0.0 1), respectively, in the medial and gelatinosus subdivisions of the NTS. These same regions received dense oxytocin axon innervation, whereas CRH immunoreactivity was not as prevalent in these areas. In areas outside the NTS, such as the dorsal motor nucleus of the vagus (DMV), Fos activation was absent despite a dense oxytocin and CRH innervation. To investigate whether CCK-induced reductions of food intake require intact oxytocin signaling, we performed a separate study in which CCK injection was preceded by injection into the fourth ventricle of an oxytocin receptor antagonist [d(CH2)(5), Tyr (Me)(2), Orn(8)]-vasotocin (OVT). This study showed CCK was 23% and 22% less effective at inhibiting food intake at 30 min (p < 0.05) and I h (p < 0.05) food intake, respectively, in the presence of OVT. Taken together, the data indicate that oxytocin axons within the descending pathway from the PVN to the NTS are anatomically positioned to interact with NTS neurons that respond to vagally mediated peripheral CCK signals such as those that occur following ingestion of a meal. These findings support the hypothesis that oxytocin exerts a tonic stimulatory effect on the response of key neurons within the NTS to CCK and further reduce meal size. Published by Elsevier B.V. C1 VA Puget Sound Hlth Care Syst, Res Serv 151, Div Endocrinol Metab, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. RP Blevins, JE (reprint author), VA Puget Sound Hlth Care Syst, Res Serv 151, Div Endocrinol Metab, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 FU NIDDK NIH HHS [DK-14047, DK-52989]; NINDS NIH HHS [NS-32273] NR 66 TC 95 Z9 96 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 12 PY 2003 VL 993 IS 1-2 BP 30 EP 41 DI 10.1016/j.brainres.2003.08.036 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 753UR UT WOS:000187249400004 PM 14642828 ER PT J AU Lennon, NJ Kho, A Bacskai, BJ Perlmutter, SL Hyman, BT Brown, RH AF Lennon, NJ Kho, A Bacskai, BJ Perlmutter, SL Hyman, BT Brown, RH TI Dysferlin interacts with Annexins A1 and A2 and mediates sarcolemmal wound-healing SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GIRDLE MUSCULAR-DYSTROPHY; MIYOSHI MYOPATHY; SKELETAL-MUSCLE; MICROARRAY ANALYSIS; MEMBRANE REPAIR; VESICLE FUSION; GENE; EXPRESSION; MUTATION; 2B AB Mutations in the dysferlin gene cause limb girdle muscular dystrophy type 2B and Miyoshi myopathy. We report here the results of expression profile analyses and in vitro investigations that point to an interaction between dysferlin and the Ca2+ and lipid-binding proteins, annexins A1 and A2, and define a role for dysferlin in Ca2+-dependent repair of sarcolemmal injury through a process of vesicle fusion. Expression profiling identified a network of genes that are co-regulated in dysferlinopathic mice. Co-immunofluorescence, co-immunoprecipitation, and fluorescence lifetime imaging microscopy revealed that dysferlin normally associates with both annexins A1 and A2 in a Ca2+ and membrane injury-dependent manner. The distribution of the annexins and the efficiency of sarcolemmal wound-healing are significantly disrupted in dysferlin-deficient muscle. We propose a model of muscle membrane healing mediated by dysferlin that is relevant to both normal and dystrophic muscle and defines the annexins as potential muscular dystrophy genes. C1 Massachusetts Gen Hosp, Day Neuromuscular Res Lab, MGH E, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Alzheimers Dis Res Lab, Charlestown, MA 02129 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Day Neuromuscular Res Lab, MGH E, 114 16th St, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG020570, AG08487]; NIBIB NIH HHS [EB00768]; NINDS NIH HHS [5PO1NS40828-02, P01 NS040828] NR 37 TC 212 Z9 218 U1 0 U2 8 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 DEC 12 PY 2003 VL 278 IS 50 BP 50466 EP 50473 DI 10.1074/jbc.M307247200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 751LH UT WOS:000187068200099 PM 14506282 ER PT J AU Gines, S Ivanova, E Seong, IS Saura, CA MacDonald, ME AF Gines, S Ivanova, E Seong, IS Saura, CA MacDonald, ME TI Enhanced Akt signaling is an early pro-survival response that reflects N-methyl-D-aspartate receptor activation in Huntington's disease knock-in striatal cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOUSE MODELS; BETA-CATENIN; MICE; TRANSCRIPTION; DYSFUNCTION; PHENOTYPES; PATHWAY; REPEAT; TRACTS; GENE AB Huntington's disease features the loss of striatal neurons that stems from a disease process that is initiated by mutant huntingtin. Early events in the disease cascade, which predate overt pathology in Hdh CAG knock-in mouse striatum, implicate enhanced N-methyl-D-aspartate ( NMDA) receptor activation, with excitotoxity caused by aberrant Ca2+ influx. Here we demonstrate in precise genetic Huntington's disease mouse and striatal cell models that these early phenotypes are associated with activation of the Akt pro-survival signaling pathway. Elevated levels of activated Ser(P)(473)-Akt are detected in extracts of Hdh(Q111/Q111) striatum and cultured mutant STHdh(Q111/Q111) striatal cells, compared with their wild type counterparts. Akt activation in mutant striatal cells is associated with increased Akt signaling via phosphorylation of GSK3beta at Ser(9). Consequent decreased turnover of transcription co-factor beta-catenin leads to increased levels of beta-catenin target gene cyclin D1. Akt activation is phosphatidylinositol 3-kinase dependent, as demonstrated by increased levels of Ser(P)(241)-PDK1 kinase and decreased Ser(P)(380)-PTEN phosphatase. Moreover, Akt activation can be normally stimulated by treatment with insulin growth factor-1 and blocked by treatment with the phosphatidylinositol 3-kinase inhibitor LY294002. However, in contrast to wild type cells, Akt activation in mutant striatal cells can be blocked by the addition of the NMDA receptor antagonist MK-801. Akt activation in mutant striatal cells is Ca2+-dependent, because treatment with EGTA reduces levels of Ser(P)(473)Akt. Thus, consistent with excitotoxicity early in the disease process, activation of the Akt pro-survival pathway in mutant knock-in striatal cells predates overt pathology and reflects mitochondrial dysfunction and enhanced NMDA receptor signaling. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. RP Gines, S (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Saura, Carlos/D-2727-2011; OI Saura, Carlos/0000-0003-3692-5657; Gines Padros, Silvia/0000-0002-9479-8185 FU NINDS NIH HHS [NS16367, NS32765] NR 27 TC 90 Z9 91 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 12 PY 2003 VL 278 IS 50 BP 50514 EP 50522 DI 10.1074/jbc.M309348200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 751LH UT WOS:000187068200104 PM 14522959 ER PT J AU Suit, HD Willers, H AF Suit, HD Willers, H TI Comment on "Tumor response to radiotherapy regulated by endothelial cell apoptosis" (I) SO SCIENCE LA English DT Editorial Material ID MULTICELLULAR SPHEROIDS; RADIATION RESPONSE; SENSITIVITY; FRACTION; MICE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, HD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 8 TC 2 Z9 2 U1 0 U2 1 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 DEC 12 PY 2003 VL 302 IS 5652 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 752NL UT WOS:000187174000028 ER PT J AU Opferman, JT Letai, A Beard, C Sorcinelli, MD Ong, CC Korsmeyer, SJ AF Opferman, JT Letai, A Beard, C Sorcinelli, MD Ong, CC Korsmeyer, SJ TI Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1 SO NATURE LA English DT Article ID RECEPTOR-DEFICIENT MICE; CELLS IN-VIVO; HEMATOPOIETIC-CELLS; IMMUNE-SYSTEM; BCL-2 FAMILY; APOPTOSIS; DEATH; CYTOKINE; SURVIVAL; REARRANGEMENT AB Regulated apoptosis is essential for both the development and the subsequent maintenance of the immune system(1,2). Interleukins, including IL- 2, IL- 4, IL- 7 and IL- 15, heavily influence lymphocyte survival during the vulnerable stages of VDJ rearrangement and later in ensuring cellular homeostasis, but the genes specifically responsible for the development and maintenance of lymphocytes have not been identified(3 - 8). The antiapoptotic protein MCL- 1 is an attractive candidate, as it is highly regulated(9), appears to enhance short- term survival(10) and functions at an apical step in genotoxic deaths(11). However, Mcl- 1 deficiency results in peri- implantation lethality(12). Here we show that mice conditional for Mcl- 1 display a profound reduction in B and T lymphocytes when MCL- 1 is removed. Deletion of Mcl- 1 during early lymphocyte differentiation increased apoptosis and arrested the development at pro- B- cell and double- negative T- cell stages. Induced deletion of Mcl- 1 in peripheral B- and T- cell populations resulted in their rapid loss. Moreover, IL- 7 both induced and required MCL- 1 to mediate lymphocyte survival. Thus, MCL- 1, which selectively inhibits the proapoptotic protein BIM, is essential both early in lymphoid development and later on in the maintenance of mature lymphocytes. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol & Med, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol & Med, Boston, MA 02115 USA. NR 30 TC 492 Z9 506 U1 2 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 11 PY 2003 VL 426 IS 6967 BP 671 EP 676 DI 10.1038/nature02067 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 752DY UT WOS:000187132800044 PM 14668867 ER PT J AU Colvin, RB AF Colvin, RB TI Chronic allograft neuropathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID WORKING CLASSIFICATION; REJECTION; NEPHROPATHY; PATHOLOGY C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 5 TC 76 Z9 83 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 11 PY 2003 VL 349 IS 24 BP 2288 EP 2290 DI 10.1056/NEJMp038178 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 752AX UT WOS:000187125000003 PM 14668453 ER PT J AU Robbins, GK De Gruttola, V Shafer, RW Smeaton, LM Snyder, SW Pettinelli, C Dube, MP Fischl, MA Pollard, RB Delapenha, R Gedeon, L van der Horst, C Murphy, RL Becker, MI D'Aquila, RT Vella, S Merigan, TC Hirsch, MS Nokta, M Johnson, V Morse, G Putnam, B Klebert, M Martinez, A Chiesi, A Tomino, C Deeks, S Testa, M Nevin, T Levin, J French, V Fennell, O Stevens, M Grosso, R Dusak, B Hodder, S Squibb, M Brothers, C Tolson, J Leavitt, R Manion, D Ruiz, N Morrisey, K Quart, B Jennings, C Dascomb, S Cooper, M Murphy, M Blakelock, K Doolan, A AF Robbins, GK De Gruttola, V Shafer, RW Smeaton, LM Snyder, SW Pettinelli, C Dube, MP Fischl, MA Pollard, RB Delapenha, R Gedeon, L van der Horst, C Murphy, RL Becker, MI D'Aquila, RT Vella, S Merigan, TC Hirsch, MS Nokta, M Johnson, V Morse, G Putnam, B Klebert, M Martinez, A Chiesi, A Tomino, C Deeks, S Testa, M Nevin, T Levin, J French, V Fennell, O Stevens, M Grosso, R Dusak, B Hodder, S Squibb, M Brothers, C Tolson, J Leavitt, R Manion, D Ruiz, N Morrisey, K Quart, B Jennings, C Dascomb, S Cooper, M Murphy, M Blakelock, K Doolan, A CA AIDS Clin Trials Group 384 Team TI Comparison of sequential three-drug regimens as initial therapy for HIV-1 infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CLINICAL-TRIALS; SUPPRESSION; ZIDOVUDINE; LAMIVUDINE; INDINAVIR AB BACKGROUND: The optimal sequencing of antiretroviral regimens for the treatment of infection with human immunodeficiency virus type 1 (HIV-1) is unknown. We compared several different antiretroviral treatment strategies. METHODS: This multicenter, randomized, partially double-blind trial used a factorial design to compare pairs of sequential three-drug regimens, starting with a regimen including zidovudine and lamivudine or a regimen including didanosine and stavudine in combination with either nelfinavir or efavirenz. The primary end point was the length of time to the failure of the second three-drug regimen. RESULTS: A total of 620 subjects who had not previously received antiretroviral therapy were followed for a median of 2.3 years. Starting with a three-drug regimen containing efavirenz combined with zidovudine and lamivudine (but not efavirenz combined with didanosine and stavudine) appeared to delay the failure of the second regimen, as compared with starting with a regimen containing nelfinavir (hazard ratio for failure of the second regimen, 0.71; 95 percent confidence interval, 0.48 to 1.06), as well as to delay the second virologic failure (hazard ratio, 0.56; 95 percent confidence interval, 0.29 to 1.09), and significantly delayed the failure of the first regimen (hazard ratio, 0.39) and the first virologic failure (hazard ratio, 0.34). Starting with zidovudine and lamivudine combined with efavirenz (but not zidovudine and lamivudine combined with nelfinavir) appeared to delay the failure of the second regimen, as compared with starting with didanosine and stavudine (hazard ratio, 0.68), and significantly delayed both the first and the second virologic failures (hazard ratio for the first virologic failure, 0.39; hazard ratio for the second virologic failure, 0.47), as well as the failure of the first regimen (hazard ratio, 0.35). The initial use of zidovudine, lamivudine, and efavirenz resulted in a shorter time to viral suppression. CONCLUSIONS: The efficacy of antiretroviral drugs depends on how they are combined. The combination of zidovudine, lamivudine, and efavirenz is superior to the other antiretroviral regimens used as initial therapy in this study. C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Social & Sci Syst, Silver Spring, MD USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Miami, Sch Med, Miami, FL USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Howard Univ, Washington, DC 20059 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Agouron Pharmaceut, La Jolla, CA USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Ist Super Sanita, I-00161 Rome, Italy. RP Robbins, GK (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. RI Robbins, Gregory/F-7988-2011; Vella, Stefano/D-4912-2015; OI Vella, Stefano/0000-0003-2347-5984; Murphy, Robert/0000-0003-3936-2052 FU NCRR NIH HHS [M01 RR005096, M01 RR000044, M01 RR000052, M01 RR000070, RR00044, RR00052, RR00070, RR05096]; NIAID NIH HHS [AI38855, AI38858, R01 AI046148, U01 AI038855, U01 AI038858] NR 16 TC 249 Z9 258 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 11 PY 2003 VL 349 IS 24 BP 2293 EP 2303 DI 10.1056/NEJMoa030264 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 752AX UT WOS:000187125000005 PM 14668455 ER PT J AU Shafer, RW Smeaton, LM Robbins, GK De Gruttola, V Snyder, SW D'Aquila, RT Johnson, VA Morse, GD Nokta, MA Martinez, AI Gripshover, BM Kaul, P Haubrich, R Swingle, M McCarty, SD Vella, S Hirsch, MS Merigan, TC Fischl, M Pollard, R Dube, M Pettinelli, C Delapenha, R Putnam, B Klebert, M Testa, M Chiesi, A Tomino, C Deeks, S Nevin, T Levin, J French, V Fennell, O Stevens, M Grosso, R Dusak, B Hodder, S Tolson, J Brothers, C Leavitt, R Manion, D Ruiz, N Morrisey, K Becker, M Quart, B Jennings, C Gedeon, L Dascomb, S Cooper, M Murphy, M Blakelock, K Doolan, A AF Shafer, RW Smeaton, LM Robbins, GK De Gruttola, V Snyder, SW D'Aquila, RT Johnson, VA Morse, GD Nokta, MA Martinez, AI Gripshover, BM Kaul, P Haubrich, R Swingle, M McCarty, SD Vella, S Hirsch, MS Merigan, TC Fischl, M Pollard, R Dube, M Pettinelli, C Delapenha, R Putnam, B Klebert, M Testa, M Chiesi, A Tomino, C Deeks, S Nevin, T Levin, J French, V Fennell, O Stevens, M Grosso, R Dusak, B Hodder, S Tolson, J Brothers, C Leavitt, R Manion, D Ruiz, N Morrisey, K Becker, M Quart, B Jennings, C Gedeon, L Dascomb, S Cooper, M Murphy, M Blakelock, K Doolan, A CA AIDS Clin Trials Grp 384 Team TI Comparison of four-drug regimens and pairs of sequential three-drug regimens as initial therapy for HIV-1 infection SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; VIROLOGICAL FAILURE; REVERSE-TRANSCRIPTASE; CLINICAL-TRIALS; RESISTANCE; NUCLEOSIDE; ZIDOVUDINE; LAMIVUDINE; EFAVIRENZ; INHIBITOR AB BACKGROUND: It is unclear whether therapy for human immunodeficiency virus type 1 (HIV-1) should be initiated with a four-drug or two sequential three-drug regimens. METHODS: In this multicenter trial we compared initial therapy involving four-drug regimens containing efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine with therapy involving two consecutive three-drug regimens the first of which contained either efavirenz or nelfinavir. RESULTS: A total of 980 subjects were followed for a median of 2.3 years. There was no significant difference in the occurrence of regimen failures between the group that received the four-drug regimen containing didanosine, stavudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with didanosine, stavudine, and nelfinavir (hazard ratio for regimen failure, 1.24) or didanosine, stavudine, and efavirenz (hazard ratio, 1.01). There was no significant difference between the group that received the four-drug regimen containing zidovudine, lamivudine, nelfinavir, and efavirenz and the groups that received the three-drug regimens beginning with zidovudine, lamivudine, and nelfinavir (hazard ratio, 1.06) or zidovudine, lamivudine, and efavirenz (hazard ratio, 1.45). A four-drug regimen was associated with a longer time to the first regimen failure than the three-drug regimens containing didanosine, stavudine, and nelfinavir (hazard ratio for a first regimen failure, 0.55); didanosine, stavudine, and efavirenz (hazard ratio, 0.63); or zidovudine, lamivudine, and nelfinavir (hazard ratio, 0.49), but not the three-drug regimen containing zidovudine, lamivudine, and efavirenz (hazard ratio, 1.21). CONCLUSIONS: There was no significant difference in the duration of successful HIV-1 treatment between a single four-drug regimen and two consecutive three-drug regimens. Among these treatment strategies, initiating therapy with the three-drug regimen of zidovudine, lamivudine, and efavirenz is the optimal choice. C1 Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Social & Sci Syst, Silver Spring, MD USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Birmingham, AL USA. SUNY Buffalo, Buffalo, NY 14260 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Calif San Diego, San Diego, CA 92103 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Ist Super Sanita, I-00161 Rome, Italy. RP Robbins, GK (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, 55 Fruit St, Boston, MA 02114 USA. RI Robbins, Gregory/F-7988-2011; Vella, Stefano/D-4912-2015 OI Vella, Stefano/0000-0003-2347-5984 FU NCRR NIH HHS [M01 RR000044, M01 RR000052, M01 RR000070, M01 RR005096, RR00044, RR00052, RR00070, RR05096]; NIAID NIH HHS [AI38855, AI38858, R01 AI046148, U01 AI038855, U01 AI038858] NR 20 TC 167 Z9 173 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 11 PY 2003 VL 349 IS 24 BP 2304 EP 2315 DI 10.1056/NEJMoa030265 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 752AX UT WOS:000187125000006 PM 14668456 ER PT J AU Kolodgie, FD Gold, HK Burke, AP Fowler, DR Kruth, HS Weber, DK Farb, A Guerrero, LJ Hayase, M Kutys, R Narula, J Finn, AV Virmani, R AF Kolodgie, FD Gold, HK Burke, AP Fowler, DR Kruth, HS Weber, DK Farb, A Guerrero, LJ Hayase, M Kutys, R Narula, J Finn, AV Virmani, R TI Intraplaque hemorrhage and progression of coronary atheroma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RED-BLOOD-CELLS; LOW-DENSITY-LIPOPROTEIN; ATHEROSCLEROTIC LESIONS; PLAQUE MORPHOLOGY; CHOLESTEROL; ERYTHROCYTES; MEMBRANE; RECEPTOR; DISEASE; HYPERCHOLESTEROLEMIA AB BACKGROUND: Intraplaque hemorrhage is common in advanced coronary atherosclerotic lesions. The relation between hemorrhage and the vulnerability of plaque to disruption may involve the accumulation of free cholesterol from erythrocyte membranes. METHODS: We stained multiple coronary lesions from 24 randomly selected patients who had died suddenly of coronary causes with an antibody against glycophorin A (a protein specific to erythrocytes that facilitates anion exchange) and Mallory's stain for iron (hemosiderin), markers of previous intraplaque hemorrhage. Coronary lesions were classified as lesions with pathologic intimal thickening, fibrous-cap atheromas with cores in an early or late stage of necrosis, or thin-cap fibrous atheromas (vulnerable plaques). The arterial response to plaque hemorrhage was further defined in a rabbit model of atherosclerosis. RESULTS: Only traces of glycophorin A and iron were found in lesions with pathologic intimal thickening or fibrous-cap atheromas with cores in an early stage of necrosis. In contrast, fibroatheromas with cores in a late stage of necrosis or thin caps had a marked increase in glycophorin A in regions of cholesterol clefts surrounded by iron deposits. Larger amounts of both glycophorin A and iron were associated with larger necrotic cores and greater macrophage infiltration. Rabbit lesions with induced intramural hemorrhage consistently showed cholesterol crystals with erythrocyte fragments, foam cells, and iron deposits. In contrast, control lesions from the same animals had a marked reduction in macrophages and lipid content. CONCLUSIONS: By contributing to the deposition of free cholesterol, macrophage infiltration, and enlargement of the necrotic core, the accumulation of erythrocyte membranes within an atherosclerotic plaque may represent a potent atherogenic stimulus. These factors may increase the risk of plaque destabilization. C1 Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. RP Virmani, R (reprint author), Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Bldg 54,Rm 2005,6825 16th St, Washington, DC 20306 USA. FU NHLBI NIH HHS [R01 HL61799-02] NR 40 TC 723 Z9 772 U1 4 U2 24 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 11 PY 2003 VL 349 IS 24 BP 2316 EP 2325 DI 10.1056/NEJMoa035655 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 752AX UT WOS:000187125000007 PM 14668457 ER PT J AU Warren, HS Gonzalez, RG Hedley-Whyte, ET Agus, M Smith, EE Jones, RM Tian, D Tan, WH AF Warren, HS Gonzalez, RG Hedley-Whyte, ET Agus, M Smith, EE Jones, RM Tian, D Tan, WH TI Case 38-2003: A 12-year-old girl with fever and coma - Meningoencephalitis and sepsis due to Neisseria meningitidis infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MENINGOCOCCAL INFECTIONS; SEPTIC SHOCK; PROTEIN-C; THERAPY C1 Massachusetts Gen Hosp, Serv Pediat, Pediat Infect Dis Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroradiol Div, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Div Neuropathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, 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 Warren, HS (reprint author), Massachusetts Gen Hosp, Serv Pediat, Pediat Infect Dis Unit, Boston, MA 02114 USA. OI Smith, Eric/0000-0003-3956-1668 NR 17 TC 7 Z9 7 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 11 PY 2003 VL 349 IS 24 BP 2341 EP 2349 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 752AX UT WOS:000187125000011 PM 14668461 ER PT J AU Lieberman, DA Prindiville, S Weiss, DG Willett, W AF Lieberman, DA Prindiville, S Weiss, DG Willett, W CA VA Cooperative Study Grp 380 TI Risk factors for advanced colonic neoplasia and hyperplastic polyps in asymptomatic individuals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID FECAL-OCCULT-BLOOD; MALE HEALTH-PROFESSIONALS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; ASPIRIN USE; LARGE-BOWEL; SCREENING SIGMOIDOSCOPY; SERUM-CHOLESTEROL; CIGARETTE-SMOKING AB Context Knowledge of risk factors for colorectal neoplasia could inform risk reduction strategies for asymptomatic individuals. Few studies have evaluated risk factors for advanced colorectal neoplasia in asymptomatic individuals, compared risk factors between persons with and without polyps, or included most purported risk factors in a multivariate analysis. Objective To determine risk factors associated with advanced colorectal neoplasia in a cohort of asymptomatic persons with complete colonoscopy. Design, Setting, and Participants Prospective, cross-sectional study of 3121 asymptomatic patients aged 50 to 75 years from 13 Veterans Affairs medical centers conducted between February 1994 and January 1997. All participants had complete colonoscopy to determine the prevalence of advanced neoplasia, defined as an adenoma that was 10 mm or more in diameter, a villous adenoma, an adenoma with high-grade dysplasia, or invasive cancer. Variables examined included history of first-degree relative with colorectal cancer, prior cholecystectomy, serum cholesterol level, physical activity, smoking, alcohol use, and dietary factors. Main Outcome Measures An age-adjusted analysis was performed for each variable to calculate the odds ratios (ORs) and 95% confidence intervals (CIS) associated with having advanced neoplasia compared with having no polyps. We developed a multivariate logistic regression model to identify the most informative risk factors. A secondary analysis examined risk factors for having hyperplastic polyps compared with having no polyps and compared with having advanced neoplasia. Results Three hundred twenty-nine participants had advanced neoplasia and 1441 had no polyps. In multivariate analyses, we found positive associations for history of a first-degree relative with colorectal cancer (OR, 1.66; 95% Cl, 1.16-2.35), current-smoking (OR, 1.85; 95% Cl, 1.33-2.58), and current moderate to heavy alcohol use (OR, 1.02; 95% Cl, 1.01 -1.03). Inverse associations were found for cereal fiber intake (OR, 0.95; 95% Cl, 0.91-0.99), vitamin D intake (OR, 0.94; 95% Cl, 0.90-0.99), and use of nonsteroidal anti-inflammatory drugs (NSAIDs) (OR, 0.66; 95% Cl, 0.48-0.91). In the univariate analysis, the inverse association was found with cereal fiber intake greater than 4.2 g/d, vitamin D intake greater than 645 IU/d, and daily use of NSAIDs. Marginal factors included physical activity, daily multivitamin use, and intake of calcium and fat derived from red meat. No association was found for body mass index, prior cholecystectomy, or serum cholesterol level. Three hundred ninety-one patients had hyperplastic polyps as the worst lesion found at colonoscopy. Risk variables were similar to those for patients with no polyps, except that past and current smoking were associated with an increased risk of hyperplastic polyps. Conclusions Our data endorse several important risk factors for advanced colonic neoplasia and provide a rationale for prudent risk reduction strategies. Further study is needed to determine if lifestyle changes can moderate the risk of colorectal cancer. C1 Dept Vet Affairs Med Ctr, Portland, OR USA. NCI, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Perry Point, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Lieberman, DA (reprint author), Portland VA Med Ctr, Div Gastroenterol, P3-GI,POB 1034, Portland, OR 97207 USA. FU NCI NIH HHS [K07CA75159] NR 57 TC 258 Z9 264 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 10 PY 2003 VL 290 IS 22 BP 2959 EP 2967 DI 10.1001/jama.290.22.2959 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 751WH UT WOS:000187112700027 PM 14665657 ER PT J AU Giugliano, RP Braunwald, E AF Giugliano, RP Braunwald, E TI Selecting the best reperfusion strategy in ST-elevation myocardial infarction - It's all a matter of time SO CIRCULATION LA English DT Article DE editorials; myocardial infarction; reperfusion; angioplasty; fibrinolysis ID OPEN ARTERY HYPOTHESIS; PRIMARY ANGIOPLASTY; THROMBOLYTIC THERAPY; MORTALITY; SURVIVAL; SALVAGE; TRIAL C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave, Boston, MA 02115 USA. NR 22 TC 40 Z9 46 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 DEC 9 PY 2003 VL 108 IS 23 BP 2828 EP 2830 DI 10.1161/01.CIR.0000106684.71725.98 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 751MD UT WOS:000187070100014 PM 14662688 ER PT J AU Breitner, JCS Costa, PT AF Breitner, JCS Costa, PT TI "At my wits' end" - Neuroticism and dementia SO NEUROLOGY LA English DT Editorial Material ID DISEASE; BRAIN C1 Univ Washington, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Div Geriatr Psychiat, Seattle, WA 98195 USA. NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Breitner, JCS (reprint author), Univ Washington, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. OI Costa, Paul/0000-0003-4375-1712 FU NIA NIH HHS [AG-11380, AG-15477] NR 11 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 9 PY 2003 VL 61 IS 11 BP 1468 EP 1469 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 751MG UT WOS:000187070400002 PM 14663023 ER PT J AU Marshall, FJ Cudkowicz, M Hayden, M Kieburtz, K Zhao, HW Penney, J Dure, L Lane, J Raymond, L Decolongon, J Marder, K Moskowitz, C Dubinsky, R Gray, C Nance, M Radtke, D Feigin, A Shannon, B Higgins, D Baic, C Shannon, K Jaglin, J Hauser, R Delgado, H Almqvist, EW Hayden, M de Blieck, EA Biglan, K Hogarth, P Brocht, A Chadwick, C Daigneault, S Donaghue, P Josephson, L Shinaman, A Slough, M Weaver, C Bourgeois, K Oakes, D Watts, A AF Marshall, FJ Cudkowicz, M Hayden, M Kieburtz, K Zhao, HW Penney, J Dure, L Lane, J Raymond, L Decolongon, J Marder, K Moskowitz, C Dubinsky, R Gray, C Nance, M Radtke, D Feigin, A Shannon, B Higgins, D Baic, C Shannon, K Jaglin, J Hauser, R Delgado, H Almqvist, EW Hayden, M de Blieck, EA Biglan, K Hogarth, P Brocht, A Chadwick, C Daigneault, S Donaghue, P Josephson, L Shinaman, A Slough, M Weaver, C Bourgeois, K Oakes, D Watts, A CA Huntington Study Grp TI Dosage effects of riluzole in Huntington's disease - A multicenter placebo-controlled study SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; STRIATAL DEGENERATION; QUINOLINIC ACID; 3-NITROPROPIONIC ACID; CONTROLLED TRIAL; CLINICAL-TRIAL; LESIONS; RATS; DISORDERS; MOVEMENTS AB Background: Riluzole retards striatal glutamate release and pathologic consequences in neurotoxic animal models of Huntington's disease ( HD). Objective: To determine the dosage- related impact of riluzole on chorea in HD. Methods: An 8- week double- blind dose- ranging multicenter study of riluzole was conducted in 63 subjects ( 32 women, 31 men) with HD who were randomized to receive placebo, riluzole 100 mg/ day, or riluzole 200 mg/ day. The prespecified outcome measure was change in the total maximal chorea score of the Unified Huntington's Disease Rating Scale ( UHDRS). Results: Fifty- six ( 89%) subjects completed the study. A reduction ( p < 0.01) in chorea at 8 weeks was found using a linear trend test with dose. Comparing the groups individually, the reduction in chorea for the riluzole 200- mg/ day group ( - 2.2 +/- 3.3) was different ( p = 0.01) from placebo ( + 0.7 +/- 3.4), but the riluzole 100- mg/ day group ( - 0.2 +/- 2.9) was not. Riluzole did not improve other motor, cognitive, behavioral, or functional components of the UHDRS. Alanine aminotransferase was elevated in a dosage- dependent fashion ( p = 0.01). Conclusions: Over 8 weeks of treatment, riluzole 200 mg/ day ameliorated chorea intensity in HD without improving functional capacity or other clinical features of illness. Riluzole 200 mg/ day was attended by reversible liver transaminase abnormalities that would require monitoring in long- term studies. C1 Univ Rochester, Dept Neurol, Rochester, NY 14620 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Alabama, Birmingham, AL USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. N Shore Univ Hosp, Manhasset, NY USA. Ohio State Univ, Columbus, OH 43210 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ S Florida, Tampa, FL USA. RP Marshall, FJ (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Ave,Suite 223, Rochester, NY 14620 USA. RI Dure, Leon/B-3243-2008; Raymond, Lynn/A-6664-2010; Hayden, Michael/D-8581-2011 OI Raymond, Lynn/0000-0002-8610-1042; Hayden, Michael/0000-0001-5159-1419 NR 39 TC 59 Z9 61 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 9 PY 2003 VL 61 IS 11 BP 1551 EP 1556 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 751MG UT WOS:000187070400020 ER PT J AU Karamohamed, S DeStefano, AL Wilk, JB Shoemaker, CM Golbe, LI Mark, MH Lazzarini, AM Suchowersky, O Labelle, N Guttman, M Currie, LJ Wooten, GF Stacy, M Saint-Hilaire, M Feldman, RG Sullivan, KM Xu, G Watts, R Growdon, J Lew, M Waters, C Vieregge, P Pramstaller, PP Klein, C Racette, BA Perlmutter, JS Parsian, A Singer, C Montgomery, E Baker, K Gusella, JF Fink, SJ Myers, RH Herbert, A AF Karamohamed, S DeStefano, AL Wilk, JB Shoemaker, CM Golbe, LI Mark, MH Lazzarini, AM Suchowersky, O Labelle, N Guttman, M Currie, LJ Wooten, GF Stacy, M Saint-Hilaire, M Feldman, RG Sullivan, KM Xu, G Watts, R Growdon, J Lew, M Waters, C Vieregge, P Pramstaller, PP Klein, C Racette, BA Perlmutter, JS Parsian, A Singer, C Montgomery, E Baker, K Gusella, JF Fink, SJ Myers, RH Herbert, A TI A haplotype at the PARK3 locus influences onset age for Parkinson's disease - The GenePD study SO NEUROLOGY LA English DT Article ID FAMILIAL AGGREGATION; CHROMOSOME 2P13; LEWY BODY; TETRAHYDROBIOPTERIN; ALPHA; BIOSYNTHESIS; ASSOCIATION; POPULATION; CANDIDATE; MUTATIONS AB Objective: To identify a haplotype influencing onset age for Parkinson's disease ( PD) in the PARK3 region on chromosome 2p13. Methods: Single nucleotide polymorphisms ( SNP) spanning 2.2 Mb and located in or near potential candidate genes were used to fine map the PARK3 region in 527 patients with familial PD, from 264 families. Results: TT homozygotes for rs1876487 ( G/ T) had a 7.4- year younger mean age at onset ( p = 0.005) compared to patients with GT and GG genotypes. Furthermore, SNP flanking the sepiapterin reductase ( 7,8- dihydrobiopterin: NADP + oxidoreductase) ( SPR) gene, rs1876487 ( p = 0.02) and rs1150500 ( p = 0.04), were associated with younger onset age among persons who did not carry the 174 allele of D2S1394. The SPR gene is implicated in dopamine synthesis. Haplotype analysis of three SNP - rs2421095, rs1876487, rs1561244 - revealed an association with onset age ( p = 0.023) and a haplotype of A- T- G alleles was associated with younger onset for PD ( p = 0.005). Conclusions: A haplotype at the PARK3 locus, harboring the SPR gene, is associated with onset age of PD. This may suggest a role for the SPR gene in modifying the age at onset of PD. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08903 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. Univ Calgary, Dept Med Genet, Calgary, AB, Canada. Univ Toronto, Dept Med, Div Neurol, Toronto, ON, Canada. Univ Virginia Hlth Syst, Dept Neurol, Charlottesville, VA USA. Barrow Clin, Dept Neurol, Phoenix, AZ USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurogenet Unit, Boston, MA USA. Univ So Calif, Dept Neurol, Los Angeles, CA USA. Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Gen Reg Hosp Bolzano, Dept Neurol, Bolzano, Italy. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Louisville, Hlth Sci Ctr, Dept Mol & Cellular Biol, Louisville, KY 40292 USA. Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44195 USA. RP Karamohamed, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St, Boston, MA 02118 USA. RI Pramstaller, Peter/C-2357-2008 FU NINDS NIH HHS [R0-1 NS36711-05] NR 45 TC 35 Z9 39 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 9 PY 2003 VL 61 IS 11 BP 1557 EP 1561 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 751MG UT WOS:000187070400021 PM 14663042 ER PT J AU Lisi, S Pinchera, A McCluskey, RT Willnow, TE Refetoff, S Marcocci, C Vitti, P Menconi, F Grasso, L Luchetti, F Collins, AB Marino, M AF Lisi, S Pinchera, A McCluskey, RT Willnow, TE Refetoff, S Marcocci, C Vitti, P Menconi, F Grasso, L Luchetti, F Collins, AB Marino, M TI Preferential megalin-mediated transcytosis of low-hormonogenic thyroglobulin: A control mechanism for thyroid hormone release SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; CIRCULATING THYROGLOBULIN; ENDOCYTIC RECEPTOR; RAT THYROGLOBULIN; HEYMANN NEPHRITIS; CELLS; GP330; IDENTIFICATION; BINDING; HYPOTHYROIDISM AB Hormone secretion by thyrocytes occurs by fluid phase uptake and lysosomal degradation of the prohormone thyroglobulin (Tg). However, some Tg internalized by megalin bypasses lysosomes and is transcytosed across cells and released into the bloodstream. Because the hormone content of Tg is variable, we investigated whether this affects transcytosis. We found that rat Tg with a low hormone content [low-hormonogenic rat Tg (low-horm-rTg)] is transcytosed by megalin across thyroid FRTL-5 cells to a greater extent than rat Tg with a high hormone content [hormonogenic rat Tg (horm-rTg)]. In immunoprecipitation experiments, the Tg sequence Arg-2489-Lys-2503 (required for binding to megalin and heparan sulfate proteoglycans) was found to be more exposed in low-horm-rTg, which accounted for its preferential transcytosis. Thus, removal of surface heparan sulfate proteoglycans from FRTL-5 cells or blocking of 2489-2503 reduced transcytosis of low-horm-rTg to a greater extent than that of horm-rTg. Preferential transcytosis of low-horm-rTg affected hormone release. Thus, the increase in hormone release from horm-rTg in FRTL-5 cells determined by megalin blocking (due to reduced transcytosis and enhanced Tg degradation) was rescued by low-horm-rTg, suggesting that megalin is required for effective hormone release. This finding was confirmed in a small number of megalin-deficient mice, which had serological features resembling mild hypothyroidism. Reduced hormone formation within Tg in vivo, due to treatment of rats with aminotriazole or of patients with Graves' disease with methimazole, resulted in increased Tg transcytosis via megalin, in confirmation of results with FRTL-5 cells. Our study points to a major role of megalin in thyroid homeostasis with possible implications in thyroid diseases. C1 Univ Pisa, Dept Endocrinol, I-56124 Pisa, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. RP Marino, M (reprint author), Univ Pisa, Dept Endocrinol, Via Paradisa 2, I-56124 Pisa, Italy. FU NIDDK NIH HHS [DK15070, R37 DK015070, R01 DK015070] NR 39 TC 30 Z9 33 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 2003 VL 100 IS 25 BP 14858 EP 14863 DI 10.1073/pnas.2432267100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 753JA UT WOS:000187227200047 PM 14657389 ER PT J AU Murtaugh, LC Stanger, BZ Kwan, KM Melton, DA AF Murtaugh, LC Stanger, BZ Kwan, KM Melton, DA TI Notch signaling controls multiple steps of pancreatic differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BETA-CELLS; ENDOCRINE DEVELOPMENT; INSULIN GENE; EXPRESSION; PROGENITORS; PATHWAY; REVEALS AB Multiple cell types of the pancreas appear asynchronously during embryogenesis, which requires that pancreatic progenitor cell potential changes over time. Loss-of-function studies have shown that Notch signaling modulates the differentiation of these progenitors, but it remains unclear how and when the Notch pathway acts. We established a modular transgenic system to heritably activate mouse Notch1 in multiple types of progenitors and differentiated cells. We find that misexpression of activated Notch in Pdx1-expressing progenitor cells prevents differentiation of both exocrine and endocrine lineages. Progenitors remain trapped in an undifferentiated state even if Notch activation occurs long after the pancreas has been specified. Furthermore, endocrine differentiation is associated with escape from this activity, because Ngn3-expressing endocrine precursors are susceptible to Notch inhibition, whereas fully differentiated endocrine cells are resistant. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Melton, DA (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 02138 USA. NR 19 TC 437 Z9 445 U1 1 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 9 PY 2003 VL 100 IS 25 BP 14920 EP 14925 DI 10.1073/pnas.2436557100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 753JA UT WOS:000187227200058 PM 14657333 ER PT J AU Reusch, JEB Regensteiner, JG Watson, PA AF Reusch, JEB Regensteiner, JG Watson, PA TI Novel actions of thiazolidinediones on vascular function and exercise capacity SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; SMOOTH-MUSCLE-CELLS; BINDING PROTEIN-DELTA; FACTOR-ALPHA-RECEPTOR; LOW CARDIORESPIRATORY FITNESS; UPTAKE KINETIC RESPONSES; DIABETES-MELLITUS; INSULIN-RESISTANCE; GENE-EXPRESSION; BLOOD-PRESSURE AB The endothelium is the first line of defense for maintaining normal vascular function in the vessel wall; however, the endothelium is sensitive to metabolic stress. In patients with insulin resistance or type 2 diabetes mellitus, a set of metabolic insults-namely high plasma levels of glucose and free fatty acids, increased inflammation, dyslipidemia, and hypertension-cause endothelial dysfunction and a transition from an antiatherogenic endothelium to a proatherogenic endothelium. Disruption of endothelial function leads to activation of platelets and macrophages, increased thrombotic potential, transition of macrophages to foam cells, stimulation of cytokine secretion, and proliferation of vascular smooth muscle cells. Insulin-sensitizing agents, such as the thiazolidinediones (TZDs), improve flow-mediated vasodilation, decrease macrophage and smooth muscle cell activation, proliferation, and migration, and decrease plaque formation. The TZDs exert multifaceted effects on the vasculature by regulating the expression of transcription factors and orchestrating whole-gene programs that restore vascular physiology to the healthy state. Exercise training and increased levels of habitual physical activity have therapeutic benefit in terms of both preventing and treating insulin resistance and diabetes. However, this benefit of exercise training and increased physical activity is complicated by the fact that individuals with insulin resistance or type 2 diabetes have decreased maximal exercise capacity or maximal oxygen consumption and have slower oxygen uptake kinetics at the beginning of exercise. Both of these abnormalities contribute to the decreased levels of habitual physical activity observed in patients with diabetes. Preliminary data suggest that TZDs improve measures of cardiac function and exercise capacity, and investigators are assessing the impact of treatment with rosiglitazone on exercise capacity in an ongoing clinical trial. (C) 2003 by Excerpta Medica, Inc. C1 Denver VA Med Ctr 111H, Denver, CO 80220 USA. RP Reusch, JEB (reprint author), Denver VA Med Ctr 111H, 1055 Clermont St, Denver, CO 80220 USA. NR 53 TC 4 Z9 4 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 8 PY 2003 VL 115 SU 8A BP 69 EP 74 DI 10.1016/j.amjmed.2003.09.012 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 754JD UT WOS:000187311800012 ER PT J AU Abrahamson, MJ AF Abrahamson, MJ TI Clinical use of thiazolidinediones: Recommendations SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID TYPE-2 DIABETES-MELLITUS; BLOOD-GLUCOSE CONTROL; BETA-CELL FUNCTION; GLYCEMIC CONTROL; METFORMIN; INSULIN; ROSIGLITAZONE; COMPLICATIONS; THERAPY; TRIAL AB Type 2 diabetes mellitus is characterized by progressive beta-cell secretory dysfunction against a background of insulin resistance, which is present many years before the onset of hyperglycemia in most patients. Intensive treatment of diabetes reduces the risk of the onset and progression of microvascular complications and may impact the risk of development of macrovascular complications, notably coronary artery disease. Therefore, aggressive treatment with the goal of achieving serum glucose concentrations as close to normal as possible is warranted. Although medical nutritional therapy and exercise remain the cornerstones of therapy for type 2 diabetes, >90% of patients ultimately require pharmacologic therapy, and most need >1 agent to achieve therapeutic objectives. When considering which agent or agents to use to treat type 2 diabetes, one must consider the mechanism of action of the drug, its ability to lower serum glucose concentrations, the durability of effect, and potential adverse effects. In addition, some medications have potential benefits that extend beyond glucose lowering. These include beneficial effects on the adverse metabolic consequences of insulin resistance and possibly beta-cell preservation. Thiazolidinediones should be considered as early as possible in the natural history of type 2 diabetes because of their persistent glucose-lowering effect and their ability to reduce insulin resistance as well as because these agents may preserve beta-cell function and reverse some of the adverse metabolic consequences of insulin resistance. (C) 2003 by Excerpta Medica, Inc. C1 Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. RP Abrahamson, MJ (reprint author), Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. NR 36 TC 6 Z9 6 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 8 PY 2003 VL 115 SU 8A BP 116 EP 120 DI 10.1016/S0002-9343(03)00522-9 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 754JD UT WOS:000187311800020 ER PT J AU Sasaki, H Dai, M Auclair, D Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y Chen, LB AF Sasaki, H Dai, M Auclair, D Kaji, M Fukai, I Kiriyama, M Yamakawa, Y Fujii, Y Chen, LB TI Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients (vol 172, pg 37, 2001) SO CANCER LETTERS LA English DT Correction C1 Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, Nagoya, Aichi 4678601, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Sasaki, H (reprint author), Nagoya City Univ, Sch Med, Dept Surg 2, Mizuho Ku, 1 Kawasumi,Mizhuo Cho, Nagoya, Aichi 4678601, Japan. NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 8 PY 2003 VL 202 IS 1 BP 117 EP 117 DI 10.1016/S0304-3835(03)00217-9 PG 1 WC Oncology SC Oncology GA 753NK UT WOS:000187237300014 ER PT J AU Stipp, CS Kolesnikova, TV Hemler, ME AF Stipp, CS Kolesnikova, TV Hemler, ME TI EWI-2 regulates alpha 3 beta 1 integrin-dependent cell functions on laminin-5 SO JOURNAL OF CELL BIOLOGY LA English DT Article DE integrins; tetraspanins; laminin-5; CD9; CD81 ID TETRASPANIN PROTEINS; CD151; CD81; COMPLEXES; MEMBRANE; SURFACE; ALPHA-6-BETA-4; HEMIDESMOSOMES; ASSOCIATION; MIGRATION AB EWI-2, a cell surface immunoglobulin SF protein of unknown function, associates with tetraspanins CD9 and CD81 with high stoichiometry. Overexpression of EWI-2 in A431 epidermoid carcinoma cells did not alter cell adhesion or spreading on laminin-5, and had no effect on reaggregation of cells plated on collagen 1 (alpha2beta1 integrin ligand). However, on laminin-5 (alpha3beta1 integrin ligand), A431 cell reaggregation and motility functions were markedly impaired. Immunodepletion and reexpression experiments revealed that tetraspanins CD9 and CD81 physically link EWI-2 to alpha3beta1 integrin, but not to other integrins. CD81 also controlled EWI-2 maturation and cell surface localization. EWI-2 overexpression not only suppressed cell migration, but also redirected CD81 to cell filopodia and enhanced alpha3beta1-CD81 complex formation. In contrast, an EWI-2 chimeric mutant failed to suppress cell migration, redirect CD81 to filopodia, or enhance alpha3beta1-CD81 complex formation. These results show how laterally associated EWI-2 might regulate alpha3beta1 function in disease and development, and demonstrate how tetraspanin proteins can assemble multiple nontetraspanin proteins into functional complexes. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Rm D1430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA42368, R01 CA042368]; NIGMS NIH HHS [R01 GM038903, GM38903] NR 41 TC 57 Z9 59 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 8 PY 2003 VL 163 IS 5 BP 1167 EP 1177 DI 10.1083/jcb.200309113 PG 11 WC Cell Biology SC Cell Biology GA 755UU UT WOS:000187430500022 PM 14662754 ER PT J AU Altfeld, M Addo, MA Rosenberg, ES Hecht, FA Lee, PK Vogel, M Yu, XG Draenert, R Johnston, MN Strick, D Allen, TA Feeney, ME Kahn, JO Sekaly, RP Levy, JA Rockstroh, JK Goulder, PJR Walker, BD AF Altfeld, M Addo, MA Rosenberg, ES Hecht, FA Lee, PK Vogel, M Yu, XG Draenert, R Johnston, MN Strick, D Allen, TA Feeney, ME Kahn, JO Sekaly, RP Levy, JA Rockstroh, JK Goulder, PJR Walker, BD TI Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection SO AIDS LA English DT Article DE cytotoxic T lymphocytes; HLA-B57; CTL epitopes; immunodominance; acute HIV-1 infection ID CYTOTOXIC T-LYMPHOCYTE; VIRUS TYPE-1 INFECTION; CELLULAR IMMUNE-RESPONSES; LONG-TERM NONPROGRESSORS; HLA CLASS-I; DISEASE PROGRESSION; SLOW PROGRESSORS; ESCAPE VARIANTS; HOMOSEXUAL-MEN; AIDS AB Background: HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not known. Methods: Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed. HIV-1-specific T-cell responses were determined by peptide-specific interferon-gamma production measured using Elispot assay and flow-based intracellular cytokine quantification. Results: Individuals expressing HLA-B57 presented significantly less frequently with symptomatic acute HIV-1 infection (4/116, 3.4%) than expected from the frequency of chronically infected individuals expressing this allele (43/446, 9.6%; P < 0.05). During acute infection, virus-specific CD8 T-cell responses were dominated by HLA-B57-restricted responses, with significantly broader (P < 0.02) and stronger (P < 0.03) responses restricted by HLA-B57 than restricted by all other co-expressed HLA class I alleles combined. Six out of nine individuals expressing HLA-B57 controlled HIV-1 viremia in the absence of therapy at levels < 5000 copies/ml (median, 515 copies/ml) during up to 29 months following acute infection. Conclusion: These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control. (C) 2003 Lippincott Williams Wilkins. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. UCSF, Posit Hlth Program, San Francisco, CA USA. Univ Bonn, Dept Internal Med, D-5300 Bonn, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA USA. Harvard Univ, Sch Med, Div Aids, Boston, MA USA. Inst Rech Clin Montreal, Immunol Lab, Montreal, PQ H2W 1R7, Canada. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Nuffield Dept Med, Dept Paediat, Oxford, England. RP Walker, BD (reprint author), MGH E, CNY 5212,149 13th St, Charlestown, MA 02129 USA. RI Allen, Todd/F-5473-2011 NR 55 TC 235 Z9 241 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD DEC 5 PY 2003 VL 17 IS 18 BP 2581 EP 2591 DI 10.1097/01.aids.0000096870.36052.b6 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 809YU UT WOS:000220672800005 PM 14685052 ER PT J AU Fabbri, F Henry, ME Renshaw, PF Nadgir, S Ehrenberg, BL Franceschini, MA Fantini, S AF Fabbri, F Henry, ME Renshaw, PF Nadgir, S Ehrenberg, BL Franceschini, MA Fantini, S TI Bilateral near-infrared monitoring of the cerebral concentration and oxygen-saturation of hemoglobin during right unilateral electro-convulsive therapy SO BRAIN RESEARCH LA English DT Article DE electro-convulsive therapy; near-infrared spectroscopy; seizure; cerebral hemodynamics ID STRONGLY SCATTERING MEDIA; BLOOD-FLOW; SEIZURE THRESHOLD; SPECTROSCOPY NIRS; BRAIN GLUCOSE; HUMAN ADULTS; SPECTROPHOTOMETRY; HEMODYNAMICS; ACTIVATION; TOPOGRAPHY AB Reductions in right prefrontal cerebral blood flow have been correlated with symptomatic improvement in depressed individuals receiving electroconvulsive therapy (ECT). Non-invasive near infrared spectroscopy has previously been shown to reliably measure changes in cerebral hemoglobin concentrations and oxygen saturation. In this study, we measured the concentration and oxygen saturation of hemoglobin on the right and left frontal brain regions of nine patients during right unilateral ECT. In all patients, we have found that the electrically induced seizure causes a stronger cerebral deoxygenation on the side ipsilateral to the electrical current (-21 +/- 5%) with respect to the contralateral side (-6 +/- 4%). On the brain side ipsilateral to the ECT electrical discharge, we have consistently observed a discharge-induced decrease in the total hemoglobin concentration, i.e. in the cerebral blood volume, by -7 +/- 3 muM, as opposed to an average increase by 6 +/- 3 muM on the contralateral side. The ipsilateral decrease in blood volume is assigned to a vascular constriction associated with the electrical discharge, as indicated by the observed decrease in cerebral oxy-hemoglobin concentration and minimal change in deoxy-hemoglobin concentration during the electrical discharge on the side of the discharge. These findings provide indications about the cerebral hemodynamic/metabolic mechanisms associated with ECT, and may lead to useful parameters to predict the individual clinical outcome of ECT. (C) 2003 Elsevier B.V. All rights reserved. C1 Tufts Univ, Ctr Bioengn, Dept Biomed Engn, Medford, MA 02155 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. McLean Hosp, Belmont, MA 02478 USA. RP Fabbri, F (reprint author), Tufts Univ, Ctr Bioengn, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA. FU NIDA NIH HHS [DA14178]; NIMH NIH HHS [MH62854, MH64175, R01 MH062854, R01 MH062854-01, R01 MH062854-02] NR 35 TC 27 Z9 27 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 5 PY 2003 VL 992 IS 2 BP 193 EP 204 DI 10.1016/j.brainres.2003.08.034 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 748YE UT WOS:000186887900005 PM 14625058 ER PT J AU Lichtenthaler, SF Dominguez, D Westmeyer, GG Reiss, K Haass, C Saftig, P De Strooper, B Seed, B AF Lichtenthaler, SF Dominguez, D Westmeyer, GG Reiss, K Haass, C Saftig, P De Strooper, B Seed, B TI The cell adhesion protein P-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; ALZHEIMERS BETA-SECRETASE; GAMMA-SECRETASE; TNF RECEPTOR; CLEAVAGE; DISEASE; PRESENILIN; GENERATION; INHIBITOR; PSGL-1 AB The aspartyl protease BACE1 cleaves the amyloid precursor protein and the sialyltransferase ST6Gal I and is important in the pathogenesis of Alzheimer's disease. The normal function of BACE1 and additional physiological substrates have not been identified. Here we show that BACE1 acts on the P-selectin glycoprotein ligand 1 (PSGL-1), which mediates leukocyte adhesion in inflammatory reactions. In human monocytic U937 and human embryonic kidney 293 cells expressing endogenous or transfected BACE1, PSGL-1 was cleaved by BACE1 to generate a soluble ectodomain and a C-terminal transmembrane fragment. No evidence of the cleavage fragment was seen in primary cells derived from mice deficient in BACE1. By using deletion constructs and enzymatic deglycosylation of the C-terminal PSGL-1 fragments, the cleavage site in PSGL-1 was mapped to the juxtamembrane region within the ectodomain. In an in vitro assay BACE1 catalyzed the formation of the PSGL-1 products seen in vivo. The cleavage occurred at a Leu-Ser peptide bond as identified by mass spectrometry using a synthetic peptide. We conclude that PSGL-1 is an additional substrate for BACE1. C1 Univ Munich, A Butenandt Inst, D-80336 Munich, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Katholieke Univ Leuven, Ctr Human Genet, B-3000 Louvain, Belgium. Univ Kiel, Inst Biochem, D-24098 Kiel, Germany. RP Lichtenthaler, SF (reprint author), Univ Munich, A Butenandt Inst, Schillerstr 44, D-80336 Munich, Germany. RI Saftig, Paul/A-7966-2010; Reiss, Karina/B-3175-2010; De Strooper, Bart/F-6507-2012; Lichtenthaler, Stefan/B-6587-2016 OI De Strooper, Bart/0000-0001-5455-5819; Lichtenthaler, Stefan/0000-0003-2211-2575 FU NIAID NIH HHS [AI46731, AI27849] NR 40 TC 186 Z9 189 U1 0 U2 9 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 DEC 5 PY 2003 VL 278 IS 49 BP 48713 EP 48719 DI 10.1074/jbc.M303861200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 747WL UT WOS:000186829000026 PM 14507929 ER PT J AU Pastor-Soler, N Beaulieu, V Litvin, TN Da Silva, N Chen, YQ Brown, D Buck, J Levin, LR Breton, S AF Pastor-Soler, N Beaulieu, V Litvin, TN Da Silva, N Chen, YQ Brown, D Buck, J Levin, LR Breton, S TI Bicarbonate-regulated adenylyl cyclase (sAC) is a sensor that regulates pH-dependent V-ATPase recycling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALE REPRODUCTIVE-TRACT; RAT EPIDIDYMIS; PROTON SECRETION; VAS-DEFERENS; POSTNATAL-DEVELOPMENT; H+-ATPASE; CELLS; TRANSPORT; COLOCALIZATION; ACIDIFICATION AB Modulation of environmental pH is critical for the function of many biological systems. However, the molecular identity of the pH sensor and its interaction with downstream effector proteins remain poorly understood. Using the male reproductive tract as a model system in which luminal acidification is critical for sperm maturation and storage, we now report a novel pathway for pH regulation linking the bicarbonate activated soluble adenylyl cyclase (sAC) to the vacuolar H+ ATPase (V-ATPase). Clear cells of the epididymis and vas deferens contain abundant V-ATPase in their apical pole and are responsible for acidifying the lumen. Proton secretion is regulated via active recycling of V-ATPase. Here we demonstrate that this recycling is regulated by luminal pH and bicarbonate. sAC is highly expressed in clear cells, and apical membrane accumulation of V-ATPase is triggered by a sAC-dependent rise in cAMP in response to alkaline luminal pH. As sAC is expressed in other acid/base transporting epithelia, including kidney and choroid plexus, this cAMP-dependent signal transduction pathway may be a widespread mechanism that allows cells to sense and modulate extracellular pH. C1 Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA. RP Breton, S (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St 149-8000, Charlestown, MA 02129 USA. OI Levin, Lonny/0000-0002-5204-6356 FU NICHD NIH HHS [F32 HD008684, HD38722, HD40793, HD42060, R01 HD038722, R01 HD040793]; NIDDK NIH HHS [DK38452, DK42956, DK43351, DK57521, P01 DK038452, P30 DK043351, P30 DK057521, R01 DK042956, R37 DK042956]; NIGMS NIH HHS [GM62328, R01 GM062328] NR 34 TC 163 Z9 164 U1 2 U2 7 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 DEC 5 PY 2003 VL 278 IS 49 BP 49523 EP 49529 DI 10.1074/jbc.M309543200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 747WL UT WOS:000186829000122 PM 14512417 ER PT J AU White, MF AF White, MF TI Insulin signaling in health and disease SO SCIENCE LA English DT Article ID STIMULATES TYROSINE PHOSPHORYLATION; RECEPTOR SUBSTRATE-2; RESISTANCE; GROWTH; CELLS; PROTEIN; OBESITY AB The signaling pathways used by insulin have been identified [M. White, Insulin Signaling Pathway, Sci. STKE (Connections Map, as seen November 2003), http://stke.sciencemag. org/cgi/cm/cmp_12069]. Now our challenge is to understand how the failure of these signals is associated with obesity and the progressive failure of pancreatic beta cells that leads to diabetes. Whether better management of chronic inflammation can improve insulin action is an important area of investigation. Drugs that stimulate IRS2 (insulin receptor substrate protein 2) synthesis or signaling might be a good starting point. This knowledge will lead to rational strategies that prevent or cure diabetes. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. NR 21 TC 338 Z9 366 U1 5 U2 28 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 DEC 5 PY 2003 VL 302 IS 5651 BP 1710 EP 1711 DI 10.1126/science.1092952 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 750AX UT WOS:000186970100034 PM 14657487 ER PT J AU Pardee, AB Reddy, GPV AF Pardee, AB Reddy, GPV TI Beginnings of feedback inhibition, allostery and multi-protein complexes SO GENE LA English DT Review DE allostery; aspartate transcarbamylase; feedback inhibition; metabolic regulation; protein complex; replitase ID ESCHERICHIA-COLI; ASPARTATE TRANSCARBAMOYLASE; TRIPHOSPHATE SYNTHETASE; PYRIMIDINE BIOSYNTHESIS; CATALYTIC ACTIVITY; ENZYME ACTIVITY; MECHANISM; DNA; ISOLEUCINE; COMPARTMENTATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Vattikuti Urol Inst Henry Ford, Hlth Sci Ctr, Detroit, MI USA. RP Pardee, AB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 64 TC 19 Z9 19 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 4 PY 2003 VL 321 BP 17 EP 23 DI 10.1016/S0378-1119(03)00839-4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 753WA UT WOS:000187252900002 PM 14636988 ER PT J AU Tuch, DS Reese, TG Wiegell, MR Wedeen, VJ AF Tuch, DS Reese, TG Wiegell, MR Wedeen, VJ TI Diffusion MRI of complex neural architecture SO NEURON LA English DT Article ID ORIENTATIONAL STRUCTURE FACTOR; BRAIN WHITE-MATTER; MAGNETIC-RESONANCE; WATER DIFFUSION; WEIGHTED MRI; IN-VIVO; AXONAL PROJECTIONS; PROPAGATOR REPRESENTATION; SPIN-ECHO; RAT-BRAIN AB While functional brain imaging methods can locate the cortical regions subserving particular cognitive functions, the connectivity between the functional areas of the human brain remains poorly understood. Recently, investigators have proposed a method to image neural connectivity noninvasively using a magnetic resonance imaging method called diffusion tensor imaging (DTI). DTI measures the molecular diffusion of water along neural pathways. Accurate reconstruction of neural connectivity patterns from DTI has been hindered, however, by the inability of DTI to resolve more than a single axon direction within each imaging voxel. Here, we present a novel magnetic resonance imaging technique that can resolve multiple axon directions within a single voxel. The technique, called q-ball imaging, can resolve intravoxel white matter fiber crossing as well as white matter insertions into cortex. The ability of q-ball imaging to resolve complex intravoxel fiber architecture eliminates a key obstacle to mapping neural connectivity in the human brain noninvasively. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Tuch, DS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Charlestown, MA 02129 USA. FU NCRR NIH HHS [RR14075]; NIMH NIH HHS [MH64044]; NINDS NIH HHS [NS46532] NR 61 TC 397 Z9 402 U1 2 U2 25 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 4 PY 2003 VL 40 IS 5 BP 885 EP 895 DI 10.1016/S0896-6273(03)00758-X PG 11 WC Neurosciences SC Neurosciences & Neurology GA 751FM UT WOS:000187042200006 PM 14659088 ER PT J AU Enzinger, PC Mayer, RJ AF Enzinger, PC Mayer, RJ TI Medical progress - Esophageal cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PROSPECTIVE RANDOMIZED TRIAL; SQUAMOUS-CELL CARCINOMA; SYMPTOMATIC GASTROESOPHAGEAL REFLUX; ADVANCED ESOPHAGOGASTRIC CANCER; EXPANDABLE METAL STENTS; HIGH-GRADE DYSPLASIA; PHASE-II TRIAL; TERM FOLLOW-UP; BARRETTS-ESOPHAGUS; GASTRIC CARDIA C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Enzinger, PC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 122 TC 1484 Z9 1580 U1 10 U2 88 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 4 PY 2003 VL 349 IS 23 BP 2241 EP 2252 DI 10.1056/NEJMra035010 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 749LH UT WOS:000186921700012 PM 14657432 ER PT J AU Harper, CG Xu, SL Rogers, AB Feng, Y Shen, ZL Taylor, NS Dewhirst, FE Paster, BJ Miller, M Hurley, J Fox, JG AF Harper, CG Xu, SL Rogers, AB Feng, Y Shen, ZL Taylor, NS Dewhirst, FE Paster, BJ Miller, M Hurley, J Fox, JG TI Isolation and characterization of novel Helicobacter spp. from the gastric mucosa of harp seals Phoca groenlandica SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE harp seal; pinniped; helicobacter infection; gastritis; Cryptosporidium ID SYRIAN-HAMSTERS; SP-NOV.; CRYPTOSPORIDIUM; CANIS; PHYLOGENY; PINNIPEDS; DISEASES; DOLPHINS; AURATI; DOGS AB Since the recent discovery of Helicobacter cetorum in cetaceans and its role in the development of gastritis, speculation has existed as to whether pinnipeds have Helicobacter spp. associated gastritis and peptic ulcer disease. The gastric mucosa of 4 stranded harp seals Phoca groenlandica from the Massachusetts coastline were assessed for Helicobacter spp. by culture and PCR. We cultured 2 novel Helicobacter spp. from the pyloric antrum of 1 of the 4 harp seals studied, and identified these by PCR in 2 of the 4 seals. Both gram-negative bacterial isolates were catalase- and oxidase-positive. However, a fusiform helicobacter with flexispira morphology was urease-positive, and a spiral-shaped helicobacter was urease-negative. Slender, spiral and fusiform-shaped bacteria were detected in the gastric mucosa by the Warthin-Starry stain. Histopathologic analysis revealed mild diffuse lymphoplasmacytic gastritis within the superficial mucosa of the pyloric antrum of both infected seals. The 2 bacterial isolates were classified by 16S rRNA analysis; they clustered with other enteric helicobacters and represent 2 novel Helicobacter spp. The urease-negative bacterial isolate clustered with H. canis and the urease-positive isolate clustered with an isolate from a sea lion and isolates from sea otters. This cluster of pinniped isolates has 97% similarity to a number of Helicobacter species, but appears to be most closely related to other helicobacters with flexispira morphology. These findings suggest that the novel Helicobacter spp. may play a role in the etiopathogenesis of gastrointestinal diseases in pinnipeds. To our knowledge, this represents the first isolation and characterization of a novel Helicobacter spp. from pinnipeds. C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Calif Dept Fish & Game, Santa Cruz, CA 95060 USA. Univ Calif Davis, Marine Wildlife Vet Care & Res Ctr, Santa Cruz, CA 95060 USA. Calif State Univ, Moss Landing Marine Lab, Moss Landing, CA 95039 USA. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave,Bldg 16,Room 825C, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCRR NIH HHS [T32-RR07036]; NIAID NIH HHS [R01-AI37750]; NIDCR NIH HHS [R01-DE10374] NR 33 TC 15 Z9 17 U1 0 U2 10 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD DEC 3 PY 2003 VL 57 IS 1-2 BP 1 EP 9 DI 10.3354/dao057001 PG 9 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 779CH UT WOS:000189277700001 PM 14735915 ER PT J AU Pierluissi, E Fischer, MA Campbell, AR Landefeld, CS AF Pierluissi, E Fischer, MA Campbell, AR Landefeld, CS TI Discussion of medical errors in morbidity and mortality conferences SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MISTAKES; PHYSICIANS; QUALITY; IMPACT; CARE AB Context Morbidity and mortality conferences in residency programs are intended to discuss adverse events and errors with a goal to improve patient care. Little is known about whether residency training programs are accomplishing this goal, Objective To determine the frequency at-which morbidity and mortality conference case presentations include adverse events and errors and whether the errors are discussed and attributed to a particular cause. Design, Setting, and Participants Prospective survey conducted by trained physician observers from July 2000 through April 2001 on 332 morbidity and mortality conference case presentations and discussions in internal medicine (n = 100) and surgery (n =232) at 4 US academic hospitals. Main Outcome Measures Frequencies of presentation of adverse events and errors, discussion of errors, and attribution of errors. Results In internal medicine morbidity and mortality conferences, case presentations and discussions were 3 times longer than in surgery conferences (34.1 minutes vs 11.7 minutes; P=.001), more time was spent listening to invited speakers (43.1% vs 0%; P<.001), and less time was spent in audience discussion (15.2% vs 36.6% P<.001). Fewer internal medicine case presentations included adverse events (37 [37%] vs 166 surgery case presentations [72%]; P<.001) or errors causing an adverse event (18 [18%] vs 98 [42%], respectively; P=.001). When an error caused an adverse event, the error was discussed as an error less often in internal medicine (10 errors [48%] vs 85 errors in surgery (77%]; P=.02). Errors were attributed to a particular cause less often in medicine than in surgery conferences (8 [38%] of 21 medicine errors vs 88 [79%] of 112 surgery errors; P<.001). In discussions of cases with errors, conference leaders in both internal medicine and surgery infrequently used explicit language to signal that an error was being discussed and infrequently acknowledged having made an error. Conclusions Our findings call into question whether adverse events and errors are routinely discussed in internal medicine training programs. Although adverse events and errors were discussed frequently in surgery cases, teachers in both surgery and internal medicine missed opportunities to model recognition of error and to use explicit language in error discussion by acknowledging their personal experiences with error. C1 Univ Calif San Francisco, Sch Med, San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, San Francisco Gen Hosp, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Stanford Univ, Palo Alto Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. RP Pierluissi, E (reprint author), San Mateo Med Ctr, 222 W 39th St, San Mateo, CA 94403 USA. FU NIA NIH HHS [K-07 AG00912] NR 27 TC 130 Z9 131 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 3 PY 2003 VL 290 IS 21 BP 2838 EP 2842 DI 10.1001/jama.290.21.2838 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 748QP UT WOS:000186872800026 PM 14657068 ER PT J AU Nathan, DM AF Nathan, DM TI Isolated pancreas transplantation for type 1 diabetes - A doctor's dilemma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID QUALITY-OF-LIFE; LONG-TERM COMPLICATIONS; RENAL-TRANSPLANTATION; INTENSIVE TREATMENT; NEPHROPATHY; MELLITUS; KIDNEY; PROGRESSION; THERAPY; TRIAL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Nathan, DM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Diabet, Boston, MA 02114 USA. EM dnathan@partners.org NR 22 TC 5 Z9 7 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 3 PY 2003 VL 290 IS 21 BP 2861 EP 2863 DI 10.1001/jama.290.21.2861 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 748QP UT WOS:000186872800030 PM 14657072 ER PT J AU Levine, RA Hung, J AF Levine, RA Hung, J TI Ischemic mitral regurgitation, the dynamic lesion: Clues to the cure SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID LEFT-VENTRICULAR DYSFUNCTION; CORONARY-ARTERY-DISEASE; PAPILLARY-MUSCLE DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; 3-DIMENSIONAL ECHOCARDIOGRAPHY; ORIFICE AREA; VALVE REPAIR; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; BICYCLE EXERCISE C1 Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Levine, RA (reprint author), Harvard Univ, Cardiac Ultrasound Lab, Massachusetts Gen Hosp, Dept Med, 55 Fruit St,VBK 508, Boston, MA 02114 USA. EM rlevine@partners.org FU NHLBI NIH HHS [K23 HL04504, K24 HL67434, R01 HL38176] NR 57 TC 26 Z9 28 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 DEC 3 PY 2003 VL 42 IS 11 BP 1929 EP 1932 DI 10.1016/j.jacc.2003.09.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 749JU UT WOS:000186917200011 PM 14662254 ER PT J AU Blackwell, TK Walker, AK AF Blackwell, TK Walker, AK TI Transcription elongation: TLKing to chromatin? SO CURRENT BIOLOGY LA English DT Editorial Material ID RNA-POLYMERASE-II; HISTONE METHYLATION; GENE-EXPRESSION; HUMAN ASF1; IN-VIVO; P-TEFB; CAF-1 AB The tousled-like kinases have been implicated in chromatin deposition, but surprising new findings in Caenorhabditis elegans indicate they have a role in transcription elongation. Are these apparently distinct functions of tousled-like kinases related? C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM062891] NR 17 TC 3 Z9 4 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 2 PY 2003 VL 13 IS 23 BP R915 EP R916 DI 10.1016/j.cub.2003.11.013 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 750NG UT WOS:000187002200013 PM 14654017 ER PT J AU Meigs, JB AF Meigs, JB TI Epidemiology of cardiovascular complications in type 2 diabetes mellitus SO ACTA DIABETOLOGICA LA English DT Article; Proceedings Paper CT Conference of the Diabetes-International-Research-and-Education-Cooperation-Team CY MAY 08-13, 2003 CL BUDAPEST, HUNGARY SP Diabet Int Res & Educ Cooperat Team DE epidemiology; risk factors; type 2 diabetes; cardiovascular disease; insulin resistance; prevention ID INSULIN-RESISTANCE SYNDROME; PRIOR MYOCARDIAL-INFARCTION; CORONARY HEART-DISEASE; METABOLIC SYNDROME; MORTALITY; RISK; IMPACT; PREVALENCE; POPULATION; DIAGNOSIS AB Type 2 diabetes is increasing in epidemic proportions worldwide, and is strongly associated with atherosclerotic cardiovascular disease (CVD). Hyperglycaemia increases risk of CVD, but glycaemic control does not substantially reduce CVD risk. There are several potential explanations for this apparent paradox, including the roles of the metabolic syndrome and post-load hyperglycaemia in the association of type 2 diabetes and CVD. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St 9th Floor, Boston, MA 02114 USA. NR 29 TC 34 Z9 35 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD DEC PY 2003 VL 40 SU 2 BP S358 EP S361 DI 10.1007/s00592-003-0120-0 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 758HP UT WOS:000187628600009 PM 14704869 ER PT J AU Suit, H Goldberg, S Niemierko, A Trofimov, A Adams, J Paganetti, H Chen, GTY Bortfeld, T Rosenthal, S Loeffler, J Delaney, T AF Suit, H Goldberg, S Niemierko, A Trofimov, A Adams, J Paganetti, H Chen, GTY Bortfeld, T Rosenthal, S Loeffler, J Delaney, T TI Proton beams to replace photon beams in radical dose treatments SO ACTA ONCOLOGICA LA English DT Article ID HIGH ENERGY PROTONS; THERAPY; RADIOTHERAPY; IRRADIATION; CANCER; SKULL; TRIAL; BASE AB With proton beam radiation therapy a smaller volume of normal tissues is irradiated at high dose levels for most anatomic sites than is feasible with any photon technique. This is due to the Laws of Physics, which determine the absorption of energy from photons and protons. In other words, the dose from a photon beam decreases exponentially with depth in the irradiated material. In contrast, protons have a finite range and that range is energy dependent. Accordingly, by appropriate distribution of proton energies, the dose can be uniform across the target and essentially zero deep to the target and the atomic composition of the irradiated material. The dose proximal to the target is lower compared with that in photon techniques, for all except superficial targets. This resultant closer approximation of the planning treatment volume (PTV) to the CTV/GTV (grossly evident tumor volume/subclinical tumor extensions) constitutes a clinical gain by definition; i.e. a smaller treatment volume that covers the target three dimensionally for the entirety of each treatment session provides a clinical advantage. Several illustrative clinical dose distributions are presented and the clinical outcome results are reviewed briefly. An important technical advance will be the use of intensity modulated proton radiation therapy, which achieves contouring of the proximal edge of the SOBP (spread out Bragg peak) as well as the distal edge. This technique uses pencil beam scanning. To permit further progressive reductions of the PTV, 4-D treatment planning and delivery is required. The fourth dimension is time, as the position and contours of the tumor and the adjacent critical normal tissues are not constant. A potentially valuable new method for assessing the clinical merits of each of a large number of treatment plans is the evaluation of multidimensional plots of the complication probabilities for each of 'n' critical normal tissues/structures for a specified tumor control probability. The cost of proton therapy compared with that of very high technology photon therapy is estimated and evaluated. The differential is estimated to be approximate to 1.5 provided there were to be no charge for the original facility and that there were sufficient patients for operating on an extended schedule (6-7 days of 14-16 h) with greater than or equal to two gantries and one fixed horizontal beam. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, 55 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA 21239] NR 17 TC 81 Z9 84 U1 2 U2 12 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0284-186X J9 ACTA ONCOL JI Acta Oncol. PD DEC PY 2003 VL 42 IS 8 BP 800 EP 808 DI 10.1080/02841860310017676 PG 9 WC Oncology SC Oncology GA 752FK UT WOS:000187149200002 PM 14968940 ER PT J AU Lehtinen, J Tingart, MJ Apreleva, M Zurakowski, D Palmer, W Warner, JJP AF Lehtinen, J Tingart, MJ Apreleva, M Zurakowski, D Palmer, W Warner, JJP TI Practical assessment of rotator cuff muscle volumes using shoulder MRI SO ACTA ORTHOPAEDICA SCANDINAVICA LA English DT Article ID REPAIR; TEARS AB Reliable quantitative assessment of rotator cuff (RC) muscle volumes can be done by reconstructing multiple MRI images of the entire shoulder. However, an equally reliable, but less time-consuming, method is needed for clinical practice. We compared the only method reported for estimation of volume with a new simple MRI technique. Both methods were validated by multiple MRI image reconstruction. We performed MRI scans of 10 cadaver shoulders and determined the cross-sectional areas of RC muscles with two methods, using image analyzing software. In Method 1, the cross-sections were determined on a single image, previously described as a Y-shaped image. In Method 2, the cross-sections were calculated from two images: the Y-shaped and an image located medially, twice the distance from the glenoid articular surface compared to the Y-shaped image. We compared the results of these two methods with the volume of multiple MRI image reconstruction, which took into account all images consisting of RC cross-sections. Pearson correlations for Method 1 were 0.96, 0.94 and 0.75, and for Method 2, 0.96, 0.97 and 0.93 for the supraspinatus, infraspinatus/teres minor and subscapularis muscle volumes when compared with the volumes determined by the multiple image reconstruction method. The Bland-Altman method showed better agreement with multiple MRI image reconstruction, using Method 2, to determine supraspinatus, infraspinatus, and subscapularis muscle volumes (p < 0.001 for each). The mean intra- and inter-observer variabilities of Method 1 was 3.9% and 2.9% and that of Method 2, 3.0% and 1.7%, respectively. Both methods can be used for quantitative assessment of RC muscle volumes. However, Method 2, using two easily reproducible MRI images is more accurate for the evaluation of the supraspinatus and infraspinatus/teres minor muscles and particularly for the subscapularis muscle. C1 Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA USA. RP Lehtinen, J (reprint author), Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA. NR 16 TC 15 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6470 J9 ACTA ORTHOP SCAND JI Acta Orthop. Scand. PD DEC PY 2003 VL 74 IS 6 BP 722 EP 729 DI 10.1080/00016470310018270 PG 8 WC Orthopedics SC Orthopedics GA 754GC UT WOS:000187295200017 PM 14763706 ER PT J AU Perlis, RH Alpert, J Nierenberg, AA Mischoulon, D Yeung, A Rosenbaum, JF Fava, M AF Perlis, RH Alpert, J Nierenberg, AA Mischoulon, D Yeung, A Rosenbaum, JF Fava, M TI Clinical and sociodemographic predictors of response to augmentation, or dose increase among depressed outpatients resistant to fluoxetine 20 mg/day SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article DE depression; antidepressive agents; fluoxetine; lithium carbonate; desipramine ID MAJOR DEPRESSION; LITHIUM AUGMENTATION; ANTIDEPRESSANT TREATMENT; UNIPOLAR DEPRESSION; DISORDER; REMISSION; NONRESPONDERS; EPIDEMIOLOGY; METAANALYSIS; DEFINITIONS AB Objective: Patients with major depressive disorder often show only partial or no response to antidepressants, necessitating next-step interventions such as dose increase or augmentation. Factors moderating response to these next-step interventions are not well-studied. Method: In this randomized, double-blind investigation of next-step treatments in 101 outpatients who failed to respond to fluoxetine 20 mg for 8 weeks, the impact of depressive course and sociodemographic factors on likelihood of treatment response following dose increase or lithium or desipramine augmentation was examined. Results: After controlling for depression severity at baseline, current marriage and earlier onset of depression were associated with greater likelihood of response in a logistic regression. Intervention strategy was not predictive of response. Conclusion: Marital status and earlier onset of depression may be clinically useful in predicting outcome following any next-step intervention for treatment resistance, rather than with particular strategies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Perlis, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01 MH 48483-05] NR 42 TC 17 Z9 19 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD DEC PY 2003 VL 108 IS 6 BP 432 EP 438 DI 10.1046/j.0001-690X.2003.00168.x PG 7 WC Psychiatry SC Psychiatry GA 740RL UT WOS:000186415300006 PM 14616224 ER PT J AU Busuttil, RA Rubio, M Dolle, MET Campisi, J Vijg, J AF Busuttil, RA Rubio, M Dolle, MET Campisi, J Vijg, J TI Oxygen accelerates the accumulation of mutations during the senescence and immortalization of murine cells in culture SO AGING CELL LA English DT Article DE aging; cancer; DNA damage; genomic integrity; oxidative damage ID OXIDATIVE DNA-DAMAGE; DIPLOID FIBROBLAST CELLS; TRANSGENIC MOUSE MODEL; REPLICATIVE LIFE-SPAN; IN-VIVO MUTATIONS; GENOME REARRANGEMENTS; SOMATIC MUTATIONS; EMBRYO CELLS; MICE; GROWTH AB Oxidative damage is a causal factor in aging and cancer, but it is still not clear how DNA damage, the cellular responses to such damage and its conversion to mutations by misrepair or misreplication contribute to these processes. Using transgenic mice carrying a lacZ mutation reporter, we have previously shown that mutations increase with age in most organs and tissues in vivo. It has also been previously shown that mouse cells respond to oxidative stress, typical of standard culture conditions, by undergoing cellular senescence. To understand better the consequences of oxidative stress, we cultured mouse embryo fibroblasts (MEFs) from lacZ mice under physiological oxygen tension (3%) or the high oxygen tension (20%) associated with standard culture, and determined the frequency and spectrum of mutations. Upon primary culture, the mutation frequency was found to increase approximately three-fold relative to the embryo. The majority of mutations were genome rearrangements. Subsequent culture in 20% oxygen resulted in senescence, followed by spontaneous immortalization. Immortalization was accompanied by an additional three-fold increase in mutations, most of which were G:C to T:A transversions, a signature mutation of oxidative DNA damage. In 3% oxygen, by contrast, MEFs did not senesce and the mutation frequency and spectrum remained similar to primary cultures. These findings demonstrate for the first time the impact of oxidative stress on the genomic integrity of murine cells during senescence and immortalization. C1 Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, STCBM, San Antonio, TX 78245 USA. Lawrence Berkeley Lab, Div Life Sci, Berkeley, CA USA. Buck Inst Age Res, Novato, CA USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Vijg, J (reprint author), Univ Texas, Hlth Sci Ctr, Sam & Ann Barshop Ctr Longev & Aging Studies, STCBM, 15355 Lambda Dr,STCBM, San Antonio, TX 78245 USA. FU NIA NIH HHS [AG17242] NR 32 TC 107 Z9 112 U1 0 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD DEC PY 2003 VL 2 IS 6 BP 287 EP 294 DI 10.1046/j.1474-9728.2003.00066.x PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 753GW UT WOS:000187224500001 PM 14677631 ER PT J AU Safren, SA Hendriksen, ES Desousa, N Boswell, SL Mayer, KH AF Safren, SA Hendriksen, ES Desousa, N Boswell, SL Mayer, KH TI Use of an on-line pager system to increase adherence to antiretroviral medications SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID SELF-REPORTED ADHERENCE; HIV-INFECTED PATIENTS; PATIENT ADHERENCE; CLINICAL-TRIALS; DRUG-RESISTANCE; PROTEASE INHIBITORS; THERAPY; ZIDOVUDINE; REGIMENS; OUTCOMES AB Adherence to antiretroviral therapy is critical for treatment success. Antiretroviral therapy typically requires multiple pills at multiple dosing times. To address this, we tested the feasibility, utility, and efficacy of a customizable reminder system using pagers, which were programmed using web-based technology, to increase and maintain proper adherence in patients with pre-existing adherence problems. After a two-week monitoring period with an electronic pill-cap, participants with less than 90% adherence were randomized to continue monitoring or to receive a pager. The group who received the pagers had greater improvements in adherence from baseline to Week 2 and Week 12 than those who monitored their medications only. However, adherence in both groups at the outcome assessments points was still poor. While the provision of a reminder system helped improve adherence, it is likely that more intensive interventions are required for patients with pre-existing problems. C1 Massachusetts Gen Hosp, Dept Psychiat, WACC 815, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Fenway Community Hlth, Boston, MA USA. Brown Univ, Providence, RI 02912 USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 815, 15 Parkman St, Boston, MA 02114 USA. NR 31 TC 71 Z9 74 U1 0 U2 3 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids/Hiv PD DEC PY 2003 VL 15 IS 6 BP 787 EP 793 DI 10.1080/09540120310001618630 PG 7 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 742ZA UT WOS:000186546900005 PM 14617500 ER PT J AU Safren, SA Gershuny, BS Hendriksen, E AF Safren, SA Gershuny, BS Hendriksen, E TI Symptoms of posttraumatic stress and death anxiety in persons with HIV and medication adherence difficulties SO AIDS PATIENT CARE AND STDS LA English DT Article ID SOCIAL SUPPORT QUESTIONNAIRE; MOTOR-VEHICLE ACCIDENTS; PERITRAUMATIC DISSOCIATION; PROTEASE INHIBITORS; FEMALE VICTIMS; SEXUAL ASSAULT; BREAST-CANCER; DISORDER; PREDICTORS; PTSD AB The present study examined the frequency and correlates of self-reported symptoms of posttraumatic stress among patients with HIV and medication adherence problems. Self-report data revealed that more than half of participants met diagnostic criteria for posttraumatic stress disorder (PTSD) according to the Posttraumatic Diagnostic Scale PDS. Death anxiety was associated with overall PTSD symptom severity scores as well as severity scores for re-experiencing, avoidance, and arousal symptoms. The association between death anxiety and total PTSD severity, reexperiencing and avoidance symptom scores remained after controlling for depression and satisfaction with social support. Anxiety, as manifested by PTSD symptoms should be routinely assessed among patients with HIV, and variables such as death anxiety, social support, and depression are appropriate targets for mental health interventions. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Fenway Community Hlth, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Safren, SA (reprint author), Massachusetts Gen Hosp, Dept Psychiat, ACC 812,15 Parkman St, Boston, MA 02114 USA. NR 54 TC 70 Z9 70 U1 1 U2 7 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD DEC PY 2003 VL 17 IS 12 BP 657 EP 664 DI 10.1089/108729103771928717 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 760NG UT WOS:000187840000006 PM 14746659 ER PT J AU Kampov-Polevoy, AB Ziedonis, D Steinberg, ML Pinsky, I Krejci, J Eick, C Boland, G Khalitov, E Crews, FT AF Kampov-Polevoy, AB Ziedonis, D Steinberg, ML Pinsky, I Krejci, J Eick, C Boland, G Khalitov, E Crews, FT TI Association between sweet preference and paternal history of alcoholism in psychiatric and substance abuse patients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE sweet preference; alcoholism; genetic risk ID PITUITARY BETA-ENDORPHIN; HEDONIC RESPONSE; SACCHARIN INTAKE; TASTE RESPONSES; FAMILY-HISTORY; WISTAR RATS; SUCROSE; ETHANOL; CONSUMPTION; DRINKING AB Background: The relationship between preference for stronger sweet solutions and propensity to excessive alcohol drinking is supported by both animal and human studies. This study was designed to test the hypothesis that sweet preference is associated with the genetic risk of alcoholism as measured by a paternal history of alcoholism. Methods: Participants were 180 patients admitted to a residential treatment program for the treatment of alcoholism, drug dependence, or psychiatric conditions. In addition to a routine medical examination, patients completed the standard sweet preference test twice (on the 9th and 24th days after admission), and the family history of alcoholism was evaluated. Results: Sweet preference was shown to be stable over time. It was strongly associated with a paternal history of alcoholism, with family history-positive patients approximately 5 times more likely to prefer stronger sweet solutions than family history-negative subjects. Such factors as dependence on alcohol, cocaine, opiates, cannabis, other drugs (including prescription drugs), and tobacco smoking, as well as demographics (gender and age), did not significantly interfere with association between sweet preference and paternal history of alcoholism. Conclusions: These findings provide some support for the hypothesis that preference for stronger sweet solutions is associated with a genetic predisposition to alcoholism as measured by a paternal history of alcoholism. C1 Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Div Addict Psychiat, Bronx, NY 10468 USA. Univ Med & Dent, Piscataway, NJ USA. Robert Wood Johnson Med Sch, Div Addict Psychiat, Piscataway, NJ USA. Pavillon Int, Mill Spring, NC USA. Univ Minnesota, Sch Stat, Minneapolis, MN 55455 USA. Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC USA. RP Kampov-Polevoy, AB (reprint author), Bronx Vet Affairs Med Ctr, Mt Sinai Sch Med, Div Addict Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. OI Steinberg, Marc/0000-0001-8180-8682 NR 68 TC 30 Z9 31 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2003 VL 27 IS 12 BP 1929 EP 1936 DI 10.1097/01.ALC.0000099265.60216.23 PG 8 WC Substance Abuse SC Substance Abuse GA 758WF UT WOS:000187674000010 PM 14691380 ER PT J AU Bush, KR Kivlahan, DR Davis, TM Dobie, DJ Sporleder, JL Epler, AJ Bradley, KA AF Bush, KR Kivlahan, DR Davis, TM Dobie, DJ Sporleder, JL Epler, AJ Bradley, KA TI The TWEAK is weak for alcohol screening among female veterans affairs outpatients SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol screening; TWEAK; AUDIT; AUDIT-C ID BRIEF PHYSICIAN ADVICE; IDENTIFICATION TEST AUDIT; BENEFIT-COST-ANALYSIS; AT-RISK DRINKING; PRIMARY-CARE; BRIEF INTERVENTIONS; USE DISORDERS; GENERAL-POPULATION; PROBLEM DRINKERS; LIKELIHOOD RATIOS AB Background: The optimal brief questionnaire for alcohol screening among female patients has not yet been identified. This study compared the performance of the TWEAK (tolerance, worried, eye-opener, amnesia, cutdown), the Alcohol Use Disorders Identification Test (AUDIT), and the AUDIT Consumption (AUDIT-C) as self-administered screening tests for hazardous drinking and/or active alcohol abuse or dependence among female Veterans Affairs (VA) outpatients. Methods: Women were included in the study if they received care at VA Puget Sound and completed both a self-administered survey containing the AUDIT and TWEAK screening questionnaires and subsequent in-person inter-views with the Alcohol Use Disorders and Associated Disabilities Interview Schedule. Sensitivities, specificities, positive and negative likelihood ratios, and areas under Receiver Operating Characteristic curves were computed for each screening questionnaire compared with two interview-based comparison standards: (1) active DSM-IV alcohol abuse or dependence and (2) hazardous drinking and/or active DSM-IV alcohol abuse or dependence, the more appropriate target for primary care screening. Results: Of 393 women who completed screening questionnaires and interviews, 39 (9.9%) met diagnostic criteria for alcohol abuse or dependence, and 89 (22.7%) met criteria for hazardous drinking or alcohol abuse or dependence. The TWEAK had relatively low sensitivities (0.62 and 0.44) but adequate specificities (0.86 and 0.89) for both interview-based comparison standards, even at its lowest cut-point ( 1). The AUDIT and AUDIT-C were superior, with the following areas under the receiver operating characteristic curve for active alcohol abuse or dependence and hazardous drinking and/or active alcohol abuse or dependence, respectively: AUDIT, 0.90 [95% confidence interval (CI), 0.85-0.95] and 0.87 (95% CI, 0.84-0.91); AUDIT-C, 0.91 (95% CI, 0.88-0.95) and 0.91 (95% CI, 0.88-0.94); and TWEAK, 0.76 (95% CI, 0.66-0.86) and 0.67 (95% CI, 0.60-0.74). Conclusions: The TWEAK has low sensitivity as an alcohol-screening questionnaire among female VA outpatients and should be evaluated further before being used in other female primary care populations. The three-item AUDIT-C was the optimal brief alcohol-screening questionnaire in this study. C1 VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Dept Vet Affairs, Vet Hlth Adm, Seattle, WA 98108 USA. Veteran Womens Alcohol Problems Study, Hlth Serv Res & Dev Serv, Seattle, WA USA. Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Primary & Specialty Med Care Serv, Seattle, WA USA. Washington Univ, Dept Psychiat, Seattle, WA USA. Washington Univ, Dept Behav Sci, Seattle, WA USA. Washington Univ, Dept Med, Seattle, WA USA. Washington Univ, Dept Hlth Serv, Seattle, WA USA. RP Bush, KR (reprint author), VA Puget Sound Hlth Care Syst, Ctr Excellence Subst Abuse Treatment & Educ, Dept Vet Affairs, Vet Hlth Adm, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NIAAA NIH HHS [K23 AA00313] NR 57 TC 7 Z9 7 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2003 VL 27 IS 12 BP 1971 EP 1978 DI 10.1097/01.ALC.0000099262.50094.98 PG 8 WC Substance Abuse SC Substance Abuse GA 758WF UT WOS:000187674000015 PM 14691385 ER PT J AU Halpern, SD Karlawish, JHT Casarett, D Berlin, JA Townsend, RR Asch, DA AF Halpern, SD Karlawish, JHT Casarett, D Berlin, JA Townsend, RR Asch, DA TI Hypertensive patients' willingness to participate in placebo-controlled trials: Implications for recruitment efficiency SO AMERICAN HEART JOURNAL LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; ACTIVE-CONTROL TRIALS; CLINICAL-TRIALS; EQUIVALENCE TRIALS; PRACTICAL ISSUES; HEALTH RESEARCH; ETHICS; AIDS AB Background Underenrollment and selective enrollment plague many clinical trials. Little is known about why hypertensive patients agree or refuse to participate in placebo-controlled trials (PCT) of antihypertensive drugs, whether the prospect of receiving placebo influences willingness to participate (WTP), or whether patients who participate differ from those who do not. Methods We described a hypothetical PCT of a new antihypertensive drug to 126 patients who would be eligible for ongoing phase III trials. We solicited patient motivations and concerns regarding trial participation by using open-ended questions, assessed the patients' stated WTP, and used logistic regression to determine patient characteristics associated with WTP. We reassessed WTP in 62 patients after revealing,, in random order, that 10%, 30%, and 50% of patients would receive placebo. Results The most commonly cited motivations for participating included personal health benefits (40%), helping other patients (37%), and contributing to scientific knowledge (15%). The most common concerns were having to stop current medications (56%), inconvenience/annoyance (38%), fear of known side effects (35%), and the possibility of receiving placebo (24%). Overall, 47% of patients (95% confidence interval, 38% to 56%) were willing to participate. Younger patients (57% versus 37%; P = .01), nonsmokers (50% versus 24%; P = .04), and patients who had participated in research previously (77% versus 20%; P = .009) were all significantly more willing to participate. Fewer patients were willing to participate as the percentage who would receive placebo increased (P = .02), but randomly assigning fully half of patients to placebo still yielded maximal recruitment efficiency. Conclusions Hypertensive patients participate in trials for altruistic and personal health reasons. Differences between patients who do or do not participate may influence trial outcomes. The proportion of patients receiving placebo influences some patients' enrollment decisions but is not a key determinant of recruitment efficiency. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Halpern, SD (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 108 Blackley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. OI Asch, David/0000-0002-7970-286X NR 41 TC 43 Z9 44 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2003 VL 146 IS 6 BP 985 EP 992 DI 10.1016/S0002-8703(03)00507-6 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 751RF UT WOS:000187080200012 PM 14660989 ER PT J AU Mozaffarian, D Bryson, CL Spertus, JA McDonell, MB Fihn, SD AF Mozaffarian, D Bryson, CL Spertus, JA McDonell, MB Fihn, SD TI Anginal symptoms consistently predict total mortality among outpatients with coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 43rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05-08, 2003 CL MIAMI, FLORIDA SP Amer Heart Assoc ID ACUTE MYOCARDIAL-INFARCTION; PROGNOSTIC IMPORTANCE; NONDIABETIC PATIENTS; FUNCTIONAL STATUS; STABLE ANGINA; HEART-DISEASE; HEALTH-STATUS; ANGIOGRAPHY; ASSOCIATION; ISCHEMIA AB Background Age, race, education, and diabetes have been associated with differences in anginal symptoms, treatments, and outcomes among outpatients with coronary artery disease (CAD), but there is little data on whether such characteristics affect relationships between anginal symptoms and mortality. Methods Using a prospective cohort design, we examined associations of anginal symptoms, as assessed by the Seattle Angina Questionnaire, with total mortality among 8908 outpatients with CAD to investigate whether this relationship is influenced by patient demographic or clinical characteristics. Potential effect modification was primarily assessed for age, race, education, and diabetes, and secondarily assessed for smoking, prevalent congestive heart failure (CHF), myocardial infarction, and coronary revascularization. Results Over 2 years mean follow-up, there were 896 deaths. After adjustment for potential confounders, persons reporting greater physical limitation due to angina had higher mortality: 27% higher with mild limitation (hazard ratio [HR] 1.27, 95% CI 0.98-1.64), 61% higher with moderate limitation (HR 1.61, 95% CI 1.27-2.05), and 2.5-fold higher with the greatest limitation (HR 2.55, 95% CI 1.97-3.30), compared with little or no limitation (P for trend <.001). Anginal instability was also independently predictive of mortality. There was little evidence that these relationships varied by age, race, education, diabetes, smoking, or presence of CHF, prior myocardial infarction, or prior coronary revascularization (P for each interaction >.28). Anginal symptoms predicted higher mortality risk comparable to a decade of age difference, presence of diabetes, or presence of CHF. Conclusions Among outpatients with CAD, self-reported anginal symptoms consistently predict mortality irrespective of differences in age, race, education, or clinical comorbidities. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98195 USA. Mid Amer Heart Inst, Kansas City, MO USA. RP Mozaffarian, D (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave,Bldg 2 Rm 315, Boston, MA 02115 USA. RI Mozaffarian, Dariush/B-2276-2008 NR 31 TC 47 Z9 50 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2003 VL 146 IS 6 BP 1015 EP 1022 DI 10.1016/S0002-8703(03)00436-8 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 751RF UT WOS:000187080200016 PM 14660993 ER PT J AU Ferencik, M Moselewski, F Ropers, D Hoffmann, U Baum, U Anders, K Pomerantsev, EV Abbara, S Brady, TJ Achenbach, S AF Ferencik, M Moselewski, F Ropers, D Hoffmann, U Baum, U Anders, K Pomerantsev, EV Abbara, S Brady, TJ Achenbach, S TI Quantitative parameters of image quality in multidetector spiral computed tomographic coronary imaging with submillimeter collimation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ELECTRON-BEAM CT; MAGNETIC-RESONANCE ANGIOGRAPHY; ARTERY STENOSES; HEART-RATE; VISUALIZATION; RECONSTRUCTION; EXPERIENCE AB Multidetector computed tomography (MDCT) permits visualization of the coronary arteries, but limited spatial and temporal resolution can lead to artifacts-We quantitatively evaluated the image quality that can be obtained with the latest generation of MDCT scanners with submillimeter collimation and increased gantry rotation speed. Thirty patients with angiographically proved absence of significant coronary artery stenoses (mean age 56 +/- 13 years, mean heart rate 62 +/- 13 beats/min) were studied by MDCT (12 x 0.75 mm collimation, 420-ms tube rotation, 210-ms temporal resolution, 500 mA, 120 kVp, retrospective electrocardiographic gating). In multiplanar reconstructions of the 4 major coronary arteries (left main, left anterior descending, left circumflex, and right coronary artery), the overall visualized vessel length and the length of segments without motion artifacts were measured. Vessel diameters at 8 predefined locations were measured in MDCT maximum intensity projections and in corresponding invasive angiograms. The mean lengths of visualized coronary arteries were left main 13 +/- 6 mm, left anterior descending 138 +/- 39 mm, left circumflex 84 +/- 34 mm, and right coronary artery 155 +/- 41 mm. On average, 93 +/- 13% of the total visualized vessel length was depicted without motion artifacts (left main 100 +/- 0%, left anterior descending 93 +/- 12%, left circumflex 91 +/- 17%, and right coronary artery 87 +/- 14%). The percentage of vessel length visualized free of motion artifacts was significantly higher in patients with a heart rate less than or equal to60 beats/min compared with patients with a heart rate >60 beats/min (96 +/- 8% vs 89 +/- 17%, p <0.05). Vessel diameters in MDCT correlated closely to quantitative coronary angiography (R-2 0.83 to 0.87). In conclusion, MDCT with submillimeter collimation and improved temporal resolution permits reliable visualization of the vessel lumen and accurate measurements of vessel dimensions. (C) 2003 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Internal Med 2, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Diagnost Radiol, D-8520 Erlangen, Germany. RP Ferencik, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 27 TC 44 Z9 50 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2003 VL 92 IS 11 BP 1257 EP 1262 DI 10.1016/j.amjcard.2003.08.003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 747FL UT WOS:000186794500001 PM 14636899 ER PT J AU Hussein, MR Hassan, M Wood, GS AF Hussein, MR Hassan, M Wood, GS TI Morphological changes and apoptosis in radial growth phase melanoma cell lines following ultraviolet-B irradiation SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE radial growth phase (RGP); transmission electron microscopy (TEM); terminal deoxymicleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick-end labeling (TUNEL); ultraviolet irradiation (UVR); Wistar melanoma (WM) ID CUTANEOUS MALIGNANT-MELANOMA; ELECTRON-MICROSCOPY; HUMAN MELANOCYTES; MISMATCH REPAIR; PROMOTER REGION; PIGMENTED NEVI; P53; UV; EXPRESSION; HMSH2 AB Background: Knowledge about the morphologic changes following ultraviolet irradiation in the earliest stages of melanomas is still lacking. Methods: To investigate these changes, an in vitro system consisting of radial growth phase Wistar melanoma cell lines (WM35 and WM3211) was established. Cells were irradiated with a single erythemogenic dose of UVB (10 mJ/cm(2)) and evaluated for morphologic changes. Results: When compared with the non-irradiated cells, inverted light microscopy revealed increased cellular branching, cytoplasmic size, and multinucleation in the irradiated cells. Transmission electron microscopy revealed the features of increased metabolic activity (hyperplasia of the mitochondria and Golgi) and those of ultrastructural atypia (pleomorphism of the nuclei and nucleoli, increased euchromatin, and nucleolar margination) in the irradiated cells. Moreover, UVB irradiation caused an increase in the apoptotic activity. These alterations were associated with up-regulation of p53, Bcl-2, and the second mismatch repair protein (hMSH2), as revealed by Western blot analysis. Conclusions: UVB irradiation can induce apoptosis, morphologic changes, and altered expression of p53, Bcl-2, and hMSH2 in radial growth phase melanoma cell lines. Up-regulation of p53, Bcl-2, and hMSH2 suggests that these factors are involved in the altered balance between survival and apoptosis induced by UVB. Further investigation will be needed to determine if apoptosis and ultrastructural atypia reflect underlying DNA damage and genomic instability induced by UVB. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Case Western Reserve Univ, Dept Pathol, Vet Hosp, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. FU NIAMS NIH HHS [AR02136] NR 41 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD DEC PY 2003 VL 25 IS 6 BP 466 EP 472 DI 10.1097/00000372-200312000-00003 PG 7 WC Dermatology SC Dermatology GA 747FZ UT WOS:000186795700003 PM 14631187 ER PT J AU Sands, BE Arsenault, JE Rosen, MJ Alsahli, M Bailen, L Banks, P Bensen, S Bousvaros, A Cave, D Cooley, JS Cooper, HL Edwards, ST Farrell, RJ Griffin, MJ Hay, DW John, A Lidofsky, S Olans, LB Peppercorn, MA Rothstein, RI Roy, MA Saletta, MJ Shah, SA Warner, AS Wolf, JL Vecchio, J Winter, HS Zawacki, JK AF Sands, BE Arsenault, JE Rosen, MJ Alsahli, M Bailen, L Banks, P Bensen, S Bousvaros, A Cave, D Cooley, JS Cooper, HL Edwards, ST Farrell, RJ Griffin, MJ Hay, DW John, A Lidofsky, S Olans, LB Peppercorn, MA Rothstein, RI Roy, MA Saletta, MJ Shah, SA Warner, AS Wolf, JL Vecchio, J Winter, HS Zawacki, JK TI Risk of early surgery for Crohn's disease: Implications for early treatment strategies SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CLINICAL-COURSE; CIGARETTE-SMOKING; NATURAL-HISTORY; RECURRENCE; PROGNOSIS; COLITIS AB OBJECTIVES: In this study we aimed to define the rate of early surgery for Crohn's disease and to identify risk factors associated with early surgery as a basis for subsequent studies of early intervention in Crohn's disease. METHODS: We assembled a retrospective cohort of patients with Crohn's disease diagnosed between 1991 and 1997 and followed for at least 3 yr, who were identified in 16 community and referral-based practices in New England. Chart review was performed for each patient. Details of baseline demographic and disease features were recorded. Surgical history including date of surgery, indication, and procedure were also noted. Risk factors for early surgery (defined as major surgery for Crohn's disease within 3 yr of diagnosis, exclusive of major surgery at time of diagnosis) were identified by univariate analysis. Multiple logistic regression was used to identify independent risk factors. RESULTS: Of 345 eligible patients, 69 (20.1%) required surgery within 3 yr of diagnosis, excluding the 14 patients (4.1%) who had major surgery at the time of diagnosis. Overall, the interval between diagnosis and surgery was short; one half of all patients who required surgery underwent operation within 6 months of diagnosis. Risk factors identified by univariate analysis as significantly associated with early surgery included the following: smoking; disease of small bowel without colonic involvement; nausea and vomiting or abdominal pain on presentation; neutrophil count; and steroid use in the first 6 months. Disease localized to the colon only, blood in the stool, use of 5-aminosalicylate, and lymphocyte count were inversely associated with risk of early surgery. Logistic regression confirmed independent associations with smoking as a positive risk factor and involvement of colon without small bowel as a negative risk factor for early surgery. CONCLUSIONS: The rate of surgery is high in the first 3 yr after diagnosis of Crohn's disease, particularly in the first 6 months. These results suggest that improved risk stratification and potent therapies with rapid onset of action are needed to modify the natural history of Crohn's disease. C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Ctr Study IBD, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Gastroenterol, Boston, MA 02215 USA. Tufts Univ New England Med Ctr, Dept Gastroenterol, Boston, MA 02111 USA. Brigham & Womens Hosp, Div Gastroenterol & Hepatol, Boston, MA 02115 USA. Dartmouth Hitchcock Med Ctr, Dept Gastroenterol, Lebanon, NH 03766 USA. Dartmouth Hitchcock Med Ctr, Dept Pediat, Lebanon, NH 03766 USA. Childrens Hosp, Dept Gastroenterol, Boston, MA 02115 USA. St Elizabeths Med Ctr, Div Gastroenterol, Brighton, MA USA. N Shore Med Ctr, Dept Med, Salem, MA USA. Mid Maine Gastroenterol, Waterville, ME USA. Associates Gastroenterol, Burlington, VT USA. Univ Gastroenterol, Providence, RI USA. Portland Gastroenterol Associates, Portland, ME USA. Gastroenterol Associates, Providence, RI USA. Lahey Clin Med Ctr, Burlington, MA 01803 USA. Univ Vermont, Div Gastroenterol & Hepatol, Burlington, VT USA. Univ Massachusetts, Med Ctr, Div Gastroenterol, Worcester, MA USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, 55 Fruit St,GRJ 7, Boston, MA 02114 USA. OI Rosen, Michael/0000-0002-5149-718X FU NIDDK NIH HHS [K23 DK 02850, R01 DK 55512] NR 17 TC 73 Z9 78 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2003 VL 98 IS 12 BP 2712 EP 2718 DI 10.1016/S0002-9270(03)01707-6 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 756TM UT WOS:000187498500022 PM 14687822 ER PT J AU Skluzacek, PA Szewc, RG Nolan, CR Riley, DJ Lee, S Pergola, PE AF Skluzacek, PA Szewc, RG Nolan, CR Riley, DJ Lee, S Pergola, PE TI Prediction of GFR in liver transplant candidates SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE lothalamate; creatinine clearance (C-Cr); cirrhosis; ascites; Model for End-Stage Liver Disease (MELD) score; kidney function ID GLOMERULAR-FILTRATION RATE; PLASMA-CLEARANCE; CREATININE CLEARANCE; SERUM CREATININE; RENAL-FUNCTION; IOTHALAMATE; DISEASE; INULIN; INSUFFICIENCY; SURVIVAL AB Background Kidney function frequently is impaired in patients with cirrhosis; however, glomerular filtration rate (GFR) is difficult to estimate in these patients by using standard clinical markers. The aim of our study is to compare GFR calculated from renal clearance of iodine 125-labeled iothalamate (I-125-lothalamate) with the plasma decay technique and the Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault (CG) prediction equations. Methods: We performed a cross-sectional study of patients with liver cirrhosis being evaluated for transplantation (50% Child's class C); 89% had ascites or edema and 44% were men aged 55 +/- 2 years. Average pretest blood urea nitrogen level was 16 +/- 2 mg/dL (5.7 +/- 0.7 mmol/L); serum creatinine, 1.0 +/- 0.1 mg/dL (88 +/- 9 mumol/L; range, 0.6 to 1.7 mg/dL [53 to 150 mumol/L]); plasma albumin, 3.14 +/- 0.16 g/dL (31.4 +/- 1.6 g/L); and total bilirubin, 4.0 +/- 0.7 mg/dL (67 +/- 11.3 mumol/L). Kidney function was measured by means of simultaneous plasma and renal clearance of I-125-lothala mate (Glofil-125; Cypros Pharmaceutical Corp, Carlsbad, CA) and the MDRD and CG equations. Results: GFRs were 58.2 +/- 5.1 mL/min/1.73 m(2) by renal clearance of I-125-iothalamate and 76.7 +/- 7.2 mL/min/1.73 m(2) by the plasma decay technique (+18.5 mL/min, or 32%; P = 0.0004). GFR by the MDRD equation was 76.9 +/- 7.8 mL/min/1.73 m(2) (+18.7 mL/min, or 32%; P = 0.0004 versus renal lothalamate; r(2) = 0.57). GFR by the CG equation was the least accurate (+30.1 mL/min, or 52%; P = 0.0001 versus renal iothalamate). Conclusion: The current clinically used CG and MDRD equations to estimate kidney function in patients with cirrhosis and volume excess and the I-125-lothalamate plasma decay technique are inaccurate because they overestimate GFR. It seems very unlikely that accurate and reliable formulas will be developed that are able to replace the formal measurement of GFR in patients with liver cirrhosis. Therefore, we conclude that despite the additional complexity, renal clearance techniques should be used to assess GFR accurately in patients with liver cirrhosis and ascites. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Wilford Hall USAF Med Ctr, Dept Med, Lackland AFB, TX 78236 USA. S Texas Vet Hlth Care Syst, Res & Dev Serv, Audie L Murphy Div, San Antonio, TX USA. RP Pergola, PE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 24 TC 79 Z9 82 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2003 VL 42 IS 6 BP 1169 EP 1176 DI 10.1053/S0272-6386(03)01104-1 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 751RH UT WOS:000187080400009 PM 14655188 ER PT J AU Goldie, SJ Paltiel, AD Weinstein, MC Losina, E Seage, GR Kimmel, AD Walensky, RP Sax, PE Freedberg, KA AF Goldie, SJ Paltiel, AD Weinstein, MC Losina, E Seage, GR Kimmel, AD Walensky, RP Sax, PE Freedberg, KA TI Projecting the cost-effectiveness of adherence interventions in persons with human immunodeficiency virus infection SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-AVIUM COMPLEX; SELF-ADMINISTERED THERAPY; PLASMA VIRAL LOAD; VIROLOGICAL FAILURE; HIV-1 INFECTION; INCREASE ADHERENCE; CARINII-PNEUMONIA; PLUS INDINAVIR; CELL COUNTS AB PURPOSE: To explore the cost-effectiveness of interventions to improve adherence to combination antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. METHODS: A simulation model of HIV infection, incorporating CD4 cell count and HIV ribonucleic acid levels as predictors of disease progression, was used to estimate the lifetime costs and quality-adjusted life expectancy associated with clinical interventions to improve adherence to antiretroviral therapy (e.g., directly observed therapy, automatic medication dispensers, beepers, portable alarms) in a clinical trial cohort with early disease (mean CD4 count, 350 cells/muL), a clinical trial cohort with advanced disease (mean CD4 count, 87 cells/muL), and an urban cohort (mean CD4 count, 217 cells/muL). Data were from clinical trials, national databases, and published literature. RESULTS: For relatively healthy patients with early disease, interventions that reduced virologic failure rates by 10% increased quality-adjusted life expectancy by 3.2 months, whereas those that reduced failure by 80% increased quality-adjusted life expectancy by 34.8 months, as compared with standard care. The cost-effectiveness ratio was below $50,000 per quality-adjusted life-year (QALY) for interventions costing $100 per month provided that failure rates were reduced by at least 10%, and for those costing $500 per month provided that failure rates were reduced by more than 50%. For both patients with advanced disease and those from an urban cohort, adherence interventions costing about $500 per month (e.g., directly observed therapy) had to reduce failure by about 25% to have cost-effectiveness ratios below $50,000 per QALY. CONCLUSION: In patients with lower baseline levels of adherence or advanced disease, even very expensive, moderately effective adherence interventions are likely to confer cost-effectiveness benefits that compare favorably with other interventions. (C)2003 by Excerpta Medica Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Yale Univ, Sch Med, New Haven, CT USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Infect Dis, Boston, MA USA. RP Goldie, SJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 718 Huntington Ave,2nd Floor, Boston, MA 02115 USA. EM sgoldie@hsph.harvard.edu OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R01 AI042006, AI01794, AI42006, K23 AI001794, P30 AI042851, U01 AI038858, P30AI42851]; PHS HHS [U0138838, HA 00176] NR 57 TC 80 Z9 82 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 DEC 1 PY 2003 VL 115 IS 8 BP 632 EP 641 DI 10.1016/j.amjmed.2003.07.007 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 748WK UT WOS:000186883800006 PM 14656616 ER PT J AU Joffe, H Cohen, LS Harlow, BL AF Joffe, H Cohen, LS Harlow, BL TI Impact of oral contraceptive pill use on premenstrual mood: Predictors of improvement and deterioration SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE oral contraceptive pill; depression; premenstrual mood syndrome ID MAJOR DEPRESSION; PREVALENCE; WOMEN; SYMPTOMS; SEROTONIN; HARVARD; CYCLES AB OBJECTIVES: The purpose of this study was to estimate risk factors for the deterioration and improvement of premenstrual mood disturbance with oral contraceptive pill use. STUDY DESIGN: Predictors of the deleterious and beneficial effects of oral contraceptive pill use on premenstrual mood were analyzed with the use of logistic regression in a nested case-control study within a community-based cohort of 976 premenopausal women in Massachusetts. RESULTS: Of 658 women who were using oral contraceptive pills, 16.3% of the women reported oral contraceptive pill-related premenstrual mood deterioration, and 12.3% of the women reported premenstrual mood improvement. In adjusted models, previous depression was the only significant predictor of mood deterioration (odds ratio, 2.0; 95% CI, 1.1-3.8); early-onset premenstrual mood disturbance and dysmenorrhea were significant predictors of oral contraceptive pill-related mood improvement (odds ratio, 3.1 [95% CI, 1.9-5.2] and odds ratio, 2.3 [95% CI, 1.4-3.9], respectively). CONCLUSION: Oral contraceptive pills do not influence premenstrual mood in most women. Premenstrual mood is most likely to deteriorate in women with a history of depression and to improve in women with early-onset premenstrual mood disturbance or dysmenorrhea. C1 Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. Brigham & Womens Hosp, Obstet & Gynecol Epidemiol Ctr, Boston, MA 02115 USA. RP Joffe, H (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC, Boston, MA 02114 USA. EM hjoffe@partners.org FU NIMH NIH HHS [R01 MH 50013, T32 MH 17119] NR 23 TC 62 Z9 63 U1 5 U2 11 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2003 VL 189 IS 6 BP 1523 EP 1530 DI 10.1016/S0002-9378(03)00927-X PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 760UP UT WOS:000187853900002 PM 14710055 ER PT J AU Ecker, J Shah, A Wolf, M Smirnakis, K Sauk, J Jimenez-Kimble, R Thadhani, R AF Ecker, J Shah, A Wolf, M Smirnakis, K Sauk, J Jimenez-Kimble, R Thadhani, R TI High leukocyte count portends development of gestational diabetes mellitus SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med C1 Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2003 VL 189 IS 6 SU S MA 160 BP S107 EP S107 DI 10.1016/j.ajog.2003.10.159 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 761LP UT WOS:000187910500160 ER PT J AU Ecker, J Karumanchi, A Roberts, J Taylor, R Levine, R Thadhani, R AF Ecker, J Karumanchi, A Roberts, J Taylor, R Levine, R Thadhani, R TI First-trimester placental growth factor, SFLT-1, and risk for preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med C1 Harvard Univ, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2003 VL 189 IS 6 SU S MA 14 BP S60 EP S60 DI 10.1016/j.ajog.2003.10.013 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 761LP UT WOS:000187910500015 ER PT J AU Levine, R Maynard, S Qian, C Lim, KH England, L Yu, K Schisterman, E Thadhani, R Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A AF Levine, R Maynard, S Qian, C Lim, KH England, L Yu, K Schisterman, E Thadhani, R Sachs, B Epstein, F Sibai, B Sukhatme, V Karumanchi, A TI Acute rise in circulating SFLT-1 may herald preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med C1 NICHD, DHHS, Bethesda, MD USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Allied Technol Grp, Rockville, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2003 VL 189 IS 6 SU S MA 6 BP S57 EP S57 DI 10.1016/j.ajog.2003.10.006 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 761LP UT WOS:000187910500007 ER PT J AU Wolfberg, A Lee-Parritz, A Cohen, A Holmes, L Lieberman, E AF Wolfberg, A Lee-Parritz, A Cohen, A Holmes, L Lieberman, E TI Maternal hypothyroid disease is not associated with poor obstetric or neonatal SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LOUISIANA SP Soc Maternal Fetal Med C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2003 VL 189 IS 6 SU S MA 464 BP S187 EP S187 DI 10.1016/j.ajog.2003.10.468 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 761LP UT WOS:000187910500459 ER PT J AU Ramsanahie, A Duxbury, MS Grikscheit, TC Perez, A Rhoads, DB Gardner-Thorpe, J Ogilvie, J Ashley, SW Vacanti, JP Whang, EE AF Ramsanahie, A Duxbury, MS Grikscheit, TC Perez, A Rhoads, DB Gardner-Thorpe, J Ogilvie, J Ashley, SW Vacanti, JP Whang, EE TI Effect of GLP-2 on mucosal morphology and SGLT1 expression in tissue-engineered neointestine SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE tissue engineering; neomucosa; glucagon-like peptide-2; sodium-glucose cotransporter 1 ID GLUCAGON-LIKE PEPTIDE-2; GROWTH-FACTOR DELIVERY; EPITHELIAL ORGANOID UNITS; SMALL-INTESTINE; MESSENGER-RNA; NA+/GLUCOSE COTRANSPORTER; POLYMER SCAFFOLDS; TRANSPORT; SYSTEM; MICE AB Using tissue-engineering techniques, we have developed a neointestine that regenerates the structural and dynamic features of native small intestine. In this study, we tested neointestinal responsiveness to glucagon-like peptide 2 (GLP-2). Neointestinal cysts were engineered by seeding biodegradable polymers with neonatal rat intestinal organoid units. The cysts were matured and anastomosed to the native jejunum of syngeneic adult recipients. Animals were treated with GLP-2 [Gly(2)] (twice daily, 1 mug/g body wt) or vehicle alone (control) for 10 days. Rats were then killed, and tissues were harvested for analysis. Na+-glucose cotransporter (SGLT1) mRNA expression was assessed with Northern blotting and in situ hybridization. SGLT1 protein was localized by using immunofluorescence. GLP-2 administration resulted in 1.8- and 1.7-fold increases (P<0.05) in neointestinal villus height and crypt depth, respectively. GLP-2 administration also resulted in a 2.4-fold increase (P<0.01) in neomucosal SGLT1 mRNA expression. SGLT1 mRNA expression was localized to enterocytes throughout the villi, and SGLT1 protein was localized to the brush border of enterocytes along the entire length of villi from the neointestine of GLP-2-treated animals. The response of tissue-engineered neointestine to exogenous GLP-2 includes mucosal growth and enhanced SGLT1 expression. Therefore, tissue-engineering principles may help in dissecting the regulatory mechanisms mediating complex processes in the intestinal epithelium. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Whang, EE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-60424]; NIDDK NIH HHS [DK-02786] NR 38 TC 35 Z9 35 U1 0 U2 3 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 DEC 1 PY 2003 VL 285 IS 6 BP G1345 EP G1352 DI 10.1152/ajpgi.00374.2002 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 742MH UT WOS:000186521100031 PM 12919941 ER PT J AU Beckman, JA Goldfine, AB Gordon, MB Garrett, LA Keaney, JF Creager, MA AF Beckman, JA Goldfine, AB Gordon, MB Garrett, LA Keaney, JF Creager, MA TI Oral antioxidant therapy improves endothelial function in Type 1 but not Type 2 diabetes mellitus SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE endothelium; nitric oxide ID NITRIC-OXIDE SYNTHASE; ALPHA-TOCOPHEROL SUPPLEMENTATION; VITAMIN-E SUPPLEMENTATION; LOW-DENSITY LIPOPROTEINS; CORONARY-ARTERY DISEASE; FREE FATTY-ACIDS; DEPENDENT VASODILATION; SUPEROXIDE-PRODUCTION; OXIDATIVE STRESS; PHYSIOLOGICAL CONCENTRATIONS AB Oxidative stress decreases the bioavailability of endothelium-derived nitric oxide in diabetic patients. We investigated whether impaired endothelium-dependent vasodilation (EDV) in diabetes can be improved by long-term administration of oral antioxidants. Forty-nine diabetic subjects [26 Type 1 (T1) and 23 Type 2 (T2)] and 45 matched healthy control subjects were randomized to receive oral vitamin C (1,000 mg) and vitamin E (800 IU) daily or matching placebo for 6 mo. Vascular ultrasonography was used to determine brachial artery EDV and endothelium-independent vasodilation (EIV). EDV was decreased in both T1 (4.9+/-0.9%, P=0.015) and T2 (4.1+/-1.0%, P<0.01) subjects compared with control subjects (7.7&PLUSMN;0.7%). EIV was decreased in T2 (15.0&PLUSMN;1.2%, P<0.01) but not T1 subjects (18.5+/-2.3%, P=0.3) compared with controls (21.8+/-1.8%). Administration of antioxidant vitamins increased EDV in T1 (by 3.4+/-1.4%, P=0.023) but not T2 subjects (by 0.5.+/-0.4%, P=0.3). Antioxidant therapy had no signigicant affect on EIV. Oral antioxidant therapy improves EDV in T1 but not T2 diabetes. These results are consistent with the lack of clinical benefit in studies that have included primarily T2 diabetic patients. C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. RP Creager, MA (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL-48743, HL-56607, K23 HL-04169] NR 57 TC 66 Z9 69 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC 1 PY 2003 VL 285 IS 6 BP H2392 EP H2398 DI 10.1152/ajpheart.00403.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 742MN UT WOS:000186521700017 PM 12881209 ER PT J AU Ichinose, F Hataishi, R Wu, JC Kawai, N Rodrigues, ACT Mallari, C Post, JM Parkinson, JF Picard, MH Bloch, KD Zapol, WM AF Ichinose, F Hataishi, R Wu, JC Kawai, N Rodrigues, ACT Mallari, C Post, JM Parkinson, JF Picard, MH Bloch, KD Zapol, WM TI A selective inducible NOS dimerization inhibitor prevents systemic, cardiac, and pulmonary hemodynamic dysfunction in endotoxemic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE nitric oxide synthase; inflammation; inhibitors ID NITRIC-OXIDE SYNTHASE; SEPTIC SHOCK; RAT MODEL; HYPOTENSION; VASOCONSTRICTION; HYPERTENSION; PRESSURE; OUTPUT; HEART AB Increased nitric oxide ( NO) production by inducible NO synthase (NOS2), an obligate homodimer, is implicated in the cardiovascular sequelae of sepsis. We tested the ability of a highly selective NOS2 dimerization inhibitor (BBS-2) to prevent endotoxin-induced systemic hypotension, myocardial dysfunction, and impaired hypoxic pulmonary vasoconstriction (HPV) in mice. Mice were challenged with Escherichia coli endotoxin before treatment with BBS-2 or vehicle. Systemic blood pressure was measured before and 4 and 7 h after endotoxin challenge, and echocardiographic parameters of myocardial function were measured before and 7 h after endotoxin challenge. The pulmonary vasoconstrictor response to left mainstem bronchus occlusion, which is a measure of HPV, was studied 22 h after endotoxin challenge. BBS-2 treatment alone did not alter baseline hemodynamics. BBS-2 treatment blocked NOS2 dimerization and completely inhibited the endotoxin-induced increase of plasma nitrate and nitrite levels. Treatment with BBS-2 after endotoxin administration prevented systemic hypotension and attenuated myocardial dysfunction. BBS-2 also prevented endotoxin-induced impairment of HPV. In contrast, treatment with N-G-nitro-L-arginine methyl ester, which is an inhibitor of all three NOS isoforms, prevented the systemic hypotension but further aggravated the myocardial dysfunction associated with endotoxin challenge. Treatment with BBS-2 prevented endotoxin from causing key features of cardiovascular dysfunction in endotoxemic mice. Selective inhibition of NOS2 dimerization with BBS-2, while sparing the activities of other NOS isoforms, may prove to be a useful treatment strategy in sepsis. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Berlex Biosci, Richmond, CA 94804 USA. RP Ichinose, F (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-70896, HL-57172, HL-42397] NR 33 TC 34 Z9 36 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD DEC 1 PY 2003 VL 285 IS 6 BP H2524 EP H2530 DI 10.1152/ajpheart.00530.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 742MN UT WOS:000186521700032 PM 12907425 ER PT J AU Sundgren, NC Giraud, GD Schultz, JM Lasarev, MR Stork, PJS Thornburg, KL AF Sundgren, NC Giraud, GD Schultz, JM Lasarev, MR Stork, PJS Thornburg, KL TI Extracellular signal-regulated kinase and phosphoinositol-3 kinase mediate IGF-1 induced proliferation of fetal sheep cardiomyocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE hyperplasia; hypertrophy; UO-126; LY-294002 ID GROWTH-FACTOR-I; BINUCLEATED CARDIAC MYOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSGENIC MICE; MYOCARDIAL-CONTRACTILITY; ANGIOTENSIN-II; RAT-HEART; CELL-SIZE; INSULIN; HYPERTROPHY AB Growth of the fetal heart involves cardiomyocyte enlargement, division, and maturation. Insulin-like growth factor-1 (IGF-1) is implicated in many aspects of growth and is likely to be important in developmental heart growth. IGF-1 stimulates the IGF-1 receptor (IGF1R) and downstream signaling pathways, including extracellular signal-regulated kinase (ERK) and phosphoinositol-3kinase (PI3K). We hypothesized that IGF-1 stimulates cardiomyocyte proliferation and enlargement through stimulation of the ERK cascade and stimulates cardiomyocyte differentiation through the PI3K cascade. In vivo administration of Long R3 IGF-1 (LR3 IGF-1) did not stimulate cardiomyocyte hypertrophy but led to a decreased percentage of cells that were binucleated in vivo. In culture, LR3 IGF-1 increased myocyte bromodeoxyuridine (BrdU) uptake by three-to five-fold. The blockade of either ERK or PI3K signaling (by UO-126 or LY-294002, respectively) completely abolished BrdU uptake stimulated by LR3 IGF-1. LR3 IGF-1 did not increase footprint area, but as expected, phenylephrine stimulated an increase in binucleated cardiomyocyte size. We conclude that 1) IGF-1 through IGF1R stimulates cardiomyocyte division in vivo; hyperplastic growth is the most likely explanation of IGF-1 stimulated heart growth in vivo; 2) IGF-1 through IGF1R does not stimulate binucleation in vitro or in vivo; 3) IGF-1 through IGF1R does not stimulate hypertrophy either in vivo or in vitro; and 4) IGF-1 through IGF1R requires both ERK and PI3K signaling for proliferation of near-term fetal sheep cardiomyocytes in vitro. C1 Oregon Hlth & Sci Univ, Sch Med, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Med Cardiol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Surg, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA. RP Thornburg, KL (reprint author), Oregon Hlth & Sci Univ, Sch Med, Heart Res Ctr, L464, Portland, OR 97239 USA. RI Powers, Donald/A-1704-2009; OI Powers, Donald/0000-0003-1126-7141; Thornburg, Kent/0000-0002-5561-4785 FU NICHD NIH HHS [2PO1-HD-4430] NR 50 TC 56 Z9 57 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD DEC 1 PY 2003 VL 285 IS 6 BP R1481 EP R1489 DI 10.1152/ajpregu.00232.2003 PG 9 WC Physiology SC Physiology GA 742ZE UT WOS:000186547300025 PM 12947030 ER PT J AU Budisavljevic, MN Hodge, L Barber, K Fulmer Jr Durazo-Arvizu, RA Self, SE Kuhlmann, M Raymond Jr Greene, EL AF Budisavljevic, MN Hodge, L Barber, K Fulmer, JR Durazo-Arvizu, RA Self, SE Kuhlmann, M Raymond, JR Greene, EL TI Oxidative stress in the pathogenesis of experimental mesangial proliferative glomerulonephritis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE alpha-lipoic acid; anti-Thy 1 nephritis; extracellular signal-regulated kinase; alpha-smooth muscle actin; transforming growth factor-beta(1) ID ACTIVATED PROTEIN-KINASE; EXPERIMENTAL MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS; ALPHA-LIPOIC ACID; SIGNAL-TRANSDUCTION; GLOMERULAR INJURY; CELLS; ANTIOXIDANT; ACTIN; DIFFERENTIATION; TRANSFORMATION AB Reactive oxygen species (ROS) are increasingly believed to be important intracellular signaling molecules in mitogenic pathways involved in the pathogenesis of glomerulonephritis (GN). We explored the effects of the antioxidants alpha-lipoic acid and N-acetyl-L-cysteine on ERK activation in cultured mesangial cells and the role of ERK activation in the severity of glomerular injury in a rat model of anti-Thy 1 GN. In cultured mesangial cells, growth factors stimulated ERK phosphorylation by 150 - 450%. Antioxidants reduced this increase by 50 - 60%. Induction of anti-Thy 1 nephritis in rats led to a 210% increase in glomerular ERK phosphorylation. This increase in phosphorylated ERK was reduced by 50% in animals treated with alpha-lipoic acid. Treatment with alpha-lipoic acid resulted in significant improvement of glomerular injury. Cellular proliferation was reduced by 100%, and the number of proliferating cell nuclear antigen-positive cells was reduced by 64%. The increased expression of glomerular transforming growth factor-beta(1) protein and mRNA in rats with anti-Thy 1 nephritis was significantly attenuated and mesangial cell transformation into myofibroblasts was completely prevented by treatment with alpha-lipoic acid. The effects of alpha-lipoic acid were at least partially due to inhibition of oxidative stress. In rats with anti-Thy 1 nephritis, ROS production was increased 400 - 500%, and this increase was inhibited by 55% by treatment with alpha-lipoic acid. We suggest that ROS may mediate glomerular injury by inducing ERK phosphorylation. alpha-Lipoic acid should be considered a potential therapeutic agent in certain types of human GN. C1 Med Univ S Carolina, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Serv, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Res Serv, Charleston, SC 29425 USA. Univ Saarlandes Kliniken, Dept Internal Med, D-66421 Homburg, Germany. Mayo Clin & Mayo Fdn, Dept Med, Div Nephrol, Rochester, MN 55905 USA. RP Budisavljevic, MN (reprint author), Med Univ S Carolina, Div Nephrol, 171 Ashley Ave, Charleston, SC 29425 USA. EM budisamn@musc.edu FU NHLBI NIH HHS [HL 03710]; NIDDK NIH HHS [DK 52448] NR 40 TC 38 Z9 42 U1 0 U2 0 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 DEC PY 2003 VL 285 IS 6 BP F1138 EP F1148 DI 10.1152/ajprenal.00397.2002 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 739VH UT WOS:000186366800013 PM 14600028 ER PT J AU Tohen, M Zarate, CA Hennen, J Khalsa, HMK Strakowski, SM Gebre-Medhin, P Salvatore, P Baldessarini, RJ AF Tohen, M Zarate, CA Hennen, J Khalsa, HMK Strakowski, SM Gebre-Medhin, P Salvatore, P Baldessarini, RJ TI The McLean-Harvard first-episode mania study: Prediction of recovery and first recurrence SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PROSPECTIVE FOLLOW-UP; BIPOLAR-I DISORDER; PSYCHOTIC FEATURES; MOOD-CONGRUENT; RATING-SCALE; HOSPITALIZATION; DIAGNOSIS; SYMPTOMS; EPISODE AB Objective: Since improved prediction of illness course early in bipolar disorder is required to guide treatment planning, the authors evaluated recovery, first recurrence, and new illness onset following first hospitalization for mania. Method: Bipolar disorder patients (N= 166) were followed 2-4 years after their first hospitalization for a manic or mixed episode to assess timing and predictors of outcomes. Three aspects of recovery were measured: syndromal (DSM-IV criteria for disorder no longer met), symptomatic (Young Mania Rating Scale score less than or equal to5 and Hamilton Depression Rating Scale score less than or equal to8), and functional (regaining of premorbid occupational and residential status). Rates of remission (syndromal recovery sustained greater than or equal to8 weeks), switching (onset of new dissimilar illness before recovery), relapse (new episode of mania within 8 weeks of syndromal recovery), and recurrence (new episode postremission) were also assessed. Results: By 2 years, most subjects achieved syndromal recovery (98%, with 50% achieving recovery by 5.4 weeks); 72% achieved symptomatic recovery. Factors associated with a shorter time to syndromal recovery for 50% of the subjects were female sex, shorter index hospitalization, and lower initial depression ratings. Only 43% achieved functional recovery; these subjects were more often older and had shorter index hospitalizations. Within 2 years of syndromal recovery, 40% experienced a new episode of mania (20%) or depression (20%), and 19% switched phases without recovery. Predictors of mania recurrence were initial mood-congruent psychosis, lower premorbid occupational status, and initial manic presentation. Predictors of depression onset were higher occupational status, initial mixed presentation, and any comorbidity. Antidepressant treatment was marginally related to longer time to recovery and earlier relapse. Conclusions: Within 2-4 years of first lifetime hospitalization for mania, all but 2% of patients experienced syndromal recovery, but 28% remained symptomatic, only 43% achieved functional recovery, and 57% switched or had new illness episodes. Risks of new manic and depressive episodes were similar but were predicted by contrasting factors. C1 Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. Massachusetts Gen Hosp, McLean Div, Int Consortium Bipolar Disorders Res, Belmont, MA USA. RP Tohen, M (reprint author), Lilly Res Labs, Brougher Bldg,525 S Meridian, Indianapolis, IN 46225 USA. FU NIMH NIH HHS [MH-04844, MH-10948] NR 45 TC 266 Z9 272 U1 3 U2 13 PU AMER PSYCHIATRIC PRESS, 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 DEC PY 2003 VL 160 IS 12 BP 2099 EP 2107 DI 10.1176/appi.ajp.160.12.2099 PG 9 WC Psychiatry SC Psychiatry GA 748VN UT WOS:000186881900007 PM 14638578 ER PT J AU Iosifescu, DV Nierenberg, AA Alpert, JE Smith, M Bitran, S Dording, C Fava, M AF Iosifescu, DV Nierenberg, AA Alpert, JE Smith, M Bitran, S Dording, C Fava, M TI The impact of medical comorbidity on acute treatment in major depressive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ILLNESS RATING-SCALE; MYOCARDIAL-INFARCTION; FUNCTIONAL STATUS; PHYSICAL ILLNESS; ILL PATIENTS; FOLLOW-UP; SYMPTOMS; PREVALENCE; DISEASE; ATHEROSCLEROSIS AB Objective: The authors investigated the impact of medical comorbidity on the acute phase of antidepressant treatment in subjects with major depressive disorder. Method: A total of 384 outpatients meeting DSM-III-R criteria for major depressive disorder enrolled in 8-week open treatment with fluoxetine, 20 mg/day. The authors used the Cumulative Illness Rating Scale to measure the burden of medical comorbidity and the 17-item Hamilton Rating Scale for Depression to assess changes in depressive symptoms. The outcome measures were response to treatment (greater than or equal to50% reduction in score) and clinical remission (score less than or equal to7 at the end of the trial). Results: Compared to responders to fluoxetine, nonresponders had significantly higher Cumulative Illness Rating Scale scores and a greater number of Cumulative Illness Rating Scale categories were endorsed. Compared to subjects who achieved remission with antidepressant treatment, those who did not achieve remission had significantly higher Cumulative Illness Rating Scale scores and a greater number of Cumulative Illness Rating Scale categories were endorsed (i.e., more organs were affected by medical illness). The final Hamilton depression scale score was directly correlated with the total Cumulative Illness Rating Scale score and the number of Cumulative Illness Rating Scale categories endorsed. Conclusions: The total burden of medical illness and the number of organ systems affected by medical illness had a significantly negative predictive value for clinical outcome in the acute phase of treatment in major depressive disorder. C1 Massachusetts Gen Hosp, Psychiat Dept, Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Iosifescu, DV (reprint author), Massachusetts Gen Hosp, Psychiat Dept, Depress Clin & Res Program, 50 Staniford St,Suite 401, Boston, MA 02114 USA. EM diosifescu@partners.org OI Alpert, Jonathan/0000-0002-4332-908X NR 47 TC 56 Z9 56 U1 3 U2 4 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 DEC PY 2003 VL 160 IS 12 BP 2122 EP 2127 DI 10.1176/appi.ajp.160.12.2122 PG 6 WC Psychiatry SC Psychiatry GA 748VN UT WOS:000186881900010 PM 14638581 ER PT J AU Mitelman, SA Shihabuddin, L Brickman, AM Hazlett, EA Buchsbaum, MS AF Mitelman, SA Shihabuddin, L Brickman, AM Hazlett, EA Buchsbaum, MS TI MRI assessment of gray and white matter distribution in Brodmann's areas of the cortex in patients with schizophrenia with good and poor outcomes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 155th Annual Meeting of the American-Psychiatric-Association CY MAY 18-23, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Amer Psychiat Assoc ID SCHIZOTYPAL PERSONALITY-DISORDER; TEMPORAL-LOBE; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; KRAEPELINIAN SCHIZOPHRENIA; GLUCOSE-METABOLISM; BRAIN MORPHOLOGY; VOLUME DEFICITS; ABNORMALITIES; REDUCTION AB Objective: High-resolution magnetic resonance imaging (MRI) was used to compare cortical gray and white matter and CSF volumes in schizophrenia patients with poor outcomes, schizophrenia patients with good outcomes, and healthy comparison subjects. Method: T-1-weighted, 1.2-mm-thick MR images were acquired for 37 patients with schizophrenia and 37 healthy, age- and sex-matched comparison subjects. The patients were assigned to subgroups with poor outcomes (N=13) and good outcomes (N=24) on the basis of clinical characteristics. Poor-outcome patients were those who were continuously hospitalized or completely dependent on others for basic needs, were unemployed, and had severe negative symptoms and severe formal thought disorder. The MR images were reoriented to standard position parallel to the anterior commissure-posterior commissure line and segmented into CSF, gray matter, and white matter tissue types. The tissue types were assigned to Brodmann's areas by using the Perry postmortem histological atlas, and tissue-type volumes in the three subject groups were compared. Results: Compared to the healthy subjects, the overall patient group had a significantly smaller mean cortical gray matter volume and significantly larger mean CSF volume, especially in the frontal lobe and left temporal lobe. The smaller frontal lobe volume in schizophrenia was confirmed for unadjusted volumes and for volumes with adjustment for whole brain volumes. Compared to patients with good outcomes, patients with poor outcomes (Kraepelinian schizophrenia) had significantly smaller gray matter volumes in the temporal and occipital lobes, but no difference between groups was found for total frontal lobe volume. Only 21% of the healthy subjects had volumes 0.5 standard deviations below the mean for healthy subjects in any area of the frontal or temporal lobes, compared with 62% of poor-outcome patients. Conclusions: Poor outcome in patients with schizophrenia may be associated with a more posterior distribution (posteriorization) of gray matter deficits across widely distributed cortical regions. C1 CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. RP Mitelman, SA (reprint author), CUNY Mt Sinai Sch Med, Dept Psychiat, Box 1505,1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIMH NIH HHS [MH-56489, MH-60384, MH-60023, MH-42827, MH-56140] NR 60 TC 83 Z9 88 U1 0 U2 2 PU AMER PSYCHIATRIC PRESS, 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 DEC PY 2003 VL 160 IS 12 BP 2154 EP 2168 DI 10.1176/appi.ajp.160.12.2154 PG 15 WC Psychiatry SC Psychiatry GA 748VN UT WOS:000186881900015 PM 14638586 ER PT J AU Dickey, CC McCarley, RW Voglmaier, MM Niznikiewicz, MA Seidman, LJ Demeo, S Frumin, M Shenton, ME AF Dickey, CC McCarley, RW Voglmaier, MM Niznikiewicz, MA Seidman, LJ Demeo, S Frumin, M Shenton, ME TI An MRI study of superior temporal gyrus volume in women with schizotypal personality disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Soc Biol Psychiat ID SCHIZOPHRENIA; GENDER; LOBE; BRAIN; ABNORMALITIES AB Objective: An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder. Method: The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29). Results: There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction be-tween hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech. Conclusions: This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left-right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Clin Neurosci Div,Lab Neurosci, Brockton, MA 02401 USA. Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab,MRI Div, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA USA. RP McCarley, RW (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Psychiat,Clin Neurosci Div,Lab Neurosci, Psychiat 116A,940 Belmont St, Brockton, MA 02401 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [R01 MH050740, MH-01110, MH-40799, MH-50740, MH-52807, R01 MH040799, R01 MH050740-14, R01 MH052807] NR 15 TC 32 Z9 32 U1 1 U2 2 PU AMER PSYCHIATRIC PRESS, 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 DEC PY 2003 VL 160 IS 12 BP 2198 EP 2201 DI 10.1176/appi.ajp.160.12.2198 PG 4 WC Psychiatry SC Psychiatry GA 748VN UT WOS:000186881900019 PM 14638590 ER PT J AU Ayanian, JZ Zaslavsky, AM Weissman, JS Schneider, EC Ginsburg, JA AF Ayanian, JZ Zaslavsky, AM Weissman, JS Schneider, EC Ginsburg, JA TI Undiagnosed hypertension and hypercholesterolemia among uninsured and insured adults in the Third National Health and Nutrition Examination Survey SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID HIGH BLOOD CHOLESTEROL; UNITED-STATES ADULTS; TREATMENT PANEL; POPULATION; PREVALENCE; INSURANCE; RISK C1 Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Amer Soc Internal Med, Amer Coll Phys, Washington, DC USA. RP Ayanian, JZ (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, 180 Longwood Ave, Boston, MA 02115 USA. OI Schneider, Eric/0000-0002-1132-5084 NR 15 TC 65 Z9 65 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2003 VL 93 IS 12 BP 2051 EP 2054 DI 10.2105/AJPH.93.12.2051 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 748WH UT WOS:000186848400023 PM 14652333 ER PT J AU Lewinsohn, DA Heinzel, AS Gardner, JM Zhu, LQ Alderson, MR Lewinsohn, DM AF Lewinsohn, DA Heinzel, AS Gardner, JM Zhu, LQ Alderson, MR Lewinsohn, DM TI Mycobacterium tuberculosis-specific CD8(+) T cells preferentially recognize heavily infected cells SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE antigen presentation; CD4-positive T lymphocytes; CD8-positive T lymphocytes; cytotoxic T lymphocytes ID INTERFERON-GAMMA; CYTOLYTIC MECHANISMS; MACROPHAGE APOPTOSIS; MICE DEFICIENT; IN-VITRO; RESISTANCE; LYMPHOCYTES; RESPONSES; PERFORIN; CD4(+) AB Both CD4(+) and CD8(+) T cells are important for successful immunity to tuberculosis and have redundant effector functions, such as cytolysis and release of potent antimycobacterial cytokines such as interferon-gamma and tumor necrosis factor-alpha. We hypothesized that CD8(+) T cells play a unique role in host defense to Mycobacterium tuberculosis infection as well. Possibilities include preferential and/or enhanced release of granular constituents and/or preferential recognition of heavily infected cells. Utilizing human, Mycobacterium tuberculosis-specific, CD4(+) and CD8(+) T cell clones, we demonstrate that, after recognition of antigen-presenting cells displaying peptide antigen, CD4(+) T cells preferentially release interferon-gamma, whereas CD8(+) T cells preferentially lyse antigen-presenting cells. Furthermore, utilizing dendritic cells infected with Mycobacterium tuberculosis expressing green fluorescent protein, we show that CD8(+) T cells preferentially recognize heavily infected cells that constitute the minority of infected cells. These data support the hypothesis that the central role of CD8(+) T cells in the control of infection with Mycobacterium tuberculosis may be that of surveillance; in essence, recognition of cells in which the containment of Mycobacterium tuberculosis is no longer effective. C1 Oregon Hlth Sci Univ, Dept Pediat, CDRCP, Div Infect Dis, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Pediat, CDRCP, Div Infect Dis, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Mol Microbiol & Immunol, Vaccine & Gene Therapy Ctr, Div Infect Dis, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med, Div Pulm & Crit Care Med, Portland, OR 97201 USA. Corixa Corp, Seattle, WA USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Lewinsohn, DA (reprint author), Oregon Hlth Sci Univ, Dept Pediat, CDRCP, Div Infect Dis, 707 SW Gaines Rd, Portland, OR 97239 USA. RI Lewinsohn, David/I-4936-2013 OI Lewinsohn, David/0000-0001-9906-9494 FU NIAID NIH HHS [1K08AI01644, 1KO8AI01645, R01AI48090]; NICHD NIH HHS [HD33703] NR 55 TC 72 Z9 75 U1 1 U2 7 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2003 VL 168 IS 11 BP 1346 EP 1352 DI 10.1164/rccm.200306-837OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 747KU UT WOS:000186804300018 PM 12969871 ER PT J AU Blake, MA Krishnamoorthy, SK Boland, GW Sweeney, AT Pitman, MB Harisinghani, M Mueller, PR Hahn, PF AF Blake, MA Krishnamoorthy, SK Boland, GW Sweeney, AT Pitman, MB Harisinghani, M Mueller, PR Hahn, PF TI Low-density pheochromocytoma on CT: A mimicker of adrenal adenoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 102nd Annual Meeting of the American-Roentgen-Ray-Society CY APR 28-MAY 03, 2002 CL ATLANTA, GEORGIA SP Amer Roentgen Ray Soc ID CONTRAST-ENHANCED CT; MEDULLARY HYPERPLASIA; MASSES; DIFFERENTIATION; NONADENOMAS; DIAGNOSIS; WASHOUT; LESIONS; TUMORS; BENIGN AB OBJECTIVE. Attenuation values on CT of less than 10 H are considered characteristic of adrenal adenomas. Adrenal pheochromocytomas can infrequently contain fat that could result in low attenuation on CT The purpose of our study was to determine if pheochromocytomas could be confused with adenomas by virtue of their attenuation values on unenhanced CT. MATERIALS AND METHODS. CT attenuation and size of nine adrenal nodules producing pheochromocytoma syndrome were measured on unenhanced CT in nine patients. For five patients who received IV contrast material, washout profiles were also calculated. RESULTS. Two of the nine patients had adrenal lesions with attenuation values of less than 10 H; one had a pheochromocytoma with an attentuation of 9.0 H, and the other had a medullary hyperplasia with an attenuation of 1.8 H. These two nodules showed evidence of microscopic fat at histologic examination. No macroscopic fat was seen on the CT scans. The remaining seven patients had lesions with attenuation values exceeding 10 H (mean value, 25.6 H; range, 1.8-41 H). Mean diameter of the nine tumors (including the hyperplastic nodule) was 3.2 cm (range, 0.8-6.7 cm; SD, +/- 2.3 cm). The two low-attenuation lesions also mimicked adenomas by displaying more than 60% contrast washout on 10-min-delayed contrast-enhanced scans, unlike the other three pheochromocytomas for which we had washout data. CONCLUSION. On CT, pheochromocytomas may have attenuation values less than 10 H and also may display more than 60% washout of contrast agents on delayed scanning. Adrenal pheochromocytomas should be included with adenomas in the differential diagnosis both for masses with low attenuation on unenhanced CT and for lesions exhibiting a high percentage of contrast washout. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. St Elizabeths Med Ctr, Dept Med, Div Endocrinol, Boston, MA 02135 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Blake, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, 55 Fruit St,White 270, Boston, MA 02114 USA. NR 36 TC 69 Z9 77 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 DEC PY 2003 VL 181 IS 6 BP 1663 EP 1668 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 746MG UT WOS:000186749700037 PM 14627592 ER PT J AU Akintola-Ogunremi, O Pfeifer, JD Tan, BR Yan, Y Zhu, XP Hart, J Goldblum, JR Burgart, L Lauwers, GY Montgomery, E Lewin, D Washington, K Bronner, M Xiao, SY Greenson, JK Lamps, L Lazenby, A Wang, HLL AF Akintola-Ogunremi, O Pfeifer, JD Tan, BR Yan, Y Zhu, XP Hart, J Goldblum, JR Burgart, L Lauwers, GY Montgomery, E Lewin, D Washington, K Bronner, M Xiao, SY Greenson, JK Lamps, L Lazenby, A Wang, HLL TI Analysis of protein expression and gene mutation of c-kit in colorectal neuroendocrine carcinomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 22-28, 2003 CL WASHINGTON, D.C. SP US & Canadian Acad Pathol DE colon; c-kit; CD 117; neuroendocrine carcinoma; small cell carcinoma ID GASTROINTESTINAL STROMAL TUMORS; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; SOFT-TISSUE SARCOMAS; BETA-CATENIN; COLON; GROWTH; DIAGNOSIS; CD117; FIBROMATOSIS AB Primary neuroendocrine carcinomas of the colon are rare but highly aggressive malignancies. The recent observations that c-kit protooncogene, a tyrosine kinase, is overexpressed in a subset of small cell lung cancer and that selective kinase inhibitors block the in vitro growth of small cell lung cancer cell lines prompted us to investigate the expression and mutation status of the c-kit gene in colorectal neuroendocrine carcinomas. Sixty-six cases of primary colorectal neuroendocrine carcinoma were collected from 13 institutions, including 36 small cell carcinomas and 30 moderately differentiated neuroendocrine carcinomas. Immunohistochemical studies using a polyclonal antibody against c-kit protein (CD117) demonstrated a strong and diffuse cytoplasmic staining in 15 cases (23%), which were relatively equally distributed in the small cell and moderately differentiated subgroups. As controls, 25 conventional colorectal adenocarcinomas, 26 colorectal adenomas and 19 colorectal carcinoid tumors were all negative, whereas 15 gastrointestinal stromal tumors were all positive, for kit expression. In contrast to gastrointestinal stromal tumors, kit-overexpressing neuroendocrine carcinomas showed no mutations in the juxtamembrane domain (exon 11) of the c-kit gene as determined by mutational analysis. Kaplan-Meier analysis with the log-rank test revealed that the patients with kit-positive tumors did not differ significantly in survival from those with kit-negative tumors (P = 0.77). These results indicate that c-kit overexpression observed in a subset of colorectal neuroendocrine carcinomas may not be mediated via activating mutations, and does not appear to be an initiating event during tumorigenesis because of lack of c-kit expression in other types of colorectal epithelial neoplasms. More importantly, our observations may have potential therapeutic implications since specific tyrosine kinase inhibitors have shown promise in the management of patients with kit-expressing malignancies. C1 Washington Univ, Sch Med, Lab Surg Pathol, Dept Pathol & Immunol, St Louis, MO 63110 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Mayo Clin, Cleveland, OH USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Vanderbilt Univ, Nashville, TN 37240 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Arkansas, Fayetteville, AR 72701 USA. Univ Alabama, Birmingham, AL USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Wang, HLL (reprint author), Washington Univ, Sch Med, Lab Surg Pathol, Dept Pathol & Immunol, Campus Box 8118,660 S Euclid Ave, St Louis, MO 63110 USA. RI Xiao, Shu-Yuan/E-2215-2012; OI Yan, Yan/0000-0002-5917-1475 NR 52 TC 25 Z9 29 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 DEC PY 2003 VL 27 IS 12 BP 1551 EP 1558 DI 10.1097/00000478-200312000-00008 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 747TH UT WOS:000186820600008 PM 14657715 ER PT J AU Knosalla, C Gollackner, B Buhler, L Mueller, NJ Houser, S Mauiyyedi, S Sachs, DH Robson, SC Fishman, J Schuurman, HJ Awwad, M Cooper, DKC AF Knosalla, C Gollackner, B Buhler, L Mueller, NJ Houser, S Mauiyyedi, S Sachs, DH Robson, SC Fishman, J Schuurman, HJ Awwad, M Cooper, DKC TI Correlation of biochemical and hematological changes with graft failure following pig heart and kidney transplantation in baboons SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE acute humoral xenograft rejection; baboon; consumptive coagulopathy; endothelial cell activation; heart transplantation; kidney transplantation; pig ID ANTI-GAL-ALPHA-1-3GAL ANTIBODY; ORGAN XENOTRANSPLANTATION; TOLERANCE INDUCTION; XENOGRAFT REJECTION; PORCINE KIDNEY; TROPONIN-T; PRIMATES; THERAPY; HUMANS AB We have explored biochemical and hematologic parameters that might indicate acute humoral xenograft rejection (AHXR) following pig organ transplantation in baboons. Baboons (n = 15) received an immunosuppressive regimen, and underwent a miniature swine or hDAF kidney (Group 1, n = 6) or heart (Group 2, n = 7) transplantation. Control,baboons (Group 3, n = 2) received the immunosuppressive regimen without organ transplantation. Blood chemistry and hematologic parameters were measured daily. Baboon and porcine cytomegalovirus were monitored. In Groups 1 and 2, organ grafts survived for up to 29 days. A plasma fibrinogen of <80 mg/dL on 2 consecutive days, and a serum lactate dehydrogenase of >600 U/L and aspartate transaminase of >300 U/L, were associated with the development of AHXR in both heart and kidney grafts. In Group 1, a decrease in platelet count of >150 000/muL within 3 days, or a count of <50 000/μL, were associated with AHXR. In Group 2, a creatine phosphokinase of >500 U/L was associated with graft failure. In Group 3, no abnormalities were observed. The possibility that porcine CMV may play a role in graft injury could not be excluded. Noninvasive parameters were identified that have predictive potential for AHXR. Monitoring of these might enable therapeutic intervention to reverse rejection. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Immunobiol, Boston, MA USA. Immerge BioTherapeut, Cambridge, MA USA. RP Cooper, DKC (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. RI Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 FU PHS HHS [1P01A145897] NR 16 TC 22 Z9 22 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD DEC PY 2003 VL 3 IS 12 BP 1510 EP 1519 DI 10.1046/j.1600-6135.2003.00258.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 754EK UT WOS:000187289600008 PM 14629281 ER PT J AU Gowda, V Roberts, M Wolfe, R Klaustermeyer, WB AF Gowda, V Roberts, M Wolfe, R Klaustermeyer, WB TI Recurrent cough and normal sweat chloride test SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS; CYSTIC-FIBROSIS; HEREDITARY PANCREATITIS; CFTR; MUTATION; GENE; PHENOTYPES; DIAGNOSIS; PATIENT C1 Univ Calif Los Angeles, Div Allergy & Immunol 111R, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,David Geffen Sch Med, Los Angeles, CA 90073 USA. RP Klaustermeyer, WB (reprint author), Univ Calif Los Angeles, Div Allergy & Immunol 111R, Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med,David Geffen Sch Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2003 VL 91 IS 6 BP 527 EP 530 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 757KF UT WOS:000187561000006 PM 14700435 ER PT J AU Zeiss, CR Gomaa, A Murphy, FM Weissman, DN Hodgson, M Foster, D Dejativongse, S Colella, K Kestenberg, K Kurup, VP Bush, RK Chiu, AM Kelly, KJ Fink, JN AF Zeiss, CR Gomaa, A Murphy, FM Weissman, DN Hodgson, M Foster, D Dejativongse, S Colella, K Kestenberg, K Kurup, VP Bush, RK Chiu, AM Kelly, KJ Fink, JN TI Latex hypersensitivity in Department of Veterans Affairs health care workers: glove use, symptoms, and sensitization SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID NATURAL-RUBBER LATEX; ALLERGY; PREVALENCE; PERFORMANCE AB Background: This report of the prevalence of latex glove allergy in 3 Department of Veterans Affairs (VA) medical centers was a collaboration of the VA, the Centers for Disease Control and Prevention, and the National Institute for Occupational Safety and Health. Objective: To enroll and evaluate personnel from across the entire hospital workforce for latex hypersensitivity and to determine the type and extent of latex glove use. Methods: A questionnaire was administered that covered demographics, job category, latex glove use, and current latex glove allergic symptoms. Skin testing to aeroallergens was performed to evaluate the presence of atopy. Blood was drawn for analyses of serum antilatex IgE antibody by CAP assay. Results: Of 1,959 subjects, 158 (8.1%) had latex glove-allergic symptoms, a positive latex CAP assay result, or both. In 1,003 subjects who reported latex glove use, 915 (91.4%) used nonpowdered gloves. A total of 133 subjects reported latex glove allergic symptoms, and 36 subjects had positive CAP assay results. Latex sensitization was correlated with atopy, race, and latex glove exposure. Latex symptoms were correlated with atopy, a positive CAP assay result, and latex glove exposure. Of the 133 subjects with latex glove allergic symptoms, only 11 had positive CAP assay results, giving a prevalence of confirmed latex glove allergy of 0.6%. Conclusions: Symptoms attributed to latex gloves and/or latex sensitization occurred in 8.1% of the employee population, with exposure, race, and atopy being the major risk factors. Few symptomatic individuals were sensitized to latex (0.6%). This low rate of confirmed latex glove allergy may have been related to nonpowdered glove use. C1 VA Chicago Hlth Care Syst, Lakeside Div, Chicago, IL 60611 USA. Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. Univ Wisconsin, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Zablocki Vet Adm Med Ctr, Milwaukee, WI 53295 USA. Vet Hlth Adm, Washington, DC USA. NIOSH, Ctr Dis Control & Prevent, Morgantown, WV USA. Northwestern Univ, Fineberg Sch Med, Chicago, IL 60611 USA. RP Zeiss, CR (reprint author), VA Chicago Hlth Care Syst, Lakeside Div, Room 160,333 E Huron St, Chicago, IL 60611 USA. NR 19 TC 9 Z9 9 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2003 VL 91 IS 6 BP 539 EP 545 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 757KF UT WOS:000187561000008 PM 14700437 ER PT J AU Schatz, M Camargo, CA AF Schatz, M Camargo, CA TI The relationship of sex to asthma prevalence, health care utilization, and medications in a large managed care organization SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID SELF-REPORTED ASTHMA; BODY-MASS INDEX; GENERAL-POPULATION; CHILDHOOD ASTHMA; EMERGENCY-DEPARTMENT; HOSPITAL ADMISSIONS; MENSTRUAL-CYCLE; WOMEN; GENDER; AGE AB Background: Age-related sex differences in asthma hospitalizations and emergency department (ED) visits have been reported, but relationships of these differences to disease prevalence and outpatient management have not been defined. Objective: To define the relationships of sex to asthma-related health care utilization and medications, accounting for age-related differences in asthma prevalence. Methods: Computerized data from Southern California Kaiser-Permanente were used to identify asthmatic patients, aged 2 to 64 years, enrolled continuously during 1999 and 2000. Age-specific asthma prevalence in 1999 was calculated to identify ages of male or female predominance. Males and females were compared with regard to asthma-related health care utilization outcomes (outpatient clinic visits, ED visits, and hospitalizations) and medication use (beta-agonists, inhaled steroids, and oral steroids). Hospitalizations, ED visits, and oral steroid use were considered markers of disease severity. Results: Of the 60,694 subjects, the female-male prevalence ratio was approximately 35:65 at each age between 2 and 13 years, it was inverse (65:35) between the ages of 23 and 64 years, and prevalences were relatively similar at the ages of 14 to 22 years. In patients aged 2 to 13 years, most utilization and medication variables were significantly greater in males (P < .01). Females aged 14 to 22 years had more outpatient and ED visits and used more oral steroids than males. In patients aged 23 to 64 years, all utilization variables were significantly greater in females, except P-agonist use and mean inhaled steroid dispensings. Conclusions: Asthma utilization and severity appear greater in males aged 2 to 13 years, somewhat greater in females aged 14 to 22 years, and definitely greater in females aged 23 to 64 years. The mechanisms for these striking sex differences merit further investigation. C1 Kaiser Permanente Med Care Program, Dept Allergy, San Diego, CA 92111 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Schatz, M (reprint author), Kaiser Permanente Med Care Program, Dept Allergy, 7060 Clairemont Mesa Blvd, San Diego, CA 92111 USA. FU NIAID NIH HHS [AI52338] NR 52 TC 89 Z9 91 U1 2 U2 6 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD DEC PY 2003 VL 91 IS 6 BP 553 EP 558 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 757KF UT WOS:000187561000010 PM 14700439 ER PT J AU Netscher, DT Eladoumikdachi, F AF Netscher, DT Eladoumikdachi, F TI Two case reports of pollicization of a previously syndactylized index finger for congenitally absent thumb SO ANNALS OF PLASTIC SURGERY LA English DT Article ID RECONSTRUCTION AB Two patients with absent thumbs and complicated syndactyly were successfully treated by pollicization of the index finger. Prior surgical release of the index finger syndactyly and then pollicization of that digit carries with it an increased risk of neurovascular compromise, adverse placement of surgical scars, and a stiff or unstable thumb. With caution, very satisfying reconstructive results can nonetheless be attained. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Plast Surg Serv, Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 11 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD DEC PY 2003 VL 51 IS 6 BP 607 EP 610 DI 10.1097/01.SAP.0000067962.03244.D6 PG 4 WC Surgery SC Surgery GA 752QL UT WOS:000187178600017 PM 14646659 ER PT J AU Wright, C AF Wright, C TI Lymphogenous and hematogenous metastasis of thymic epithelial tumors - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wright, C (reprint author), Massachusetts Gen Hosp, Blake 1570,55 Fruit St, Boston, MA 02114 USA. NR 1 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2003 VL 76 IS 6 BP 1864 EP 1865 DI 10.1016/S0003-4975(03)01316-X PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 750JA UT WOS:000186986500019 ER PT J AU Yarbrough, WM Mukherjee, R Escobar, GP Hendrick, JW Sample, JA Dowdy, KB McLean, JE Mingoia, JT Crawford, FA Spinale, FG AF Yarbrough, WM Mukherjee, R Escobar, GP Hendrick, JW Sample, JA Dowdy, KB McLean, JE Mingoia, JT Crawford, FA Spinale, FG TI Modulation of calcium transport improves myocardial contractility and enzyme profiles after prolonged ischemia-reperfusion SO ANNALS OF THORACIC SURGERY LA English DT Article ID EXCHANGE INHIBITOR CARIPORIDE; PORCINE HEARTS; INFARCT SIZE; INJURY; PROTECTION; THERAPY; TRIAL AB Background. Ischemia-reperfusion (IR) injury causes myocardial dysfunction in part through intracellular calcium overload. A recently described pharmacologic compound, MCC-135 (5-methyl-2[1-piperazinyl] benzenesulfonic acid monohydrate, Mitsubishi Pharma Corporation), alters intracellular calcium levels. This project tested the hypothesis that MCC-135 would influence regional myocardial contractility when administered at reperfusion and after a prolonged period of ischemia. Methods. A circumflex snare and sonomicrometry crystals within remote and area-at-risk regions were placed in pigs (n = 18, 32 kg). Coronary occlusion was instituted for 120 minutes followed by 180 minutes of reperfusion. At 105 minutes of ischemia pigs were randomly assigned to IR only (n = 11) or MCC-135 (IR-MCC [300 mug . kg(-1) . h(-1), n = 7]) administered intravenously. Regional myocardial contractility was determined by calculation of the regional end-systolic pressure-dimension relation (RESPDR [mm Hg/cm]). Myocardial injury was determined by measurement of plasma levels of myocyte-specific enzymes. Results. At 90 minutes ischemia, mean troponin-I was 35 +/- 8 ng/mL with no significant difference between groups. At 180 minutes reperfusion, heart rate was increased by 18% +/- 5% in the IR only group (p < 0.05) and was reduced by 11% +/- 4% with IR-MCC (p < 0.05). At 90 minutes ischemia RESPDR was reduced from baseline by 51% +/- 6% (P < 0.05). By 30 minutes reperfusion, reductions in RESPDR were attenuated with IR-MCC compared with IR only values. The CK-MB levels were increased at 180 minutes reperfusion in the IR only group (52 +/- 9 ng/mL) compared with baseline (6 +/- 1 ng/mL, p < 0.05) but were attenuated with IR-MCC (24 +/- 4 ng/mL, p < 0.05) compared with IR only values. Conclusions. Despite similar degrees of injury at 90 minutes ischemia MCC-135 improved regional contractility and reduced the egress of CK-MB. Moreover MCC-135 was associated with decreased heart rate, a determinant of myocardial oxygen demand. Pharmacologic modulation of calcium transport ameliorates myocardial dysfunction in the acute IR period. (C) 2003 by The Society of Thoracic Surgeons. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Assoc Med Ctr, Charleston, SC USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,770 MUCS Complex,Suite 62, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-07260, HL-97012, HL-45024] NR 24 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2003 VL 76 IS 6 BP 2054 EP 2061 DI 10.1016/S0003-4975(03)01059-2 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 750JA UT WOS:000186986500059 PM 14667641 ER PT J AU Vallieres, E Gonzalez, X Pedersen, KM Sears, GK Springmeyer, SC AF Vallieres, E Gonzalez, X Pedersen, KM Sears, GK Springmeyer, SC TI Novel surgical system for reducing lung tissue and preventing air leaks SO ANNALS OF THORACIC SURGERY LA English DT Article ID VOLUME REDUCTION SURGERY; RESECTION; EMPHYSEMA; DISEASE AB Purpose. This study assessed the feasibility of using the VALR surgical system (Spiration Inc, Redmond, WA), limited by federal law to investigational use, for capturing and reducing a selected portion of affected lobes in patients undergoing lobectomy. Description. The tested system consists of a hand-held vacuum-regulated introducer loaded with a flexible, silicone sleeve. Targeted tissue is drawn into the introducer and the silicone sleeve is deployed and sutured in place. The end of the proximal sleeve includes a compression band for applying uniform radial pressure, suture ports, and silicone lugs lining the inner lumen for reinforcing sleeve position. Evaluation. The system was effective in capturing 25% to 30% tissue of each lobe tested. Mean intraoperative test time was 8.5 minutes. The compression sleeve did not slip or dislodge after suturing, and no tissue damage or leaks were observed. Conclusions. It was feasible using vacuum to draw and isolate a portion of pulmonary tissue within a silicone sleeve. The system was intuitive to apply, easy to use, and produced effective reduction and sealing of tissue. (C) 2003 by The Society of Thoracic Surgeons. C1 Univ Washington, Vet Affairs Puget Sound Healthcare Syst, Div Cardiothorac Surg, Seattle, WA 98195 USA. RP Vallieres, E (reprint author), Univ Washington, Vet Affairs Puget Sound Healthcare Syst, Div Cardiothorac Surg, Box 356310, Seattle, WA 98195 USA. OI Vallieres, Eric/0000-0003-1732-2658 NR 10 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD DEC PY 2003 VL 76 IS 6 BP 2071 EP 2074 DI 10.1016/S0003-4975(03)00900-7 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 750JA UT WOS:000186986500063 PM 14667645 ER PT J AU Andes, D Craig, WA AF Andes, D Craig, WA TI Pharmacodynamics of the new des-F(6)-quinolone garenoxacin in a murine thigh infection model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CIPROFLOXACIN; RESISTANCE; BMS-284756; PARAMETERS; QUINOLONE AB Garenoxacin is a new des-F(6)-quinolone with broad-spectrum activity against both gram-positive cocci and gram-negative bacilli. We used the neutropenic murine thigh infection model to characterize the time course of antimicrobial activity of garenoxacin and determine which pharmacokinetic-pharmacodynamic (PK-PD) parameter best correlated with efficacy. Serum drug levels following three fourfold-escalating single-dose levels of garenoxacin were measured by microbiologic assay. In vivo postantibiotic effects (PAEs) were determined after doses of 16 and 64 mg/kg of body weight. Mice had 10(6.5) to 10(6.7) CFU of Streptococcus pneumoniae strain ATCC 10813 or Staphylococcus aureus strain ATCC 33591 per thigh when they were treated for 24 h with garenoxacin at a dose of 4 to 128 mg/kg/day fractionated for 3-, 6-, 12-, and 24-hour dosing regimens. Nonlinear regression analysis was used to determine which PK-PD parameter best correlated with the measurement of CFU/thigh at 24 h. Pharmacokinetic studies yielded peak/dose values of 0.2 to 0.3, area under the concentration-time curve (AUC)/dose values of 0.1 to 0.5, and half-lives of 0.7 to 1.6 h. Garenoxacin produced in vivo PAEs of 1.4 to 8.2 h with S. pneumoniae ATCC 10813, 7.6 to > 12.4 h with S. aureus ATCC 25923, and 0 to 1.5 h with Klebsiella pneumoniae ATCC 43816. The 24-h AUC/MIC ratio was the PK-PD parameter that best correlated with efficacy (R-2 = 71 to 90% for the two organisms compared with 43 to 56% for the peak/MIC ratio and 47 to 75% for percent time above the MIC [% T>MIC]). In subsequent studies we used the neutropenic murine thigh infection model to determine if the magnitude of the AUC/MIC ratio needed for efficacy of garenoxacin varied among pathogens (including resistant strains). Mice had 10(5.9) to 10(7.2) CFU of 6 strains of S. aureus (2 methicillin resistant), 11 strains of S. pneumoniae (5 penicillin susceptible, 1 penicillin intermediate, and 5 penicillin resistant, and of the resistant strains, 3 were also ciprofloxacin resistant), and 4 gram-negative strains per thigh when treated for 24 h with 1 to 64 mg of garenoxacin per kg every 12 h. A sigmoid dose-response model was used to estimate the doses (mg/kg/24 h) required to achieve a net bacteriostatic effect over 24 h. MICs ranged from 0.008 to 4 mug/ml. The free drug 24-h AUC/MIC ratios for each static dose (2.8 to 128 mg/kg/day) varied from 8.2 to 145. The mean 24-h AUC/MIC ratios +/- standard deviations for S. pneumoniae, S. aureus, and gram-negative strains were 33 +/- 18, 81 +/- 37, and 33 +/- 30, respectively. Methicillin, penicillin, or ciprofloxacin resistance did not alter the magnitude of the AUC/MIC ratio required for efficacy. C1 Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Dept Med, Clin Pharmacol Sect, Madison, WI USA. RP Andes, D (reprint author), Univ Wisconsin, Sch Med, Dept Med, Infect Dis Sect, Room H4-570,600 Highland Ave, Madison, WI 53792 USA. NR 18 TC 37 Z9 38 U1 0 U2 3 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 DEC PY 2003 VL 47 IS 12 BP 3935 EP 3941 DI 10.1128/AAC.47.12.3935-3941.2003 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 749LG UT WOS:000186921500041 PM 14638504 ER PT J AU Zembowicz, A Mastalerz, L Setkowicz, M Radziszewski, W Szczeklik, A AF Zembowicz, A Mastalerz, L Setkowicz, M Radziszewski, W Szczeklik, A TI Safety of cyclooxygenase 2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs SO ARCHIVES OF DERMATOLOGY LA English DT Article ID ASPIRIN-INDUCED ASTHMA; ANTI-IGE AUTOANTIBODIES; FC-EPSILON-RI; RECEPTOR ANTAGONIST; CUTANEOUS REACTIONS; CLASSIFICATION; INTOLERANCE; MONTELUKAST; PATHOGENESIS; EXPRESSION AB Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) exacerbate various forms of urticaria by a nonallergic mechanism involving inhibition of cyclooxygenases. Objectives: To assess safety of cyclooxygenase inhibitors in patients with chronic idiopathic urticaria (CIU) and NSAID sensitivity and to evaluate a role of cysteinyl leukotriene metabolism and mast cell activation in sensitivity to NSAIDs in CIU. Design: Aspirin challenge test followed by randomized, prospective, double-blind, placebo-controlled crossover trial with cyclooxygenase 2 inhibitors. Setting: Tertiary referral center of a university hospital. Patients: Thirty-six patients with CIU. Interventions: Aspirin challenge test (up to 500 mg); randomized trial with rofecoxib (up to 37.5 mg) and celecoxib (up to 300 mg) in aspirin-sensitive patients. After completion of the trial, 7 patients received naproxen sodium (500 mg) as a positive, control. Main Outcome Measures: Standardized skin examination, skin biopsy with mast cell count, urinary levels of leukotriene E-4 (LTE4), and serum levels of mast cell tryptase. Results: Aspirin induced skin eruption in 18 patients. Rofecoxib or celecoxib did not elicit skin eruption in any of the aspirin-sensitive patients. Patients with CIU had higher urinary excretion of LTE4 than healthy control subjects. Basal urinary levels of LTE4 and serum mast cell tryptase were increased in aspirin-sensitive compared with aspirin-tolerant patients. Severity and duration of aspirin-induced urticaria showed a positive correlation with urinary LTE4 excretion. Naproxen precipitated urticaria in 5 of 7 aspirin-sensitive patients and caused further increase in urinary LTE4. Conclusions: Cyclooxygenase 2 inhibitors do not induce urticaria in patients with CIU sensitive to NSAIDs. Sensitivity to NSAIDs in CIU is associated with overproduction of cysteinyl leukotrienes and mast cell activation and most likely depends on inhibition of cyclooxygenase 1. C1 Jagiellonian Univ, Sch Med, Dept Med, Allergy & Immunol Clin, PL-31066 Krakow, Poland. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Jagiellonian Univ, Sch Med, Dept Med, Krakow, Poland. Dohme Idea Inc, Warsaw, Poland. Merck Sharp, Warsaw, Poland. RP Szczeklik, A (reprint author), Jagiellonian Univ, Sch Med, Dept Med, Allergy & Immunol Clin, Ul Skawinska 8, PL-31066 Krakow, Poland. NR 44 TC 67 Z9 70 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2003 VL 139 IS 12 BP 1577 EP 1582 DI 10.1001/archderm.139.12.1577 PG 6 WC Dermatology SC Dermatology GA 753KP UT WOS:000187230800006 PM 14676074 ER PT J AU Bevona, C Goggins, W Quinn, T Fullerton, J Tsao, H AF Bevona, C Goggins, W Quinn, T Fullerton, J Tsao, H TI Cutaneous melanomas associated with nevi SO ARCHIVES OF DERMATOLOGY LA English DT Article ID MALIGNANT-MELANOMA; MELANOCYTIC NEVI; HISTOLOGIC ASSOCIATION; PRECURSOR LESIONS; TUMOR PROGRESSION; DYSPLASTIC NEVUS; PIGMENTED MOLES; POPULATION; RISK; THICKNESS AB Objective: To determine the frequency of and the histologic and clinical factors associated with melanoma existing in histologic contiguity with a nevus. Design: Pathology reports from melanomas collected from January 1, 1993, to December 31, 1997, were retrospectively reviewed. Setting: Independent, community-based dermatopathology laboratory. Patients: A total of 1606 patients with a histologic diagnosis of melanoma. Intervention: None. Main Outcome Measures: Differences in histologic (subtype, Breslow thickness, and Clark level) and clinical (age, sex, and anatomic location) features between melanomas that are associated and unassociated with a nevus. Results: Twenty-six percent of the melanomas reviewed were histologically associated with nevi (dysplastic nevi, 43.0%; and other nevi, 57.0%). Factors that were significantly associated with an increased likelihood of a melanoma being histologically contiguous with a nevus included younger age, superficial spreading subtype, truncal location, Breslow thickness, and Clark level. However, after multivariate analysis, only younger age (odds ratio, 1.27; 95% confidence interval, 1.19-1.37), superficial spreading subtype (odds ratio, 2.96; 95% confidence interval, 2.17-4.02), and truncal location (odds ratio, 3.26; 95% confidence interval, 2.55-4.19) remained significant. Conclusions: Most melanomas were not histologically contiguous with a nevus. Younger age, superficial spreading subtype, and truncal location are independent significant predicators of a melanoma being histologically associated with a nevus. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Hong Kong Baptist Coll, Dept Math, Hong Kong, Hong Kong, Peoples R China. Pathol Serv Inc, Cambridge, MA USA. RP Tsao, H (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,Bartlett 622, Boston, MA 02114 USA. NR 28 TC 100 Z9 102 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2003 VL 139 IS 12 BP 1620 EP 1624 DI 10.1001/archderm.139.12.1620 PG 5 WC Dermatology SC Dermatology GA 753KP UT WOS:000187230800014 PM 14676081 ER PT J AU Longo, MI Nghiem, P AF Longo, MI Nghiem, P TI Merkel cell carcinoma treatment with radiation - A good case despite no prospective studies SO ARCHIVES OF DERMATOLOGY LA English DT Editorial Material ID MOHS MICROGRAPHIC SURGERY; TRABECULAR CARCINOMA; CASE SERIES; MANAGEMENT; SKIN; RADIOTHERAPY; EXCISION; THERAPY; NECK; HEAD C1 Dana Farber Canc Inst, Cutaneous Oncol Unit, Boston, MA 02115 USA. RI Nghiem, Paul/A-9210-2011 OI Nghiem, Paul/0000-0003-2784-963X NR 23 TC 4 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD DEC PY 2003 VL 139 IS 12 BP 1641 EP 1643 DI 10.1001/archderm.139.12.1641 PG 3 WC Dermatology SC Dermatology GA 753KP UT WOS:000187230800020 PM 14676085 ER PT J AU Ritchie, CW Bush, AI Mackinnon, A Macfarlane, S Mastwyk, M MacGregor, L Kiers, L Cherny, R Li, QX Tammer, A Carrington, D Mavros, C Volitakis, I Xilinas, M Ames, D Davis, S Volitakis, I Xilinas, M Ames, D Davis, S Beyreuther, K Tanzi, RE Masters, CL AF Ritchie, CW Bush, AI Mackinnon, A Macfarlane, S Mastwyk, M MacGregor, L Kiers, L Cherny, R Li, QX Tammer, A Carrington, D Mavros, C Volitakis, I Xilinas, M Ames, D Davis, S Volitakis, I Xilinas, M Ames, D Davis, S Beyreuther, K Tanzi, RE Masters, CL TI Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting A beta amyloid deposition and toxicity in Alzheimer disease - A pilot phase 2 clinical trial SO ARCHIVES OF NEUROLOGY LA English DT Article ID DOUBLE-BLIND; NEUROTOXICITY; MICE AB Background: Alzheimer disease (AD) may be caused by the toxic accumulation of beta-amyloid (Abeta). Objective: To test this theory, we developed a clinical intervention using clioquinol, a metal-protein-attenuating compound (MPAC) that inhibits zinc and copper ions from binding to Abeta, thereby promoting Abeta dissolution and diminishing its toxic properties. Methods: A pilot phase 2 clinical trial in patients with moderately severe Alzheimer disease. Results: Thirty-six subjects were randomized. The effect of treatment was significant in the more severely affected group (baseline cognitive subscale score of the Alzheimer's Disease Assessment Scale, 25), due to a substantial worsening of scores in those taking placebo compared with minimal deterioration for the clioquinol group. Plasma Abeta(42) levels declined in the clioquinol group and increased in the placebo group. Plasma zinc levels rose in the clioquinol-treated group. The drug was well tolerated. Conclusion: Subject to the usual caveats inherent in studies with small sample size, this pilot phase 2 study supports further investigation of this novel treatment strategy using a metal-protein-attenuating compound. C1 Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Parkville, Vic 3010, Australia. Univ Melbourne, Dept Med, Mental Hlth Res Inst Victoria, Parkville, Vic 3010, Australia. Univ Melbourne, Dept Psychiat, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. UCL, Dept Psychiat & Behav Sci, London, England. Monash Univ, Dept Psychol Med, Clayton, Vic 3168, Australia. Royal Melbourne Hosp, Dept Neurol, Parkville, Vic 3050, Australia. Univ Gothenburg, Inst Clin Neurosci, Gothenburg, Sweden. Univ Heidelberg, Ctr Biol Mol, Heidelberg, Germany. Massachusetts Gen Hosp, Genet & Aging Res Unit, Boston, MA USA. RP Masters, CL (reprint author), Univ Melbourne, Dept Pathol, Mental Hlth Res Inst Victoria, Parkville, Vic 3010, Australia. EM c.masters@unimelb.edu.au RI Mackinnon, Andrew/A-4901-2008; Davis, Stephen/L-5260-2013; Bush, Ashley/A-1186-2007 OI Davis, Stephen/0000-0003-0962-2300; Bush, Ashley/0000-0001-8259-9069 NR 17 TC 617 Z9 644 U1 6 U2 40 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2003 VL 60 IS 12 BP 1685 EP 1691 DI 10.1001/archneur.60.12.1685 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 752QM UT WOS:000187178700003 PM 14676042 ER PT J AU Seddon, JM Cote, J Rosner, B AF Seddon, JM Cote, J Rosner, B TI Progression of age-related macular degeneration - Association with dietary fat, transunsaturated fat, nuts, and fish intake SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; SUDDEN CARDIAC DEATH; CLASSIFICATION-SYSTEM; VITAMIN-C; RISK; MACULOPATHY; CONSUMPTION; WOMEN; SMOKING AB Background: Individuals with early or intermediate stages of age-related macular degeneration (AMD) make up a large, growing segment of the elderly population. Evidence is sparse regarding modifiable factors that may decrease the risk of progression to the advanced forms of AMD. Objective: To advise patients with a high risk for advanced forms of AMD about preventive measures through our evaluation of the relationship between dietary fat intake and the progression of early or intermediate AMD to the advanced stages of the disease associated with visual loss. Design: A prospective cohort study with an average follow-up time of 4.6 years. Setting: A hospital-based clinical retinal practice specializing in macular degeneration. Patients: The 261 participants were aged 60 years and older and had some sign of nonexudative AMD and visual acuity of 20/200 or better in at least 1 eye. Main Outcome Measure: Progression to advanced AMD, which was defined as having geographic atrophy or neovascular disease. Results: Higher total fat intake increased the risk of progression to the advanced forms of AMD, with a relative risk (RR) of 2.90 (95% confidence interval, 1.15-7.32) for the highest fat-intake quartile relative to the lowest fat-intake quartile, after controlling for other factors (P trend=.01). Animal fat intake was associated with a 2-fold increased risk of progression (RR, 2.29 for the highest quartile compared with the lowest quartile; 95% confidence interval, 0.91-5.72), although the trend for increasing risk with higher animal fat intake was not significant (P=.09). Higher vegetable fat intake had a stronger relationship with increased risk of AMD progression with an RR of 3.82 (95% confidence interval, 1.58-9.28) for the highest quartile compared with the lowest quartile (P trend=.003). Saturated, monounsaturated, polyunsaturated, and transunsaturated fats increased the likelihood of progression (RR, 2.09 and P trend=.08; RR, 2.21 and P trend=.04; RR, 2.28 and P trend=.04; RR, 2.39 and P trend=.008, respectively). Higher fish intake was associated with a lower risk of AMD progression among subjects with lower linoleic acid intake. Processed baked goods, which are higher in some of these fats, increased the rate of AMD progression approximately 2-fold, and huts were protective. Conclusions: Among individuals with the early or intermediate stages of AMD, total and specific types of fat intake, as well as some fat-containing food groups, modified the risk of progression to advanced AMD. Fish intake and nuts reduced risk. Since advanced AMD is associated with visual loss and reduced quality of life, these preventive measures deserve additional research and greater emphasis. C1 Massachusetts Eye & Ear Infirm, Epidemiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02138 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Seddon, JM (reprint author), Massachusetts Eye & Ear Infirm, Epidemiol Unit, 243 Charles St, Boston, MA 02114 USA. NR 37 TC 197 Z9 210 U1 1 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2003 VL 121 IS 12 BP 1728 EP 1737 DI 10.1001/archopht.121.12.1728 PG 10 WC Ophthalmology SC Ophthalmology GA 751XK UT WOS:000187115200008 PM 14662593 ER PT J AU Kang, JH Pasquale, LR Rosner, BA Willett, WC Egan, KM Faberowski, N Hankinson, SE AF Kang, JH Pasquale, LR Rosner, BA Willett, WC Egan, KM Faberowski, N Hankinson, SE TI Prospective study of cigarette smoking and the risk of primary open-angle glaucoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Glaucoma-Society CY MAR 01-04, 2001 CL NEWPORT BEACH, CALIFORNIA SP Amer Glaucoma Soc ID CAPILLARY BLOOD-FLOW; OPTIC-NERVE HEAD; INTRAOCULAR-PRESSURE; OCULAR HYPERTENSION; PREVALENCE; EPIDEMIOLOGY; CIRCULATION; REDUCTION; WOMEN; EYE AB Objective: To examine the association between cigarette smoking and incident primary open-angle glaucoma (POAG). Methods: Female nurses and male health professionals were prospectively followed up from 1980 and 1986, respectively, to 1996. Participants were at least 40 years old, were free of diagnosed glaucoma at baseline, and reported being examined by an ophthalmologist or optometrist during follow-up. Smoking history and other POAG risk factors were updated with biennial questionnaires. A total of 450 incident cases of POAG were identified. Both cohort-specific proportional hazards analyses and analyses pooled across cohorts were conducted. Results: After controlling for potential risk factors of POAG, including age, hypertension, and African American heritage, neither current smokers (relative risk, 0.85; 95% confidence interval, 0.62-1.18) nor past smokers (relative risk, 0.91; 95% confidence interval, 0.63-1.32) were at greater risk for POAG than those who had never smoked. Heavier smoking did not increase the risk of POAG. A modest inverse association was observed with pack-years of smoking: those with 30 or more pack-years had a 22% reduced risk of POAG (relative risk, 0.78; 95% confidence interval, 0.55-1.11; P for linear trend, .06) than those who had never smoked. Conclusion: Cigarette smoking is not an important risk factor for POAG. C1 Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA. RP Kang, JH (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA87969]; NEI NIH HHS [EY09611]; NHLBI NIH HHS [HL35464]; PHS HHS [A55075] NR 30 TC 30 Z9 33 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2003 VL 121 IS 12 BP 1762 EP 1768 DI 10.1001/archopht.121.12.1762 PG 7 WC Ophthalmology SC Ophthalmology GA 751XK UT WOS:000187115200012 PM 14662597 ER PT J AU Ray, S Loewenstein, J AF Ray, S Loewenstein, J TI Atypical manifestation of multiple evanescent white dot syndrome with large peripapillary lesion SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Loewenstein, J (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD DEC PY 2003 VL 121 IS 12 BP 1794 EP 1796 DI 10.1001/archopht.121.12.1794 PG 3 WC Ophthalmology SC Ophthalmology GA 751XK UT WOS:000187115200021 PM 14662606 ER PT J AU Eibling, DE AF Eibling, DE TI To go home again SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15213 USA. RP Eibling, DE (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, 200 Lothrop St,Suite 500, Pittsburgh, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD DEC PY 2003 VL 129 IS 12 BP 1267 EP 1267 DI 10.1001/archotol.129.12.1267 PG 1 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 752QK UT WOS:000187178500001 ER PT J AU Foran, SE Flood, JG Lewandrowski, KB AF Foran, SE Flood, JG Lewandrowski, KB TI Measurement of mercury levels in concentrated over-the-counter fish oil preparations - Is fish oil healthier than fish? SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; HEART-DISEASE; FATTY-ACIDS; CORONARY; RISK; OMEGA-3-FATTY-ACIDS; DEPRESSION; PREGNANCY; TRIAL; DEATH AB Context.-Fish consumption has been associated with a decreased risk of coronary artery disease. Recent studies have illustrated that the high mercury content in cold-water fish may negate the cardiovascular benefits of fish meals. Fish oils have similar antiatherogenic properties to fish, and similar studies should be performed to determine the level of mercury in fish oils. Objective.-To determine the concentration of mercury in 5 over-the-counter brands of fish oil. Results.-The levels of mercury in the 5 different brands of fish oil ranged from nondetectable (<6 mug/L) to negligible (10-12 mug/L). The mercury content of fish oil was similar to the basal concentration normally found in human blood. Conclusions.-Fish are rich in omega-3 fatty acids, and their consumption is recommended to decrease the risk of coronary artery disease. However, fish such as swordfish and shark are also a source of exposure to the heavy metal toxin, mercury. The fish oil brands examined in this manuscript have negligible amounts of mercury and may provide a safer alternative to fish consumption. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, 55 Fruit St,GRJ 5, Boston, MA 02114 USA. NR 28 TC 56 Z9 60 U1 4 U2 8 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD DEC PY 2003 VL 127 IS 12 BP 1603 EP 1605 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 751XY UT WOS:000187116800012 PM 14632570 ER PT J AU Rosenthal, MJ Felton, RM Nastasi, AE Naliboff, BD Harker, J Navach, JH AF Rosenthal, MJ Felton, RM Nastasi, AE Naliboff, BD Harker, J Navach, JH TI Healing of advanced pressure ulcers by a generic total contact seat: 2 randomized comparisons with low air loss bed treatments SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE beds; pressure; pressure ulcers; rehabilitation ID SORES; COMPLICATIONS; PREVENTION; THERAPY; REST AB Objective: To compare a therapeutic seat with low air loss bed treatment for healing rates of stage III and IV pressure ulcers. Design: Randomized prospective cohort study. Setting: Long-term care facilities. Participants: Two hundred seven subjects with stage III or IV pressure ulcers. Intervention: Two separate randomized control studies of advanced pressure ulcers that compared wound healing on 3 different support surfaces. Subjects were allocated to low air loss bed, upgraded bed overlay (only in study 1), or 4h/d sitting on an experimental generic total contact seat. The seat was designed using prosthetics principles aimed at distributing pressure off bony prominences onto. less pressure-sensitive areas. Subjects were followed for 6 months or until they were totally healed. Main Outcome Measures: Number of subjects who totally healed, time to total healing, and pressure ulcer status score after 4 weeks of treatment. Interface pressures and functional capacity were also measured at 4 weeks. Results: In study 1, 3 subjects worsened on the bed overlay condition and were withdrawn from the study. None worsened on low air loss or generic total contact seat. At 4 weeks in both studies, pressure ulcer status score was lowest for the generic total contact seat (P<.0001), compared with the other surfaces. Subject populations were similar, so to analyze total healing, results from both studies were combined. Total healing of pressure ulcers occurred as early as 4 weeks in some subjects using the generic total contact seat. Even at 8 weeks, total healing was primarily seen with use of that seat, on which interface pressures, function, and seating tolerance were best. Conclusions: Faster healing and better function indicate that treatment using the generic total contact seat is superior to low air loss bed therapy, which is standard care for advanced pressure ulcers. C1 Greater Los Angeles VAMC, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. Greater Los Angeles VAMC, Spinal Cord Injury Disorders Serv, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Div Geriatr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biomed Technol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Div Phys Med & Rehabil, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Rosenthal, MJ (reprint author), GRECC 11E, 16111 Plummer St, Sepulveda, CA 91343 USA. NR 26 TC 4 Z9 5 U1 2 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2003 VL 84 IS 12 BP 1733 EP 1742 DI 10.1016/S0003-9993(03)00435-0 PG 10 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 751JY UT WOS:000187064400001 PM 14669176 ER PT J AU da Cunha, IT Henson, H Qureshy, H Williams, AL Holmes, SA Protas, EJ AF da Cunha, IT Henson, H Qureshy, H Williams, AL Holmes, SA Protas, EJ TI Differential responses to measures of gait performance among healthy and neurologically impaired individuals SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE cerebrovascular accident; gait; oxygen consumption; rehabilitation; spinal cord injuries ID 6-MINUTE WALK TEST; OXYGEN-UPTAKE; HEART-RATE; STROKE PATIENTS; AMBULATION; EXERCISE; REHABILITATION; IMPAIRMENTS; PARAPLEGIA AB Objectives: To compare gait during a 5-minute walk among healthy individuals, persons with spinal cord injury (SCI), and stroke survivors and to investigate whether simultaneous measures of oxygen consumption enhance information about performance. Design: Descriptive study. Setting: Veterans Affairs medical center. Participants: Thirty-nine healthy individuals, 10 persons with SCI, and 20 stroke survivors. Interventions: Participants were fitted with a portable gas analyzer and walked on a 5-m walkway for 5 minutes. Main Outcome Measures: Measures of walk distance, gait speed, gait energy expenditure (GEE), and gait cost were obtained, along with measures of ventilation ((V) over dot E), ventilation and carbon dioxide production slope ((V) over dot E.(V) over dot CO2), oxygen pulse, and heart rate. Results: The SCI group (127.65 +/- 81.74m) walked less than the stroke survivors (148.80+/-64.3m) or the healthy group (268.90+/-35.01m) but had higher energy demands, as shown by GEE (SCI group, 13.28 +/- 3.23mL.kg(-1).min(-1); stroke group, 10.18 +/- 2.14mL.kg(-1).min(-1); healthy group, 9.61 +/- I.90mL.kg(-1).min(-1)) and by gait cost (SCI group,.57+/-.40 mL.kg(-1).m(-1); stroke group, .40+/-.52mL.kg(-1).m(-1); healthy group,. 18+/-.02mL.kg(-1).m(-1)). Compared with the healthy group, the stroke group had higher (V) over dot E (stroke group, 22,34+/-5.20L/min vs healthy group, 16.11+/-3.22L/min) and (V) over dot E.(V) over dot CO2 slope (24.22 +/- 8.80 vs 18.73+/-5.44, respectively). Conclusion: Use of metabolic assessment during the 5-minute walk was feasible and provided further information for evaluating gait performance with the subjects studied. C1 Univ Texas, Med Branch, Dept Phys Therapy, Galveston, TX 77555 USA. Texas Womans Univ, Sch Phys Therapy, Houston, TX USA. Houston Vet Affairs Med Ctr, Phys Med & Rehabil Serv, Houston, TX USA. Houston Vet Affairs Med Ctr, Spinal Cord Injury Serv, Houston, TX USA. Houston Vet Affairs Med Ctr, Rehabil Res & Dev Ctr Excellence Healthy Aging Di, Houston, TX USA. UNI BH, Belo Horizonte, MG, Brazil. RP Protas, EJ (reprint author), Univ Texas, Med Branch, Dept Phys Therapy, 301 Univ Blvd, Galveston, TX 77555 USA. NR 23 TC 9 Z9 9 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2003 VL 84 IS 12 BP 1774 EP 1779 DI 10.1016/S0003-9993(03)00373-3 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 751JY UT WOS:000187064400007 ER PT J AU Corfman, TA Cooper, RA Fitzgerald, SG Cooper, R AF Corfman, TA Cooper, RA Fitzgerald, SG Cooper, R TI Tips and falls during electric-powered wheelchair driving: Effects of seatbelt use, legrests, and driving speed SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE accidental falls; rehabilitation; safety; wheelchairs ID UNITED-STATES; ACCIDENTS; DUMMY AB Objective: To measure the response of a test dummy while traversing common obstacles encountered by users of electric-powered wheelchairs (EPWs) to determine whether optimal wheelchair fit, use of seatbelts, and driving speed affect the frequency and severity of EPW tips and falls. Design: Repeated-measures comparison study. Setting: Constructed environment both in and around a Veterans Affairs medical center. Participant: A 50th percentile Hybrid II anthropometric test dummy (ATD) was used to simulate a person driving an EPW. Interventions: The ATD was driven in 4 different EPWs over commonly encountered obstacles at speeds of 1 and 2m/s, with and without the use of a seatbelt, and at varying legrest heights. Main Outcome Measures: The response and motion of the ATD were observed and recorded as no fall, loss of control (the ATD falls forward or sideways but remains in the EPW), the ATD falls out of the EPW, or the EPW tips completely. Results: A total of 97 adverse events out of 1700 trials were recorded: 88 were losses of control (instability) and 9 were ATD falls. No complete tips of any EPW occurred. Univariate statistical analysis indicated a significant relationship between the adverse events and the use of seatbelts, legrest condition, and test obstacles (P<.05). A mixed-model analysis confirmed the significant relationships between the adverse events and the use of seatbelts, legrest condition, and test obstacles (P<.05). However, the mixed model indicated that (1) there was no significant relationship between the adverse events and driving speed and (2) no one obstacle was designated to be the most problematic. Conclusion: Persons who use EPWs should use seatbelts and legrests while driving their EPWs, and clinicians should include common driving tasks when assessing the proper set-up of EPWs. C1 Univ Pittsburgh, Dept Rehabil Sci & Technol Phys Med & Rehabil & B, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151R1, VA Ctr Excellence Wheelchairs & Related Technol, 7180 Highland Dr, Pittsburgh, PA 15261 USA. FU ODCDC CDC HHS [R49/CCR 310285-04] NR 20 TC 20 Z9 20 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD DEC PY 2003 VL 84 IS 12 BP 1797 EP 1802 DI 10.1016/S0003-9993(03)00467-2 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 751JY UT WOS:000187064400011 PM 14669186 ER PT J AU Wagner, DD Burger, PC AF Wagner, DD Burger, PC TI Platelets in inflammation and thrombosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE platelets; inflammation; thrombosis; atherosclerosis; hemostasis ID VON-WILLEBRAND-FACTOR; SELECTIN-DEFICIENT MICE; WEIBEL-PALADE BODIES; SURFACE-ADHERENT PLATELETS; HUMAN-ENDOTHELIAL CELLS; NECROSIS-FACTOR-ALPHA; SOLUBLE P-SELECTIN; IN-VIVO; ACTIVATED PLATELETS; TISSUE FACTOR AB For many years it has been known that platelets play an important role in thrombosis and hemostasis. In recent times, however, it has become evident that platelets also have relevant functions in inflammation. It was shown that thrombosis and inflammation share several key molecular mechanisms and in fact are 2 intrinsically linked processes. In this review, we intend to give a short overview with emphasis on work stemming from our laboratory. C1 Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R01 HL053756, R01 HL53756, R37 HL041002, R37 HL41002] NR 91 TC 283 Z9 296 U1 1 U2 13 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 DEC PY 2003 VL 23 IS 12 BP 2131 EP 2137 DI 10.1161/01.ATV.0000095974.95122.EC PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 753NC UT WOS:000187236600005 PM 14500287 ER PT J AU Wu, DW de Pablo, P Lieberman, E Michaud, K Wolfe, F Choi, HK AF Wu, DW de Pablo, P Lieberman, E Michaud, K Wolfe, F Choi, HK TI Conventional and disease-specific risk factors for congestive heart failure in rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Natl Data Bank Rheumat Dis, Wichita, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2003 VL 48 IS 12 BP 3634 EP 3635 PG 2 WC Rheumatology SC Rheumatology GA 752QR UT WOS:000187179100074 ER PT J AU Gupta, AR Fraenkel, L Choi, HK Michaud, K Wolfe, F AF Gupta, AR Fraenkel, L Choi, HK Michaud, K Wolfe, F TI Utilization of antilipemic agents and gender differences among subjects with rheumatoid arthritis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Yale Sch Med, New Haven, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Databank Rheumat Dis, Wichita, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2003 VL 48 IS 12 BP 3646 EP 3646 PG 1 WC Rheumatology SC Rheumatology GA 752QR UT WOS:000187179100095 ER PT J AU Goldstein, JL Gibofsky, A Eisen, G Lewis, B Gralnek, I Fort, JG Zlotnick, S Simms, L AF Goldstein, JL Gibofsky, A Eisen, G Lewis, B Gralnek, I Fort, JG Zlotnick, S Simms, L TI Small bowel mucosal lesions and drug tolerability with naproxen plus omeprazole, celecoxib and placebo in healthy subjects using capsule endoscopy: Results from a double-blind, randomized, controlled trial. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 67th Annual Scientific Meeting of the American-College-of-Rheumatology/38th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals CY OCT 23-28, 2003 CL ORLANDO, FLORIDA C1 Univ Chicago, Chicago, IL 60637 USA. New York Weill Cornell Med Ctr, New York, NY USA. Vanderbilt Univ, Nashville, TN USA. Mt Sinai Med Ctr, New York, NY 10029 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Pfizer Inc, Peapack, NJ USA. Pfizer, Markham, ON, Canada. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2003 VL 48 IS 12 BP 3662 EP 3662 PG 1 WC Rheumatology SC Rheumatology GA 752QR UT WOS:000187179100119 ER PT J AU Millett, PJ Clavert, P Warner, JJP AF Millett, PJ Clavert, P Warner, JJP TI Arthroscopic management of anterior, posterior, and multidirectional shoulder instability: Pearls and pitfalls SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Arthroscopy-Association-of-North-America CY APR 24-27, 2003 CL PHOENIX, ARIZONA SP Arthroscopy Assoc N Amer ID ROTATOR INTERVAL CAPSULE; GLENOHUMERAL JOINT; FOLLOW-UP; STABILITY; BANKART; CAPSULORRHAPHY; INFERIOR; LESION; STABILIZATION; SHIFT C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, 275 Cambridge St,Suite 403A, Boston, MA 02114 USA. NR 39 TC 21 Z9 21 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD DEC PY 2003 VL 19 IS 10 SU 1 BP 86 EP 93 DI 10.1016/j.arthro.2003.09.031 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 754RH UT WOS:000187344800012 PM 14673424 ER PT J AU Ding, D Cooper, RA Kaminski, BA Kanaly, JR Allegretti, A Chaves, E Hubbard, S AF Ding, D Cooper, RA Kaminski, BA Kanaly, JR Allegretti, A Chaves, E Hubbard, S TI Integrated control and related technology of assistive devices SO ASSISTIVE TECHNOLOGY LA English DT Review DE assistive device; integrated control; computer access; environment control unit; wheelchair guidance ID HANDICAPPED PEOPLE; SYSTEM; MOBILITY; DISABILITIES; WHEELCHAIRS; INTERFACE AB Assistive devices are now available that allow persons with severe physical disabilities to complete tasks independently. When the user has severe physical limitations, it may be advantageous to have an integrated control system where a single control interface (e.g., joystick, head switches, voice recognition system, keypad) is used to operate two or more assistive devices (e.g., power wheelchairs, augmentative communication devices, computers, environmental control units, and other devices that are controlled electronically). The advantages of integrated control are that persons with limited motor control can access several devices with one access site without assistance, and the user does not need to learn a different operating mechanism for each device. The purpose of this review is to convey the depth and breadth of the research that has been conducted on integrated control systems, as well as to provide some insights into future directions. We reviewed research works pertaining to communication and environmental control, computer access, and wheelchair guidance systems. Information gathered in this study will help people become fully aware of the status of contemporary integrated control technology in order to increase the quality of life of people who use electronic assistive devices. C1 Human Engn Res Labs, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Technol, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), Human Engn Res Labs, VA Pittsburgh Healthcare Syst, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. NR 53 TC 19 Z9 19 U1 1 U2 8 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD WIN PY 2003 VL 15 IS 2 BP 89 EP 97 PG 9 WC Rehabilitation SC Rehabilitation GA 883OM UT WOS:000226022600001 PM 15137725 ER PT J AU Guo, SF Cooper, RA Corfman, T Ding, D Grindle, G AF Guo, SF Cooper, RA Corfman, T Ding, D Grindle, G TI Influence of wheelchair front caster wheel on reverse directional stability SO ASSISTIVE TECHNOLOGY LA English DT Article DE electric powered wheelchair; wheelchair reverse directional stability; caster wheel orientation; motor back-emf ID UNITED-STATES; ACCIDENTS; USERS AB The purpose of this research was to study directional stability during reversing of rear-wheel drive, electric-powered wheelchairs (EPW) under different initial front caster orientations. Specifically, the weight distribution differences caused by certain initial caster orientations were examined as a possible mechanism for causing directional instability that could lead to accidents. Directional stability was quantified by measuring the drive direction error of the EPW by a motion analysis system. The ground reaction forces were collected to determine the load on the front casters, as well as back-emf data to attain the speed of the motors. The drive direction error was found to be different for various initial caster orientations. Drive direction error was greatest when both casters were oriented 90degrees to the left or right, and least when both casters were oriented forward. The results show that drive direction error corresponds to the loading difference on the casters. The data indicates that loading differences may cause asymmetric drag on the casters, which in turn causes unbalanced torque load on the motors. This leads to a difference in motor speed and drive direction error. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, SHRS, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. RP Guo, SF (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr 151R-1, Pittsburgh, PA 15206 USA. NR 15 TC 3 Z9 3 U1 1 U2 2 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD WIN PY 2003 VL 15 IS 2 BP 98 EP 104 PG 7 WC Rehabilitation SC Rehabilitation GA 883OM UT WOS:000226022600002 PM 15137726 ER PT J AU Fitzgerald, SG Arva, J Cooper, RA Dvorznak, MJ Spaeth, DM Boninger, ML AF Fitzgerald, SG Arva, J Cooper, RA Dvorznak, MJ Spaeth, DM Boninger, ML TI A pilot study on community usage of a pushrim-activated, power-assisted wheelchair SO ASSISTIVE TECHNOLOGY LA English DT Article DE wheelchairs; propulsion; driving characteristics ID PROPULSION; USERS; PERFORMANCE; PEDOMETER; LIFE; PAIN AB Manual wheelchair propulsion combined with other stresses to the upper extremities may result in secondary injury. Possible solutions would be to devise alternative methods of propulsion, such as a pushrim-activated, power-assist wheelchair (PAPAW). The goals of this study were to examine the usage of the PAPAW in a real world setting and to characterize the driving habits of manual wheelchair users. Feedback was also obtained regarding subjects' opinions with respect to the PAPAW: their likes and dislikes. A PAPAW was provided to subjects for 2 weeks. Usage (average and total distance traveled and velocity) was tracked for both the PAPAW and the subjects' own wheelchairs. Significant differences in usage were not seen between the personal wheelchairs or the PAPAW. As a result, weeks were combined to provide an overall examination of driving characteristics. The average distance traveled over an average day was 1,671.4 +/- 314.8 m with an average velocity of 0.44 +/- 0.09 m/second. This pilot study provides an idea of manual wheelchair usage in a population of individuals with spinal cord injury. The lack of significant findings between the PAPAW and the subjects' own wheelchairs may be a function of study methodology such as sample size and length of follow-up in the new wheelchair. Future studies should expand upon the pilot work completed here, strengthening the design. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Permobil Inc, Nashville, TN USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, VA Rehabil Res & Dev Ctr, 151-R1,7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 24 TC 14 Z9 14 U1 2 U2 4 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD WIN PY 2003 VL 15 IS 2 BP 113 EP 119 PG 7 WC Rehabilitation SC Rehabilitation GA 883OM UT WOS:000226022600004 PM 15137728 ER PT J AU DiGiovine, CP Cooper, RA Wolf, E Fitzgerald, SG Boninger, ML AF DiGiovine, CP Cooper, RA Wolf, E Fitzgerald, SG Boninger, ML TI Analysis of whole-body vibration during manual wheelchair propulsion: A comparison of seat cushions and back supports for individuals without a disability SO ASSISTIVE TECHNOLOGY LA English DT Article DE back supports; manual wheelchair propulsion; seat cushions; seating systems; wheelchairs; whole-body vibration ID VERTICAL VIBRATION; SUSPENSION DESIGN; APPARENT MASS; PAIN; TRANSMISSION; POSTURE; HEAD; DISCOMFORT; EXPOSURE; SUBJECT AB Whole-body vibration exposure has been found to be detrimental to the health of humans owing to effects such as degraded comfort, disc degeneration, and lower back pain. The purpose of this study was to determine if selected seat cushions and back supports minimize the transmission of vibrations during manual wheelchair propulsion. Ten unimpaired participants traversed an activities of daily living course using four seat cushions and four back supports. Vibrations were measured using triaxial accelerometers. The time domain and frequency domain transmissibility was used to determine if differences exist among seat cushions and back supports. Differences were found among the four seat cushions and four back supports. Seat cushion and back support manufacturers should concentrate on single-event shocks and repeated shocks, as opposed to oscillatory motions and self-generated vibrations, because the vibrations generated by these events tend to reside in the range of frequencies most sensitive to humans. Vibrations in this range of frequencies have the greatest effect on the transmission of whole-body vibration during manual wheelchair propulsion. Differences among the seat cushions and back supports appear to be due to the seat cushion/back support design and postural support. From a clinical perspective, the time domain transmissibility best describes the transmission of whole-body vibration. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, VA Rehabil Res & Dev Ctr, Pittsburgh, PA 15206 USA. Univ Illinois, Dept Disabil & Human Dev, Assist Technol Unit, Chicago, IL 60680 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, VA Rehabil Res & Dev Ctr, 151R-1,7180 Highland Dr, Pittsburgh, PA 15206 USA. RI DiGiovine, Carmen/E-2982-2011; OI Wolf, Erik/0000-0002-6353-7978; Boninger, Michael/0000-0001-6966-919X NR 43 TC 5 Z9 5 U1 0 U2 0 PU R E S N A PRESS PI ARLINGTON PA 1700 MOORE ST, STE 1540, ARLINGTON, VA 22209-1903 USA SN 1040-0435 J9 ASSIST TECHNOL JI Assist. Technol. PD WIN PY 2003 VL 15 IS 2 BP 129 EP 144 PG 16 WC Rehabilitation SC Rehabilitation GA 883OM UT WOS:000226022600006 PM 15137730 ER PT J AU Braunwald, E Shepherd, J AF Braunwald, E Shepherd, J TI Optimal strategies in preventing the next event: The role of statins in cardiovascular protection - Foreword SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Editorial Material ID ACUTE CORONARY SYNDROMES; PRAVASTATIN; THERAPY; TRIAL; PLAQUE C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Glasgow, Glasgow Royal Infirm, Dept Pathol Biochem, Glasgow G4 0SF, Lanark, Scotland. RP Braunwald, E (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD DEC PY 2003 VL 4 IS 5 BP 1 EP 2 DI 10.1016/S1567-5688(03)90000-6 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 762VE UT WOS:000188002200001 ER PT J AU Cannon, CP AF Cannon, CP TI The next step in cardiovascular protection SO ATHEROSCLEROSIS SUPPLEMENTS LA English DT Article; Proceedings Paper CT 25th Congress of the European-Society-of-Cardiology CY AUG 30-SEP 03, 2003 CL VIENNA, AUSTRIA SP European Soc Cardiol DE pravastatin; PROVE-IT; acute coronary syndrome; clinical equivalence; inflammation; lipids ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; RECURRENT ISCHEMIC EVENTS; CHOLESTEROL LEVELS; CHLAMYDIA-PNEUMONIAE; SEROLOGICAL EVIDENCE; AMERICAN-COLLEGE; UNSTABLE ANGINA; ARTERY-DISEASE AB While aggressive interventional therapy and anti-thrombotic therapy have revolutionized the management of acute coronary syndromes (ACS), defined as acute myocardial infarction (MI) or unstable angina (UA), long-term event rates remain high. Elevated lipids, inflammation and infection have each been implicated as additional mechanisms contributing to instability of vulnerable plaques. The new frontier in ACS management has focussed on treatment of these components of vascular disease. Preliminary trials have shown that early treatment with statins after ACS reduces coronary events but additional studies are needed to confirm this benefit. Furthermore, it is not clear what degree of low-density lipoprotein cholesterol (LDL-C) lowering is needed to stabilize the ACS patient. Chlamydia pneumoniae has been implicated in the development of coronary heart disease (CHD) but the results of preliminary trials investigating anti-chlamydial antibiotics have been inconsistent. Therefore, the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT TIMI 22) trial has been designed specifically to determine whether standard LDL-C reduction (with pravastatin 40 mg) provides a similar clinical benefit to more aggressive LDL-C reduction (with atorvastatin 80 mg). In 4162 ACS patients over a 2-year period, this trial will also evaluate the long-term effect of the quinolone antibiotic, gatifloxacin, in reducing cardiovascular events. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 25 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1567-5688 J9 ATHEROSCLEROSIS SUPP JI Atheroscler. Suppl. PD DEC PY 2003 VL 4 IS 5 BP 3 EP 9 DI 10.1016/S1567-5688(03)90001-8 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 762VE UT WOS:000188002200002 PM 14980229 ER PT J AU Fortier, CB Disterhoft, JF Capozzi, S Kilduff, P Cronin-Golomb, A McGlinchey, RE AF Fortier, CB Disterhoft, JF Capozzi, S Kilduff, P Cronin-Golomb, A McGlinchey, RE TI Conditional discrimination learning in patients with bilateral medial temporal lobe amnesia SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID HIPPOCAMPECTOMY DISRUPTS; QUANTITATIVE-ANALYSIS; LESIONS; MEMORY; SYSTEM; AWARENESS; ACQUISITION; RESPONSES; RETENTION; RATS AB The ability of bilateral medial temporal lobe amnesic patients (MT; n = 8) and normal participants (NC; n = 8) to acquire a conditional discrimination in trace and delay eyeblink conditioning paradigms was investigated. Experiment 1 assessed trace conditional discrimination learning by using a light conditional stimulus (S+/S-) and tone conditioned stimulus (CS) separated by a 1-s trace. NCs responded differentially on S+ trials (mean percent conditioned responses = 66) versus S- trials (30), whereas MTs were impaired in their acquisition of the conditional discrimination (S+ = 51, S- = 43). In Experiment 2, the temporal separation was eliminated. NCs acquired the conditional discrimination (S+ = 70, S- = 29). MTs were unable to respond differentially (S+ = 42, S- = 37). The findings indicate that the hippocampal system is essential in acquiring a conditional discrimination, even in a delay paradigm. C1 VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA 02130 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Northwestern Univ, Feinberg Med Sch, Dept Physiol, Evanston, IL 60208 USA. RP Fortier, CB (reprint author), VA Boston Healthcare Syst, Ctr Geriatr Res Educ & Clin, MDRC 151 A,Bldg 9,150 S Huntington Ave, Boston, MA 02130 USA. RI McGlinchey, Regina/R-1971-2016; OI Disterhoft, John/0000-0002-8817-7913 FU NIAAA NIH HHS [R01 AA014205, R01 AA014205-01A2]; NIMH NIH HHS [MH47340, R01 MH047340, R56 MH047340]; NINDS NIH HHS [1P50NS26985, P50 NS026985, P50 NS026985-09A1] NR 34 TC 18 Z9 20 U1 2 U2 3 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD DEC PY 2003 VL 117 IS 6 BP 1181 EP 1195 DI 10.1037/0735-7044.117.6.1181 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 755KP UT WOS:000187402300007 PM 14674839 ER PT J AU Ferrando, AA Look, AT AF Ferrando, AA Look, AT TI Gene expression profiling: will it complement or replace immunophenotyping? SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE DNA microarrays; flow cytometry; immunophenotyping; classification of leukaemias and lymphomas; prognostic evaluation AB Gene expression profiling using DNA microarrays represents a major advance in the diagnosis of haematological malignancies; it enables the analysis of RNA expression by clonal populations of leukaemia and lymphoma cells on a genome-wide scale. Currently, flow cytometric analysis of differentiation-linked surface antigens expressed by malignant cells is essential for the accurate diagnosis and optimal therapeutic planning for patients with leukaemias and lymphomas. Given the astonishing pace of research in microarray technology, a key question for the haematopathologist is: will gene expression profiling using DNA microarrays replace immunophenotyping, or will these two technologies evolve together as complementary approaches to improve diagnosis and therapy? In this chapter, we review the technical advantages and pitfalls of each of these two approaches and provide an assessment of their differences and potentially synergistic applications. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Vice Chair Res,Dana Farber Canc Inst, Boston, MA 02115 USA. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Vice Chair Res,Dana Farber Canc Inst, Mayer 630, Boston, MA 02115 USA. EM adolfo_ferrando@dfci.harvard.edu NR 18 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2003 VL 16 IS 4 BP 645 EP 652 DI 10.1053/ybeha.2003.280 PG 8 WC Hematology SC Hematology GA V41ZH UT WOS:000202837300008 PM 14592648 ER PT J AU Edge, ASB AF Edge, ASB TI Deglycosylation of glycoproteins with trifluoromethanesulphonic acid: elucidation of molecular structure and function SO BIOCHEMICAL JOURNAL LA English DT Review DE carbohydrate; deglycosylation; glycoprotein; post-translational modification; protein structure; trifluoromethanesulphonic acid (TFMS) ID GLOMERULAR-BASEMENT-MEMBRANE; HEPARAN-SULFATE PROTEOGLYCAN; INSULIN-RECEPTOR CARBOHYDRATE; SURFACE-LAYER GLYCOPROTEIN; CELLULAR IMMUNE-RESPONSES; O-SPECIFIC POLYSACCHARIDE; KERATAN SULFATE; ZONA-PELLUCIDA; CORE-PROTEIN; MYCOBACTERIUM-TUBERCULOSIS AB The alteration of proteins by post-translational modifications, including phosphorylation, sulphation, processing by proteolysis, lipid attachment and glycosylation, gives rise to a broad range of molecules that can have an identical underlying protein core. An understanding of glycosylation of proteins is important in clarifying the nature of the numerous variants observed and in determining the biological roles of these modifications. Deglycosylation with TFMS (trifluoromethanesulphonic acid) [Edge, Faltynek, Hof, Reichert, and Weber, (1981) Anal. Biochem. 118, 131-137] has been used extensively to remove carbohydrate from glycoproteins, while leaving the protein backbone intact. Glycosylated proteins from animals, plants, fungi and bacteria have been deglycosylated with TFMS, and the most extensively studied types of carbohydrate chains in mammals, the N-linked, O-linked and glycosaminoglycan chains, are all removed by this procedure. The method is based on the finding that linkages between sugars are sensitive to cleavage by TFMS, whereas the peptide bond is stable and is not broken, even with prolonged deglycosylation. The relative susceptibility of individual sugars in glycosidic linkage varies with the substituents at C-2 and the occurrence of amido and acetyl groups, but even the most stable sugars are removed under conditions that are sufficiently mild to prevent scission of peptide bonds. The post-translational modifications of proteins have been shown to be required for diverse biological functions, and selective procedures to remove these modifications play an important role in the elucidation of protein structure and function. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Edge, ASB (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 121 TC 84 Z9 88 U1 2 U2 31 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2003 VL 376 BP 339 EP 350 DI 10.1042/BJ20030673 PN 2 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753UY UT WOS:000187250000002 PM 12974674 ER PT J AU Condray, R Siegle, GJ Cohen, JD van Kammen, DP Steinhauer, SR AF Condray, R Siegle, GJ Cohen, JD van Kammen, DP Steinhauer, SR TI Automatic activation of the semantic network in schizophrenia: Evidence from event-related brain potentials SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; semantic priming; N400; automatic activation ID INFORMATION-PROCESSING DEFICITS; STIMULUS ONSET ASYNCHRONIES; BACKWARD-MASKING; WORD PRONUNCIATION; LEXICAL DECISION; WORKING-MEMORY; ABNORMALITIES; N400; FACILITATION; HALOPERIDOL AB Background: Language disorder associated with schizophrenia might be due to disturbances in both automatic activation and mechanisms of controlled attention. The contribution of each process to semantic memory dysfunction has not been determined for schizophrenia, and the semantic priming paradigm is well-suited for addressing this question. In the present report, event-related potentials (ERPs) elicited under conditions assumed to reveal automatic activation (short prime-target interval and low proportion of related words) are compared directly with ERPs elicited under conditions associated with controlled processing (long prime-target interval and high proportion of related words). Methods: Visual ERPs were recorded during a lexical decision task, in which semantic relationship (associated and unassociated words), expectancy (relatedness proportions), and prime-target interval (250- and 850-msec inter-stimulus intervals (ISIS)) were varied. Diagnosis and expectancy were between-subjects factors; semantic relationship and ISI were repeated measures. The N400 priming effect (enhanced negativity to unassociated words) was compared between 34 male normal control subjects tested once and 37 male schizophrenia inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. Results: The N400 priming effect for patients was significantly reduced during both pharmacologic phases, compared with controls. During haloperidol treatment, however, patients showed a significant N400 priming effect over the anterior scalp region and additionally under the automatic activation condition. The N400 priming effect was enhanced under the controlled processing condition for control subjects; this effect was not observed for patients. N400 amplitude elicited under the rapid presentation rate (250-msec ISI) differed between medicated patients and controls; groups did not differ for the 850-msec ISI. Conclusions: Findings suggest that automatic activation and mechanisms of controlled attention are both disrupted during semantic memory access for schizophrenia patients. Pharmacologic agents, such as haloperidol, might enhance automatic activation of the semantic network in this patient population, as indexed by the N400 component of the ERP. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Healthcare Syst, Highland Dr Div, Pittsburgh, PA USA. Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA. Aventis Pharmaceut, Bridgewater, NJ USA. RP Condray, R (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH50631] NR 50 TC 49 Z9 50 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2003 VL 54 IS 11 BP 1134 EP 1148 DI 10.1016/S0006-3223(03)00699-1 PG 15 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 747EM UT WOS:000186792300002 PM 14643080 ER PT J AU Spiryda, LB Laufer, MR Soiffer, RJ Antin, JA AF Spiryda, LB Laufer, MR Soiffer, RJ Antin, JA TI Graft-versus-host disease of the vulva and/or vagina: Diagnosis and treatment SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE vagina; graft-versus-host disease ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; MYELOID-LEUKEMIA; STENOSIS AB We describe a series of women after allogeneic stem cell transplantation with vaginal graft-versus-host disease (GVHD) who were treated with topical cyclosporine, surgery, or both. We reviewed the medical charts of 11 women who presented with vaginal pain, discomfort, and vaginal scarring (inability to perform a Papanicolaou test or have vaginal intercourse because of pain). Vaginal symptoms develop an average of 10 months from bone marrow transplantation. Symptoms and physical findings include excoriated and ulcerated mucosa, thickened mucosa, narrowed introitus, and obliterated introitus from dense scar tissue that does not resolve with systemic or topical estrogens. The severity of symptoms and the physical findings in our study population did not correlate with age, type of leukemia, type of transplant, or severity or acute or chronic GVHD. Excoriated mucosa and moderately thickened mucosa were successfully treated with topical cyclosporine. Extensive synechiae and complete obliteration of the vaginal canal required surgical lysis with postoperative topical cyclosporine. Vaginal GVHD can successfully be treated with topical cyclosporine when mild to moderate disease is present. Surgical lysis with topical cyclosporine is required when more severe disease ensues. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Laufer, MR (reprint author), Childrens Hosp, Div Gynecol, 300 Longwood Ave, Boston, MA 02115 USA. NR 13 TC 35 Z9 35 U1 1 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD DEC PY 2003 VL 9 IS 12 BP 760 EP 765 DI 10.1016/j.bbmt.2003.08.001 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 759NZ UT WOS:000187744900004 PM 14677115 ER PT J AU Wang, M Hanfelt, JJ AF Wang, M Hanfelt, JJ TI Adjusted profile estimating function SO BIOMETRIKA LA English DT Article DE adjusted profile likelihood; bias correction; Neyman-Scott problem; nuisance parameter; pairwise association; profile estimating function; sparse data ID LIKELIHOOD; MODELS AB In settings where the full probability model is not specified, consider a general estimating function g(theta, (λ) over cap (theta); y) that involves not only the parameters of interest, theta, but also some nuisance parameters, lambda. We consider methods for reducing the effects on g of fitting nuisance parameters. We propose Cox-Reid-type adjustment to the profile estimating function, g(theta, (λ) over cap (theta); y), that reduces its bias by two orders. Typically, only the first two moments of the response variable are needed to form the adjustment. Important applications of this method include the estimation of the pairwise association and main effects in stratified, clustered data and estimation of the main effects in a matched pair study. A brief simulation study shows that the proposed method considerably reduces the impact of the nuisance parameters. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wang, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. NR 17 TC 10 Z9 10 U1 0 U2 3 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON WC1E 6BT, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2003 VL 90 IS 4 BP 845 EP 858 DI 10.1093/biomet/90.4.845 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 754MT UT WOS:000187321500007 ER PT J AU Malo, MS Abedrapo, M Chen, A Mozumder, M Pushpakaran, P Alkhoury, F Zhang, WY Fleming, E Hodin, RA AF Malo, MS Abedrapo, M Chen, A Mozumder, M Pushpakaran, P Alkhoury, F Zhang, WY Fleming, E Hodin, RA TI Improved eukaryotic promoter-detection vector carrying two luciferase reporter genes SO BIOTECHNIQUES LA English DT Article ID THYROID-HORMONE; MAMMALIAN-CELLS; MARKER C1 Harvard Univ, Sch Med, Boston, MA USA. RP Hodin, RA (reprint author), Massachusetts Gen Hosp, Dept Surg, Gray 504,55 Fruit St, Boston, MA 02114 USA. RI pushpakaran, dr prem raj/D-3540-2009 OI pushpakaran, dr prem raj/0000-0002-2289-5277 FU NIDDK NIH HHS [DK50623, DK47186] NR 13 TC 14 Z9 14 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2003 VL 35 IS 6 BP 1150 EP + PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753UX UT WOS:000187249900006 PM 14682048 ER PT J AU Li, LH Akashi, K AF Li, LH Akashi, K TI Unraveling the molecular components and genetic blueprints of stem cells SO BIOTECHNIQUES LA English DT Review ID BONE-MARROW; HEMATOPOIETIC-CELLS; CDNA LIBRARY; SUBTRACTIVE HYBRIDIZATION; LINEAGE COMMITMENT; PROGENITOR CELLS; SONIC-HEDGEHOG; HUMAN HOMOLOG; G-CSF; EXPRESSION AB Remarkable progress in stem cell biology research over the past few years has provoked a promise for the future of tissue regeneration and gene therapies; so much so, that the use of stem cells in clinical therapy seemed to be just around the corner However we now realize there is still a huge task before us to improve our understanding of the nature of stem cells before utilizing them to benefit human health. Stem cell behavior is determined by specific gene products; thus, unraveling the molecular components and genetic blueprints of stein cells will provide important insight into understanding stem cell properties. Here we summarize the research of various groups using microarray technology and other approaches to determine the gene expression profiles in stem cells, particularly in hematopoietic stein cells (HSCs). These works have, to a certain degree, helped to narrow down the candidate genes predominantly expressed in HSCs, revealed a list of stemness genes, and indirectly demonstrated the wide-open chromatin state of stein cells and, with it, the molecular basis of the multipotentiality of stem cells. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Li, LH (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. NR 68 TC 15 Z9 15 U1 0 U2 1 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2003 VL 35 IS 6 BP 1233 EP 1239 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 753UX UT WOS:000187249900018 PM 14682058 ER PT J AU Lyon, HM Holmes, LB Huang, TS AF Lyon, HM Holmes, LB Huang, TS TI Multiple congenital anomalies associated with in utero exposure of phenytoin: Possible hypoxic ischemic mechanism? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID FETAL-HYDANTOIN SYNDROME; PHALANGEAL HYPOPLASIA; ANTICONVULSANT DRUGS; K+ CHANNELS; GENE; DEFECTS; TERATOGENICITY; MONOTHERAPY; INHIBITION; EPILEPSY AB BACKGROUND: The characteristics of the phenotype of the malformed phenytoin-exposed infant can help to clarify the mechanism of the drug's teratogenesis. One postulated mechanism is vascular disruption. CASE: An infant who was exposed to phenytoin as monotherapy throughout pregnancy was born with the following abnormalities: midface hypoplasia, digit hypoplasia with syndactyly in the hands and feet, meningomyelocele, talipes equinovarus, and a long skin pedicle on the back. The mother was also exposed to cigarette smoking and alcohol during the pregnancy. CONCLUSIONS: The malformations of the hands and feet, and the talipes deformity are potential effects of vascular disruption, a postulated fetal effect of both phenytoin and cigarette smoking. The mechanism of the teratogenicity of phenytoin may have included episodes of bradyarrhythmia in the fetus; however, no such episodes were documented. (C) 2003 Wiley-Liss, Inc. C1 Univ Calif Irvine, Dept Pediat, Div Genet, Irvine, CA 92697 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Pediat,Genet & Teratol Unit, Boston, MA USA. RP Huang, TS (reprint author), Univ Calif Irvine, Dept Pediat, Div Genet, Robert R Sprague Hall,Rm 314, Irvine, CA 92697 USA. NR 32 TC 4 Z9 5 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD DEC PY 2003 VL 67 IS 12 BP 993 EP 996 DI 10.1002/bdra.10100 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 756BF UT WOS:000187445400009 PM 14745921 ER PT J AU Means, RT AF Means, RT TI Ras signaling in erythropoiesis: Going with the flow SO BLOOD LA English DT Editorial Material C1 Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Charleston, SC USA. RP Means, RT (reprint author), Ralph H Johnson VA Med Ctr, Charleston, SC USA. RI Means, Robert/A-4454-2008 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2003 VL 102 IS 12 BP 3858 EP 3859 DI 10.1182/blood-2003-09-3181 PG 2 WC Hematology SC Hematology GA 750JH UT WOS:000186987200006 ER PT J AU Savage, KJ Monti, S Kutok, JL Cattoretti, G Neuberg, D de Leval, L Kurtin, P Dal Cin, P Ladd, C Feuerhake, F Aguiar, RCT Li, SG Salles, G Berger, F Jing, W Pinkus, GS Habermann, T Dalla-Favera, R Harris, NL Aster, JC Golub, TR Shipp, MA AF Savage, KJ Monti, S Kutok, JL Cattoretti, G Neuberg, D de Leval, L Kurtin, P Dal Cin, P Ladd, C Feuerhake, F Aguiar, RCT Li, SG Salles, G Berger, F Jing, W Pinkus, GS Habermann, T Dalla-Favera, R Harris, NL Aster, JC Golub, TR Shipp, MA TI The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma SO BLOOD LA English DT Article ID REED-STERNBERG CELLS; DEFECTIVE IMMUNOGLOBULIN TRANSCRIPTION; NF-KAPPA-B; TNF RECEPTOR; INTERLEUKIN-13 RECEPTOR; T-CELLS; EXPRESSION; TUMOR; GENE; DISEASE AB Mediastinal large B-cell lymphoma (MLBCL) is a recently identified subtype of diffuse large B-cell lymphoma (DLBCL) that characteristically presents as localized tumors in young female patients. Although MLBCL has distinctive pathologic features, it clinically resembles the nodular sclerosis subtype of classical Hodgkin lymphoma (cHL). To elucidate the molecular features of MLBCL, we compared the gene expression profiles of newly diagnosed MLBCL and DLBCL and developed a classifier of these diseases. MLBCLs had low levels of expression of multiple components of the B-cell receptor signaling cascade, a profile resembling that of Reed-Sternberg cells of cHL. Like cHLs, MLBCLs also had high levels of expression of the interleukin-13 (IL-13) receptor and downstream effectors of IL-13 signaling (Janus kinase-2 [JAK2] and signal transducer and activator of transcription-1 [STAT1]), tumor necrosis factor (TNF) family members, and TNF receptor-associated factor-1 (TRAF1). Increased expression of STAT1 and TRAF1 in MLBCL was confirmed by immunohistochemistry. Given the TRAF1 expression and known link to nuclear factor-kappaB (NF-kappaB), MLBCLs were also evaluated for nuclear translocation of c-REL protein. In almost all cases, c-REL was localized to the nucleus, consistent with activation of the NF-kappaB pathway. These studies identify a molecular link between MLBCL and cHL and a shared survival pathway. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Columbia Univ, Inst Canc Genet, New York, NY USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Mayo Clin, Dept Pathol, Rochester, MN USA. Ctr Hosp Lyon Sud, Dept Hematol, Lyon, France. Ctr Hosp Lyon Sud, Dept Pathol, Lyon, France. Mayo Clin, Div Hematol, Rochester, MN USA. Mayo Clin, Dept Med, Rochester, MN USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. OI Cattoretti, Giorgio/0000-0003-3799-3221 NR 77 TC 433 Z9 456 U1 0 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 DEC 1 PY 2003 VL 102 IS 12 BP 3871 EP 3879 DI 10.1182/blood-20036-06-1841 PG 9 WC Hematology SC Hematology GA 750JH UT WOS:000186987200013 PM 12933571 ER PT J AU Tiwari, S Italiano, JE Barral, DC Mules, EH Novak, EK Swank, RT Seabra, MC Shivdasani, RA AF Tiwari, S Italiano, JE Barral, DC Mules, EH Novak, EK Swank, RT Seabra, MC Shivdasani, RA TI A role for Rab27b in NF-E2-dependent pathways of platelet formation SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR NF-E2; LOCUS-CONTROL REGION; BETA-GLOBIN LOCUS; HYPERSENSITIVE SITE 2; HERMANSKY-PUDLAK-SYNDROME; GENE IN-VIVO; MYOSIN-VA; MURINE MEGAKARYOCYTES; THROMBOXANE SYNTHASE; MELANOSOME TRANSPORT AB Megakaryocytes release platelets by reorganizing the cytoplasm into proplatelet extensions. Fundamental to this process is the need to coordinate transport of products and organelles in the appropriate abundance to nascent platelets. The importance of the Rab family of small GTPases (guanosine 5'-triphosphatases) in platelet biogenesis is revealed in gun-metal (gm/gm) mice, which show deficient Rab isoprenylation and macrothrombocytopenia with few granules and abnormal megakaryocyte morphology. Although some Rab, proteins are implicated in vesicle and organelle transport along microtubules or actin, the role of any Flab protein in platelet biogenesis is unknown. The limited number of Rab proteins with defective membrane association in gm/gm megakaryocytes prominently includes Rab27a and Rab27b. Normal expression of Rab27b is especially increased with terminal megakaryocyte differentiation and dependent on nuclear factor-erythroid 2 (NF-E2), a transcription factor required for thrombopoiesis. Chromatin immuno-precipitation demonstrates recruitment of NF-E2 to the putative Rab27B promoter. Inhibition of endogenous Rab27 function in primary megakaryocytes causes severe quantitative and qualitative defects in proplatelet formation that mimic findings in gm/gm cells. Rab27b localizes to alpha and dense granules in megakaryocytes. These results establish a role for Rab27 in platelet synthesis and suggest that Rab27b in particular may coordinate proplatelet formation with granule transport, possibly by recruiting specific effector pathways. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ London Imperial Coll Sci Technol & Med, Fac Med, Div Biomed Sci, London, England. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 1 Jimmy Fund Way, Boston, MA 02115 USA. RI Barral, Duarte/E-7548-2013; Tiwari, Sanjay/Q-1853-2016; OI Barral, Duarte/0000-0001-8867-2407; Tiwari, Sanjay/0000-0002-3804-3300; Seabra, Miguel/0000-0002-6404-4892 FU NCI NIH HHS [CA16056]; NEI NIH HHS [R01EY12104]; NHLBI NIH HHS [R01HL51480, R01HL63143, R01HL68130] NR 66 TC 56 Z9 58 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2003 VL 102 IS 12 BP 3970 EP 3979 DI 10.1182/blood-2003-03-0977 PG 10 WC Hematology SC Hematology GA 750JH UT WOS:000186987200026 PM 12907454 ER PT J AU Wilkinson, K Velloso, ERP Lopes, LF Lee, C Aster, JC Shipp, MA Aguiar, RCT AF Wilkinson, K Velloso, ERP Lopes, LF Lee, C Aster, JC Shipp, MA Aguiar, RCT TI Cloning of the t(l;5)(q23;q33) in a myeloproliferative disorder associated with eosinophilia: involvement of PDGFRB and response to imatinib SO BLOOD LA English DT Article ID FACTOR RECEPTOR-BETA; CHRONIC MYELOMONOCYTIC LEUKEMIA; FUSION; TRANSLOCATION; GENE; DISEASE; BLOOD; 8P11 AB Eosinophilia is common in myeloproliferative disorders (MPDs) with abnormalities of chromosome band 5q31-33, including those that present with t(11; 5)(q23;q33). With the development of rational drug therapy, characterization of the molecular targets for these translocations could guide treatment and affect patient survival. We cloned the t(l; 5)(q23;q33) and showed that it fuses platelet-derived growth factor receptor beta (PDGFRB) to the coiled-coil do-mains of a novel partner protein, myomegalin. Using two-color interphase fluorescence in situ hybridization (FISH), we also demonstrated that the eosinophils are clonal in these disorders. Imatinib mesylate has recently been shown to be efficacious in MPDs with PDGFR activation. Therefore, following our molecular studies, we were able to redirect this patient's treatment. Although she had refractory and progressive disease, once imatinib was started, complete clinical and hematologic remission, as well as major cytogenetic response, was achieved. Given the therapeutic implications, our findings stress the need to aggressively investigate the molecular basis of these diseases, with emphasis on the PDGFR family. (C) 2003 by The American Society of Hematology. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Hosp AC Camargo Fund Antonio Prudente, Sao Paulo, Brazil. Univ Sao Paulo, Hosp Clin, Sao Paulo, Brazil. RP Aguiar, RCT (reprint author), Dana Farber Canc Inst, 44 Binney St,M514, Boston, MA 02115 USA. RI Velloso, Elvira/K-7634-2013; Lopes, Luiz Fernando/L-5513-2016 NR 23 TC 82 Z9 90 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2003 VL 102 IS 12 BP 4187 EP 4190 DI 10.1182/blood-2003-04-1150 PG 4 WC Hematology SC Hematology GA 750JH UT WOS:000186987200054 PM 12907457 ER PT J AU Knutson, MD Vafa, MR Haile, DJ Wessling-Resnick, M AF Knutson, MD Vafa, MR Haile, DJ Wessling-Resnick, M TI Iron loading and erythrophagocytosis increase ferroportin 1 (FPN1) expression in J774 macrophages SO BLOOD LA English DT Article ID AUTOSOMAL-DOMINANT HEMOCHROMATOSIS; NITRIC-OXIDE; HUMAN MONOCYTES; IDIOPATHIC HEMOCHROMATOSIS; DIFFERENTIAL REGULATION; ERYTHROLEUKEMIA-CELLS; REGULATORY PROTEINS; NATURAL-RESISTANCE; MOLECULAR CONTROL; OXIDATIVE STRESS AB The expression of ferroportin1 (FPN1) in reticuloendothelial macrophages supports the hypothesis that this iron-export protein participates in iron recycling from senescent erythrocytes. To gain insight into FPN1's role in macrophage iron metabolism, we examined the effect of iron status and erythrophagocytosis on FPN1 expression in J774 macrophages. Northern analysis indicated that FPN1 mRNA levels decreased with iron depletion and increased on iron loading. The iron-induced induction of FPN1 mRNA was blocked by actinomycin D, suggesting that transcriptional control was responsible for this effect. After erythrophagocytosis, FPN1 mRNA levels were also upregulated, increasing 8-fold after 4 hours and returning to basal levels by 16 hours. Western analysis indicated corresponding increases in FPN1 protein levels, with maximal induction after 10 hours. Iron chelation suppressed FPN1 mRNA and protein induction after erythrophagocytosis, suggesting that FPN1 induction results from erythrocyte-derived iron. Comparative Northern analyses of iron-related genes after erythrophagocytosis revealed a 16-fold increase in FPN1 levels after 3 hours, a 10-fold increase in heme oxygenase-1 (HO-1) after 3 hours, a 2-fold increase in natural resistance macrophage-associated protein 1 (Nramp1) levels after 6 hours, but no change in divalent metal ion transporter 1 (DMT1) levels. The rapid and strong induction of FPN1 expression after erythrophagocytosis suggests that FPN1 plays a role in iron recycling. (C) 2003 by The American Society of Hematology. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Rafsanjan Univ Med Sci, Dept Social Med, Sch Med, Rafsanjan, Iran. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie Murphy Vet Affairs Hosp, S Texas Vet Hlth Syst, San Antonio, TX USA. RP Wessling-Resnick, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, Bldg 2,Rm 205,665 Huntington Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK56160, DK59429, DK09998] NR 54 TC 135 Z9 140 U1 0 U2 7 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 DEC 1 PY 2003 VL 102 IS 12 BP 4191 EP 4197 DI 10.1182/blood-2003-04-1250 PG 7 WC Hematology SC Hematology GA 750JH UT WOS:000186987200055 PM 12907459 ER PT J AU Bergmeier, W Burger, PC Piffath, CL Hoffmeister, KM Hartwig, JH Nieswandt, B Wagner, DD AF Bergmeier, W Burger, PC Piffath, CL Hoffmeister, KM Hartwig, JH Nieswandt, B Wagner, DD TI Metalloproteinase inhibitors improve the recovery and hemostatic function of in vitro-aged or -injured mouse platelets SO BLOOD LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; VON-WILLEBRAND-FACTOR; SURFACE P-SELECTIN; GLYCOPROTEIN-IB; MONOCLONAL-ANTIBODIES; BLOOD COMPONENTS; CELL-DEATH; GPIB-IX; APOPTOSIS; STORAGE AB Platelet transfusions are a crucial component of support for patients with severe thrombocytopenia. Storage of platelet concentrates, however, is associated with a reduction in platelet posttransfusion recovery and hemostatic function. In this study, we established a model of mitochondrial injury that resembles platelet storage lesion. Mitochondrial injury, provoked by incubation of platelets with carbonyl cyanide m-chlorophenylhydrazone (CCCP), led to reduced posttransfusion recovery in mice, an effect that directly correlated with the duration of treatment. Damaged platelets were characterized by shape change, disruption of membrane asymmetry, surface expression of P-selectin, and profound proteolysis of GPlbalpha. Using our model, we identified a key role for endogenous metalloproteinase(s) in platelet clearance, as their inhibition markedly improved posttransfusion recovery of both the mitochondria-injured and in vitro-aged mouse platelets. Metalloproteinase inhibition also prevented proteolysis of GPlbalpha on damaged platelets, thereby improving the hemostatic function of these cells in vivo. We propose that inhibition of metalloproteinase activity during storage could significantly improve the effectiveness of platelet transfusions. Surface expression of GPlbalpha might be a powerful marker to determine the quality of platelet concentrates, because it reflects metalloproteinase activity in vitro. (C) 2003 by The American Society of Hematology. C1 CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. Univ Wurzburg, Rudolf Virchow Ctr Expt Biomed, Wurzburg, Germany. RP Wagner, DD (reprint author), CBR Inst Biomed Res Inc, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [P01 HL056949, P01 HL56949, R37 HL041002] NR 49 TC 90 Z9 92 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2003 VL 102 IS 12 BP 4229 EP 4235 DI 10.1182/blood-2003-04-1305 PG 7 WC Hematology SC Hematology GA 750JH UT WOS:000186987200060 PM 12907434 ER PT J AU Scadden, DT AF Scadden, DT TI Stem cells and immune reconstitution in AIDS SO BLOOD REVIEWS LA English DT Review DE stem cells; hematopoiesis; immune reconstitution; human immunodeficiency virus; acquired immunodeficiency syndrome ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; BONE-MARROW; T-CELLS; LYMPHOID-TISSUES; CD34(+) CELLS; IN-VITRO; CD4(+); GENE AB The hematopoietic system generally has reserve sufficient to tolerate significant insult and regenerative capacity to overcome most damage due to infectious agents. However, HIV infection results in a progressive decline in hematopoietic function and even in the context of potent, anti-retroviral therapy is able to only incompletely reconstitute immune function. The ability of the immune system to respond to HIV itself remains compromised, a defect that leaves infected individuals with a lifelong dependence on medications. The capability of stem cells and the thymus to restore function and their limitations in the context of HIV infection are discussed in this review. (C) 2003 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Room 5212,149 13th St, Boston, MA 02129 USA. NR 35 TC 10 Z9 10 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD DEC PY 2003 VL 17 IS 4 BP 227 EP 231 DI 10.1016/S0268-960X(03)00021-3 PG 5 WC Hematology SC Hematology GA 740QY UT WOS:000186414100005 PM 14556777 ER PT J AU Alyea, E Weller, E Schlossman, R Canning, C Mauch, P Ng, A Fisher, D Gribben, J Freeman, A Parikh, B Richardson, P Soiffer, R Ritz, J Anderson, KC AF Alyea, E Weller, E Schlossman, R Canning, C Mauch, P Ng, A Fisher, D Gribben, J Freeman, A Parikh, B Richardson, P Soiffer, R Ritz, J Anderson, KC TI Outcome after autologous and allogeneic stem cell transplantation for patients with multiple myeloma: impact of graft-versus-myeloma effect SO BONE MARROW TRANSPLANTATION LA English DT Article DE multiple myeloma; stem cell transplantation; graft-versus-myeloma ID BONE-MARROW-TRANSPLANTATION; DONOR LYMPHOCYTE INFUSION; LEUKOCYTE INFUSIONS; THERAPY; BLOOD; RISK; CHEMOTHERAPY; TRIAL AB A total of 228 patients with multiple myeloma (MM), 166 patients receiving autologous transplantation (124 PBSC and 38 BM) and 66 patients receiving T-cell-depleted allogeneic transplantation were analyzed to compare overall survival (OS), progression-free survival (PFS) and risk of relapse. Patients receiving autologous transplantation had a significantly improved OS (P = 0.006) and PFS (P = 0.002) at 2 years with OS and PFS for autologous transplant 74% and 48%, respectively, compared with 51% and 28% for allogeneic transplantation. By 4 years after transplantation, outcome was similar with OS and PFS for autologous transplantation 41% and 23%, respectively, compared with 39% and 18% for allogeneic transplantation. The 4-year cumulative incidence of nonrelapse mortality was significantly higher in patients receiving allogeneic transplantation (24% vs 13%) (P = 0.004). Relapse was the principle cause of treatment failure for both groups; however, there was a significantly reduced risk of relapse associated with allogeneic transplantation at 4 years: 46% for allograft vs 56% for autograft (P = 0.02). Despite a lower risk of relapse after allogeneic transplantation, autologous transplantation is associated with improved OS and PFS compared with allogeneic transplantation in patients with MM. Strategies focused on reducing nonrelapse mortality in allogeneic transplantation may translate into an improved outcome for patients receiving allogeneic transplantation. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. RP Alyea, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02215 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA78378] NR 28 TC 46 Z9 50 U1 0 U2 1 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 DEC PY 2003 VL 32 IS 12 BP 1145 EP 1151 DI 10.1038/sj.bmt.1704289 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 748ZE UT WOS:000186892300005 PM 14647268 ER PT J AU Colleoni, M Zarieh, D Gelber, RD Viale, G Luini, A Veronesi, P Intra, M Galimberti, V Renne, G Goldhirsch, A AF Colleoni, M Zarieh, D Gelber, RD Viale, G Luini, A Veronesi, P Intra, M Galimberti, V Renne, G Goldhirsch, A TI Preoperative systemic treatment: prediction of responsiveness SO BREAST LA English DT Article; Proceedings Paper CT 8th International Conference on Primary Therapy of early Breast Cancer CY MAR 12-15, 2003 CL ST GALLEN, SWITZERLAND DE predictive factors; preoperative therapy; breast cancer ID GENE-EXPRESSION PATTERNS; OPERABLE BREAST-CANCER; PRIMARY TUMOR REMOVAL; NEOADJUVANT CHEMOTHERAPY; RANDOMIZED TRIAL; CARCINOMA; RECEPTORS; THERAPY; GROWTH AB The use of predictive factors allows a more effective use of available therapies by enabling clinicians to distinguish patients likely to obtain substantial benefit from treatment from those for whom the same therapy is less likely to be effective. A most relevant aspect of clinical research is thus to develop alternative therapeutic approaches which are more efficacious for this latter group, particularly important since treatment effects are likely to be small. In the preoperative setting several predictors of response were identified. They include: diameter of the lesion (larger lesions respond less than smaller lesions), MIB-1 increased expression associated with increased response to chemotherapy, and estrogen receptor (ER) and progesterone receptor (PgR) expression in the tumor typically associated with increased response to endocrine therapies. Other factors include HER-2/neu overexpression, which is a target for treatment with the humanized monoclonal antibody against its extracellular domain, is hypothesized to increase response to anthracycline combination chemotherapy and to lead to an improved response to some endocrine agents (e.g. letrozole) rather than to others. Although primary endocrine therapy demonstrated activity and low profile of side effects in selected populations of older patients, it is infrequently used. On the other hand, chemotherapy remains the mainstay of treatment being considered to be a more active and better documented option. Experience at the European Institute of Oncology on 399 patients with large or locally advanced breast cancer (cT2-T4, N0-2, M0) treated with primary chemotherapy, indicated that a proper selection of primary treatment should be based on tumor characteristics such as ER and PgR status. In particular, patients with tumors with no ER and PgR expression (endocrine-unresponsive disease) at the baseline core-biopsy had a significantly higher response rate to chemotherapy if compared with tumors with some ER/PgR expression. In fact, the absence of ER and PgR expression was the strongest predictors of pCR at the multivariate analysis (P<0.0001). Information on endocrine responsiveness before primary systemic therapy will lead to better tailoring of treatment modalities, thus avoiding chemotherapy in selected populations where other approaches (e.g. endocrine primary therapy) might be more useful. (C) 2003 Elsevier Ltd. All rights reserved. C1 European Inst Oncol, Dept Med, Div Med Oncol, I-20141 Milan, Italy. Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. European Inst Oncol, Div Senol, Milan, Italy. European Inst Oncol, Div Pathol, Milan, Italy. RP Colleoni, M (reprint author), European Inst Oncol, Dept Med, Div Med Oncol, Via Ripamonti 435, I-20141 Milan, Italy. NR 21 TC 20 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2003 VL 12 IS 6 BP 538 EP 542 DI 10.1016/S0960-9776(03)00163-2 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 756BR UT WOS:000187446400030 PM 14659132 ER PT J AU Gelber, RD Bonetti, M Castiglione-Gertsch, M Coates, AS Goldhirsch, A AF Gelber, RD Bonetti, M Castiglione-Gertsch, M Coates, AS Goldhirsch, A CA Int Breast Canc Study Grp TI Tailoring adjuvant treatments for the individual breast cancer patient SO BREAST LA English DT Article; Proceedings Paper CT 8th International Conference on Primary Therapy of early Breast Cancer CY MAR 12-15, 2003 CL ST GALLEN, SWITZERLAND DE breast cancer; adjuvant therapy; predictive factors; chemotherapy; tamoxifen; estrogen receptor; progesterone receptor; STEPP ID RANDOMIZED TRIALS; CHEMOTHERAPY; ENDOCRINE; SUBSETS; POLYCHEMOTHERAPY; RESPONSIVENESS; TAMOXIFEN; THERAPY; TUMORS AB Background: Chemotherapy, tamoxifen and ovarian function suppression have all demonstrated their effectiveness for treating women with early breast cancer. Treatment selection for individual patients, however, requires estimates on the magnitude of treatment effects to be achieved from the application of each modality. Unfortunately, information currently available is insufficient to properly tailor adjuvant treatments. Methods: We consider predictive factors to improve our understanding about selection of adjuvant therapies, reassessment of data from previous clinical trials and design of future studies. Results: Estrogen receptor (ER) and progesterone receptor (PgR) are the primary measures available today to tailor adjuvant therapies. Patient age/menopausal status (ability to obtain treatment effects via ovarian function suppression), measures of the metastatic potential of the tumor (such as number of positive axillary lymph nodes), and concurrent use of chemotherapy and tamoxifen are other factors that modify the magnitude of relative effect associated with chemotherapy and endocrine therapies. The Subpopulation Treatment Effect Pattern Plots (STEPP) method displays the patterns of treatment effects within randomized clinical trials or datasets from meta-analyses to identify features that predict responsiveness to the treatments under study without relying on retrospective subset analysis. Confirmation of hypotheses using independent clinical trial databases is recommended. Discussion: All findings from clinical trials and meta-analyses should be presented primarily according to steroid hormone receptor status and patient age. Future studies should be designed as tailored treatment investigations, with endocrine therapies evaluated within populations of patients with endocrine responsive tumors, and chemotherapy questions focused within populations of patients with endocrine nonresponsive disease. (C) 2003 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat Sci, Boston, MA 02115 USA. IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. Univ Sydney, IBCSG Sci Committee, Sydney, NSW 2001, Australia. Canc Council Australia, Sydney, NSW 2001, Australia. Osped Civile, IBCSG Sci Committee, CH-6903 Lugano, Switzerland. European Inst Oncol, I-20141 Milan, Italy. RP Gelber, RD (reprint author), Dana Farber Canc Inst, IBCSG Stat Ctr, Dept Biostat Sci, 44 Binney Str, Boston, MA 02115 USA. OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA-06516, CA-75362] NR 24 TC 14 Z9 15 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2003 VL 12 IS 6 BP 558 EP 568 DI 10.1016/S0960-9776(03)00166-8 PG 11 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 756BR UT WOS:000187446400033 PM 14659135 ER PT J AU Senn, HJ Thurlimann, B Goldhirsch, A Wood, WC Gelber, RD Coates, AS AF Senn, HJ Thurlimann, B Goldhirsch, A Wood, WC Gelber, RD Coates, AS TI Comments on the St. Gallen consensus 2003 on the primary therapy of early breast cancer SO BREAST LA English DT Article; Proceedings Paper CT 8th International Conference on Primary Therapy of early Breast Cancer CY MAR 12-15, 2003 CL ST GALLEN, SWITZERLAND DE breast cancer; adjuvant therapy; primary treatment of breast cancer; Consensus conference ID SURGICAL-ADJUVANT-BREAST; RANDOMIZED CLINICAL-TRIALS; QUALITY-OF-LIFE; FOLLOW-UP; PREMENOPAUSAL PATIENTS; EXPRESSING ESTROGEN; RADICAL-MASTECTOMY; ENDOCRINE THERAPY; YOUNG-WOMEN; CYCLIN-E AB This final paper of the proceedings of the recent Eighth St. Gallen Conference 2003 on the Primary Therapy of Early Breast Cancer comments on the Consensus Paper put forth by the international expert panel and emphasizes new information, that has emerged during the 2 years since the seventh such meeting in 2001. More than 3200 breast cancer specialists from various medical fields-coming from 75 countries and all six continents-have attended the meeting and the process of scientific consensus development. Recommendations for patient care are so critically dependent on assessment of endocrine responsiveness that the importance of high-quality steroid hormone receptor determination and standardized quantitative reporting cannot be overemphasized. The Panel modified and simplified the risk categories so that only endocrine receptor-absent status was sufficient to reclassify an otherwise low-risk, node-negative disease into the category of average risk. Absence of steroid hormone receptors was also recognized as indicating endocrine non-responsiveness. Some important areas highlighted especially in the 2003 consensus include: recognition of the separate nature of endocrine non-responsive breast cancer, both invasive cancers and ductal carcinoma in situ (DCIS); improved understanding of the mechanisms of acquired endocrine resistance, offering exciting prospects for extending the impact of successful sequential endocrine therapies; presentation of high-quality evidence indicating that chemotherapy and tamoxifen should be used sequentially rather than concurrently; availability of a potential alternative to tamoxifen for treatment of postmenopausal women with endocrine responsive disease; promise of newly defined prognostic and predictive markers. (C) 2003 Elsevier Ltd. All rights reserved. C1 Ctr Tumordetect & Prevent ZeTuP, CH-9006 St Gallen, Switzerland. Kantonsspital, Senol Ctr Eastern Switzerland, CH-9007 St Gallen, Switzerland. Oncol Inst So Switzerland, Int Breast Canc Study Grp, CH-6903 Lugano, Switzerland. European Inst Oncol, I-20141 Milan, Italy. Emory Univ, Dept Surg, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Canc Council Australia, Sydney, NSW 2001, Australia. Univ Sydney, Sydney, NSW 2001, Australia. RP Senn, HJ (reprint author), Ctr Tumordetect & Prevent ZeTuP, Rorschacherstr 150, CH-9006 St Gallen, Switzerland. NR 109 TC 28 Z9 28 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD DEC PY 2003 VL 12 IS 6 BP 569 EP 582 DI 10.1016/j.breast.2003.09.007 PG 14 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 756BR UT WOS:000187446400034 PM 14659136 ER PT J AU Burger, R Bakker, F Guenther, A Baum, W Schmidt-Arras, D Hideshima, T Tai, YT Shringarpure, R Catley, L Senaldi, G Gramatzki, M Anderson, KC AF Burger, R Bakker, F Guenther, A Baum, W Schmidt-Arras, D Hideshima, T Tai, YT Shringarpure, R Catley, L Senaldi, G Gramatzki, M Anderson, KC TI Functional significance of novel neurotrophin-1/B cell-stimulating factor-3 (cardiotrophin-like cytokine) for human myeloma cell growth and survival SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE novel neurotrophin-1/B cell-stimulating factor-3; cardiotrophin-like cytokine; multiple myeloma; gp130; signal transducer and activator of transcription 3 ID INTERLEUKIN-6 TRANSGENIC MICE; LEUKEMIA INHIBITORY FACTOR; RECEPTOR-ALPHA-COMPONENT; SIGNAL TRANSDUCER GP130; MULTIPLE-MYELOMA; ONCOSTATIN-M; APOPTOSIS; FAMILY; STAT3; DEXAMETHASONE AB Cytokines of the gp130 family, particularly interleukin 6 (IL-6), play a central role in the growth and survival of malignant plasma cells. Recently, novel neurotrophin-1 (NNT-1)/B cell-stimulating factor-3 (BSF-3), also reported as cardiotrophin-like cytokine (CLC), was identified as a cytokine belonging to the gp130 family. BSF-3, similar to IL-6, exerts regulatory effects on normal B cell functions, but its functional significance in haematological malignancies has not been defined. The purpose of this study was to evaluate the biological effects and signalling pathways that are induced by BSF-3 in malignant plasma cells. Recombinant human BSF-3 was found to have growth stimulatory activity on plasmacytoma cell lines and primary tumour cells. In addition, BSF-3 was able to protect from Dexamethasone (Dex)-induced apoptosis. BSF-3 stimulated cell growth could not be inhibited by neutralizing anti-IL-6 or anti-IL-6 receptor antibodies, but was abrogated by anti-gp130 antibodies. In INA-6.Tu11 cells, a subline of the IL-6-dependent human plasma cell line INA-6 expressing gp130 and the receptor for leukaemia inhibitory factor (LIF), stimulation with BSF-3 induced tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). AG490, an inhibitor of Janus kinases, decreased BSF-3 induced cell growth in a dose-dependent manner. This correlated with a reduction of STAT3 phosphorylation levels, while p44/42 mitogen-activated protein kinase (MAPK) phosphorylation was not affected. In conclusion, BSF-3 is a novel myeloma growth and survival factor with a potential role in the pathophysiology of the disease. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Med 3, Div Hematol Oncol, Erlangen, Germany. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. RI Gramatzki, Martin/A-9533-2010; Catley, Laurence/E-5313-2013 NR 35 TC 22 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2003 VL 123 IS 5 BP 869 EP 878 DI 10.1046/j.1365-2141.2003.04686.x PG 10 WC Hematology SC Hematology GA 745NX UT WOS:000186695700012 PM 14632778 ER PT J AU Marvizon, JCG Wang, XR Lao, LJ Song, BB AF Marvizon, JCG Wang, XR Lao, LJ Song, BB TI Effect of peptidases on the ability of exogenous and endogenous neurokinins to produce neurokinin 1 receptor internalization in the rat spinal cord SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE Aminopeptidase; C-fiber; dorsal horn; dipeptidyl carboxypeptidase; EC 3.4.15.1; EC 3.4.24.11; neutral endopeptidase; neurokinin 1 receptor; neurokinin; primary afferent; substance P; tachykinin ID DORSAL-HORN NEURONS; SUBSTANCE-P RELEASE; TACHYKININ NK1 RECEPTOR; ANGIOTENSIN-CONVERTING ENZYME; ENKEPHALIN-DEGRADING ENZYMES; PRIMARY AFFERENT SYNAPSES; CAPSAICIN-EVOKED RELEASE; MIXED INHIBITOR PRODRUG; LONG-TERM DEPRESSION; MU-OPIOID RECEPTOR AB 1 The ability of peptidases to restrict neurokinin I receptor (NK1R) activation by exogenously applied or endogenously released neurokinins was investigated by measuring NK1R internalization in rat spinal cord slices. 2 Concentration-response curves for substance P and neurokinin A were obtained in the presence and absence of 10 muM thiorphan, an inhibitor of neutral endopeptidase (EC 3.4.24.11), plus 10 muM captopril, an inhibitor of dipeptidyl carboxypeptidase (EC 3.4.15.1). These inhibitors significantly decreased the EC50 of substance P to produce NK1R internalization from 32 to 9 rim, and the EC50 Of neurokinin A from 170 to 60 rim. 3 Substance P was significantly more potent than neurokinin A, both with and without these peptidase inhibitors. 4 In the presence of peptidase inhibitors, neurokinin B was 10 times less potent than neurokinin A and 64 times less potent than substance P (EC50 = 573 nM). 5 Several aminopeptidase inhibitors (actinonin, amastatin, bacitracin, bestatin and puromycin) failed to further increase the effect of thiorphan plus captopril on the NK1R internalization produced by 10 nM substance P. 6 Electrical stimulation of the dorsal root produced NK1R internalization by releasing endogenous neurokinins. Thiorphan plus captopril increased NK1R internalization produced by 1 Hz stimulation, but not by 30 Hz stimulation. 7 Therefore, NEN and DCP restrict NK1R activation by endogenous neurokinins when they are gradually released by low-frequency firing of primary afferents, but become saturated or inhibited when primary afferents fire at a high frequency. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med,Div Digest Dis,CURE Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90095 USA. RP Marvizon, JCG (reprint author), Vet Adm Greater Los Angeles Hlth Ctr, Bldg 115,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDA NIH HHS [R01-DA12609, R01 DA012609] NR 62 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD DEC PY 2003 VL 140 IS 8 BP 1389 EP 1398 DI 10.1038/sj.bjp.0705578 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 755PZ UT WOS:000187419400006 PM 14623771 ER PT J AU Kalra, MK Maher, MM Mueller, PR Saini, S AF Kalra, MK Maher, MM Mueller, PR Saini, S TI State-of-the-art imaging of pancreatic neoplasms SO BRITISH JOURNAL OF RADIOLOGY LA English DT Review ID ISLET-CELL TUMORS; MULTIDETECTOR CT ANGIOGRAPHY; PAPILLARY MUCINOUS TUMOR; HELICAL CT; MR CHOLANGIOPANCREATOGRAPHY; INTRAOPERATIVE ULTRASOUND; PATHOLOGICAL CORRELATION; MANGAFODIPIR TRISODIUM; NEUROENDOCRINE TUMORS; ENDOSCOPIC ULTRASOUND AB Pancreatic imaging with multidetector CT allows multiphase acquisition of thin slices in a single breath-hold and is especially valuable in obtaining isotropic three-dimensional reformations that improves our ability to provide accurate pre-operative vascular mapping. Advanced MR technology allows faster imaging of pancreas, thus facilitating MR cholangiopancreatography. Use of tissue-specific MR contrast agents, endoscopic ultrasound and PET in pancreatic imaging has evolved considerably. This review article discusses the role of CT, MR, endoscopic ultrasound and PET imaging in pancreas. C1 Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Abdominal Imaging & Intervent, 55 Fruit St, Boston, MA 02114 USA. NR 59 TC 67 Z9 73 U1 1 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD DEC PY 2003 VL 76 IS 912 BP 857 EP 865 DI 10.1259/bjr/16642775 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 768TD UT WOS:000188590400003 PM 14711772 ER PT J AU Podolsky, SH AF Podolsky, SH TI Heredity and infection: The history of disease transmission. SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Podolsky, SH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD WIN PY 2003 VL 77 IS 4 BP 970 EP 971 DI 10.1353/bhm.2003.0187 PG 2 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 750VV UT WOS:000187019900030 ER PT J AU Tingart, MJ Bouxsein, ML Zurakowski, D Warner, JP Apreleva, M AF Tingart, MJ Bouxsein, ML Zurakowski, D Warner, JP Apreleva, M TI Three-dimensional distribution of bone density in the proximal humerus SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE proximal humerus; bone mineral density; dual-energy X-ray absorptiometry; peripheral quantitative computed tomography humeral fracture; rotator cuff tear ID SURGICAL NECK FRACTURES; ROTATOR CUFF REPAIRS; SUTURE ANCHORS; MECHANICAL-PROPERTIES; TRABECULAR BONE; FIXATION; PREVALENCE; STRENGTH AB Bone quality of the proximal humerus is important for the surgical treatment of proximal humeral fractures and rotator cuff tears. However, very few studies have evaluated the a real bone mineral density (BMD) of the proximal humerus. The aim of this study was to analyze the volumetric BMD (vBMD) using peripheral-quantitative-computed-tomography. Total, trabecular and cortical vBMD were determined separately for the proximal and distal half of the humeral head, the surgical neck and seven specific regions of interest. The greater tuberosity (GT) was divided into three regions, and the lesser tuberosity (LT) and articular surface (AS) were each divided into two regions. The proximal head showed a significantly higher trabecular (+46%) and cortical vBMD (+15%) than the distal one. The mean trabecular vBMD of AS was significantly higher (+80%), and the cortical vBMD was significantly lower (-11%) than that of the tuberosities. In the proximal half of GT, trabecular vBMD was higher in the posterior than in the middle and anterior regions. Cortical vBMD was higher in middle region than in the anterior and posterior ones. In the distal half of GT, trabecular vBMD was significantly higher in the posterior than in the middle region, and cortical vBMD was significantly higher in the anterior than in the middle region. In the proximal half of AS, trabecular vBMD was significantly higher in the posterior region than in the anterior one. These results point to bone sites that may provide stronger fixation for implants, reduce the risk of implant loosening, and therefore improve patient outcome. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Apreleva, M (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Orthopaed Biomech Lab, Boston, MA 02115 USA. NR 27 TC 33 Z9 34 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD DEC PY 2003 VL 73 IS 6 BP 531 EP 536 DI 10.1007/s00223-003-0013-9 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752NH UT WOS:000187173700003 PM 14740644 ER PT J AU Freedland, SJ Aronson, WJ Terris, MK Kane, CJ Amling, CL Dorey, F Presti, JC AF Freedland, SJ Aronson, WJ Terris, MK Kane, CJ Amling, CL Dorey, F Presti, JC TI The percentage of prostate needle biopsy cores with carcinoma from the more involved side of the biopsy as a predictor of prostate specific antigen recurrence after radical prostatectomy - Results from the shared equal access regional cancer hospital (SEARCH) database SO CANCER LA English DT Article DE prostate carcinoma; radical prostatectomy; prostate needle biopsy; cores; prostate specific antigen recurrence ID SEXTANT BIOPSIES; EXTRACAPSULAR EXTENSION; BIOCHEMICAL RECURRENCE; INDEPENDENT PREDICTOR; SYSTEMATIC SEXTANT; POSITIVE BIOPSIES; GLEASON SCORE; STAGE; RISK; MEN AB BACKGROUND. The authors previously found that, although the total percentage of prostate needle biopsy cores with carcinoma was a significant predictor of prostate specific antigen (PSA) failure among men undergoing radical prostatectomy (RP), there was a trend toward a lower risk of recurrence in patients with positive bilateral biopsies, suggesting that high-volume, unilateral disease was a worse predictor of outcome than an equivalent number of positive cores distributed over two lobes. In the current study, the authors sought to compare the total percentage of cores with carcinoma directly with the percentage of cores from the more involved or dominant side of the prostate with carcinoma for their ability to predict outcome among men who underwent RP. METHODS. A retrospective survey of 535 patients from the Shared Equal Access Regional Cancer Hospital database who underwent RP at 4 different equal-access medical centers between 1988 and 2002 was undertaken. The total percentage of cores positive was compared with the percentage of cores positive from the dominant and nondominant sides for their ability to predict biochemical recurrence after RP. The best predictor then was compared with the standard clinical variables PSA, biopsy Gleason score, and clinical stage in terms of ability to predict time to PSA recurrence after RIP using multivariate analysis. RESULTS. The adverse pathologic features of positive surgical margins and extracapsular extension were significantly more likely to be ipsilateral to the dominant side on the prostate biopsy. The percentage of cores positive from the dominant side provided slightly better prediction (concordance index [C] = 0.636) for PSA failure than the total percentage of cores positive (C = 0.596) and markedly better than the percentage of cores from the nondominant side (C = 0.509). Cutoff points for percentage of cores positive from the dominant side were identified (< 34%, 34-67%, and > 67%) that provided significant risk stratification for PSA failure (P < 0.001). On multivariate analysis, the percentage of cores positive from the dominant side was the strongest independent predictor of PSA recurrence (P < 0.001). Biopsy Gleason score (P = 0.017) also was a significant, independent predictor of recurrence. There was a trend, which did not reach statistical significance, toward an association between greater PSA values and biochemical failure (P = 0.052). Combining the PSA level, biopsy Gleason score, and percentage of cores positive from the dominant side of the prostate resulted in a model that provided a high degree of prediction for PSA failure (C = 0.671). CONCLUSIONS. The percentage of cores positive from the dominant side of the prostate was a slightly better predictor of PSA recurrence than was the total percentage of cores positive. Using the percentage of cores from the dominant side along with the PSA level and the biopsy Gleason score provided significant risk stratification for PSA failure. Published 2003 by the American Cancer Society. C1 Univ Calif Los Angeles, Dept Urol, Los Angeles, CA USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Vet Affairs Palo Alto Hlth Care Syst, Urol Sect, Palo Alto, CA USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. USN, Ctr Med, Dept Urol, San Diego, CA 92152 USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA USA. Stanford Univ, Sch Med, Dept Urol, Palo Alto, CA 94304 USA. RP Freedland, SJ (reprint author), Johns Hopkins Sch Med, Brady Urol Inst, Dept Urol, Marburg 130,600 N Wolfe St, Baltimore, MD 21287 USA. NR 24 TC 29 Z9 33 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 DEC 1 PY 2003 VL 98 IS 11 BP 2344 EP 2350 DI 10.1002/cncr.11809 PG 7 WC Oncology SC Oncology GA 745EU UT WOS:000186677000006 PM 14635068 ER PT J AU Ma, PC Maulik, G Christensen, J Salgia, R AF Ma, PC Maulik, G Christensen, J Salgia, R TI c-Met: Structure, functions and potential for therapeutic inhibition SO CANCER AND METASTASIS REVIEWS LA English DT Review DE c-Met; hepatocyte growth factor; signal transduction; motility; metastasis; inhibitors ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; RECEPTOR TYROSINE KINASE; INTERNAL TANDEM DUPLICATION; PAPILLARY RENAL CARCINOMAS; ACUTE MYELOID-LEUKEMIA; MARROW STROMAL CELLS; NF-KAPPA-B; INVASIVE GROWTH; HGF RECEPTOR AB Studies on signal transduction pathways have generated various promising molecular targets for therapeutic inhibition in cancer therapy. Receptor tyrosine kinases represent an important class of such therapeutic targets. c-Met is a receptor tyrosine kinase that has been shown to be overexpressed and/or mutated in a variety of malignancies. A number of c-Met activating mutations, many of which are located in the tyrosine kinase domain, have been detected in various solid tumors and have been implicated in invasion and metastasis of tumor cells. It is known that stimulation of c-Met via its natural ligand, hepatocyte growth factor (also known as scatter factor, HGF/SF) results in a plethora of biological and biochemical effects in the cell. Activation of c-Met signaling can lead to scattering, angiogenesis, proliferation, enhanced cell motility, invasion, and eventual metastasis. In this review, the role of c-Met dysregulation in tumor progression and metastasis is discussed in detail with particular emphasis on c-Met mutations. Moreover, we summarize current knowledge on various pathways of c-Met signal transduction, highlighting the central role in the cytoskeletal functions. In this summary is included recent data in our laboratory indicating that phosphorylation of focal adhesion proteins, such as paxillin, p125FAK, and PYK2, occurs in response to c-Met stimulation in lungcancer cells. Most importantly, current data on c-Met suggest that when mutated or overexpressed in malignant cells, c-Met would serve as an important therapeutic target. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Dept Hematol Oncol, Boston, MA 02111 USA. Sugen Inc, San Francisco, CA 94080 USA. RP Salgia, R (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 126 TC 307 Z9 328 U1 4 U2 28 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2003 VL 22 IS 4 BP 309 EP 325 DI 10.1023/A:1023768811842 PG 17 WC Oncology SC Oncology GA 678FL UT WOS:000182854500002 PM 12884908 ER PT J AU Sicinska, E Aifantis, L Le Cam, L Swat, W Borowski, C Yu, QY Ferrando, AA Levin, SD Geng, Y von Boehmer, H Sicinski, P AF Sicinska, E Aifantis, L Le Cam, L Swat, W Borowski, C Yu, QY Ferrando, AA Levin, SD Geng, Y von Boehmer, H Sicinski, P TI Requirement for cyclin D3 in lymphocyte development and T cell leukemias SO CANCER CELL LA English DT Article ID THYMOCYTE DEVELOPMENT; V(D)J RECOMBINATION; DEPENDENT KINASES; SQUAMOUS-CELL; ACTIVATED LCK; MUTANT MICE; D1 PROTEIN; ALPHA-BETA; PT-ALPHA; EXPRESSION AB The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3(-/-) animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. Univ Washington, Dept Immunol, Seattle, WA 98195 USA. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RI Le Cam, Laurent/O-1408-2016 FU NCI NIH HHS [R01 CA85296] NR 62 TC 213 Z9 216 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2003 VL 4 IS 6 BP 451 EP 461 DI 10.1016/S1535-6108(03)00301-5 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 757VY UT WOS:000187583200008 PM 14706337 ER PT J AU Kau, TR Schroeder, F Ramaswamy, S Wojciechowski, CL Zhao, JJ Roberts, TM Clardy, J Sellers, WR Silver, PA AF Kau, TR Schroeder, F Ramaswamy, S Wojciechowski, CL Zhao, JJ Roberts, TM Clardy, J Sellers, WR Silver, PA TI A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells SO CANCER CELL LA English DT Article ID PROTEIN-KINASE-B; HAMSTER OVARY CELLS; FACTOR FKHR; FACTOR AFX; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; PHOSPHORYLATION SITES; SUPPRESSOR PROTEIN; AKT; ACTIVATION; SURVIVAL AB The PI3K/PTEN/Akt signal transduction pathway plays a key role in many tumors. Downstream targets of this pathway include the Forkhead family of transcription factors (FOXO1a, FOXO3a, FOXO4). In PTEN null cells, FOXO1a is inactivated by PI3K-dependent phosphorylation and mislocalization to the cytoplasm, yet still undergoes nucleocytoplasmic shuttling. Since forcible localization of FOXO1a to the nucleus can reverse tumorigenicity of PTEN null cells, a high-content, chemical genetic screen for inhibitors of FOXO1a nuclear export was performed. The compounds detected in the primary screen were retested in secondary assays, and structure-function relationships were identified. Novel general export inhibitors were found that react with CRM1 as well as a number of compounds that inhibit PI3K/Akt signaling, among which are included multiple antagonists of calmodulin signaling. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM william_sellers@dfci.harvard.edu; pamela_silver@dfci.harvard.edu FU NCI NIH HHS [5T32CA09361-22, 2T32 CA09361-21A1, CA30002, CA67786, CA85912, CA89021]; NIAID NIH HHS [AI07386-11]; NIGMS NIH HHS [GM36373] NR 58 TC 246 Z9 252 U1 3 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD DEC PY 2003 VL 4 IS 6 BP 463 EP 476 DI 10.1016/S1535-6108(03)00303-9 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 757VY UT WOS:000187583200009 PM 14706338 ER PT J AU Kircher, MF Mahmood, U King, RS Weissleder, R Josephson, L AF Kircher, MF Mahmood, U King, RS Weissleder, R Josephson, L TI A multimodal nanoparticle for preoperative magnetic resonance imaging and intraoperative optical brain tumor delineation SO CANCER RESEARCH LA English DT Article ID INTRACRANIAL CONTRAST ENHANCEMENT; SUPERPARAMAGNETIC IRON-OXIDE; PHARMACOKINETICS; GLIOMAS; AGENT; MRI AB The determination of brain tumor margins both during the presurgical planning phase and during surgical resection has long been a challenging task in the therapy of brain tumor patients. Using a model of gliosarcoma, with stably green fluorescence protein-expressing 9L glioma cells, we explored a multimodal (near-infrared fluorescent and magnetic) nanoparticle as a preoperative magnetic resonance imaging contrast agent and intraoperative optical probe. Key features of nanoparticle metabolism, namely intracellular sequestration by microglia and the combined optical and magnetic properties of the probe, allowed delineation of brain tumors both by preoperative magnetic resonance imaging and by intraoperative optical imaging. This prototypical multimodal nanoparticle has unique properties that may allow radiologists and neurosurgeons to see the same probe in the same cells and may offer a new approach for obtaining tumor margins. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 13th St,Bldg 149,room 5406, Charlestown, MA 02129 USA. FU NCI NIH HHS [P50 CA86355] NR 21 TC 384 Z9 398 U1 8 U2 90 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 DEC 1 PY 2003 VL 63 IS 23 BP 8122 EP 8125 PG 4 WC Oncology SC Oncology GA 756DQ UT WOS:000187450900010 PM 14678964 ER PT J AU Schuch, G Heymach, JV Nomi, M Machluf, M Force, J Atala, A Eder, JP Folkman, J Soker, S AF Schuch, G Heymach, JV Nomi, M Machluf, M Force, J Atala, A Eder, JP Folkman, J Soker, S TI Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells SO CANCER RESEARCH LA English DT Article ID I CLINICAL-TRIAL; BONE-MARROW; PRECURSOR CELLS; ANGIOGENESIS; APOPTOSIS; THERAPY; NEOVASCULARIZATION; EXPRESSION; VIABILITY; INFUSION AB Circulating endothelial cells (CECs) are present in peripheral blood and have been shown to contribute to normal and pathological neovascularization. Antiangiogenic molecules can inhibit neovascularization in tumors and other sites, but their effect on CECs has not yet been determined. We hypothesize that angiogenic factors will increase the number of CECs, and conversely, antiangiogenic treatment will reduce these numbers. Mice treated with high levels of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1-positive cells in peripheral blood and endothelial cell colonies compared with vehicle-treated controls. These changes were accompanied by increased bone marrow neovascularization. In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and reduced bone marrow vascularization. Endostatin-induced apoptosis was probably responsible for the decreased number of CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the VEGF-induced increase in CECs. These results were further confirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of beta-galactosidase-expressing peripheral blood mononuclear cells. We propose that endothelial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs can serve as a surrogate marker for the biological activity of antiangiogenic treatment. C1 Childrens Hosp, Dept Urol, Boston, MA 02115 USA. Childrens Hosp, Div Surg Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Thorac Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. RP Soker, S (reprint author), Childrens Hosp, Dept Urol, 300 Longwood Ave, Boston, MA 02115 USA. OI Atala, Anthony/0000-0001-8186-2160 FU NCI NIH HHS [CA45548] NR 33 TC 90 Z9 94 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2003 VL 63 IS 23 BP 8345 EP 8350 PG 6 WC Oncology SC Oncology GA 756DQ UT WOS:000187450900041 PM 14678995 ER PT J AU Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Mitsiades, C MItsiades, N Gong, BQ Bonham, L de Vries, P Munshi, N Richardson, PG Singer, JW Anderson, KC AF Hideshima, T Chauhan, D Hayashi, T Podar, K Akiyama, M Mitsiades, C MItsiades, N Gong, BQ Bonham, L de Vries, P Munshi, N Richardson, PG Singer, JW Anderson, KC TI Antitumor activity of lysophosphatidic acid acyltransferase-beta inhibitors, a novel class of agents, in multiple myeloma SO CANCER RESEARCH LA English DT Article ID OVERCOMES DRUG-RESISTANCE; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; DEXAMETHASONE-INDUCED APOPTOSIS; ENDOTHELIAL GROWTH-FACTOR; HIGH-DOSE THERAPY; PROTEASOME INHIBITOR; PHOSPHATIDYLINOSITOL 3-KINASE AB In this study, we examined the effects of isoform-specific functional inhibitors of lysophosphatidic acid acyltransferase (LPAAT), which converts lysophosphatidic acid to phosphatidic acid, on multiple myeloma (MM) cell growth and survival. The LPAAT-beta inhibitors CT-32176, CT-32458, and CT-32615 induced >95% growth inhibition (P < 0.01) in MMAS, U266, and RPMI8226 MM cell lines, as well as MM cells from patients (IC50, 50-200 nM). We further characterized this LPAAT-beta inhibitory effect using CT-32615, the most potent inhibitor of MM cell growth. CT-32615 triggered apoptosis in MM cells vi caspase-8, caspase-3, caspase-7, and poly (ADP-ribose) polymerase cleavage. Neither interleukin 6 nor insulin-like growth factor I inhibited CT-32615-induced apoptosis. Dexamethasone and immunomodulatory derivatives of thalidomide (IMiDs), but not proteasome inhibitor PS-341, augmented MM cell apoptosis triggered by LPAAT-beta inhibitors. CT-32615-induced apoptosis was associated with phosphorylation of p53 and c-Jun NH2-terminal kinase (JNK); conversely, JNK inhibitor SP600125 and dominant-negative JNK inhibited CT-32615-induced apoptosis. Importantly, CT-32615 inhibited tumor necrosis factor-alpha-triggered nuclear factor-kappaB activation but did not affect either tumor necrosis factor-alpha-induced p38 mitogen-activated protein kinase phosphorylation or interleukin 6-triggered signal transducers and activators of transcription 3 phosphorylation. Finally, although binding of MM cells to bone marrow stromal cells augments MM cell growth and protects against dexamethasone-induced apoptosis, CT-32615 induced apoptosis even of adherent MM cells. Our data therefore demonstrate for the first time that inhibiting LPAAT-beta induces cytotoxicity in MM cells in the bone marrow milieu, providing the framework for clinical trials of these novel agents in MM. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cell Therapeut Inc, Seattle, WA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Mayer 557,44 Binney St, Boston, MA 02115 USA. OI Singer, Jack/0000-0003-4001-4549 FU NCI NIH HHS [R0-1 CA 50947, IP50 CA10070-01]; PHS HHS [P01- 78378] NR 70 TC 51 Z9 52 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2003 VL 63 IS 23 BP 8428 EP 8436 PG 9 WC Oncology SC Oncology GA 756DQ UT WOS:000187450900052 PM 14679006 ER PT J AU Dieter, RS Patel, AK Yandow, D Pacanowski, JP Bhattacharya, A Gimelli, G Kosolcharoen, P Russell, D AF Dieter, RS Patel, AK Yandow, D Pacanowski, JP Bhattacharya, A Gimelli, G Kosolcharoen, P Russell, D TI Conservative vs. invasive treatment of aortocoronary saphenous vein graft aneurysms: treatment algorithm based upon a large series SO CARDIOVASCULAR SURGERY LA English DT Article DE coronary artery bypass graft; saphenous vein graft; aneurysm; treatment; complication ID VENOUS BYPASS GRAFT; CORONARY-ARTERY; COMPUTED-TOMOGRAPHY; FALSE ANEURYSM; RIGHT ATRIUM; DIAGNOSIS; SURGERY; EMBOLIZATION; FISTULA AB Background. The development of a saphenous vein graft aneurysm (SVGA) after coronary artery bypass graft surgery is a rare occurrence. There are approximately 60 cases reported in the literature, the majority being single case reports. There is no consensus on the treatment of SVGA. Methods: Retrospective analysis of the patients treated with SVGA was performed at our institution. Demographic and co-morbidity data were acquired on the patients. Patients who underwent surgical treatment were compared to those treated conservatively with the primary outcome being survival time from diagnosis of the SVGA. Results: Thirteen patients with 15 SVGA were identified. The average age at the time of the most recent coronary artery bypass grafting (CABG) was similar in the conservative and the surgically treated groups (55 vs. 56.5 years, respectively). The average number of grafts per patient at the most recent CABG was similar (3.83 vs. 4.0, respectively). The average time from CABG to diagnosis was similar in both the groups (12.6 vs. IS years, respectively). The average survival from diagnosis was similar in both the groups (2.3 vs. 1.5 years, respectively, p > 0.05). Conclusions: Early surgical treatment of SVGA does not provide longer short-term survival compared with conservative management. A treatment algorithm for SVGA based upon patient co-morbidities and aneurysm characteristics is proposed. (C) 2003 The International Society for Cardiovascular Surgery. Published by Elsevier Ltd. All rights reserved. C1 Univ Wisconsin, Sect Cardiovasc Med, Dept Med, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Cardiol Sect, Madison, WI USA. Univ Wisconsin, Dept Radiol, Madison, WI 53792 USA. Univ Tennessee, Vasc Surg Sect, Knoxville, TN 37996 USA. Univ Wisconsin, Gen Clin Res Ctr, Madison, WI 53792 USA. RP Dieter, RS (reprint author), Univ Wisconsin, Sect Cardiovasc Med, Dept Med, 600 Highland Ave, Madison, WI 53792 USA. FU NHLBI NIH HHS [T32 HL07936] NR 31 TC 31 Z9 31 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0967-2109 J9 CARDIOVASC SURG JI Cardiovasc. Surg. PD DEC PY 2003 VL 11 IS 6 BP 507 EP 513 DI 10.1016/S0967-2109(03)00108-X PG 7 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 752RL UT WOS:000187180900013 PM 14627974 ER PT J AU MacNeill, BD Harding, SA Bazari, H Patton, KK Colon-Hernadez, P deJoseph, D Jang, IK AF MacNeill, BD Harding, SA Bazari, H Patton, KK Colon-Hernadez, P deJoseph, D Jang, IK TI Prophylaxis of contrast-induced nephropathy in patients undergoing coronary angiography SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE acetylcysteine; contrast nephropathy; cardiac catheterization; nephropathy ID ACUTE-RENAL-FAILURE; RADIOGRAPHIC-CONTRAST; ACETYLCYSTEINE; PREVENTION; AGENT; TRIAL; NEPHROTOXICITY; INTERVENTION; SALINE; MEDIA AB Contrast-induced nephropathy (CIN) is a common complication of cardiac catheterization, reported to result in a 15% incidence of acute renal failure. Convincing evidence supports the prophylactic use of prehydration and low volumes of contrast medium. Recently, the antioxidant acetylcysteine has been shown to have a potential preventive role. The aim of this study was to examine the hypothesis that acetylcysteine prevents CIN. Patients undergoing cardiac catheterization with a serum creatinine greater than or equal to 1.5 mg/dl were prospectively randomized to receive acetylcysteine or placebo. A total of five doses of acetylcysteine 600 mg b.i.d. or placebo was administered, commencing on the day of the procedure. All patients were prehydrated with 0.45% saline and during the catheterization a nonionic low-osmolality contrast medium was used. Serum creatinine and urea were measured at 24, 48, and 72 hr postprocedure. A total of 43 patients were studied. There was no significant difference between the groups in terms of baseline characteristics, including baseline renal function. No adverse events were experienced with acetylcysteine treatment. Serum creatinine levels at 48 and 72 hr remained largely unchanged in the acetylcysteine group but continued to rise at 48 and 72 hr in the placebo group. By 72 hr, the incidence of CIN, defined as a 25% increase in baseline creatinine, was significantly lower in the acetylcysteine arm compared to placebo (5% for acetylcysteine vs. 32% for placebo; P = 0.046). In patients with mild to moderate renal impairment undergoing cardiac catheterization, prophylactic treatment with oral acetylcysteine reduces the incidence of contrast-induced nephropathy. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jang, IK (reprint author), Massachusetts Gen Hosp, Div Cardiol, 55 Fruit St,Gray Bigelow 800, Boston, MA 02114 USA. RI Patton, Kristen/A-5626-2008; OI Patton, Kristen K./0000-0002-9034-6966 NR 16 TC 56 Z9 60 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2003 VL 60 IS 4 BP 458 EP 461 DI 10.1002/ccd.10684 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 752AQ UT WOS:000187124200003 PM 14624421 ER PT J AU Lowe, HC Schwartz, RS Mac Neill, BD Jang, LK Hayase, M Rogers, C Oesterle, SN AF Lowe, HC Schwartz, RS Mac Neill, BD Jang, LK Hayase, M Rogers, C Oesterle, SN TI The porcine coronary model of in-stent restenosis: Current status in the era of drug-eluting stents SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Review DE stent; restenosis; animal model ID ANIMAL-MODELS; NEOINTIMAL HYPERPLASIA; ARTERIAL INJURY; BALLOON ANGIOPLASTY; GENE DELIVERY; PACLITAXEL; ATHEROSCLEROSIS; PROLIFERATION; MECHANISMS; CARDIOLOGY AB Drug-eluting stents are revolutionizing interventional cardiology. Sirolimus-eluting stents are in widespread clinical use, associated with well-documented remarkably low restenosis rates, and a number of other agents appear promising in clinical trials. These human studies have been preceded by numerous animal studies, foremost among them the pig coronary model of in-stent restenosis (ISR). The histologic response to porcine coronary stenting was described over a decade ago. Porcine stenting studies now provide examinations not only of histology, but also mechanisms of action, toxicity, and biocompatibility. This review therefore examines the current status of this porcine coronary model of ISR. Contemporary methods of pig coronary stenting are discussed. The morphometric, cellular, and molecular analyses of the responses to stent injury are then described. Finally, recent pig coronary drug-eluting stent studies are examined, with a discussion of their advantages, limitations, and possible future modifications. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Minnesota Cardiovasc Res Inst, Minneapolis Heart Inst Fdn, Minneapolis, MN USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Lowe, HC (reprint author), Concord Hosp, Dept Cardiol, Hosp Rd, Sydney, NSW 2139, Australia. NR 51 TC 45 Z9 48 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2003 VL 60 IS 4 BP 515 EP 523 DI 10.1002/ccd.10705 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 752AQ UT WOS:000187124200015 PM 14624433 ER PT J AU Sader, MA De Moor, M Pomerantsev, E Palacios, IF AF Sader, MA De Moor, M Pomerantsev, E Palacios, IF TI Percutaneous transcatheter patent Foramen ovale closure using the right internal jugular venous approach SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE cardiology; catheterization; heart septal defects ID CARDIAC-CATHETERIZATION; DECOMPRESSION-SICKNESS; STROKE PATIENTS; EMBOLISM; CHILDREN; DIVERS AB Percutaneous transcatheter closure of a patent foramen ovale (PFO) is a therapeutic option in patients with paradoxical embolism. For patients in whom PFO closure is indicated when a femoral venous approach is not possible, we describe the successful closure of two PFOs using the right internal jugular venous approach. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Massachusetts Gen Hosp,Sch Med, Cardiac Unit, Cardiac Catheterizat Lab & Intervant Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Pediat Cardiol, Boston, MA 02115 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp,Sch Med, Cardiac Unit, Cardiac Catheterizat Lab & Intervant Cardiol, Bulfinch 105,Fruit St, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD DEC PY 2003 VL 60 IS 4 BP 536 EP 539 DI 10.1002/ccd.10702 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 752AQ UT WOS:000187124200019 PM 14624437 ER PT J AU Takahashi, T Kinsman, S Makris, N Grant, E Haselgrove, C McInerney, S Kennedy, DN Takahashi, T Fredrickson, K Mori, S Caviness, VS AF Takahashi, T Kinsman, S Makris, N Grant, E Haselgrove, C McInerney, S Kennedy, DN Takahashi, T Fredrickson, K Mori, S Caviness, VS TI Semilobar holoprosencephaly with midline 'seam': A topologic and morphogenetic model based upon MRI analysis SO CEREBRAL CORTEX LA English DT Article ID SONIC-HEDGEHOG GENE; HUMAN-BRAIN; NEURAL-TUBE; HUMAN-EMBRYO; NERVOUS-SYSTEM; 1ST APPEARANCE; DORSAL CYST; MALFORMATIONS; PERSPECTIVES; SPECIFICATION AB We present an MRI-based anatomic analysis of a series of seven human brains with the semilobar form of holoprosencephaly. The analysis defines a set of common descriptors for a pattern of topological anomaly which is uniform for the set of seven brains. The core of the anomaly is a rostro-caudally aligned midline gray matter 'seam' that extends from the telencephalic-suprachiasmatic junctional region to abut the posterior aspect of the callosal commissure. The seam forms the ventricular roof throughout its extent. Rostrally it is formed by the conjoined heads of caudate/accumbens nuclei. It continues caudally as a gray matter bridge in the fundus of the interhemispheric fissure, where it bridges right and left neocortex. Fornix, septal nuclei and septal limb of the choroid plexus are absent, and the telencephalic ventricles communicate with the diencephalic via open septal limbs of the choroid fissures. By contrast, the temporal limb of hippocampal formation and the choroid plexus are normal and the temporal limb of the choroid fissure is closed. This topological anomaly of conjoined left and right cortical and nuclear gray matter into a midline seam and absent septal structures is thus confined to the region of the midline telencephalic hemisphere evagination. Total telencephalic growth is strongly correlated with the length of this topologically abnormal midline telencephalic segment. The set of findings is consistent with graded failure of induction of rostral to caudal specification in the midline rostral telencephalic zone. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Keio Univ, Sch Med, Tokyo, Japan. Kennedy Krieger Inst, Baltimore, MD USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Caviness, VS (reprint author), Massachusetts Gen Hosp, CMA, 149 13th St, Charlestown, MA 02129 USA. RI Kennedy, David/H-3627-2012 FU NIDA NIH HHS [DA 09467]; NINDS NIH HHS [NS12005, NS34189] NR 64 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD DEC PY 2003 VL 13 IS 12 BP 1299 EP 1312 DI 10.1093/cercour/bhg077 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 745QJ UT WOS:000186699300004 PM 14615296 ER PT J AU Haggarty, SJ Koeller, KM Kau, TR Silver, PA Roberge, M Schreiber, SL AF Haggarty, SJ Koeller, KM Kau, TR Silver, PA Roberge, M Schreiber, SL TI Small molecule modulation of the human chromatid decatenation checkpoint SO CHEMISTRY & BIOLOGY LA English DT Article ID DNA TOPOISOMERASE-II; HISTONE DEACETYLASE INHIBITORS; G(2) CHECKPOINT; G2 CHECKPOINT; CELL-CYCLE; DAMAGE CHECKPOINT; NUCLEAR EXPORT; TUMOR-CELLS; CHROMOSOME; ATR AB After chromosome replication, the intertwined sister chromatids are disentangled by topoisomerases. The integrity of this process is monitored by the chromatid decatenation checkpoint. Here, we describe small molecule modulators of the human chromatid decatenation checkpoint identified using a cell-based , chemical genetic modifier screen. Similar to 1,2,7-tri-methylyxanthine (caffeine), these small molecules suppress the G(2)-phase arrest caused by ICRF-193, a small molecule inhibitor of the enzymatic activity of topoisomerase II. Analysis of specific suppressors, here named suptopins for suppressor of Topoisomerase II inhibition, revealed distinct effects on cell cycle progression, microtubule stability, nucleocytoplasmic transport of cyclin B1, and no effect on the chromatin deacetylation checkpoint induced by trichostatin A. The suptopins provide new molecular tools for dissecting the role of topoisomerases in maintaining genomic stability and determining whether inhibiting the chromatid decatenation checkpoint sensitizes tumor cells to chemotherapeutics. C1 Harvard Univ, Dept Mol & Cell Biol, Cambridge, MA 02138 USA. Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. Harvard Univ, ICB Initiat Chem Genet, Cambridge, MA 02138 USA. Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada. RP Schreiber, SL (reprint author), Harvard Univ, Dept Mol & Cell Biol, 12 Oxford St, Cambridge, MA 02138 USA. OI Haggarty, Stephen J./0000-0002-7872-168X FU NIGMS NIH HHS [GM38627] NR 53 TC 19 Z9 20 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD DEC PY 2003 VL 10 IS 12 BP 1267 EP 1279 DI 10.1016/j.chembiol.2003.11.014 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 758KP UT WOS:000187633800017 PM 14700634 ER PT J AU Bauer, KA AF Bauer, KA TI New pentasaccharides for prophylaxis of deep vein thrombosis - Pharmacology SO CHEST LA English DT Article DE fondaparinux; idraparinux; low-molecular-weight heparin; pentasaccharide; pharmacokinetics; thrombopropylaxis; venous thromboembolism ID SYNTHETIC HEPARIN MIMETICS; MOLECULAR-WEIGHT HEPARIN; HIP-REPLACEMENT SURGERY; FACTOR-XA INHIBITOR; FONDAPARINUX SODIUM; VENOUS THROMBOEMBOLISM; ANTITHROMBIN-III; IN-VITRO; POSTOPERATIVE FONDAPARINUX; BINDING PENTASACCHARIDE AB Fondaparinux is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. By binding rapidly and strongly to antithrombin, its sole physiologic target in plasma, fondaparinux catalyzes specifically the inhibition of factor Xa, which results in effective and linear dose-dependent inhibition of thrombin generation. Fondaparinux does not bind to platelets. Its antithrombotic effect has been demonstrated in several animal models of arterial and venous thrombosis. At equivalent antithrombotic concentrations, fondaparinux induced less bleeding than unfractionated heparin in experimental bleeding models. Furthermore, it did not cross-react with sera from patients with heparin-induced thrombocytopenia. Administered subcutaneously, the absorption of fondaparinux is complete, rapid, and independent of dose. it has a linear pharmacokinetic profile, and its half-life of approximately 17 h allows for once-daily dosing. Fondaparinux is almost completely excreted by the kidneys. Owing to the limited intrasubject and intersubject variability, routine monitoring and dose adjustments should not be required for most patients. Fondaparinux has been approved for use in thromboprophylaxis after major orthopedic surgery, where it has demonstrated its efficacy compared to a low-molecular-weight heparin. Its clinical development in other indications is ongoing. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Hematol Sect,VA Boston Healthcare Syst, Boston, MA 02115 USA. RP Bauer, KA (reprint author), Beth Israel Deaconess Med Ctr, 330 Brookline Ave, Boston, MA 02215 USA. NR 49 TC 17 Z9 17 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD DEC PY 2003 VL 124 IS 6 SU S BP 364S EP 370S DI 10.1378/chest.124.6_suppl.364S PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756ZC UT WOS:000187514800004 PM 14668419 ER PT J AU Turpie, AGG Eriksson, BI Bauer, KA Lassen, MR AF Turpie, AGG Eriksson, BI Bauer, KA Lassen, MR TI New pentasaccharides for the prophylaxis of venous thromboembolism - Clinical studies SO CHEST LA English DT Article DE deep-vein thrombosis; enoxaparin; fondaparinux; low-molecular-weight heparin; orthopedic surgery; pentasaccharide; thromboprophylaxis; venous thromboembolism ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; ELECTIVE HIP-REPLACEMENT; RANDOMIZED DOUBLE-BLIND; MAJOR ORTHOPEDIC-SURGERY; FACTOR-XA INHIBITOR; PULMONARY-EMBOLISM; SYNTHETIC PENTASACCHARIDE; POSTOPERATIVE FONDAPARINUX; SYSTEMATIC REVIEW/ AB Fondaparinux, a selective inhibitor of factor Xa, is the first of a new class of antithrombotic compounds, the synthetic pentasaccharides. Its benefit-to-risk ratio in preventing venous thromboembolism after major orthopedic surgery was investigated in four randomized, double-blind international phase III trials in patients undergoing surgery for hip fracture, elective hip replacement, and major knee surgery. Compared to enoxaparin, fondaparinux administered at a subcutaneous dose of 2.5 mg qd, starting postoperatively, reduced the overall incidence of venous thromboembolism up to day 11 by 55.2% (p < 0.001). The incidence of clinically. relevant bleeding was low and did not differ between the two groups. Overall, fondaparinux achieved optimal-efficacy and safety when treatment was initiated : 6 h after the surgical procedure. In a further randomized double-blind trial, 4 weeks of prophylaxis with fondaparinux after hip fracture surgery reduced the risk of venous thromboembolism by 96% as compared to I week of prophylaxis, and was well tolerated. Fondaparinux has been recently approved for use in thromboprophylaxis. after major orthopedic surgery. The clinical development of fondaparinux in other thromboprophylactic indications is ongoing. C1 Hamilton Gen Hosp, Hamilton Hlth Sci, Dept Med, Hamilton, ON L8L 2X2, Canada. Sahlgrens Univ Hosp, OSTRA, S-41345 Gothenburg, Sweden. VA Boston Healthcare Syst, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Copenhagen, DK-3400 Hillerod, Denmark. RP Turpie, AGG (reprint author), Hamilton Gen Hosp, Hamilton Hlth Sci, Dept Med, 237 Barton St E, Hamilton, ON L8L 2X2, Canada. NR 42 TC 27 Z9 27 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 DEC PY 2003 VL 124 IS 6 SU S BP 371S EP 378S DI 10.1378/chest.124.6_suppl.371S PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 756ZC UT WOS:000187514800005 PM 14668420 ER PT J AU Yeo, KTJ Wu, AHB Apple, FS Kroll, MH Christenson, RH Lewandrowski, KB Sedor, FA Butch, AW AF Yeo, KTJ Wu, AHB Apple, FS Kroll, MH Christenson, RH Lewandrowski, KB Sedor, FA Butch, AW TI Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay SO CLINICA CHIMICA ACTA LA English DT Article DE brain natriuretic peptides; NT-proBNP; BNP; cardiac markers; congestive heart failure ID BRAIN NATRIURETIC PEPTIDE; CONGESTIVE-HEART-FAILURE; VENTRICULAR SYSTOLIC DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; EMERGENCY DIAGNOSIS; IMPAIRMENT; PROGNOSIS; SECRETION; ELEVATION; SURVIVAL AB Background: Brain natriuretic peptides (BNPs) are useful in the assessment of heart failure, left ventricular dysfunction, and acute coronary syndromes. Methods: We performed a multicenter evaluation of the automated Roche NT-proBNP assay and compared its performance to the Biosite Triage BNP assay. Results: The N-terminal (1 -76) pro brain natriuretic peptide (NT-proBNP) method is precise (CV less than or equal to 6.1%), has a wide dynamic measuring range (30-35,000 ng/l), is free from common interferences, and does not cross-react with BNP. EDTA or heparinized plasma samples collected in glass or plastic tubes can be used, and samples are stable at room temperature or 4 degreesC for up to 3 days. In contrast, the Biosite BNP assay has >2-fold higher CV, and plasma samples are more labile when stored at room temperature and 4 degreesC. Comparison studies showed a reasonable correlation between NT-proBNP and BNP assays, with a substantially higher slope bias of 6-20 for the NT-proBNP assay. Conclusions: The automated Roche NT-proBNP assay has good analytical performance and better precision than the Biosite BNP assay. Unlike BNP, NT-proBNP is stable in EDTA plasma for 3 days at room temperature or longer at 4 degreesC. The Roche NT-proBNP is fully automated and will accommodate the testing of large numbers of clinical samples for assessing cardiac dysfunction. (C) 2003 Elsevier B.V. All rights reserved. C1 Dartmouth Coll Sch Med, Dept Pathol, Lebanon, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03756 USA. Hartford Hosp, Hartford, CT 06102 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Univ Texas, SW Med Sch, Dallas, TX 75216 USA. Vet Affairs Med Ctr, Dallas, TX 75216 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90095 USA. RP Yeo, KTJ (reprint author), Dartmouth Coll Sch Med, Dept Pathol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. NR 28 TC 192 Z9 216 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD DEC PY 2003 VL 338 IS 1-2 BP 107 EP 115 DI 10.1016/j.cccn.2003.08.016 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 750YJ UT WOS:000187025800016 PM 14637274 ER PT J AU Heinrich, MC AF Heinrich, MC TI Is KIT an important therapeutic target in small cell lung cancer? Commentary re: B. E. Johnson et al., phase II study of imatinib in patients with small cell lung cancer. Clin. Cancer Res., 9 : 5880-5887, 2003. SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS; C-KIT; KINASE INHIBITORS; GROWTH; EXPRESSION; MUTATIONS; STI571; ACTIVATION; CARCINOMA; EFFICACY C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP Heinrich, MC (reprint author), R&D 19 3710 SW,US Vet Hosp Rd, Portland, OR 97201 USA. NR 26 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 BP 5825 EP 5828 PN 1 PG 4 WC Oncology SC Oncology GA 756FC UT WOS:000187454300004 PM 14676102 ER PT J AU Mace, JR Keohan, ML Bernardy, H Junge, K Niebch, G Romeis, P Thoma, A Wagner, T Mueller, U Demetri, G Baker, LH AF Mace, JR Keohan, ML Bernardy, H Junge, K Niebch, G Romeis, P Thoma, A Wagner, T Mueller, U Demetri, G Baker, LH TI Crossover randomized comparison of intravenous versus intravenous/oral mesna in soft tissue sarcoma treated with high-dose ifosfamide SO CLINICAL CANCER RESEARCH LA English DT Article ID 2-MERCAPTOETHANE SULFONATE MESNA; PHASE-1 CLINICAL-TRIAL; ISOPHOSPHAMIDE NSC-109724; LUNG-CANCER; ORAL MESNA; PHARMACOKINETICS; CYCLOPHOSPHAMIDE; BIOAVAILABILITY; UROTOXICITY; ACTIVATION AB Purpose: We conducted our study to determine the pharmacokinetics (PK) and clinical efficacy of oral mesna in patients receiving ifosfamide for soft tissue sarcoma. Experimental Design: Seventeen patients were enrolled in a randomized prospective Phase I/II study. Seventeen patients were exposed to study medication. Ifosfamide was given at a dose of 2 g/m(2)/day for 5 days on a 21-day cycle. Before the first cycle, all patients were randomized onto a crossover design and received either the approved i.v. or i.v./oral mesna regimen, with crossover for the second cycle of chemotherapy. The i.v. mesna regimen consisted of dosings (20% ifosfamide dose) at 0, 4, and 8 h. The i.v./oral arm consisted of an i.v. mesna dosing (20% ifosfamide dose) at 0 h, followed by oral tablet dosing (40% ifosfamide dose) at 2 and 6 h. In-patient clinical monitoring and phlebotomy and urine sampling for mesna, dimesna, and ifosfamide PK were performed on all chemotherapy days. Results: Thirteen patients were evaluable for PK and 17 for efficacy and toxicity. No significant differences were detected in the plasma PK of the concomitantly infused ifosfamide. Rates of hemorrhagic cystitis were similar across mesna schedules. C1 Univ Michigan, Ctr Comprehens Canc, Div Hematol Oncol, Ann Arbor, MI 48109 USA. Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. ASTA Med AG, Biometr Dept, Frankfurt, Germany. Univ Hosp Luebeck, Lubeck, Germany. Harvard Univ, Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. RP Baker, LH (reprint author), Div Hematol Med Oncol, 1500 E Med Ctr Dr,7216 CCGC, Ann Arbor, MI 48109 USA. NR 29 TC 10 Z9 10 U1 1 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 DEC 1 PY 2003 VL 9 IS 16 BP 5829 EP 5834 PN 1 PG 6 WC Oncology SC Oncology GA 756FC UT WOS:000187454300005 PM 14676103 ER PT J AU Johnson, BE Fischer, T Fischer, B Dunlop, D Rischin, D Silberman, S Kowalski, MO Sayles, D Dimitrijevic, S Fletcher, C Hornick, J Salgia, R Le Chevalier, T AF Johnson, BE Fischer, T Fischer, B Dunlop, D Rischin, D Silberman, S Kowalski, MO Sayles, D Dimitrijevic, S Fletcher, C Hornick, J Salgia, R Le Chevalier, T TI Phase II study of imatinib in patients with small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; GASTRIN-RELEASING-PEPTIDE; C-KIT PROTOONCOGENE; GASTROINTESTINAL STROMAL TUMORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; UNTREATED PATIENTS; GROWTH-INHIBITION; CARCINOMA CELLS; NEUROMEDIN-B AB Purpose: The purpose of our study was to assess the objective response to imatinib administered to patients with small cell lung cancer (SCLC). Experimental Design: Eligible patients were those with SCLC who either had chemotherapy-naive extensive-stage or had SCLC in a sensitive relapse. Patients enrolled on the trial were treated with 600 mg of imatinib daily. The response was assessed using Southwest Oncology Group (SWOG) criteria after 3 and 6 weeks. Tumor specimens were examined by immunohistochemistry for the KIT receptor. Results: Nineteen patients with SCLC entered on the study, including 16 men and 3 women. Nine patients had previously untreated extensive-stage disease and 10 patients had sensitive relapse. A central pathology review confirmed SCLC in only 14 of the 19 patients. There were no objective responses; however, one patient with sensitive-relapse disease had prolonged stabilization of disease (>3 months) while on imatinib therapy. The median time to progression was 0.8 months (range, 0.6-1.3 months) and 1.2 months (range, 0.2-4.1 months) in the previously untreated and sensitive-relapse groups, respectively. Tumor tissue samples from 4 (21 %) of the 19 patients had the KIT receptor (CD117). Conclusions: There was no observed antitumor activity in this limited Phase II trial of patients with SCLC, of which only a few tumors showed expression of the imatinib target. The results of this trial are, thus, inconclusive about the antitumor activity of imatinib against SCLC with the targeted KIT receptor (CD117). Further testing of imatinib in patients with SCLC will focus on demonstration of KIT expression in the setting of confirmed SCLC histology. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Mainz Klinikum, Mainz, Germany. Glasgow Royal Infirm, Glasgow G4 0SF, Lanark, Scotland. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. Novartis Oncol, E Hanover, NJ USA. Novartis Oncol, Basel, Switzerland. Inst Gustave Roussy, Villejuif, France. RP Johnson, BE (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Room D1234,44 Binney St, Boston, MA 02115 USA. NR 47 TC 132 Z9 138 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 DEC 1 PY 2003 VL 9 IS 16 BP 5880 EP 5887 PN 1 PG 8 WC Oncology SC Oncology GA 756FC UT WOS:000187454300012 PM 14676110 ER PT J AU Means-Markwell, M Linnoila, RI Williams, J Janne, PA Kaye, F O'Neil, K Johnson, BE AF Means-Markwell, M Linnoila, RI Williams, J Janne, PA Kaye, F O'Neil, K Johnson, BE TI Prospective study of the airways and pulmonary parenchyma of patients at risk for a second lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID SPIRAL COMPUTED-TOMOGRAPHY; FLUORESCENCE BRONCHOSCOPIC SURVEILLANCE; PLACEBO-CONTROLLED TRIAL; CARCINOMA IN-SITU; BRONCHIAL EPITHELIUM; FORMER SMOKERS; FOLLOW-UP; SQUAMOUS METAPLASIA; ACTION PROJECT; PRIMARY TUMORS AB surgical resection alone, but additional patients will need to be studied. Purpose: We conducted our study to compare the number of preneoplastic lesions in the airways and nodules in the pulmonary parenchyma of patients with resected non-small cell lung cancer with the patients whose treatment included chest radiotherapy. Experimental Design: Patients were eligible if they had successfully resected stage I and II non-small cell lung cancer or advanced stage non-small cell or small cell lung cancer treated with chest radiotherapy with or without chemotherapy and were free of cancer for >2 years. Patients underwent a history and physical examination, white light and fluorescence bronchoscopy, and computerized tomography of the chest. The airway epithelium was examined for preneoplastic histological changes, and the pulmonary parenchyma was examined for the presence of nodules. Results: Twenty-nine patients at risk for lung cancer were studied between 1997 and 1999. Two patients treated with chest radiotherapy had an area of moderate dysplasia (n = 1) and carcinoma in situ (n = 1), whereas one patient treated with surgical resection alone had an area of mild dysplasia. Six other patients had metaplasia detected in their airway epithelium. Ten of the 13 patients treated with chest radiotherapy had pulmonary nodules compared with 5 of the 13 patients treated with surgical resection alone. Conclusions: Mild dysplasia, moderate dysplasia, severe dysplasia, and carcinoma in situ are unusual in patients with resected lung cancer who have stopped smoking for an extended period of time. Patients with lung cancer treated with chest irradiation may be at higher risk for preneoplastic lesions and pulmonary nodules than patients treated with surgical resection alone, but additional patients will need to be studied. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Boston, MA 02445 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Natl Canc Inst, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD USA. Natl Naval Med Res Inst, Dept Med, Bethesda, MD USA. Natl Naval Med Res Inst, Dept Pathol, Bethesda, MD USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Dept Adult Oncol, Room D1234,44 Binney St, Boston, MA 02445 USA. EM BEJOHNSON@PARTNERS.ORG RI kaye, frederic/E-2437-2011 NR 37 TC 2 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 BP 5915 EP 5921 PN 1 PG 7 WC Oncology SC Oncology GA 756FC UT WOS:000187454300017 PM 14676115 ER PT J AU Mayer, B Parra, A Funke, I Klement, G Kerbel, RS Jauch, KW AF Mayer, B Parra, A Funke, I Klement, G Kerbel, RS Jauch, KW TI Validation of predinical test systems used in drug screening. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. Dana Faber Inst, Boston, MA USA. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6069S EP 6070S PN 2 PG 2 WC Oncology SC Oncology GA 756LU UT WOS:000187467300006 ER PT J AU Dalgarno, DC Bohacek, R Stehle, T Narula, S Metcalf, C Wang, Y Shakespeare, W Sundaramoorthi, R Ram, M Keats, J Adams, S Van Schravendijk, MR Weigele, M Sawyer, T AF Dalgarno, DC Bohacek, R Stehle, T Narula, S Metcalf, C Wang, Y Shakespeare, W Sundaramoorthi, R Ram, M Keats, J Adams, S Van Schravendijk, MR Weigele, M Sawyer, T TI Structure-based design and X-ray crystallographic analysis of a potent and selective site tyrosine kinase inhibitor for the treatment of cancer SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 ARIAD Pharmaceut Inc, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6070S EP 6070S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300007 ER PT J AU Lecesne, A Demetri, G Misset, JL Blay, J Judson, I Yovine, A Van Oosterom, A Radford, J Verweij, J Maki, R Brain, E Herait, P Izquierdo, MA Gomez, J Nieto, A Saro, J Jimeno, J AF Lecesne, A Demetri, G Misset, JL Blay, J Judson, I Yovine, A Van Oosterom, A Radford, J Verweij, J Maki, R Brain, E Herait, P Izquierdo, MA Gomez, J Nieto, A Saro, J Jimeno, J TI Impact of Yondeli (TM) (trabectedin, ET-743) in the natural history of patients (pts) with pretreated advanced soft tissue sarcomas (PASTS): Long term follow-up results. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 IGR, Villejuif, France. Dana Farber Canc Inst, Boston, MA 02115 USA. Hop St Louis, Paris, France. Ctr Leon Berard, F-69373 Lyon, France. Royal Marsden Hosp, London SW3 6JJ, England. Hop Paul Brousse, Villejuif, France. Dienst Gezwelziekten, Louvain, Belgium. Christie Hosp, Manchester, Lancs, England. Erasmus Med Ctr, Rotterdam, Netherlands. MSKCC, New York, NY USA. Canc Ctr Rene Huguenin, St Cloud, France. CAC, Paris, France. Pharma Mar, Madrid, Spain. RI Radford, John/N-1331-2015; Blay, Jean-Yves/N-3966-2016 OI Radford, John/0000-0001-7898-2786; Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6076S EP 6076S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300032 ER PT J AU Lynch, T Ranson, M Herbst, R Fukuoka, M AF Lynch, T Ranson, M Herbst, R Fukuoka, M TI Skin toxicity is not a clinically meaningful prognostic marker for tumor response to gefitinib ('Iressa', ZD 1839) in pretreated patients with advanced non-small-cell lung cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Christie Hosp, Manchester, Lancs, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Kinki Univ, Sch Med, Osaka 589, Japan. NR 0 TC 4 Z9 4 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 DEC 1 PY 2003 VL 9 IS 16 SU S BP 6086S EP 6086S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300071 ER PT J AU Monks, NR Pardee, AB Baile, SR Biswas, DK AF Monks, NR Pardee, AB Baile, SR Biswas, DK TI Specific inhibition of NF-kB activation by dominant negative IKK-beta and siRNA in ER-negative human breast cancer cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Monks, Noel/B-5886-2013 OI Monks, Noel/0000-0001-6587-9827 NR 0 TC 0 Z9 0 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 DEC 1 PY 2003 VL 9 IS 16 SU S BP 6102S EP 6103S PN 2 PG 2 WC Oncology SC Oncology GA 756LU UT WOS:000187467300137 ER PT J AU Bendell, JC Eder, JP Clark, JW Fidias, P Lynch, TJ Seiden, MV Ryan, DP AF Bendell, JC Eder, JP Clark, JW Fidias, P Lynch, TJ Seiden, MV Ryan, DP TI Phase I dose escalation study of(E)-2'-deoxy-2'-(fluoromethylene) cytidine (tezacitabine) in combination with fluorouracil (5-FU) in patients with advanced solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6116S EP 6116S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300189 ER PT J AU Rubin, JB Kung, AL Klein, RS Chan, J Warrington, N Sun, Y Schmidt, K Kieran, M Segal, RA AF Rubin, JB Kung, AL Klein, RS Chan, J Warrington, N Sun, Y Schmidt, K Kieran, M Segal, RA TI Systemic delivery of a small molecule inhibitor of CXCR4 blocks the growth of intracranial xenografts of glioblastoma multiforme and medulloblastoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Washington Univ, Sch Med, St Louis, MO USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6126S EP 6127S PN 2 PG 2 WC Oncology SC Oncology GA 756LU UT WOS:000187467300235 ER PT J AU Berkenblit, A Supko, JG Eder, JP Proper, J Royer, ES Dahl, TA Dezube, BJ AF Berkenblit, A Supko, JG Eder, JP Proper, J Royer, ES Dahl, TA Dezube, BJ TI A phase I study of STA-4783, an inducer of heat shock protein 70, combined with paclitaxel in patients with advanced solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Synta Pharmaceut Corp, Lexington, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6131S EP 6131S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300253 ER PT J AU Mitsiades, CS Kung, AL Mitsiades, N Anderson, K Holmann, F Garcia-Echeverria, C AF Mitsiades, CS Kung, AL Mitsiades, N Anderson, K Holmann, F Garcia-Echeverria, C TI Characterization of selective small molecule kinase inhibitors of IGF-IR and their in vitro and in vivo activity against multiple myeloma, other hematologic malignancies and solid tumors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharma AG, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6138S EP 6138S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300279 ER PT J AU De Bazelaire, C Alsop, D Rofsky, N Wang, Y Mietlowski, W Reitsma, D Laurent, D Michaelson, D Kantoff, P George, D AF De Bazelaire, C Alsop, D Rofsky, N Wang, Y Mietlowski, W Reitsma, D Laurent, D Michaelson, D Kantoff, P George, D TI MRI-assessed changes in tumor blood flow following treatment with PTK/ZK correlate with subsequent tumor shrinkage or growth in patients with metastatic renal cell carcinoma. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Novartis Pharmaceut, E Hanover, NJ USA. Schering AG, D-1000 Berlin, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Clin Res Inst, Durham, NC USA. RI Alsop, David/J-5764-2013 OI Alsop, David/0000-0002-8206-1995 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6139S EP 6140S PN 2 PG 2 WC Oncology SC Oncology GA 756LU UT WOS:000187467300284 ER PT J AU Heymach, MJ Force, JM Beaudry, P Wang, AC Baker, C Ryan, A Folkman, J Soker, S AF Heymach, MJ Force, JM Beaudry, P Wang, AC Baker, C Ryan, A Folkman, J Soker, S TI Effects of the VEGFR-2 tyrosine kinase inhibitor ZD6474 and docetaxel on circulating endothetial cells (CEC): Implications for use as a surrogate marker. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. AstraZeneca, Macclesfield, Cheshire, England. RI Ryan, Anderson/O-7701-2015 OI Ryan, Anderson/0000-0001-6241-7969 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6141S EP 6141S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300289 ER PT J AU Hanna, NN Nemunaitis, J Mundt, A Vijayakuma, S Rosemurgy, A Mani, S Chu, K Kessler, P Kufe, D Weichselbaum, R Senzer, N AF Hanna, NN Nemunaitis, J Mundt, A Vijayakuma, S Rosemurgy, A Mani, S Chu, K Kessler, P Kufe, D Weichselbaum, R Senzer, N TI Safety of TNFerade combined with radiation therapy in the treatment of cancer: Results of phase I evaluations SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Univ Kentucky, Med Ctr, Lexington, KY USA. US Oncol, Dallas, TX USA. Univ Chicago, Chicago, IL 60637 USA. Univ Illinois, Chicago, IL USA. Univ S Florida, Tampa, FL USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. GenVec Inc, Gaithersburg, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6144S EP 6144S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300302 ER PT J AU Yee, KO Streit, M Hawighorst, T Detmar, M Lawler, J AF Yee, KO Streit, M Hawighorst, T Detmar, M Lawler, J TI Overexpression of the type-1 repeats of thrombospondin-1 inhibits tumor growth through activation of TGF-[betal]. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6145S EP 6145S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300304 ER PT J AU Hofmann, F Kung, AL Mitsiades, CS Brueggen, J Capraro, HG Cozens, R Evans, DB Fabbro, D Ferrari, S Furet, P Geiger, T Porta, DG Liebetanz, J Maira, MS Marti, A Baron, GM Mestan, J Meyer, T Pearson, MA Ruetz, S Schnell, C Stolz, B Wood, J Zimmermann, J Garcia-Echeverria, C AF Hofmann, F Kung, AL Mitsiades, CS Brueggen, J Capraro, HG Cozens, R Evans, DB Fabbro, D Ferrari, S Furet, P Geiger, T Porta, DG Liebetanz, J Maira, MS Marti, A Baron, GM Mestan, J Meyer, T Pearson, MA Ruetz, S Schnell, C Stolz, B Wood, J Zimmermann, J Garcia-Echeverria, C TI In vivo anti-tumor and anti-angiogenic activity of novel IGF-IR kinase inhibitors. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Novartis Pharma AG, Basel, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6177S EP 6177S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300444 ER PT J AU Majumder, PK Bikoff, R Xue, Q Berger, R Shim, J Bhattacharya, N Lane, HA Loda, M Sellers, WR AF Majumder, PK Bikoff, R Xue, Q Berger, R Shim, J Bhattacharya, N Lane, HA Loda, M Sellers, WR TI Inhibition ofanAkt-dependent cell survival signal in vivo by the mTOR pathway inhibitor RADOO I: A potential candidate for use as a therapeutic agent in prostate cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC ID NEOPLASIA; AKT C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Pathol,Dept Med Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6177S EP 6177S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300443 ER PT J AU Bubley, GJ Masiello, D McKnight, N Smith, B Mohi, G Neel, B Balk, S AF Bubley, GJ Masiello, D McKnight, N Smith, B Mohi, G Neel, B Balk, S TI The effect of combination growth factor receptor and mTOR inhibitors in androgen-independent prostate cancer cell tines. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 BIDMC, Boston, MA USA. Cell Signaling Technol, Beverly, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6179S EP 6180S PN 2 PG 2 WC Oncology SC Oncology GA 756LU UT WOS:000187467300455 ER PT J AU Mohi, MG Boulton, CT Gu, TL Sternberg, D Griffin, J Gilliland, DG Neel, B AF Mohi, MG Boulton, CT Gu, TL Sternberg, D Griffin, J Gilliland, DG Neel, B TI Combination signal transduction-based approaches for the treatment of leukemias caused by oncogenic PTKs. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6179S EP 6179S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300451 ER PT J AU Mitsiades, CS Mitsiades, N McMullan, CJ Faircloth, G Martin, JAL Otero-Serrano, G Anderson, KC AF Mitsiades, CS Mitsiades, N McMullan, CJ Faircloth, G Martin, JAL Otero-Serrano, G Anderson, KC TI Pre-clinical studies in support of the clinical development of Aplidin (R) (APL) for the treatment of Multiple Myeloma (MM). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. PharmaMar SA, Cambridge, MA USA. PharmaMar SA, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6204S EP 6204S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300553 ER PT J AU Eder, JP Berkenblit, A Appleman, L Proper, J Ryan, DP He, XY Wolanski, A Kirvan-Visevatti, M Shapiro, GI Supko, JG AF Eder, JP Berkenblit, A Appleman, L Proper, J Ryan, DP He, XY Wolanski, A Kirvan-Visevatti, M Shapiro, GI Supko, JG TI A phase I clinical trial of iv continuous infusion (IVCI) KRN5500. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6205S EP 6205S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300556 ER PT J AU Li, YQ Yu, WH Ren, J Chen, W Huang, L Kharbanda, S Loda, M Kufe, D AF Li, YQ Yu, WH Ren, J Chen, W Huang, L Kharbanda, S Loda, M Kufe, D TI Nucleolar targeting of gamma-catenin by MUC1 oncoprotein. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Ilex Prod Inc, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6241S EP 6241S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300700 ER PT J AU Rosow, DE Balcom, JH Fernandez-Del Castillo, C Warshaw, AL Thayer, SP AF Rosow, DE Balcom, JH Fernandez-Del Castillo, C Warshaw, AL Thayer, SP TI Chemically induced pancreatic ductal adenocarcinomas in mice misexpress sonic hedgehog. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6242S EP 6242S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300703 ER PT J AU Li, YQ Liu, D Chen, DS Kharbanda, S Kufe, D AF Li, YQ Liu, D Chen, DS Kharbanda, S Kufe, D TI Human DF3/MUC1 carcinoma-associated protein functions as an oncogene. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Ilex Prod Inc, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6251S EP 6251S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300738 ER PT J AU Armstrong, SA AF Armstrong, SA TI Identification of therapeutic targets by gene expression based classification of acute leukemias. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6269S EP 6269S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300811 ER PT J AU Kung, AL AF Kung, AL TI In vivo models for the assessment of targeted therapeutics. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract CT AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics CY NOV 17-21, 2003 CL BOSTON, MASSACHUSETTS SP AACR, NCI, EORTC C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 1 PY 2003 VL 9 IS 16 SU S BP 6278S EP 6278S PN 2 PG 1 WC Oncology SC Oncology GA 756LU UT WOS:000187467300831 ER PT J AU Bringhurst, FR AF Bringhurst, FR TI Circulating forms of parathyroid hormone: Peeling back the onion SO CLINICAL CHEMISTRY LA English DT Editorial Material ID INTACT-PTH ASSAYS; RENAL-FAILURE; IMMUNORADIOMETRIC ASSAY; CALCIUM-CONCENTRATION; FRAGMENTS; BONE; OSTEODYSTROPHY; METABOLISM; RECEPTOR; IMPROVEMENT C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. NR 28 TC 14 Z9 15 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 DEC PY 2003 VL 49 IS 12 BP 1973 EP 1975 DI 10.1373/clinchem.2003.026948 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 746HW UT WOS:000186741800001 PM 14633866 ER PT J AU Parada, JP Deloria-Knoll, M Chmiel, JS Arozullah, AM Phan, L Ali, SN Goetz, MB Weinstein, RA Campo, R Jacobson, J Dehovitz, J Berland, D Bennett, CL AF Parada, JP Deloria-Knoll, M Chmiel, JS Arozullah, AM Phan, L Ali, SN Goetz, MB Weinstein, RA Campo, R Jacobson, J Dehovitz, J Berland, D Bennett, CL TI Relationship between health insurance and medical care for patients hospitalized with human immunodeficiency virus-related Pneumocystis carinii pneumonia, 1995-1997: Medicaid, bronchoscopy, and survival SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MORTALITY; HIV; COVERAGE; THERAPY AB In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients. C1 Edward Hines Jr Vet Adm Hosp, Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL USA. Vet Affairs Chicago Healthcare Syst, Lakeside Div, Chicago, IL USA. Vet Affairs Chicago Healthcare Syst, Westside Div, Chicago, IL USA. Univ Illinois, Coll Med, Dept Med, Chicago, IL USA. Cook Cty Hosp, Dept Med, Chicago, IL USA. Rush Med Coll, Chicago, IL 60612 USA. Sinai Hlth Syst, Dept Med, Chicago, IL USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Miami, Sch Med, Div Infect Dis, Miami, FL USA. Mt Sinai Med Ctr, AIDS Ctr, New York, NY USA. SUNY Hlth Sci Ctr, Dept Med, Brooklyn, NY USA. RP Parada, JP (reprint author), Edward Hines Jr Vet Adm Hosp, Ctr Hlth Serv & Policy Res, 151H,Roosevelt Ave,5th Ave, Hines, IL 60141 USA. RI Bennett, Charles/C-2050-2008; OI Goetz, Matthew/0000-0003-4542-992X FU NIDA NIH HHS [5R01 DA10628-02] NR 19 TC 6 Z9 6 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 DEC 1 PY 2003 VL 37 IS 11 BP 1549 EP 1555 DI 10.1086/379512 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 743LD UT WOS:000186572500018 PM 14614679 ER PT J AU Gulec, SA Faries, MB Lee, CC Kirgan, D Glass, C Morton, DL Essner, R AF Gulec, SA Faries, MB Lee, CC Kirgan, D Glass, C Morton, DL Essner, R TI The role of fluorine-18 deoxyglucose positron emission tomography in the management of patients with metastatic melanoma: Impact on surgical decision making SO CLINICAL NUCLEAR MEDICINE LA English DT Article DE FDG; PET; melanoma; metastases; therapeutic decisions; surgery ID CUTANEOUS MALIGNANT-MELANOMA; FDG-PET; FLUORODEOXYGLUCOSE; CANCER; 2-FLUORINE-18-FLUORO-2-DEOXY-D-GLUCOSE; FLUORINE-18-FLUORODEOXYGLUCOSE; SURVIVAL AB Malignant melanoma can metastasize to almost any organ site. Optimal management requires sensitive radiographic evaluation of the entire body. The optimal management of patients with metastatic melanoma requires accurate assessment of extent of disease (EOD). The objective of this study was to evaluate the accuracy of fluorine-18 deoxyglucose (FDG) whole-body positron emission tomography (PET) in determination of EOD in patients with metastatic melanoma and its impact on surgical and medical management decisions. Forty-nine patients (30 men, 19 women; aged 25-83 years) with known or suspected metastatic melanoma under-went EOD evaluation using computerized tomography (CT) of the chest, abdomen, and pelvis, and magnetic resonance imaging (MRI) of the brain. After formulation of an initial treatment plan, the patients underwent FDG-PET imaging. The EOD determined by PET was compared with physical examination and conventional radiography findings. Fifty-one lesions were pathologically evaluated. The impact of PET on patient management was assessed based on the alterations made in the initial treatment plan after reevaluation of the patients using the information obtained by PET. The PET scan identified more metastatic sites in 27 of 49 (55%) of the patients who had undergone a complete set of imaging studies, including CT scans of the chest, abdomen, and pelvis, and MRI of the brain. In 6 of those 27 patients, PET detected disease outside the fields of CT and MRI. Fifty-one lesions were resected surgically. Of these, 44 were pathologically confirmed to be melanoma. All lesions larger than I cm (29 of 29) were positive on PET, whereas only 2 of 15 (13%) lesions smaller than I cm were detected by PET. The results of PET led treatment changes in 24 patients (49%). Eighteen of these changes (75%) were surgical. In 12 cases (67%), the planned operative procedure was cancelled, and in 6 cases (33%), an additional operation(s) was performed. In 6 of 24 (25%) patients, biochemotherapy, radiation therapy, or an experimental immunotherapy protocol was prompted by identification of new foci of disease. Compared with conventional imaging, FDG-PET provides more accurate assessment of EOD in patients with metastatic melanoma. Significant surgical and medical treatment alterations were made based on PET results. C1 John Wayne Canc Inst, Santa Monica, CA 90404 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. RP Essner, R (reprint author), John Wayne Canc Inst, 2200 Santa Monica Blvd, Santa Monica, CA 90404 USA. NR 27 TC 72 Z9 75 U1 0 U2 1 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 DEC PY 2003 VL 28 IS 12 BP 961 EP 965 DI 10.1097/01.rlu.0000099805.36471.aa PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 746WR UT WOS:000186771100002 PM 14663316 ER PT J AU Bragdon, CR Doherty, AM Rubash, HE Jasty, M Li, XJ Seeherman, H Harris, WH AF Bragdon, CR Doherty, AM Rubash, HE Jasty, M Li, XJ Seeherman, H Harris, WH TI The efficacy of BMP-2 to induce bone ingrowth in a total hip replacement model SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Hip-Society CY FEB 08, 2003 CL NEW ORLEANS, LOUISIANA SP Hip Soc ID MORPHOGENETIC PROTEIN-2; FEMORAL COMPONENTS; NONHUMAN PRIMATE; COATED IMPLANTS; SPINAL-FUSION; LONG-TERM; CANINE; PHOSPHATE; ARTHROPLASTY; ARTHRODESIS AB The purpose of this canine total hip arthroplasty (THA) study was fourfold: (1) to quantify the efficacy of rhBMP-2 in a carrier (alphaBSM) versus alphaBSM alone, and versus untreated controls to induce bone formation across a defect between a porous acetabular component and host bone; (2) to quantify whether rhBMP-2/alphaBSM improves bone growth into the porous surface beneath that defect; (3) to quantify the efficacy of rhBMP-2/alphaBSM in inducing bone ingrowth into the porous layer at points of intimate bone-implant contact; and (4) to determine whether rhBMP-2/alphaBSM placed in the lateral uncovered aspect of the porous acetabular component promotes de novo bone formation. Fifteen dogs were sacrificed 12 weeks after uncemented THA. Five dogs received rhBMP-2/alphaBSM, five dogs received alphaBSM, and five dogs were controls. In contrast to the controls in which no bone filled the defect, the rhBMP-2/alphaBSM induced defect filling and full bone formation in the underlying porous coating. The aBSNI produced an intermediary response. However, no increase in new bone formation occurred at sites of intimate bone porous surface contact. Recombinant bone morphogenetic protein-2/alphaBSM promoted defect filling and bone ingrowth into the porous coating beneath the defect region, both of potential value in future total joint replacement surgery. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Adult Reconstruct Unit, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. Wyeth Pharmaceut Inc, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. RP Bragdon, CR (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson Bld 1206,55 Fruit St, Boston, MA 02114 USA. EM cbragdon@partners.org NR 27 TC 53 Z9 54 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2003 IS 417 BP 50 EP 61 DI 10.1097/01.blo.0000096811.78689.2b PG 12 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 770ZH UT WOS:000188760900007 PM 14646702 ER PT J AU Harris, WH AF Harris, WH TI Results of uncemented cups - A critical appraisal at 15 years SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Hip-Society CY FEB 08, 2003 CL NEW ORLEANS, LA SP Hip Soc ID TOTAL HIP-ARTHROPLASTY; CEMENTLESS ACETABULAR RECONSTRUCTION; MOLECULAR-WEIGHT POLYETHYLENE; LOW-FRICTION ARTHROPLASTY; FOLLOW-UP; CONGENITAL DISLOCATION; RHEUMATOID-ARTHRITIS; YOUNG-PATIENTS; REVISION; COMPONENT AB One of the most important advances in total hip arthroplasty is the development of successful cementless acetabular components. Cemented acetabular components in older patients showed increasing loss of fixation after the first decade. Loosening commonly occurred during the first decade in young patients and after revision surgeries. Although some cementless designs failed, the hemispheric design with a porous exterior surface now is adopted widely. Assessment of acetabular reconstructions should be evaluated as primary operations in the older age group, primary operations in younger patients, and revisions. In all three categories, the cementless hemispheric design has proven remarkably successful. For example, a compilation of three reports on acetabular revisions using the HGP design revealed that by 12.5 years, only five of 263 shells required shell rerevision (2%). Periprosthetic osteolysis and dislocation are problems, but are being addressed by improved articulations and designs. These advances are remarkable in generating successful long-term acetabular reconstructions. C1 Harvard Univ, Orthopaed Biomech & Biomat Lab, Massachusetts Gen Hosp, Med Sch,Dept Orthopaed Surg, Boston, MA 02114 USA. RP Harvard Univ, Orthopaed Biomech & Biomat Lab, Massachusetts Gen Hosp, Med Sch,Dept Orthopaed Surg, GRJ 1206, Boston, MA 02114 USA. EM wharris.obbl@partners.org NR 35 TC 23 Z9 28 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2003 IS 417 BP 121 EP 125 DI 10.1097/01.blo.0000096824.67494.aa PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 770ZH UT WOS:000188760900014 PM 14646709 ER PT J AU Chiang, PP Burke, DW Freiberg, AA Rubash, HE AF Chiang, PP Burke, DW Freiberg, AA Rubash, HE TI Osteolysis of the pelvis - Evaluation and treatment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Hip-Society CY FEB 08, 2003 CL NEW ORLEANS, LOUISIANA SP Hip Soc ID TOTAL HIP-REPLACEMENT; CEMENTLESS ACETABULAR COMPONENTS; SURGICAL-TREATMENT; POLYETHYLENE WEAR; ARTHROPLASTY; RETENTION AB Osteolysis of the pelvis is a common and well-recognized complication associated with total hip arthroplasty. The diagnosis and treatment of osteolysis of the pelvis is a challenging and controversial problem. Osteolysis of the pelvis often is asymptomatic and does not present with symptoms until considerable bone loss and loosening of the acetabular socket occur. Radiographs are the most common way to detect and monitor osteolysis around an implant. However, lesions viewed radiographically usually are underestimations of the lesions found intraoperatively. Moreover, some advocate computed tomography scanning to evaluate these lesions. The indications for treatment of osteolysis with cemented acetabular components are defined more clearly than with a cementless component. If the cemented or cementless acetabular component is loose, then revision is necessary. However, it is less clear when to intervene surgically with a well-fixed cup with osteolysis. Many early reports advocated the removal of a well-fixed socket during revision surgery for osteolysis and polyethylene wear. However, the removal of a well-fixed socket has the potential for significant damage and loss of the surrounding bone resulting in loss of integrity of a column or pelvic discontinuity, which may compromise placing another acetabular component. Recently, a new treatment strategy of retaining a well-fixed socket, exchanging the liner, and grafting lesions has proven successful. Without the removal of the acetabular shell, different techniques are needed to graft the osteolytic lesions. Osteolysis is a difficult problem; however, with radiographic surveillance to monitor patients for lesions, proper indications, and good surgical techniques, the treatment of osteolysis of the pelvis can result in a well-functioning total hip arthroplasty. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Rubash, HE (reprint author), 55 Fruit St,White 601, Boston, MA 02114 USA. EM hrubash@partners.org NR 31 TC 43 Z9 46 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2003 IS 417 BP 164 EP 174 DI 10.1097/01.blo.0000096816.78689.e5 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 770ZH UT WOS:000188760900019 PM 14646714 ER PT J AU Muratoglu, OK Merrill, EW Bragdon, CR O'Connor, D Hoeffel, D Burroughs, B Jasty, M Harris, WH AF Muratoglu, OK Merrill, EW Bragdon, CR O'Connor, D Hoeffel, D Burroughs, B Jasty, M Harris, WH TI Effect of radiation, heat, and aging on in vitro wear resistance of polyethylene SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID MOLECULAR-WEIGHT POLYETHYLENE; LOW-FRICTION ARTHROPLASTY; TOTAL JOINT REPLACEMENTS; CROSS-LINKING; HIP; UHMWPE; STERILIZATION; OSTEOLYSIS; SIMULATOR; OXIDATION AB Radiation cross-linking increases the wear resistance of polyethylene used in total hip replacement. Radiation also generates residual free radicals, which are detrimental to long-term properties of polyethylene. Two approaches are used to stabilize the residual free radicals and terminally sterilize the components. One is postirradiation annealing with gas sterilization and the other is postirradiation melting with gamma sterilization in nitrogen. The hypothesis of the current study is that post-irradiation annealing followed by gamma sterilization in nitrogen will result in more free radicals in polyethylene than gamma sterilization either in air or in nitrogen alone. To test this hypothesis, concentration of residual free radicals was quantified in polyethylene that was annealed and gamma sterilized in nitrogen and control polyethylenes gamma sterilized in air versus in nitrogen. Three cross-linked polyethylenes that were melted and gas sterilized also were included in the study. The effects of residual free radicals were studied by accelerated aging. Oxidation levels and weight loss in bidirectional pin-on-disk tests were determined before and after aging. Polyethylene that was subjected to postirradiation annealing and gamma sterilization resulted in 58% more residual free radicals than control polyethylenes. Weight loss of the annealed polyethylene increased by 16-fold on accelerated aging and had three times higher oxidation levels than that measured in control polyethylenes after aging. In contrast, polyethylenes that were stabilized with postirradiation melting and terminally gas sterilized showed no detectable residual free radicals. Accelerated aging did not affect the weight loss and oxidation levels of melted polyethylenes. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Dept Orthopaed Surg, GRJ 1206,55 Fruit St, Boston, MA 02114 USA. EM omuratoglu@partners.org NR 29 TC 56 Z9 57 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD DEC PY 2003 IS 417 BP 253 EP 262 DI 10.1097/01/blo.0000093004.90435.d1 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 770ZH UT WOS:000188760900029 PM 14646724 ER PT J AU Miller, MW AF Miller, MW TI Personality and the etiology and expression of PTSD: A three-factor model perspective SO CLINICAL PSYCHOLOGY-SCIENCE AND PRACTICE LA English DT Review DE personality; PTSD; negative emotionality; positive emotionality; constraint ID POSTTRAUMATIC-STRESS-DISORDER; MALE VIETNAM VETERANS; CONCURRENT PSYCHIATRIC-ILLNESS; COMMON MENTAL-DISORDERS; DSM-III-R; RISK-FACTORS; ANTISOCIAL PERSONALITY; TRAUMATIC EVENTS; ANXIETY DISORDERS; CHILDHOOD TRAUMA AB This review provides an overview of research on the influence of personality on the development course, and behavioral expression of posttraumatic stress disorder (FTSD). The existing literature is discussed in relation to three broad-band personality traits that have been emphasized in personality and psychopathology research: negative emotionality (NEM), positive emotionality (PEM), and constraint/inhibition (CON). The primary conclusion derived from this review is that high NEM is the primary personality risk factor for the development of PTSD whereas low CON and low PEM serve as moderating factors that influence the form and expression of the disorder through their interaction with NEM. From this standpoint, a premorbid personality characterized by high NEM combined with low PEM is thought to predispose the trauma-exposed individual towards an internalizing form of posttraumatic response characterized by marked social avoidance, anxiety, and depression. On the other hand, high NEM combined with low CON is hypothesized to predict an externalizing form of posttraumatic reaction characterized by marked impulsivity, aggression, and a propensity towards antisociality and substance abuse. C1 VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, Boston, MA 02130 USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 NR 177 TC 66 Z9 68 U1 10 U2 27 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0969-5893 J9 CLIN PSYCHOL-SCI PR JI Clin. Psychol.-Sci. Pract. PD WIN PY 2003 VL 10 IS 4 BP 373 EP 393 DI 10.1093/clipsy/bpg040 PG 21 WC Psychology, Clinical SC Psychology GA 751HE UT WOS:000187059200001 ER PT J AU Lui, KW Gervais, DA Arellano, RA Mueller, PR AF Lui, KW Gervais, DA Arellano, RA Mueller, PR TI Radiofrequency ablation of renal cell carcinoma SO CLINICAL RADIOLOGY LA English DT Review DE radiofrequency ablation; renal cell carcinoma; interventional radiology ID NEPHRON SPARING SURGERY; TISSUE ABLATION; THERMAL ABLATION; RADIO-FREQUENCY; COAGULATION NECROSIS; LIVER METASTASES; TUMOR ABLATION; IN-VIVO; HEPATOCELLULAR-CARCINOMA; CLINICAL-EXPERIENCE AB Small renal cell carcinomas of less than 4 cm diameter have been detected increasingly in asymptomatic patients because of the widespread use of cross-sectional imaging. Radical or partial nephrectomy is generally considered the reference for the treatment of a solitary renal cell carcinoma. However, for those patients who are not candidates for surgery, minimally invasive procedures may be desirable. Although percutaneous radiofrequency ablation for the treatment of renal cell carcinoma is a recent innovation, the results of preliminary clinical series and animal studies are encouraging, and show it to be technically feasible with minimal morbidity. In this article, we review the technique, indications, imaging findings, as well as the results of clinical and animal studies of radiofrequency ablation for the treatment of renal cell carcinoma. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. Chang Gung Mem Hosp, Dept Diagnost Radiol 1, Tao Yuan, Taiwan. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White Bldg,Room 270, Boston, MA 02114 USA. NR 50 TC 35 Z9 35 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 DEC PY 2003 VL 58 IS 12 BP 905 EP 913 DI 10.1016/S0009-9260(03)00222-8 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753UD UT WOS:000187248200001 PM 14654022 ER PT J AU McCollum, M Rhew, DC Parodi, S AF McCollum, M Rhew, DC Parodi, S TI Cost analysis of switching from IV vancomycin to PO linezolid for the management of methicillin-resistant Staphylococcus species SO CLINICAL THERAPEUTICS LA English DT Article DE pharmacoeconomics; linezolid; vancomycin; costs; Staphylococcus; drug resistance ID INSERTED CENTRAL CATHETERS; BLOOD-STREAM INFECTIONS; INTENSIVE-CARE-UNIT; PHARMACOECONOMIC ANALYSES; ATTRIBUTABLE MORTALITY; ANTIMICROBIAL THERAPY; AUREUS INFECTION; CANCER-PATIENTS; HOSPITALS; COMMUNITY AB Background: Infections with methicillin-resistant Staphylococcus species (MRSS) are associated with higher treatment costs than infections with methicillin-sensitive Staphylococcus species in the United States-partly because of an increased length of hospital stay (LOS). Objective: This study used pharmacoeconomic modeling to evaluate the costs and outcomes associated with the use of IV vancomycin compared with PO linezolid in the treatment of MRSS-infected patients. Methods: A retrospective chart review was used to determine the number of cases with confirmed or presumed MRSS infections treated with IV vancomycin during calendar-year 2000 at the Veterans Affairs Greater Los Angeles Healthcare System inpatient facility Patients who were eligible for a switch to PO linezolid with or without early discharge to home were identified. Cost differences associated with conversion from IV to PO therapy (compared with continued IV therapy) were estimated based on a mean decreased LOS and a decrease in the costs associated with catheter-related adverse events. Rates and costs of catheter-related adverse events were based on estimates from the literature. Sensitivity analyses were performed by variation of the estimated mean LOS decrease in the SD and by variation of the estimates for incidence and costs related to catheter complications. Costs were measured in year-2000 US dollars, and differences were not assessed for statistical significance. Results: Of 177 patients treated with IV vancomycin, 103 (58%) were eligible for conversion to PO linezolid and 55 (31%) were eligible for early discharge from the hospital with continuation of PO therapy Early discharge was associated with a mean (SD) LOS decrease of 3.3 (2.9) days. Annual mean total cost savings in patients eligible for conversion from TV vancomycin to PO linezolid with early discharge were $294,750 (range, $35,730-$553,790). For cases eligible for inpatient conversion from IV vancomycin to PO linezolid therapy (n = 48), the mean total annual cost difference was an increase of $6340 for PO linezolid (range, -$12,910 to $11,900). Conclusion: These results-although partly based on estimates from the literature, rather than direct measurements-support the use of PO linezolid with or without early discharge as a potential cost-savings alternative for eligible patients treated with a full course of IV vancomycin for suspected or confirmed MRSS infection. Copyright (C) 2003 Excerpta Medica, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Sch Pharm, Denver, CO USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Dept Med, Zynx Hlth Inc, Los Angeles, CA USA. Cedars Sinai Hlth Syst, Dept Hlth Serv Res, Zynx Hlth Inc, Los Angeles, CA USA. RP McCollum, M (reprint author), 4200 E 9th Ave,Box C-238, Denver, CO 80262 USA. EM marianne.mccollum@uchsc.edu NR 50 TC 18 Z9 19 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD DEC PY 2003 VL 25 IS 12 BP 3173 EP 3189 DI 10.1016/S0149-2918(03)90101-9 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 763MK UT WOS:000188089600013 PM 14749155 ER PT J AU Post, RM Baldassano, CF Perlis, RH Ginsberg, DL AF Post, RM Baldassano, CF Perlis, RH Ginsberg, DL TI Treatment of bipolar depression SO CNS SPECTRUMS LA English DT Review ID PLACEBO-CONTROLLED TRIAL; INDUCED WEIGHT-GAIN; DOUBLE-BLIND; MAJOR DEPRESSION; MOOD DISORDERS; ANTIDEPRESSANT DISCONTINUATION; DYSPHORIC MANIA; FOLIC-ACID; FOLLOW-UP; LITHIUM AB Bipolar disorder is underdiagnosed and often mistaken for unipolar depression. Bipolar patients spend 33% of their time in a state of depression compared to 11% of time spent in a manic state. Duration of time depressed and severity of depression are associated with increased risk for suicide, which occurs in 10% to 20% of bipolar patients. Antidepressants are increasingly being used as adjuncts in the depressed phase of bipolar disorder, although they provide a moderate risk for switch into mania. Lithium and some antlepileptics and atypical antipsychotics have shown antidepressant effects in the treatment of bipolar disorder. Other adjuncts for treatment-refractory patients include monoamine oxidase inhibitors and electroconvulsive therapy. C1 Bipolar Collaborat Network, Chevy Chase, MD USA. Hosp Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Mood & Anxiety Disorder Inst, Psychopharmacol Consultat Serv, Boston, MA 02114 USA. RP Post, RM (reprint author), Bipolar Collaborat Network, Chevy Chase, MD USA. NR 63 TC 1 Z9 1 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD DEC PY 2003 VL 8 IS 12 BP A1 EP A10 PG 10 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 895UW UT WOS:000226890300012 ER PT J AU Goebel-Fabbri, AE Fikkan, J Franko, DL AF Goebel-Fabbri, AE Fikkan, J Franko, DL TI Beyond the manual: The flexible use of cognitive behavioral therapy for bulimia nervosa SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID BINGE-EATING DISORDER; INTERPERSONAL PSYCHOTHERAPY; PREDICTORS; WEIGHT AB The treatment manual applying cognitive behavioral therapy principles for bulimia nervosa originally was used in early treatment outcome studies and was later expanded and enhanced by Fairburn, Marcus, and Wilson (1993)for broader clinical use. The manual is well researched as an effective treatment and currently is advocated as the first-line treatment for bulimia nervosa. However, despite the research data supporting its use, these manual-based techniques are still not widely practiced in the treatment of eating disorders outside of academic research settings. This article aims to elaborate on aspects of the manual that may have hindered some therapists in its use. We focus on clarifying aspects of the treatment process that may assist clinicians to flexibly apply the treatment manual's specific techniques by emphasizing stylistic approaches to help facilitate treatment adherence, diminish risks of treatment dropout, and address behaviors that interfere with treatment. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Behav Mental Hlth Unit, Boston, MA 02215 USA. Univ Massachusetts, Dartmouth, MA USA. RP Goebel-Fabbri, AE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Behav Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. NR 26 TC 4 Z9 4 U1 0 U2 1 PU ASSOC ADV BEHAVIOR THERAPY PI NEW YORK PA 305 7TH AVE #16A, NEW YORK, NY 10001-6008 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD WIN PY 2003 VL 10 IS 1 BP 41 EP 50 DI 10.1016/S1077-7229(03)80007-X PG 10 WC Psychology, Clinical SC Psychology GA 918NU UT WOS:000228550600006 ER PT J AU Yu, DT Platt, R Lanken, PN Black, E Sands, KE Schwartz, JS Hibberd, PL Graman, PS Kahn, KL Snydman, DR Parsonnet, J Moore, R Bates, DW AF Yu, DT Platt, R Lanken, PN Black, E Sands, KE Schwartz, JS Hibberd, PL Graman, PS Kahn, KL Snydman, DR Parsonnet, J Moore, R Bates, DW CA AMCC Sepsis Project Working Grp TI Relationship of pulmonary artery catheter use to mortality and resource utilization in patients with severe sepsis SO CRITICAL CARE MEDICINE LA English DT Article DE catheter; mortality; resource utilization; severe sepsis; bacteremia; sepsis; cohort study ID CRITICALLY-ILL PATIENTS; RISK SURGICAL PATIENTS; INTENSIVE-CARE UNITS; INFLAMMATORY RESPONSE SYNDROME; ACUTE MYOCARDIAL-INFARCTION; MAXIMIZING OXYGEN DELIVERY; SEPTIC SHOCK; PROPENSITY SCORE; RANDOMIZED TRIAL; MORBIDITY AB Objective: To examine the relationship of pulmonary artery catheter (PAC) use to patient outcomes, including mortality rate and resource utilization, in patients with severe sepsis in eight academic medical centers. Design: Case-control, nested within a prospective cohort study. Setting: Eight academic tertiary care centers. Patients. Stratified random sample of 1,010 adult admissions with severe sepsis. Interventions. None. Measurements and Main Results. The main outcome measures were in-hospital mortality, total hospital charge, and length of stay (LOS) for patients with and without PAC use. The case-matched subset of patients included 141 pairs managed with and without the use of a PAC. The mortality rate was slightly but not statistically significantly lower among the PAC use group compared with those not using a PAC (41.1% vs. 46.8%, p = .34). Even this trend disappeared after we adjusted for the Charlson comorbidity score and sepsis-specific Acute Physiology and Chronic Health Evaluation (APACHE) III (adjusted odds ratio, 1.02; 95% confidence interval, 0.61-1.72). In linear regression models adjusted for the Charlson comorbidity score, sepsis-specific APACHE III, surgical status, receipt of a steroid before sepsis onset, presence of a Hickman catheter, and preonset LOS, no significant differences were found for total hospital charges (US$139,207 vs. 148,190, adjusted mean comparing PAC and non-PAC group, p = .57), postonset LOS (23.4 vs. 26.9 days, adjusted mean, p = .32), or total LOS in intensive care unit (18.2 vs. 18.8 days, adjusted mean, p = .82). Conclusions. Among patients with severe sepsis, PAC placement was not associated with a change in mortality rate or resource utilization, although small nonsignificant trends toward lower resource utilization were present in the PAC group. C1 Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Johns Hopkins Univ Hosp, Div Infect Dis, Baltimore, MD 21287 USA. Dartmouth Hitchcock Med Ctr, Infect Dis Sect, Lebanon, NH 03766 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Tufts Univ New England Med Ctr, Dept Pathol & Med, Div Infect Dis, Boston, MA 02111 USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. Univ Rochester, Sch Med, Dept Med, Div Gen Internal Med, Rochester, NY USA. Univ Rochester, Sch Med, Dept Med, Infect Dis Unit, Rochester, NY USA. Univ Penn, Leonard Davis Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Pulm Allergy & Crit Care Div, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. RP Yu, DT (reprint author), Brigham & Womens Hosp, Dept Med, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 37 TC 36 Z9 39 U1 0 U2 1 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 DEC PY 2003 VL 31 IS 12 BP 2734 EP 2741 DI 10.1097/01.CCM.0000098028.68323.64 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 755KY UT WOS:000187403100003 PM 14668609 ER PT J AU Badjatia, N Topcuoglu, MA Smith, EE Nogueira, RG Buonanno, FS Singhal, AB Carter, BS Ogilvy, CS AF Badjatia, N Topcuoglu, MA Smith, EE Nogueira, RG Buonanno, FS Singhal, AB Carter, BS Ogilvy, CS TI Hyperglycemia after subarachnoid hemorrhage: A modifiable risk factor for development of symptomatic vasospasm SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 33rd Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 20-25, 2004 CL ORLANDO, FLORIDA SP Soc Critical Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2003 VL 31 IS 12 SU S MA 76 BP A20 EP A20 PN 2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 758LW UT WOS:000187636500076 ER PT J AU Bigatello, LM Gettings, E Kwo, J Hess, D AF Bigatello, LM Gettings, E Kwo, J Hess, D TI Longitudinal outcome of patients undergoing prolonged mechanical ventilation SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 33rd Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 20-25, 2004 CL ORLANDO, FLORIDA SP Soc Critical Care Med C1 Massachusetts Gen Hosp, Resp Care Serv, 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2003 VL 31 IS 12 SU S MA 348 BP A96 EP A96 PN 2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 758LW UT WOS:000187636500340 ER PT J AU Pisegna, JR Oh, D Karlstadt, R Graepel, J Field, B AF Pisegna, JR Oh, D Karlstadt, R Graepel, J Field, B TI Perioperative use of IV pantoprazole (FVP) effectively controls gastric volume (GV) and acid output (GAO) in NPO patients in the perioperative period: Analysis of results from the perioperative IVP pilot study SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 33rd Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 20-25, 2004 CL ORLANDO, FLORIDA SP Soc Critical Care Med C1 VA Greater LA Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Wyeth Pharmaceut, Collegeville, PA 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2003 VL 31 IS 12 SU S MA 308 BP A84 EP A84 PN 2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 758LW UT WOS:000187636500298 ER PT J AU Schmidt, U Gettings, E Toon, H Hurford, WE Bigatello, LM Hess, D AF Schmidt, U Gettings, E Toon, H Hurford, WE Bigatello, LM Hess, D TI Evaluation of emergency intubation outcomes: An observational study of airway management SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 33rd Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 20-25, 2004 CL ORLANDO, FLORIDA SP Soc Critical Care Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 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 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2003 VL 31 IS 12 SU S MA 240 BP A64 EP A64 PN 2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 758LW UT WOS:000187636500231 ER PT J AU Yasukawa, T Kaneki, M Yasuhara, S Martyn, JAJ AF Yasukawa, T Kaneki, M Yasuhara, S Martyn, JAJ TI Steroidal nondepolarizing muscle relaxants do not simulate the effects of glucocorticoids on glucocorticoid receptor-mediated transcription in cultured skeletal muscle cells SO CRITICAL CARE MEDICINE LA English DT Meeting Abstract CT 33rd Critical Care Congress of the Society-of-Critical-Care-Medicine CY FEB 20-25, 2004 CL ORLANDO, FLORIDA SP Soc Critical Care Med C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD DEC PY 2003 VL 31 IS 12 SU S MA 147 BP A38 EP A38 PN 2 PG 1 WC Critical Care Medicine SC General & Internal Medicine GA 758LW UT WOS:000187636500137 ER PT J AU Ghosh, PM Malik, S Bedolla, R Kreisberg, JI AF Ghosh, PM Malik, S Bedolla, R Kreisberg, JI TI Akt in prostate cancer: Possible role in androgen-independence SO CURRENT DRUG METABOLISM LA English DT Review DE Akt; PI3K; androgen receptor; MAPK; PTEN; prostate cancer ID ACTIVATED PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; CARCINOMA CELL-LINE; B C-AKT; BETA-CATENIN; SIGNAL-TRANSDUCTION; RECEPTOR GENE; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVITY AB Akt, a downstream effector of phosphatidylinositol 3-kinase (PI3K), has often been implicated in prostate cancer. Studies in prostate tumor cell lines revealed that Akt activation is probably important for the progression of prostate cancer to an androgen-independent state. Investigations of human prostate cancer tissues show that although there is neither Akt gene amplification nor enhanced protein expression in prostate cancer compared to normal tissue, poorly differentiated tumors exhibit increased expression of a phosphorylated (activated) form of Akt compared to normal tissue, prostatic intraepithelial neoplasia (PIN) or well-differentiated prostate cancer. Akt phosphorylation is accompanied by the inactivation of ERK, a member of the mitogen activated protein kinase (MAPK) family. In this article, we postulate that Akt promotes androgen-independent survival of prostate tumor cells by modulating the expression and activation of the androgen receptor (AR). C1 Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Vet Adm Hosp, San Antonio, TX USA. RP Kreisberg, JI (reprint author), Univ Texas, Hlth Sci Ctr, Dept Surg, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 101 TC 68 Z9 71 U1 2 U2 7 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD DEC PY 2003 VL 4 IS 6 BP 487 EP 496 DI 10.2174/1389200033489226 PG 10 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 751LD UT WOS:000187067800002 PM 14683476 ER PT J AU Huang, PL AF Huang, PL TI Endothelial nitric oxide synthase and endothelial dysfunction SO CURRENT HYPERTENSION REPORTS LA English DT Article ID DOUBLE-KNOCKOUT MICE; PROTEIN-KINASE AKT; ACCELERATED ATHEROSCLEROSIS; GENETIC DEFICIENCY; CEREBRAL-ISCHEMIA; MOLECULAR-CLONING; SMOOTH-MUSCLE; IN-VIVO; PHOSPHORYLATION; LACKING AB Nitric oxide (NO) regulates vascular tone and local blood flow, platelet aggregation and adhesion, and leukocyte-endothelial cell interactions. Abnormalities in NO production by the vascular endothelium result in endothelial dysfunction, which occurs in hypertension, diabetes, aging, and as a prelude to atherosclerosis. The common feature of endothelial dysfunction is a decrease in the amount of bioavailable NO. In this article, the physiologic roles of NO and the mechanisms of endothelial dysfunction are reviewed. Regulation of endothelial NO synthase (eNOS) activity by fatty acid modifications, intracellular localization, interactions with heat shock protein 90 (hsp90) and caveolin, substrate and cofactor dependence, and phosphorylation might all affect the level of bioavailable NO. A hypothesis is proposed that the final common pathway of diverse causes of endothelial dysfunction involves abnormalities in eNOS phosphorylation at Ser 1179 and other key phosphorylation sites. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Div Cardiovasc, Charlestown, MA 02129 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 Thirteenth St, Charlestown, MA 02129 USA. NR 45 TC 57 Z9 61 U1 0 U2 7 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD DEC PY 2003 VL 5 IS 6 BP 473 EP 480 DI 10.1007/s11906-003-0055-4 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 744WE UT WOS:000186655200006 PM 14594566 ER PT J AU Bogdanov, A AF Bogdanov, A TI In vivo imaging in the development of gene therapy vectors SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE expression vector; gene delivery; gene therapy; luminescence; molecular imaging; MRI; radioisotope ID POSITRON-EMISSION-TOMOGRAPHY; PROTEIN-PROTEIN INTERACTIONS; REPORTER GENE; LIVING MICE; THYMIDINE KINASE; PLASMID DNA; EXPRESSION; DELIVERY; ANIMALS; RECEPTOR AB The availability of imaging techniques and reporter probes that provide information regarding the biodistribution of gene therapy vectors and expression of encoded genes in living animals, has the potential to accelerate the development and testing of new gene therapies. Techniques using novel imaging markers and labeled reporter molecules enable longitudinal studies that provide quantitative or semi-quantitative data reflecting gene expression regulation in living animals, which may significantly assist in the development of therapeutics targeted to individual organs or cell populations. Non-invasive imaging studies performed in animal models of human disease are crucial for translational research for future clinical development. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St, Charlestown, MA 02129 USA. EM bogdanov@helix.mgh.harvard.edu NR 47 TC 3 Z9 4 U1 0 U2 0 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD DEC PY 2003 VL 5 IS 6 BP 594 EP 602 PG 9 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 763MP UT WOS:000188090000004 PM 14755885 ER PT J AU Goodman, RB Pugin, J Lee, JS Matthay, MA AF Goodman, RB Pugin, J Lee, JS Matthay, MA TI Cytokine-mediated inflammation in acute lung injury SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE chemokine; interleukins; acute respiratory distress syndrome (ARDS); pulmonary edema ID RESPIRATORY-DISTRESS-SYNDROME; TUMOR-NECROSIS-FACTOR; BRONCHOALVEOLAR LAVAGE FLUID; MIGRATION-INHIBITORY FACTOR; TRANSFORMING GROWTH FACTOR-BETA-1; INTERLEUKIN-1 RECEPTOR ANTAGONIST; NEUTROPHIL-ACTIVATING PEPTIDE-2; PULMONARY-EDEMA FLUID; RANDOMIZED CONTROLLED-TRIAL; ALVEOLAR EPITHELIAL REPAIR AB Clinical acute lung injury (ALI) is a major cause of acute respiratory failure in critically ill patients. There is considerable experimental and clinical evidence that pro- and anti-inflammatory cytokines play a major role in the pathogenesis of inflammatory-induced lung injury from sepsis, pneumonia, aspiration, and shock. A recent multi-center clinical trial found that a lung-protective ventilatory strategy reduces mortality by 22% in patients with ALI. Interestingly, this protective ventilatory strategy was associated with a marked reduction in the number of neutrophils and the concentration of pro- inflammatory cytokines released into the airspaces of the injured lung. Further research is needed to establish the contribution of cytokines to both the pathogenesis and resolution of ALI. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Washington, Sch Med,Div Pulm & Crit Care, VA Puget Sound Med Ctr,Dept Vet Affairs, VA Puget Sound Hlth Care Syst,VA Pulm Res Labs, Seattle, WA 98108 USA. Univ Washington, Sch Med,Div Pulm & Crit Care, VA Puget Sound Med Ctr,Dept Med, VA Puget Sound Hlth Care Syst,VA Pulm Res Labs, Seattle, WA 98108 USA. Univ Hosp Geneva, Dept Med, Div Med Intens Care, CH-1211 Geneva 14, Switzerland. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anesthesia, San Francisco, CA 94143 USA. RP Matthay, MA (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, 505 Parnassus Ave,HSW-825, San Francisco, CA 94143 USA. FU NHLBI NIH HHS [HL30542, HL51854, HL51856, HL69955, HL70178, HR46059] NR 170 TC 301 Z9 338 U1 3 U2 39 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD DEC PY 2003 VL 14 IS 6 BP 523 EP 535 DI 10.1016/S1359-6101(03)00059-5 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 741ZX UT WOS:000186491200007 PM 14563354 ER PT J AU Sutherland, DJ Li, MF Liu, XQ Stefancsik, R Raftery, LA AF Sutherland, DJ Li, MF Liu, XQ Stefancsik, R Raftery, LA TI Stepwise formation of a SMAD activity gradient during dorsal-ventral patterning of the Drosophila embryo SO DEVELOPMENT LA English DT Article DE BMP; morphogen gradient; SMAD; dorsal-ventral patterning; Drosophila ID SHORT GASTRULATION GENE; MORPHOGEN GRADIENT; SIGNAL-TRANSDUCTION; DPP RESPONSES; I RECEPTORS; CELL FATES; PATHWAY; GROWTH; ACTIVATION; BRINKER AB Genetic evidence suggests that the Drosophila ectoderm is patterned by a spatial gradient of bone morphogenetic protein (BMP). Here we compare patterns of two related cellular responses, both signal-dependent phosphorylation of the BMP-regulated R-SMAD, MAD, and signal-dependent changes in levels and sub-cellular distribution of the co-SMAD Medea. Our data demonstrate that nuclear accumulation of the co-SMAD Medea requires a BMP signal during blastoderm and gastrula stages. During this period, nuclear co-SMAD responses occur in three distinct patterns. At the end of blastoderm, a broad dorsal domain of weak SMAD response is detected. During early gastrulation, this domain narrows to a thin stripe of strong SMAD response at the dorsal midline. SMAD response levels continue to rise in the dorsal midline region during gastrulation, and flanking plateaus of weak responses are detected in dorsolateral cells. Thus, the thresholds for gene expression responses are implicit in the levels of SMAD responses during gastrulation. Both BMP ligands, DPP and Screw, are required for nuclear co-SMAD responses during these stages. The BMP antagonist Short gastrulation (SOG) is required to elevate peak responses at the dorsal midline as well as to depress responses in dorsolateral cells. The midline SMAD response gradient can form in embryos with reduced dpp gene dosage, but the peak level is reduced. These data support a model in which weak BMP activity during blastoderm defines the boundary between ventral neurogenic ectoderm and dorsal ectoderm. Subsequently, BMP activity creates a step gradient of SMAD responses that patterns the amnioserosa and dorsomedial ectoderm. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Raftery, LA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Raftery, Laurel/H-1406-2012; OI Raftery, Laurel/0000-0003-4797-4163; Liu, Xiao-Qing/0000-0002-4034-5156; Stefancsik, Raymund/0000-0001-8314-2140 FU NIGMS NIH HHS [GM60501, R01 GM060501] NR 56 TC 50 Z9 56 U1 1 U2 7 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 DEC PY 2003 VL 130 IS 23 BP 5705 EP 5716 DI 10.1242/dev.00801 PG 12 WC Developmental Biology SC Developmental Biology GA 755JN UT WOS:000187399900012 PM 14534137 ER PT J AU Shu, XD Cheng, KR Patel, N Chen, FH Joseph, E Tsai, HJ Chen, JN AF Shu, XD Cheng, KR Patel, N Chen, FH Joseph, E Tsai, HJ Chen, JN TI Na,K-ATPase is essential for embryonic heart development in the zebrafish SO DEVELOPMENT LA English DT Article DE heart development; zebrafish; Na,K-ATPase ID ALPHA-SUBUNIT; K+-ATPASE; CARDIOVASCULAR-SYSTEM; EXPRESSION; TUBE; NA; IDENTIFICATION; NA+,K+-ATPASE; CALCIUM; OUABAIN AB Na,K-ATPase is an essential gene maintaining electrochemical gradients across the plasma membrane. Although previous studies have intensively focused on the role of Na,K-ATPase in regulating cardiac function in the adults, little is known about the requirement for Na,K-ATPase during embryonic heart development. Here, we report the identification of a zebrafish mutant, heart and mind, which exhibits multiple cardiac defects, including the primitive heart tube extension abnormality, aberrant cardiomyocyte differentiation, and reduced heart rate and contractility. Molecular cloning reveals that the heart and mind lesion resides in the alpha1B1 isoform of Na,K-ATPase. Blocking Na,K-ATPase alpha1B1 activity by pharmacological means or by morpholino antisense oligonucleotides phenocopies the patterning and functional defects of heart and mind mutant hearts, suggesting crucial roles for Na,K-ATPase alpha1B1 in embryonic zebrafish hearts. In addition to alpha1B1, the Na,K-ATPase alpha2 isoform is required for embryonic cardiac patterning. Although the alpha1B1 and alpha2 isoforms share high degrees of similarities in their coding sequences, they have distinct roles in patterning zebrafish hearts. The phenotypes of heart and mind mutants can be rescued by supplementing alpha1B1, but not alpha2, mRNA to the mutant embryos, demonstrating that alpha1B1 and alpha2 are not functionally equivalent. Furthermore, instead of interfering with primitive heart tube formation or cardiac chamber differentiation, blocking the translation of Na,K-ATPase alpha2 isoform leads to cardiac laterality defects. C1 Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Jonsson Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Cardiovasc Res Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Dev Biol Lab, Charlestown, MA 02129 USA. Natl Taiwan Univ, Coll Life Sci, Inst Mol & Cell Biol, Taipei 10764, Taiwan. RP Chen, JN (reprint author), Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA. OI Chen, Jau-Nian/0000-0001-8807-3607 NR 32 TC 70 Z9 73 U1 1 U2 5 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 DEC PY 2003 VL 130 IS 25 BP 6165 EP 6173 DI 10.1242/dev.00844 PG 9 WC Developmental Biology SC Developmental Biology GA 755JT UT WOS:000187400300002 PM 14602677 ER PT J AU Liu, TX Howlett, NG Deng, M Langenau, DM Hsu, K Rhodes, J Kanki, JP D'Andrea, AD Look, AT AF Liu, TX Howlett, NG Deng, M Langenau, DM Hsu, K Rhodes, J Kanki, JP D'Andrea, AD Look, AT TI Knockdown of zebrafish Fancd2 causes developmental abnormalities via p53-dependent apoptosis SO DEVELOPMENTAL CELL LA English DT Article ID EMBRYONIC CELLULAR PROLIFERATION; FANCONI-ANEMIA PROTEIN; TARGETED DISRUPTION; POSITIONAL CLONING; MORPHOLINO OLIGOS; HUMAN-DISEASE; DNA-REPAIR; GENE LEADS; BRCA1; MODEL AB Mechanisms underlying the multiple developmental defects observed in Fanconi anemia (FA) patients are not well defined. We have identified the zebrafish homolog of human FANCD2, which encodes a nuclear effector protein that is monoubiquitinated in response to DNA damage, targeting it to nuclear foci where it preserves chromosomal integrity. Fancd2-deficient zebrafish embryos develop defects similar to those found in children with FA, including shortened body length, microcephaly, and microophthalmia, which are due to extensive cellular apoptosis. Developmental defects and increased apoptosis in Fancd2-deficient zebrafish were corrected by injection of human FANCD2 or zebrafish bcl2 mRNA, or by knockdown of p53, indicating that in the absence of Fancd2, developing tissues spontaneously undergo p53-dependent apoptosis. Thus, Fancd2 is essential during embryogenesis to prevent inappropriate apoptosis in neural cells and other tissues undergoing high levels of proliferative expansion, implicating this mechanism in the congenital abnormalities observed in human infants with FA. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 56 TC 63 Z9 67 U1 2 U2 11 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD DEC PY 2003 VL 5 IS 6 BP 903 EP 914 DI 10.1016/S1534-5807(03)00339-3 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 757BE UT WOS:000187528300011 PM 14667412 ER PT J AU Payne-Ferreira, TL Yelick, PC AF Payne-Ferreira, TL Yelick, PC TI Alk8 is required for neural crest cell formation and development of pharyngeal arch cartilages SO DEVELOPMENTAL DYNAMICS LA English DT Article DE neural crest cells; BMP gradients; embryonic patterning; alk8; pharyngeal arch cartilages; TGF-beta signaling ID SERINE/THREONINE KINASE RECEPTOR; DORSOVENTRAL PATTERN-FORMATION; BONE MORPHOGENETIC PROTEIN-4; ZEBRAFISH EMBRYO; TGF-BETA; TRANSGENIC ZEBRAFISH; LINEAGE RESTRICTIONS; XENOPUS EMBRYOS; QUAIL EMBRYO; BMP ACTIVITY AB The type I TGFbeta family member receptor alk8 acts in bone morphogenetic protein (BMP) signaling pathways to establish dorsoventral patterning in the early zebrafish embryo. Here, we present evidence that alk8 is required for neural crest cell (NCC) formation and that alk8 signaling gradients direct the proper patterning of premigratory NCCs. We extend our previous functional studies of alk8 to demonstrate that ectopic expression of constitutively active and dominant negative AM, consistently results in more medially or laterally positioned premigratory NCCs, respectively. We also demonstrate that patterning defects in premigratory NCCs, induced by alk8 misexpression, correlate with subsequent defects in NCC-derived pharyngeal arch cartilages. Furthermore, an anteroposterior effect is revealed, where overexpression of Alk8 more severely affects anterior arch cartilages and decreased Alk8 activity more severely affects posterior arch cartilage formation. Ectopic expression studies of alk8 are supported by analyses of zygotic and maternal-zygotic laf/alk8 mutants and of several BMP pathway mutants. Pharyngeal mesodermal and endodermal defects in laf/alk8 mutants suggest additional roles for alk8 in patterning of these tissues. Our results provide insight into alk8-mediated BMP signaling gradients and the establishment of premigratory NCC mediolateral positioning, and extend the model for BMP patterning of the neural crest to include that of NCC-derived pharyngeal arch cartilages. (C) 2003 Wiley-Liss, Inc. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Craniofacial & Dev Biol, Boston, MA 02138 USA. RP Yelick, PC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE12076, DE12024, DE05736] NR 74 TC 14 Z9 14 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD DEC PY 2003 VL 228 IS 4 BP 683 EP 696 DI 10.1002/dvdy.10417 PG 14 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 749WY UT WOS:000186954100013 PM 14648845 ER PT J AU Khaodhiar, L Niemi, JB Earnest, R Lima, C Harry, JD Veves, A AF Khaodhiar, L Niemi, JB Earnest, R Lima, C Harry, JD Veves, A TI Enhancing sensation in diabetic neuropathic foot with mechanical noise SO DIABETES CARE LA English DT Article ID STOCHASTIC RESONANCE; OLDER ADULTS; TACTILE SENSATION; MECHANORECEPTORS; MULTICENTER; PREVENTION; ULCERS; RISK AB OBJECTIVE - Localized low-level mechanical or electrical noise call significantly enhance tactile sensitivity in healthy young subjects and older adults. This phenomenon is termed stochastic resonance (SR). In this study, we examined the effect of SR on vibratory and tactile sersation in patients with moderate to severe diabetic peripheral neuropathy. RESEARCH DESIGN AND METHODS - A total of 20 subjects were included in the Study. The vibration perception threshold (VPT) test and the Semmes-Weinstein filament (SWF) threshold at the plantar surface of the left foot and the big toe were determined under two mechanical noise Stimulus conditions: null (no noise) condition and at 10% lower than each subject's mechanical noise threshold of perception. RESULTS - The baseline values (mean +/- SD) were as follows Neuropathy Symptom Score (NSS) 5.2 +/- 2.5, Neuropathy Disability Score (NDS) 5.0 +/- 2.1, VPT 24 +/- 11 V, and SWF threshold 5.6 +/- 0.8 at the plantar surface of the foot and 5.3 +/- 0.9 at the big Lee. The VPT improved significantly from 24 +/- 11 under null condition to 1.9 +/- 10 with mechanical noise(P < 0.0001). Mechanical noise also significantly increased the number of detections of the SWF at the plantar surface of the feet (detection rate 66 +/- 11 vs. 59 +/- 15%, P < 0.02) but not at the, big toe (63 +/- 10 vs. 61 +/- 16%, P = NS). CONCLUSIONS - Mechanical noise stimulation improves vibration and tactile perception in diabetic patients with moderate to severe neuropathy. Additional studies are required to examine the effect of long-term noise stimulation on parameters of nerve function. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Joslin Beth Israel Deaconess Foot Ctr, Dept Med, Boston, MA 02215 USA. Joslin Beth Israel Deaconess Foot Ctr, Dept Surg, Boston, MA 02215 USA. Afferent Corp, Providence, RI USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,1 Deaconess Rd, Boston, MA 02215 USA. EM Aveves@bidmc.harvard.edu FU NIDDK NIH HHS [R43-DK-60295-01] NR 24 TC 18 Z9 18 U1 1 U2 4 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 DEC PY 2003 VL 26 IS 12 BP 3280 EP 3283 DI 10.2337/diacare.26.12.3280 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746AM UT WOS:000186724000012 PM 14633814 ER PT J AU Rasmussen, DD AF Rasmussen, DD TI Chronic daily ethanol and withdrawal - 5. Diurnal effects on plasma thyroid hormone levels SO ENDOCRINE LA English DT Article DE alcohol; ethanol; thyroid; T3; T4; TSH; diurnal ID LONG-TERM CHANGES; GENE-EXPRESSION; ALCOHOL INTAKE; AXIS; DEPRESSION; RATS; TRH; HYPOTHYROIDISM; STIMULATION; INHIBITION AB We previously demonstrated that chronic daily ethanol consumption and daily withdrawal by male rats in a modified ethanol liquid diet paradigm produced (a) chronically increased adrenal glucocorticoid activity; (b) decreased plasma testosterone; (c) decreased fore-brain proopiomelanocortin gene expression; and (d) corresponding alterations in plasma leptin levels-all of which are consistent with reported changes during alcohol abuse and alcoholism. Each of these systems interact with hypothalamo-pituitary-thyroid (HPT) regulation, and links between chronic alcohol abuse and thyroid dysfunction have been suggested by both human and rat studies. Accordingly, we have begun to investigate potential HPT mediation of, or response to, alterations in these systems by investigating plasma thyroid hormone levels in the same chronic daily ethanol/withdrawal paradigm. Chronic daily episodes of ethanol consumption and withdrawal by male Sprague-Dawley rats decreased plasma levels of free (non-protein-bound) triiodothyronine (T3) (p < 0.01) and free thyroxine (T4) (p < 0.05) in the morning but not in the afternoon, relative to both ad libitum-fed and pair-fed controls (n = 9/treatment). Plasma total T4 levels were likewise suppressed (p < 0.01) in the morning, whereas total T3 levels were increased (p < 0.05) in the afternoon. These changes eliminated normal diurnal patterns (higher in the morning) of plasma free T3, free T4, and total T3 concentrations. Three weeks after cessation of ethanol consumption, morning plasma levels of free and total T3 and T4, as well as plasma thyroid-stimulating hormone (TSH), were all not significantly changed by the prior ethanol consumption or pair-feeding. These results reveal that plasma thyroid hormone concentrations are suppressed in a time of day dependent manner by chronic daily ethanol consumption and daily withdrawal in this model of chronic ethanol abuse. During subsequent long-term "abstinence," these thyroid hormones returned to control levels. These results are consistent with evidence that thyroid function is commonly diminished in alcoholism, with variable reports of recovery during abstinence. Further investigations with this rat model of daily ethanol consumption and daily withdrawal will help resolve interactions and roles of the HPT axis in alcohol abuse. C1 VA Puget Sound Hlth Care Syst, VA Med Ctr, MIRECC S116, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Rasmussen, DD (reprint author), VA Puget Sound Hlth Care Syst, VA Med Ctr, MIRECC S116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM drasmuss@u.washington.edu FU NIAAA NIH HHS [AA 10567] NR 27 TC 6 Z9 6 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD DEC PY 2003 VL 22 IS 3 BP 329 EP 334 DI 10.1385/ENDO:22:3:329 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 766YW UT WOS:000188412200016 PM 14709806 ER PT J AU Demay, M AF Demay, M TI Muscle: A nontraditional 1,25-dihydroxyvitamin D target tissue exhibiting classic hormone-dependent vitamin D receptor actions SO ENDOCRINOLOGY LA English DT Editorial Material ID MINERAL ION HOMEOSTASIS; KNOCKOUT MICE; ABLATED MICE; ALOPECIA; DIFFERENTIATION; EXPRESSION; RICKETS; SYSTEM C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Demay, M (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 501,50 Blossom St, Boston, MA 02114 USA. NR 19 TC 27 Z9 27 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD DEC 1 PY 2003 VL 144 IS 12 BP 5135 EP 5137 DI 10.1210/en.2003-1096 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746WZ UT WOS:000186771800001 PM 14645209 ER PT J AU Williams, DL Grill, HJ Cummings, DE Kaplan, JM AF Williams, DL Grill, HJ Cummings, DE Kaplan, JM TI Vagotomy dissociates short- and long-term controls of circulating ghrelin SO ENDOCRINOLOGY LA English DT Article ID ACYLATED PEPTIDE; ACTIVE FORM; SECRETION; RATS; ENDOCRINE; ANOREXIA; FEEDBACK; AFFERENT; STOMACH; NEURONS AB Plasma ghrelin levels are responsive to short- and long-term nutrient fluctuation, rapidly decreasing with food consumption and increasing with food deprivation or weight loss. We hypothesized a vagal contribution to both responses. Nutrient-related ghrelin suppression may be mediated by gastrointestinal load-related vagal afferent activity, or depend upon vagal efferent input to the foregut, where most ghrelin is produced. Similarly, the deprivation-induced ghrelin rise could require state-related vagal afferent or efferent activity. Here, we examined the role of the vagus nerve in the regulation of plasma ghrelin by sampling blood from rats with subdiaphragmatic vagotomy and from sham-operated controls over 48 h of food deprivation, and before and after gastric gavage of liquid diet. Vagotomy affected neither baseline ghrelin levels nor the suppression of ghrelin by a nutrient load. The food deprivation-induced elevation of plasma ghrelin levels ( similar to 160% of baseline), however, was completely prevented by subdiaphragmatic vagotomy. In a separate experiment, the deprivation-related rise in plasma ghrelin was substantially reduced by atropine methyl nitrate treatment, indicating that the response to fasting is driven by increased vagal efferent tone. The dissociation between nutrient load- and deprivation-related ghrelin responses indicates that the regulation of circulating ghrelin levels involves separate mechanisms operating through anatomically distinct pathways. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, Seattle, WA 98108 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. RP Williams, DL (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Dept Med, 1660 S Columbian Way,Mail Stop 111-ENDO, Seattle, WA 98108 USA. RI Williams, Diana/C-1699-2014 OI Williams, Diana/0000-0002-3548-7440 FU NIDDK NIH HHS [DK-61516, DK-21397, DK-42284] NR 22 TC 159 Z9 165 U1 1 U2 2 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 DEC 1 PY 2003 VL 144 IS 12 BP 5184 EP 5187 DI 10.1210/en.2003-1059 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 746WZ UT WOS:000186771800009 PM 14525914 ER PT J AU Maganti, R Rutecki, P Bell, B Woodard, A Jones, JC Ramirez, L Iskandar, B AF Maganti, R Rutecki, P Bell, B Woodard, A Jones, JC Ramirez, L Iskandar, B TI Epilepsy surgery outcome among US veterans SO EPILEPSY & BEHAVIOR LA English DT Article DE temporal lobectomy; outcome; quality of life; employment outcome ID TEMPORAL-LOBE EPILEPSY; QUALITY-OF-LIFE; REFRACTORY EPILEPSY; INTRACTABLE EPILEPSY; LOBECTOMY; SEIZURES; MULTIVARIATE; RESECTION AB We retrospectively studied the outcome of anterior temporal lobectomy (ATL) among a population of veterans and evaluated outcome related to comorbidities. Veterans who underwent ATL between 1990 and 2001 at the Veterans Administration Hospital in Madison, Wisconsin. were included. Data related to postoperative seizure outcome, quality of life outcome, and employment outcome were collected. Factors associated with favorable outcome and outcome related to comorbidities were evaluated. Twenty-seven patients were entered into the study. The mean age at onset of seizures was 25 years (+/-10.2). History of a non-substance abuse psychiatric diagnosis, and substance abuse was present in 26% (7/27) and 30% (9/27), respectively, prior to surgery. While 66.6% (18/27) had a good outcome (Engel's Class 1), no difference in the frequency of good outcome was seen among the patients with a history of substance abuse, other psychiatric diagnosis (71%), or no psychiatric diagnosis (67%). There was a significant correlation between seizure outcome and quality of life score (r(s) = 0.67, p < 0.001) and postoperative employment gains (r(s) = 0.48, p = 0.01). Outcomes among veterans that underwent ATL can be satisfactory even in the context of the late mean age of epilepsy onset and the psychiatric diagnoses that were present in this sample. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Neurol, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53792 USA. Univ Wisconsin, Dept Neurosurg, Madison, WI 53792 USA. RP Maganti, R (reprint author), Univ Wisconsin, Dept Neurol, Madison, WI 53792 USA. NR 28 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD DEC PY 2003 VL 4 IS 6 BP 723 EP 728 DI 10.1016/j.yebeh.2003.08.026 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 753RA UT WOS:000187243300018 PM 14698707 ER PT J AU de Groot, M Welch, G Buckland, GT Fergus, M Ruggiero, L Chipkin, SR AF de Groot, M Welch, G Buckland, GT Fergus, M Ruggiero, L Chipkin, SR TI Cultural orientation and diabetes self-care in low-income African Americans with type 2 diabetes mellitus SO ETHNICITY & DISEASE LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-of-Behavioral-Medicine CY APR 05-08, 2000 CL NASHVILLE, TN SP Soc Behav Med DE African-American; diabetes mellitus; acculturation ID STAGE RENAL-DISEASE; ETHNIC-DIFFERENCES; PHYSICAL-ACTIVITY; GLYCEMIC CONTROL; ADULTS; NIDDM; RISK; ACCULTURATION; NEPHROPATHY; AMPUTATIONS AB Objectives: The purpose of the study was to examine the relationships between cultural variables and diabetes self-care behaviors and glycemic control among African Americans with type 2 diabetes. Design: Cross-sectional survey. Methods: Questionnaires assessing traditional African-American cultural orientation, ethnic identity, self-identification, and diabetes selfcare were administered to a sample of 94 low-income, African-American, inner-city hospital outpatients with type 2 diabetes. Participants were predominantly female (64%), with an average age of 53 years, and most had attained less than or equal to a high school education (66%). Results: No significant relationships were found among ethnic identity, self-identification, glycemic control, and diabetes self-care behaviors. Traditional African-American cultural orientation was significantly associated with decreased dietary adherence scores (P<.03). Increased scores on cultural mistrust were related to decreased dietary adherence scores (P<.002). Traditional food practices showed a non-significant trend toward decreased dietary adherence in conjunction with number of dependents and income (P<.055). Conclusions: Traditional African-American cultural orientation was found to be associated with decreased dietary adherence scores in a sample of urban African Americans with type 2 diabetes. Assessment of the cultural orientation of African-American patients has the potential to assist providers in designing Culturally tailored, diabetes-specific dietary interventions. C1 Univ Rhode Isl, Dept Psychol, Kingston, RI 02881 USA. Joslin Diabet Ctr, Div Behav & Mental Hlth, Boston, MA 02215 USA. Boston Univ, Div Endocrinol Diabet & Nutr, Sch Med, Boston, MA 02215 USA. Baystate Med Ctr, Div Endocrinol Diabet & Metab, Springfield, MA USA. RP de Groot, M (reprint author), Ohio Univ, Dept Psychol, Porter Hall 239, Athens, OH 45701 USA. EM degroot@ohio.edu OI Chipkin, Stuart/0000-0003-2114-9480 FU NCRR NIH HHS [M01-RR00533]; NHLBI NIH HHS [5 T32 HL07456-18]; NIDDK NIH HHS [R01-DK48122] NR 41 TC 14 Z9 14 U1 0 U2 4 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD WIN PY 2003 VL 13 IS 1 BP 6 EP 14 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 802ML UT WOS:000220167500002 PM 12723006 ER PT J AU Shen, KZ Zhu, ZT Munhall, A Johnson, SW AF Shen, KZ Zhu, ZT Munhall, A Johnson, SW TI Dopamine receptor supersensitivity in rat subthalamus after 6-hydroxydopamine lesions SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE basal ganglia; GABA; glutamate; Parkinson's disease; presynaptic inhibition ID NEURONS IN-VITRO; NIGRA PARS RETICULATA; NUCLEUS NEURONS; MESSENGER-RNA; HORSERADISH-PEROXIDASE; NIGROSTRIATAL LESIONS; BASAL GANGLIA; TRANSMISSION; BRAIN; STIMULATION AB The subthalamic nucleus (STN) receives direct dopaminergic innervation from the substantia nigra pars compacta, but the importance of this input in the pathophysiology of parkinsonism remains to be determined. We used whole-cell patch-clamp recordings in brain slices to study presynaptic dopaminergic modulation of synaptic inputs to the STN in unilateral 6-hydroxydopamine (6-OHDA)-lesioned rats. Here, we report that dopamine was more potent for inhibiting GABA IPSCs and glutamate EPSCs in the STN ipsilateral to the lesion, and was less potent for suppressing IPSCs and EPSCs in the STN contralateral to the lesion, compared with the effects of dopamine in control STN. Dopamine reduced IPSCs with an IC50 value of 20.9 +/- 3.6 mum in control STN, whereas IC50 values were 0.83 +/- 0.15 and 55.1 +/- 11.1 mum in STN ipsilateral and contralateral to 6-OHDA lesions, respectively. Dopamine also inhibited EPSCs with an IC50 value of 12.8 +/- 2.8 mum in control STN, whereas IC50 values were 4.5 +/- 0.9 and 41.6 +/- 9.8 mum in STN ipsilateral and contralateral to 6-OHDA lesions, respectively. Results with paired stimuli to evoke EPSCs and IPSCs suggest that endogenous dopamine acts presynaptically to inhibit transmitter release in the STN. These results show that chronic dopamine denervation significantly alters the regulation of synaptic input to the STN. Our results also suggest that the STN may be an important target for levodopa therapy in Parkinson's disease. C1 Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97239 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NINDS NIH HHS [NS38175] NR 51 TC 19 Z9 20 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD DEC PY 2003 VL 18 IS 11 BP 2967 EP 2974 DI 10.1046/j.1460-9568.2003.03058.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 750PZ UT WOS:000187006400006 PM 14656292 ER PT J AU Kalra, MK Maher, MM Saini, S AF Kalra, MK Maher, MM Saini, S TI Multislice CT: update on radiation and screening SO EUROPEAN RADIOLOGY LA English DT Article; Proceedings Paper CT 4th Bracco Symposium on Multidetector-Row Computed Tomography CY MAY 09-10, 2003 CL FRANKFURT, GERMANY DE multislice CT; radiation; CT dose estimation ID NOISE-REDUCTION FILTERS; LOW-DOSE CT; COMPUTED-TOMOGRAPHY; PRACTICAL APPROACH; ONLINE MODULATION; IMAGE QUALITY; PEDIATRIC CT; TUBE CURRENT; CANCER; COLONOGRAPHY AB With ever-expanding applications, increasing availability, and accessibility of CT scanners, concerns have been raised about radiation exposure associated with CT scanning. Global statistics and projections suggest increasing use of CT scanning and its contribution to radiation exposure is a cause for concern. Several strategies based on modulation of scanning parameters and technologic improvisations have been developed in an effort to reduce associated radiation dose. This article discusses the basis for rising concern regarding radiation dose associated with CT scanning. The fundamentals of CT dose estimation are described along with strategies that aim to reduce radiation dose associated with CT scanning based on patient characteristics, study indications, and technological innovations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Div Abdominal Imaging & Intervent, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM ssaini@partners.org NR 31 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0938-7994 EI 1432-1084 J9 EUR RADIOL JI Eur. Radiol. PD DEC PY 2003 VL 13 SU 5 BP M129 EP M133 DI 10.1007/s00330-003-2107-1 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 773BL UT WOS:000188877800021 PM 14989623 ER PT J AU Saini, S Dsouza, RV AF Saini, S Dsouza, RV TI Optimizing technique for multi-slice CT SO EUROPEAN RADIOLOGY LA English DT Article; Proceedings Paper CT 4th Bracco Symposium on Multidetector-Row Computed Tomography CY MAY 09-10, 2003 CL FRANKFURT, GERMANY ID CONCENTRATION CONTRAST-MEDIA; COMPUTED-TOMOGRAPHY; HELICAL CT; SPIRAL CT; SINGLE; PRINCIPLES; RATIONALE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Saini, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, White 270-E,55 Fruit St, Boston, MA 02114 USA. EM saini.sanjay@mgh.harvard.edu NR 18 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD DEC PY 2003 VL 13 SU 5 BP M21 EP M24 DI 10.1007/s00330-003-2098-y PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 773BL UT WOS:000188877800005 PM 14989607 ER PT J AU Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW AF Song, MK Hwang, IK Rosenthal, MJ Harris, DM Yamaguchi, DT Yip, I Go, VLW TI Anti-hyperglycemic activity of zinc plus cyclo (his-pro) in genetically diabetic Goto-Kakizaki and aged rats SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE cyclo (his-pro); zinc; Goto-Kakizaki rats; diabetes mellitus; glucose uptake; aged rats ID THYROTROPIN-RELEASING-HORMONE; HUMAN SKELETAL-MUSCLE; INSULIN-RECEPTOR KINASE; ARACHIDONIC-ACID; CYCLO(HIS-PRO) LEVELS; DEFICIENT MICE; ORAL GLUCOSE; MELLITUS; RESISTANCE; TRANSPORT AB We previously reported that treatment of streptozotocin-induced diabetic rats with zinc plus cyclo (his-pro) (CHP) decreased fed blood glucose levels and water intake. The present study was conducted to examine the dose-dependent, acute, and chronic treatment effects of CHP on oral glucose tolerance (OGT), fed blood glucose levels, water intake, and plasma insulin levels in young and aged Sprague-Dawley (S-D) rats, nondiabetic Wistar rats, and genetically diabetic Goto-Kakizaki (GK) rats. Acute gastric gavage of 10 mg zinc plus 1.0 mg CHP/kg body weight significantly improved OGT in 4- and 13-month-old nondiabetic S-D rats and in 2-month-old diabetic G-K rats. Young S-D and G-K rats returned to pretreatment OGT values 1 week after acute gavage of zinc plus CHP (ZC), but improved OGT values persisted for at least 1 week after gavage in aged S-D rats. OGT values and fed blood glucose decreased to the greatest extent among other treatments when G-K rats were given free access to drinking water containing 1.0 to 1.5 mg CHP/L plus 10 mg zinc/L for 2 weeks. Although food and water intake showed a tendency to decrease, no statistically significant differences were observed in young G-K rats. Plasma insulin levels and blood glucose levels in both normal and diabetic G-K rats decreased with 2-week treatment with ZC. To test the direct effects of ZC on muscle tissue, we observed the effect of various doses of ZC on normal and G-K rat muscle slices. The optimal level of CHP alone for maximal muscle glucose uptake in muscle slices from normal rats was 10 mug/mL and 5.0 mug/mL in G-K rats, and ZC stimulated glucose uptake. However, no statistically significant difference was demonstrated between normal and G-K rat tissues in this study. These results indicate that oral intake of an optimal dose of ZC stimulates blood glucose metabolism, probably by stimulating muscle glucose utilization. C1 Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Harris, DM (reprint author), Univ Calif Los Angeles, Ctr Human Nutr, David Geffen Sch Med, 13-145 Warren Hall, Los Angeles, CA 90095 USA. EM dmharris@ucla.edu FU NIDDK NIH HHS [1 R43 DK 56546-01] NR 37 TC 52 Z9 53 U1 0 U2 3 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD DEC PY 2003 VL 228 IS 11 BP 1338 EP 1345 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 833FG UT WOS:000222321300012 PM 14681549 ER PT J AU Brown, MC de Venecia, RK Guinan, JJ AF Brown, MC de Venecia, RK Guinan, JJ TI Responses of medial olivocochlear neurons - Specifying the central pathways of the medial olivocochlear reflex SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Scientific Meeting on Central Auditory Processing - Integration with Other Systems CY MAY, 2002 CL STEFANO FRANSCINI FDN, CONF CTR, ASCONA, SWITZERLAND HO STEFANO FRANSCINI FDN, CONF CTR DE interneuron; cochlea; outer hair cell; cochlear nucleus; auditory nerve ID VENTRAL COCHLEAR NUCLEUS; AUDITORY-NERVE FIBERS; PIG SPIRAL GANGLION; MIDDLE-EAR REFLEX; GUINEA-PIG; HORSERADISH-PEROXIDASE; EFFERENT NEURONS; ELECTRICAL-STIMULATION; STAPEDIUS MOTONEURONS; CAT AB Medial olivocochlear (MOC) neurons project to outer hair cells (OHC), forming the efferent arm of a reflex that affects sound processing and offers protection from acoustic overstimulation. The central pathways that trigger the MOC reflex in response to sound are poorly understood. Insight into these pathways can be obtained by examining the responses of single MOC neurons recorded from anesthetized guinea pigs. Response latencies of MOC neurons are as short as 5 ms. This latency is consistent with the idea that type I, but not type II, auditory-nerve fibers provide the major inputs to the reflex interneurons in the cochlear nucleus. This short latency also implies that the cochlear-nucleus interneurons have rapidly conducting axons. In the cochlear nucleus, lesions of the posteroventral subdivision (PVCN), but not the anteroventral (AVCN) or dorsal (DCN) subdivisions, produce permanent disruption of the MOC reflex, based on a metric of adaptation of the distortion-product otoacoustic emission (DPOAE). This finding supports earlier anatomical results demonstrating that some PVCN neurons project to MOC neurons. Within the PVCN, there are two general types of units when classified according to poststimulus time histograms: onset units and chopper units. The MOC response is sustained and cannot be produced solely by inputs having an onset pattern. The MOC reflex interneurons are thus likely to be chopper units of PVCN. Also supporting this conclusion, chopper units and MOC neurons both have sharp frequency tuning. Thus, the most likely pathway for the sound-evoked MOC reflex begins with the responses of hair cells, proceeds with type I auditory-nerve fibers, PVCN chopper units, and MOC neurons, and ends with the MOC terminations on OHC. C1 Massachusetts Eye Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Brown, MC (reprint author), Massachusetts Eye Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcb@epl.meei.harvard.edu FU NIDCD NIH HHS [DC 01089, DC 0119] NR 62 TC 23 Z9 24 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD DEC PY 2003 VL 153 IS 4 BP 491 EP 498 DI 10.1007/s00221-003-1679-y PG 8 WC Neurosciences SC Neurosciences & Neurology GA 746JJ UT WOS:000186743000012 PM 14557911 ER PT J AU Levine, RA Abel, M Cheng, H AF Levine, RA Abel, M Cheng, H TI CNS somatosensory-auditory interactions elicit or modulate tinnitus SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Scientific Meeting on Central Auditory Processing - Integration with Other Systems CY MAY, 2002 CL STEFANO FRANSCINI FDN, CONF CTR, ASCONA, SWITZERLAND HO STEFANO FRANSCINI FDN, CONF CTR DE tinnitus; somatosensory; auditory; muscle spindle; cochlear nucleus ID INFERIOR COLLICULUS; NUCLEUS; CAT AB Evidence has accumulated linking clinical tinnitus to the somatosensory system. Most clinical tinnitus patients can change the psychoacoustic attributes of their tinnitus with forceful head and neck contractions. The significance of such somatic modulation of tinnitus was assessed by testing non-clinical subjects. Like clinical tinnitus patients, about 80% of non-clinical subjects who had ongoing tinnitus at the time of testing (whether or not they had been previously aware of it) could modulate their tinnitus with head and neck contractions. Almost 60% of those with no tinnitus at the time of testing could elicit a tinnitus-like auditory percept with head and neck contractions. Because similar results were found in the profoundly deaf, we conclude that somatosensory-auditory interactions within the central nervous system account for most, if not all, somatic modulation of tinnitus as well as the development of auditory percepts with somatic testing. Other observations implicate the muscle spindle as initiating the neural activation that ultimately modulates the central auditory pathway, including the dorsal cochlear nucleus. Somatic influences upon auditory perception are not limited to tinnitus subjects but are a fundamental property of the auditory system. C1 Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Harvard Dent Sch, MIT,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU Action on Hearing Loss [G8] NR 14 TC 82 Z9 91 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD DEC PY 2003 VL 153 IS 4 BP 643 EP 648 DI 10.1007/s00221-003-1747-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 746JJ UT WOS:000186743000027 PM 14600798 ER PT J AU Hussein, MR Wood, GS AF Hussein, MR Wood, GS TI hMLH1 and hMSH2 gene mutations are present in radial growth-phase cutaneous malignant melanoma cell lines and can be induced further by ultraviolet-B irradiation SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE CMM; cutaneous malignant melanomas; PCR; polymerase chain reaction; MMR; mismatch repair gene ID NONPOLYPOSIS COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; MISMATCH REPAIR; DYSPLASTIC NEVI; DNA DAMAGE; SKIN; METALLOTHIONEIN; REPLICATION; FIBROBLASTS; EXPRESSION AB Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about the mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for mutational changes of exon regions 13, 16 and 19 (hMLH1) and 6, 7 and 12 (hMSH2) of these genes before and after irradiation. The genomic DNAs were PCR amplified and the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and transversion (G-->T, A-->T) mutations were found in exons 6, 16 and 19. Some were present in both the sham-irradiated and UV-irradiated cells but others were only detected after UVB irradiation. hMLH1 and hMSH2 gene mutations occur early in melanoma tumorigenesis. The ability of UVB irradiation to induce additional mutations in these repair genes suggests its possible role in melanoma pathogenesis. Further investigation will be needed to determine whether mutations such as these contribute to the development of microsatellite instability in melanoma. C1 Univ Wisconsin, Dept Dermatol, Madison, WI 53715 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Wood, GS (reprint author), Univ Wisconsin, Dept Dermatol, 1 S Pk,7th Floor, Madison, WI 53715 USA. FU NIAMS NIH HHS [AR02136] NR 21 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD DEC PY 2003 VL 12 IS 6 BP 872 EP 875 DI 10.1111/j.0906-6705.2003.00104.x PG 4 WC Dermatology SC Dermatology GA 753XY UT WOS:000187274700018 PM 14714570 ER PT J AU Natsume, A Wolfe, D Hu, J Huang, SH Puskovic, V Glorioso, JC Fink, DJ Mata, M AF Natsume, A Wolfe, D Hu, J Huang, SH Puskovic, V Glorioso, JC Fink, DJ Mata, M TI Enhanced functional recovery after proximal nerve root injury by vector-mediated gene transfer SO EXPERIMENTAL NEUROLOGY LA English DT Article DE gene therapy; HSV; nerve crush; spinal injuries; apoptosis; Bcl-2; GDNF ID WALKING TRACK ANALYSIS; INDUCED CELL-DEATH; MICE LACKING GDNF; MOTOR-NEURONS; NEUROTROPHIC FACTOR; PERIPHERAL-NERVE; SCIATIC-NERVE; PROTOONCOGENE BCL-2; EXPRESSION; APOPTOSIS AB In order to test the functional implication of herpes simplex virus (HSV) vector-mediated gene transfer after axonal injury, we injected replication-incompetent HSV vectors coding for the anti-apoptotic peptide Bcl-2 and the glial cell-derived neurotrophic factor (GDNF), separately or in combination into ventral spinal cord 30 min after a crush injury to the proximal spinal root that was combined with moderate mechanical traction. HSV-mediated expression of Bcl-2 or GDNF enhanced functional recovery assessed by histologic, electrophysiologic, and behavioral parameters up to 5 months after injury. The most sensitive measure of distal motor function, the sciatic function index, was significantly improved in animals injected with the two vectors together. These results suggest an approach to root trauma that might be used to enhance functional recovery after injury. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15217 USA. Univ Pittsburgh, Dept Mol Genet & Biochem, Pittsburgh, PA 15217 USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA 15217 USA. RP Fink, DJ (reprint author), Univ Pittsburgh, Dept Neurol, S-521 ST,200 Lothrop St, Pittsburgh, PA 15217 USA. RI Natsume, Atsushi/I-7364-2014 OI Natsume, Atsushi/0000-0002-9113-0470 NR 40 TC 15 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD DEC PY 2003 VL 184 IS 2 BP 878 EP 886 DI 10.1016/S0014-4886(03)00334-0 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 758KW UT WOS:000187634400034 PM 14769380 ER PT J AU Panigrahy, D Shen, LQ Kieran, MW Kaipainen, A AF Panigrahy, D Shen, LQ Kieran, MW Kaipainen, A TI Therapeutic potential of thiazolidinediones as anticancer agents SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE angiogenesis; apoptosis; cancer; differentiation; growth inhibition; PPAR-gamma; TZDs ID ACTIVATED-RECEPTOR-GAMMA; HUMAN PROSTATE-CANCER; RETINOID-X-RECEPTOR; INHIBIT CELL-GROWTH; HUMAN BREAST-CANCER; PPAR-GAMMA; CARCINOMA-CELLS; IN-VITRO; GENE-EXPRESSION; GASTRIC-CANCER AB Thiazolidinediones (TZDs) are synthetic ligands; that activate the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These compounds are widely used in the treatment of Type 2 diabetes. TZDs have antitumour activity in a wide variety of experimental cancer models, in vitro and in vivo, by affecting the cell cycle, induction of cell differentiation and apoptosis as well as by inhibiting tumour angiogenesis. These effects are mediated through both PPAR-gamma-dependent and -independent pathways depending on concentration and tumour cell type. Angiogenesis inhibition mechanisms of TZDs include directly inhibiting endothelial cell proliferation and migration as well as decreasing tumour cell vascular endothelial growth factor production. Further studies suggest that TZDs may be effective in prevention of certain cancers and in the treatment of cancer as adjuvant therapy. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kaipainen, A (reprint author), Childrens Hosp, 300 Longwood Ave,Res Bldg,Floor 12, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 153 TC 58 Z9 61 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD DEC PY 2003 VL 12 IS 12 BP 1925 EP 1937 DI 10.1517/13543784.12.12.1925 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758LH UT WOS:000187635500002 PM 14640937 ER PT J AU Porter, D Polyak, K AF Porter, D Polyak, K TI Cancer target discovery using SAGE SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE cancer; expression profile; molecular marker; oncogene; SAGE (Serial Analysis of Gene Expression); therapeutic targets; tumour suppressor ID METASTATIC BREAST-CANCER; CELL LUNG-CANCER; DIFFERENTIALLY EXPRESSED GENES; MAMMARY EPITHELIAL-CELLS; SCALE SERIAL ANALYSIS; OVARIAN-CANCER; DESMOPLASTIC RESPONSE; DNA HYPERMETHYLATION; PANCREATIC-CARCINOMA; MOLECULAR MARKERS AB Cancer is a genetic disease. Genetic events including mutations, chromosomal gains, losses and rearrangements, along with epigenetic alterations, lead to significant transcriptional changes in cancer cells. Changes in the expression of many genes associated with the onset and progression of cancer likely contribute to the cancerous phenotype. SAGE (Serial Analysis of Gene Expression) is an expression profiling method that allows for global, unbiased and quantitative characterisation of transcriptomes. The expression of thousands of genes can be analysed simultaneously without prior knowledge of their sequence, thus leading to the discovery of novel transcripts. In addition to characterising normal and malignant gene expression patterns, SAGE can be used to identify downstream targets of tumour suppressors and oncogenes; and further annotate genomes. Comprehensive analyses of expression profiles using SAGE will yield many new diagnostic and prognostic markers as well as therapeutic targets in cancer. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, 44 Binney St,D740C, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu NR 94 TC 7 Z9 10 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD DEC PY 2003 VL 7 IS 6 BP 759 EP 769 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 754LN UT WOS:000187318800006 PM 14640911 ER PT J AU Lok, ASF Lai, CL Leung, N Yao, GB Cui, ZY Schiff, ER Dienstag, JL Heathcote, EJ Little, NR Griffiths, DA Gardner, SD Castiglia, M AF Lok, ASF Lai, CL Leung, N Yao, GB Cui, ZY Schiff, ER Dienstag, JL Heathcote, EJ Little, NR Griffiths, DA Gardner, SD Castiglia, M TI Long-term safety of lamivudine treatment in patients with chronic hepatitis B SO GASTROENTEROLOGY LA English DT Article ID ADEFOVIR DIPIVOXIL; VIRUS; THERAPY; RESISTANCE; TRIAL; REPLICATION; MUTATIONS; INFECTION; VARIANTS AB Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of the lamivudine-treated patients in year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine resistance remained stable during the first 4 years with mutations and increased afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease. C1 Univ Michigan, Med Ctr, Div Gastroenterol, Taubman Ctr 3912, Ann Arbor, MI 48109 USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ Toronto, Univ Hlth Network, Toronto, ON, Canada. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Miami, Sch Med, Miami, FL USA. Beijing Ditan Hosp, Beijing, Peoples R China. Shanghai Jingan Qu Cent Hosp, Shanghai, Peoples R China. Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. Queen Mary Hosp, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. RP Lok, ASF (reprint author), Univ Michigan, Med Ctr, Div Gastroenterol, Taubman Ctr 3912, Box 0362, Ann Arbor, MI 48109 USA. RI Lok, Anna /B-8292-2009; Lai, Ching Lung/C-4298-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR01066]; NIAID NIH HHS [R43-AI-51919]; NIDDK NIH HHS [N01-DK-0-2319, N01-DK-9-2323, U01-DK-57577, U01-DK-62498] NR 27 TC 497 Z9 562 U1 3 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2003 VL 125 IS 6 BP 1714 EP 1722 DI 10.1053/S0016-5085(03)01529-4 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 752QA UT WOS:000187177600023 PM 14724824 ER PT J AU Lugea, A Gukovsky, I Gukovskaya, AS Pandol, SJ AF Lugea, A Gukovsky, I Gukovskaya, AS Pandol, SJ TI Nonoxidative ethanol metabolites alter extracellular matrix protein content in rat pancreas SO GASTROENTEROLOGY LA English Estonian DT Article ID ACID ETHYL-ESTERS; HEPATIC STELLATE CELLS; NECROSIS-FACTOR-ALPHA; FAT-STORING CELLS; PLASMINOGEN-ACTIVATOR; GENE-EXPRESSION; ACINAR-CELLS; LIVER FIBROSIS; IN-VIVO; COLLAGEN AB Background & Aims: The mechanisms involved in ethanol-induced pancreas fibrosis are poorly understood. Here we show that fatty acid ethyl esters (FAEEs), nonoxidative ethanol metabolites, increase extracellular matrix (ECM) protein levels in pancreas. Methods: Rat pancreatic acini were incubated for 1-4 hours with FAEEs or acetaldehyde. In another set of experiments, rats received an intravenous infusion of FAEEs for 6 hours. Collagens were assessed by a hydroxyproline assay. Laminin and fibronectin were analyzed by Western blotting. Gene expression of ECM proteins was measured by conventional and real-time reverse-transcription polymerase chain reaction (RT-PCR). Matrix metalloproteinase (MMP), plasmin, and urokinase-type plasminogen activator (uPA) activities were determined by zymography and fluorogenic assays. Results: FAEEs increased Collagen, laminin, and fibronectin levels in pancreatic acini without affecting messenger RNA (mRNA) expression for these proteins. Actinomycin D, a transcriptional inhibitor, did not block the increase in ECM proteins induced by FAEEs. FAEEs reduced the activity of the serine protease, plasmin, and that of the uPA. Consistent with these results, the serine protease inhibitor aprotinin reproduced the effects of FAEEs and prevented the further increase in ECM proteins induced by FAEEs. In vivo administration of FAEEs reduced plasmin and uPA activities and increased ECM protein levels in pancreas. Acetaldehyde had minor effects on ECM protein levels and did not affect plasmin activity. Conclusions: FAEEs increase ECM protein levels in pancreas. The results suggest that this effect is caused primarily by an inhibition in ECM degradation via serine proteases including the plasminogen system. C1 Univ So Calif, Res Ctr Alcohol Liver & Pancreat Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Lugea, A (reprint author), Univ So Calif, Res Ctr Alcohol Liver & Pancreat Dis, Vet Affairs Greater Los Angeles Healthcare Syst, Bldg 258,Room 339,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIAAA NIH HHS [P50-AA11999] NR 68 TC 30 Z9 30 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD DEC PY 2003 VL 125 IS 6 BP 1845 EP 1859 DI 10.1053/S0016-5085(03)01508-7 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 752QA UT WOS:000187177600035 PM 14724836 ER PT J AU Bounds, BC Friedman, LS AF Bounds, BC Friedman, LS TI Lower gastrointestinal bleeding SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ARGON PLASMA COAGULATION; HEMORRHAGIC RADIATION PROCTITIS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ABDOMINAL AORTIC RECONSTRUCTION; CROHNS-DISEASE; VASCULAR ECTASIAS; NATURAL-HISTORY; LASER THERAPY; POSTPOLYPECTOMY HEMORRHAGE; INDUCED PROCTOSIGMOIDITIS AB Lower gastrointestinal bleeding is defined as blood loss that originates from a source distal to the ligament of Treitz and results in hemodynamic instability or symptomatic anemia. The annual incidence of lower gastrointestinal bleeding is approximately 0.03% in the adult population as a whole, with a greater than 200-fold increase from the second to the eighth decade [1,2]. This rise in incidence with age may be explained by the increasing prevalence of colonic diverticulosis and colonic angiodysplasia with age. The mean age of patients with lower gastrointestinal bleeding ranges from 63 to 77 years, with a reported mortality rate of 2% to 4% (Table 1) [2-7]. Although approximately 10% to 15% of patients presenting with acute severe hematochezia have an upper gastrointestinal source of bleeding identified on upper endoscopy, the most common causes of lower gastrointestinal bleeding are diverticulosis, hemorrhoids, ischemic colitis, and angiodysplasia [4,8-10]. As with upper gastrointestinal bleeding, lower gastrointestinal bleeding ceases spontaneously in most cases. Fig. 1 is an algorithm that shows diagnosis and treatment options for the patient presenting with acute severe hematochezia. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Newton Wellesley Hosp, Dept Med, Boston, MA 02114 USA. RP Bounds, BC (reprint author), Harvard Univ, Sch Med, Dept Med, 55 Fruit St,Blake 453C, Boston, MA 02114 USA. NR 108 TC 24 Z9 27 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8553 J9 GASTROENTEROL CLIN N JI Gastroenterol. Clin. North Am. PD DEC PY 2003 VL 32 IS 4 BP 1107 EP + DI 10.1016/S0889-8553(03)00086-4 PG 24 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 753WC UT WOS:000187253200005 PM 14696299 ER PT J AU Croker, BP Gilkeson, G Morel, L AF Croker, BP Gilkeson, G Morel, L TI Genetic interactions between susceptibility loci reveal epistatic pathogenic networks in murine lupus SO GENES AND IMMUNITY LA English DT Article DE lupus; genetics; epistasis; clinical heterogeneity; mice ID CONGENIC MOUSE STRAINS; YAA GENE; B-CELL; SLE PATHOGENESIS; T-CELL; ERYTHEMATOSUS; DISSECTION; MICE; COMPLEX; MODEL AB Interactions between Sle1 and other susceptibility loci were required for disease development in the NZM2410 model of lupus. Sle1 corresponds to at least three subloci, Sle1a, Sle1b, and Sle1c, each of which independently causes loss of tolerance to chromatin, but displays a distinctive immune profile. We have used congenic strains to analyze the interactions between the Sle1 subloci and other lupus susceptibility loci using Y autoimmunity accelerator (Yaa) and Fas(lpr) as sensitizing mutations. Sle1 coexpressed with either one of these single susceptibility alleles resulted in a highly penetrant nephritis, splenomegaly, production of nephrophilic antibodies, and increased expression of B- and T-cell activation markers. Here, we show that only Sle1b interacted with Yaa to produce these phenotypes, suggesting that Sle1b and Yaa belong to the same functional pathway. Interactions between the three Sle1 loci and lpr resulted in lymphocyte activation and lupus nephritis, but a significant mortality was observed only for the Sle1a. lpr combination. This suggests a major role for the FAS pathway in keeping in check the loss of tolerance mediated by the Sle1 loci, especially for Sle1a. Our results illustrate the complexity of interactions between susceptibility loci in polygenic diseases such as lupus and may explain the clinical heterogeneity of the disease. C1 Univ Florida, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. N Florida S George Vet Hlth Syst, Gainesville, FL USA. Ralph H Johnson Vet Affairs Med Coll, Med Res Serv, Charleston, SC USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Morel, L (reprint author), Univ Florida, Dept Pathol, Box 100275, Gainesville, FL 32610 USA. FU NIAID NIH HHS [AI-54054] NR 39 TC 35 Z9 35 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD DEC PY 2003 VL 4 IS 8 BP 575 EP 585 DI 10.1038/sj.gene.6364028 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 747HR UT WOS:000186799600007 PM 14647198 ER PT J AU Xu, RL Ogino, S Lip, V Fang, H Wu, BL AF Xu, RL Ogino, S Lip, V Fang, H Wu, BL TI Comparison of PCR-RFLP with allele-specific PCR in genetic testing for spinal muscular atrophy SO GENETIC TESTING LA English DT Article ID DIAGNOSIS; IDENTIFICATION; SMN1 AB PCR-based methods for the detection of homozygous deletion of exon 7 of the SMNI gene have been widely used in genetic testing for spinal muscular atrophy (SMA). We compared the most commonly used PCR-restriction fragment length polymorphism (PCR-RFLP) assay with an allele-specific PCR method, evaluating their potential application in direct testing, prenatal prediction, and preimplantation diagnosis, in terms of a range of DNA amounts used in such testing. We showed that PCR-RFLP could identify the SMN1 exon 7 by amplifying 10 pg of genomic DNA, and could differentiate SMNI from SMN2 at the 100-pg DNA level (DraI-digested SMN2 fragments served as an internal control for PCR efficiency). In contrast, allele-specific PCR for SMNI, despite some advantages in a rapid preimplantation diagnosis, quickly lost its specificity when 100 pg of genomic DNA was used. In addition, the absence of a SMNI fragment at the 10-pg DNA level may be due to a PCR amplification failure, and, thus, it is difficult to interpret without a proper internal control. Our data indicate that PCR-RFLP can be used for most diagnostic purposes, whereas the use of allele-specific PCR may be considered with caution under certain circumstances. C1 Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wu, BL (reprint author), Childrens Hosp, Dept Lab Med, 300 Longwood Ave, Boston, MA 02115 USA. EM bai-lin.wu@tch.harvard.edu OI xu, ruliang/0000-0002-9165-4610 NR 11 TC 9 Z9 12 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD WIN PY 2003 VL 7 IS 4 BP 277 EP 281 DI 10.1089/109065703322783626 PG 5 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 774WG UT WOS:000189008900001 PM 15000803 ER PT J AU Androudi, S Brazitikos, P Iaccheri, B Fiore, T Christen, W Meniconi, M Foster, CS AF Androudi, S Brazitikos, P Iaccheri, B Fiore, T Christen, W Meniconi, M Foster, CS TI Outcomes of early and late immunomodulatory treatment in patients with HLA-B27-associated chronic uveitis SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID ACUTE ANTERIOR UVEITIS; ANKYLOSING-SPONDYLITIS; CLINICAL-FEATURES; HLA-B27; ARTHRITIS; GLAUCOMA; EFFICACY; SAFETY; RISK; EYE AB Purpose: To evaluate the outcomes of early versus late immunomodulatory treatment (IMT) in patients with HLA-B27-associated chronic uveitis. Methods: Seventy-two patients (114 eyes) with HLA-B27-associated chronic uveitis received IMT at the Ocular Immunology & Uveitis Service of the Massachusetts Eye and Ear Infirmary and were evaluated retrospectively. Main outcome measures were visual acuity, control of inflammation, number of flare-ups and steroid-sparing effect. Results: The median time between diagnosis and start of IMT was 3.05 years. Accordingly, patients were divided into two groups: group A comprised those in whom initiation of IMT was within the first 3 years (36 patients), and in group B initiation of IMT was more than 3 years from the initial diagnosis (36 patients). Control of inflammation was achieved in 29 patients (80.5%) of the early-treated group and in 33 patients (91.6%) of the late-treated group. A steroid-sparing effect was achieved for 13 (81.25%) of the 16 and for 11 (73.33%) of the 15 patients who were on systemic steroid in the early- and late-treated groups respectively. The mean follow-up for the early-treated group was 2.14 years and for the late-treated group, 3.46 years. Conclusions: Immunomodulatory therapy is an effective treatment for severe HLA-B27 uveitis that fails to respond to conventional steroid treatment, regardless of the timing of its initiation. However, introduction of IMT within 3 years of the disease onset prevents the adverse effects of steroids (cataract, glaucoma) and reduces the likelihood of repeated recurrences of the uveitis. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Aristotle Univ Med Sch, Thessaloniki, Greece. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. EM fosters@uveitis.org NR 26 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD DEC PY 2003 VL 241 IS 12 BP 1000 EP 1005 DI 10.1007/s00417-003-0789-3 PG 6 WC Ophthalmology SC Ophthalmology GA 767AC UT WOS:000188400600007 PM 14605907 ER PT J AU Ostrow, JD Tiribelli, C AF Ostrow, JD Tiribelli, C TI Bilirubin, a curse and a boon SO GUT LA English DT Editorial Material ID SILICIC-ACID CHROMATOGRAPHY; GLUTATHIONE-S-TRANSFERASES; UNCONJUGATED BILIRUBIN; OXIDATIVE STRESS; RAT-LIVER; IN-VITRO; PERMEABILITY TRANSITION; URSODEOXYCHOLIC ACID; MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS AB Unconjugated bilirubin is a curse at high concentrations, producing apoptosis and cell death, but a boon at more physiological levels, protecting cells against oxidant damage. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Med, GI Hepatol Div, Seattle, WA 98195 USA. RP Ostrow, JD (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Res Serv 151L, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 55 TC 11 Z9 13 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD DEC 1 PY 2003 VL 52 IS 12 BP 1668 EP 1670 DI 10.1136/gut.52.12.1668 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 746KR UT WOS:000186746000004 PM 14633940 ER PT J AU Lea, JS Coleman, RL Garner, EO Duska, LR Miller, DS Schorge, JO AF Lea, JS Coleman, RL Garner, EO Duska, LR Miller, DS Schorge, JO TI Adenosquamous histology predicts poor outcome in low-risk stage IB1 cervical adenocarcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; PELVIC RADIATION-THERAPY; UTERINE CERVIX; RADICAL SURGERY; CANCER; SURVIVAL AB Objective. The purpose of this study was to identify poor prognostic factors of low-risk stage 113 1 cervical adenocarcinoma. Methods. All women diagnosed with stage IB1 cervical adenocarcinoma between 1982 and 2002 were identified at our three institutions. Data were extracted from medical records. Patients were retrospectively assigned to a low- or intermediate/high-risk cohort based on the surgical-pathologic eligibility criteria of two randomized controlled trials of adjuvant therapy in early stage cervical cancer, Gynecologic Oncology Group protocols 92 and 109. Multivariate analysis was performed. Results. Two hundred thirty women diagnosed with stage 1131 cervical adenocarcinoma had an overall 5-year survival of 89%. Adenosquamous cell type (P < 0.01) was the only independent risk factor of disease recurrence in the low-risk group (n = 178). The 5-year disease-free survival for low-risk adenosquamous patients was 79%, compared to 96% for other histologic subtypes (P < 0.01). Low-risk case subjects developed fewer disease recurrences than those in the intermediate/high-risk (n = 52) category (7% vs 46%; P < 0.01). The 5-year disease-free survival for intermediate/high-risk patients was 51% and no additional risk factors were identified. Conclusion. Adenosquamous histology is predictive of disease recurrence and decreased survival in low-risk stage 1131 cervical adenocarcinoma. This risk factor should be considered in future clinical trials of adjuvant therapy. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Texas, SW Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, Dallas, TX 75390 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Schorge, JO (reprint author), Univ Texas, SW Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol, 5323 Harry hines Blvd,J7-124, Dallas, TX 75390 USA. RI Miller, David/H-4604-2011 OI Miller, David/0000-0002-8215-5887 NR 19 TC 25 Z9 33 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2003 VL 91 IS 3 BP 558 EP 562 DI 10.1016/j.ygyno.2003.08.020 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 756FL UT WOS:000187455100015 PM 14675676 ER PT J AU del Carmen, MG Fuller, AF Matulonis, U Horick, NK Goodman, A Duska, LR Penson, R Campos, S Roche, M Seiden, MV AF del Carmen, MG Fuller, AF Matulonis, U Horick, NK Goodman, A Duska, LR Penson, R Campos, S Roche, M Seiden, MV TI Phase II trial of anastrozole in women with asymptomatic mullerian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE aromatase inhibitor; anastrozole; arimidex; ovarian cancer; CA-125; recurrent/persistent mullerian cancer ID ADVANCED BREAST-CANCER; ADVANCED OVARIAN-CARCINOMA; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; MEGESTROL-ACETATE; TAMOXIFEN; LETROZOLE; THERAPY; TUMORS AB Objective. To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase 11 trial in 53 women with asymptomatic recurrent/persistent mullerian cancer. Methods. Patients with ovarian, peritoneal, or fallopian tube carcinoma were eligible for enrollment. Eligible patients had an ECOG PS :! I and no clinical indication for immediate systemic chemotherapy. Patients were assigned to measurable (cohort 1) or evaluable disease (cohort 2) cohorts, respectively. Patients were treated with anastrozole I mg po daily. Monthly follow-up included interim history, physical exam, and CA-125 with radiologic evaluation every 3 months. Estrogen, progesterone, and Her-2/neu receptor status was also evaluated in archived tumor samples. Results. Fifty-three women with a median age of 63 (range, 46-86) years were enrolled. Twenty-nine women enrolled in cohort I and 24 in cohort 2. Included were 43, 7, and 3 women with ovarian, primary peritoneal, and fallopian tube carcinoma, respectively. All 53 patients were evaluable for treatment toxicity and response. The median time to disease progression was 85 days (85 days for cohort I and 82 days for cohort 2). A partial response was documented in a single patient with measurable disease. Forty-two percent of patients had stable disease (measured as time to treatment termination) for >90 days, 15% for >180 days, 7% for >270 days, and 4% for >360 days. One patient remained on anastrozole at 15 months. Toxicity was modest (grade 1) and infrequent, with the most common toxicities being fatigue and hot flashes. There were no thrombotic complications. Median time to progression for patients with estrogen receptor-positive tumors was 72 days as compared to 125 days for those with tumors negative for the estrogen receptor (P = 0.95, log-rank test). The median time to progression in patients with progesterone-positive tumors was 77 days and 91 days for patients with progesterone-negative tumors. Conclusion. In summary, anastrozole is a well-tolerated oral agent but with minimal tumoricidal activity in women with recurrent/persistent mullerian cancers. A minority of patients demonstrated prolonged stable disease while on this agent. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Obstet & Gynecol, Div Gynecol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Adult Oncol, Dept Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Div Biostat, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 21 TC 37 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD DEC PY 2003 VL 91 IS 3 BP 596 EP 602 DI 10.1016/j.ygyno.2003.08.021 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 756FL UT WOS:000187455100022 PM 14675683 ER PT J AU Scully, C Epstein, J Sonis, S AF Scully, C Epstein, J Sonis, S TI Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy: Part 1, pathogenesis and prophylaxis of mucositis SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK LA English DT Review DE mucositis; oral; radiotherapy; chemotherapy; cancer ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; NECK-CANCER-PATIENTS; STEM-CELL TRANSPLANTATION; RADIATION-INDUCED MUCOSITIS; RANDOMIZED CLINICAL-TRIAL; DOUBLE-BLIND TRIAL; REGIMEN-RELATED TOXICITIES; PLACEBO-CONTROLLED TRIAL; EPIDERMAL GROWTH-FACTOR AB Background. Oral mucositis is a common sequel of radiotherapy, chemotherapy, and radiochemotherapy in patients with cancer or patients requiring hemopoietic stem cell transplants. Mucositis has a direct and significant impact on the duration of disease remission and cure rates, because it is a cancer treatment-limiting toxicity. Mucositis also affects survival because of the risk of infection and has a significant impact on the quality of life and cost of care. Methods. This article reviews publications on the etiopatho-genesis and prevention of oral mucositis accessible from a MEDLINE search using as key words, mucositis, radiotherapy, chemotherapy, hemopoietic stem cell transplant, and oral. Conclusions. Of the current available products, ice chips and benzydamine have the strongest scientific evidence of support for prophylaxis of mucositis. (C) 2003 Wiley Periodicals, Inc. C1 UCL, Int Ctr Excellence Dent, London WC1X 8LD, England. UCL, Eastman Dent Inst Oral Hlth Care Sci, World Hlth Org Collaborating Ctr Oral Hlth Disabi, London WC1X 8LD, England. Vancouver Hosp & Hlth Sci Ctr, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Vancouver Hosp & Hlth Sci Ctr, Dept Dent, Vancouver, BC V5Z 1M9, Canada. Univ Illinois, Coll Dent, Dept Oral Med & Diagnost Sci, Chicago, IL USA. Chicago Canc Ctr, Coll Med, Interdisciplinary Program Oral Canc, Chicago, IL USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Oral Med Infect & Immun,Div Oral Med, Boston, MA 02115 USA. Harvard Univ, Sch Med,Div Oral & Maxillofacial Surg, Brigham & Womens Hosp, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Oral Med Infect & Immun,Div Dent, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Scully, C (reprint author), UCL, Int Ctr Excellence Dent, 256 Grays Inn Rd, London WC1X 8LD, England. EM c.scully@eastman.ucl.ac.uk NR 175 TC 80 Z9 83 U1 4 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1043-3074 J9 HEAD NECK-J SCI SPEC JI Head Neck-J. Sci. Spec. Head Neck PD DEC PY 2003 VL 25 IS 12 BP 1057 EP 1070 DI 10.1002/hed.10318 PG 14 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 748XN UT WOS:000186886400010 PM 14648865 ER PT J AU Sugimoto, K Ikeda, F Stadanlick, J Nunes, FA Alter, H Chang, KM AF Sugimoto, K Ikeda, F Stadanlick, J Nunes, FA Alter, H Chang, KM TI Suppression of HCV-specific T cells without differential hierarchy demonstrated ex vivo in persistent HCV infection SO HEPATOLOGY LA English DT Article ID HEPATITIS-C VIRUS; IMMUNE-RESPONSES; PERIPHERAL-BLOOD; DENDRITIC CELLS; CORE PROTEIN; QUANTITATIVE-ANALYSIS; LYMPHOCYTE RESPONSE; ENVELOPE PROTEIN; PLUS RIBAVIRIN; VIRAL LOAD AB Hepatitis C virus (HCV) has a high propensity for persistence. To better define the immunologic determinants of HCV clearance and persistence, we examined the circulating HCV-specific T-cell frequency, repertoire, and cytokine phenotype ex vivo in 24 HCV seropositive subjects (12 chronic, 12 recovered), using 361 overlapping peptides in 36 antigenic pools that span the entire HCV core, NS3-NS5. Consistent with T-cell-mediated control of HCV, the overall HCV-specific type-1 T-cell response was significantly greater in average frequency (0.24% vs. 0.04% circulating lymphocytes, P = .001) and scope (14/36 vs. 4/36 pools, P = .002) among the recovered than the chronic subjects, and the T-cell response correlated inversely with HCV titer among the chronic subjects (R = -0.51, P = .049). Although highly antigenic regions were identified throughout the HCV genome, there was no apparent difference in the overall HCV-specific T-cell repertoire or type-1/type-2 cytokine profile relative to outcome. Notably, HCV persistence was associated with a reversible CD4-mediated suppression of HCV-specific CD8 T cells and with higher frequency of CD4(+)CD25(+) regulatory T cells (7.3% chronic vs. 2.5% recovered, P = .002) that could directly suppress HCV-specific type-1 CD8 T cells ex vivo. In conclusion, we found that HCV persistence is associated with a global quantitative and functional suppression of HCV-specific T cells but not differential antigenic hierarchy or cytokine phenotype relative to HCV clearance. The high frequency of CD4(+)CD25(+) regulatory T cells and their suppression of HCV-specific CD8 T cells ex vivo suggests a novel role for regulatory T cells in HCV persistence. C1 Univ Penn, Dept Med, Div Gastroenterol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Penn Hosp, Philadelphia, PA 19107 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Chang, KM (reprint author), Univ Penn, Dept Med, GI Div, Univ & Woodland Ave, Philadelphia, PA 19104 USA. RI Yang, Chen/G-1379-2010 FU NCRR NIH HHS [M01-RR00040]; NIAAA NIH HHS [AA12849]; NIAID NIH HHS [AI47519] NR 50 TC 265 Z9 291 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD DEC PY 2003 VL 38 IS 6 BP 1437 EP 1448 DI 10.1016/j.hep.2003.09.026 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 751BC UT WOS:000187032100015 PM 14647055 ER PT J AU de Leval, L Harris, NL AF de Leval, L Harris, NL TI Variability in immunophenotype in diffuse large B-cell lymphoma and its clinical relevance SO HISTOPATHOLOGY LA English DT Review DE diffuse large B-cell lymphoma immunohistochemistry; survival prognosis ID NON-HODGKINS-LYMPHOMA; BCL-2 PROTEIN EXPRESSION; MONOCLONAL-ANTIBODY KI-67; GERMINAL-CENTER FORMATION; PARAFFIN-EMBEDDED TISSUE; TUMOR-SUPPRESSOR GENE; HIGH-GRADE MALIGNANCY; PROGNOSTIC-SIGNIFICANCE; CLINICOPATHOLOGICAL ANALYSIS; CHROMOSOMAL TRANSLOCATION AB Diffuse large B-cell lymphoma (DLBCL), the single largest category of lymphoma, is a clinically and biologically heterogeneous disease entity. Clinically, patients differ in their mode of presentation and respond variably to therapy. A combination of clinical parameters can be used to predict the patient's response to therapy and survival. The pathological variability of DLBCL is expressed in morphology, immunophenotype, cytogenetic and molecular genetic features. Numerous markers detectable by immunohistochemistry and linked to different aspects of tumour biology have been studied in DLBCL, including lineage-associated and immune markers, proliferation and apoptosis markers, cell adhesion molecules, and more recently stage-specific markers of B-cell differentiation. This review summarizes these studies in regard to their clinical significance and in the light of recent advances in our understanding of the molecular pathology and histogenesis of DLBCL. C1 CHU Liege, Dept Pathol, B-4000 Cointe Ougree, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP de Leval, L (reprint author), CHU Liege, Dept Pathol, B23, B-4000 Cointe Ougree, Belgium. NR 161 TC 54 Z9 55 U1 1 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD DEC PY 2003 VL 43 IS 6 BP 509 EP 528 DI 10.1111/j.1365-2559.2003.01758.x PG 20 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 748PR UT WOS:000186870700001 PM 14636252 ER PT J AU Brown, AB Yang, W Schmidt, NO Carroll, R Leishear, KK Rainov, NG Black, PM Breakefield, XO Aboody, KS AF Brown, AB Yang, W Schmidt, NO Carroll, R Leishear, KK Rainov, NG Black, PM Breakefield, XO Aboody, KS TI Intravascular delivery of neural stem cell lines to target intracranial and extracranial tumors of neural and non-neural origin SO HUMAN GENE THERAPY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; GENE DELIVERY; HUMAN GLIOMAS; BRAIN-TUMORS; THERAPY; VECTORS; NEURONS; GANCICLOVIR; RETROVIRUS AB The remarkable migratory and tumor-tropic capacities of neural stem cells (NSCs and/or neuroprogenitor cells) represent a potentially powerful approach to the treatment of invasive brain tumors, such as malignant gliomas. We have previously shown that whether implanted directly into or at distant sites from an experimental intracranial glioma, NSCs distributed efficiently throughout the main tumor mass and also tracked advancing tumor cells, while stably expressing a reporter transgene. As therapeutic proof-of-concept, NSCs genetically modified to produce the prodrug activating enzyme cytosine deaminase (CD), effected an 80% reduction in the resultant tumor mass, when tumor animals were treated with the systemic prodrug, 5-fluoro-cytosine. We now extend our findings of the tumor-tropic properties of NSCs (using a well-characterized, clonal NSC line C17.2), by investigating their capacity to target both intracranial and extracranial tumors, when administered into the peripheral vasculature. We furthermore demonstrate their capacity to target extracranial non-neural tumors such as prostate cancer and malignant melanoma. Well-characterized NSC lines (lacZ and/or CD-positive) were injected into the tail vein of adult nude mice with established experimental intracranial and/or subcutaneous flank tumors of neural and non-neural origin. The time course and distribution of NSCs within the tumor and internal organs was assessed in various models. Resulting data suggest that NSCs can localize to various tumor sites when injected via the peripheral vasculature, with little accumulation in normal tissues. Our findings suggest the novel use of intravascularly administered NSCs as an effective delivery vehicle to target and disseminate therapeutic agents to invasive tumors of neural and non-neural origin, both within and outside of the brain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Univ Liverpool, Dept Neurol Sci, Liverpool L69 3BX, Merseyside, England. Layton Biosci Inc, Sunnyvale, CA 94086 USA. RP Aboody, KS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Mol Neurogenet Unit, Boston, MA 02115 USA. RI Schmidt, Nils Ole/D-5696-2014 NR 29 TC 132 Z9 138 U1 0 U2 9 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC PY 2003 VL 14 IS 18 BP 1777 EP 1785 DI 10.1089/104303403322611782 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 753RX UT WOS:000187245300008 PM 14670128 ER PT J AU Lathers, DMR Achille, NJ Young, MRI AF Lathers, DMR Achille, NJ Young, MRI TI Incomplete Th2 skewing of cytokines in plasma of patients with squamous cell carcinoma of the head and neck SO HUMAN IMMUNOLOGY LA English DT Article DE cancer; cytokine; HNSCC; Th1; Th2 ID TUMOR-INFILTRATING LYMPHOCYTES; GROWTH-FACTOR BETA-1; COLORECTAL-CANCER; PERIPHERAL-BLOOD; CD34(+) CELLS; T-CELLS; IMMUNOTHERAPY; EXPRESSION; MECHANISMS AB Levels of cytokines, and in particular those that reflect Th1 or Th2 bias, were measured in the plasma of patients with head and neck squamous cell carcinomas (HNSCC). Compared with plasma cytokine levels of age-matched controls, cytokine levels in HNSCC patients suggested a shift to a Th2 bias as levels of the Th2 cytokines interleukin-4 (IL-4), IL-6, and IL-10 were increased, and levels of the Th1 cytokine interferon-gamma (IFN-gamma) were decreased. However, levels of the Th1 cytokines IL-2 and granulocyte macrophage-colony-stimulating factor (GM-CSF) were increased, which is not consistent with full Th2 skewing. Assessment of cytokine levels in patients with malignancies other than HNSCC demonstrated many similarities to HNSCC patients, but HNSCC patients exhibited a more pronounced increase in GM-CSF levels and a decline in IFN-gamma levels. For most cytokines there was no association between the shifts in cytokine levels in HNSCC patients and either the extent of tumor burden or extent of metastasis. However, patients with large HNSCC tended to be the population that demonstrated increased levels of IL-4 and IL-6. These results suggest skewing toward a Th2 bias in HNSCC patients, with the Th2 shift being incomplete and indicative of the presence, rather than the extent, of malignant disease. Human Immunology 64, 1160-1166 (2003). (C) American Society for Histocompatibility and Immunogenetics, 2003. Published by Elsevier Inc. C1 Loyola Univ, Stritch Sch Med, Dept Pathol, Maywood, IL 60153 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. RP Young, MRI (reprint author), Ralph H Johnson Vet Affairs Hosp, Res Serv 151, 109 Bee St, Charleston, SC 29401 USA. FU NCI NIH HHS [CA 79768, CA 78262, CA 85266] NR 23 TC 40 Z9 40 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD DEC PY 2003 VL 64 IS 12 BP 1160 EP 1166 DI 10.1016/j.humimm.2003.08.024 PG 7 WC Immunology SC Immunology GA 748XH UT WOS:000186885900005 PM 14630398 ER PT J AU Hauser, R Singh, NP Chen, Z Pothier, L Altshul, L AF Hauser, R Singh, NP Chen, Z Pothier, L Altshul, L TI Lack of an association between environmental exposure to polychlorinated biphenyls and p,p '-DDE and DNA damage in human sperm measured using the neutral comet assay SO HUMAN REPRODUCTION LA English DT Article DE comet assay; DDT; DNA damage; polychlorinated biphenyls; sperm ID CHROMATIN-STRUCTURE ASSAY; GEL-ELECTROPHORESIS ASSAY; TOXIC EQUIVALENCY FACTORS; DOUBLE-STRAND BREAKS; IN-VITRO; HUMAN SPERMATOZOA; PREDICTIVE VALUE; PCB METABOLITES; HUMAN-SERUM; BLOOD AB BACKGROUND: Chlorinated organic chemicals, such as polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), dichlorodiphenyl trichloroethane (DDT), and dichlorodiphenyl dichloroethene (DDE, the most stable daughter compound of DDT) are persistent lipophilic compounds found in a large portion of the general population. To explore the hypothesis that environmental exposure to these compounds is associated with altered DNA integrity in human sperm, a study of 212 male partners of a sub-fertile couple who presented to the Massachusetts General Hospital Andrology Laboratory was conducted. METHODS: The neutral single cell microgel electrophoresis assay (comet assay) was used to assess DNA integrity in sperm. VisComet image analysis software was used to measure total comet length, the proportion of DNA present in the comet tail, and tail distributed moment, an integrated measure of length and intensity. RESULTS: In the regression analyses, there were no statistically significant consistent associations between the comet assay parameters and any of the individual PCB congeners, sum of PCB, or p,p'-DDE. CONCLUSION: These results suggest that there are not strong relationships between adult levels of these chlorinated organic compounds and sperm DNA damage as measured by the comet assay. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA 02114 USA. Univ Washington, Dept Bioengn, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm Sci & Engn Program, Boston, MA 02115 USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES00002, ES09718] NR 61 TC 43 Z9 43 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD DEC PY 2003 VL 18 IS 12 BP 2525 EP 2533 DI 10.1093/humrep/deg508 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 753GY UT WOS:000187224700009 PM 14645167 ER PT J AU Kadkade, PP Benda, BJ Schmidt, PB Wall, C AF Kadkade, PP Benda, BJ Schmidt, PB Wall, C TI Vibrotactile display coding for a balance prosthesis SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE critical tracking task (CTT); manual control; sensory substitution; vestibular prosthesis; vibrotactile display ID TRACKING; FEEDBACK AB Preliminary experiments have demonstrated the potential usefulness of a precursor balance prosthesis that displays the tilt of the subject using tactile vibrators (tactors) which are in contact with the subjects skin. The device consists of a motion sensing system mounted on the head or body whose signals are converted into estimates of head or body tilt. Tilt is displayed to the subject by coding the tilt estimate into signals that are sent to the tactors using one of several schemes. Because full blown, end-to-end balance experiments are relatively time consuming and expensive, and because there are many possible display schemes, we have developed a quantitative means to evaluate the display step separately. We used a modified version of the manual control critical tracking task (CTT) to help us make an initial selection of the more promising vibrotactile display schemes for further evaluation. The classic CTT is a compensatory form of tracking in which the operator attempts to control an increasingly unstable system using a joystick to regulate a tracking error signal (system minus joystick) that is visually displayed as a dot on a cathode ray tube.. Our modification added vibrotactile display of the error signal. For a given subject and vibrotactile display scheme, the level of difficulty at which the subjects lost control, called the, critical lambda (lambda(c)), was highly repeatable. Four different coding schemes were evaluated using an array of 16 vibrators that were attached to the lower backs of 11 healthy subjects. The first scheme, called interval-based coding, modulated the interval between pulses that were sent to single tactors mounted on the subjects right and left side. A greater tracking error magnitude was displayed as a faster pulse rate. A positive error was displayed on the right side while a negative one was displayed on the left. The remaining three schemes, called position-based coding, used a horizontal row of 14 tactors. Tracking error magnitude was mapped to position of the activated vibrator so that an error near zero corresponded to a vibrator near the center of the back. The three position-based schemes tested used three, four, or seven tactors per side. Averaged over all subjects, the value of lambda(c) for the interval-based scheme was significantly less than it was for each of the three position-based schemes. There was no significant change in lambda(c) as the number of position-based tactors was increased from three to seven per side. The prediction of better actual balance performance using position-based relative to interval-based vibrotactile display was validated by a preliminary study of six normal subjects that compared the body sway produced during quiet standing while providing head tilt estimates using both display modes. Our study provides basic characterization using lambda(c) for several vibrotactile display schemes in human subjects. The quantitative CTT measure of performance can logically be extended to other applications of vibrotactile displays and to other kinds of display schemes used for rehabilitation. C1 New York Presbyterian Univ Hosp Colombia, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. New York Presbyterian Univ Hosp Cornell, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. Shriners Hosp Children, Philadelphia, PA 19140 USA. Boeing Co, Houston, TX 77059 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol,Vestibular Diagnost Lab, Boston, MA 02114 USA. RP Kadkade, PP (reprint author), New York Presbyterian Univ Hosp Colombia, Dept Otolaryngol Head & Neck Surg, New York, NY 10032 USA. EM cwall@mit.edu NR 19 TC 24 Z9 24 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1534-4320 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD DEC PY 2003 VL 11 IS 4 BP 392 EP 399 DI 10.1109/TNSRE.2003.819937 PG 8 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 768KA UT WOS:000188541100008 PM 14960115 ER PT J AU Pai, SY Truitt, ML Ting, CN Leiden, JM Glimcher, LH Ho, IC AF Pai, SY Truitt, ML Ting, CN Leiden, JM Glimcher, LH Ho, IC TI Critical roles for transcription factor GATA-3 in thymocyte development SO IMMUNITY LA English DT Article ID T-CELL DEVELOPMENT; ADAPTER PROTEIN SLP-76; RECEPTOR-ALPHA-GENE; LINEAGE COMMITMENT; NEGATIVE SELECTION; MICE LACKING; TCR SIGNALS; EXPRESSION; BETA; DIFFERENTIATION AB The transcription factor GATA-3 is expressed at every stage of thymic development, but its role in thymocyte differentiation is unknown. The fact that RAG chimeric animals lacking GATA-3 cannot generate early thymocytes from common lymphoid progenitors has thus far precluded investigation of the function of GATA-3 in the thymus. To address this, we generated mice deficient in GATA-3 at early and late stages of thymic differentiation. Our studies revealed that GATA-3 is involved in beta selection and is indispensable for single-positive CD4 thymocyte development. Thus, our data demonstrate that the coordinated and regulated expression of GATA-3 at each stage of thymic development is critical for the generation of mature T cells. C1 Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Ctr Prevent Cardiovasc Dis, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Div Infect Dis & Immunol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Ho, IC (reprint author), Dana Farber Canc Inst, Dept Pediat Hematol & Oncol, Boston, MA 02115 USA. FU NIAID NIH HHS [K08 AI50601, R01 AI029673] NR 43 TC 196 Z9 210 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2003 VL 19 IS 6 BP 863 EP 875 DI 10.1016/S1074-7613(03)00328-5 PG 13 WC Immunology SC Immunology GA 753KN UT WOS:000187230700011 PM 14670303 ER PT J AU Serbina, NV Kuziel, W Flavell, R Akira, S Rollins, B Pamer, EG AF Serbina, NV Kuziel, W Flavell, R Akira, S Rollins, B Pamer, EG TI Sequential MyD88-independent and -dependent activation of innate immune responses to intracellular bacterial infection SO IMMUNITY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; TOLL-LIKE RECEPTORS; LISTERIA-MONOCYTOGENES; MICE DEFICIENT; MACROPHAGE RECRUITMENT; CHEMOKINE RECEPTOR; MURINE LISTERIOSIS; IFN-GAMMA AB Microbial infections induce chemokine and cytokine cascades that coordinate innate immune defenses. Infection with the intracellular bacterial pathogen Listeria monocytogenes induces CCR2-dependent monocyte recruitment and activation, an essential response for host survival. Herein we show that invasive L. monocytogenes, but not killed or noninvasive bacteria, induce secretion of MCP-1, the requisite chemokine for monocyte recruitment. Induction of MCP-1, but not TNF or IL-12, following L. monocytogenes infection is MyD88 independent. Consistent with these results, MyD88 deficiency does not impair monocyte recruitment to L. monocytogenes infected spleens, but prevents monocyte activation. Our results indicate that distinct microbial signals activate innate immune responses in an ordered, step-wise fashion, providing a mechanism to specify and modulate antimicrobial effector functions. C1 Sloan Kettering Inst, Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Dept Med,Immunol Program, New York, NY 10021 USA. Univ Texas, Sect Mol Genet & Microbiol, Inst Mol & Cellular Biol, Austin, TX 78712 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. Howard Hughes Med Inst, New Haven, CT 06520 USA. Osaka Univ, ERATO, Dept Host Def, Res Inst Microbial Dis,Japan Sci & Technol Corp, Suita, Osaka 5650871, Japan. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. RP Pamer, EG (reprint author), Sloan Kettering Inst, Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Dept Med,Immunol Program, 1275 York Ave, New York, NY 10021 USA. RI Akira, Shizuo/C-3134-2009 FU NCI NIH HHS [CA 09149]; NIAID NIH HHS [AI 39301, R01 AI 42135] NR 47 TC 135 Z9 138 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD DEC PY 2003 VL 19 IS 6 BP 891 EP 901 DI 10.1016/S1074-7613(03)00330-3 PG 11 WC Immunology SC Immunology GA 753KN UT WOS:000187230700013 PM 14670305 ER PT J AU Exley, MA Bigley, NJ Cheng, O Shaulov, A Tahir, SMA Carter, QL Garcia, J Wang, C Patten, K Stills, HF Alt, FW Snapper, SB Balk, SP AF Exley, MA Bigley, NJ Cheng, O Shaulov, A Tahir, SMA Carter, QL Garcia, J Wang, C Patten, K Stills, HF Alt, FW Snapper, SB Balk, SP TI Innate immune response to encephalomyocarditis virus infection mediated by CD1d SO IMMUNOLOGY LA English DT Article ID NK T-CELLS; COXSACKIEVIRUS B3-INDUCED MYOCARDITIS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; IMMUNOGLOBULIN-E PRODUCTION; INDUCED DIABETES-MELLITUS; CUTTING EDGE; IN-VIVO; INTERFERON-PRODUCTION; MOUSE CD1; MICE AB CD1d-reactive natural killer T (NKT) cells can rapidly produce T helper type 1 (Th1) and/or Th2 cytokines, can activate antigen-presenting cell (APC) interleukin-12 (IL-12) production, and are implicated in the regulation of adaptive immune responses. The role of the CD1d system was assessed during infection with encephalomyocarditis virus (EMCV-D), a picornavirus that causes acute diabetes, paralysis and myocarditis. EMCV-D resistance depends on IL-12-mediated interferon-gamma (IFN-gamma) production. CD1d-deficient mice, which also lack CD1d-reactive NKT cells, were substantially more sensitive to infection with EMCV-D. Infected CD1d knockout mice had decreased IL-12 levels in vitro and in vivo, and indeed were protected by treatment with exogenous IL-12. IFN-gamma production in CD1d knockout mice was decreased compared with that in wild-type (WT) mice in response to EMCV-D in vitro, although differences were not detected in vivo. Treatment with anti-asialo-GM1 antibody, to deplete NK cells, caused a marked increase in susceptibility of WT mice to EMCV-D infection, whereas CD1d knockout mice were little affected, suggesting that NK-cell-mediated protection is CD1d-dependent. Therefore, these data indicate that CD1d is essential for optimal responses to acute picornaviral infection. We propose that CD1d-reactive T cells respond to early immune signals and function in the innate immune response to a physiological viral infection by rapidly augmenting APC IL-12 production and activating NK cells. C1 Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Wright State Univ, Microbiol & Immunol Program, Dayton, OH 45435 USA. Childrens Hosp Med Ctr, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Exley, MA (reprint author), Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Canc Biol Program, HIM Bldg Room 921,330 Brookline Ave, Boston, MA 02215 USA. FU NCI NIH HHS [CA89567]; NIAID NIH HHS [AI42955] NR 65 TC 56 Z9 57 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2003 VL 110 IS 4 BP 519 EP 526 DI 10.1046/j.1365-2567.2003.01779.x PG 8 WC Immunology SC Immunology GA 747GU UT WOS:000186797500016 PM 14632651 ER PT J AU Chatzinikolaou, I Hanna, H Graviss, L Chaiban, G Perego, C Arbuckle, R Champlin, R Darouiche, R Samonis, G Raad, I AF Chatzinikolaou, I Hanna, H Graviss, L Chaiban, G Perego, C Arbuckle, R Champlin, R Darouiche, R Samonis, G Raad, I TI Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: Efficacy and low risk of developing staphylococcal resistance SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 27-30, 2002 CL SAN DIEGO, CALIFORNIA ID BLOOD-STREAM INFECTIONS; BACTERIAL-RESISTANCE; IN-VITRO; ANTISEPTICS; ANTIBIOTICS; CULTURES AB In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections. C1 Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Div Internal Med, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Div Pharm, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Bone Marrow Transplantat, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Infect Dis Sect, Houston, TX USA. Univ Crete, Sch Med, Dept Infect Dis, Div Internal Med, Rethimnon, Crete, Greece. RP Hanna, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Div Internal Med, 1515 Holcombe Blvd,Unit 402, Houston, TX 77030 USA. NR 10 TC 33 Z9 35 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2003 VL 24 IS 12 BP 961 EP 963 DI 10.1086/502167 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 753MX UT WOS:000187236100014 PM 14700414 ER PT J AU Brochard, L Mancebo, J Tobin, M AF Brochard, L Mancebo, J Tobin, M TI Searching for evidence: don't forget the foundations SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID RESPIRATORY-DISTRESS SYNDROME; END-EXPIRATORY PRESSURE; STATUS-ASTHMATICUS; VENTILATION C1 Univ Paris 12, Hop Henri Mondor, Assistance Publ Hop Paris, Med Intens Care Unit, F-94010 Creteil, France. INSERM, U492, F-94010 Creteil, France. Univ Autonoma Barcelona, St Pau Hosp, Intens Care Unit, E-08193 Barcelona, Spain. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL 60141 USA. Loyola Univ Chicago, Stritch Sch Med, Hines, IL 60141 USA. RP Brochard, L (reprint author), Univ Paris 12, Hop Henri Mondor, Assistance Publ Hop Paris, Med Intens Care Unit, F-94010 Creteil, France. NR 10 TC 11 Z9 11 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2003 VL 29 IS 12 BP 2109 EP 2111 DI 10.1007/s00134-003-2012-8 PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 747VN UT WOS:000186825900001 PM 14566454 ER PT J AU Tetzlaff, K Shank, ES Muth, CM AF Tetzlaff, K Shank, ES Muth, CM TI Evaluation and management of decompression illness - an intensivist's perspective SO INTENSIVE CARE MEDICINE LA English DT Review DE decompression illness; arterial gas embolism; decompression sickness; hyperbaric oxygen therapy; diving ID ARTERIAL GAS EMBOLISM; PATENT FORAMEN OVALE; CEREBRAL AIR-EMBOLISM; HYPERBARIC-OXYGEN; BLOOD-FLOW; PULMONARY BAROTRAUMA; SICKNESS; DIVERS; ISCHEMIA; LIDOCAINE AB Decompression illness (DCI) is becoming more prevalent as more people engage in activities involving extreme pressure environments such as recreational scuba-diving. Rapid diagnosis and treatment offer these patients the best chance of survival with minimal sequelae. It is thus important that critical care physicians are able to evaluate and diagnose the signs and symptoms of DCI. The cornerstones of current treatment include the administration of hyperbaric oxygen and adjunctive therapies such as hydration and medications. However, managing patients in a hyperbaric environment does present additional challenges with respect to the particular demands of critical care medicine in an altered pressure environment. This article reviews the underlying pathophysiology, clinical presentation and therapeutic options available to treat DCI, from the intensivist's perspective. C1 Univ Kiel, Dept Med 1, D-24105 Kiel, Germany. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Univ Ulm, Dept Anaesthesiol, Sect Pathophysiol & Proc Dev, D-89073 Ulm, Germany. RP Tetzlaff, K (reprint author), Univ Kiel, Dept Med 1, Schittenhelmstr 12, D-24105 Kiel, Germany. NR 73 TC 13 Z9 13 U1 0 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD DEC PY 2003 VL 29 IS 12 BP 2128 EP 2136 DI 10.1007/s00134-003-1999-1 PG 9 WC Critical Care Medicine SC General & Internal Medicine GA 747VN UT WOS:000186825900005 PM 14600806 ER PT J AU Pivniouk, VI Snapper, SB Kettner, A Alenius, H Laouini, D Falet, H Hartwig, J Alt, FW Geha, RS AF Pivniouk, VI Snapper, SB Kettner, A Alenius, H Laouini, D Falet, H Hartwig, J Alt, FW Geha, RS TI Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE allergy and immunology; cell degranulation; receptor-mediated signal transduction; Wiskott-Aldrich syndrome ID FC-EPSILON-RI; C-KIT LIGAND; TYROSINE PHOSPHORYLATION; T-CELL; ACTIN CYTOSKELETON; IN-VIVO; NORMAL MICE; ACTIVATION; KINASE; ANAPHYLAXIS AB Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca2+ mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells. C1 Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Geha, RS (reprint author), Childrens Hosp, Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. OI Falet, Herve/0000-0003-0788-9204 FU NIAID NIH HHS [AI-35714] NR 46 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 2003 VL 15 IS 12 BP 1431 EP 1440 DI 10.1093/intimm/dxg148 PG 10 WC Immunology SC Immunology GA 753HB UT WOS:000187225000004 PM 14645152 ER PT J AU Mulroy, T Xu, YY Sen, JM AF Mulroy, T Xu, YY Sen, JM TI beta-Catenin expression enhances generation of mature thymocytes SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE positive selection; signal transduction; thymocyte maturation; thymus; Wnt signaling ID T-CELL DEVELOPMENT; TRANSCRIPTION FACTORS; LINEAGE DECISION; ADULT THYMUS; DIFFERENTIATION; APOPTOSIS; CD4; SELECTION; MODEL; TCF-1 AB T cell factor (TCF)-1 is a T-cell-specific transcription factor that is expressed at all stages of T cell development. Deletion of the TCF-1 gene leads to an early block in thymocyte maturation precluding the study of its role at late stages and during positive selection of T cells. In this report we show that beta-catenin, a central effector in the Wnt-TCF-1 signaling pathway, regulates late stages of T cell development. Specifically, transgenic expression of beta-catenin enhances generation of mature thymocytes. Interestingly, CD8-expressing mature thymocytes were affected to a greater extent than CD4-expressing cells. These data suggest that the Wnt-beta-catenin-TCF-1 signaling pathway plays a role during late stages of T cell development. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sen, JM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 32 TC 47 Z9 48 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD DEC PY 2003 VL 15 IS 12 BP 1485 EP 1494 DI 10.1093/intimm/dxg146 PG 10 WC Immunology SC Immunology GA 753HB UT WOS:000187225000009 PM 14645157 ER PT J AU Meyer, GS Battles, J Hart, JC Tang, N AF Meyer, GS Battles, J Hart, JC Tang, N TI The US Agency for Healthcare Research and Quality's activities in patient safety research SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article; Proceedings Paper CT 18th International Conference of the International-Society-for-Quality-in-Health-Care CY OCT 04, 2001 CL BUENOS AIRES, ARGENTINA SP Int Soc Quality Hlth Care DE patient safety; quality; research; US Agency for Healthcare Research and Quality AB Purpose. To update the international community on the US Agency for Healthcare Research and Quality's (AHRQ) recent and current activities in improving patient safety. Data sources. Review of the literature concerning the importance of patient safety as a health care quality issue, international perspectives on patient safety, a review of research solicitations, and early results of funded studies. Study selection. A representative sample of patient safety studies from those currently being funded by AHRQ. Results. In response to a growing interest in patient safety in general and a recent US Institute of Medicine report on patient safety in particular, the US Agency for Healthcare Research and Quality has refocused its quality research mission. In the fiscal year 2002, AHRQ spent US$55 million on patient safety research. This investment was spread across six complementary research areas: (1) health systems error reporting, analysis, and safety improvement research demonstrations; (2) Clinical Informatics to Promote Patient Safety (CLIPS); (3) Centers of Excellence for patient safety research and practice (COE); (4) Developmental Centers for Evaluation and Research in Patient Safety (DCERPS); (5) The Effect of Health Care Working Conditions on Quality of Care; and (6) Partnerships for Quality: Patient Safety Research Dissemination and Education. Internal teams of researchers at AHRQ have published studies on patient safety, such as documenting the impact of medication errors. In addition to funding research on patient safety, AHRQ is an integral partner in several national and international collaborations to form strategic synergies that build upon each member organization's strengths, reduce redundant efforts, and benefit from each other's successes. As evidence on patient safety is generated, AHRQ also serves the important mission of disseminating information to the public. Conclusion. The patient safety research field has undergone a period of rapid evolution. It is now incumbent upon the international health care quality improvement community to translate the future results of this research investment into improved safety for patients. C1 Massachusetts Gen Phys Org, Boston, MA USA. Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Rockville, MD USA. Harvard Univ, Sch Med, Boston, MA USA. RP Meyer, GS (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Bulfinch 205,55 Fruit St, Boston, MA 02114 USA. NR 15 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD DEC PY 2003 VL 15 SU 1 BP I25 EP I30 DI 10.1093/intqhc/mzg068 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 754AX UT WOS:000187281500005 PM 14660520 ER PT J AU Becker, AE Burwell, RA Navara, K Gilman, SE AF Becker, AE Burwell, RA Navara, K Gilman, SE TI Binge eating and binge eating disorder in a small-scale, indigenous society: The view from Fiji SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE binge eating; binge eating disorder; cross-cultural prevalence ID PSYCHIATRIC COMORBIDITY; SELF-EFFICACY; YOUNG-ADULTS; WOMEN; POPULATION; PREVALENCE; WEIGHT; DISTURBANCES; DEPRESSION; BEHAVIORS AB Objective: Although the cross-cultural prevalence of anorexia and bulimia nervosa has been investigated in multiple studies, little is known about the prevalence and correlates of binge eating and binge eating disorder (BED) cross-culturally. No published studies to date have explored BED in small-scale, indigenous, or developing societies. The current study investigated the prevalence and correlates of binge eating in a community sample of Fijian women living in rural Fiji. Methods: Fifty ethnic Fijian women completed a self-report measure developed for this study on dieting and attitudes toward body shape and change, a Nadroga-language questionnaire on body image, and the Questionnaire on Eating and Weight Patterns-Revised (QEWP-R). Their height and weight were also measured. Patterns of dieting, high body mass index (BMI), and attitudes toward eating and body image were compared between women with and without a history of binge eating. Results: Ten percent of respondents reported at least weekly episodes of binge eating during the past 6 months and 4% endorsed symptoms consistent with BED. Binge eating in this sample was associated significantly with a BMI value above 35, a history of dieting, and a high concern with body shape. Binge eating was not associated with several markers of acculturation in this sample, although it was associated with a key, nontraditionally Fijian (i.e., acculturated) attitude toward the body. Discussion: Binge eating occurred in a social context with traditions concerning weight and diet widely disparate from Western populations. However, correlates of binge eating in this, sample suggest that nontraditional Fijian attitudes toward weight and body shape play a contributory role. (C) 2003 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Adult Eating & Weight Disorders Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Univ Denver, Dept Psychol, Denver, CO 80208 USA. Village Hlth Stn, Rararua Village, Fiji. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Brown Univ, Sch Med, Ctr Behav & Prevent Med, Providence, RI 02912 USA. Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02906 USA. RP Becker, AE (reprint author), Massachusetts Gen Hosp, Adult Eating & Weight Disorders Program, Dept Psychiat, 15 Parkman St,WAC 816, Boston, MA 02114 USA. RI Gilman, Stephen/E-7632-2010 OI Gilman, Stephen/0000-0002-8331-6419 NR 35 TC 16 Z9 16 U1 3 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD DEC PY 2003 VL 34 IS 4 BP 423 EP 431 DI 10.1002/eat.10225 PG 9 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 737FU UT WOS:000186220400004 PM 14566929 ER PT J AU Butters, MA Sweet, RA Mulsant, BH Kamboh, MI Pollock, BG Begley, AE Reynolds, CF DeKosky, ST AF Butters, MA Sweet, RA Mulsant, BH Kamboh, MI Pollock, BG Begley, AE Reynolds, CF DeKosky, ST TI APOE is associated with age-of-onset, but not cognitive functioning, in late-life depression SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE apolipoprotein E; geriatric; late-life; depression; Alzheimer's disease ID APOLIPOPROTEIN E-EPSILON-4 FREQUENCY; MINI-MENTAL-STATE; 2-YEAR FOLLOW-UP; ALZHEIMERS-DISEASE; RISK-FACTORS; GERIATRIC DEPRESSION; REVERSIBLE DEMENTIA; PSEUDODEMENTIA; POLYMORPHISM; REANALYSIS AB Objective There is a recognized but poorly understood relationship between late-life depression (LLD) and progressive dementia. Both cognitive impairment co-occurring with LLD and a late age-of-onset of first lifetime depressive episode appear to be associated with subsequent progressive dementia. A history of major depression, especially when the first onset occurs in late-life, has been identified as a risk factor for Alzheimer's disease (AD). The major genetic risk factor for sporadic AD is carrying one or more apolipoprotein E4 (APOE4) alleles. We hypothesized that the association between LLD and dementia risk would be mediated by APOE4, specifically that APOE4 allele frequency would be associated with cognitive impairment and later age-of-depression-onset. We also predicted that APOE4 allele frequency would be increased among subjects with LLD. Methods We compared the distribution of APOE2, APOE3, and APOE4 alleles in groups of LLD (n = 160), AD (n = 568) and elderly control (EC; n = 156) subjects. Results The allele distribution of the cognitively impaired LLD subgroup was not different from either the cognitively normal subgroup or the EC group but was different from the AD group. However, mean age-of-onset of depression in APOE4 carriers (51.4 +/- 20.7) was significantly lower than non-carriers (58.8 +/- 16.8). The allele distribution in LLD overall was significantly different from the AD but not the EC group. Conclusions The finding that neither LLD, accompanying cognitive impairment, nor late age-of-onset was associated with an increased APOE4 allele frequency suggests that LLD acts as a risk factor for developing AD as well as non-AD dementia through mechanisms independent of APOE4. The unexpected finding that age-of-onset of LLD was significantly reduced in APOE4 carriers is similar to the association between APOE4 and age-of-onset in AD. Replication of the association of APOE4 with earlier age-of-depression-onset is indicated. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Neurol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Butters, MA (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. OI Kamboh, M. Ilyas/0000-0002-3453-1438 FU NIA NIH HHS [AG05133, AG13672]; NIMH NIH HHS [MH52247, MH01613, MH01684, MH37869, MH43832, MH65416, MH66231] NR 37 TC 29 Z9 31 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD DEC PY 2003 VL 18 IS 12 BP 1075 EP 1081 DI 10.1002/gps.1006 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 757XR UT WOS:000187587200001 PM 14677138 ER PT J AU Wang, SJ Bates, DW Chueh, HC Karson, AS Maviglia, SM Greim, JA Frost, JP Kuperman, GJ AF Wang, SJ Bates, DW Chueh, HC Karson, AS Maviglia, SM Greim, JA Frost, JP Kuperman, GJ TI Automated coded ambulatory problem lists: evaluation of a vocabulary and a data entry tool SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article DE vocabulary, controlled; medical record systems, computerized; medical records, problem-orientated ID MEDICAL-RECORD; SYSTEM; EXPERIENCE; CARE; TERMINOLOGIES; COVERAGE AB Background: Problem lists are fundamental to electronic medical records (EMRs). However, obtaining an appropriate problem list dictionary is difficult, and getting users to code their problems at the time of data entry can be challenging. Objective: To develop a problem list dictionary and search algorithm for an EMR system and evaluate its use. Methods: We developed a problem list dictionary and lookup tool and implemented it in several EMIR systems. A sample of 10,000 problem entries was reviewed from each system to assess overall coding rates. We also performed a manual review of a subset of entries to determine the appropriateness of coded entries, and to assess the reasons other entries were left uncoded. Results: The overall coding rate varied significantly between different EMIR implementations (63-79%). Coded entries were virtually always appropriate (99%). The most frequent reasons for uncoded entries were due to user interface failures (44-45%), insufficient dictionary coverage (20-32%), and non-problem entries (10-12%). Conclusion: The problem list dictionary and search algorithm has achieved a good coding rate, but the rate is dependent on the specific user interface implementation. Problem coding is essential for providing clinical decision support, and improving usability should result in better coding rates. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Partners HealthCare Syst, Dept Informat Syst, Wellesley, MA 02481 USA. Brigham & Womens Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Comp Sci Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Wang, SJ (reprint author), Partners HealthCare Syst, Dept Informat Syst, 93 Worcester St, Wellesley, MA 02481 USA. NR 50 TC 17 Z9 18 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1386-5056 J9 INT J MED INFORM JI Int. J. Med. Inform. PD DEC PY 2003 VL 72 IS 1-3 BP 17 EP 28 DI 10.1016/j.ijmedinf.2003.08.002 PG 12 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 754LX UT WOS:000187319600003 PM 14644303 ER PT J AU Shoelson, SE Lee, J Yuan, M AF Shoelson, SE Lee, J Yuan, M TI Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT Symposium on Complications of Obesity - The Inflammatory Link CY NOV 15-16, 2002 CL QUEBEC CITY, CANADA SP DB Brown Res Chair Obes DE salicylates; diabetes; kinases ID NECROSIS-FACTOR-ALPHA; PROTEIN-KINASE-C; DIABETES-MELLITUS; SALICYLATE; ASPIRIN; PATHOGENESIS; PREVENTION; ACTIVATION; AGENTS; MUSCLE AB Antidiabetic effects associated with salicylates have been known for years, although the underlying mechanisms were not understood. We have been reinvestigating these effects in the light of recent discoveries in the areas of signal transduction and insulin resistance. Our findings showed that signaling pathways leading to IkappaB kinase beta (IKKbeta) and NF-kappaB are activated in insulin-responsive tissues of obese and high-fat-fed animals. Since activation correlates with the development of insulin resistance, we asked whether signaling through this might be involved in the pathogenesis of insulin resistance. Heterozygous gene deletion (Ikkbeta+/-) or salicylates, working as IKKbeta inhibitors, improved insulin sensitivity in insulin-resistant rodent models. Furthermore, high doses of salicylates ( aspirin or salicylate) improved insulin sensitivity in patients with type II diabetes. Our studies implicate an inflammatory process in the pathogenesis of insulin resistance in obesity and type II diabetes mellitus and identify the IKKbeta/ NF-kappaB pathway as a molecular mediator of insulin resistance and pharmacological target for insulin sensitization. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Shoelson, SE (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [R01 DK45943, R01 DK51729] NR 20 TC 229 Z9 243 U1 4 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD DEC PY 2003 VL 27 SU 3 BP S49 EP S52 DI 10.1038/sj.ijo.0802501 PG 4 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 744MA UT WOS:000186635200013 PM 14704745 ER PT J AU Fung, CY Tarbell, NJ Lucarelli, MJ Goldberg, SI Linggood, RM Harris, NL Ferry, JA AF Fung, CY Tarbell, NJ Lucarelli, MJ Goldberg, SI Linggood, RM Harris, NL Ferry, JA TI Ocular adnexal lymphoma: Clinical behavior of distinct world health organization classification subtypes SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE non-Hodgkin's lymphoma; ocular adnexa; MALT lymphoma; radiotherapy ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; PRIMARY ORBITAL LYMPHOMA; RADIATION-THERAPY; MALT LYMPHOMA; STAGE-I; CONJUNCTIVAL LYMPHOMA; TISSUE LYMPHOMA; RADIOTHERAPY; GRADE AB Purpose: To evaluate the clinical behavior and treatment outcome of ocular adnexal lymphomas classified by the World Health Organization system, with emphasis on marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). Methods and Materials: The clinicopathologic materials from 98 consecutive patients treated for ocular adnexal lymphoma were reviewed. Fourteen patients had prior lymphoma and 84 patients had primary disease (75% Stage I, 6% Stage III, and 19% Stage IV). Radiation (photons/electrons) was administered to 102 eyes to a median dose of 30.6 Gy. The mean follow-up was 82 months. Results: The most common subtypes among the primary patients were MALT (57%) and follicular (18%) lymphoma. The 5-year actuarial local control rate in 102 irradiated eyes was 98%. Among the low-grade lymphomas, the 5-year local control rate correlated with the radiation dose in the MALT lymphoma subgroup (n = 53): 81 % for < 30 Gy and 100 % for greater than or equal to30 Gy (p < 0.01). For the non-MALT low-grade lymphomas such as follicular lymphoma (n = 30), the local control rate was 100% regardless of dose. For 39 Stage I MALT lymphoma patients treated with radiation alone, the distant relapse-free survival rate was 75% at 5 years and 45% at 10 years. Distant relapses were generally isolated and successfully salvaged by local therapy. The overall survival for this subgroup was 81% at 10 years, with no deaths from lymphoma. Conclusion: Dose-response data suggest that the optimal radiation dose for MALT lymphoma of the ocular adnexa is 30.6-32.4 Gy in 1.8-Gy fractions and follicular lymphoma is adequately controlled with doses in the mid-20 Gy range. The substantial risk of distant relapse in Stage I ocular adnexal MALT lymphoma underscores the importance of long-term follow-up for this disease and the need for additional comparative studies of MALT lymphoma of different anatomic sites. (C) 2003 Elsevier Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Fung, CY (reprint author), S Suburban Oncol Ctr, Suite 101,700 Congress St, Quincy, MA 02169 USA. NR 39 TC 120 Z9 132 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD DEC 1 PY 2003 VL 57 IS 5 BP 1382 EP 1391 DI 10.1016/S0360-3016(03)00767-3 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 745DV UT WOS:000186674600026 PM 14630277 ER PT J AU Rizzo, JF Wyatt, J Loewenstein, J Kelly, S Shire, D AF Rizzo, JF Wyatt, J Loewenstein, J Kelly, S Shire, D TI Methods and perceptual thresholds for short-term electrical stimulation of human retina with microelectrode arrays SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MORPHOMETRIC-ANALYSIS; PIGMENTOSA; IMPLANTS; BLIND; REORGANIZATION; PHOTORECEPTORS; PRESERVATION; PROSTHESIS; ELECTRODES; CORTEX AB PURPOSE. To report methods for performing epiretinal electrical stimulation with microfabricated electrode arrays and determining perceptual thresholds on awake human volunteers during acute surgical trials. METHODS. Four hypotheses were tested: (1) epiretinal stimulation can be performed during acute experiments without obviously damaging the retina or degrading vision or the health of the eye; (2) perception can be obtained 50% of the time in blind patients with charge densities below published safety limits; (3) the minimal charge needed to induce perception would be higher in patients with more severe retinal degeneration; and (4) threshold charge would be lower at shorter stimulus durations. Five subjects with severe blindness from retinitis pigmentosa and one with normal vision (who underwent enucleation of the eye because of orbital cancer) were studied. Electrical stimulation of the retina was performed on awake volunteers by placing a single 250-mum diameter hand-held needle electrode or a 10-mum thick microfabricated array of iridium oxide electrodes (400-, 100-, or 50-mum diameter) on the retina. Current sources outside the eye delivered charge to the electrodes. Assessment of damage was made by observing the clinical appearance of the eyes, comparing pre- and postoperative Visual acuity, obtaining retinal histology in one case, and comparing perceptual thresholds with published safety limits. RESULTS. No clinically visible damage to the eye or loss of vision occurred. Even at sites removed from stimulation, histology revealed swollen photoreceptor inner and outer segments, which were believed to be nonspecific findings. Percepts could not be reliably elicited with 50-mum diameter electrodes using safe charges in one blind patient. With the two larger electrodes, only the normal-sighted patient had thresholds at charge densities below 0.25 and 1.0 millicoulombs (mC)/cm(2) for 400- and 100-mum diameter electrodes, respectively, which is one seemingly reasonable estimate of safety derived from the product of charge per phase and charge density per phase. In blind patients, thresholds always exceeded these levels, although most were close to these limits in patient 6. The range of charge density thresholds with the 400-mum electrode in blind patients was 0.28 to 2.8 mC/cm(2). The normal-sighted patient had a threshold of 0.08 mC/cm(2) with a 400-mum electrode, roughly one quarter of the lowest threshold in the blind patients. Strength- duration curves obtained in two blind patients revealed the lowest threshold charge at the 0.25- or 1.0-ms stimulus duration. CONCLUSIONS. Threshold charge densities in severely blind patients were substantially higher than that in a normal-sighted patient. Charge densities in blind patients always exceeded one seemingly reasonable estimate of safe stimulation. The potential adversity of long-term stimulation of the retina by a prosthesis has yet to be determined. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Vet Adm Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Cornell Univ, Nanofabricat Lab, Ithaca, NY 14853 USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. OI Kelly, Shawn/0000-0003-3533-5268 NR 28 TC 222 Z9 226 U1 0 U2 15 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2003 VL 44 IS 12 BP 5355 EP 5361 DI 10.1167/iovs.02-0819 PG 7 WC Ophthalmology SC Ophthalmology GA 747JJ UT WOS:000186801200042 PM 14638738 ER PT J AU Rizzo, JF Wyatt, J Loewenstein, J Kelly, S Shire, D AF Rizzo, JF Wyatt, J Loewenstein, J Kelly, S Shire, D TI Perceptual efficacy of electrical stimulation of human retina with a microelectrode array during short-term surgical trials SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VISUAL-PERCEPTION; PROSTHESIS; PIGMENTOSA; BLIND; IMPLANTS; CORTEX; REORGANIZATION AB PURPOSE. This work is part of a feasibility assessment of a retinal prosthesis as a means to restore vision to patients with blindness caused by retinitis pigmentosa. The primary goal was to assess the concordance of the form of induced perception and the pattern of electrical stimulation of the retina, and the reproducibility of the responses. METHODS. Five volunteers with severe retinitis pigmentosa and one with normal vision were studied. A companion paper in this issue provides details on demographics, visual function, surgical methods, general stimulation strategy, and data analysis. Volunteers were awake during surgery while a 10-mum-thick, microfabricated electrode array was placed on the retina. The array was connected to extraocular current sources that delivered charges to 50-, 100-, and 400-mum-diameter electrodes. Negative control trials were randomly included. Perceptual quality was judged by the similarity between the form of stimulation and perception (i.e., accuracy) and the reproducibility of responses. RESULTS. Only 1 of 40 control tests yielded a false-positive result. On average, volunteers 3, 5, and 6 reported percepts that matched the stimulation pattern 48% and 32% of the time for single- and multiple-electrode trials, respectively. Two-point discrimination in the best cases may have been achieved in two blind subjects using (center-to-center) electrode separation of 600 and 1960 Am. Reproducibility was achieved 66% of the time in the blind subjects. By comparison, in the normal-sighted subject, perceptual form was reported accurately 57% of the time, with 82% reproducibility, and two-point discrimination may have been achieved in one trial with 620-mum electrode spacing and in two trials each with 1860- and 2480-mum electrode spacing. In subjects 5 and 6, perceptual size was inconsistently related to the charge, although relatively large differences in charge (median: 0.55 microcoulombs [muC]) between two trials produced differently sized percepts. Longer stimuli did not produce rounder percepts. CONCLUSIONS. Single percepts induced by single-electrode stimulation were relatively small, but the form of percepts, especially after multielectrode stimulation, often did not match the stimulation pattern, even in a normal-sighted volunteer. Reproducible percepts were more easily generated than those that matched the stimulation pattern. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Vet Adm Hosp, Ctr Innovat Visual Rehabil, Boston, MA USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Cornell Univ, Nanofabricat Lab, Ithaca, NY 14853 USA. RP Rizzo, JF (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. OI Kelly, Shawn/0000-0003-3533-5268 NR 25 TC 264 Z9 271 U1 1 U2 16 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD DEC PY 2003 VL 44 IS 12 BP 5362 EP 5369 DI 10.1167/iovs.02-0817 PG 8 WC Ophthalmology SC Ophthalmology GA 747JJ UT WOS:000186801200043 PM 14638739 ER PT J AU Guinan, JJ Backus, BC Lilaonitkul, W Aharonson, V AF Guinan, JJ Backus, BC Lilaonitkul, W Aharonson, V TI Medial olivocochlear efferent reflex in humans: Otoacoustic emission (OAE) measurement issues and the advantages of stimulus frequency OAEs SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE olivocochlear efferents; otoacoustic emissions; stimulus frequency otoacoustic emissions; cochlear physiology; acoustic reflexes ID OUTER HAIR-CELLS; COCHLEAR MICROMECHANICAL PROPERTIES; GUINEA-PIG COCHLEA; DISTORTION-PRODUCT; CONTRALATERAL SUPPRESSION; MODULATED TONES; STIMULATION; SYSTEM; NOISE; CAT AB Otoacoustic emissions (OAEs) are useful for studying medial olivocochlear (MOC) efferents, but several unresolved methodological issues cloud the interpretation of the data they produce. Most efferent assays use a "probe stimulus" to produce an OAE and an "elicitor stimulus" to evoke efferent activity and thereby change the OAE. However, little attention has been given to whether the probe stimulus itself elicits efferent activity. In addition, most studies use only contralateral (re the probe) elicitors and do not include measurements to rule out middle-ear muscle (MEM) contractions. Here we describe methods to deal with these problems and present a new efferent assay based on stimulus frequency OAEs (SFOAEs) that incorporates these methods. By using a postelicitor ivindow, we make measurements in individual subjects of efferent effects from contralateral, ipsilateral, and bilateral elicitors. Using our SFOAE assay, we demonstrate that commonly used probe sounds (clicks, tone pips, and tone pairs) elicit efferent activity, by themselves. Thus, results of efferent assays using these probe stimuli can be confounded by unwanted efferent activation. In contrast, the single 40 dB SPL tone used as the probe sound for SFOAE-based measurements evoked little or no efferent activity. Since they evoke efferent activation, clicks, tone pips, and tone pairs can be used in an adaptation efferent assay, but such paradigms are limited in measurement scope compared to paradigms that separate probe and elicitor stimuli. Finally, we describe tests to distinguish middle-ear muscle (MEM) effects from MOC effects for a number of OAE assays and show results from SFOAE-based tests. The SFOAE assay used in this study provides a sensitive, flexible, frequency-specific assay of medial efferent activation that uses a low-level probe sound that elicits little or no efferent activity, and thus provides results that can be interpreted without the confound of unintended efferent activation. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Dept Otolaryngol, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Guinan, JJ (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM jjg@epl.meei.harvard.edu OI Aharonson, Vered/0000-0002-4406-6525 FU NIDCD NIH HHS [T32 DC000038, R01 DC005977, T32 DC00038, P01 DC00119] NR 47 TC 97 Z9 103 U1 1 U2 11 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2003 VL 4 IS 4 BP 521 EP 540 DI 10.1007/s10162-002-3037-3 PG 20 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 761RE UT WOS:000187926500006 PM 12799992 ER PT J AU Oxenham, AJ Shera, CA AF Oxenham, AJ Shera, CA TI Estimates of human cochlear tuning at low levels using forward and simultaneous masking SO JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY LA English DT Article DE cochlear tuning; psychoacoustics; auditory filters; masking ID AUDITORY FILTER SHAPES; BASILAR-MEMBRANE NONLINEARITY; NORMAL-HEARING; NERVE-FIBERS; FREQUENCY-SELECTIVITY; 2-TONE SUPPRESSION; CHINCHILLA COCHLEA; NOTCHED-NOISE; GUINEA-PIG; PURE-TONE AB Auditory filter shapes were derived from psychophysical measurements in eight normal-hearing listeners using a variant of the notched-noise method for brief signals in forward and simultaneous masking. Signal frequencies of 1, 2, 4, 6, and 8 kHz were tested. The signal level was fixed at 10 dB above absolute threshold in the forward-m asking conditions and fixed at either 10 or 35 dB above absolute threshold in the simultaneous-masking conditions. The results show that filter equivalent rectangular bandwidths (ERBs) are substantially narrower in forward masking than has been found in previous studies using simultaneous masking. Furthermore, in contrast to earlier studies, the sharpness of tuning doubles over the range of frequencies tested, giving Q(ERB) values of about 10 and 20 at signal frequencies of I and 8 kHz, respectively. It is argued that the new estimates of auditory filter bandwidth provide a more accurate estimate of human cochlear tuning at low levels than earlier estimates using simultaneous masking at higher levels, and that they are therefore more suitable for comparison to cochlear tuning data from other species. The data may also prove helpful in defining the parameters for nonlinear models of human cochlear processing. C1 MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. RP Oxenham, AJ (reprint author), MIT, Elect Res Lab, Bldg 36-763, Cambridge, MA 02139 USA. EM oxenham@mit.edu FU NIDCD NIH HHS [R01 DC 03687, R01 DC003687, R01 DC003909-05, R01 DC 03909, R01 DC003909] NR 57 TC 104 Z9 109 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1525-3961 J9 JARO-J ASSOC RES OTO JI JARO PD DEC PY 2003 VL 4 IS 4 BP 541 EP 554 DI 10.1007/s10162-002-3058-y PG 14 WC Neurosciences; Otorhinolaryngology SC Neurosciences & Neurology; Otorhinolaryngology GA 761RE UT WOS:000187926500007 PM 14716510 ER PT J AU Yeap, BY Catalano, PJ Ryan, LM Davidian, M AF Yeap, BY Catalano, PJ Ryan, LM Davidian, M TI Robust two-stage approach to repeated measurements analysis of chronic ozone exposure in rats SO JOURNAL OF AGRICULTURAL BIOLOGICAL AND ENVIRONMENTAL STATISTICS LA English DT Article DE ANOVA; hierarchical nonlinear model; M-estimation; Michaelis-Menten; mixed effects; outlier ID DOSE-DEPENDENT TOLERANCE; MIXED EFFECTS MODELS AB A robust two-stage approach is used to reanalyze the repeated measurements from an experiment of airway responsiveness in rats randomized to long-term exposure at four ozone doses. The concentration-response data generated for each rat may be represented as a hierarchical nonlinear model encompasing the sources of variation within and between individuals, leading to the possibility of outliers at each sampling level. By estimating an individual profile for each rat, the conditional modeling approach can assess the adequacy of an assumed mean model, a fundamental advantage not intrinsic to marginal techniques. The two-stage population inference is based on the estimated individual parameters, thus maintaining an intuitive appeal to the toxicologists who traditionally have fitted a separate curve for each animal and then applied ANOVA to the summary statistics. However, we formally adjust the standard errors for the extra variability due to the initial estimation of the individual parameters and also allow for their within-rat correlation. The robust two-stage method appropriately downweights the aberrant responses arising sporadically within individuals and, more importantly, the rats which may be outlying relative to the usual population variation. The true effect of chronic ozone exposure, including a significant gender interaction, may be masked by a few rats which exert undue influence on the population estimates in a nonrobust analysis. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. RP Yeap, BY (reprint author), Harvard Univ, Sch Med, Dept Med, 50 Staniford St,Suite 560, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 20 TC 5 Z9 5 U1 0 U2 2 PU AMER STATISTICAL ASSOC & INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1444 I ST NW, STE 700, WASHINGTON, DC 20005 USA SN 1085-7117 J9 J AGR BIOL ENVIR ST JI J. Agric. Biol. Environ. Stat. PD DEC PY 2003 VL 8 IS 4 BP 438 EP 454 DI 10.1198/1085711032552 PG 17 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 760CB UT WOS:000187792200003 ER PT J AU Contreras, JP Ly, NR Gold, DR He, HZ Wand, M Weiss, ST Perkins, DL Platts-Mills, TAE Finn, PW AF Contreras, JP Ly, NR Gold, DR He, HZ Wand, M Weiss, ST Perkins, DL Platts-Mills, TAE Finn, PW TI Allergen-induced cytokine production, atopic disease, IgE, and wheeze in children SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE children; cytokines; IFN-gamma; IL-13; allergy; atopy; cockroach; dust mite ID INTERFERON-GAMMA; ASTHMA; BLOOD; RISK; PREVALENCE; RESPONSES; CHILDHOOD; ECZEMA; IL-13; CELLS AB Background: The early childhood allergen-induced immune responses associated with atopic disease and IgE production in early life are not well understood. Objective: We assessed the relationship of allergen-induced cytokine production by PBMCs to both atopic disease and to IgE increase in a cohort of children with a parental history of allergy or asthma (n = 112) at a median of 2 years of age. We examined cockroach (Bla g I)-induced, house dust mite (Der f 1)-induced, and cat (Fel d 1)-induced cytokine secretion, including secretion of IFN-gamma, IL-13, IL-10, and TNF-alpha. We investigated whether distinct cytokine patterns associated with atopic disease can be detected in immune responses of children. Methods: PBMCs were isolated, and allergen-induced cytokine secretion was analyzed by means of ELISA. Atopic disease was defined as physician- or nurse-diagnosed eczema or hay fever. Increased IgE was defined as an IgE level of greater than 35 U/mL to dust mite, cockroach, cat, and egg white or a total IgE level of 60 U/mL or. greater. Results: Compared with children without atopic disease, children with atopic disease had lower Der f 1 (P = .005) and Bla g 2 (P = .03) allergen-induced IFN-gamma levels. Compared with children without increased IgE (n = 95), those with increased IgE (n = 16) had higher Der f 1-induced (P = .006) and Fel d I-induced (P = .005) IL-13 levels and lower Bla g 2-induced (P =.03) IFN-gamma levels. Compared with children with neither atopic disease nor repeated wheeze, children with both atopic disease and repeated wheeze had lower levels of allergen-induced IFN-gamma (P = .01 for Der f 1 and P = .02 for Bla g 2) cytokine secretion. Conclusion: In young children at risk for asthma or allergy, decreased allergen-induced IFN-gamma secretion is associated with atopic disease and, in some cases, with increased IgE levels. Increased allergen-induced IL-13 secretion is most strongly associated with early life increase of IgE. C1 Brigham & Womens Hosp, Pulm & Crit Care Div, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Lab Mol Immunol, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Virginia, Asthma & Allerg Dis Ctr, Charlottesville, VA USA. RP Finn, PW (reprint author), Brigham & Womens Hosp, Pulm & Crit Care Div, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HLBI20433]; NIAID NIH HHS [AI 45007, AI/EHS35786, AI/EHS45007] NR 21 TC 25 Z9 26 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2003 VL 112 IS 6 BP 1072 EP 1077 DI 10.1016/j.jaci.2003.08.036 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 752HC UT WOS:000187154200007 PM 14657861 ER PT J AU Santillan, AA Camargo, CA Ramirez-Rivera, A Delgado-Enciso, I Rojas-Martinez, A Cantu-Diaz, F Barrera-Saldana, HA AF Santillan, AA Camargo, CA Ramirez-Rivera, A Delgado-Enciso, I Rojas-Martinez, A Cantu-Diaz, F Barrera-Saldana, HA TI Association between beta(2)-adrenoceptor polymorphisms and asthma diagnosis among Mexican adults SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE alleles; asthma; beta 2-adrenoceptor polymorphism; case-control studies; genetics; genotype; phenotype ID BRONCHIAL HYPERRESPONSIVENESS; BETA-2-ADRENERGIC RECEPTOR; GENETIC POLYMORPHISMS; ADRENOCEPTOR; POPULATION; RESPONSIVENESS; EXPRESSION; HAPLOTYPES; PROMOTER; REGION AB Background: Recent studies demonstrate that genetic variations in the human beta(2)-adrenergic receptor (beta(2)AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain. Objective: We determined frequencies of these polymorphisms to explore the association between beta(2)AR haplotypes and asthma diagnosis and phenotype. Methods: This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at beta(2)AR was identified by polymerase chain reaction-restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between beta(2)AR haplotype status and asthma diagnosis. Results: A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the "Gly16 allele without Glu27" (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6). Conclusions: Variation in the beta(2)AR gene is associated in the pathogenesis of asthma and acts as a disease modifier in nocturnal asthma. C1 Univ Autonoma Nuevo Leon, Dept Bioquim, Fac Med, Monterrey, Mexico. Hosp Enfermedades Cardiovasc & Torax, Lab Fisiol Pulmonar, Ctr Med Nacl Norte, IMSS, Monterrey, Mexico. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. RI ROJAS-MARTINEZ, AUGUSTO/D-1710-2011 OI ROJAS-MARTINEZ, AUGUSTO/0000-0003-3765-6778 FU NHLBI NIH HHS [HL-03533] NR 30 TC 39 Z9 40 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2003 VL 112 IS 6 BP 1095 EP 1100 DI 10.1016/j.jaci.2003.09.029 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 752HC UT WOS:000187154200010 PM 14657864 ER PT J AU Gross, RD Atwood, CW Grayhack, JP Shaiman, S AF Gross, RD Atwood, CW Grayhack, JP Shaiman, S TI Lung volume effects on pharyngeal swallowing physiology SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE deglutition; dysphagia; dynamic; subglottic mechanoreceptors; subglottic air pressure ID PASSY-MUIR VALVE; FUNDAMENTAL-FREQUENCY; NECK-CANCER; ASPIRATION; TRACHEOSTOMY; COORDINATION; PRESSURE; DYSPHAGIA; STROKE; RESPIRATION AB The experiment was a prospective, repeated-measures design intended to determine how the variation of lung volume affects specific measures of swallowing physiology. Swallows were recorded in 28 healthy subjects, who ranged in age from 21 to 40 yr (mean age of 29 yr), by using simultaneous videofluoroscopy, bipolar intramuscular electromyography, and respiratory inductance plethysmography. Each subject swallowed three standardized pudding-like consistency boluses at three randomized lung volumes: total lung capacity, functional residual capacity, and residual volume. The results showed that pharyngeal activity duration of deglutition for swallows produced at residual volume was significantly longer than those occurring at total lung capacity or at functional residual capacity. No significant differences were found for bolus transit time or intramuscular electromyography of the superior constrictor. The results of this experiment lend support to the hypothesis that the respiratory system may have a regulatory function related to swallowing and that positive subglottic air pressure may be important for swallowing integrity. Eventually, new treatment paradigms for oropharyngeal dysphagia that are based on respiratory physiology may be developed. C1 Vet Affairs Pittsburgh Healthcare Syst, Dept Speech Pathol & Audiol, Pittsburgh, PA 15240 USA. Vet Affairs Pittsburgh Healthcare Syst, Pulm Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Commun Sci & Disorders, Pittsburgh, PA 15260 USA. RP Gross, RD (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Dept Speech Pathol & Audiol, Univ Dr C 132A-U, Pittsburgh, PA 15240 USA. NR 49 TC 24 Z9 26 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2003 VL 95 IS 6 BP 2211 EP 2217 DI 10.1152/japplphysiol.00316.2003 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 750PF UT WOS:000187004400004 PM 12909607 ER PT J AU O'Neill, K Venegas, JG Richter, T Harris, RS Layfield, JDH Musch, G Winkler, T Melo, MFV AF O'Neill, K Venegas, JG Richter, T Harris, RS Layfield, JDH Musch, G Winkler, T Melo, MFV TI Modeling kinetics of infused (NN)-N-13-saline in acute lung injury SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE right-to-left shunt; pulmonary gas exchange; mathematical model; positron emission tomography; functional imaging ID POSITRON-EMISSION-TOMOGRAPHY; ACUTE RESPIRATORY-FAILURE; END-EXPIRATORY PRESSURE; PULMONARY GAS-EXCHANGE; PRONE POSITION; REGIONAL VENTILATION; QUANTITATIVE MEASUREMENT; DIFFUSION IMPAIRMENT; GENERAL-ANESTHESIA; MATHEMATICAL-MODEL AB A mathematical model was developed to estimate right-to-left shunt (F-s) and the volume of distribution of (NN)-N-13 in alveolar gas (V-A) and shunt tissue (V-s). The data obtained from this model are complementary to, and obtained simultaneously with, pulmonary functional positron emission tomography (PET). The model describes (NN)-N-13 kinetics in four compartments: central mixing volume, gas-exchanging lung, shunting compartment, and systemic recirculation. To validate the model, five normal prone (NP) and six surfactant-depleted sheep in the supine (LS) and prone (LP) positions were studied under general anesthesia. A central venous bolus of (NN)-N-13-labeled saline was injected at the onset of apnea as PET imaging and arterial (NN)-N-13 sampling were initiated. The model fit the tracer kinetics well (mean r(2) = 0.93). Monte Carlo simulations showed that parameters could be accurately identified in the presence of expected experimental noise. F-s derived from the model correlated well with shunt estimates derived from 02 blood concentrations and from PET images. F-s was higher for LS (54 +/- 18%) than for LP (5 +/- 4%) and NP (1 +/- 1%, P < 0.01). V-A, as a fraction of PET-measured lung gas volume, was lower for LS (0.18 &PLUSMN; 0.09) than for LP (0.96 &PLUSMN; 0.28, P < 0.01), whereas V-A, as a fraction of PET-measured lung tissue volume, was higher for LS (0.46 +/- 0.26) than for LP (0.05 +/- 0.08, P < 0.01). The main conclusions are as follows: 1) the model accurately describes measured arterial (NN)-N-13 kinetics and provides estimates of F-s, and 2) in this animal model of acute lung injury, the fraction of available gas volume participating in gas exchange is reduced in the supine position. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Dresden Univ Technol, Univ Clin Carl Gustav Carus, Clin Anesthesiol & Intens Care Med, D-01307 Dresden, Germany. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cardiac Anesthesia Grp, 55 Fruit St,Clin 255, Boston, MA 02114 USA. RI Torsten, Richter/E-3708-2010; Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [HL-56879] NR 40 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD DEC PY 2003 VL 95 IS 6 BP 2471 EP 2484 DI 10.1152/japplphysiol.00401.2003 PG 14 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 750PF UT WOS:000187004400039 PM 12897030 ER PT J AU Welt, CK Schneyer, AL Heist, K Mantzoros, CS AF Welt, CK Schneyer, AL Heist, K Mantzoros, CS TI Leptin and soluble leptin receptor in follicular fluid SO JOURNAL OF ASSISTED REPRODUCTION AND GENETICS LA English DT Article DE activin; estradiol; follistatin; leptin; oocyte ID POLYCYSTIC OVARIAN SYNDROME; OB GENE-EXPRESSION; IN-VITRO; BINDING-ACTIVITY; ADIPOSE-TISSUE; BOUND LEPTIN; NORMAL WOMEN; OBESE GENE; SERUM; INHIBIN AB Purpose: Previous studies suggest that follicular fluid leptin levels predict successful assisted reproduction. The relationship between intrafollicular leptin and the soluble leptin receptor, ovarian hormones, and oocyte quality was examined to determine potential factors contributing to this finding. Methods: Follicular fluid leptin, soluble leptin receptor, hormones, and oocyte quality were examined in 84 individual follicles from 30 women undergoing in vitro fertilization. Results: Follicular fluid leptin and soluble leptin receptor levels correlated inversely with each other (r = -0.354; p = 0.001). Follicular fluid leptin levels correlated with intrafollicular estradiol (r = 0.42; p < 0.001), progesterone (r = 0.48; p < 0.001), and androstenedione (r = 0: 49; p < 0.001), whereas soluble leptin receptor levels correlated with activin (r = 0.38; p < 0.001) and follistatin (r = 0.35; p < 0.002). There was no relationship between follicular fluid leptin or soluble leptin receptor levels and pretreatment serum hormone levels, stimulated serum estradiol, follicle number, oocyte quality, fertilization, or embryo grade. Conclusion: The data demonstrate that leptin and the soluble leptin receptor are highly interrelated with each other and with other intrafollicular hormones, but not with markers of oocyte quality, fertilization, or embryo grade. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Endocrinol, Boston, MA USA. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, BHX 511,55 Fruit St, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NICHD NIH HHS [R01HD31894, U54HD29164]; PHS HHS [R01-58785] NR 34 TC 24 Z9 24 U1 0 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1058-0468 J9 J ASSIST REPROD GEN JI J. Assist. Reprod. Genet. PD DEC PY 2003 VL 20 IS 12 BP 495 EP 501 DI 10.1023/B:JARG.0000013649.38415.2a PG 7 WC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology SC Genetics & Heredity; Obstetrics & Gynecology; Reproductive Biology GA 768FB UT WOS:000188532000003 PM 15035548 ER PT J AU Correia, FF Plummer, AR Ellen, RP Wyss, C Boches, SK Galvin, JL Paster, BJ Dewhirst, FE AF Correia, FF Plummer, AR Ellen, RP Wyss, C Boches, SK Galvin, JL Paster, BJ Dewhirst, FE TI Two paralogous families of a two-gene subtilisin operon are widely distributed in oral treponemes SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER SHEATH; SACCHAROLYTIC SPIROCHETE; PERIODONTAL-DISEASES; PRTP GENE; DENTICOLA; PROTEASE; PROTEINS; MEMBRANE; INACTIVATION; DENTILISIN AB Certain oral treponemes express a highly proteolytic phenotype and have been associated with periodontal diseases. The periodontal pathogen Treponema denticola produces dentilisin, a serine protease of the subtilisin family. The two-gene operon prcA-prtP is required for expression of active dentilisin (PrtP), a putative lipoprotein attached to the treponeme's outer membrane or sheath. The purpose of this study was to examine the diversity and structure of treponemal subtilisin-like proteases in order to better understand their distribution and function. The complete sequences of five prcA-prtP operons were determined for Treponema lecithinolyticum, "Treponema vincentii," and two canine species. Partial operon sequences were obtained for T. socranskii subsp. 04 as well as 450- to 1,000-base fragments of prtP genes from four additional treponeme strains. Phylogenetic analysis demonstrated that the sequences fall into two paralogous families. The first family includes the sequence from T. denticola. Treponemes possessing this operon family express chymotrypsin-like protease activity and can cleave the substrate N-succinyl-alanyl-alanyl-prolyl-phenylalanine-p-nitroanilide (SAAPFNA). Treponemes possessing the second paralog family do not possess chymotrypsin-like activity or cleave SAAPFNA. Despite examination of a range of protein and peptide substrates, the specificity of the second protease family remains unknown. Each of the fully sequenced prcA and prtP genes contains a 5' hydrophobic leader sequence with a treponeme lipobox. The two paralogous families of treponeme subtilisins represent a new subgroup within the subtilisin family of proteases and are the only subtilisin lipoprotein family. The present study demonstrated that the subtilisin paralogs comprising a two-gene operon are widely distributed among treponemes. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Univ Toronto, CIHR Grp Matrix Dynam, Toronto, ON M5G 1G6, Canada. Univ Zurich, Inst Orale Mikrobiol & Allgemeine Immunol, CH-8028 Zurich, Switzerland. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Dewhirst, FE (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-10374, R01 DE010374] NR 39 TC 26 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2003 VL 185 IS 23 BP 6860 EP 6869 DI 10.1128/JB.185.23.6860-6869.2003 PG 10 WC Microbiology SC Microbiology GA 745BY UT WOS:000186669500013 PM 14617650 ER PT J AU Ince, D Hooper, DC AF Ince, D Hooper, DC TI Quinolone resistance due to reduced target enzyme expression SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA TOPOISOMERASE-IV; STAPHYLOCOCCUS-AUREUS; ESCHERICHIA-COLI; FLUOROQUINOLONE RESISTANCE; SALMONELLA-TYPHIMURIUM; ANTIBIOTIC-RESISTANCE; HOMEOSTATIC CONTROL; COUMARIN ACTIVITY; BIOLOGICAL COST; GYRASE AB We report for the first time low-level quinolone resistance mediated by decreased expression of topoisomerase W in Staphylococcus aureus. A single-step mutant of wild-type S. aureus strain ISP794, P18 selected by using twice the MIC of premafloxacin, had four- and four- to eightfold greater MICs of premafloxacin and ciprofloxacin, respectively, than the wild type. Sequencing of parEC and gyrBA with their promoter regions revealed a point mutation (G-->A) 13 bp upstream of the start codon of parE. Genetic linkage studies showed that there was a high level of correlation between the mutation and the resistance phenotype, and allelic exchange confirmed the contribution of the mutation to resistance. Decreased expression of ParE and decreased steady-state levels of parEC transcripts in P18 and in resistant allelic exchange mutants were observed. The steady-state levels of gyrBA and topB transcripts were increased in P18 but not in two resistant allelic exchange mutants, and sequencing upstream of either gene did not reveal a difference between ISP794 and P18. The steady-state levels of topA transcripts were similar in the various strains. Growth competition experiments performed at 30, 37, and 41degreesC with a susceptible allelic exchange strain and a resistant allelic exchange strain suggested that loss of fitness was associated with reduced levels of ParE at 41degreesC. However, P18 had a growth advantage over ISP794 at all temperatures, suggesting that a compensatory mechanism was associated with the increased levels of gyrBA and topB transcripts. Thus, reduced levels of ParE appear to be compatible with cell survival, although there may be a fitness cost during rapid cell multiplication, which might be overcome by compensatory mechanisms without reversion of the resistance phenotype. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. RP Hooper, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01 AI023988, R01 AI23988] NR 56 TC 36 Z9 41 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD DEC PY 2003 VL 185 IS 23 BP 6883 EP 6892 DI 10.1128/JB.185.23.6883-6892.2003 PG 10 WC Microbiology SC Microbiology GA 745BY UT WOS:000186669500015 PM 14617652 ER PT J AU Epstein, S Inzerillo, AM Caminis, J Zaidi, M AF Epstein, S Inzerillo, AM Caminis, J Zaidi, M TI Disorders associated with acute rapid and severe bone loss SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Review ID GLUCOCORTICOID-INDUCED OSTEOPOROSIS; HORMONE REPLACEMENT THERAPY; CORTICOSTEROID-INDUCED OSTEOPOROSIS; OSTEOBLAST-LIKE CELLS; A-INDUCED OSTEOPENIA; ORTHOTOPIC LIVER-TRANSPLANTATION; TREATED RHEUMATOID-ARTHRITIS; RANDOMIZED CONTROLLED-TRIAL; PRIMARY BILIARY-CIRRHOSIS; ESTROGEN PLUS PROGESTIN AB We describe a constellation of bone diseases characterized by the common feature of acute, rapid, and severe bone loss accompanied by dramatic fracture rates. These disorders are poorly recognized, resulting mainly from systemic diseases, frailty, immobilization, and immunosuppressive drugs, such as glucocorticoids and the calcineurin inhibitors. The opportunity to prevent or treat fractures is commonly missed because they are often not detected. Ideally, patients need to be identified early and preventative therapy initiated promptly to avoid the rapid bone loss and fractures. The most effective therapy at present seems to be the bisphosphonates, particularly when bone resorption is predominant. However, more severe forms of bone loss that result from an osteoblastic defect and reduced bone formation may benefit potentially more from newer anabolic agents, such as recombinant human parathyroid hormone (rhPTH). C1 Mt Sinai Bone Program, Mt Sinai Sch Med, Bronx VA Med Ctr, Dept Med, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Med, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Med, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Geriatr, Sch Med, Div Endocrinol, New York, NY 10029 USA. Bronx Vet Adm Med Ctr, Dept Physiol, Sch Med, Div Endocrinol, New York, NY 10029 USA. Novartis Pharmaceut Corp, Arthrit Bone Sect, E Hanover, NJ USA. RP Epstein, S (reprint author), Mt Sinai Bone Program, Mt Sinai Sch Med, Bronx VA Med Ctr, Dept Med, 1 Gustave L Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [R01-AG 14197-08] NR 161 TC 35 Z9 41 U1 2 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2003 VL 18 IS 12 BP 2083 EP 2094 DI 10.1359/jbmr.2003.18.12.2083 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745WB UT WOS:000186712700001 PM 14672343 ER PT J AU Kammerer, CM Schneider, JL Cole, SA Hixson, JE Samollow, PB O'Connell, JR Perez, R Dyer, TD Almasy, L Blangero, J Bauer, RL Mitchell, BD AF Kammerer, CM Schneider, JL Cole, SA Hixson, JE Samollow, PB O'Connell, JR Perez, R Dyer, TD Almasy, L Blangero, J Bauer, RL Mitchell, BD TI Quantitative trait loci on chromosomes 2p, 4p, and 13q influence bone mineral density of the forearm and hip in Mexican Americans SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE genetic; linkage; bone density; forearm; genome scan ID LINKAGE ANALYSIS; GENOME SCREEN; OSTEOPOROSIS; GENE; OSTEOBLASTS; PEDIGREES; FRACTURES; SUGGESTS; CELLS; SCAN AB Introduction: The San Antonio Family Osteoporosis Study (SAFOS) was designed to identify genes and environmental factors that influence bone mineral density (BMD) using data from large Mexican-American families. Materials and Methods: We performed a genome-wide linkage analysis using 416 highly polymorphic microsatellite markers spaced approximately 9.5 cM apart to locate and identify quantitative trait loci (QTL) that affect BMD of the forearm and hip. Multipoint variance components linkage analyses were done using data on all 664 subjects, as well as two subgroups of 259 men and 261 premenopausal women, from 29 families for which genotypic and phenotypic data were available. Results: We obtained significant evidence for a QTL affecting forearm (radius midpoint) BMD in men and women combined on chromosome 4p near D4S2639 (maximum LOD = 4.33, genomic p = 0.006) and suggestive evidence for a QTL on chromosome 12q near locus D12S2070 (maximum conditional LOD = 2.35). We found suggestive evidence for a QTL influencing trochanter BMD on chromosome 6 (maximum LOD = 2.27), but no evidence for QTL affecting the femoral neck in men and women combined. In men, we obtained evidence for QTL affecting neck and trochanter BMD on chromosomes 2p near D2S1780 (maximum LOD = 3.98, genomic p = 0.013) and 13q near D13S788 (maximum LOD = 3.46, genomic p = 0.039), respectively. We found no evidence for QTL affecting forearm or hip BMD in premenopausal women. Conclusion: These results provide strong evidence that a QTL on chromosome 4p affects radius BMD in Mexican-American men and women, as well as evidence that QTL on chromosomes 2p and 13q affect hip BMD in men. Our results are consistent with some reports in humans and mice. C1 Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. Univ Maryland, Sch Med, Div Endocrinol, Baltimore, MD 21201 USA. Audie L Murphy Mem Vet Adm Med Ctr, Dept Med, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Kammerer, CM (reprint author), Univ Pittsburgh, Dept Human Genet, Grad Sch Publ Hlth, 130 DeSoto St,A310 Crabtree Hall, Pittsburgh, PA 15261 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NCRR NIH HHS [M01-RR-01346]; NHLBI NIH HHS [P01-HL45522]; NIAMS NIH HHS [R01 AR43351] NR 35 TC 80 Z9 84 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD DEC PY 2003 VL 18 IS 12 BP 2245 EP 2252 DI 10.1359/jbmr.2003.18.12.2245 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 745WB UT WOS:000186712700019 PM 14672361 ER PT J AU Baile, WF Schapira, L AF Baile, WF Schapira, L TI AACE launches a new section of cancer communication SO JOURNAL OF CANCER EDUCATION LA English DT Editorial Material C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. RP Baile, WF (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD WIN PY 2003 VL 18 IS 4 BP 180 EP 181 DI 10.1207/s15430154jce1804_3 PG 2 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 776MW UT WOS:000189120600003 PM 14959762 ER PT J AU Reddy, VY Jongnarangsin, K Albert, CM Sabbour, H Keane, D Mela, T McGovern, B Ruskin, JN AF Reddy, VY Jongnarangsin, K Albert, CM Sabbour, H Keane, D Mela, T McGovern, B Ruskin, JN TI Para-Hisian Entrainment: A novel pacing maneuver to differentiate orthodromic atrioventricular reentrant tachycardia from atrioventricular nodal reentrant tachycardia SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE tachyarrhythmias; tachycardia; mapping; entrainment; atrioventricular nodal reentrant tachycardia; atrioventricular reentrant tachycardia; supraventricular tachycardia ID SUPRAVENTRICULAR TACHYCARDIA; PATHWAY AB Para-Hisian Entrainment. Introduction: Para-Hisian pacing during sinus rhythm can help to identify the presence of an accessory pathway (AP). In this maneuver, the retrograde activation time and pattern are compared during capture and loss-of-capture of the His bundle while pacing from a para-Hisian position. However, identification of a retrograde AP does not necessitate that it is operative during the tachycardia of interest; conversely, slowly conducting or "distant" bypass tracts may not be identified. We evaluated the utility of entrainment or resetting of tachycardias from the para-Hisian position to help distinguish atrioventricular nodal reentrant tachycardia (AVNRT) from orthodromic atrioventricular tachycardia (AVRT). Methods and Results: Para-Hisian entrainment/resetting was evaluated in 50 patients: 33 with AVNRT and 17 with AVRT. The maneuvers were performed using a standard quadripolar catheter placed at the His position: low output for right ventricular (RV) capture and high output for both RV and His capture. The retrograde atrial activation sequence, SA interval (interval from stimulus to earliest retrograde atrial activation), and "local" VA interval (interval between the ventricular and atrial electrograms at the site of earliest retrograde atrial activation) were compared between His and His/RV capture. The DeltaSA was >40 ms in patients with AVNRT and was <40 ms in all but one patient with AVRT. In concert with the DeltaSA interval, the DeltaVA interval was able to fully define the mechanism of the tachycardia in all patients studied. Conclusion: Para-Hisian entrainment/resetting can determine the course of retrograde conduction operative during narrow complex tachycardias. It is a useful diagnostic maneuver in differentiating AVNRT and orthodromic AVRT. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. NR 7 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD DEC PY 2003 VL 14 IS 12 BP 1321 EP 1328 DI 10.1046/j.1540-8167.2003.03239.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 755TE UT WOS:000187426900010 PM 14678108 ER PT J AU Azar, DT Scally, A Hannush, SB Soukiasian, S Terry, M AF Azar, DT Scally, A Hannush, SB Soukiasian, S Terry, M TI Epithelial-defect-masquerade syndrome after laser in situ keratomileusis - Characteristic clinical findings and visual outcomes SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID DIFFUSE LAMELLAR KERATITIS; INGROWTH; KERATECTOMY; FLAP; MICROSCOPY; MANAGEMENT; INTERFACE AB Purpose: To describe a potentially serious complication of laser in situ keratomileusis (LASIK) that can masquerade as a persistent epithelial defect. Setting: Refractive surgery centers in academic institutions. Methods: Charts of 4 eyes in which epithelial-defect-masquerade syndrome was diagnosed were reviewed to determine the time to diagnosis and the presence of associated features that may have contributed to the delay in diagnosis. Clinical findings and outcomes of medical and surgical intervention were recorded. Results: All eyes developed an epithelial defect involving the edge of the flap during surgery. The diagnosis of epithelial ingrowth was delayed because of the presence of stromal edema (n = 4), diffuse lamellar keratitis (n = 3), and contraction of the flap leading to gutter widening (n = 4). Epithelial ingrowth was diagnosed 5, 7, 15, and 60 days after LASIK All eyes satisfied the following criteria: convexity of the peripheral epithelium at the edge of the flap associated with light reflections at the end of the flap, fluorescein pooling in the gutter, stromal edema, reduced best spectacle-corrected visual acuity (<20/60 in 3 eyes), and partial healing of the epithelial defect limited to the flap hinge. One eye developed stromal scarring and ulceration that required fortified antibiotics. Surgical repair included epithelial scraping after the flap was lifted and ironing followed by placement of a contact lens after surgery. The epithelial defect healed 5, 7, 21, and 24 days after surgery. The final uncorrected visual acuity ranged from 20/15 to 20/100. Conclusions: Epithelial ingrowth following LASIK- associated epithelial defects may masquerade as stromal edema associated with a persistent epithelial defect. A high index of suspicion for epithelial ingrowth is essential to avoid a delayed diagnosis, which can result in irreversible visual loss due to stromal melting and infectious keratitis. (C) 2003 ASCRS and ESCRS. C1 Harvard Univ, Corneal & Refract Surg Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Thomas Jefferson Univ, Jefferson Med Coll, Wills Eye Hosp, Philadelphia, PA 19107 USA. Lahey Eye Inst, Peabody, MA USA. Devers Eye Inst, Portland, OR USA. RP Azar, DT (reprint author), Harvard Univ, Corneal & Refract Surg Serv, Dept Ophthalmol, Sch Med,Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu NR 21 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 0886-3350 J9 J CATARACT REFR SURG JI J. Cataract. Refract. Surg. PD DEC PY 2003 VL 29 IS 12 BP 2358 EP 2365 DI 10.1016/S0886-3350(03)00333-X PG 8 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 760NC UT WOS:000187839600024 PM 14709297 ER PT J AU Nielsen-Preiss, SM Silva, SR Gillette, JM AF Nielsen-Preiss, SM Silva, SR Gillette, JM TI Role of PTEN and Akt in the regulation of growth and apoptosis in human osteoblastic cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE apoptosis; cell cycle; osteosarcoma; kinase; phosphatase inhibitor ID TUMOR-SUPPRESSOR PTEN; LIPID PHOSPHATASE-ACTIVITY; PHOSPHATIDYLINOSITOL 3-KINASE; OSTEOGENIC-SARCOMA; HUMAN OSTEOSARCOMA; LUNG METASTASES; G(1) ARREST; ALLELE LOSS; PROTEIN; KINASE AB Cancer cells are characterized by either an increased ability to proliferate or a diminished capacity to undergo programmed cell death. PTEN is instrumental in regulating the balance between growth and death in several cell types and has been described as a tumor suppressor. The chromosome arm on which PTEN is located is deleted in a subset of human osteosarcoma tumors. Therefore, we predicted that the loss of PTEN expression was contributing to increased Akt activation and the subsequent growth and survival of osteosarcoma tumor cells. Immunoblot analyses of several human osteosarcoma cell lines and normal osteoblasts revealed relatively abundant levels of PTEN. Furthermore, stimulation of cell growth or induction of apoptosis in osteosarcoma cells failed to affect PTEN expression or activity. Therefore, routine regulation of osteosarcoma cell growth and survival appears to be independent of changes in PTEN. Subsequently, the activation of a downstream target of PTEN activity, the survival factor Akt, was analyzed. Inappropriate activation of Akt could bypass the negative regulation by PTEN. Analyses of Akt expression in several osteosarcoma cell lines and normal osteoblasts revealed uniformly low basal levels of phosphorylated Akt. The levels of phosphorylated Akt did not increase following growth stimulation. In addition, osteosarcoma cell growth was unaffected by inhibitors of phosphatidylinositol-3 kinase, an upstream activator of the Akt signaling pathway. These data further suggest that the Akt pathway is not the predominant signaling cascade required for osteoblastic growth. However, inhibition of PTEN activity resulted in increased levels of Akt phosphorylation and enhanced cell proliferation. These data suggest that while abundant levels of PTEN normally maintain Akt in an inactive form in osteoblastic cells, the Akt signaling pathway is intact and functional. (C) 2003 Wiley-Liss, Inc. C1 Univ Colorado, Hlth Sci Ctr, Dept Orthopaed, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Cellular & Dev Biol, Denver, CO 80262 USA. RP Nielsen-Preiss, SM (reprint author), Denver VA Med Ctr, Dept Endocrinol, 1055 Clermont St,Bldg 1,9C-115,Mailstop 111H, Denver, CO 80220 USA. NR 66 TC 17 Z9 19 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD DEC 1 PY 2003 VL 90 IS 5 BP 964 EP 975 DI 10.1002/jcb.10709 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 747UH UT WOS:000186822900010 PM 14624456 ER PT J AU Dijkhuizen, RM Nicolay, K AF Dijkhuizen, RM Nicolay, K TI Magnetic resonance imaging in experimental models of brain disorders SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; APPARENT DIFFUSION-COEFFICIENT; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; TISSUE-PLASMINOGEN ACTIVATOR; CONTROLLED CORTICAL IMPACT; SLOW AXONAL-TRANSPORT; EMBOLIC STROKE MODEL; NEONATAL RAT-BRAIN; IN-VIVO; BLOOD-FLOW AB This review gives an overview of the application of magnetic resonance imaging (MRI) in experimental models of brain disorders. MRI is a noninvasive and versatile imaging modality that allows longitudinal and three-dimensional assessment of tissue morphology, metabolism, physiology, and function. MRI can be sensitized to proton density, T-1, T-2, susceptibility contrast, magnetization transfer, diffusion, perfusion, and flow. The combination of different MRI approaches (e.g., diffusion-weighted MRI, perfusion MRI, functional MRI, cell-specific MRI, and molecular MRI) allows in vivo multiparametric assessment of the pathophysiology, recovery mechanisms, and treatment strategies in experimental models of stroke, brain tumors, multiple sclerosis, neurodegenerative diseases, traumatic brain injury, epilepsy, and other brain disorders. This report reviews established MRI methods as well as promising developments in MRI research that have advanced and continue to improve our understanding of neurologic diseases and that are believed to contribute to the development of recovery improving strategies. C1 Univ Utrecht, Ctr Med, Image Sci Inst, NL-3584 CJ Utrecht, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Eindhoven Univ Technol, Dept Biomed NMR, NL-5600 MB Eindhoven, Netherlands. RP Univ Utrecht, Ctr Med, Image Sci Inst, Bolognalaan 50, NL-3584 CJ Utrecht, Netherlands. EM rick@invivonmr.uu.nl RI Dijkhuizen, Richard/A-6506-2008; Nicolay, Klaas/F-4192-2010; OI Nicolay, Klaas/0000-0002-4179-616X NR 162 TC 78 Z9 80 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0271-678X EI 1559-7016 J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD DEC PY 2003 VL 23 IS 12 BP 1383 EP 1402 DI 10.1097/01.WCB.0000100341.78607.EB PG 20 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 757CY UT WOS:000187532300001 PM 14663334 ER PT J AU Biederman, J Lopez, F Earl, CQ Swanson, JM Boellner, S AF Biederman, J Lopez, F Earl, CQ Swanson, JM Boellner, S TI Modafinil improves ADHD symptoms in children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY MAY 27-30, 2003 CL BOCA RATON, FLORIDA SP New Clin Drug Evaluat Unit, NIMH C1 Massachusetts Gen Hosp, Cambridge, MA USA. Childrens Dev Ctr PA, Maitland, FL USA. Cephalon Inc, W Chester, PA USA. Univ Calif Irvine, Irvine, CA USA. Neurol & Clin Study Ctr, Little Rock, AR USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2003 VL 13 IS 4 BP 419 EP 420 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 772QB UT WOS:000188851800017 ER PT J AU Gonzalez-Heydrich, J Raches, D Hsin, O Pravdova, I Hollander, SB Biederman, J Masek, B AF Gonzalez-Heydrich, J Raches, D Hsin, O Pravdova, I Hollander, SB Biederman, J Masek, B TI An open trial of the safety and efficacy of mirtazapine in children and adolescents with social phobia SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 43rd Annual Meeting of the New-Clinical-Drug-Evaluation-Unit CY MAY 27-30, 2003 CL BOCA RATON, FLORIDA SP New Clin Drug Evaluat Unit, NIMH C1 Harvard Univ, Sch Med, Childrens Hosp Boston, Psychopharmacol Program, Boston, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2003 VL 13 IS 4 BP 423 EP 424 PG 2 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 772QB UT WOS:000188851800024 ER PT J AU Wozniak, J AF Wozniak, J TI Pediatric bipolar disorder: The new perspective on severe mood dysfunction in children SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wozniak, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 12 Z9 14 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2003 VL 13 IS 4 BP 449 EP 451 DI 10.1089/104454603322724832 PG 3 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 772QB UT WOS:000188851800030 PM 14977457 ER PT J AU Mick, E Biederman, J Faraone, SV Murray, K Wozniak, J AF Mick, E Biederman, J Faraone, SV Murray, K Wozniak, J TI Defining a developmental subtype of bipolar disorder in a sample of nonreferred adults by age at onset SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; CONDUCT DISORDER; REFERRED CHILDREN; FAMILIAL SUBTYPE; PANIC DISORDER; ADHD CHILDREN; MANIA; COMORBIDITY; ADOLESCENTS AB Objective: To test the hypothesis that the age at onset of bipolar disorder would identify a developmental subtype of bipolar disorder in adults characterized by increased levels of irritability, chronic course, rapid cycling, and comorbidity with attention deficit hyperactivity disorder. Methods: Forty-four adult subjects diagnosed with bipolar disorder were selected from large family studies of youth with and without attention deficit hyperactivity disorder. These subjects were stratified by the age at onset in childhood (younger than 13 years; n = 8, 18%), adolescence (13-18 years; n = 12, 27%, or adulthood (older than 19 years; n = 24, 55%). All subjects were administered structure diagnostic interviews and a brief cognitive battery. Results: In contrast with adult-onset bipolar disorder, child-onset bipolar disorder was associated with a longer duration of illness, more irritability than euphoria, a mixed presentation, a more chronic or rapid-cycling course, and increased comorbidity with childhood disruptive behavior disorders and anxiety disorders. Conclusion: Stratification by age at onset of bipolar disorder identified subgroups of adult subjects with differing clinical correlates. This pattern of correlates is consistent with findings documented in children with pediatric bipolar disorder and supports the hypothesis that child-onset bipolar disorder may represent a developmental subtype of the disorder. C1 Massachusetts Gen Hosp, Pediat Psychopharm Unit, Child Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharm Unit, Child Psychiat Serv, Boston, MA 02114 USA. EM mick@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [R01 HD36317-01]; NIMH NIH HHS [R01 MH50657-07] NR 48 TC 35 Z9 36 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2003 VL 13 IS 4 BP 453 EP 462 DI 10.1089/104454603322724841 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 772QB UT WOS:000188851800031 PM 14977458 ER PT J AU Wilens, TE Biederman, J Forkner, P Ditterline, J Morris, M Moore, H Galdo, M Spencer, TJ Wozniak, J AF Wilens, TE Biederman, J Forkner, P Ditterline, J Morris, M Moore, H Galdo, M Spencer, TJ Wozniak, J TI Patterns of comorbidity and dysfunction in clinically referred preschool and school-age children with bipolar disorder SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; JUVENILE MANIA; DRUG-USE; SEMISTRUCTURED INTERVIEW; PSYCHIATRIC-DISORDERS; PREPUBERTAL CHILDREN; BEHAVIOR PROBLEMS; CONDUCT DISORDER; YOUNG-CHILDREN AB Objective: Despite its common onset in preschool years, few studies have examined the characteristics of bipolar disorder (BPD) in preschoolers. This study reports on the clinical characteristics, psychiatric comorbidity, and functioning of preschoolers identified with BPD who were referred to a pediatric psychiatric clinic. Methods: Structured psychiatric interviews assessing lifetime psychopathology by Diagnostic and Statistical Manual of Mental Disorders (third edition, revised) criteria were completed with parents about their children and confirmed by clinical interview of the child. Family, social, and overall functioning were also assessed at intake. Findings from preschoolers ages 4 to 6 years were compared with a group of children ages 7 to 9 years (school age). Results: We identified 44 preschoolers and 29 consecutively ascertained school-age youth with BPD. Preschoolers had similar rates of comorbid psychopathology compared to school-age youth with BPD. Preschoolers and school-age children with BPD typically manifest symptoms of mania and major depression simultaneously (mixed states). Both preschoolers and school-age children had substantial impairment in school, social, and overall functioning. Conclusions: These results suggest that clinically referred preschoolers with BPD share with school-age children with BPD high rates of comorbid psychopathology and impaired functioning. Follow-up of these clinically referred preschoolers with BPD evaluating the stability of their diagnoses, treatment response, and their long-term outcome is necessary. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stanley Fdn Study Bipolar Disorder, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Johnson & Johnson Ctr Study Pediat Psychopatol,Pe, Boston, MA 02115 USA. RP Wilens, TE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stanley Fdn Study Bipolar Disorder, Boston, MA 02115 USA. EM twilens@partners.org FU NIDA NIH HHS [R01 DA12945] NR 63 TC 49 Z9 50 U1 6 U2 10 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD WIN PY 2003 VL 13 IS 4 BP 495 EP 505 DI 10.1089/104454603322724887 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 772QB UT WOS:000188851800035 PM 14977462 ER PT J AU Misra, M Miller, KK Bjornson, J Hackman, A Aggarwal, A Chung, J Ott, M Herzog, DB Johnson, ML Klibanski, A AF Misra, M Miller, KK Bjornson, J Hackman, A Aggarwal, A Chung, J Ott, M Herzog, DB Johnson, ML Klibanski, A TI Alterations in growth hormone secretory dynamics in adolescent girls with anorexia nervosa and effects on bone metabolism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the Endocrine-Society CY JUN 19-22, 2003 CL PHILADELPHIA, PA SP Endocrine Soc ID MINERAL DENSITY; FACTOR-I; HYPOTHALAMIC AMENORRHEA; CORTISOL SECRETION; BODY-COMPOSITION; GH SECRETION; WOMEN; MASS; DEFICIENCY; FEMALES AB Anorexia nervosa (AN) is a disorder that is increasing in frequency in adolescents, and the age of onset is often in the prepubertal years, potentially affecting the development of peak bone mass and linear growth. The GH-IGF-I axis plays an important role in bone formation, and alterations in GH secretory patterns have been described in adult women with AN. However, GH secretory dynamics in adolescents with AN have not been described, and the effects of alterations in GH secretory patterns and GH concentration on bone metabolism in AN are not known. We examined patterns of GH secretion by deconvolutional analysis, and GH concentration by Cluster analysis, in adolescent girls with AN (n = 22) and controls ( n = 20) of comparable bone age and pubertal stage. We also examined the roles of cortisol, leptin, and estradiol in the regulation of GH secretion and concentration, and the relationship of GH secretory patterns and concentration to bone metabolism. Basal GH secretion and secretory pulse number in adolescent girls with AN were increased compared with control values ( P = 0.03 and 0.007, respectively), and increased disorderliness of GH secretion ( approximate entropy) was found in AN ( P = 0.004). Mean and nadir GH concentrations and total area under the concentration curve were increased ( P = 0.03, 0.002, and 0.03, respectively), and IGF-I levels were decreased ( P = 0.0002) in girls with AN compared with healthy adolescent girls. IGF-I levels correlated negatively with nadir GH concentrations (r = - 0.35; P = 0.02). Serum cortisol levels were higher in girls with AN than in controls ( P < 0.0001) and correlated inversely with IGF-I ( r = - 0.58; P = 0.0001) and weakly with GH concentration ( area under the concentration curve; r = - 0.43; P = 0.05). A strong inverse relationship between markers of nutritional status ( body mass index, fat mass, and leptin) and basal and pulsatile GH secretion, and mean and nadir GH concentrations was observed. GH concentration predicted levels of all markers of bone formation and a marker of bone resorption (N-telopeptide) in healthy controls, but not in AN. We demonstrate increases in basal GH secretion, number of secretory bursts, and GH concentration in adolescents with AN compared with controls, accompanied by low IGF-I levels. These data are consistent with the hypothesis that an acquired GH resistance occurs in this undernourished group. We also demonstrate that GH secretion and concentration are nutritionally regulated, and that the effects of nutrition exceed the effects of cortisol on GH concentration. Acquired GH resistance may play a role in the osteopenia and decreased peak bone mass frequently associated with AN. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Eating Disorders Unit, Boston, MA 02114 USA. Eating Disorders Ctr, Dover, NH USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, BUL 457B,55 Fruit St, Boston, MA 02114 USA. EM aklibanski@partners.org FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [DK-07703] NR 54 TC 128 Z9 130 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC 1 PY 2003 VL 88 IS 12 BP 5615 EP 5623 DI 10.1210/jc.2003-030532 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752TZ UT WOS:000187184400006 PM 14671143 ER PT J AU Shoback, DM Bilezikian, JP Turner, SA McCary, LC Guo, MD Peacock, M AF Shoback, DM Bilezikian, JP Turner, SA McCary, LC Guo, MD Peacock, M TI The calcimimetic cinacalcet normalizes serum calcium in subjects with primary hyperparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID EXTRACELLULAR CA2+-SENSING RECEPTOR; POSTMENOPAUSAL WOMEN; PARATHYROID SURGERY; ALENDRONATE; CA2+ AB Calcimimetics increase the sensitivity of the calcium-sensing receptor (CaR) to circulating serum calcium, reducing the secretion of PTH and the serum calcium concentration. We evaluated the calcimimetic cinacalcet, a novel therapy for the management of primary hyperparathyroidism. In this randomized, double-blind, dose-finding study, patients (n = 22) with primary hyperparathyroidism were given cinacalcet ( 30, 40, or 50 mg) or placebo twice daily for 15 d and observed for an additional 7 d. Serum calcium, plasma PTH, and 24-h and fasting urine calcium were measured. Baseline mean serum calcium was 10.6 mg/dl for the combined cinacalcet-treated patients (normal range, 8.4 - 10.3 mg/dl), compared with 10.4 mg/dl for the placebo group. Mean PTH at baseline was 102 pg/ml (normal range, 10 - 65 pg/ml) for the combined cinacalcet-treated patients, compared with 100 pg/ml in the placebo group. Serum calcium normalized after the second dose on d 1 and remained normal through d 15 in all cinacalcet dose groups. Maximum decreases in PTH of over 50% occurred 2 - 4 h after dosing in all cinacalcet-treated groups. The fasting and 24-h urine calcium to creatinine ratios were similar in the cinacalcet and placebo groups. This study demonstrates that cinacalcet safely normalized serum calcium and lowered PTH concentrations without increasing urinary calcium excretion in the study subjects, indicating the potential benefit of cinacalcet as a medical treatment for primary hyperparathyroidism. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Endocrine Unit 111N, Dept Med, San Francisco, CA 94121 USA. Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. RP Shoback, DM (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Endocrine Unit 111N, Dept Med, 4150 Clement St, San Francisco, CA 94121 USA. EM Dolores@itsa.ucsf.edu FU NIDDK NIH HHS [R01 DK032333] NR 21 TC 152 Z9 156 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC 1 PY 2003 VL 88 IS 12 BP 5644 EP 5649 DI 10.1210/jc.2002-021597 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752TZ UT WOS:000187184400010 PM 14671147 ER PT J AU Purnell, JQ Weigle, DS Breen, P Cummings, DE AF Purnell, JQ Weigle, DS Breen, P Cummings, DE TI Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GH-RELEASING HORMONE; PLASMA GHRELIN; FOOD-INTAKE; CIRCULATING GHRELIN; HUMAN OBESITY; WEIGHT-LOSS; STOMACH; SECRETION; GLUCOSE; LIPASE AB The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r = - 0.39; P = 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r = 0.38; P = 0.003), and high-density lipoprotein cholesterol levels (r = 0.33; P = 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r = 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin. C1 Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, Portland, OR 97201 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Harborview Med Ctr, Seattle, WA 98108 USA. RP Purnell, JQ (reprint author), Oregon Hlth & Sci Univ, Div Endocrinol Diabet & Clin Nutr, L607,3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. EM purnellj@ohsu.edu FU NCRR NIH HHS [M01RR00334, M01RR00037]; NIDDK NIH HHS [R01 DK61516, P30DK17047, R01 DK55460, K23 DK02689, K24 DK02860] NR 30 TC 187 Z9 194 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD DEC 1 PY 2003 VL 88 IS 12 BP 5747 EP 5752 DI 10.1210/jc.2003-030513 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 752TZ UT WOS:000187184400027 PM 14671163 ER PT J AU Reinders, MEJ Sho, M Izawa, A Wang, P Mukhopadhyay, D Koss, KE Geehan, CS Luster, AD Sayegh, MH Briscoe, DM AF Reinders, MEJ Sho, M Izawa, A Wang, P Mukhopadhyay, D Koss, KE Geehan, CS Luster, AD Sayegh, MH Briscoe, DM TI Proinflammatory fimctions of vascular endothelial growth factor in afloimmunity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID LYMPHOCYTE-INDUCED ANGIOGENESIS; RENAL-ALLOGRAFT REJECTION; HUMAN CARDIAC ALLOGRAFTS; FACTOR MESSENGER-RNA; SMOOTH-MUSCLE CELLS; FACTOR-KAPPA-B; FACTOR EXPRESSION; PERMEABILITY FACTOR; IN-VIVO; T-CELLS AB Vascular endothelial growth factor (VEGF), an established angiogenesis factor, is expressed in allografts undergoing rejection, but its function in the rejection process has not been defined. Here, we initially determined that VEGF is functional in the trafficking of human T cells into skin allografts in vivo in the humanized SCID mouse. In vitro, we found that VEGF enhanced endothelial cell expression of the chemokines monocyte chemoattractant protein 1 and IL-8, and in combination with IFN-gamma synergistically induced endothelial cell production of the potent T cell chemoattractant IFN-inducible protein-10 (IP-10). Treatment of BALB/c (H-2(d)) recipients of fully MHC-mismatched CS7BL/6 (H-2(b)) donor hearts with anti-VEGF markedly inhibited T cell infiltration of allografts and acute rejection. Anti-VEGF failed to inhibit T cell activation responses in vivo, but inhibited intragraft expression of several endothelial cell adhesion molecules and chemokines, including IP-10. In addition, whereas VEGF expression was increased, neovascularization was not associated with acute rejection, and treatment of allograft recipients with the angiogenesis inhibitor endostatin failed to inhibit leukocyte infiltration of the grafts. Thus, VEGF appears to be functional in acute allograft rejection via its effects on leukocyte trafficking. Together, these observations provide mechanistic insight into the proinflammatory function of VEGF in immunity. C1 Childrens Hosp, Div Nephrol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Dept Med, Boston, MA 02114 USA. RP Briscoe, DM (reprint author), Childrens Hosp, Div Nephrol, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA069212, CA069212]; NIAID NIH HHS [AI46756, R01 AI046756] NR 58 TC 141 Z9 147 U1 0 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2003 VL 112 IS 11 BP 1655 EP 1665 DI 10.1172/JCI17712 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 751VY UT WOS:000187111800010 PM 14660742 ER PT J AU Krauss, S Zhang, CY Scorrano, L Dalgaard, LT St-Pierre, J Grey, ST Lowell, BB AF Krauss, S Zhang, CY Scorrano, L Dalgaard, LT St-Pierre, J Grey, ST Lowell, BB TI Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OXYGEN SPECIES PRODUCTION; FREE FATTY-ACIDS; OB-OB MICE; INSULIN-SECRETION; OXIDATIVE STRESS; GLUTATHIONE-PEROXIDASE; ENERGY-METABOLISM; GLUCOSE TOXICITY; CHRONIC EXPOSURE; CONCANAVALIN-A AB Failure to secrete adequate amounts of insulin in response to increasing concentrations of glucose is an important feature of type 2 diabetes. The mechanism for loss of glucose responsiveness is unknown. Uncoupling protein 2 (UCP2), by virtue of its mitochondrial proton leak activity and consequent negative effect on ATP production, impairs glucose-stimulated insulin secretion. Of interest, it has recently been shown that superoxide, when added to isolated mitochondria, activates UCP2-mediated proton leak. Since obesity and chronic hyperglycemia increase mitochondrial superoxide production, as well as UCP2 expression in pancreatic beta cells, a superoxide-UCP2 pathway could contribute importantly to obesity- and hyperglycemia-induced beta cell dysfunction. This study demonstrates that endogenously produced mitochondrial superoxide activates UCP2-mediated proton leak, thus lowering ATP levels and impairing glucose-stimulated insulin secretion. Furthermore, hyperglycemia- and obesity-induced loss of glucose responsiveness is prevented by reduction of mitochondrial superoxide production or gene knockout of UCP2. Importantly, reduction of superoxide has no beneficial effect in the absence of UCP2, and superoxide levels are increased further in the absence of UCP2, demonstrating that the adverse effects of superoxide on beta cell glucose sensing are caused by activation of UCP2. Therefore, superoxide-mediated activation of UCP2 could play an important role in the pathogenesis of beta cell dysfunction and type 2 diabetes. C1 Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA USA. RP Lowell, BB (reprint author), Beth Israel Deaconess Med Ctr, Div Endocrinol, Res N RN-325,99 Brookline Ave, Boston, MA 02215 USA. RI Scorrano, Luca/A-6652-2008; Grey, Shane/B-3020-2008; Dalgaard, Louise/O-3788-2015 OI Scorrano, Luca/0000-0002-8515-8928; Grey, Shane/0000-0003-2160-1625; Dalgaard, Louise/0000-0002-3598-2775 FU NIDDK NIH HHS [R37 DK053477]; Telethon [TCP02016]; Fondazione Telethon NR 54 TC 242 Z9 254 U1 0 U2 11 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD DEC PY 2003 VL 112 IS 12 BP 1831 EP 1842 DI 10.1172/JCI200319774 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 754TT UT WOS:000187348300010 PM 14679178 ER PT J AU Small, EJ Smith, MR Seaman, JJ Petrone, S Kowalski, MO AF Small, EJ Smith, MR Seaman, JJ Petrone, S Kowalski, MO TI Combined analysis of two multicenter, randomized, placebo-controlled studies of pamidronate disodium for the palliation of bone pain in men with metastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; ADVANCED MULTIPLE-MYELOMA; SKELETAL COMPLICATIONS; BREAST-CANCER; ORAL CLODRONATE; DOUBLE-BLIND; CONTROLLED TRIAL; ZOLEDRONIC ACID; PAGETS-DISEASE; CARCINOMA AB Purpose: Bone metastases occur in approximately 80% of patients with advanced prostate cancer. Pain is common in these patients. The purpose of this study was to evaluate the effect of an intravenous bisphosphonate, pamidronate disodium, on pain control in metastatic prostate cancer patients. Patients and Methods: Two multicenter, double-blind, randomized, placebo-controlled trials were conducted in patients with bone pain due to metastatic prostate cancer, with disease progression after first-line hormonal therapy. Intravenous pamidronate disodium (90 mg) or placebo was administered every 3 weeks for 27 weeks. Efficacy was measured via self-reported pain score (Brief Pain Inventory), analgesic use, the proportion of patients with a skeletal-related event (SIZE; defined as pathologic fracture, radiation or surgery to bone, spinal cord compression, or hypercalcemia), and a pilot quantitative measurement of mobility. Laboratory evaluations included serum prostate-specific antigen, interleukin-6, bone alkaline phosphatase, and urinary bone resorption markers. Results: Results of the two trials were pooled. There were no sustained significant differences between the pamidronate and placebo groups in self-reported pain measurements, analgesic use, proportion of patients with an SIZE, or mobility at week 9 or 27. Urinary bone resorption markers were suppressed in the pamidronate group compared with placebo. Conclusion: Pamidronate disodium failed to demonstrate a significant overall treatment benefit compared with placebo in palliation of bone pain or reduction of SREs. Evaluation of more potent bisphosphonates in patients with prostate cancer is warranted. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Novartis Pharmaceut, E Hanover, NJ USA. RP Small, EJ (reprint author), Univ Calif San Francisco, Ctr Comprehens Canc, 1600 Divisadero St,A718, San Francisco, CA 94115 USA. NR 51 TC 193 Z9 198 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 DEC 1 PY 2003 VL 21 IS 23 BP 4277 EP 4284 DI 10.1200/JCO.2003.05.147 PG 8 WC Oncology SC Oncology GA 749HB UT WOS:000186912900007 PM 14581438 ER PT J AU Kerlikowske, K Miglioretti, DL Ballard-Barbash, R Weaver, DL Buist, DSM Barlow, WE Cutter, G Geller, BM Yankaskas, B Taplin, SH Carney, PA AF Kerlikowske, K Miglioretti, DL Ballard-Barbash, R Weaver, DL Buist, DSM Barlow, WE Cutter, G Geller, BM Yankaskas, B Taplin, SH Carney, PA TI Prognostic characteristics of breast cancer among postmenopausal hormone users in a screened population SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; PLUS PROGESTIN; WOMENS HEALTH; COLLABORATIVE REANALYSIS; TUMOR CHARACTERISTICS; MENOPAUSAL ESTROGEN; FAMILY HISTORY; RISK; MAMMOGRAPHY; DENSITY AB Purpose: We determined the risk of breast cancer and tumor characteristics among current postmenopausal hormone therapy users compared with nonusers, by duration of use. Methods: From January 1996 to December 2000, data were collected prospectively on 374,465 postmenopausal women aged 50 to 79 years who underwent screening mammography. We calculated the relative risk (RR) of breast cancer (invasive or ductal carcinoma-in-situ) and type of breast cancer within 12 months of postmenopausal therapy use among current hormone users with a uterus (proxy for estrogen and progestin use) and without a uterus (proxy for estrogen use), compared with nonusers. Results: Compared with nonusers, women using estrogen and progestin for greater than or equal to 5 years were at increased risk of breast tumors of stage O or I (RR, 1.51; 95% CI, 1.37 to 1.66), stage II or higher (RR, 1.46; 95% CI, 1.30 to 1.63), size less than or equal to 20 mm (RR, 1.59; 95% CI, 1.43 to 1.76), size greater than 20 mm (RR, 1.24; 95% CI, 1.09 to 1.42), grade 1 or 2 (RR, 1.60; 95% CI, 1.44 to 1.77), grade 3 or 4 (RR, 1.54; 95% CI, 1.37 to 1.73), and estrogen receptor-positive (RR, 1.72; 95%a CI, 1.55 to 1.90). Estrogen-only users were slightly more likely to have estrogen receptor-positive breast cancer compared with nonusers (RR, 1.14; 95% CI, 1.06 to 1.23). Conclusion: Use of estrogen and progestin postmenopausal hormone therapy for five years or more increased the likelihood of developing breast cancer, including both tumors with favorable prognostic features and tumors with unfavorable prognostic features. (C) 2003 by American Society of Clinical Oncology. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Gen Internal Med Sect, Dept Vet Affairs, San Francisco, CA 94143 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Nevada, Sch Med, Appl Res Facil, Ctr Res Design & Stat Methods, Reno, NV 89557 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Dept Community & Family Med, Dartmouth Med Sch, Lebanon, NH 03766 USA. RP Kerlikowske, K (reprint author), San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, 111A1,4150 Clement St, San Francisco, CA 94121 USA. FU NCI NIH HHS [U01CA70040, U01CA63731, U01CA63740, U01CA70013, U01CA86082, U01CA86076, U01CA69976, U01CA63736] NR 49 TC 93 Z9 97 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 DEC 1 PY 2003 VL 21 IS 23 BP 4314 EP 4321 DI 10.1200/JCO.2003.05.151 PG 8 WC Oncology SC Oncology GA 749HB UT WOS:000186912900012 PM 14645420 ER PT J AU Heinrich, MC Corless, CL Demetri, GD Blanke, CD von Mehren, M Joensuu, H McGreevey, LS Chen, CJ Van den Abbeele, AD Druker, BJ Kiese, B Eisenberg, B Roberts, PJ Singer, S Fletcher, CDM Silberman, S Dimitrijevic, S Fletcher, JA AF Heinrich, MC Corless, CL Demetri, GD Blanke, CD von Mehren, M Joensuu, H McGreevey, LS Chen, CJ Van den Abbeele, AD Druker, BJ Kiese, B Eisenberg, B Roberts, PJ Singer, S Fletcher, CDM Silberman, S Dimitrijevic, S Fletcher, JA TI Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; C-KIT MUTATION; DOMAIN MUTATIONS; INHIBITOR STI571; BLAST CRISIS; IN-VITRO; RESISTANCE; GROWTH AB Purpose: Most gastrointestinal stromal tumors (GISTs) express constitutively activated mutant isoforms of KIT or kinase platelet-derived growth factor receptor alpha (PDGFRA) that are potential therapeutic targets for imatinib mesylate. The relationship between mutations in these kinases and clinical response to imatinib was examined in a group of patients with advanced GIST. Patients and Methods: GISTs from 127 patients enrolled onto a phase II clinical study of imatinib were examined for mutations of KIT or PDGFRA. Mutation types were correlated with clinical outcome. Results: Activating mutations of KIT or PDGFRA were found in 112 (88.2%) and six (4.7%) GISTs, respectively. Most KIT mutations involved exon 9 (n = 23) or exon 1 1 (n = 85). All KIT mutant isoforms, but only a subset of PDGFRA mutant isoforms, were sensitive to imatinib, in vitro. In patients with GISTs harboring exon 1 1 KIT mutations, the partial response rate (PR) was 83.5%, whereas patients with tumors containing an exon 9 KIT mutation or no detectable mutation of KIT or PDGFRA had PR rates of 47.8% (P =.0006) and 0.0% (P <.0001), respectively. Patients whose tumors contained exon 11 KIT mutations had a longer event-free and overall survival than those whose tumors expressed either exon 9 KIT mutations or had no detectable kinase mutation. Conclusion: Activating mutations of KIT or PDGFRA are found in the vast majority of GISTs, and the mutational status of these oncoproteins is predictive of clinical response to imatinib. PDGFRA mutations can explain response and sensitivity to imatinib in some GISTs lacking KIT mutations. (C) 2003 by American Society of Clinical Oncology. C1 Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Boston, MA 02115 USA. Univ Turku, Turku, Finland. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Helsinki, Helsinki, Finland. Novartis Oncol, Basel, Switzerland. RP Heinrich, MC (reprint author), R&D-19 3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. NR 41 TC 1298 Z9 1383 U1 5 U2 44 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 DEC 1 PY 2003 VL 21 IS 23 BP 4342 EP 4349 DI 10.1200/JCO.2003.04.190 PG 8 WC Oncology SC Oncology GA 749HB UT WOS:000186912900016 PM 14645423 ER PT J AU Bhatia, S Yasui, Y Robison, LL Birch, JM Bogue, MK Diller, L DeLaat, C Fossati-Bellani, F Morgan, E Oberlin, O Reaman, G Ruymann, FB Tersak, J Meadows, AT AF Bhatia, S Yasui, Y Robison, LL Birch, JM Bogue, MK Diller, L DeLaat, C Fossati-Bellani, F Morgan, E Oberlin, O Reaman, G Ruymann, FB Tersak, J Meadows, AT TI High risk of subsequent neoplasms continues with extended follow-up of childhood Hodgkin's disease: Report from the late effects study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FLORIDA SP Amer Soc Hematol ID 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; BREAST-CANCER; RADIATION-THERAPY; FIELD RADIATION; THYROID-CANCER; YOUNG-WOMEN; RADIOTHERAPY; IRRADIATION; POPULATION AB Purpose: We present an update of a previously reported Late Effects Study Group cohort of 1,380 children with Hodgkin's disease (HD) diagnosed between 1955 and 1986 in patients aged 16 years or younger. We describe the pattern and incidence of subsequent neoplasms (SNs) occurring with extended follow-up. Patients and Methods: Median age at diagnosis of HD was 11.7 years (range, 0.3 to 16.9 years) and at last follow-up was 27.8 years. Median length of follow-up was 17.0 years. Results: An additional 103 SNs were ascertained (total SNs = 212). The cohort was at an 18.5-fold increased risk of developing SNs compared with the general population (standardized incidence ratio [SIR], 18.5, 95% CI, 15.6 to 21.7). The cumulative incidence of any second malignancy was 10.6% at 20 years, increasing to 26.3% at 30 years; and of solid malignancies was 7.3% at 20 years, increasing to 23.5% at 30 years. Breast cancer was the most common solid malignancy (SIR, 56.7). Other commonly occurring solid malignancies included thyroid cancer (SIR, 36.4), bone tumors (SIR, 37.1), and colorectal (SIR, 36.4), lung (SIR, 27.3), and gastric cancers (SIR, 63.9). Risk factors for solid tumors included young age at HD and radiation-based therapy. Thirty-two patients developed third neoplasms, with the cumulative incidence approaching 21% at 10 years from diagnosis of second malignancy. Conclusion: Additional follow-up of this large cohort of HD survivors documents an increasing occurrence of known radiation-associated solid tumors, (breast and thyroid cancers), as well as emergence of epithelial neoplasms common in adults, (colon and lung cancers) at a younger age than expected in the general population, necessitating ongoing surveillance of this high risk population. (C) 2003 by American Society of Clinical Oncology. C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Minnesota, Minneapolis, MN USA. Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Ist Nazl Tumori, I-20133 Milan, Italy. Inst Gustave Roussy, Villejuif, France. Columbus Childrens Hosp, Columbus, OH USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Bhatia, S (reprint author), City Hope Natl Med Ctr, 1500 E Duarte Rd, Duarte, CA 91010 USA. RI Yasui, Yutaka/E-2564-2015 OI Yasui, Yutaka/0000-0002-7717-8638 NR 47 TC 317 Z9 324 U1 0 U2 7 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 DEC 1 PY 2003 VL 21 IS 23 BP 4386 EP 4394 DI 10.1200/JCO.2003.11.059 PG 9 WC Oncology SC Oncology GA 749HB UT WOS:000186912900022 PM 14645429 ER PT J AU Mager, DL Haffajee, AD Socransky, SS AF Mager, DL Haffajee, AD Socransky, SS TI Effects of periodontitis and smoking on the microbiota of oral mucous membranes and saliva in systemically healthy subjects SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE soft-tissue microbiota; saliva; periodontal disease; smoking; systemically healthy ID BLACK-PIGMENTED BACTEROIDES; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; CIGARETTE-SMOKING; PORPHYROMONAS-GINGIVALIS; BACTERIAL ADHERENCE; EXTRACREVICULAR LOCATIONS; EXPERIMENTAL GINGIVITIS; PREVOTELLA-INTERMEDIA; MOUTH DISINFECTION; MUCOSAL SURFACES AB Background/aim: To examine the differences in the proportions of 40 bacterial species in samples from eight oral soft-tissue surfaces and saliva in systemically healthy adult subjects with and without periodontitis and in smokers and nonsmokers. Methods: Saliva and microbial samples were taken from eight oral soft-tissue surfaces in 229 systemically healthy subjects stratified by periodontal and smoking status. Subjects included 84 periodontally healthy and 145 periodontitis individuals. Of these, there were 182 nonsmokers and 47 smokers. Soft-tissue samples were taken using a "buccal brush" and saliva was taken by expectoration. All samples were individually evaluated for their content of 40 bacterial species using checkerboard DNA-DNA hybridization. The percentage of total DNA probe count was determined for each species at each sample location and averaged across subjects. The significance of differences among the proportions of the 40 test species at different sample locations was sought in these populations using the Kruskall-Wallis test and adjusted for multiple comparisons. Results: When stratified for periodontal status or smoking status, microbial profiles at most sites did not differ significantly. Generally, periodontal pathogens were found at higher levels on the soft tissues of periodontitis subjects than in periodontally healthy subjects, and at higher levels in smokers than nonsmokers. Few significant differences were found, although trends in the populations were noted. Conclusions: Small differences in the proportions of bacterial species were observed on soft tissues and in saliva comparing periodontally healthy and periodontitis subjects. Somewhat greater differences between smokers and nonsmokers were found; however, these were not statistically significant. C1 Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Mager, DL (reprint author), Forsyth Inst, Dept Periodontol & Mol Genet, 140 Fenway, Boston, MA 02115 USA. NR 54 TC 37 Z9 42 U1 1 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 2003 VL 30 IS 12 BP 1031 EP 1037 DI 10.1046/j.0303-6979.2003.00418.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 746NX UT WOS:000186753400003 PM 15002888 ER PT J AU Craig, RG Yip, JK Mijares, DQ LeGeros, RZ Socransky, SS Haffajee, AD AF Craig, RG Yip, JK Mijares, DQ LeGeros, RZ Socransky, SS Haffajee, AD TI Progression of destructive periodontal diseases in three urban minority populations: role of clinical and demographic factors SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE periodontitis; racial disparities; socioeconomic factors ID DWELLING OLDER ADULTS; ATTACHMENT LOSS; RISK INDICATORS; NATURAL-HISTORY; UNITED-STATES; ESTABLISHED PERIODONTITIS; CIGARETTE-SMOKING; PREVALENCE; 10-YEAR; HEALTH AB Background aims: Differences in prevalence, severity and risk factors for destructive periodontal diseases have been reported for ethnic/racial groups. However, it is not certain whether this disparity is due to ethnicity/race or factors associated with ethnicity/race. Therefore, the present study addressed whether the rates of disease progression and clinical and demographic factors associated with disease progression varied among three ethnic/racial groups. Methods: The study population consisted of 53 Asian-, 69 African- and 62 Hispanic-Americans. Clinical measurements included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration and plaque. Disease progression was defined as a >2 mm loss of attachment 2 months post baseline. The demographic variables examined included occupational status, report of a private dentist, years resident in the United States and smoking history. Results: The rate of attachment loss for the entire population was 0.04 mm or 0.24 mm/year. No significant differences were found among the three ethnic/racial groups. Variables associated with subsequent attachment loss for the entire population were age, male gender, mean whole-mouth plaque, erythema, bleeding upon probing, suppuration, attachment loss and probing depth, and belonging to the "unskilled" occupational group. No differences in risk profiles were found among the 3 ethnic/racial groups. Using stepwise logistic regression analysis, a model was developed to relate the clinical and demographic variables examined with subsequent attachment loss. The model indicated that prior attachment loss, gingival erythema, suppuration, being a current smoker and belonging to the "unskilled" occupational group conferred high risk of >1 site of attachment loss of >2 mm. Conclusions: The results of this study suggest that variables associated with ethnicity/race, such as occupational status, are largely responsible for the observed disparity in destructive periodontal disease progression in these populations. C1 NYU, Coll Dent, Div Biol Sci Med & Surg, Dept Basic Sci & Craniofacial Biol, New York, NY 10010 USA. NYU, Coll Dent, Dept Periodont, New York, NY 10010 USA. NYU, Coll Dent, Dept Biomat & Biomimet, New York, NY 10010 USA. Forsyth Inst, Dept Periodontol, Boston, MA USA. RP Craig, RG (reprint author), NYU, Coll Dent, Div Biol Sci Med & Surg, Dept Basic Sci & Craniofacial Biol, 345 E 24th St,Mail Code 9436, New York, NY 10010 USA. FU NIDCR NIH HHS [DE 04881, P50 DE 10593] NR 37 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD DEC PY 2003 VL 30 IS 12 BP 1075 EP 1083 DI 10.1046/j.0303-6979.2003.00421.x PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 746NX UT WOS:000186753400009 PM 15002894 ER PT J AU Street, AE King, LA King, DW Riggs, DS AF Street, AE King, LA King, DW Riggs, DS TI The associations among male - Perpetrated partner violence, wives' psychological distress and children's behavior problems: A structural equation modeling analysis SO JOURNAL OF COMPARATIVE FAMILY STUDIES LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; MATERNAL DEPRESSIVE SYMPTOMATOLOGY; VIETNAM COMBAT VETERANS; DOMESTIC VIOLENCE; FAMILY VIOLENCE; BATTERED WOMEN; ADJUSTMENT; CONFLICT; VICTIMS; QUALITY AB Male-perpetrated partner violence is receiving increased clinical and research attention in recent years as awareness grows that violence within intimate relationships is a significant public health concern. It is conservatively estimated that 1.6 million American women are beaten by their intimate partners each year (Straus & Gelles, 1986). Military and veteran populations appear to be at particular risk for male-perpetrated marital violence, with military. couples reporting higher rates of violence against women (Bohannon & Dosser, 1995), greater severity of violence against women (Shupe, et al., 1987), and greater risk of victim injury associated with violence against women (Cantos, et al., 1994) when compared to their civilian counterparts. Male-perpetrated partner violence is associated with significant physical health consequences for its female victims. For example, one investigation of women presenting to emergency rooms found that battering was responsible for more injuries to women than automobile accidents, rapes, and muggings combined (McLeer & Anwar, 1989). In addition, male-perpetrated partner violence has been shown to have wide-ranging negative consequences for the female partner's mental health, including depression (e.g., Straus, 1992), anxiety (e.g., Russell, et al., 1989), posttraumatic stress disorder (PTSD; e.g., Astin, et al., 1995), social withdrawal (e.g., Star, et al., 1979), and low self-esteem (e.g., Aguilar & Nightingale, 1994). C1 VA Boston Healthcare System, Natl Ctr PTSF, Womens Hlth Sci Div, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare System, Natl Ctr PTSF, Behav Sci Div, Boston, MA 02130 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Street, AE (reprint author), VA Boston Healthcare System, Natl Ctr PTSF, Womens Hlth Sci Div, 150 S Huntington ave, Boston, MA 02130 USA. NR 71 TC 15 Z9 15 U1 1 U2 9 PU J COMPARATIVE FAMILY STUDIES PI CALGARY PA UNIV CALGARY-DEPT SOCIOLOGY 2500 UNIVERSITY DRIVE NW, CALGARY, AB T2N 1N4, CANADA SN 0047-2328 J9 J COMP FAM STUD JI J. Comp. Fam. Stud. PD WIN PY 2003 VL 34 IS 1 BP 23 EP + PG 20 WC Family Studies SC Family Studies GA 645QP UT WOS:000180990100003 ER PT J AU Koenen, KC Stellman, JM Stellman, SD Sommer, JF AF Koenen, KC Stellman, JM Stellman, SD Sommer, JF TI Risk factors for course of posttraumatic stress disorder among Vietnam veterans: A 14-year follow-up of American Legionnaires SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID SOCIAL SUPPORT; COMBAT; EXPERIENCE; EXPOSURE; SAMPLE; FEMALE; PREDICTORS; TRAUMA; HEALTH; ANGER AB Risk factors affecting the course of posttraumatic stress disorder (PTSD) are poorly understood. As part of a larger study on characterizing exposure to herbicides in Vietnam, the authors investigated this issue in a random sample of 1,377 American Legionnaires who had served in Southeast Asia during the Vietnam War and were followed over a 14-year period. High combat exposure. perceived negative community attitudes at homecoming, minority race, depression symptoms at Time 1. and more anger at Time 1 predicted a more chronic course. Community involvement at Time 1 was protective and associated with decreased risk at Time 2. Discomfort in disclosing Vietnam experiences was associated with an increased risk for developing PTSD but did not predict its course. Combat exposure predicted PTSD course more strongly than any other risk factor. Findings suggest recovery from PTSD is significantly influenced by perceived social support. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy & Management, New York, NY 10032 USA. Natl Ctr Posttraumat Stress Disorder, Womens Hlth Sci Div, VA Boston Healthcare Syst, Boston, MA USA. Boston Med Ctr, Dept Child & Adolescent Psychiat, Boston, MA USA. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA. Amer Leg, Washington, DC USA. RP Stellman, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Hlth Policy & Management, 600 W 168th St,6th Floor, New York, NY 10032 USA. FU NCI NIH HHS [CA-17613, CA-68384, CA-91401]; NIMH NIH HHS [5T32MH13043] NR 31 TC 127 Z9 127 U1 3 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2003 VL 71 IS 6 BP 980 EP 986 DI 10.1037/0022-006X.71.6.980 PG 7 WC Psychology, Clinical SC Psychology GA 745MZ UT WOS:000186693600003 PM 14622073 ER PT J AU Manne, S DuHamel, K Winkel, G Ostroff, J Parsons, S Martini, R Williams, SE Mee, L Austin, J Redd, WH AF Manne, S DuHamel, K Winkel, G Ostroff, J Parsons, S Martini, R Williams, SE Mee, L Austin, J Redd, WH TI Perceived partner critical and avoidant behaviors as predictors of anxious and depressive symptoms among mothers of children undergoing hemopaietic stem cell transplantation SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; SOCIAL SUPPORT; CANCER; ADJUSTMENT; PARENTS; ANXIETY; STRESS; INVENTORY; DISTRESS; MODELS AB This prospective study examined the role of perceived partner criticism and avoidance in the anxiety and depressive symptoms of 148 mothers of children undergoing hemopaietic stem cell transplantation (HSCT). The roles of indicators of transplantation risk and postransplantation medical course were also examined. Perceived partner criticism (e.g., criticizing coping efforts) and perceived partner avoidance (e.g., changing the topic), objective indicators of transplantation risk. and anxiety and depressive symptoms were assessed at the time of HSCT and again 3 and 6 months later. Growth curve modeling analyses indicated that perceived partner criticism was associated with higher average depressive symptoms. However. perceived partner criticism did not predict changes in mother's anxiety. Contrary to predictions, perceived partner avoidance was associated with decreases in maternal anxiety. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19012 USA. Mt Sinai Sch Med, Ruttenberg Canc Ctr, Canc Prevent & Control Program, New York, NY USA. CUNY, Dept Psychol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat, New York, NY 10021 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Childrens Mem Hosp, Dept Psychiat, Evanston, IL 60208 USA. Stanford Univ, Sch Med, Packard Childrens Hosp, Stanford, CA 94305 USA. Emory Univ, Med Ctr, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. RP Manne, S (reprint author), Fox Chase Canc Ctr, Div Populat Sci, 333 Cottman Ave,PP 1100, Philadelphia, PA 19012 USA. OI Ostroff, Jamie/0000-0003-2671-5680 FU NIMH NIH HHS [MH 57738] NR 35 TC 14 Z9 14 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD DEC PY 2003 VL 71 IS 6 BP 1076 EP 1083 DI 10.1037/0022-006X.71.6.1076 PG 8 WC Psychology, Clinical SC Psychology GA 745MZ UT WOS:000186693600013 PM 14622083 ER PT J AU Haffajee, A AF Haffajee, A TI Clinical intervention in periodontal disease. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 35th Annual Meeting of the Interantional-Association-for-Dental-Research CY NOV 08-09, 2002 CL Buenos Aires, ARGENTINA SP Int Assoc Dent Res C1 Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2003 VL 82 SI C BP 110 EP 110 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 775UD UT WOS:000189078300605 ER PT J AU Roberts, A Socransky, SS Matthews, JB Chapple, ILC AF Roberts, A Socransky, SS Matthews, JB Chapple, ILC TI Growth responses of periodontal bacteria to a stress-associated autoinducer of microbial growth. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 1st Annual Meeting of the International-Association-for-Dental-Research CY SEP 18, 2002 CL Cardiff, WALES C1 Birmingham Sch Dent, Birmingham, W Midlands, England. Forsyth Dent Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2003 VL 82 SI C BP 506 EP 506 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 775UD UT WOS:000189078303063 ER PT J AU Balto, K White, R Muller, R Stashenko, P AF Balto, K White, R Muller, R Stashenko, P TI Inflammatory apical root resorption is associated with infection induced bone resorption: An in invo model SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT Annual Meeting of the International-Association-for-Dental-Research CY JAN 04-06, 2003 CL Riyadh, SAUDI ARABIA C1 King Abdulaziz Univ, Fac Dent, Jeddah 21413, Saudi Arabia. Harvard Sch Dent Med, Boston, MA USA. Harvard Univ, Sch Med, Orthopaed Biomech Lab, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2003 VL 82 SI C BP 599 EP 599 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 775UD UT WOS:000189078303623 ER PT J AU Zoellner, A Zoellner, S Scobe, Z Weber, HP AF Zoellner, A Zoellner, S Scobe, Z Weber, HP TI Clinical and SEM evaluation of direct and indirect relined removable partial dentures using a light-curing resin. SO JOURNAL OF DENTAL RESEARCH LA English DT Meeting Abstract CT 17th Annual Meeting of the International-Association-for-Dental-Research CY SEP 18-20, 2002 CL Hong Kong, PEOPLES R CHINA C1 Univ Witten Herdecke, Witten, Germany. Forsyth Inst, Boston, MA USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. EM axel_zollner@hsdm.harvard.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD DEC PY 2003 VL 82 SI C BP 638 EP 638 PG 1 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 775UD UT WOS:000189078303818 ER PT J AU Stein, MT Jellinek, M Wells, RD AF Stein, MT Jellinek, M Wells, RD TI The difficult parent: A reflective pediatrician's response SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Editorial Material DE the difficult patient; doctor-patient communication; Asperger syndrome C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Chief Child Psychiat Serv, Boston, MA 02115 USA. RP Stein, MT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Chief Child Psychiat Serv, Boston, MA 02115 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD DEC PY 2003 VL 24 IS 6 BP 434 EP 437 PG 4 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 755TV UT WOS:000187428300006 PM 14671478 ER PT J AU Kaazempur-Mofrad, MR Younis, HF Patel, S Isasi, A Chung, C Chan, RC Hinton, DP Lee, RT Kamm, RD AF Kaazempur-Mofrad, MR Younis, HF Patel, S Isasi, A Chung, C Chan, RC Hinton, DP Lee, RT Kamm, RD TI Cyclic strain in human carotid bifurcation and its potential correlation to atherogenesis: Idealized and anatomically-realistic models SO JOURNAL OF ENGINEERING MATHEMATICS LA English DT Article DE atherosclerosis; cyclic strain; finite-element analysis; endothelial-cell proliferation; leaky junctions ID SMOOTH-MUSCLE-CELLS; FIBROBLAST GROWTH-FACTOR; MECHANICAL STRAIN; RESIDUAL-STRESSES; ATHEROSCLEROSIS; EXPRESSION; ARTERIES; WALL; TRANSPORT; FLOW AB Various mechanical phenomena are thought to contribute to the pathogenesis of atherosclerosis. Most finite-element analyses of arterial-wall mechanics to date have focused on the quantification of mechanical wall stresses, despite an abundance of experimental evidence suggesting that endothelial and smooth muscle cells readily respond to cyclic strain. In this study, we calculate the physiologic cyclic strains in the carotid bifurcation, a common site of disease. Several geometries are constructed in this study, namely (i) a 3-D, but idealized geometry of the human carotid bifurcation, (ii) 3-D subject-specific geometries based on in vivo images of healthy volunteers' carotid bifurcations, and (iii) 2-D models based on histology-derived patient-specific anatomy and intra-plaque components. Results in both types of 3-D model show that the highest variations in cyclic strain are found at the adjoining wall of the external-common carotid and at the carotid apex, both frequent sites of early inflammation, as well as immediately distal to the carotid bulb, a site of late-stage disease, suggesting that cyclic strain may play a role in inflammation in that region as well. The 2-D models of diseased arteries show generally muted cyclic strain, but also regions such as in the shoulder regions of a fibrous cap adjacent to a lipid pool where cyclic strains are considerably elevated. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. MIT, Div Biol Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc, Boston, MA USA. RP Kamm, RD (reprint author), 77 Massachusetts Ave,Room NE 47-321, Cambridge, MA 02139 USA. NR 37 TC 26 Z9 27 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0022-0833 J9 J ENG MATH JI J. Eng. Math. PD DEC PY 2003 VL 47 IS 3-4 BP 299 EP 314 DI 10.1023/B:ENGI.0000007974.82115.16 PG 16 WC Engineering, Multidisciplinary; Mathematics, Interdisciplinary Applications SC Engineering; Mathematics GA 752WY UT WOS:000187200200007 ER PT J AU Kern, BE Balcom, JH Antoniu, BA Warshaw, AL Fernandez-del Castillo, C AF Kern, BE Balcom, JH Antoniu, BA Warshaw, AL Fernandez-del Castillo, C TI Troponin I peptide (Glu94-Leu123), a cartilage-derived angiogenesis inhibitor: In vitro and in vivo effects on human endothelial cells and on pancreatic cancer SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 18-22, 2003 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract DE angiogenesis; troponin I; pancreatic cancer ID GROWTH-FACTOR; TUMOR; EXPRESSION; PROLIFERATION; METASTASIS AB Several inhibitors of angiogenesis have been identified in bovine and shark cartilage. One of them is troponin I, which is the molecule responsible for the inhibition of the actomyosin ATPase during muscle contraction. In this study we sought to investigate if the active site of troponin I (peptide Glu94-Leu123; pTnI) is also the one responsible for the antiangiogenic properties of this protein. The effects of pTnI on endothelial cell tube formation and endothelial cell division were investigated using human umbilical vein endothelial cells, Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and production of vascular endothelial growth factor by pancreatic cancer cells (CAPAN-1) were also investigated, as was its efficacy in a mouse model of pancreatic cancer metastases. Our results show that concentrations as low as I pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that endothelial cell division was inhibited at 96 hours by 3 mug/ml pTnI (P = 0.0001). No effects were seen using troponin peptide 124-181 as a control. pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1 downregulated ICAM-1 expression on human umbilical vein endothelial cells up to 10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor production was seen by treating CAPAN-1 cells with up to 1 mug/ml pTnI. After intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P = 0.03). The active region of troponin I is the one responsible for its antiangiogenic effect. The mechanism of action of this peptide is probably multifactorial. (C) 2003 The Society for Surgery of the Alimentary Tract. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,55 Fruit St, Boston, MA 02114 USA. NR 22 TC 16 Z9 22 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD DEC PY 2003 VL 7 IS 8 BP 961 EP 968 DI 10.1016/j.gassur.2003.08.003 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 758DH UT WOS:000187617000010 PM 14675705 ER PT J AU Siddique, A Malo, MS Ocuin, LM Hinnebusch, BF Abedrapo, MA Henderson, JW Zhang, WY Mozumder, M Yang, VW Hodin, RA AF Siddique, A Malo, MS Ocuin, LM Hinnebusch, BF Abedrapo, MA Henderson, JW Zhang, WY Mozumder, M Yang, VW Hodin, RA TI Convergence of the thyroid hormone and gut-enriched Kruppel-like factor pathways in the context of enterocyte differentiation SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 18-22, 2003 CL ORLANDO, FLORIDA SP Soc Surg Alimentary Tract DE intestine; differentiation; transcription factors; thyroid hormone; gut-enriched Kruppel-like factor ID ENZYME GENE-EXPRESSION; COLONIC CELL-GROWTH; HUMAN KERATIN 4; TRANSCRIPTION FACTORS; POSTNATAL-DEVELOPMENT; RECEPTOR VARIANT; TR-ALPHA; RAT; PROMOTER; INTESTINE AB The gut-enriched Kruppel-like factor (KLF4) and the ligand-bound thyroid hormone receptor (TR) have each been shown to play a critical role in mammalian gut development and differentiation. We investigated an interrelationship between these two presumably independent pathways using the differentiation marker gene, intestinal alkaline phosphatase (UP). Transient transfections were performed in Cos-7 cells using luciferase reporter plasmids containing a 2.5 kb segment of the proximal human UP 5' regulatory region, as well as multiple deletions. Cells were cotransfected with TR and/or KLF4 expression vectors and treated +/- 100 nmol/L thyroid hormone (T3). IAP reporter gene transactivation was increased independently by KLF4 (ninefold) and ligand-bound TRbeta1 (sevenfold). Cells cotransfected with KLF4 and TRbeta1 in the presence of T3 showed synergistic activation (70-fold). A similar pattern was seen with the other T3 receptor isoform, TRalpha1. The synergistic effect was lost with deletions of the T3 and KLF4 response elements in the UP promoter and was completely or partially abolished in the case of mutant KLF4 expression vectors. The thyroid hormone receptor complex and KLF4 synergistically activate the enterocyte differentiation marker gene IAP, suggesting a previously unrecognized interrelationship between these two transcription factor pathways. (C) 2003 The Society for Surgery of the Alimentary Tract. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hodin, RA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Gray Bigelow 504,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK50623, DK47168] NR 55 TC 8 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD DEC PY 2003 VL 7 IS 8 BP 1053 EP 1061 DI 10.1016/j.gassur.2003.09.006 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 758DH UT WOS:000187617000034 PM 14675715 ER PT J AU Simonova, M Shtanko, O Sergeyev, N Weissleder, R Bogdanov, A AF Simonova, M Shtanko, O Sergeyev, N Weissleder, R Bogdanov, A TI Engineering of technetium-99m-binding artificial receptors for imaging gene expression SO JOURNAL OF GENE MEDICINE LA English DT Article DE metallothionein; osteonectin; cell-surface expression; nuclear imaging ID VIRUS THYMIDINE KINASE; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; ENDOPLASMIC-RETICULUM; REPORTER GENE; SOMATOSTATIN RECEPTOR; ADENOVIRAL VECTOR; LIVING ANIMALS; CELL-SURFACE; METALLOTHIONEIN AB Background Optimization of gene therapy protocols requires accurate and non-invasive quantification of vector delivery and gene expression. To facilitate non-invasive imaging of gene expression, we have genetically engineered 'artificial receptors', i.e. membrane proteins that bind Tc-99m-oxotechnetate ((TcOT)-Tc-99m) via transchelation from a complex with glucoheptonate. The latter is a component of a widely used clinical imaging kit. Methods The engineered marker proteins were designed as type I and II membrane proteins and consisted of (1) an (TcOT)-Tc-99m-binding domain, metallothionein (MT), and (2) a membrane-anchoring domain. Engineered constructs were used for transfection of COS-1 and 293 cells; the expression of mRNA was verified by RT-PCR. Results Immunofluorescent analysis, cell fractionation and immunoblotting revealed expression of marker proteins on plasma membrane. Transfection of cells resulted in strong positive staining of plasma membrane with anti-His-tag antibodies. Scintigraphic imaging in vitro confirmed the ability of transfected cells to bind 99mTcOT. The fraction of bound radioactivity reached a peak (3.53%) when 0.93 MBq (TcOT)-Tc-99m was added to transfected COS-1 cells. The experiment-to-control signal ratio was equal to 32 at the same added dose. Conclusions (1) Both types of engineered 'artificial receptors' were expressed on the surface of eukaryotic cells; (2) marker proteins were functional in binding (TcOT)-Tc-99m; and (3) type II membrane proteins were more efficient in binding 99mTcOT than type I proteins. We anticipate that the developed approach could be useful for 'tagging' transfected cells with (TcOT)-Tc-99m enabling imaging of tracking in vivo transduced cells or cell therapies. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Rm 5420,Bldg 149,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [R21 CA85657, P01CA69246] NR 44 TC 12 Z9 12 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD DEC PY 2003 VL 5 IS 12 BP 1056 EP 1066 DI 10.1002/jgm.448 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 757ND UT WOS:000187567600006 PM 14661181 ER PT J AU Ubel, PA Jepson, C Asch, DA AF Ubel, PA Jepson, C Asch, DA TI Misperceptions about beta-blockers and diuretics - A national survey of primary care physicians SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hypertension treatment; physician survey; pharmaceutical promotion ID SINGLE-DRUG THERAPY; QUALITY-OF-LIFE; COMMERCIAL SOURCES; UNITED-STATES; HYPERTENSION; BEHAVIOR; TRENDS; REPRESENTATIVES; MANAGEMENT; MORBIDITY AB BACKGROUND: Based on a series of clinical trials showing no difference in the effectiveness or tolerability of most major classes of antihypertensive medications, the Joint National Commission on High Blood Pressure Treatment recommends that physicians prescribe beta-blockers or diuretics as initial hypertensive therapy unless there are compelling indications for another type of medication. Nevertheless, many physicians continue to favor more expensive medications like angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers as first line agents. The persistent use of these agents raises questions as to whether physicians perceive ACE inhibitors and calcium channel blockers to be better than beta-blockers and diuretics. METHODS: We surveyed 1,200 primary care physicians in 1997, and another 500 primary care physicians in 2000, and asked them to estimate the relative effectiveness and side effects of 4 classes of medication in treating a hypothetical patient with uncomplicated hypertension: ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. In addition, we asked them to indicate whether they ever provided free samples of hypertension medications to their patients. RESULTS: Perceptions of the relative effectiveness and side effects of the 4 classes of hypertension medications did not significantly change over the 3 years, nor did prescription recommendations. Physicians perceive that diuretics are less effective at lowering blood pressure than the other 3 classes (P < .001). They also perceive that beta-blockers are less tolerated than the other 3 classes (P < .001). In a multivariate model, perceptions of effectiveness and tolerability displayed significant associations with prescription preference independent of background variables. The only other variable to contribute significantly to the model was provision of free medication samples to patients. CONCLUSIONS: Despite numerous clinical trials showing no difference in the effectiveness or side-effect profiles of these 4 classes of drugs, most physicians believed that diuretics were less effective and beta-blockers were less tolerated than other medications. Moreover, their prescription practices were associated with their provision of free samples provided by pharmaceutical representatives, even after adjusting for other demographic characteristics. Efforts to increase physicians' prescribing of beta-blockers and diuretics may need to be directed at overcoming misunderstandings about the effectiveness and tolerability of these medicines. C1 Univ Michigan, Program Improving Hlth Care Decis, Ann Arbor, MI 48109 USA. VA Ann Arbor Healthcare Syst, VA Hlth Serv Res & Dev Ctr Excellence, Ann Arbor, MI USA. Univ Michigan, Div Gen Internal Med, Ann Arbor, MI 48109 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equity Res & Promot, Philadelphia, PA USA. RP Ubel, PA (reprint author), Univ Michigan, Program Improving Hlth Care Decis, 300 N Ingalls,Room 7C27, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [R01-CA78052-01] NR 24 TC 34 Z9 34 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2003 VL 18 IS 12 BP 977 EP 983 DI 10.1111/j.1525-1497.2003.20414.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 756DK UT WOS:000187450400002 PM 14687255 ER PT J AU Van Voorhees, BW Cooper, LA Rost, KM Nutting, P Rubenstein, LV Meredith, L Wang, NY Ford, DE AF Van Voorhees, BW Cooper, LA Rost, KM Nutting, P Rubenstein, LV Meredith, L Wang, NY Ford, DE TI Primary care patients with depression are less accepting of treatment than those seen by mental health specialists SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 2002 CL ATLANTA, GEORGIA SP Soc Gen Internal Med DE attitudes; depression; quality improvement ID NATIONAL COMORBIDITY SURVEY; YOUNG-ADULTS; MAJOR DEPRESSION; UNITED-STATES; SEEKING HELP; DISORDERS; SERVICES; QUALITY; RISK; DISTURBANCES AB OBJECTIVE: This study examined whether depressed patients treated exclusively in primary care report less need for care and less acceptability of treatment options than those depressed patients treated in the specialty mental health setting after up to 6 months of treatment. DESIGN: Cross-sectional study. SETTING: Forty-five community primary care practices. PARTICIPANTS: A total of 881 persons with major depression who had received mental health services in the previous 6 months and who enrolled in 3 of the 4 Quality Improvement for Depression Collaboration Studies. MEASUREMENTS AND RESULTS: Patients were categorized into 1 of 2 groups: 1) having received mental health services exclusively from a primary care provider (45%), or 2) having received any services from a mental health specialist (55%) in the previous 6 months. Compared with patients who received care from mental health specialists, patients who received mental health services exclusively from primary care providers had 2.7-fold the odds (95% confidence interval [CI], 1.6 to 4.4) of reporting that no treatment was definitely acceptable and had 2.4-fold the odds (95% CI, 1.5 to 3.9) of reporting that evidence-based treatment options (antidepressant medication) were definitely not acceptable. These results were adjusted for demographic, social/behavioral, depression severity, and economic factors using multiple logistic regression analysis. CONCLUSIONS: Patients with depression treated exclusively by primary care providers have attitudes and beliefs more averse to care than those seen by mental health specialists. These differences in attitudes and beliefs may contribute to lower quality depression care observed in comparisons of primary care and specialty mental health providers. C1 Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Univ Colorado, Hlth Sci Ctr, Dept Family Med, Denver, CO USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RAND Corp, Hlth Program, Santa Monica, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. RP Ford, DE (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Internal Med, 2024 E Monument St,Suite 2500, Baltimore, MD 21205 USA. OI Wang, Nae-Yuh/0000-0001-6513-9730 FU BHP HRSA HHS [T32PE10025]; NIMH NIH HHS [5-R01MH5443] NR 55 TC 36 Z9 36 U1 4 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD DEC PY 2003 VL 18 IS 12 BP 991 EP 1000 DI 10.1111/j.1525-1497.2003.21060.x PG 10 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 756DK UT WOS:000187450400004 PM 14687257 ER PT J AU Najarro, P Lee, HJ Fox, J Pease, J Smith, GL AF Najarro, P Lee, HJ Fox, J Pease, J Smith, GL TI Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1 SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID ALLERGIC AIRWAY DISEASE; VACCINIA VIRUS; COUPLED RECEPTOR; SEQUENCE-ANALYSIS; SWINEPOX VIRUS; TANAPOX VIRUS; T-CELLS; VMIP-I; CCR8; IDENTIFICATION AB Yaba-like disease virus (YLDV) genes 7L and 145R are located on opposite ends of the genome and are predicted to encode 7-transmembrane proteins (7-TM) that share 53 and 44% amino acid identity, respectively, to human CC chemokine receptor 8 (hCCR8). In this report, we demonstrate that early after infection with YLDV, cells acquire the ability to bind human CCL1. By expression of genes 7L and 145R in vaccinia virus, we demonstrated that each protein is glycosylated and is exposed on the cell surface with the N terminus outside the cell. Protein 7L, but not 145R, is able to bind hCCL1 (K-d = 0.6 +/- 0.13 nM) and couple to heterotrimeric G-proteins and to activate the extracellular signal-regulated kinases (ERK1/2). 7L binds several chemokines including the viral chemokines vMIPI and vMIPII and hCCL7/MCP3. This binding seems species-specific as 7L does not bind the murine orthologues of CCL1 and CCL7 in the assays used. This represents the first example of a poxviral 7-TM chemokine receptor that has functional interactions with a human chemokine. C1 Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Virol, London W2 1PG, England. Univ London Imperial Coll Sci Technol & Med, Fac Med, Dept Leukocyte Biol, London SW1 2AZ, England. RP Smith, GL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet, Boston, MA 02114 USA. EM glsmith@imperial.ac.uk OI Fox, James/0000-0002-2473-7029 NR 47 TC 10 Z9 12 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD DEC PY 2003 VL 84 BP 3325 EP 3336 DI 10.1099/vir.0.19591-0 PN 12 PG 12 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 806WZ UT WOS:000220465300014 PM 14645913 ER PT J AU Adeoye, OM Ferrell, RE Kirshner, MA Mulsant, BH Seligman, K Begley, AE Reynolds, CF Pollock, BG AF Adeoye, OM Ferrell, RE Kirshner, MA Mulsant, BH Seligman, K Begley, AE Reynolds, CF Pollock, BG TI alpha 1-acid glycoprotein in late-life depression: Relationship to medical burden and genetics SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article DE alpha 1-acid glycoprotein; AAG; late-life depression; CIRS-G ID IMIPRAMINE; BINDING; DISORDERS; ORM1; AGE AB Serum alpha1-acid glycoprotein (AAG) concentrations were examined in relationship to age, medical burden, depression, and mental status in elderly control (n = 19, mean age = 72.1 +/- 6.8 years) and depressed (n = 58, mean age = 71.9 +/- 7.1 years) subjects. DNA was analyzed for allelic variants of the AGP1 (ORM1) gene in both groups. Depressed subjects' AAG serum levels were measured at baseline and after 6 weeks of antidepressant treatment. Before treatment, depressed subjects had significantly higher serum AAG concentrations than nondepressed controls (t(49.2) = -3.48, P =.0011). Pretreatment AAG levels also correlated with degree of medical burden, measured by the Cumulative Illness Rating Scale-Geriatrics (r = 0.28, P =.0303), but not with age, depression severity, or cognitive scores. There was no significant difference between responders and nonresponders on changes in AAG levels from baseline to week 6. Frequency differences in ORM1 allelic variants apparently did not influence increased AAG concentrations in depressed patients. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Cincinnati, Dept Emergency Med, Cincinnati, OH USA. VA Pittsburgh Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Pollock, BG (reprint author), Univ Pittsburgh, Dept Psychiat, Thomas Detre Hall,3811 O Hara St, Pittsburgh, PA 15213 USA. EM pollockbg@upmc.edu FU NIMH NIH HHS [MH65416, MH01613, MH52247, MH30915, MH59666] NR 16 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD DEC PY 2003 VL 16 IS 4 BP 235 EP 239 DI 10.1177/0891988703258321 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 847GK UT WOS:000223380500008 PM 14653433 ER PT J AU Bertho, N Cerny, J Kim, YM Fiebiger, E Ploegh, H Boes, M AF Bertho, N Cerny, J Kim, YM Fiebiger, E Ploegh, H Boes, M TI Requirements for T cell-polarized tubulation of class II+ compartments in dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN PRESENTATION; IMMUNOLOGICAL SYNAPSE; TETRASPAN MICRODOMAINS; ACTIVATION; TRANSPORT; MOLECULES; COMPLEXES; CYTOSKELETON; EXPRESSION; CDW78 AB Activation of naive CD4 T cells by dendritic cells requires the sequential interaction of many TCR molecules with peptide-class II complexes of the appropriate specificity. Such interaction results in morphological transformation of class II MHC-containing endosomal compartments. In this study, we analyze the requirements for long tubular endosomal structures that polarize toward T cell contact sites using dendritic cells from I-A(b) class II-enhanced green fluorescent protein knock-in mice and I-A(b)-restricted CD4 T cells specific for OVA. Clustering of membrane proteins and ligation of T cell adhesion molecules LFA-1 and CD2 are involved in induction of endosomal tubulation. Activation of T cells increases their ability to induce class II-enhanced green fluorescent protein-positive tubules in dendritic cells, in part through up-regulation of CD40 ligand. Remarkably, and in stark contrast with the result obtained with dendritic cells loaded with intact OVA, OVA peptide added to dendritic cells failed to evoke T cell-polarized endosomal tubulation even though both conditions allowed T cell stimulation. These results suggest the existence of microdomains on the membrane of dendritic cells that allow Ag-speeific T cells to evoke tubulation in the dendritic cell. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Charles Univ, Fac Sci, Prague, Czech Republic. RP Ploegh, H (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Cerny, Jan/C-1887-2012; Kim, You-Me/I-5553-2013 OI Kim, You-Me/0000-0001-8780-704X NR 39 TC 25 Z9 26 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2003 VL 171 IS 11 BP 5689 EP 5696 PG 8 WC Immunology SC Immunology GA 746UZ UT WOS:000186767200009 PM 14634076 ER PT J AU Carman, CV Jun, CD Salas, A Springer, TA AF Carman, CV Jun, CD Salas, A Springer, TA TI Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule I engagement of leukocyte LFA-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; TRANSENDOTHELIAL MIGRATION; VASCULAR ENDOTHELIUM; LYMPHOCYTE MIGRATION; T-LYMPHOCYTES; POLYMORPHONUCLEAR LEUKOCYTES; INTEGRIN ALPHA-L-BETA-2; NEUTROPHIL MIGRATION; ICAM-1 AB Specific leukocyte/endothelial interactions are critical for immunity and inflammation, yet the molecular details of this interaction interface remain poorly understood. Thus, we investigated, with confocal microscopy, the distribution dynamics of the central adhesion molecules ICAM-1 and LFA-1 in this context. Monolayers of activated HUVECs stained with fluorescent anti-ICAM-1 Fabs or Chinese hamster ovary-K1 cells expressing ICAM-1-green fluorescent protein were allowed to bind LFA-1-bearing monocytes, neutrophils, or K562 LFA-1 transfectants. ICAM-1 was rapidly relocalized to newly formed microvilli-like membrane projections in response to binding LFA-1 on leukocytes. These ICAM-1-enriched projections encircled the leukocytes extending up their sides and clustered LFA-1 underneath into linear tracks. Projections formed independently of VCAM-1/very late Ag 4 interactions, shear, and proactive contributions from the LFA-1-bearing cells. In the ICAM-1-bearing endothelial cells, projections were enriched in actin but not microtubules, required intracellular calcium, and intact microfilament and microtubule cytoskeletons and were independent of Rho/Rho kinase signaling. Disruption of these projections with cytochalasin D, colchicine, or BAPTA-AM had no affect on firm adhesion. These data show that in response to LFA-1 engagement the endothelium proactively forms an ICAM-1-enriched cup-like structure that surrounds adherent leukocytes but is not important for firm adhesion. This finding leaves open a possible role in leukocyte transendothelial migration, which would be consistent with the geometry and kinetics of formation of the cup-like structure. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. RI Carman, Christopher/L-8108-2016; OI Carman, Christopher/0000-0001-7358-2548; Salas, Azucena/0000-0003-4572-2907 FU NCI NIH HHS [CA31798] NR 35 TC 132 Z9 136 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2003 VL 171 IS 11 BP 6135 EP 6144 PG 10 WC Immunology SC Immunology GA 746UZ UT WOS:000186767200062 PM 14634129 ER PT J AU Noh, YH Matsuda, K Hong, YK Kunstfeld, R Riccardi, L Koch, M Oura, H Dadras, SS Streit, M Detmar, M AF Noh, YH Matsuda, K Hong, YK Kunstfeld, R Riccardi, L Koch, M Oura, H Dadras, SS Streit, M Detmar, M TI An N-terminal 80 kDa recombinant fragment of human thrombospondin-2 inhibits vascular endothelial growth factor induced endothelial cell migration in vitro and tumor growth and angiogenesis in vivo SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE angiogenesis; cancer; thrombospondin-2; vascular endothelial growth factor ID ANTIANGIOGENIC ACTIVITY; MICE; PROTEIN; EXPRESSION; LYMPHANGIOGENESIS; IDENTIFICATION; CARCINOGENESIS; PROLIFERATION; ANGIOSTATIN; MECHANISMS AB We have previously shown that stable overexpression of the thrombospondin-2 (TSP-2) gene inhibited the tumor growth and angiogenesis of human squamous cell carcinoma xenotransplants. To investigate the potential antitumoral efficacy of systemic TSP-2 therapy, we expressed a recombinant 80 kDa fragment of human TSP-2 (TSP-2/NTF), encompassing the N-terminal globular region through the three type 1 repeats, in human kidney 293 EBNA cells, using a modified pCEP4 expression vector. Daily intraperitoneal injections of TSP-2/NTF resulted in a significant inhibition of the growth of human A431 squamous cell carcinomas in vivo and in reduced tumor vascularization. To further investigate possible mechanisms of the antiangiogenic activity of TSP-2/NTF, several in vitro angiogenesis assays were performed in human dermal microvascular endothelial cells. TSP-2/NTF inhibited vascular endothelial growth factor induced migration of human dermal microvascular endothelial cells and inhibited tube formation on Matrigel in vitro. TSP-2/NTF also inhibited vascular endothelial growth factor induced angiogenesis in an in vivo Matrigel assay. Moreover, TSP-2/NTF potently induced human dermal microvascular endothelial cell apoptosis in vitro but did not affect A431 tumor cell proliferation or apoptosis. These findings identify TSP-2/NTF as a potent systemic inhibitor of tumor growth and angiogenesis, acting by direct inhibition of several endothelial cell functions involved in neovascularization. C1 Massachusetts Gen Hosp, Dept Dermatol, CBRC, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Detmar, M (reprint author), Massachusetts Gen Hosp, Dept Dermatol, CBRC, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69184, CA91861, CA92644] NR 53 TC 35 Z9 35 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD DEC PY 2003 VL 121 IS 6 BP 1536 EP 1543 DI 10.1046/j.1523-1747.2003.12643.x PG 8 WC Dermatology SC Dermatology GA 752UB UT WOS:000187184600043 PM 14675207 ER PT J AU Anstead, GM Chandrasekar, B Zhang, Q Melby, PC AF Anstead, GM Chandrasekar, B Zhang, Q Melby, PC TI Multinutrient undernutrition dysregulates the resident macrophage proinflammatory cytokine network, nuclear factor-kappa B activation, and nitric oxide production SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE transcription factor; immunodeficiency; tumor necrosis factor-alpha; interleukin-6; interleukin-10 ID TUMOR-NECROSIS-FACTOR; PROTEIN-CALORIE MALNUTRITION; BLOOD MONONUCLEAR-CELLS; ALPHA MESSENGER-RNA; REGULATORY FACTOR-I; GROWTH-FACTOR-I; INTERFERON-GAMMA; TNF-ALPHA; INTERLEUKIN-6 GENE; HUMAN MONOCYTES AB We have described previously a murine model of multinutrient undernutrition that reproduced the features of moderate human malnutrition and led to increased early dissemination of Leishmania donovani. Peritoneal cells from these malnourished mice produced decreased NO after stimulation with IFN-gamma/LPS. We hypothesized that malnutrition may cause a deficit in NF-kappaB activation, a principal transcription pathway for inducible NO synthase and proinflammatory cytokines. Macrophages from malnourished mice, stimulated with IFN-gamma/LPS, showed increased IL-6 production and decreased IL-10 and TNF-alpha, production. Neutralization of TNF-alpha in macrophage cultures from the control mice mimicked the effect of malnutrition on NO and IL-10 production, whereas supplemental TNF-alpha added to cultures of macrophages from malnourished mice increased NO secretion. NF-kappaB nuclear binding activity in macrophages from the malnourished mice was reduced early after stimulation, but increased to supranormal values by 16- or 24-h poststimulation. Blocking NO production in the macrophages from the control mice reproduced the effect of malnutrition on the late activation of NF-kappaB, whereas supplemental NO decreased the late NF-kappaB activation in the malnourished mice. Thus, in macrophages from the malnourished mice, initial deficits in NF-kappaB activity probably lead to decreased TNF-alpha, which results in decreased NO; however, IL-6 is regulated independently from NF-kappaB and TNF-alpha. The late activation of NF-kappaB in the macrophages from malnourished mice is due to absence of negative feedback from NO. J. Leukoc. Biol. 74: 982-991; 2003. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Med Serv, Dept Vet Affairs Med Ctr, San Antonio, TX USA. RP Anstead, GM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NHLBI NIH HHS [HL-68020] NR 69 TC 30 Z9 30 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD DEC PY 2003 VL 74 IS 6 BP 982 EP 991 DI 10.1189/jlb.0203064 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 755FJ UT WOS:000187392600005 PM 12960263 ER PT J AU Kuhtrelber, WM Hayashi, T Dale, EA Faustman, DL AF Kuhtrelber, WM Hayashi, T Dale, EA Faustman, DL TI Central role of defective apoptosis in autoimmunity SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Review ID NONOBESE DIABETIC MICE; NF-KAPPA-B; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GLUTAMIC-ACID DECARBOXYLASE; NECROSIS-FACTOR-ALPHA; FAS LIGAND EXPRESSION; BETA-CELL DESTRUCTION; REGULATORY T-CELLS; YOUNG NOD MICE; UBIQUITIN-PROTEASOME PATHWAY AB Lymphocyte development, selection and education represent tightly controlled immune processes that normally prevent autoimmunity. Lymphocyte development likely induces cellular selection through apoptosis to remove potentially autoreactive cells. Dysregulated apoptosis, both interrupted as well as accelerated apoptosis, are now demonstrated as central defects in diverse murine autoimmune disease. In murine models of autoimmune lupus, mutations in cell death receptor Fas (CD95) and its ligand, FasL (CD95 L), have been identified. These errors create a lymphoid system resistant to apoptosis. In contrast, select lymphoid subpopulations of maturing autoimmune prone non-obese diabetic mice have identifiable and pathogenic T cells with both in vivo and in vitro heightened apoptosis after drug interventions. In part, these defects are due to faulty activation of transcription factors such as nuclear factor-kappaB (NF-kappaB) that normally protect against apoptotic death. The genetic basis of interrupted NF-kappaB in pathogenic memory T cells in diabetes is attributable to a developmentally controlled gene defect in an essential subunit of the proteasome. No specific gene in most common forms of human autoimmune disease has yet been identified. Functional assays from diverse laboratories repeatedly demonstrate heightened apoptosis in multiple cellular signaling pathways for cell death, suggesting a common theme in disease causality. C1 Massachusetts Gen Hosp, Immunobiol Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Faustman, DL (reprint author), Massachusetts Gen Hosp E, Immunobiol Lab, Bldg 149,13th St, Charlestown, MA 02129 USA. EM faustman@helix.mgh.harvard.edu NR 298 TC 30 Z9 33 U1 0 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD DEC PY 2003 VL 31 IS 3 BP 373 EP 399 DI 10.1677/jme.0.0310373 PG 27 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 761TH UT WOS:000187930300004 PM 14664701 ER PT J AU Taylor, E AF Taylor, E TI Varieties of religion today: William James revisited SO JOURNAL OF MORAL EDUCATION LA English DT Book Review C1 Harvard Univ, Sch Med, Saybrook Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Taylor, E (reprint author), Harvard Univ, Sch Med, Saybrook Inst, 5 Emerson Pl, Boston, MA 02114 USA. EM etaylor@igc.org NR 4 TC 0 Z9 0 U1 0 U2 1 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0305-7240 J9 J MORAL EDUC JI J. Moral Educ. PD DEC PY 2003 VL 32 IS 4 BP 437 EP 439 PG 3 WC Education & Educational Research SC Education & Educational Research GA 767PK UT WOS:000188459500012 ER PT J AU Moskowitz, MA AF Moskowitz, MA TI Nitric oxide and the brain microcirculation SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE eNOS; knockout mice; nitric oxide; statins; steroids C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 25 EP 25 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200083 ER PT J AU Macklis, JD AF Macklis, JD TI Activation of endogenous neural precursors/stem cells in situ: induction of neurogenesis in neocortex of adult mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE CNS repair; cortex; neural precursors/stem cells; neurogenesis; neuronal differentiation C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Nervous Syst Repair Neurol Neurosurg & Neuros, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 32 EP 32 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200109 ER PT J AU Narender, N Shailendra, G Avtar, S Inderjit, S AF Narender, N Shailendra, G Avtar, S Inderjit, S TI Anti-inflammatory effect of lovastatin in multiple sclerosis by inducing Th2 immune responses involving GATA3/STAT6 transcription SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE cytokines; EAE; signal transduction; statin; T-cells C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Dept Pathol, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 98 EP 98 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200342 ER PT J AU Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I AF Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I TI Correlation of very long chain fatty acids accumulation and inflammatory disease progression in childhood X-ALD SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE human childhood X-ALD brain; inflammatory cytokines and chemokines; super gene array; very long chain fatty acids C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 101 EP 101 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200354 ER PT J AU Bush, AI Puglielli, L Nagano, S Kovacs, DM AF Bush, AI Puglielli, L Nagano, S Kovacs, DM TI Cholesterol oxidase activity mediates neurotoxicity of the Alzheimer beta-amyloid cuproprotein SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE Alzheimer's disease; amyloid; cholesterol; copper; oxidative stress C1 Massachusetts Gen Hosp, Charlestown, MA USA. RI Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 103 EP 103 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200362 ER PT J AU Kittel, A Csapo, Z Csizmadia, E Robson, SC AF Kittel, A Csapo, Z Csizmadia, E Robson, SC TI Co-localization of the P2Y1 ADP receptor and the NTPDase1/CD39 in caveolae SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE adenosine triphosphatases; adenosine triphosphate; G-protein coupled receptors; purinergic receptors; signal transduction C1 Hungarian Acad Sci, Inst Expt Med, Budapest, Hungary. Semmelweis Univ, Dept Obstet & Gynecol, Budapest, Hungary. Harvard Univ, Sch Med, Dept Med, BIDMC, Boston, MA 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 111 EP 111 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200390 ER PT J AU Khan, M Giri, S Shah, EH Kawada, Y Singh, I Singh, AK AF Khan, M Giri, S Shah, EH Kawada, Y Singh, I Singh, AK TI Galactosylsphingosine (psychosine) inhibits lipid metabolism of peroxisomes in glial cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT Joint Meeting of the International-Society-for-Neurochemistry/Asian-Pacific-Society-for-Neuro chemistry CY AUG 03-08, 2003 CL WANCHAI, PEOPLES R CHINA SP Int soc Neurochem, Asian Pacific Soc Neurochem DE antioxidant; glial cells; peroxisomes; plasmalogens; psychosine C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph Johnson VA Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 SU 1 BP 157 EP 157 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 753PR UT WOS:000187240200567 ER PT J AU Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V AF Dracheva, S Elhakem, SL Marcus, SM Siever, LJ McGurk, SR Haroutunian, V TI RNA editing and alternative splicing of human serotonin 2C receptor in schizophrenia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alternative splicing; dorsolateral prefrontal cortex; real-time PCR; RNA editing; schizophrenia; serotonin 2C receptor ID PRE-MESSENGER-RNAS; ADENOSINE-DEAMINASE; 5-HT2C RECEPTOR; MOLECULAR BEACONS; PREFRONTAL CORTEX; MULTIPLEX DETECTION; ELDERLY PATIENTS; GLUR-B; EXPRESSION; CLONING AB Serotonin 2C receptor (5-HT2CR) heterogeneity in the brain occurs mostly from two different sources: (i) 5-HT2CR mRNA undergoes adenosine-to-inosine editing events at five positions, which leads to amino acid substitutions that produce receptor variants with different pharmacological properties; (ii) 5-HT2CR mRNA is alternatively spliced, resulting in a truncated mRNA isoform (5-HT2CR-tr) which encodes a non-functional serotonin receptor. 5-HT2CR mRNA editing efficiencies and the expression of the full-length and the truncated 5-HT2CR mRNA splice isoforms were analyzed in the prefrontal cortex of elderly subjects with schizophrenia vs. matched controls (ns = 15). No significant differences were found, indicating that there are no alterations in editing or alternative splicing of 5-HT(2C)Rs that are associated with schizophrenia in persons treated with antipsychotic medications. Quantitation of 5-HT2CR and 5-HT2CR-tr mRNA variants revealed that the expression of 5-HT2CR-tr was similar to 50% of that observed for the full-length isoform. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. RP Haroutunian, V (reprint author), Bronx Vet Affairs Med Ctr, Dept Psychiat, 30 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 46 TC 52 Z9 54 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD DEC PY 2003 VL 87 IS 6 BP 1402 EP 1412 DI 10.1046/j.1471-4159.2003.02115.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 749GU UT WOS:000186912100009 PM 14713296 ER PT J AU Dougherty, DD Weiss, AP Cosgrove, GR Alpert, NM Cassem, EH Nierenberg, AA Price, BH Mayberg, HS Fischman, AJ Rauch, SL AF Dougherty, DD Weiss, AP Cosgrove, GR Alpert, NM Cassem, EH Nierenberg, AA Price, BH Mayberg, HS Fischman, AJ Rauch, SL TI Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression SO JOURNAL OF NEUROSURGERY LA English DT Article DE neurosurgery; positron emission tomography; prefrontal cortex; thalamus; neuroimaging ID SUBGENUAL PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; MOOD DISORDERS; CINGULATE CORTEX; BRAIN ACTIVITY; AMYGDALA; REDUCTION; ORGANIZATION; PATHWAYS; SADNESS AB Object. Neurosurgical procedures are a viable intervention for severe, treatment-refractory major depression, although they have been associated with only modest rates of efficacy. The purpose of this study was to identify possible neuroimaging predictors of treatment response to anterior cingulotomy in patients with major depression. Methods. Thirteen patients underwent stereotactic anterior cingulotomy for treatment-refractory major depression. Symptom severity was measured using the Beck Depression Inventory (BDI) both before and approximately 12 months after surgery. The authors performed [F-18]fluorodeoxyglucose-positron emission tomography (PET) studies in all patients preoperatively. Statistical parametric mapping methods were used to test for loci of significant correlation between preoperative regional cerebral metabolism and postoperative reduction in BDI scores. The mean ( standard deviation) change in the BDI score from the preoperative period (43.7 +/- 7.8) to the postoperative period (30.5 +/- 21.3) was 33.1 +/- 45.4%. Two loci-the left subgenual prefrontal cortex and left thalamus-were identified as sites at which preoperative metabolism was significantly correlated with subsequent improvement in depressive symptom severity following cingulotomy. Specifically, higher preoperative rates of metabolism at these loci were associated with better postoperative results. Conclusions. Possible PET scanning predictors of treatment response were identified in patients with major depression who had undergone anterior cingulotomy. Further research will be necessary to determine the reproducibility of this finding. If confirmed, the availability of an index for noninvasively predicting a patient's response to cingulotomy for the treatment of major depression would be of great clinical value. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. McLean Hosp, Dept Neurol, Belmont, MA 02178 USA. Univ Toronto, Rotman Res Inst, Dept Psychiat, Toronto, ON, Canada. Univ Toronto, Rotman Res Inst, Dept Neurol, Toronto, ON, Canada. RP Rauch, SL (reprint author), Massachusetts Gen Hosp E, Dept Psychiat, 9th Floor,Bldg 149,13th St, Charlestown, MA 02129 USA. NR 46 TC 101 Z9 102 U1 3 U2 8 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD DEC PY 2003 VL 99 IS 6 BP 1010 EP 1017 DI 10.3171/jns.2003.99.6.1010 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 751VX UT WOS:000187111700012 PM 14705729 ER PT J AU Melo, MFV Layfield, D Harris, RS O'Neill, K Musch, G Richter, T Winkler, T Fischman, AJ Venegas, JG AF Melo, MFV Layfield, D Harris, RS O'Neill, K Musch, G Richter, T Winkler, T Fischman, AJ Venegas, JG TI Quantification of regional ventilation-perfusion ratios with PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE lung; mathematic model; PET; sheep; ventilation-perfusion ID PULMONARY BLOOD-FLOW; CONTINUOUS DISTRIBUTIONS; EMISSION-TOMOGRAPHY; HYPERPOLARIZED HE-3; DISSOCIATION CURVE; GAS-EXCHANGE; V/Q RATIOS; SCINTIGRAPHY; EMBOLISM; HUMANS AB The topographic matching of alveolar ventilation ((V) over dot V-A) and perfusion ((Q) over dot ) is the main determinant of gas exchange efficiency of the lung. However, no pulmonary functional imaging technique has been shown to predict whole-lung gas exchange in health and disease. This study aims to present a PET-based method to estimate regional alveolar ventilation-to-perfusion ratios ((V) over dot(A)/(Q) over dot) predictive of arterial blood gases. Methods: The method is based on the regional tracer kinetics of N-13-nitrogen ((NN)-N-13) after an intravenous bolus injection during a breath-hold period and subsequent washout from the lungs with resumption of breathing. The method takes into account the presence of inter- and intraregional nonuniformities at length scales smaller than the imaging spatial resolution. An algorithm used regional tracer washout to classify regional (V) over dot/(Q) over dot uniformity. Intraregional (V)over dot(A)/(Q) over dot mismatch in nonuniform regions was described with a 2-compartment model. Regional (V) over dot(A)/(Q) over dot estimates were combined into a whole-lung distribution of (V) over dot(A)/(Q) over dot ratios and were used to compute global arterial blood gases. The method was applied to 3-dimensional PET data from anesthetized and mechanically ventilated sheep before and after methacholine bronchoconstriction (n = 3) and pulmonary embolism (n = 3) and after saline lung lavage (n = 3). Results: PET images revealed regional changes in ventilation and perfusion consistent with the different disease models. Quantification of the images using PET-derived (V) over dot(A)/(Q) over dot distributions showed unimodal and narrow distributions in control conditions that became wider and unimodal after pulmonary embolism and saline lung lavage and bimodal after bronchoconstriction. Images of regional gas exchange allowed for visualization of regional gas exchange. Arterial blood gases estimated from the PET-based (V) over dot(A)/(Q) over dot distributions closely agreed with measured values (partial pressure of oxygen, arterial [Pao(2)]: r(2) = 0.97, P < 0.001; partial pressure of carbon dioxide, arterial [Paco(2)]: r(2) = 0.96, P < 0.001). Conclusion: Tracer kinetics analysis of PET images after an intravenous injection of BNN provides a quantitative assessment of regional (V) over dot(A)/(Q) over dot heterogeneity including that corresponding to length scales smaller than the spatial resolution of the imaging method. Quantification of (V) over dot(A)/(Q) over dot mismatch obtained with the presented technique is directly related to severity of gas exchange impairment as determined by arterial blood gases. C1 Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. MIT, Sch Engn, Boston, MA USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Dept Med, Boston, MA 02114 USA. Dresden Univ Technol, Univ Clin Carl Gustav Carus, D-8027 Dresden, Germany. Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. RP Melo, MFV (reprint author), Massachusetts Gen Hosp, Cardiac Anesthesia Grp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. RI Torsten, Richter/E-3708-2010; Winkler, Tilo/B-5337-2009 OI Winkler, Tilo/0000-0002-7276-5550 FU NHLBI NIH HHS [HL-56879] NR 40 TC 72 Z9 72 U1 0 U2 4 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD DEC PY 2003 VL 44 IS 12 BP 1982 EP 1991 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 753EP UT WOS:000187219400027 PM 14660725 ER PT J AU Coakley, E Scoble, KB AF Coakley, E Scoble, KB TI A reflective model for organizational assessment and interventions SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article AB A visionary academic medical center in Colombia, South America, engaged the Institute for Nursing Healthcare Leadership in a multifaceted project for the overall goal of strengthening the model of professional practice. The authors describe a reflective model for organizational assessment that steered the in-depth assessment of the organization. The model combines the constructs of culture, theory, patterns, and phenomenon with an iterative process. The organizational reflection process is applied to assessing key nursing roles and the nursing care delivery system. Recommendations and interventions that emerged from the assessment are included. C1 Inst Nursing Healthcare Leadership, Int Nurso Collaborat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Elms Coll, Chicopee, MA USA. RP Scoble, KB (reprint author), Inst Nursing Healthcare Leadership, Int Nurso Collaborat, 1 Deaconess Rd, Boston, MA 02215 USA. EM kbscoble@aol.com NR 18 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD DEC PY 2003 VL 33 IS 12 BP 660 EP 669 DI 10.1097/00005110-200312000-00009 PG 10 WC Nursing SC Nursing GA 824PO UT WOS:000221698700008 PM 14665831 ER PT J AU Bui, CH Seldin, EB Dodson, TB AF Bui, CH Seldin, EB Dodson, TB TI Types, frequencies, and risk factors for complications after third molar extraction SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3RD MOLAR SURGERY; LOCALIZED ALVEOLAR OSTEITIS; INFERIOR ALVEOLAR; NERVE DAMAGE; DRY SOCKET; POSTOPERATIVE COMPLICATIONS; SURGICAL REMOVAL; DYSESTHESIA; MORBIDITY; SMOKING AB Objectives: The study objective was to identify the types, frequency, and risk factors for complications after third molar (M3) extractions. Study Design: This retrospective cohort study consisted of patients who had 1 or more M3s removed between 1996 and 2001. Risk factors were grouped into demographic, general health, anatomic, and operative. Outcome variables were operative or inflammatory complications. Data were analyzed using descriptive, bivariate, and multivariate statistics. Results: The study sample was composed of 583 patients (57.0% male) with a mean age of 26.4 +/- 8.4 years. The overall complication rate was 4.6%. Increasing age, a positive medical history, and the position of the M3 relative to the inferior alveolar nerve were associated with an increased risk for complications. Conclusion: While age, medical history, and M3 anatomy cannot be altered directly, these factors may be modified indirectly, resulting in a potential decrease for postoperative complications. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Univ N Carolina, Sch Dent, Dept Orthodont, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Dodson, TB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, 55 Fruit St,Warren 1201, Boston, MA 02114 USA. FU NIDCR NIH HHS [K24 DE000448] NR 43 TC 93 Z9 104 U1 2 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD DEC PY 2003 VL 61 IS 12 BP 1379 EP 1389 DI 10.1016/j.joms.2003.04.001 PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 745WM UT WOS:000186714000002 PM 14663801 ER PT J AU Marcus, KJ Shamberger, R Litman, H von Allmen, D Grupp, SA Nancarrow, CM Goldwein, J Grier, HE Diller, L AF Marcus, KJ Shamberger, R Litman, H von Allmen, D Grupp, SA Nancarrow, CM Goldwein, J Grier, HE Diller, L TI Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE neuroblastoma; autologous transplantation; chemotherapy ID HIGH-RISK NEUROBLASTOMA; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE THERAPY; INTENSIVE CHEMOTHERAPY; MULTIMODALITY THERAPY; C NEUROBLASTOMA; RADIOTHERAPY; CHILDREN; IMPACT; AGE AB Objective: To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants. Methods: Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablalive regimens included 12 Gy of total body irradiation. Results: Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, I recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and I had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%. Conclusions: The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Epidemiol, Boston, MA 02115 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Marcus, KJ (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Radiat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. NR 17 TC 29 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD DEC PY 2003 VL 25 IS 12 BP 934 EP 940 DI 10.1097/00043426-200312000-00005 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 753AE UT WOS:000187208200003 PM 14663275 ER PT J AU Blais, MA Holdwick, DJ McLean, RYS Otto, MW Pollack, MH Hilsenroth, MJ AF Blais, MA Holdwick, DJ McLean, RYS Otto, MW Pollack, MH Hilsenroth, MJ TI Exploring the psychometric properties and construct validity of the MCMI-III anxiety and avoidant personality scales SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article; Proceedings Paper CT Midwinter Meeting of the Society-for-Personality-Assessment CY FEB, 1998 CL BOSTON, MASSACHUSETTS SP Soc Personal Assessment ID MEASURING DEPRESSION; INVENTORY; DISORDER; STATES AB The Millon Clinical Multiaxial Inventory (MCMI; Millon, 1983) is a commonly used self-report instrument designed to aid in the assessment of Axis 1 and Axis 11 disorders. Concerns have been expressed regarding the procedures used in the normative research for the current version of the MCMI (MCMI-III; Millon, 1994) leading to a call for additional validity research on the MCMI-III (Retzlaff, 1996). In this study, we investigated the psychometric properties of the MCMI-III's Anxiety and Avoidant personality scales in a sample of patients diagnosed with Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) anxiety disorders. Our results suggest that the MCMI-III Avoidant scale is reliable (r =.89) and it was found to demonstrate appropriate convergent and divergent validity with other self-report measures. The MCMI-III Anxiety scale also showed adequate reliability (r =.78); however, our findings raise some concerns about the discriminant validity of this scale. A scale composed of the MCMI-III core anxiety items was found to have better discriminant validity. These findings are consistent with those reported by other researchers regarding the relationship between self-report measure's of anxiety, avoidance, and depression. We conclude that the MCMI-III measures of anxiety and avoidance are consistent with other measures of these constructs and may provide valuable clinical information in this regard. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA 02114 USA. Wyoming State Hosp, Psychol Serv, Evanston, WY USA. Adelphi Univ, Garden City, NY 11530 USA. RP Blais, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 4 Z9 5 U1 1 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 237 EP 241 DI 10.1207/S15327752JPA8103_06 PG 5 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000006 PM 14638448 ER PT J AU Blais, MA AF Blais, MA TI Mental health care of deaf people: A culturally affirmative approach. SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 3 U2 20 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 293 EP 294 PG 2 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000016 ER PT J AU Blais, MA AF Blais, MA TI Conduct and oppositional defiant disorders: Epidemiology, risk factors, and treatment. SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 3 U2 20 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 293 EP 293 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000015 ER PT J AU Blais, MA AF Blais, MA TI Applied multiple regression/correlation analysis for the behavioral sciences (3rd ed.) SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blak 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 3 U2 20 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 293 EP 293 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000014 ER PT J AU Blais, MA AF Blais, MA TI Setting performance standards, concepts, methods, and perspectives. SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 3 U2 20 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 293 EP 293 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000013 ER PT J AU Blais, MA AF Blais, MA TI Behavioral, social, and emotional assessment of children and adolescents (2nd ed.). SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 294 EP 294 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000018 ER PT J AU Blais, MA AF Blais, MA TI Positive psychological assessment: A handbook of models and measures. SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Book Review C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD DEC PY 2003 VL 81 IS 3 BP 294 EP 294 PG 1 WC Psychology, Clinical; Psychology, Social SC Psychology GA 751WX UT WOS:000187114000017 ER PT J AU Shen, KZ Johnson, SW AF Shen, KZ Johnson, SW TI Group II metabotropic glutamate receptor modulation of excitatory transmission in rat subthalamic nucleus SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID PROTEIN-KINASE-C; NEURONS IN-VITRO; SYNAPTIC-TRANSMISSION; BASAL GANGLIA; PARKINSONS-DISEASE; MESSENGER-RNA; PRESYNAPTIC REGULATION; HIPPOCAMPAL SLICES; PERFORANT PATH; CA2+ CHANNELS AB Patch pipettes were used to record currents in whole-cell configuration to study the effects of group II metabotropic glutamate receptor (mGluR) stimulation on synaptic transmission in slices of rat subthalamic nucleus. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were reversibly reduced by the selective group II mGluR agonist (2'S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) in a concentration-dependent manner, with an IC50 Of 0.19 +/- 0.05 muM. DCG IV (1 mum) had no effect on inhibitory postsynaptic currents mediated by GABA. DCG IV-induced inhibition of EPSCs was reversed by the selective group II mGluR antagonist LY 341495 (100 nM) and mimicked by another selective group II agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1). Inhibition of EPSC amplitude by DCG IV and L-CCG-1 was associated with an increase in the paired-pulse ratio of EPSCs. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (2 muM) reduced the inhibitory effect of DCG IV on EPSCs. However, the response to DCG IV was not affected by the protein kinase A (PKA) activator forskolin (20 muM), by the adenylyl cyclase inhibitor MDL 12230A (20 muM), or by the phosphodiesterase inhibitor Ro 20-1724 (50 muM). DCG IV-induced inhibition of EPSCs was reduced by the non-selective protein kinase inhibitors H-7 (100 muM), H-8 (50 muM) and HA-1004 (100 muM). These results suggest that group II mGluR stimulation acts presynaptically to inhibit glutamate release by a PKC-dependent mechanism in the subthalamic nucleus. C1 Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Vet Adm Med Ctr, Portland, OR 97207 USA. RP Johnson, SW (reprint author), Portland VA Med Ctr, R&D 61,3710 SW US Vet Hosp Rd, Portland, OR 97207 USA. FU NINDS NIH HHS [NS 38175, R01 NS038175] NR 47 TC 9 Z9 9 U1 1 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD DEC 1 PY 2003 VL 553 IS 2 BP 489 EP 496 DI 10.1113/jphysiol.2003.052209 PG 8 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 754AC UT WOS:000187279700014 PM 14500768 ER PT J AU Beck, JG Gudmundsdottir, B Shipherd, JC AF Beck, JG Gudmundsdottir, B Shipherd, JC TI PTSD and emotional distress symptoms measured after a motor vehicle accident: Relationships with pain coping profiles SO JOURNAL OF PSYCHOPATHOLOGY AND BEHAVIORAL ASSESSMENT LA English DT Article DE pain; PTSD; motor vehicle accident; comorbidity ID POSTTRAUMATIC-STRESS-DISORDER; FIBROMYALGIA SYNDROME PATIENTS; LOW-BACK-PAIN; RELIABILITY; INVENTORY; SCALE; DISABILITY; SUBGROUPS; ANXIETY; IMPACT AB This study explored differences among pain patients classified as Dysfunctional, Interpersonally Distressed, and Adaptive Copers on the Multidimensional Pain Inventory with respect to PTSD symptomatology, anxiety, and depression. Eighty-five patients with pain complaints who had experienced a serious motor vehicle accident were classified into these three pain coping categories and assessed using clinician and self-report measures. Results indicated that patients classified as Adaptive Copers (n = 24) showed less PTSD symptomatology, anxiety, and depressed mood, relative to individuals classified as Dysfunctional (n = 36) and as nterpersonally Distressed (n = 25), who did not differ on these dimensions. Emotional responses during the accident (fear, helplessness, danger, perceived control, and certainty that one would die) did not differentiate the groups. Pain profiles contributed to the prediction of self-reported PTSD symptoms, controlling for state anxiety. These data suggest that pain patients with both Dysfunctional and Interpersonally Distressed coping profiles are at elevated risk for a range of posttrauma problems following a serious motor vehicle accident. C1 SUNY Buffalo, Dept Psychol, Buffalo, NY 14260 USA. Boston VA Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. RP Beck, JG (reprint author), SUNY Buffalo, Dept Psychol, Pk Hall, Buffalo, NY 14260 USA. NR 33 TC 12 Z9 12 U1 5 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0882-2689 J9 J PSYCHOPATHOL BEHAV JI J. Psychopathol. Behav. Assess. PD DEC PY 2003 VL 25 IS 4 BP 219 EP 227 DI 10.1023/A:1025817111293 PG 9 WC Psychology, Clinical SC Psychology GA 725HX UT WOS:000185539100001 ER PT J AU Hazlett-Stevens, H Craske, MG Mayer, EA Chang, L Naliboff, BD AF Hazlett-Stevens, H Craske, MG Mayer, EA Chang, L Naliboff, BD TI Prevalence of irritable bowel syndrome among university students - The roles of worry, neuroticism, anxiety sensitivity and visceral anxiety SO JOURNAL OF PSYCHOSOMATIC RESEARCH LA English DT Article DE anxiety sensitivity; generalized anxiety disorder; irritable bowel syndrome; neuroticism; worry ID FUNCTIONAL GASTROINTESTINAL DISORDERS; REPORT DIAGNOSTIC MEASURE; PANIC DISORDER; QUESTIONNAIRE; DEPRESSION; CARE; VALIDATION; SYMPTOMS; SEEKING AB Objective: Relationships between presence of irritable bowel syndrome (IBS) and generalized anxiety disorder (GAD), chronic worry, neuroticism, anxiety sensitivity and anxiety about visceral sensations were examined among university students. Methods: College student participants were administered self-report diagnostic measures of IBS and GAD, the Penn State Worry Questionnaire (PSWQ), the Neuroticism subscale of the Eysenck Personality Questionnaire, the Anxiety Sensitivity Index (ASI) and five additional items designed to measure visceral anxiety. Results: The prevalence of IBS and its associated characteristics among students were similar to previous community survey studies, with the exception of lower symptom severity in the university sample. IBS was associated with a higher frequency of GAD and greater worry, neuroticism, anxiety sensitivity and visceral anxiety. Logistic regression analyses further showed that the measure of anxiety specific to visceral sensations was the strongest predictor of IBS diagnostic status. Conclusion: While various aspects of anxiety appear related to IBS, specific anxiety about visceral sensations appears to be the most significant factor. Implications of the associations between anxiety-related variables, particularly anxiety about visceral sensations, are discussed. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Nevada, Dept Psychol, Reno, NV 89557 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, CURE Digest Dis Res Ctr, Neuroentric Dis Program, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. RP Hazlett-Stevens, H (reprint author), Univ Nevada, Dept Psychol, Reno, NV 89557 USA. NR 30 TC 78 Z9 80 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3999 J9 J PSYCHOSOM RES JI J. Psychosomat. Res. PD DEC PY 2003 VL 55 IS 6 BP 501 EP 505 DI 10.1016/S0022-3999(03)00019-9 PG 5 WC Psychiatry SC Psychiatry GA 754BG UT WOS:000187282400005 PM 14642979 ER PT J AU Suarez-Almazor, ME Drummond, M AF Suarez-Almazor, ME Drummond, M TI Regulatory issues and economic efficiency SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT International Conference on Health Economics in Rheumatology CY APR 08-09, 2003 CL ROCHESTER, MINNESOTA SP Natl Inst Arthritis, Musculoskeletal & Skin Dis C1 Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. Univ York, Ctr Hlth Econ, York YO10 5DD, N Yorkshire, England. RP Suarez-Almazor, ME (reprint author), Baylor Coll Med, Houston, TX 77030 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD DEC PY 2003 VL 30 SU 68 BP 5 EP 7 PG 3 WC Rheumatology SC Rheumatology GA 758LM UT WOS:000187635900002 ER PT J AU Cheyne, HA Hanson, HM Genereux, RP Stevens, KN Hillman, RE AF Cheyne, HA Hanson, HM Genereux, RP Stevens, KN Hillman, RE TI Development and testing of a portable vocal accumulator SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE ambulatory monitoring; voice assessment; vocal function; voice disorders ID VOICE ACCUMULATOR; INTENSITY; DEVICE; ABUSE AB This research note describes the design and testing of a device for unobtrusive, long-term ambulatory monitoring of voice use, named the Portable Vocal Accumulator (PVA). The PVA contains a digital signal processor for analyzing input from a neck-placed miniature accelerometer. During its development, accelerometer recordings were obtained from 99 participants with normal or dysphonic voices. The recordings were used to (a) test the specifications and capabilities of the PVA for monitoring normal and dysphonic voices and (b) explore potentially useful displays for the large quantity of data generated by long-term monitoring. The current prototype PVA is pocket-sized (12 x 8.5 x 2 cm), lightweight (200 g), and capable of sampling 11 hr of voice-use data, including estimates of fundamental frequency, sound pressure level, and phonation duration. C1 Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. Sensimetr Corp, Somerville, NJ USA. RP Cheyne, HA (reprint author), Massachusetts Eye & Ear Infirm, Voice & Speech Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R44DC02917] NR 10 TC 58 Z9 58 U1 1 U2 4 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD DEC PY 2003 VL 46 IS 6 BP 1457 EP 1467 DI 10.1044/1092-4388(2003/113) PG 11 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 753DL UT WOS:000187216700015 PM 14700368 ER PT J AU Hess, MJ Zhan, EH Foo, DK Yalla, SV AF Hess, MJ Zhan, EH Foo, DK Yalla, SV TI Bladder cancer in patients with spinal cord injury SO JOURNAL OF SPINAL CORD MEDICINE LA English DT Article DE bladder cancer; spinal cord injuries; neurogenic bladder; cystoscopy; cytology ID SCREENING CYSTOSCOPY; TUMORS; RISK AB Objective: The incidence of bladder cancer in spinal cord injury (SCI) is 16 to 28 times higher than that in the general population. The objective of this study was to investigate the characteristics of bladder cancer that are unique to the SCI population. Design: Retrospective review. Methods: The charts of 16 patients diagnosed with bladder cancer from 1982 to 2001 were reviewed for type of cancer, exposure to risk factors, presenting symptoms, and survival time. Results: The presenting manifestations were gross hematuria in 14 patients, papillary urethral growth in 1 patient, and acute obstructive renal failure in 1 patient. The diagnosis was made on initial cystoscopic evaluation in 16 patients; 3 patients required further evaluation. Eight of the 11 screening cytologies were suspicious for a malignancy prior to the diagnosis. Seven patients had transitional cell carcinoma, 6 patients had squamous cell carcinoma (SCCA), and 3 patients had both. The bladder was managed with chronic indwelling catheter in 12 patients. Nine patients died of bladder cancer metastases and the remaining 3 patients died of other causes. Six patients survived 5 years or more; 4 were still alive at the completion of this study. Conclusion: Gross hematuria in individuals with SCI warrants aggressive assessment for bladder cancer. Chronic indwelling catheter, smoking, and renal and bladder stones are important risk factors for cancer. The incidence of SCCA in the SCI population is much higher than in the general population. Cystoscopic and cytologic evaluation in patients with advanced disease may fail to confirm the diagnosis in a high proportion of patients. C1 VA Boston Healthcare Syst, SCI Dept, W Roxbury Div, W Roxbury, MA 02132 USA. VA Boston Healthcare Syst, Urol Serv, W Roxbury Div, W Roxbury, MA 02132 USA. RP Hess, MJ (reprint author), VA Boston Healthcare Syst, SCI Dept, W Roxbury Div, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 17 TC 27 Z9 29 U1 2 U2 2 PU AMER PARAPLEGIA SOC PI JACKSON HWIGHTS PA 75-20 ASTORIA BLVD, JACKSON HWIGHTS, NY 11370-1177 USA SN 1079-0268 J9 J SPINAL CORD MED JI J. Spinal Cord. Med. PD WIN PY 2003 VL 26 IS 4 BP 335 EP 338 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 755ER UT WOS:000187391200005 PM 14992333 ER PT J AU Danforth, N Schlozman, SC AF Danforth, N Schlozman, SC TI Our offices: Safe and tolerant places SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Grad Sch Educ, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Danforth, N (reprint author), Massachusetts Gen Hosp, Dept Child Psychiat, 15 Parkman St,WACC-725, Boston, MA 02114 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD DEC PY 2003 VL 42 IS 12 BP 1522 EP 1523 DI 10.1097/01.chi.0000091510.46853.aa PG 2 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 746CP UT WOS:000186729200021 PM 14627889 ER PT J AU Chuang, KH Covinsky, KE Sands, LP Fortinsky, RH Palmer, RM Landefeld, CS AF Chuang, KH Covinsky, KE Sands, LP Fortinsky, RH Palmer, RM Landefeld, CS TI Diagnosis-related group-adjusted hospital costs are higher in older medical patients with lower functional status SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY 08-12, 2002 CL WASHINGTON, D.C. SP Amer Geriatr Soc DE diagnosis-related groups; functional status; healthcare costs; Medicare; reimbursement methods ID PROSPECTIVE-PAYMENT SYSTEM; MORTALITY; ADULTS; CARE; CONSUMPTION; VALIDATION; SEVERITY; CHARGES; ELDERS; INDEX AB Objectives: To determine whether hospital costs are higher in patients with lower functional status at admission, defined as dependence in one or more activities of daily living (ADLs), after adjustment for Medicare Diagnosis-Related Group (DRG) payments. Design: Prospective study. General medical service at a teaching hospital. Setting: One thousand six hundred twelve patients aged 70 and older. Measurements: The hospital cost of care for each patient was determined using a cost management information system, which allocates all hospital costs to individual patients. Results: Hospital costs were higher in patients dependent in ADLs on admission than in patients independent in ADLs on admission ($5,300 vs $4,060, P<.01). Mean hospital costs remained higher in ADL-dependent patients than in ADL-independent patients in an analysis that adjusted for DRG weight ($5,240 vs $4,140, P<.01), and in multivariate analyses adjusting for age, race, sex, Charlson comorbidity score, acute physiology and chronic health evaluation score, and admission from a nursing home as well as for DRG weight ($5,200 vs $4,220, P<.01). This difference represents a 23% (95% confidence interval=15-32%) higher cost to take care of older dependent patients. Conclusion: Hospital cost is higher in patients with worse ADL function, even after adjusting for DRG payments. If this finding is true in other hospitals, DRG-based payments provide hospitals a financial incentive to avoid patients dependent in ADLs and disadvantage hospitals with more patients dependent in ADLs. C1 San Francisco VA Med Ctr, Div Geriatr, Vet Affairs Natl Qual Scholars Fellowship Program, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Purdue Univ, Sch Nursing, W Lafayette, IN 47907 USA. Univ Connecticut, Ctr Hlth, Ctr Aging, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Div Geriatr, Farmington, CT USA. Cleveland Clin Fdn, Geriatr Med Sect, Cleveland, OH 44195 USA. RP Chuang, KH (reprint author), San Francisco VA Med Ctr, Div Geriatr, Vet Affairs Natl Qual Scholars Fellowship Program, 4150 Clement St,181G, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU AHRQ HHS [K02HS00006-01]; NIA NIH HHS [AG00412, AG10418] NR 30 TC 43 Z9 43 U1 5 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD DEC PY 2003 VL 51 IS 12 BP 1729 EP 1734 DI 10.1046/j.1532-5415.2003.51556.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 743FU UT WOS:000186562400006 PM 14687350 ER PT J AU Sosnovik, DE Januzzi, JL Church, CC Mertsch, JA Sears, AL Fetterman, RC Walovitch, RC Picard, MH AF Sosnovik, DE Januzzi, JL Church, CC Mertsch, JA Sears, AL Fetterman, RC Walovitch, RC Picard, MH TI Measurement of radial artery contrast intensity to assess cardiac microbubble behavior SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID ECHO-CONTRAST; MYOCARDIAL CONTRAST; FLOW QUANTIFICATION; DOPPLER; AGENT; POWER; ECHOCARDIOGRAPHY; CURVES; OPACIFICATION; DESTRUCTION AB Objectives: We sought to determine whether analysis of the contrast signal from the radial artery is, better able to reflect changes in left ventricular (LV) microbubble dynamics than the signal from the LV itself. Background: Assessment of microbubble behavior from images of the LV may be affected by attenuation from overlying microbubbles and nonuniform background signal intensities. The signal intensity from contrast in a peripheral artery is not affected by these artifacts and may, thus, be more accurate. Methods. After injection of a contrast bolus into a peripheral vein, signal intensity was followed simultaneously in the LV and radial artery. The measurements were repeated using continuous, triggered, low and high mechanical index harmonic imaging of the LV. Results: Peak and integrated signal intensities ranged from 25 dB and 1550 dB/s, respectively, with radial artery imaging to 5.6 dB and 471 dB/s with ventricular imaging. Although differences in micro-bubble behavior during the different imaging protocols could be determined from both the LV and radial artery curves, analysis of the radial artery curves yielded more consistent and robust differences. Conclusions. The signal from microbubbles in the radial artery is not affected by shadowing and is, thus, a more accurate reflection of microbubble behavior in the LV than the signal from the LV itself. This may have important implications for the measurement of myocardial perfusion by contrast echocardiography. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Univ Mississippi, Natl Ctr Phys Acoust, Oxford, MS USA. Acusphere Inc, Watertown, MA USA. RP Picard, MH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, VBK-5-508,55 Fruit St, Boston, MA 02114 USA. OI Picard, Michael/0000-0002-9264-3243 NR 21 TC 0 Z9 1 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2003 VL 16 IS 12 BP 1267 EP 1273 DI 10.1067/j.echo.2003.08.009 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 750VL UT WOS:000187019100011 PM 14652606 ER PT J AU Nesta, F Otsuji, Y Handschumacher, MD Messas, E Leavitt, M Carpentier, A Levine, RA Hung, J AF Nesta, F Otsuji, Y Handschumacher, MD Messas, E Leavitt, M Carpentier, A Levine, RA Hung, J TI Leaflet concavity: A rapid visual clue to the presence and mechanism of functional mitral regurgitation SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID LEFT-VENTRICULAR SHAPE; DOPPLER COLOR-FLOW; PAPILLARY-MUSCLE DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; HEART-FAILURE; DILATED CARDIOMYOPATHY; ECHOCARDIOGRAPHIC ASSESSMENT; PROGNOSTIC IMPLICATIONS; VENA CONTRACTA; VALVE REPAIR AB Repairing mitral regurgitation (MR) requires an understanding of its mechanism. Evaluating restricted leaflet closure in functional MR is challenging. Tenting area between leaflets and annulus in long-axis (LAX) views correlates with MR, but is positive even in control subjects; in the 4-chamber view, the incomplete mitral leaflet closure (IMLC) tenting pattern may be subtle and variable. We tested the hypothesis that leaflet concavity toward the left atrium in the LAX view, a rapid visual clue indicating abnormal tethering predominantly by intermediate chords, is a strong indicator of functional MR. We reviewed 90 patients:.40- with inferior myocardial infarction and ejection fraction greater than or equal to 50%; 40 with global left ventricular dysfunction and ejection fraction < 50%; and 10 control subjects. We assessed leaflet, shape (concave or convex toward the left atrium) and maximum systolic proximal MR jet width in the LAX views. To quantify shape, we measured the leaflet concavity area between the anterior leaflet and a line connecting its ends. Conventional IMLC area was also assessed. Patients with leaflet concavity had significantly greater MR than those without this finding (jet width of 4.6 +/- 0.7 vs 0.5 +/- 0.1 mm, P < .0001), indicating mild-moderate versus trace MR, with differences comparable in those with inferior myocardial infarction and left ventricular dysfunction. Leaflet concavity area most strongly predicted MR by multivariate regression (R-2 = 0.7). Conventional IMLC area did not uniquely distinguish patients with or without MR and correlated more weakly with MR (R-2 = 0.30 vs 0.73). Mitral leaflet concavity in the LAX view provides rapid and reliable recognition of functional MR, with greater reliability than IMLC area. This shape, consistent with tethering by intermediate chords, may have implications for potential intervention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Med, Boston, MA 02114 USA. Fac Med Necker Enfants Malad, Div Cardiol, Paris, France. Univ Paris, Hop Europeen Georges Pompidou, Dept Cardiac Surg, F-75252 Paris, France. RP Hung, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab,Dept Med, 55 Fruit St,VBK-508, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01 HL 38176, K24 HL67434, K23 HL04504] NR 51 TC 31 Z9 32 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD DEC PY 2003 VL 16 IS 12 BP 1301 EP 1308 DI 10.1067/j.echo.2003.09.003 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 750VL UT WOS:000187019100015 PM 14652610 ER PT J AU Berger, AR Bradley, WG Brannagan, TH Busis, NA Cros, DP Dalakas, MC Danon, MJ Donofrio, PD Engel, WK England, JD Feldman, EL Freeman, RL Kinsella, LJ Lacomis, D Latov, N Menkes, DL Sander, HW Thomas, FP Triggs, WJ Windebank, AJ Wolfe, GI AF Berger, AR Bradley, WG Brannagan, TH Busis, NA Cros, DP Dalakas, MC Danon, MJ Donofrio, PD Engel, WK England, JD Feldman, EL Freeman, RL Kinsella, LJ Lacomis, D Latov, N Menkes, DL Sander, HW Thomas, FP Triggs, WJ Windebank, AJ Wolfe, GI CA Neuropathy Assoc Med Advisory Comm TI Guidelines for the diagnosis and treatment of chronic inflammatory demyelinating polyneuropathy SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Article ID CLINICAL-FEATURES; RESEARCH CRITERIA; CIDP; POLYRADICULONEUROPATHY; NEUROPATHY; SPECTRUM C1 Cornell Univ, Weill Med Coll, Peripheral Neuropathy Ctr, New York, NY 10022 USA. Univ Florida, Dept Neurol, Shands Jacksonville, FL USA. Univ Florida, Inst Neurosci, Shands Jacksonville, FL USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33152 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, EMG Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Peripheral Neuropathy Ctr, Boston, MA 02114 USA. NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ So Calif, Sch Med, Los Angeles, CA 90089 USA. Beaconess Billings Clin, Billings, MT USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Ctr Auton & Peripheral Nerve Disorders, Boston, MA 02215 USA. St Louis Univ, St Louis, MO 63103 USA. Tenet Forest Pk Hosp, St Louis, MO USA. Neuropathy Assoc, New York, NY USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Florida, Inst Brain, Gainesville, FL 32611 USA. Peripheral Nerve Soc, Rochester, MN USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA. Univ Texas, SW Med Ctr, Peripheral Neuropathy Ctr, Dallas, TX 75230 USA. RP Latov, N (reprint author), Cornell Univ, Weill Med Coll, Peripheral Neuropathy Ctr, 635 Madison Ave,Suite 400, New York, NY 10022 USA. NR 21 TC 29 Z9 30 U1 0 U2 3 PU WOODLAND PUBLICATIONS, INC PI NEW YORK PA 69 MURRAY ST, NEW YORK, NY 10007 USA SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD DEC PY 2003 VL 8 IS 4 BP 282 EP 284 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 755UF UT WOS:000187429300010 PM 14641652 ER PT J AU Yarbrough, WM Mukherjee, R Escobar, GP Sample, JA McLean, JE Dowdy, KB Hendrick, JW Gibson, WC Hardin, AE Mingoia, JT White, PC Stiko, A Armstrong, RC Crawford, FA Spinale, FG AF Yarbrough, WM Mukherjee, R Escobar, GP Sample, JA McLean, JE Dowdy, KB Hendrick, JW Gibson, WC Hardin, AE Mingoia, JT White, PC Stiko, A Armstrong, RC Crawford, FA Spinale, FG TI Pharmacologic inhibition of intracellular caspases after myocardial infarction attenuates left ventricular remodeling: A potentially novel pathway SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 83rd Annual Meeting of the American-Association-for-Thoracic-Surgery CY MAY 04-07, 2003 CL BOSTON, MASSACHUSETTS SP Amer Assoc Thorac Surg ID ANGIOTENSIN-CONVERTING ENZYME; MYOCYTE CELL-DEATH; ISCHEMIA-REPERFUSION; CARDIAC MYOCYTES; HEART-FAILURE; APOPTOSIS; INJURY; RATS; OVEREXPRESSION; DYSFUNCTION AB Objective: Myocyte death occurs by necrosis and caspase-mediated apoptosis in the setting of myocardial infarction. In vitro studies suggest that caspase activation within myocytes causes contractile protein degradation without inducing cell death. Thus, caspase activation may evoke left ventricular remodeling through 2 independent processes post-myocardial infarction. However, the effects of caspase activation on left ventricular geometry post-myocardial infarction remain unclear. This project applied broad-spectrum caspase inhibition to a chronic porcine model of myocardial infarction. Methods: Coronary snares and sonomicrometry crystals in remote and area-at-risk regions were placed in pigs (n = 22, 34 kg). Geometric measurements at end diastole and end systole, including-left ventricular area by echocardiography and interregional distance by sonomicrometry, were obtained at baseline. Coronary occlusion was instituted for 60 minutes, followed by reperfusion and repeated geometric measurements at 7 days, including left ventriculography. At reperfusion, pigs were randomized to saline (n 12) or caspase inhibition (n = 10, IDN6734, 2 mg/kg intravenously, then 2 mg . kg . h for 24 hours) at a dose that achieved desired plasma concentrations (790 +/- 142 ng/mL) as predicted by prior pharmacokinetic studies. Results: Infarct size and 24-hour troponin-I values were not significantly different between the saline and caspase inhibition groups (51% +/- 8% vs 42% +/- 6% and 189 20 ng/mL vs 152 +/- 26 ng/mL, respectively, P >.10). At 7 days, end-diastole volume was increased in both groups compared with reference control values (47 1 mL, P <.05), but it was decreased with caspase inhibition (72 +/- 4 mL) compared with saline (84 +/- 4 mL, P <.05). Similarly, end-diastole and end-systole areas increased by 32% +/- 3% and 81% +/- 16% in the saline group but were attenuated with caspase inhibition (19% +/- 3% and 31% +/- 10%, respectively, P <.05). End-diastole interregional distance increased by 30% +/- 7% in the saline group but was attenuated with caspase inhibition (12% +/- 5%, P <.05). Conclusion: Despite equivalent degrees of myocardial injury, caspase inhibition reduced post-myocardial infarction left ventricular remodeling as evidenced by multiple, independent assessments of left ventricular dilation. Thus, caspase activation alters left ventricular geometry in the absence of significant effects on myocardial injury. C1 Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Assoc Med Ctr, Charleston, SC USA. Idun Pharmaceut Inc, San Diego, CA USA. RP Spinale, FG (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, 770 MUSC Complex,STRB,Suiite 625, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL-97012, HL-07260, HL-45024] NR 28 TC 20 Z9 21 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD DEC PY 2003 VL 126 IS 6 BP 1892 EP 1899 DI 10.1016/j.jtcvs.2003.08.012 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 757JZ UT WOS:000187560400033 PM 14688702 ER PT J AU Wong, P Harding, S Inglessis, I Choi, CJ Walters, D Chang, YC Gimelli, G Jang, IK AF Wong, P Harding, S Inglessis, I Choi, CJ Walters, D Chang, YC Gimelli, G Jang, IK TI The effect of glycoprotein IIb/IIIa receptor inhibitor on the microcirculation in patients undergoing high-risk coronary stenting; A prospective, randomized study SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article DE acute coronary syndrome; angioplasty; coronary flow reserve; coronary stenting; embolization; glycoprotein IIb/IIIa inhibitor; microcirculation ID ACUTE MYOCARDIAL-INFARCTION; BALLOON-ANGIOPLASTY; CONTROLLED TRIAL; BLOCKADE; ARTERY; FLOW AB Structured abstract. Objectives: We evaluated the effect of the glycoprotein IIb/IIIa inhibitor, tirofiban, on the microcirculation measured by Doppler coronary flow reserve (CFR) in patients undergoing high-risk coronary stenting. Background: The mechanisms by which glycoprotein IIb/IIIa inhibitors benefit patients undergoing high-risk angioplasty are not fully understood. This may be due to prevention of distal embolization of the coronary clot at the site of angioplasty. Methods: Thirty two consecutive patients with acute coronary syndrome within 72 hours or with high-risk angiographic features were randomized into 2 groups. Group A (n = 17) received tirofiban (10 mug/ kg bolus followed 0.15 mug/kg/min). Group B ( n = 15) received placebo bolus and infusion. Coronary flow reserve was measured by Doppler wire technique at baseline, post balloon angioplasty and post-stenting. Platelet aggregation was measured at baseline, 10 minutes, 6 hours and 12 hours post bolus. Results: There was no significant difference in CFR between the groups at baseline and after balloon angioplasty. Post-stenting CFR, however, was significantly higher in the group pretreated with tirofiban (2.94 vs. 2.25, p = 0.014). The inhibition of platelet aggregation was 94% at 10 minutes, 97% at 6 hours and 94% at 12 hours in the tirofiban group. Conclusion: In patients undergoing high-risk coronary stenting, tirofiban protects and improves the microcirculation measured by Doppler wire technique. This may be due to prevention of distal embolization of clot by tirofiban and explain the clinical benefit. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Jang, IK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Bulfinch 105,55 Fruit St, Boston, MA 02114 USA. EM Jang.ik@mgh.harvard.edu RI Walters, Darren/A-7069-2011 NR 7 TC 6 Z9 9 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD DEC PY 2003 VL 16 IS 3 BP 163 EP 166 DI 10.1023/B:THRO.0000024054.53591.a8 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 812OH UT WOS:000220848300005 PM 15087602 ER PT J AU Carroll, PR Benaron, DA Blackledge, G Coakley, FV D'Amico, AV Higano, CS Iversen, P Kattan, M Nanus, DM Nelson, JB Oh, WK Roach, M Sellers, WR Smith, MR McMann, MC Kantoff, PW AF Carroll, PR Benaron, DA Blackledge, G Coakley, FV D'Amico, AV Higano, CS Iversen, P Kattan, M Nanus, DM Nelson, JB Oh, WK Roach, M Sellers, WR Smith, MR McMann, MC Kantoff, PW TI Third International Conference on Innovations and Challenges in Prostate Cancer: Prevention, detection and treatment SO JOURNAL OF UROLOGY LA English DT Editorial Material DE diagnostic imaging; tyrosine kinase; bone; metastasis; prostate-specific antigen C1 Univ Calif San Francisco, Mt Zion Med Ctr, Sch Med, Dept Urol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Mt Zion Med Ctr, Sch Med, Dept Radiol, San Francisco, CA 94115 USA. Stanford Univ, Sch Med, Biomed Opt Imaging Lab, Palo Alto, CA 94304 USA. AstraZeneca Pharmaceut, Macclesfield, Cheshire, England. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA. Univ Copenhagen, Rigshosp, Dept Urol, DK-2100 Copenhagen, Denmark. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. New York Presbyterian Hosp, New York, NY USA. Cornell Univ, Weil Med Coll, New York, NY USA. Univ Pittsburgh, Med Ctr, Shadyside Med Ctr, Pittsburgh, PA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. Ctr Comprehens Canc, San Francisco, CA USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. InforMED Inc, Carlisle, MA USA. RP Carroll, PR (reprint author), Univ Calif San Francisco, Mt Zion Med Ctr, Sch Med, Dept Urol, 1600 Divisadero St,3d Floor, San Francisco, CA 94115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 2 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2003 VL 170 IS 6 BP S3 EP S5 DI 10.1097/01.ju0000095101.18470.ao PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 742QH UT WOS:000186529100001 PM 14610403 ER PT J AU D'Amico, AV Cote, K Loffredo, M Renshaw, AA Schultz, D AF D'Amico, AV Cote, K Loffredo, M Renshaw, AA Schultz, D TI Determinants of prostate cancer specific survival following radiation therapy during the prostate specific antigen era SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 3rd international Conference on Innovations and challenges in Prostate Cancer CY NOV 15-16, 2002 CL CAMBRIDGE, MASSACHUSETTS DE prostatic neoplasms; survival/analysis; prostate-specific antigen; radiation therapy; outcome study ID RADICAL PROSTATECTOMY; RANDOMIZED TRIAL; RECURRENCE; RADIOTHERAPY; PROGRESSION; FAILURE AB Purpose: Identifying pretreatment and posttreatment predictors of time to prostate cancer specific death (PCSD) following external beam radiation therapy (RT) is the subject of this study. Materials and Methods: A Cox regression analysis was used to evaluate the ability of the pretreatment risk group to predict time to PCSD for 381 patients who underwent RT for clinically localized prostate cancer. Posttreatment factors analyzed for the 94 patients who experienced prostate specific antigen (PSA) failure included the time to failure, posttreatment PSA doubling time (DT) and timing of salvage hormonal therapy. Results: Despite a median age of 73 at diagnosis, 45% of patients with high risk disease were estimated to die of prostate cancer within 10 years following RT compared to 0% (p=0.004) and 6% (p=0.05) of those with low or intermediate risk disease, respectively. Predictors of time to PCSD following PSA failure included PSA DT (p=0.01) and delayed use of hormonal therapy (pless than or equal to0.002). Nearly identical estimates of PCSD and all cause death following PSA failure were noted for patients with a short PSA DT (ie 12 months or less). Conclusions: Prostate cancer was a major cause of death during the first decade following RT for patients with clinically localized but high risk disease, and the cause of death for patients with a short PSA DT following RT was nearly always prostate cancer. These data provide evidence to propose the hypothesis that a short posttreatment PSA DT may serve as a possible surrogate for PCSD. Prospective validation is needed. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA. Millersville Univ, Dana Farber Canc Inst, Boston, MA USA. Millersville Univ, Dept Math, Boston, MA USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. NR 18 TC 47 Z9 47 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2003 VL 170 IS 6 BP S42 EP S46 DI 10.1097/01.ju.0000094800.63501.15 PN 2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 742QH UT WOS:000186529100012 PM 14610409 ER PT J AU Febbo, PG Sellers, WR AF Febbo, PG Sellers, WR TI Use of expression analysis to predict outcome after radical prostatectomy SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 3rd international Conference on Innovations and challenges in Prostate Cancer CY NOV 15-16, 2002 CL CAMBRIDGE, MASSACHUSETTS DE gene expression profiling; oligonucleotide array sequence analysis; prostatic neoplasms; prostatectomy ID GENE-EXPRESSION; LUNG CARCINOMAS; BREAST-CANCER; ADENOCARCINOMA; CLASSIFICATION; RECURRENCE; SURVIVAL; TUMORS AB Purpose: We summarize and discuss our recent work exploring the use of gene expression analysis for the prediction of histopathological features of prostate cancer and patient outcome following radical prostatectomy. Materials and Methods: Using "gene chips" capable of analyzing expression of greater than 10,000 genes simultaneously, expression data were collected from prostate tumors and adjacent normal tissue taken from patients undergoing radical prostatectomy between 1995 and 1997 at our hospital. Differentially expressed genes were analyzed using a signal-to-noise metric and by Pearson correlation, while predictive models were built and tested using nearest-neighbor prediction and leave-one-out cross validation. Patient outcome data were analyzed using Kaplan-Meier plots. Results: Robust expression differences were readily detected between tumor and normal tissue, and computer models were built that could predict the identity of tumor or normal differences with 92% accuracy. We were able to find gene expression correlates of Gleason score and, more importantly, a preliminary 5-gene model was found that could separate cases into recurrent and nonrecurrent groups based on the expression patterns found in the primary tumors. Conclusions: These data suggest that it may be possible to predict prostate tumor behavior based on expression signatures present at the time of surgery. A critical next step will be to try and validate such findings in larger independent datasets. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02118 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med, Boston, MA 02118 USA. RP Sellers, WR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02118 USA. NR 25 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2003 VL 170 IS 6 BP S11 EP S19 DI 10.1097/01.ju.0000095567.03807.a1 PN 2 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 742QH UT WOS:000186529100004 PM 14610405 ER PT J AU Oh, WK AF Oh, WK TI The evolving role of chemotherapy and other systemic therapies for managing localized prostate cancer SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 3rd international Conference on Innovations and challenges in Prostate Cancer CY NOV 15-16, 2002 CL CAMBRIDGE, MASSACHUSETTS DE prostatic neoplasms; chemotherapy ID PHASE-II TRIAL; RADICAL PROSTATECTOMY; NEOADJUVANT CHEMOTHERAPY; BREAST-CANCER; ESTRAMUSTINE PHOSPHATE; ANDROGEN ABLATION; HORMONAL-THERAPY; WEEKLY DOCETAXEL; ANGIOGENESIS; GROWTH AB Purpose: The recent literature is reviewed regarding the use of neoadjuvant and adjuvant chemotherapy, and promising new molecular targeted agents in patients with high risk localized prostate cancer. Materials and Methods: A MEDLINE literature review was performed of studies evaluating chemotherapy and other systemic therapies for localized prostate cancer. Results: Patients with prostate cancer at high risk for recurrence despite local therapy include those with clinical stage T3 disease, biopsy Gleason scores of 8 to 10 or serum prostate specific antigen greater than 20 ng/ml. Although hormonal therapy has palliative benefit for the majority of patients with metastatic disease, randomized trials have not demonstrated a survival benefit from its administration before surgery for high risk localized disease. Recent trials have shown that cytotoxic chemotherapy has significant activity in hormone refractory prostate cancer, which has led to ongoing clinical trials that are investigating the use of chemotherapy in the neoadjuvant setting. Published and ongoing clinical trials in the use of systemic therapy for localized prostate cancer are reviewed. Conclusions: Systemic therapy for advanced prostate cancer is improving. Efforts to use such therapies for managing localized disease are ongoing. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 51 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2003 VL 170 IS 6 BP S28 EP S32 DI 10.1097/01.ju.0000095356.02647.64 PN 2 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 742QH UT WOS:000186529100008 PM 14610407 ER PT J AU Smith, MR AF Smith, MR TI Bisphosphonates to prevent skeletal complications in men with metastatic prostate cancer SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 3rd international Conference on Innovations and challenges in Prostate Cancer CY NOV 15-16, 2002 CL CAMBRIDGE, MASSACHUSETTS DE bisphosphonates; prostatic neoplasms; bones; metastases ID BONE-RESORPTION; ZOLEDRONIC ACID; DOUBLE-BLIND; CARCINOMA; PAMIDRONATE; ETIDRONATE; DISODIUM; MARKERS; DISEASE AB Purpose: The literature on clinical trials of bisphosphonates in men with metastatic prostate cancer is reviewed to familiarize the reader with biology of bone metastases and rationale for use of bisphosphonates. Materials and Methods: A MEDLINE review of the literature on prostate cancer and bisphosphonates was performed. Results: In uncontrolled clinical trials bisphosphonates improved pain and analgesic scores in men with symptomatic bone metastases. In a randomized controlled trial of men with bone metastases and progressive disease after first line hormonal therapy zoledronic acid decreased the skeletal related events, a composite end point defined as fracture, surgery or radiation therapy to bone, or change in antineoplastic therapy for bone pain. Randomized controlled trials with other bisphosphonates reported no significant benefit in men with bone metastases. Problems with the study populations, drug bioavailability and potency, statistical power and end point definition may have contributed to the negative results of these other studies. Conclusions: Zoledronic acid decreases the risk of skeletal related events in men with bone metastases and disease progression after first line hormonal therapy. Additional clinical research is needed to evaluate the optimal timing, schedule and duration of bisphosphonate treatment in men with metastatic prostate cancer. Additional research is also necessary to determine whether bisphosphonates can prevent bone metastases in men with high risk nonmetastatic prostate cancer. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 26 TC 8 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD DEC PY 2003 VL 170 IS 6 BP S55 EP S57 DI 10.1097/01.ju.0000095102.34708.bc PN 2 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 742QH UT WOS:000186529100016 PM 14610411 ER PT J AU Chandran, K Parker, JSL Ehrlich, M Kirchhausen, T Nibert, ML AF Chandran, K Parker, JSL Ehrlich, M Kirchhausen, T Nibert, ML TI The delta region of outer-capsid protein mu 1 undergoes conformational change and release from reovirus particles during cell entry SO JOURNAL OF VIROLOGY LA English DT Article ID MEMBRANE-PENETRATION PROTEIN; IN-VITRO; MAMMALIAN REOVIRUSES; ATTACHMENT PROTEIN; SUBVIRAL PARTICLES; CRYOELECTRON MICROSCOPY; MEDIATED ENDOCYTOSIS; STRUCTURAL PROTEINS; INDUCED APOPTOSIS; CHROMIUM RELEASE AB Cell entry by reoviruses requires a large, transcriptionally active subvirion particle to gain access to the cytoplasm. The features of this particle have been the subject of debate, but three primary candidates-the infectious subvirion particle (ISVP), ISVP*, and core particle forms-that differ in whether putative membrane penetration protein mu1 and adhesin sigma1. remain particle bound have been identified. Experiments with antibody reagents in this study yielded new information about the steps in particle disassembly during cell entry. Monoclonal antibodies specific for the delta region of mu1 provided evidence for a conformational change in mu1 and for release of the delta proteolytic fragment from entering particles. Antiserum raised against cores provided evidence for entry-related changes in particle structure and identified entering particles that largely lack the delta fragment inside cells. Antibodies specific for sigma1 showed that it is also largely shed from entering particles. Limited coimmunostaining with markers for late endosomes and lysosomes indicated the particles lacking delta and sigma1 did not localize to those subcellular compartments, and other observations suggested that both the particles and free delta were released into the cytoplasm. Essentially equivalent findings were obtained with native ISVPs and highly infectious recoated particles containing wild-type proteins. Poorly infectious recoated particles containing a hyperstable mutant form of mu1, however, showed no evidence for the in vitro and intracellular changes in particle structure normally detected by antibodies, and these particles instead accumulated in late endosomes or lysosomes. Recoated particles with hyperstable mu1 were also ineffective at mediating erythrocyte lysis in vitro and promoting alpha-sarcin coentry and intoxication of cells in cultures. Based on these and other findings, we propose that ISVP* is a transient intermediate in cell entry which mediates membrane penetration and is then further uncoated in the cytoplasm to yield particles, resembling cores, that largely lack the delta fragment of mu1. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Nibert, ML (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. RI Chandran, Kartik/I-2232-2012 FU NIAID NIH HHS [K08 AI052209, K08 AI52209, R01 AI046440, R01 AI46440]; NIGMS NIH HHS [R01 GM036548, R01 GM36548] NR 73 TC 59 Z9 62 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2003 VL 77 IS 24 BP 13361 EP 13375 DI 10.1128/JVI.77.24.13361-13375.2003 PG 15 WC Virology SC Virology GA 750YF UT WOS:000187025500043 PM 14645591 ER PT J AU Carr, PL Szalacha, L Barnett, R Caswell, C Inui, T AF Carr, PL Szalacha, L Barnett, R Caswell, C Inui, T TI A "ton of feathers": Gender discrimination in academic medical careers and how to manage it SO JOURNAL OF WOMENS HEALTH LA English DT Article ID WOMEN PHYSICIANS; SCHOOL FACULTIES; PERCEPTIONS; PROMOTION AB Purpose: To evaluate the experience of gender discrimination among a limited sample of women in academic medicine, specifically, the role of discrimination in hindering careers, coping mechanisms, and perceptions of what institutions and leaders of academic medicine can do to improve the professional workplace climate for women. Methods: In-depth, semistructured telephonic individual interviews of 18 women faculty who experienced or may have experienced discrimination in the course of their professional academic medical careers from 13 of the 24 institutions of the National Faculty Survey. A consensus taxonomy for classifying content evolved from comparisons of coding. Themes expressed by multiple faculty were studied for patterns of connection and grouped into broader categories. Results: Forty percent of respondents ranked gender discrimination first out of 11 possible choices for hindering their career in academic medicine. Thirty-five percent ranked gender discrimination second to either "limited time for professional work" or "lack of mentoring." Respondents rated themselves as poorly prepared to deal with gender discrimination and noted effects on professional self-confidence, self-esteem, collegiality, isolation, and career satisfaction. The hierarchical structure in academe is perceived to work against women, as there are few women at the top. Women faculty who have. experienced gender discrimination perceive that little can be done to directly address this issue. Institutions need to be proactive and recurrently evaluate the gender climate, as well as provide transparent. information and fair scrutiny of promotion and salary decisions. Conclusions: According to this subset of women who perceive that they have been discriminated against based on gender, sexual bias and discrimination are subtly pervasive and powerful. Such environments may have consequences for both women faculty and academic medicine, affecting morale and dissuading younger trainees from entering academic careers. Medical schools need to evaluate and may need to improve the environment for women in academe. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Educ, Boston, MA 02115 USA. Radcliffe Inst, Boston, MA USA. New England Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. RP Carr, PL (reprint author), Boston Univ, Sch Med, 715 Albany St,Room L109, Boston, MA 02118 USA. EM plcarr@bu.edu NR 22 TC 55 Z9 55 U1 2 U2 9 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD DEC PY 2003 VL 12 IS 10 BP 1009 EP 1018 DI 10.1089/154099903322643938 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 768FL UT WOS:000188532900008 PM 14709189 ER PT J AU Saran, AM Yuan, HP Takeuchi, E McLaughlin, M Salant, DJ AF Saran, AM Yuan, HP Takeuchi, E McLaughlin, M Salant, DJ TI Complement mediates nephrin redistribution and actin dissociation in experimental membranous nephropathy SO KIDNEY INTERNATIONAL LA English DT Article DE passive Heymann nephritis; cytoskeleton; proteinuria; podocyte; slit diaphragm ID GLOMERULAR EPITHELIAL-CELLS; CONGENITAL NEPHROTIC SYNDROME; PASSIVE HEYMANN NEPHRITIS; SLIT-DIAPHRAGM; BASEMENT-MEMBRANE; ATTACK COMPLEX; C5B-9 COMPLEX; PROTEIN; CYTOSKELETON; COMPONENT AB Background. The onset of proteinuria in passive Heymann nephritis, (PHN), a rat model of human membranous nephropathy (MN), is complement-dependent and is associated with altered podocyte slit diaphragm integrity and dissociation of nephrin from the actin cytoskeleton. These studies examined if complement is responsible for these podocyte changes. Methods. PHN was induced with sheep anti-Fx1A. Controls were injected with normal sheep globulin. A third group was injected with anti-Fx1A and depleted of complement with cobra venom factor. Four days later, proteinuria was measured, slit diaphragm integrity was examined by electron microscopy, nephrin distribution was studied by immunofluorescence, and the glomerular content of nephrin and its association with actin were assessed by sequential extraction of isolated glomeruli and Western blotting. Results. Four days after immunization, seven out of eight PHN rats were proteinuric, whereas none of the complement depleted group had proteinuria despite similar levels of antibody deposition. Complement depletion preserved slit diaphragm morphology. Immunofluorescence microscopy with an antibody to the extracellular domain of nephrin showed a normal staining pattern in the rats depleted of complement and a shift to a more dispersed and clustered pattern in the PHN group. Western blot analysis of the glomerular extracts showed a significant reduction in the total amount of nephrin and in the fraction of actin-associated nephrin in the PHN group, whereas the amounts in the complement-depleted rats were similar to normal controls. Conclusion. The onset of proteinuria in the PHN model of MN is coincident with complement-dependent alterations in the association of nephrin with the actin cytoskeleton and loss of podocyte slit diaphragm integrity. C1 Boston Univ, Med Ctr, Renal Sect, EBRC 504, Boston, MA 02118 USA. Boston Univ, Med Ctr, Evans Biomed Res Ctr, Dept Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Salant, DJ (reprint author), Boston Univ, Med Ctr, Renal Sect, EBRC 504, 650 Albany St, Boston, MA 02118 USA. FU NIDDK NIH HHS [DK 43351, DK30932, DK57521, F32-DK62567, T32-DK07053] NR 29 TC 43 Z9 62 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2003 VL 64 IS 6 BP 2072 EP 2078 DI 10.1046/j.1523-1755.2003.00305.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 740YV UT WOS:000186431600013 PM 14633129 ER PT J AU Larsson, T Nisbeth, U Ljunggren, O Juppner, H Jonsson, KB AF Larsson, T Nisbeth, U Ljunggren, O Juppner, H Jonsson, KB TI Circulating concentration of FGF-23 increases as renal function declines in patients with chronic kidney disease, but does not change in response to variation in phosphate intake in healthy volunteers SO KIDNEY INTERNATIONAL LA English DT Article DE FGF-23; renal disease; hyperphosphatemia; phosphate loading; phosphate homeostasis ID ONCOGENIC OSTEOMALACIA; HYPOPHOSPHATEMIA; HYPERPHOSPHATEMIA; RICKETS; FGF23; FIBROBLAST-GROWTH-FACTOR-23; RICKETS/OSTEOMALACIA; DEPRIVATION; METABOLISM; FAILURE AB Background. Hyperphosphatemia is a risk factor for the development of several different complications of chronic kidney disease (CKD), including secondary hyperparathyroidism and cardiovascular complications, due to the formation of calcium-phosphate deposits. Fibroblast growth factor-23 (FGF-23) is a recently discovered protein that is mutated in autosomal-dominant hypophosphatemic rickets, an inherited phosphate wasting disorder, and it may represent a novel hormonal regulator of phosphate homeostasis. We therefore hypothesized that FGF-23 levels may be altered in hyperphosphatemia associated with renal failure and that its concentration changes in response to different levels of phosphate intake. Methods. Using a two-site enzyme-linked immunosorbent assay (ELISA) detecting the C-terminal portion of FGF-23, serum concentration was measured in 20 patients with different stages of renal failure (creatinine range 155 to 724 mumol/L), in 33 patients with end-stage renal disease (ESRD) on dialysis treatment, and in 30 patients with functioning renal grafts. Furthermore, six healthy males were given oral phosphate binders in combination with low dietary phosphate intake for 2 days followed by 3 days of repletion with inorganic phosphate. FGF-23 levels were determined at multiple time points. Results. FGF-23 serum levels were significantly elevated in CKD with a strong correlation between serum creatinine and FGF-23 concentration. Independent correlations were also seen between FGF-23 and phosphate, calcium, parathyroid hormone (PTH), and 1,25(OH)(2)D-3. No changes in serum FGF-23 levels were observed in volunteers following ingestion of oral phosphate binders/low dietary phosphate intake, which led to a decline in phosphate excretion or during the subsequent repletion with inorganic phosphate through oral phosphate and a normal diet. Conclusion. Circulating FGF-23 was significantly elevated in patients with CKD and its concentration correlated with renal creatinine clearance. In healthy volunteers, FGF-23 levels did not change after phosphate deprivation or phosphate loading. C1 Univ Uppsala Hosp, Dept Surg Sci, SE-75185 Uppsala, Sweden. Univ Uppsala Hosp, Dept Med Sci, Uppsala, Sweden. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jonsson, KB (reprint author), Univ Uppsala Hosp, Dept Surg Sci, Ing 85,3 Tr, SE-75185 Uppsala, Sweden. NR 19 TC 390 Z9 411 U1 1 U2 6 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2003 VL 64 IS 6 BP 2272 EP 2279 DI 10.1046/j.1523-1755.2003.00328.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 740YV UT WOS:000186431600036 PM 14633152 ER PT J AU Almaden, Y Felsenfeld, AJ Rodriguez, M Canadillas, S Luque, FQ Bas, A Bravo, J Torregrosa, V Palma, A Ramos, B Sanchez, C Martin-Malo, A Canalejo, A AF Almaden, Y Felsenfeld, AJ Rodriguez, M Canadillas, S Luque, FQ Bas, A Bravo, J Torregrosa, V Palma, A Ramos, B Sanchez, C Martin-Malo, A Canalejo, A TI Proliferation in hyperplastic human and normal rat parathyroid glands: Role of phosphate, calcitriol, and gender SO KIDNEY INTERNATIONAL LA English DT Article DE calcitriol; cell proliferation; gender; hyperplasia; parathyroid gland; phosphate ID CHRONIC-RENAL-FAILURE; HORMONE GENE-EXPRESSION; IN-VITRO; SECONDARY HYPERPARATHYROIDISM; CELL-PROLIFERATION; UREMIC PATIENTS; VITAMIN-D; HEMODIALYSIS-PATIENTS; PTH SECRETION; RISK-FACTORS AB Background. Parathyroid gland hyperplasia develops in azotemic patients. A phosphate excess and calcitriol deficiency play critical roles in its development. Our goals were to determine whether differences in serum phosphate values at parathyroidectomy (PTX) in hemodialysis patients with refractory hyperparathyroidism: (1) correlated with parathyroid cell proliferation; and (2) affected the antiproliferative response to in vitro calcitriol. Studies were also performed to determine whether the phosphate concentration in the medium affected the antiproliferative response to calcitriol, and whether a high phosphate diet and calcitriol treatment affected parathyroid cell proliferation and parathyroid hormone (PTH) levels in normal rats. Methods. Forty-seven parathyroid glands from 19 hemodialysis patients were obtained at PTX. Flow cytometry was used to determine cell proliferation (percent cells in S phase) in excised parathyroid glands. Similarly, cell proliferation was determined in parathyroid tissue incubated for 24 hours in medium with or without 10(-7) mol/L calcitriol and with 1 or 4 mmol/L phosphate. In normal rats, the effect of 3 days of a high phosphate diet (1.2% P) and calcitriol treatment (100 pmol/kg) on PTH values and cell proliferation was evaluated. Results. In cells from freshly removed parathyroid glands obtained at PTX from hemodialysis patients, there were no significant correlations between the percent cells in S phase and age, gender, and serum phosphate, calcium, and PTH. While incubation of parathyroid tissue with 10 7 mol/L calcitriol did reduce cell proliferation (P < 0.001), both the pre-PTX serum phosphate value (P = 0.003) and female gender (P = 0.003) were associated with a decreased response to calcitriol. Incubation of parathyroid tissue in medium containing 4 mmol/L phosphate did not increase cell proliferation. In normal rats, a high phosphate diet for 3 days increased cell proliferation (P < 0.05) and PTH levels (P < 0.05), and calcitriol treatment was without effect. Conclusion. Our findings suggest a high phosphate burden, as well as female gender, favor parathyroid cell proliferation and both may reduce the inhibition of parathyroid function by calcitriol. C1 Univ Huelva, Dept Environm Biol & Publ Hlth, Huelva 21071, Spain. Hosp Univ Reina Sofia, Unit Invest, Cordoba, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hosp Univ Reina Sofia, Serv Nephrol, Cordoba, Spain. Hosp Clin, Serv Nephrol, Granada, Spain. Hosp Clin Barcelona, Serv Nephrol, Barcelona, Spain. Hosp Virgen Macarena, Serv Nephrol, Seville, Spain. Hosp Carlos Haya, Serv Nephrol, Malaga, Spain. Hosp Ciudad Jaen, Serv Nephrol, Jaen, Spain. RP Canalejo, A (reprint author), Univ Huelva, Dept Environm Biol & Publ Hlth, Campus Carmen,Avd Fuerzas Armadas S-N, Huelva 21071, Spain. RI Rodriguez, teresa/H-5452-2011; Canalejo, Antonio/L-8407-2014 OI Canalejo, Antonio/0000-0003-2098-8960 NR 42 TC 26 Z9 29 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD DEC PY 2003 VL 64 IS 6 BP 2311 EP 2317 DI 10.1046/j.1523-1755.2003.00331.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 740YV UT WOS:000186431600040 PM 14633156 ER PT J AU Rabhar, R Resto, VA Robson, CD Perez-Atayde, AR Goumnerova, LC McGill, TJ Healy, GB AF Rabhar, R Resto, VA Robson, CD Perez-Atayde, AR Goumnerova, LC McGill, TJ Healy, GB TI Nasal glioma and encephalocele: Diagnosis and management SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Triological-Society CY JAN 24-26, 2003 CL BOSTON, MA SP Amer Triolog Soc DE nasal mass; glioma; encephalocele ID MASS AB Objective. To review the biology of nasal glioma and encephalocele and to present an algorithm for preoperative evaluation and surgical management. Design: Retrospective review and analysis. Setting. Tertiary care medical center: 1970 to 2002. Patient. Sixteen patients with glioma (n = 10) and encephalocele (n = 6). Outcome: Age at the time of presentation, sex, signs and symptoms, imaging findings, surgical approach, pathology, complications, rate of recurrence, and follow-up were recorded. Results. Ten patients presented with nasal glioma with a mean age of 9 months. All patients underwent surgical excision. No complication was encountered with a mean follow-up of 3.5 years. Six patients presented with encephaloceles with a mean age of 15.5 months. All patients underwent surgical excision. Complications included cerebrospinal fluid leak (n = 1) and epiphora (n = 1). Follow-up was 1 to 14 years (mean, 4 years). Conclusion. Nasal glioma and encephalocele are rare, benign, congenital lesions with a potential for intracranial extension. Evaluation should include a complete rhinologic and neurologic examination. Preoperative imaging with a thin-cut axial and coronal computed tomography scan and/or multiplanar magnetic resonance imaging is essential. Surgical intervention should be performed soon after diagnosis to alleviate the increased risk of meningitis. A frontal craniotomy approach is recommended if intracranial extension is identified based on preoperative evaluation, followed by an extracranial resection. If there is no evidence of intracranial extension, a conservative extracranial approach is recommended. C1 Harvard Univ, Dept Otolaryngol, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Dept Otol & Laryngol, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Dept Pathol, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Dept Radiol, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Dept Radiol, Dept Neurosurg, Childrens Hosp, Boston, MA 02115 USA. RP Rabhar, R (reprint author), Harvard Univ, Dept Otolaryngol, Sch Med, Childrens Hosp, 300 Longwood Ave, Boston, MA 02115 USA. EM reza.rahbar@tch.harvard.edu RI Resto, Vicente/D-9891-2014; OI Robson, Caroline/0000-0001-5592-249X NR 18 TC 5 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2003 VL 113 IS 12 BP 2069 EP 2077 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 957DI UT WOS:000231349300003 ER PT J AU Nadol, JB AF Nadol, JB TI William W. Montgomery, MD SO LARYNGOSCOPE LA English DT Biographical-Item C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Nadol, JB (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Joseph_Nadol@meei.Harvard.edu NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD DEC PY 2003 VL 113 IS 12 BP 2228 EP 2229 DI 10.1097/00005537-200312000-00036 PG 2 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 957DI UT WOS:000231349300032 PM 14660933 ER PT J AU Cherry, AM Brockman, SR Paternoster, SF Hicks, GA Neuberg, D Higgins, RR Bennett, JM Greenberg, PL Miller, K Tallman, MS Rowe, J Dewald, GW AF Cherry, AM Brockman, SR Paternoster, SF Hicks, GA Neuberg, D Higgins, RR Bennett, JM Greenberg, PL Miller, K Tallman, MS Rowe, J Dewald, GW TI Comparison of interphase FISH and metaphase cytogenetics to study myelodysplastic syndrome: an Eastern Cooperative Oncology Group (ECOG) study SO LEUKEMIA RESEARCH LA English DT Article DE FISH; myelodysplastic syndrome; cytogenetics; chromosome; hematology ID IN-SITU HYBRIDIZATION; ACUTE MYELOID-LEUKEMIA; SCORING SYSTEM; MONOSOMY-7; TRISOMY-8; ABNORMALITIES; DISORDERS; EXPOSURE AB Cytogenetic analysis can be important in determining the prognosis and diagnosis of a number of hematological disorders, including myelodysplastic syndromes (MDS). Here, we compared metaphase chromosomal analyses on bone marrow aspirates from MDS patients with interphase fluorescence in situ hybridization (FISH) using probes specific for chromosomes nos. 5, 7, 8, 11, 13 and 20. Forty-three patients enrolled in ECOG protocol E1996 for low risk MDS and live patients enrolled in ECOG protocol E3996 for high risk MDS were studied by both metaphase chromosomal analysis and interphase FISH. Excluding those with a clonal loss of the Y chromosome, an abnormal clone was detected by cytogenetic analysis in 18 of 48 samples (37.5%). In comparison, our FISH panel detected an abnormal clone in 17 of 48 samples (35.4%). Twenty-nine of 30 samples with apparently normal karyotypes, including those with a missing Y chromosome, were also normal by our FISH panel. One patient had an occult deletion of chromosome 11 that was detected by FISH. These results indicate that around 60% of patients with MDS do not have abnormalities that are detectable by either chromosomal or FISH studies. In addition, it appears that interphase FISH studies are nearly as sensitive as cytogenetic analyses and can be a useful tool in studying bone marrow aspirates where cytogenetic analysis is not possible. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Stanford Hosp & Clin, Cytogenet Lab, Dept Pathol, Stanford, CA 94305 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Div Biostat, Brookline, MA 02146 USA. Abbott NW Hosp, Cytogenet Lab, Minneapolis, MN 55407 USA. Univ Rochester, Med Ctr, Med Oncol Unit, Rochester, NY 14642 USA. Palo Alto Vet Adm Hlth Care Syst, Palo Alto, CA 94304 USA. Tufts Univ, New England Med Ctr Hosp, Boston, MA 02111 USA. Northwestern Univ, Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Technion Israel Inst Technol, Rambam Med Ctr, Haifa, Israel. RP Cherry, AM (reprint author), Stanford Hosp & Clin, Cytogenet Lab, Dept Pathol, 300 Pasteur Dr,Room H1517, Stanford, CA 94305 USA. NR 27 TC 49 Z9 52 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD DEC PY 2003 VL 27 IS 12 BP 1085 EP 1090 DI 10.1016/S0145-2126(03)00104-8 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 723KK UT WOS:000185431400004 PM 12921944 ER PT J AU Wu, CL Taylor, JL He, WL Zepeda, AG Halpern, EF Bielecki, A Gonzalez, RG Cheng, LL AF Wu, CL Taylor, JL He, WL Zepeda, AG Halpern, EF Bielecki, A Gonzalez, RG Cheng, LL TI Proton high-resolution magic angle spinning NMR analysis of fresh and previously frozen tissue of human prostate SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE HRMAS; proton NMR; human prostate; tissue freezing; intact tissue ID MAGNETIC-RESONANCE-SPECTROSCOPY; CANCER; CITRATE; MRS AB The previously observed improvement in spectral resolution of tissue proton NMR with high-resolution magic angle spinning (HRMAS) was speculated to be due largely to freeze-thawing artifacts resulting from tissue storage. In this study, 12 human prostate samples were analyzed on a 14.1T spectrometer at 3degreesC, with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured from fresh and previously frozen samples were identical for all metabolites except citrate and acetate. The metabolite intensities of fresh and freeze-thawed samples depend on the quantification procedures used; however, in this experiment the differences of means were <30%. As expected, it was found that tissue storage impacts tissue quality for pathological analysis, and HRMAS conditions alone are not sufficiently destructive to impair pathological evaluation. Furthermore, although storage conditions affect absolute metabolite concentrations in NMR analysis, relative metabolite concentrations are less affected. (C) 2003 Wiley-Liss, Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. Harvard Univ, MIT, Francis Bitter Magnet Lab, Cambridge, MA USA. RP Cheng, LL (reprint author), CNY 7, Pathol Res, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA77727, CA80901]; NCRR NIH HHS [RR00995] NR 13 TC 33 Z9 33 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD DEC PY 2003 VL 50 IS 6 BP 1307 EP 1311 DI 10.1002/mrm.10645 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 750LE UT WOS:000186991500023 PM 14648580 ER PT J AU Gesundheit, B Klement, G Senger, C Kerbel, R Kieran, M Baruchel, S Becker, L AF Gesundheit, B Klement, G Senger, C Kerbel, R Kieran, M Baruchel, S Becker, L TI Differences in vasculature between pilocytic and anaplastic astrocytomas of childhood SO MEDICAL AND PEDIATRIC ONCOLOGY LA English DT Article; Proceedings Paper CT 33rd Meeting of the International-Society-for-Pediatric-Oncology CY OCT, 2001 CL BRISBANE, AUSTRALIA SP Int Soc Pediatr Oncol DE pilocytic astrocytoma; anaplastic astrocytoma; angiogenesis; microvascular density; anti-angiogenic therapy ID ENDOTHELIAL GROWTH-FACTOR; TUMOR ANGIOGENESIS; GLIOBLASTOMA-MULTIFORME; MICROVESSEL DENSITY; IONIZING-RADIATION; BLOOD-VESSELS; FACTOR VEGF; EXPRESSION; CELLS; RECEPTORS AB Background The clinical manifestations of childhood pilocytic astrocytoma (PA) and anaplastic astrocytoma (AA) markedly differ, especially in the time to progression and prognosis. Because of the aggressive course and poor survival rate of AA, one would expect it to be associated with a high angiogenic index. Counterintuitively, we often find higher microvessel density counts in PA than in AA. Procedure. We examined the differences in type or density of microvasculature between the two neoplasms. To differentiate established, mature vessels from immature growing ones, we used antibodies to Factor VIII (FVIII) to stain endothelial cells (ECs) of blood vessels and a-smooth muscle actin (alpha-SMA) antibodies to stain vessels supported by adventitia. Results. We found that large, mature, alpha-SMA-positive vessels predominated in PA, and small, immature, alpha-SMA-negative vessels in AA. The vessel maturation index was 54.5% for PA, and 6.1% for AA. Immunostaining with vascular endothelial growth factor (VEGF) and anti-flt-1/VEGF receptor-1 antibodies showed distinct tissue patterns. VEGF immunoreactivity occurred mainly in the processes of the tumor astrocytes in PA; the opposite was observed in AA. flt-1/VEGFR-1 was detected in the tumor cells of AA but not in those of PA. Conclusions. We propose that the predominance of small, a-SMA-negative vessels in AA represents immature, unstable vasculature with a potentially greater susceptibility to anti-angiogenic therapy. The expression of both flt-1 and VEGF by AA tumor cells also suggests a possible autocrine growth-promoting function for VEGF in addition to its role as paracrine pro-angiogenic growth factor for activated ECs, thus making anti-angiogenesis an attractive therapeutic target in the treatment of AA. (C) 2003 Wiley-Liss, Inc. C1 Dana Farber Canc Inst, Dept Pediat Neuroncol, Boston, MA 02115 USA. New Agent & Innovat Therapy Program, Div Haematol Oncol, Dept Paediat, Toronto, ON, Canada. Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON M5G 1X8, Canada. Sunnybrook & Womens Coll Hosp, Dept Mol & Cellular Biol, Toronto, ON, Canada. RP Klement, G (reprint author), Dana Farber Canc Inst, Dept Pediat Neuroncol, 44 Binney St,Rm 342, Boston, MA 02115 USA. OI Kieran, Mark/0000-0003-2184-7692 NR 48 TC 20 Z9 21 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0098-1532 J9 MED PEDIATR ONCOL JI Med. Pediatr. Oncol. PD DEC PY 2003 VL 41 IS 6 BP 516 EP 526 DI 10.1002/mpo.10308 PG 11 WC Oncology; Pediatrics SC Oncology; Pediatrics GA 741HQ UT WOS:000186453000003 PM 14595708 ER PT J AU Washington, DL Bernstein, SJ Kahan, JP Leape, LL Kamberg, CJ Shekelle, PG AF Washington, DL Bernstein, SJ Kahan, JP Leape, LL Kamberg, CJ Shekelle, PG TI Reliability of clinical guideline development using mail-only versus in-person expert panels SO MEDICAL CARE LA English DT Article DE practice guidelines; Delphi technique; reproducibility of results; myocardial revascularization/utilization; hysterectomy/utilization ID NEW-YORK-STATE; CORONARY ANGIOGRAPHY; MEDICAL PROCEDURES; APPROPRIATENESS; CARE; REVASCULARIZATION; EMERGENCY; UNDERUSE AB BACKGROUND. Clinical practice guidelines quickly become outdated. One reason they might not be updated as often as needed is the expense of collecting expert judgment regarding the evidence. The RAND-UCLA Appropriateness Method is one commonly used method for collecting expert opinion. We tested whether a less expensive, mail-only process could substitute for the standard in-person process normally used. METHODS. We performed a 4-way replication of the appropriateness panel process for coronary revascularization and hysterectomy, conducting 3 panels using the conventional in-person method and 1 panel entirely by mail. All indications were classified as inappropriate or not (to evaluate overuse), and coronary revascularization indications were classified as necessary or not (to evaluate underuse). Kappa statistics were calculated for the comparison in ratings from the 2 methods. RESULTS. Agreement beyond chance between the 2 panel methods ranged from moderate to substantial. The kappa statistic to detect overuse was 0.57 for coronary revascularization and 0.70 for hysterectomy. The kappa statistic to detect coronary revascularization underuse was 0.76. There were no cases in which coronary revascularization was considered inappropriate by 1 method, but necessary or appropriate by the other. Three of 636 (0.5%) hysterectomy cases were categorized as inappropriate by 1 method but appropriate by the other. CONCLUSIONS. The reproducibility of the overuse and underuse assessments from the mail-only compared with the conventional in-person conduct of expert panels in this application was similar to the underlying reproducibility of the process. This suggests a potential role for updating guidelines using an expert judgment process conducted entirely through the mail. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Vet Affairs Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. RAND Europe, Leiden, Netherlands. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RAND, Arlington, VA USA. RAND, Santa Monica, CA USA. RP Washington, DL (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,111G, Los Angeles, CA 90073 USA. FU AHRQ HHS [HS07185-02] NR 23 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD DEC PY 2003 VL 41 IS 12 BP 1374 EP 1381 DI 10.1097/01.MLR.0000100583.76137.3E PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 748RE UT WOS:000186874200008 PM 14668670 ER PT J AU Glover, D Ibrahim, J Kirkwood, J Glick, J Karp, D Stewart, J Ewell, M Borden, E AF Glover, D Ibrahim, J Kirkwood, J Glick, J Karp, D Stewart, J Ewell, M Borden, E TI Phase II randomized trial of cisplatin and WR-2721 versus cisplatin alone for metastatic melanoma: an Eastern Cooperative Oncology Group Study (E1686) SO MELANOMA RESEARCH LA English DT Article DE amifostine; chemotherapy; melanoma; WR2721 AB This study was designed to evaluate the toxicity and efficacy of cisplatin and WR-2721 in contrast to cisplatin alone for the therapy of measurable metastatic melanoma. Ninety-four patients with metastatic melanoma were randomized to receive either cisplatin at a dose of 150 mg/m(2) and WR-2721 at a dose of 910 mg/m(2), or cisplatin alone at a dose of 120 mg/m(2). WR-2721 did not mitigate the toxic effects of cisplatin, and toxicity was increased in the WR-2721 plus cisplatin arm compared with cisplatin alone. For patients receiving cisplatin alone, the response rate was 16.3%; for those receiving cisplatin plus WR-2721, the response rate was 23.3%. The duration of response was 7.3 months. Median survival in the intent-to-treat analysis was 7.58 months. The study was terminated after accrual of 94 patients, with inadequate power to define an effect of WR-2721 on the duration of response and survival. In conclusion, cisplatin with WR-2721 showed an improved response rate over cisplatin alone. The lack of improved duration of response or impact on survival may be the result of the limited improvement of efficacy with the higher dosage of cisplatin in conjunction with WR-2721, or the limited number of patients accrued to this study. These factors, coupled with the failure of the combination to diminish toxicity, dampen enthusiasm for this combination. (C) 2003 Lippincott Williams Wilkins. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Presbyterian Med Ctr, Philadelphia, PA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. RP Kirkwood, J (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Res Pavil Suite 1-32,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM KirkwoodJM@upmc.edu FU NCI NIH HHS [CA07190, CA15488, CA18653, CA21076, CA21115, CA23318, CA66636] NR 4 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD DEC PY 2003 VL 13 IS 6 BP 619 EP 626 DI 10.1097/01.cmr.0000056286.15046.24 PG 8 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 814KM UT WOS:000220973600012 PM 14646626 ER PT J AU Finlayson, CA Chappell, J Leitner, JW Goalstone, ML Garrity, M Nawaz, S Ciaraldi, TP Draznin, B AF Finlayson, CA Chappell, J Leitner, JW Goalstone, ML Garrity, M Nawaz, S Ciaraldi, TP Draznin, B TI Enhanced insulin signaling via Shc in human breast cancer SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NEGATIVE ALPHA-SUBUNIT; SMOOTH-MUSCLE-CELLS; DIABETES-MELLITUS; GROWTH-FACTOR; RECEPTOR; FARNESYLTRANSFERASE; RESISTANCE; FARNESYL; PATHWAY; PROTEIN AB Insulin is a mild mitogen and has been shown to potentiate mitogenic influence of other growth factors. Because hyperinsulinema and/or overexpression of insulin receptors have been linked to development, progression, and outcome of breast cancer, we attempted to evaluate the mechanism of these associations. We have compared the expression of insulin receptors and the magnitude of insulin signaling in breast tumors and adjacent normal mammary tissue samples obtained from 20 patients. We observed that insulin binding more than doubled in the tumors as compared with the normal tissue (P < .1 by paired t est). Insulin signaling to Shc, judged by the magnitude of its phosphorylation, was also significantly enhanced in the tumors. In contrast, the phosphorylation of the insulin-receptor substrate-1 (IRS-1), Akt, and mitogen -activated protein (MAP) kinase were identical in the tumorous and normal mammary tissues. Finally, tumors displayed significantly increased amounts of farnesylated p21 Ras and geranylgeranylated Rho-A (P < .1), consistent with Shc-dependent activation of farnesyl (FTase) and geranylgeranyl transferases (GGTase) in the tumor tissue. We conclude that the mechanism of the mitogenic influence of insulin in breast cancer may include increased expression of insulin receptors, preferential hyperphosphorylation of Shc, and increased amounts of prenylated p21 Ras and Rho-A in tumor tissue as compared with adjacent normal mammary tissue. (C) 2003 Elsevier Inc. All rights reserved. C1 VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Surg, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. San Diego VA Med Ctr, Res Serv, La Jolla, CA USA. Denver VA Med Ctr, Pathol Serv, Denver, CO USA. RP Draznin, B (reprint author), VA Med Ctr, 151,1055 Clermont St, Denver, CO 80220 USA. NR 43 TC 23 Z9 27 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD DEC PY 2003 VL 52 IS 12 BP 1606 EP 1611 DI 10.1016/S0026-0495(03)00311-1 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 754MH UT WOS:000187320600016 PM 14669164 ER PT J AU Mino, M Pilch, BZ Faquin, WC AF Mino, M Pilch, BZ Faquin, WC TI Expression of KIT (CD117) in neoplasms of the head and neck: An ancillary marker for adenoid cystic carcinoma SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 91st Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 23-MAR 01, 2002 CL CHICAGO, ILLINOIS SP US & Canadian Acad Pathol DE adenoid cystic carcinoma; CD117; head and neck neoplasms; KIT; salivary gland ID STEM-CELL FACTOR; GASTROINTESTINAL STROMAL TUMORS; SALIVARY-GLAND CARCINOMA; ACUTE MYELOID-LEUKEMIA; PROTOONCOGENE C-KIT; DIFFERENTIAL-DIAGNOSIS; DOMAIN MUTATIONS; TYROSINE KINASE; GROWTH-FACTOR; PROTEIN AB Adenoid cystic carcinoma is an indolent salivary gland malignancy that is associated with a poor long-term prognosis. The distinction of adenoid cystic carcinoma from other head and neck neoplasms can occasionally be problematic, particularly in small biopsies. Recent studies suggest that IUT (CD 117) might be useful as an ancillary marker for adenoid cystic carcinoma; however, the expression of IUT in other benign and malignant head and neck neoplasms, including those that might mimic adenoid cystic carcinoma, has not been well studied. Here we use two different antibodies against I(IT to evaluate its expression in a series of 66 adenoid cystic carcinomas compared with its expression in 98 other neoplasms of the head and neck. Overall, 94% (n = 62) of adenoid cystic carcinomas from various anatomic sites and of various histologic subtypes were positive for at least one of the IUT antibodies, and 77% (n = 50) of adenoid cystic carcinoma cases were positive for both antibodies. This contrasted with only 8% (n = 8) of other head and neck neoplasms that were positive for both KIT antibodies (P < .001). It was of note that certain neoplasms, including pleomorphic adenoma, basal cell adenoma, polymorphous low-grade adenocarcinoma, and basal cell carcinoma, that can show histologic overlap with adenoid cystic carcinoma had significantly less IUT immunoreactivity than did adenoid cystic carcinoma (P < .001). In contrast, I(IT expression did not reliably distinguish adenoid cystic carcinoma from basal cell adenocarcinoma and basaloid squamous carcinoma (P > .05). The overall sensitivity of the two IUT antibodies for adenoid cystic carcinoma was 82-89%, and the specificity was 87-88%. The findings in this study support the potential use of IUT immunoexpression for distinguishing adenoid cystic carcinoma from many other benign and malignant head and neck neoplasms. C1 Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Faquin, WC (reprint author), Harvard Univ, Dept Pathol, Sch Med, Massachusetts Gen Hosp, Warrren 219,55 Fruit St, Boston, MA 02114 USA. NR 51 TC 79 Z9 84 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD DEC PY 2003 VL 16 IS 12 BP 1224 EP 1231 DI 10.1097/01.MP.0000096046.42833.C7 PG 8 WC Pathology SC Pathology GA 758VR UT WOS:000187672300007 PM 14681323 ER PT J AU Theunissen, JWF Kaplan, MI Hunt, PA Williams, BR Ferguson, DO Alt, FW Petrini, JHJ AF Theunissen, JWF Kaplan, MI Hunt, PA Williams, BR Ferguson, DO Alt, FW Petrini, JHJ TI Checkpoint failure and chromosomal instability without lymphomagenesis in Mre11(ATLD1/ATLD1) mice SO MOLECULAR CELL LA English DT Article ID STRAND BREAK REPAIR; S-PHASE CHECKPOINT; DEPENDENT NUCLEAR-DYNAMICS; CELL-CYCLE CHECKPOINT; DNA-DAMAGE CHECKPOINT; SACCHAROMYCES-CEREVISIAE; ATAXIA-TELANGIECTASIA; MRE11 COMPLEX; HOMOLOGOUS RECOMBINATION; PROTEIN COMPLEX AB In this study, mice expressing one of the two Mre11 alleles inherited in the human ataxia-telangiectasia like disorder (A-TLD) were derived. The mutation had a profound maternal effect on embryonic viability, revealing an acute requirement for Mre11 complex function in early embryogenesis. Mre11(ATLD1/ATLD1) mice exhibited several indices of impaired ATM function. The mice also exhibited pronounced chromosomal instability. Despite this phenotypic spectrum, the animals were not prone to malignancy. These data indicate that defective cell cycle checkpoints and chromosomal instability are insufficient to significantly enhance the initiation of tumorigenesis. In contrast, the latency of malignancy in p53(+/-) mice was dramatically reduced. We propose that in Mre11(ATLD1/ATLD1) mice, genome instability and cell cycle checkpoint defects reduce viability in early embryos and in proliferating cells, while promoting malignancy in the context of an initiating lesion. C1 Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA. Univ Wisconsin, Sch Med, Genet Lab, Madison, WI 53706 USA. Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Petrini, JHJ (reprint author), Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. FU NCI NIH HHS [CA92625]; NHLBI NIH HHS [K08 HL67580]; NIAID NIH HHS [AI35714]; NICHD NIH HHS [HD37502]; NIGMS NIH HHS [GM59413] NR 68 TC 120 Z9 123 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD DEC PY 2003 VL 12 IS 6 BP 1511 EP 1523 DI 10.1016/S1097-2765(03)00455-6 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 756XT UT WOS:000187511600019 PM 14690604 ER PT J AU Gensure, RC Shimizu, N Tsang, J Gardella, TJ AF Gensure, RC Shimizu, N Tsang, J Gardella, TJ TI Identification of a contact site for residue 19 of parathyroid hormone (PTH) and PTH-related protein analogs in transmembrane domain two of the type 1 PTH receptor SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID PHOTOAFFINITY CROSS-LINKING; (PTH)/PTH-RELATED PEPTIDE RECEPTOR; N-TERMINAL REGION; SECRETIN RECEPTOR; EXTRACELLULAR LOOP; GLUCAGON RECEPTOR; AMINO-TERMINUS; MOLECULAR CHARACTERIZATION; CONSTITUTIVE ACTIVITY; JUXTAMEMBRANE REGION AB Recent functional studies have suggested that position 19 in PTH interacts with the portion of the PTH-1 receptor (P1R) that contains the extracellular loops and seven transmembrance helices (TMs) (the J domain). We tested this hypothesis using the photoaffinity cross-linking approach. A PTHrP(1-36) analog and a conformationally constrained PTH(1-21) analog, each containing para-benzoyl-L-phenylalanine (Bpa) at position 19, each cross-linked efficiently to the P1R expressed in COS-7 cells, and digestive mapping analysis localized the cross-linked site to the interval (Leu232-Lys240) at the extracellular end of TM2. Point mutation analysis identified Ala234, Val235, and Lys240 as determinants of cross-linking efficiency, and the Lys240-->Ala mutation selectively impaired the binding of PTH(1-21) and PTH(1-19) analogs, relative to that of PTH(1-15) analogs. The findings support the hypothesis that residue 19 of the receptor-bound ligand contacts, or is close to, the P1R J domain - specifically, Lys240 at the extracellular end of TM2. The findings also support a molecular model in which the 1-21 region of PTH binds to the extracellular face of the P1R J domain as an alpha-helix. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Endocrine Unit, 50 Blossom St,WEL 501, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794] NR 63 TC 38 Z9 38 U1 0 U2 1 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD DEC 1 PY 2003 VL 17 IS 12 BP 2647 EP 2658 DI 10.1210/me.2003-0275 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 751NF UT WOS:000187072900022 PM 12947048 ER PT J AU Hughes, JAI Weckert, HA Pellekaan, CV Benson, EM Dunn, IS AF Hughes, JAI Weckert, HA Pellekaan, CV Benson, EM Dunn, IS TI Translocations into human chromosome 14J(H) region: factors influencing downstream abortive immunoglobulin class switching SO MOLECULAR IMMUNOLOGY LA English DT Article DE translocation; class switch recombination; somatic hypermutation ID HEAVY-CHAIN LOCUS; DIRECT SEQUENCE-ANALYSIS; B-CELL LYMPHOMAS; SOMATIC HYPERMUTATION; FOLLICULAR LYMPHOMA; FREQUENTLY OCCURS; MYC ONCOGENE; CD40 LIGAND; RECOMBINATION; GENE AB Bcl-2 translocations in follicular lymphomas (FL) are often associated with downstream immunoglobulin class switch recombination (CSR) on the translocated allele. We studied cell lines with different translocations into the IgH locus to gauge any common features associated with downstream CSR events. CSR associated with chromosomal rearrangements was observed in cells (RL) with translocations similar to those frequently observed in FL (bcl-2-J(H)), and such CSR was also seen with a myc (near exon 040 intron translocation (MC116), but not for far 5'-myc-J(H)5 intron (P3HR-1) or myc-Smu translocations (Ramos). Both MC116 and P3HR-1 myc translocations showed evidence for an origin from somatic hypermutation. Therefore, the association of J(H) translocations with CSR on the translocated allele is unlikely to be linked with specific translocation mechanisms, and the P3HR-1 configuration indicated that the downstream class switching is not a necessary consequence of (orprecondition for) such a translocation event. MC116 and RL, but not P3HR-1 cells, showed constitutive transcription through the translocated IgH alleles, suggesting that transcription through this region or the processing of such transcripts may promote CSR. However, while CSR events clearly occurred in the precursors of MC116 and RL, neither cell line could undergo complete class switching. (C) 2003 Elsevier Ltd. All rights reserved. C1 Westmead Hosp, Inst Immunol & Allergy Res, Westmead, NSW 2145, Australia. Westmead Hosp, Dept Immunopathol, Westmead, NSW 2145, Australia. RP Dunn, IS (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 508,100 Blossom St, Boston, MA 02114 USA. OI Thoms, Julie/0000-0002-4876-7230 NR 50 TC 3 Z9 3 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD DEC PY 2003 VL 40 IS 9 BP 573 EP 583 DI 10.1016/j.molimm.2003.09.001 PG 11 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 745PB UT WOS:000186696100002 PM 14597160 ER PT J AU Wang, XY Lo, EH AF Wang, XY Lo, EH TI Triggers and mediators of hemorrhagic transformation in cerebral ischemia SO MOLECULAR NEUROBIOLOGY LA English DT Review DE stroke; neuroprotection; neuromuscular unit; endothelial; blood-brain barrier ID BLOOD-BRAIN-BARRIER; TISSUE-PLASMINOGEN ACTIVATOR; MATRIX-METALLOPROTEINASE EXPRESSION; NECROSIS-FACTOR-ALPHA; MICROVASCULAR ENDOTHELIAL-CELLS; ACUTE INTRACEREBRAL HEMORRHAGE; ADHESION MOLECULE-1 ICAM-1; HYPOXIA-REOXYGENATION; SUPEROXIDE-DISMUTASE; TIGHT JUNCTIONS AB Intracerebral hemorrhagic transformation is a multifactorial phenomenon in which ischemic brain tissue converts into a hemorrhagic lesion with blood-vessel leakage, extravasation, and further brain injury. It has been estimated that up to 30-40% of all ischemic strokes undergo spontaneous hemorrhagic transformation, and this phenomenon may become even more prevalent with the increasing use of thrombolytic stroke therapy. An emerging conceptual model suggests that the loss of microvascular integrity and disruption of neurovascular homeostasis connects the experimental findings of blood-cell extravasation to brain injury after hemorrhage. In this short article, we examine mechanisms related to reperfusion injury and oxidative stress, leukocyte infiltration, vascular activation, and dysregulated extracellular proteolysis as potential triggers of hemorrhagic transformation. Perturbations in cell-cell and cell-matrix signaling within the hypothesized neurovascular unit may ultimately lead to neuroinflammation and apoptotic-like cell death in the parenchyma. Further investigations into the molecular mediators of hemorrhagic transformation may reveal new therapeutic targets for this clinically complex problem. C1 Massachusetts Gen Hosp, Neuroprot Res Lab, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuroprot Res Lab, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Neurosci Program, Cambridge, MA 02138 USA. RP Massachusetts Gen Hosp, Neuroprot Res Lab, Dept Neurol, Boston, MA 02114 USA. EM Wangxi@helix.mgh.harvard.edu; Lo@helix.mgh.harvard.edu FU NINDS NIH HHS [R01 NS 40529, P50 NS 10828, R01 NS 37074, R02 NS 38731] NR 125 TC 107 Z9 115 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0893-7648 EI 1559-1182 J9 MOL NEUROBIOL JI Mol. Neurobiol. PD DEC PY 2003 VL 28 IS 3 BP 229 EP 244 DI 10.1385/MN:28:3:229 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 756HC UT WOS:000187458900003 PM 14709787 ER PT J AU Samii, A Dahlen, DD Spence, AM Maronian, NC Kraus, EE Lennon, VA AF Samii, A Dahlen, DD Spence, AM Maronian, NC Kraus, EE Lennon, VA TI Paraneoplastic movement disorder in a patient with non-Hodgkin's lymphoma and CRMP-5 autoantibody SO MOVEMENT DISORDERS LA English DT Article DE chorea; dystonia; B-cell lymphoma; autoimmunity; rituximab ID CHOREA; CANCER; ENCEPHALITIS; PARKINSONISM; OPSOCLONUS; CARCINOMA; DYSTONIA AB The paraneoplastic autoantibody, collapsin response-mediator protein (CRMP)-5 immunoglobulin G (IgG), is specific for neuronal cytoplasmic CRMP-5, and is usually associated with small-cell lung carcinoma or thymoma. We report on details of a movement disorder that followed anti-B-cell therapy in a patient with lymphoma, and was accompanied by CRMP-5 IgG. (C) 2003 Movement Disorder Society. C1 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Mayo Clin, Dept Immunol, Rochester, MN USA. Univ Washington, Sch Med, Dept Otolaryngol, Seattle, WA USA. Univ Washington, Sch Med, Dept Hematol, Seattle, WA USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. RP Samii, A (reprint author), VA Puget Sound Hlth Care Syst, Mailstop 127,1660 S Columbian Way, Seattle, WA 98108 USA. NR 18 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD DEC PY 2003 VL 18 IS 12 BP 1556 EP 1558 DI 10.1002/md.10616 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 756FV UT WOS:000187455900025 PM 14673901 ER PT J AU Vucic, S Chong, PST Cros, D AF Vucic, S Chong, PST Cros, D TI Atypical presentations of primary amyloid neuropathy SO MUSCLE & NERVE LA English DT Article DE AL neuropathy; amyloidosis; multiple mononeuropathies; primary demyelinating polyneuropathy ID PRIMARY SYSTEMIC AMYLOIDOSIS; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; PERIPHERAL NEUROPATHY; AL AMYLOIDOSIS; NATURAL-HISTORY; NERVE; PARAPROTEINEMIA; HEREDITARY; MELPHALAN; ROOT AB Primary amyloidosis (AL) may be complicated by peripheral neuropathy in 15-35% of cases. We report on four patients with atypical neurological presentations of AL neuropathy, whose diagnoses were delayed due to varied clinical presentations. The clinical presentation included painful sensory neuropathy (two patients), mononeuropathy multiplex (one patient), and primary demyelinating polyneuropathy (one patient). The latter two types of presentation have not been reported previously. The diagnosis was established by fat pad biopsy in two patients, lymph node biopsy in one, and sural nerve biopsy in one. Two patients were treated with high-dose melphalan followed by stem cell rescue, and one was treated with oral melphalan and prednisone. All three cases experienced stabilization of neuropathic symptoms. We report these cases in order to raise awareness of the varied clinical presentation of AL neuropathy. C1 Massachusetts Gen Hosp, Dept Neurophysiol, Boston, MA 02114 USA. RP Chong, PST (reprint author), Massachusetts Gen Hosp, Dept Neurophysiol, Bigelow 1256,55 Fruit St, Boston, MA 02114 USA. NR 26 TC 19 Z9 20 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD DEC PY 2003 VL 28 IS 6 BP 696 EP 702 DI 10.1002/mus.10505 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 749GT UT WOS:000186912000005 PM 14639583 ER PT J AU Scortegagna, M Ding, K Oktay, Y Gaur, A Thurmond, F Yan, LJ Marck, BT Matsumoto, AM Shelton, JM Richardson, JA Bennett, MJ Garcia, JA AF Scortegagna, M Ding, K Oktay, Y Gaur, A Thurmond, F Yan, LJ Marck, BT Matsumoto, AM Shelton, JM Richardson, JA Bennett, MJ Garcia, JA TI Multiple organ pathology, metabolic abnormalities and impaired homeostasis of reactive oxygen species in Epas1(-/-) mice SO NATURE GENETICS LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; HYPOXIA-INDUCIBLE FACTOR-1; SYSTEMIC CARNITINE DEFICIENCY; LUNG EPITHELIAL-CELLS; GENE-EXPRESSION; OXIDATIVE STRESS; MITOCHONDRIAL ABNORMALITIES; DILATED CARDIOMYOPATHY; ENDOTHELIAL-CELLS; KNOCKOUT MICE AB Hypoxia-inducible factor (HIF) transcription factors respond to multiple environmental stressors, including hypoxia and hypoglycemia. We report that mice lacking the HIF family member HIF-2alpha (encoded by Epas1) have a syndrome of multiple-organ pathology, biochemical abnormalities and altered gene expression patterns. Histological and ultrastructural analyses showed retinopathy, hepatic steatosis, cardiac hypertrophy, skeletal myopathy, hypocellular bone marrow, azoospermia and mitochondrial abnormalities in these mice. Serum and urine metabolite studies showed hypoglycemia, lactic acidosis, altered Krebs cycle function and dysregulated fatty acid oxidation. Biochemical assays showed enhanced generation of reactive oxygen species (ROS), whereas molecular analyses indicated reduced expression of genes encoding the primary antioxidant enzymes (AOEs). Transfection analyses showed that HIF-2alpha could efficiently transactivate the promoters of the primary AOEs. Prenatal or postnatal treatment of Epas1(-/-) mice with a superoxide dismutase (SOD) mimetic reversed several aspects of the null phenotype. We propose a rheostat role for HIF-2alpha that allows for the maintenance of ROS as well as mitochondrial homeostasis. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. Univ Washington, Sch Med, Dept Med,VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Mol Biol, Dallas, TX 75390 USA. Childrens Med Ctr, Dept Pathol, Dallas, TX 75235 USA. RP Garcia, JA (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. RI Oktay, Yavuz/F-2703-2015; Oktay, Yavuz/G-4794-2015; OI Oktay, Yavuz/0000-0002-0158-2693; Yan, Liang-Jun/0000-0002-5815-5430 FU NHLBI NIH HHS [K08 HL067154] NR 50 TC 295 Z9 299 U1 2 U2 18 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD DEC PY 2003 VL 35 IS 4 BP 331 EP 340 DI 10.1038/ng1266 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 747DY UT WOS:000186791000014 PM 14608355 ER PT J AU Xu, YY Banerjee, D Huelsken, J Birchmeier, W Sen, JM AF Xu, YY Banerjee, D Huelsken, J Birchmeier, W Sen, JM TI Deletion of beta-catenin impairs T cell development SO NATURE IMMUNOLOGY LA English DT Article ID CHAIN GENE REARRANGEMENT; THYMOCYTE DEVELOPMENT; PRE-TCR; LINEAGE DECISION; IN-VIVO; DIFFERENTIATION; EXPRESSION; SURVIVAL; SIGNALS; TRANSCRIPTION AB T cells encounter two main checkpoints during development in the thymus. These checkpoints are critically dependent on signals derived from the thymic microenvironment as well as from the pre-T cell receptor (pre-TCR) and the TCR. Here we show that T cell-specific deletion of beta-catenin impaired T cell development at the beta-selection checkpoint, leading to a substantial decrease in splenic T cells. In addition, beta-catenin also seemed to be a target of TCR-CD3 signals in thymocytes and mature T cells. These data indicate that beta-catenin-mediated signals are required for normal T cell development. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brandeis Univ, Rosenstiel Ctr Biomed Res, Waltham, MA 02540 USA. Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sen, JM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Huelsken, Joerg/C-3861-2009 NR 35 TC 116 Z9 118 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD DEC PY 2003 VL 4 IS 12 BP 1177 EP 1182 DI 10.1038/ni1008 PG 6 WC Immunology SC Immunology GA 746VZ UT WOS:000186769500010 PM 14608382 ER PT J AU Sykes, M AF Sykes, M TI JAKing up immunosuppression SO NATURE MEDICINE LA English DT Editorial Material ID TOLERANCE; REJECTION AB new immunosuppressive agent makes its debut in primate models of kidney transplantation. The drug has the potential to join the ranks of immunosuppressants currently used in transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD DEC PY 2003 VL 9 IS 12 BP 1458 EP 1459 DI 10.1038/nm1203-1458 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 748CV UT WOS:000186845400017 PM 14647518 ER PT J AU Chiao, CC Masland, RH AF Chiao, CC Masland, RH TI Contextual tuning of direction-selective retinal ganglion cells SO NATURE NEUROSCIENCE LA English DT Article ID RABBIT RETINA; RESPONSES AB A direction-selective (DS) retinal ganglion cell responds well to a small object moving within its receptive field center, but less well when there is also a moving stimulus in the surrounding area; this has been described as tuning for local motion. We show here an additional selectivity, such that the surround has less effect if there is a discontinuity-that is, a difference in spatial phase, spatial frequency or velocity-between the center stimulus and that present in the surround. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 300, Taiwan. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. NR 11 TC 22 Z9 22 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD DEC PY 2003 VL 6 IS 12 BP 1251 EP 1252 DI 10.1038/nn1147 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 746BC UT WOS:000186725600007 PM 14595442 ER PT J AU Chen, JF Salas, A Springer, TA AF Chen, JF Salas, A Springer, TA TI Bistable regulation of integrin adhesiveness by a bipolar metal ion cluster SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID FUNCTION-ASSOCIATED ANTIGEN-1; CELL-ADHESION; I-DOMAIN; FIRM ADHESION; EXTRACELLULAR SEGMENT; PHYSIOLOGICAL FLOW; CRYSTAL-STRUCTURE; DIVALENT-CATIONS; BINDING; COMPLEX AB Integrin alpha(4)beta(7) mediates rolling adhesion in Ca2+ and Ca2+ + Mg2+, and firm adhesion in Mg2+ and Mn2+, mimicking the two key steps in leukocyte accumulation in inflamed vasculature. We mutated an interlinked linear array of three divalent cation-binding sites present in integrin beta-subunit I-like domains. The middle, metal ion dependent adhesion site ( MIDAS) is required for both rolling and firm adhesion. One polar site, that adjacent to MIDAS (ADMIDAS), is required for rolling because its mutation results in firm adhesion. The other polar site, the ligand-induced metal binding site ( LIMBS), is required for firm adhesion because its mutation results in rolling. The LIMBS mediates the positive regulatory effects of low Ca2+ concentrations, whereas the ADMIDAS mediates the negative regulatory effects of higher Ca2+ concentrations, which are competed by Mn2+. The bipolar sites thus stabilize two alternative phases of adhesion. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. OI Salas, Azucena/0000-0003-4572-2907 NR 35 TC 82 Z9 86 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD DEC PY 2003 VL 10 IS 12 BP 995 EP 1001 DI 10.1038/nsb1011 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 746BF UT WOS:000186725900008 PM 14608374 ER PT J AU Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I AF Paintlia, AS Gilg, AG Khan, M Singh, AK Barbosa, E Singh, I TI Correlation of very long chain fatty acid accumulation and inflammatory disease progression in childhood X-ALD: implications for potential therapies SO NEUROBIOLOGY OF DISEASE LA English DT Article DE human childhood X-ALD brain; very long chain fatty acids; inflammatory cytokines and chemokines; super gene array ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MONOCYTE CHEMOATTRACTANT PROTEIN-1; MULTIPLE-SCLEROSIS LESIONS; COLONY-STIMULATING FACTOR; BLOOD MONONUCLEAR-CELLS; TUMOR-NECROSIS-FACTOR; LINKED ADRENOLEUKODYSTROPHY AB This study was designed to understand the role of inflammatory mediators involved in the neurobiology of childhood adrenoleukodystrophy (cALD) by comparing the differential expression of the inflammatory mediators with metabolite very long chain fatty acids that accumulate in this disease. Histopathological examinations indicated extensive demyelination and accumulation of infiltrates in perivascular cuffs in plaque area (PA) and inflammatory area (IA) compared to normal looking area (NLA) of the cALD brain and controls. The PA had excessive accumulation of cholesterol ester (25-30-fold), VLC fatty acids (8-12-fold), and exhaustive depletion of cholesterol (60-70%) and sphingomyelin (50-55%) in comparison to controls. The mRNA expression of cytokines (IL-1alpha, IL-2, IL-3, IL-6, TNF-alpha, and GM-CSF), chemokines (CCL2, -4, -7, -11, -16, -21, -22, CXCL1, CX3CL1, and SDF-2) and NOS in IA was significantly increased compared to NLA of the cALD and controls determined by gene array, semiquantitative RT-PCR, and immunohistochemistry. These results indicate that accumulation of VLC fatty acid contents in membrane domains associated with signal transduction pathways may trigger the inflammatory process through activation of resident glial cells (microglia and astrocytes) resulting in loss of myelin and oligodendrocytes. (C) 2003 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Singh, I (reprint author), Med Univ S Carolina, Dept Pediat, 316-CSB,96 Jonathan Lucas St, Charleston, SC 29425 USA. OI Paintlia, Ajaib/0000-0003-4525-5333 FU NINDS NIH HHS [NS-40144, NS-37766, NS-34741, NS-22576] NR 81 TC 68 Z9 69 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD DEC PY 2003 VL 14 IS 3 BP 425 EP 439 DI 10.1016/j.nbd.2003.08.012 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 754XJ UT WOS:000187358300012 PM 14678759 ER PT J AU Fu, SS Ma, GX Tu, XM Siu, PT Metlay, JP AF Fu, SS Ma, GX Tu, XM Siu, PT Metlay, JP TI Cigarette smoking among Chinese Americans and the influence of linguistic acculturation SO NICOTINE & TOBACCO RESEARCH LA English DT Article; Proceedings Paper CT SGIM 2001 Annual Meeting CY MAY 02-05, 2001 CL SAN DIEGO, CALIFORNIA SP SGIM ID MEXICAN-AMERICANS; SCALE; HISPANICS; VALIDATION; ADULTS; GENDER AB Less acculturated Chinese Americans experience cultural and language barriers. The present study assessed the relationship between linguistic aspects of acculturation and cigarette smoking among Chinese Americans. A cross-sectional, self-administered survey was administered to a consecutive sample of 541 Chinese American adults (aged 18 years or older) attending four pediatric, medical, or dental practices located in Philadelphia's Chinatown from November 2000 to February 2001. Linguistic acculturation was measured by adapting a reliable and valid acculturation scale developed for Southeast Asians. English and Chinese language proficiency subscales were utilized to analyze the association between language proficiency and current smoking. Whereas 25% of Chinese American men reported current smoking, only 3% of Chinese American women reported current smoking. Chinese American men with lower English proficiency reported significantly higher rates of current smoking compared with Chinese American men with a higher level of English proficiency (33% vs. 18%, p<.01). Less English-proficient Chinese American male smokers were less likely to have received advice from a physician to quit smoking (50% vs. 85%, p=.01). In multivariate analysis, increased English proficiency was associated with decreased odds of current smoking (OR=0.38, 95% CI=0.16-0.89) among Chinese American men after controlling for confounding variables. In conclusion, higher English proficiency was associated with decreased current smoking among Chinese American men. Chinese American men with limited English proficiency should especially be targeted for tobacco control interventions. Further research is needed to assess whether acculturation is associated with smoking among Chinese American women and with use of smoking cessation treatments and services by Chinese American smokers. C1 CCDOR, Gen Internal Med Sect, Dept Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Temple Univ, Dept Hlth Studies, Philadelphia, PA 19122 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Fu, SS (reprint author), CCDOR, Gen Internal Med Sect, VA Med Ctr 1110, 1 Vet Dr, Minneapolis, MN 55417 USA. EM steven.fu@med.va.gov FU BHP HRSA HHS [T32PE10026] NR 38 TC 28 Z9 28 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD DEC PY 2003 VL 5 IS 6 BP 803 EP 811 DI 10.1080/14622200310001614566 PG 9 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 764ZL UT WOS:000188241000002 PM 14668064 ER PT J AU Park, EJ Chan, DW Park, JH Oettinger, MA Kwon, J AF Park, EJ Chan, DW Park, JH Oettinger, MA Kwon, J TI DNA-PK is activated by nucleosomes and phosphorylates H2AX within the nucleosomes in an acetylation-dependent manner SO NUCLEIC ACIDS RESEARCH LA English DT Article ID STRAND BREAK REPAIR; KINASE CATALYTIC SUBUNIT; PROTEIN-KINASE; HISTONE H2AX; GENOMIC INSTABILITY; V(D)J CLEAVAGE; HUMAN PLACENTA; KU PROTEIN; COMPLEX; AUTOPHOSPHORYLATION AB Eukaryotic DNA is organized into nucleosomes and higher order chromatin structure, which plays an important role in the regulation of many nuclear processes including DNA repair. Non-homologous end-joining, the major pathway for repairing DNA double-strand breaks (DSBs) in mammalian cells, is mediated by a set of proteins including DNA-dependent protein kinase (DNA-PK). DNA-PK is comprised of a large catalytic subunit, DNA-PKcs, and its regulatory subunit, Ku. Current models predict that Ku binds to the ends of broken DNA and DNA-PKcs is recruited to form the active kinase complex. Here we show that DNA-PK can be activated by nucleosomes through the ability of Ku to bind to the ends of nucleosomal DNA, and that the activated DNA-PK is capable of phosphorylating H2AX within the nucleosomes. Histone acetylation has little effect on the steps of Ku binding to nucleosomes and subsequent activation of DNA-PKcs. However, acetylation largely enhances the phosphorylation of H2AX by DNA-PK, and this acetylation effect is observed when H2AX exists in the context of nucleosomes but not in a free form. These results suggest that the phosphorylation of H2AX, known to be important for DSB repair, can be regulated by acetylation and may provide a mechanistic basis on which to understand the recent observations that histone acetylation critically functions in repairing DNA DSBs. C1 Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. Ewha Womans Univ, Ctr Cell Signalling Res, Seoul 120750, South Korea. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Kwon, J (reprint author), Ewha Womans Univ, Div Mol Life Sci, Seoul 120750, South Korea. NR 40 TC 104 Z9 110 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD DEC 1 PY 2003 VL 31 IS 23 BP 6819 EP 6827 DI 10.1093/nar/gkg921 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 747JY UT WOS:000186802500020 PM 14627815 ER PT J AU Monzillo, LU Hamdy, O AF Monzillo, LU Hamdy, O TI Evaluation of insulin sensitivity in clinical practice and in research settings SO NUTRITION REVIEWS LA English DT Review DE insulin resistance; insulin sensitivity; clinical practice ID GLUCOSE-TOLERANCE TEST; HOMEOSTASIS MODEL ASSESSMENT; DEPENDENT DIABETES-MELLITUS; POLYCYSTIC-OVARY-SYNDROME; CORONARY-HEART-DISEASE; BETA-CELL FUNCTION; CARDIOVASCULAR RISK-FACTORS; MUSCLE GLYCOGEN-SYNTHESIS; MINIMAL-MODEL; ORAL GLUCOSE AB Insulin resistance is the core metabolic abnormality in type 2 diabetes. Its high prevalence and its association with dyslipidemia, hypertension, hyperinsulinemia, and high coronary and cerebrovascular mortality put it in the forefront as the plausible target for aggressive intervention. Measurements of insulin sensitivity provide clinicians and clinical researchers with invaluable instruments to objectively evaluate the efficiency of both current and potentially useful interventional tools. Although several methods had been developed and validated to evaluate insulin sensitivity, none of these methods can be universally used in all patients. Nonetheless, a method suitable for use in clinical or basic research may not necessarily be a practical method for use in clinical practice or for epidemiologic research. We reviewed the currently used methods for assessment of insulin sensitivity. For each method, we summarized its procedure, normal value, cut-off value for defining insulin resistance, advantages and limitations, validity, accuracy for each patient population, and suitability for use in clinical practice and in research settings. The methods reviewed include fasting plasma insulin, homeostatic model assessment, quantitative insulin sensitivity check index, glucose-to-insulin ratio, continuous infusion of glucose with model assessment, indices based on oral glucose tolerance test, insulin tolerance test, and the so called "gold standard" methods, the hyperinsulinemic euglycemic clamp and the frequently sampled-intravenous glucose tolerance test. C1 Harvard Univ, Sch Med, Clin Res Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Monzillo, LU (reprint author), Harvard Univ, Sch Med, Clin Res Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 161 TC 124 Z9 133 U1 3 U2 16 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD DEC PY 2003 VL 61 IS 12 BP 397 EP 412 DI 10.1301/nr.2003.dec.397-412 PG 16 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 903NQ UT WOS:000227433200001 PM 14968910 ER PT J AU Elosua, R Demissie, S Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Corella, D Ordovas, JM AF Elosua, R Demissie, S Cupples, LA Meigs, JB Wilson, PWF Schaefer, EJ Corella, D Ordovas, JM TI Obesity modulates the association among APOE genotype, insulin, and glucose in men SO OBESITY RESEARCH LA English DT Article DE APOE genotype; insulin; glucose; interaction ID APOLIPOPROTEIN-E POLYMORPHISM; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; POSTPRANDIAL LIPEMIA; BIETHNIC POPULATION; MENOPAUSAL STATUS; OXIDATIVE STRESS; E PHENOTYPE; E ALLELES; RESISTANCE AB Objective: Obesity, insulin resistance, and apolipoprotein E (APOE) genotype have all been associated with coronary heart disease. We examined the interaction between obesity and APOE genotype in, determining fasting insulin and glucose levels. Research Methods and Procedures: From 1991 to 1995, 3799 subjects underwent a clinical examination and fasting insulin and glucose measurement. APOE genotypes were determined on 3500 participants. Participants taking oral hypoglycemic drugs or insulin preparations or with the rare APOE2/4 genotype were excluded. Finally, 2929 individuals were included in the present analysis. Results: In men, we observed a statistically significant interaction between obesity and APOE genotype on insulin and glucose level (p = 0.003 and 0.008, respectively). Obese men with the APOE4 genotype presented with higher levels of insulin and glucose than obese men in the other genotype groups. No association between genotype and insulin or glucose in nonobese men was observed. Obesity was associated with higher insulin levels in the three APOE genotypes groups, whereas obesity was directly associated with glucose in those with the APOE4 genotype. In women, effect of interaction between APOE genotype and obesity on fasting insulin and glucose was not statistically significant. Obesity was associated with higher levels of fasting insulin and glucose. APOE genotype was not associated with insulin or glucose. Discussion: Obesity modulates the association between the APOE genotype and fasting insulin and glucose levels in men. Although weight control is important in all people, it may be especially important in APOE4 men to modify potentially elevated fasting insulin and glucose levels. C1 Tufts Univ, JMUSDA HNRCA, Nutr & Genom Lab, Boston, MA 02111 USA. Tufts Univ, JMUSDA HNRCA, Lipid Metabol Lab, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Ordovas, JM (reprint author), Tufts Univ, JMUSDA HNRCA, Nutr & Genom Lab, 711 Washington St, Boston, MA 02111 USA. OI ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776]; PHS HHS [1-38038] NR 36 TC 43 Z9 45 U1 0 U2 3 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD DEC PY 2003 VL 11 IS 12 BP 1502 EP 1508 DI 10.1038/oby.2003.201 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 759FF UT WOS:000187727100010 PM 14694215 ER PT J AU Burgio, KL Zyczynski, H Locher, JL Richter, HE Redden, DT Wright, KC AF Burgio, KL Zyczynski, H Locher, JL Richter, HE Redden, DT Wright, KC TI Urinary incontinence in the 12-month postpartum period SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BLADDER NECK MOBILITY; STRESS-INCONTINENCE; VAGINAL DELIVERY; FECAL INCONTINENCE; CIGARETTE-SMOKING; CESAREAN-SECTION; PREGNANCY; CHILDBIRTH; WOMEN; BIRTH AB OBJECTIVE: To describe the prevalence and severity of urinary incontinence in die 12-month postpartum period and to relate this incontinence to several potential risk factors including body mass index, smoking, oral contraceptives, breast-feeding, and pelvic floor muscle exercise. METHODS: Participants were 523 women, aged 14 to 42 years, who had obstetrical deliveries. The women were interviewed in their rooms on postpartum day 2 or 3 and by telephone 6 weeks, 3 months, 6 months, and 12 months postpartum. Chart abstraction was conducted to obtain obstetrical data from the index delivery. RESULTS: At 6 weeks postpartum, 11.36% of women reported some degree of urinary incontinence since the index delivery. Although the rate of incontinence did not change significantly over the postpartum year, frequency of accidents decreased over time. In the generalized estimating equation, postpartum incontinence was significantly associated with seven variables: baseline report of smoking (odds ratio [OR] 2.934; P =.002), incontinence during pregnancy (OR 2.002; P =.007), length of breast-feeding (OR 1.169; P =.023), vaginal delivery (OR 2.360; P =.002), use of forceps (OR 1.870; P =.024), and two time-varying covariates: frequency of urination (OR 1.123; P = <.001) and body mass index (OR 1.055; P =.005). Factors not associated with postpartum incontinence included age, race, education, episiotomy, number of vaginal deliveries, attendance at childbirth preparation classes, and performing pelvic floor muscle exercises during the postpartum period. CONCLUSION: Postpartum incontinence is associated with several risk factors, some of which are potentially modifiable and others that can help target at-risk women for early intervention. C1 Dept Vet Affairs Med Ctr, Birmingham Atlanta Geriatr Res Educ & Clin Ctr, Birmingham, AL USA. Univ Alabama, Sch Med, Ctr Aging, Birmingham, AL USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Burgio, KL (reprint author), Birmingham VA Med Ctr, GRECC, 11G,700 19th St S, Birmingham, AL 35233 USA. FU NIA NIH HHS [K04 AG00431] NR 44 TC 102 Z9 109 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD DEC PY 2003 VL 102 IS 6 BP 1291 EP 1298 DI 10.1016/j.obstetgynecol.2003.09.013 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 747NX UT WOS:000186811800013 PM 14662217 ER PT J AU Wang, XR Eisen, EA Zhang, HX Sun, BX Dai, HL Pan, LD Wegman, DH Olenchock, SA Christiani, DC AF Wang, XR Eisen, EA Zhang, HX Sun, BX Dai, HL Pan, LD Wegman, DH Olenchock, SA Christiani, DC TI Respiratory symptoms and cotton dust exposure; results of a 15 year follow up observation SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ACROSS-SHIFT DROP; TEXTILE WORKERS; PULMONARY-FUNCTION; LANCASHIRE COTTON; LUNG-FUNCTION; RESPONSE RELATIONSHIPS; LONGITUDINAL CHANGES; ENDOTOXIN EXPOSURE; BYSSINOSIS; DISEASE AB Aims: To determine chronic effects of long term exposure to cotton dust and endotoxin on incidence of respiratory symptoms and the effect of cessation of exposure. Methods: Respiratory health in 429 Chinese cotton textile workers ( study group) and 449 silk textile workers ( control group) was followed prospectively from 1981 to 1996. Byssinosis, chest tightness, and non-specific respiratory symptoms were assessed by means of identical standardised questionnaires at four time points. Exposures to cotton dust and endotoxin were estimated using area samples collected at each survey. Incidence and persistence of symptoms were examined in relation to cumulative exposure and exposure cessation using generalised estimating equations (GEE). Results: Among cotton workers, the cumulative incidence of byssinosis and chest tightness was 24% and 23%, respectively, and was significantly more common in smokers than in non-smokers. A high proportion of symptoms was found to be intermittent, rather than persistent. Among silk workers, no typical byssinosis was identified; the incidence of chest tightness was 10%. Chronic bronchitis, cough, and dyspnoea were more common and persistent in the cotton group than in the silk group. Significantly lower odds ratios for symptoms were observed in cotton workers who left the cotton mills; risk was also related to years since last worked. Multivariate analysis indicated a trend for higher cumulative exposure to endotoxin in relation to a higher risk for byssinosis. Conclusion: Chronic exposure to cotton dust is related to both work specific and non-specific respiratory symptoms. Byssinosis is more strongly associated with exposure to endotoxin than to dust. Cessation of exposure may improve the respiratory health of cotton textile workers; the improvement appears to increase with time since last exposure. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Shanghai Text Bur, Hosp 1, Shanghai, Peoples R China. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. NIOSH, Morgantown, WV USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 42 TC 37 Z9 40 U1 1 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD DEC 1 PY 2003 VL 60 IS 12 BP 935 EP 941 DI 10.1136/oem.60.12.935 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 746KQ UT WOS:000186745900006 PM 14634185 ER PT J AU Ripandelli, G Scassa, C Parisi, V Gazzaniga, D D'Amico, DJ Stirpe, M AF Ripandelli, G Scassa, C Parisi, V Gazzaniga, D D'Amico, DJ Stirpe, M TI Cataract surgery as a risk factor for retinal detachment in very highly myopic eyes SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 105th Annual Meeting of the American-Academy-of-Ophthalmology CY NOV 11-14, 2001 CL NEW ORLEANS, LOUISIANA SP Amer Acad Ophthalmol ID INTRAOCULAR-LENS IMPLANTATION; AXIAL MYOPIA; EXTRACTION; CAPSULOTOMY; PHACOEMULSIFICATION AB Purpose: To evaluate the incidence of retinal detachment (RD) after cataract surgery performed by phaco-emulsification in very highly myopic eyes. Design: Retrospective, paired-eye, case-control trial. Participants and Intervention: We assessed the development of RD in 930 eyes from 930 subjects (mean age = 62.5 +/- 8.5 years) affected by very high myopia (between -15 and -30 diopters) undergoing cataract surgery after uncomplicated phacoemulsification (cataract-subjected [CS] eyes). Fellow eyes served as controls. Follow-up was 36 months. Main Outcome Measure: Detachment of the retina. Results: Retinal detachment was observed in 8.0% of CS eyes compared with 1.2% of control eyes (P<0.01, chi-square test). In CS eyes, posterior RD was most common (52.7% of eyes with RD). In control eyes, peripheral detachments with or without macular involvement were most common (47.3% of eyes with RD). Conclusion: Cataract surgery, despite the use of a safe technique such as phacoemulsification, increases the risk of RD development in very highly myopic eyes. (C) 2003 by the American Academy of Ophthalmology. C1 Fdn GB Bietti Oftalmol, Rome, Italy. Univ Roma Tor Vergata, Cattedra Clin Oculist, Rome, Italy. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. RP Ripandelli, G (reprint author), Via Pasubio 6, I-00195 Rome, Italy. NR 21 TC 41 Z9 47 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2003 VL 110 IS 12 BP 2355 EP 2361 DI 10.1016/S0161-6420(03)00819-4 PG 7 WC Ophthalmology SC Ophthalmology GA 748RT UT WOS:000186875400011 PM 14644718 ER PT J AU Miller, JW Lane, AM AF Miller, JW Lane, AM TI Anecortave acetate as monotherapy for treatment of subfoveal neovascularization in age-related macular degeneration - Twelve-month clinical outcomes - Disscussion SO OPHTHALMOLOGY LA English DT Editorial Material ID CHOROIDAL NEOVASCULARIZATION C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Angiogenesis Lab, Boston, MA 02115 USA. RP Miller, JW (reprint author), 243 Charles St, Boston, MA 02114 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD DEC PY 2003 VL 110 IS 12 BP 2384 EP 2385 DI 10.1016/j.ophtha.2003.09.001 PG 2 WC Ophthalmology SC Ophthalmology GA 748RT UT WOS:000186875400015 ER PT J AU Yelin, D Bouma, BE Iftimia, N Tearney, GJ AF Yelin, D Bouma, BE Iftimia, N Tearney, GJ TI Three-dimensional spectrally encoded imaging SO OPTICS LETTERS LA English DT Article ID ROUGH SURFACES; PROFILE MEASUREMENT; INTERFEROMETRY; ENDOSCOPY AB A method for three-dimensional surface measurements with phase-sensitive spectrally encoded imaging is demonstrated. Both transverse and depth information is transmitted through a single-mode optical fiber, allowing this scheme to be incorporated into a miniature probe. This approach is demonstrated by measurement of the profile of a lens surface and by three-dimensional imaging of the face of a small doll. (C) 2003 Optical Society of America. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Yelin, D (reprint author), Harvard Univ, Sch Med, 55 Fruit St,BAR 703, Boston, MA 02114 USA. NR 14 TC 16 Z9 17 U1 0 U2 0 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 DEC 1 PY 2003 VL 28 IS 23 BP 2321 EP 2323 DI 10.1364/OL.28.002321 PG 3 WC Optics SC Optics GA 746EW UT WOS:000186734900013 PM 14680169 ER PT J AU Rahbar, R Vargas, SO Miyamoto, CR Perez-Atayde, AR French, CA Robson, CD Licameli, GR Fletcher, JA Marcus, KC Grier, HE McGill, TJ Healy, GB AF Rahbar, R Vargas, SO Miyamoto, CR Perez-Atayde, AR French, CA Robson, CD Licameli, GR Fletcher, JA Marcus, KC Grier, HE McGill, TJ Healy, GB TI The role of chromosomal translocation (15;19) in the carcinoma of the upper aerodigestive tract in children SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID CANCER AB OBJECTIVE. To further evaluate the role of chromosomal translocation (15;19) in the presentation of the carcinoma (CA) of the upper aerodigestive tract. STUDY DESIGN AND SETTING: A retrospective study at a tertiary care pediatric medical center. RESULTS: Seven patients with a mean age of 12 years presented with CA of nasopharynx (N = 2), sinonasal region (N = 1), parotid gland (N = 2), or larynx (N = 2). Treatments included combinations of surgery (N = 5), chemotherapy (N = 5), and radiation therapy (N = 4). One patient with sinonasal CA and one patient with laryngeal CA had chromosomal translocation (15;19); these patients both died of their disease with a mean survival of 6 months. The 5 patients without translocation (15; 19) responded well to treatment and are disease-free with a mean follow-up of 47 months. CONCLUSION., The preliminary results appear to indicate poor prognosis associated with the presentation of chromosomal translocation (15; 19) despite aggressive multi-modality treatment. Further investigation is needed to better understand the cause and relationship of the translocation (15;19) and aggressive behavior of these tumors. C1 Childrens Hosp, Dept Otolaryngol, Boston, MA 02115 USA. Childrens Hosp, Dept Commun Disorders, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Childrens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Childrens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Cambridge, MA 02138 USA. RP Rahbar, R (reprint author), Childrens Hosp, Dept Otolaryngol, 300 Longwood Ave, Boston, MA 02115 USA. OI Robson, Caroline/0000-0001-5592-249X NR 19 TC 11 Z9 11 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD DEC PY 2003 VL 129 IS 6 BP 698 EP 704 DI 10.1016/S0194-5998(03)01451-7 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 753EN UT WOS:000187219300014 PM 14663438 ER PT J AU Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J AF Turk, DC Dworkin, RH Allen, RR Bellamy, N Brandenburg, N Carr, DB Cleeland, C Dionne, R Farrar, JT Galer, BS Hewitt, DJ Jadad, AR Katz, NP Kramer, LD Manning, DC McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robinson, JP Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Witter, J TI Core outcome domains for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Article DE chronic pain; clinical trials; assessment; outcomes; quality of life; physical functioning; emotional functioning; adverse events; global ratings ID QUALITY-OF-LIFE; LOW-BACK-PAIN; CONSORT STATEMENT; HEALTH-STATUS; IMPACT; RESPONSIVENESS; OSTEOARTHRITIS; MANAGEMENT; DISTRESS; SOCIETY AB Objective. To provide recommendations for the core outcome domains that should be considered by investigators conducting clinical trials of the efficacy and effectiveness of treatments for chronic pain. Development of a core set of outcome domains would facilitate comparison and pooling of data, encourage more complete reporting of outcomes, simplify the preparation and review of research proposals and manuscripts, and allow clinicians to make informed decisions regarding the risks and benefits of treatment. Methods. Under the auspices of the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT), 27 specialists from academia. governmental agencies, and the pharmaceutical industry participated in a consensus meeting and identified core outcome domains that should be considered in clinical trials of treatments for chronic pain. Conclusions. There was a consensus that chronic pain clinical trials should assess outcomes representing six core domains: (1) pain, (2) physical functioning, (3) emotional functioning, (4) participant ratings of improvement and satisfaction with treatment, (5) symptoms and adverse events, (6) participant disposition (e.g. adherence to the treatment regimen and reasons for premature withdrawal from the trial). Although consideration should be given to the assessment of each of these domains, there may be exceptions to the general recommendation to include all of these domains in chronic pain trials. When this occurs, the rationale for not including domains should be provided. It is not the intention of these recommendations that assessment of the core domains should be considered a requirement for approval of product applications by regulatory agencies or that a treatment must demonstrate statistically significant effects for all of the relevant core domains to establish evidence of its efficacy. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Rochester, Rochester, NY USA. AstraZeneca, Wilmington, DE USA. Univ Queensland, St Lucia, Qld 4067, Australia. Pfizer Pharmaceut Grp, New York, NY USA. Tufts Univ, Dept Anesthesiol, Medford, MA 02155 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. Ortho McNeil Pharmaceut Inc, Raritan, NJ USA. Univ Toronto, Toronto, ON, Canada. Univ Hlth Network, Toronto, ON, Canada. Harvard Univ, Cambridge, MA 02138 USA. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Dept Psychol, Halifax, NS, Canada. GlaxoSmithKline, Res Triangle Pk, NC USA. US FDA, Rockville, MD 20857 USA. Univ Washington, Dept Phys Med & Rehabil, Seattle, WA 98195 USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, La Jolla, CA 92093 USA. US Dept Vet Affairs, Washington, DC USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 NR 48 TC 483 Z9 491 U1 2 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD DEC PY 2003 VL 106 IS 3 BP 337 EP 345 DI 10.1016/j.pain.2003.08.001 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 753AR UT WOS:000187209600014 PM 14659516 ER PT J AU Kulich, RJ AF Kulich, RJ TI On being a legal expert - Pros and cons SO PAIN MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Tufts Univ, Sch Dent Med, Boston, MA 02111 USA. RP Kulich, RJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1526-2375 J9 PAIN MED JI Pain Med. PD DEC PY 2003 VL 4 IS 4 BP 362 EP 363 DI 10.1111/j.1526-4637.2003.3047a.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 748TH UT WOS:000186876800008 PM 14750912 ER PT J AU Takata, GS Chan, LS Morphew, T Mangione-Smith, R Morton, SC Shekelle, P AF Takata, GS Chan, LS Morphew, T Mangione-Smith, R Morton, SC Shekelle, P TI Evidence assessment of the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion SO PEDIATRICS LA English DT Review DE diagnostic methods; otitis media with effusion ID GRADIENT ACOUSTIC REFLECTOMETRY; PNEUMATIC OTOSCOPY; 3-YEAR-OLD CHILDREN; PREDICTIVE VALUE; CLINICAL-TRIALS; GLUE EAR; TYMPANOMETRY; AUDIOMETRY; IDENTIFICATION; MYRINGOTOMY AB Objectives. We report the findings of an evidence assessment on the accuracy of methods of diagnosing middle ear effusion in children with otitis media with effusion ( OME). Methods. We searched Medline ( 1966 - January 2000), the Cochrane Library ( through January 2000), and Embase ( 1980 - January 2000) and identified additional articles from reference lists in proceedings, published articles, reports, and guidelines. Excluded were nonhuman studies; case reports; editorials; letters; reviews; practice guidelines; non - English- language publications; and studies on patients with immunodeficiencies, craniofacial anomalies ( including cleft palate), primary mucosal disorders, or genetic conditions. From each eligible study, we calculated the sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and prevalence of OME in the cohort. We determined the number of studies for each comparison of a diagnostic method and a reference standard listed within the scope of our assessment. For comparisons with 3 or more studies, we derived random effects estimates of sensitivity, specificity, and prevalence rate. Using the pooled estimates, we plotted the performance of each diagnostic test in terms of sensitivity and ( 1 - specificity) and identified the best performer among the tests included in the comparison. Results. Among 8 diagnostic methods, pneumatic otoscopy had the best apparent performance with a sensitivity of 94% ( 95% confidence interval: 92% - 96%) and a specificity of 80% ( 95% confidence interval: 75% - 86%). However, examiner qualifications were reported inconsistently, and training was not specified. Conclusions. The finding that pneumatic otoscopy can do as well as or better than tympanometry and acoustic reflectometry has significant practical implications. For the typical clinician, pneumatic otoscopy should be easier to use than other diagnostic methods. The important question may be what degree of training will be needed for the clinician to be as effective with pneumatic otoscopy as were the examiners in the studies reviewed in this report. C1 Childrens Hosp Los Angeles, Div Gen Pediat, Los Angeles, CA 90027 USA. Los Angeles Cty & Univ So Calif, Med Ctr, Div Biostat & Outcomes Assessment, Los Angeles, CA USA. Univ So Calif, Dept Pediat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. RAND Corp, So Calif Evidence Based Practice Ctr, Santa Monica, CA USA. RAND Corp, Stat Grp, Santa Monica, CA USA. GReater Los Angeles Vet Affair Healthcare Syst, Hlth Serv Res & Dev Serv, Los Angeles, CA USA. RP Takata, GS (reprint author), Childrens Hosp Los Angeles, Div Gen Pediat, 4650 Sunset Blvd,MS 76, Los Angeles, CA 90027 USA. NR 68 TC 69 Z9 76 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD DEC PY 2003 VL 112 IS 6 BP 1379 EP 1387 DI 10.1542/peds.112.6.1379 PG 9 WC Pediatrics SC Pediatrics GA 749YK UT WOS:000186957500025 PM 14654613 ER PT J AU Hatch, J Gill-Body, KM Portney, LG AF Hatch, J Gill-Body, KM Portney, LG TI Determinants of balance confidence in community-dwelling elderly people SO PHYSICAL THERAPY LA English DT Article DE balance; balance confidence; falling; fear of falling; geriatric ID SELF-EFFICACY; LIVING ELDERS; OLDER-ADULTS; ABC SCALE; FEAR; FALLS; RESTRICTION; MOBILITY; PERFORMANCE; GO AB Background and Purpose. The fear of falling can have detrimental effects on physical function in the elderly population, but the relationship between a person's confidence in the ability to maintain balance and actual balance ability and functional mobility is not known. The extent to which balance confidence can be explained by balance performance, functional mobility, and sociodemographic, psychosocial, and health-related factors was the focus of this study. Subjects. The subjects were 50 community-dwelling elderly people, aged 65 to 95 years. ((X) over bar =81.7, SD=6.7). Methods. Balance was measured using the Berg Balance Scale. Functional mobility was measured using the Timed Up & Go Test. The Activities-specific Balance Scale was used to assess balance confidence. Data were analyzed using Pearson, correlation, multiple regression analysis, and t tests. Results. Fifty-seven percent of the variance in balance confidence could be explained by balance performance. Functional mobility and subject characteristics examined in this study did not contribute to balance confidence. Discussion and Conclusion. Balance performance alone is a strong determinant of balance confidence in community-dwelling elderly people. C1 Harvard Univ, Dept Phys Therapy, W Roxbury, MA USA. Massachusetts Gen Hosp, MGH Inst Hlth, Grad Programs Phys Therapy, Boston, MA 02114 USA. RP Hatch, J (reprint author), 282 Nepas Rd, Fairfield, CT 06430 USA. EM hatchjowd@yahoo.com NR 23 TC 84 Z9 89 U1 2 U2 4 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD DEC PY 2003 VL 83 IS 12 BP 1072 EP 1079 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 805XV UT WOS:000220399900001 PM 14640866 ER PT J AU Kondo, K Kim, WY Lechpammer, M Kaelin, WG AF Kondo, K Kim, WY Lechpammer, M Kaelin, WG TI Inhibition of HIF2 alpha is sufficient to suppress pVHL-defective tumor growth SO PLOS BIOLOGY LA English DT Article ID RENAL-CELL CARCINOMA; HIPPEL-LINDAU PROTEIN; FACTOR-ALPHA; CLEAR-CELL; FACTOR RECEPTOR; MESSENGER-RNAS; GENE-PRODUCT; HIF-ALPHA; VHL; EXPRESSION AB Biallelic inactivation of the von Hippel-Lindau tumor suppressor gene (VHL) is linked to the development of hereditary (VHL-associated) and sporadic clear-cell renal carcinomas as well as other abnormalities. The VHL gene product, pVHL, is part of an E3 ubiquitin ligase complex that targets the alpha subunits of the heterodimeric transcription factor HIF (hypoxia-inducible factor) for degradation in the presence of oxygen. Here we report that a HIF2alpha variant lacking both of its two prolyl hydroxylation/pVHL-binding sites prevents tumor inhibition by pVHL in a DNA-binding dependent manner. Conversely, downregulation of HIF2alpha with short hairpin RNAs is sufficient to suppress tumor formation by pVHL-defective renal carcinoma cells. These results establish that tumor suppression by pVHL is linked to regulation of HIF target genes. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Kaelin, WG (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. EM william_kaelin@dfci.harvard.edu NR 46 TC 318 Z9 324 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD DEC PY 2003 VL 1 IS 3 BP 439 EP 444 AR e83 DI 10.1371/journal.pbio.0000083 PG 6 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 772HC UT WOS:000188835600020 PM 14691554 ER PT J AU Grant, NN Anawalt, BD AF Grant, NN Anawalt, BD TI Male hypogonadism in the primary care clinic SO PRIMARY CARE LA English DT Article ID BONE-MINERAL DENSITY; TESTOSTERONE REPLACEMENT THERAPY; CORONARY-HEART-DISEASE; OBSTRUCTIVE SLEEP-APNEA; HEALTHY ADULT MEN; TRANSDERMAL SYSTEM; SERUM TESTOSTERONE; BODY-COMPOSITION; PROSTATE-CANCER; MUSCLE STRENGTH AB Hypogonadism is common in clinical practice but is freqently unrecognized and underdiagnosed. The common causes of male hypogonadism vary with the age of presentation. The overall prevalence of male hypogonadism based upon low serum total testosterone levels is high and increases with age from <5% for men in their twenties and thirties to 12%, 19%, 28%, and 49% for men in their fifties, sixties, seventies, and eighties, respectively [1]. A common cause of hypogonadism in boys and young men is Klinefelter's syndrome, a congenital abnormality occurring in approximately 1:500 men [2,3] that results in a primary testicular disorder associated with small, undeveloped testes and elevated serum gonadotropins. In older men, hypogonadism is often caused by pituitary dysfunction and gonadotropin deficiency due to hyperprolactinemia, corticosteroid excess, hemochromatosis, or pituitary tumors. As men age, serum testosterone levels tend to decline, and some older men develop a clinical syndrome consistent with hypogonadism, a common syndrome of aging called "andropause." There are many pitfalls in making the diagnosis of male hypogonadism. First, male hypogonadism is sometimes difficult to recognize because the signs and symptoms are often nonspecific and overlap with other common syndromes such as depression or are dismissed as the result of normal aging. Second, the biochemical diagnosis of male hypogonadism is not straightforward because it might not be clear which testosterone assay to select from the many that are available. Finally, even after the diagnosis of male hypogonadism is made, the patient and clinician must weigh the potential benefits and risks of androgen replacement therapy. However, new diagnostic tools and therapies are making decisions easier. C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Univ Washington, VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bradley.anawalt@med.va.gov NR 75 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0095-4543 EI 1558-299X J9 PRIMARY CARE JI Primary Care PD DEC PY 2003 VL 30 IS 4 BP 743 EP + DI 10.1016/S0095-4543(03)00091-5 PG 22 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 757GM UT WOS:000187554700007 PM 15024894 ER PT J AU Yao, JK AF Yao, JK TI Special issue: Recent advances of membrane pathology in schizophrenia - Preface SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Editorial Material C1 Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. RP Yao, JK (reprint author), Univ Pittsburgh, VA Pittsburgh Healthcare Syst, Med Ctr, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 365 EP 365 DI 10.1016/j.plefa.2003.08.007 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500001 ER PT J AU Skosnik, PD Yao, JK AF Skosnik, PD Yao, JK TI From membrane phospholipid defects to altered neurotransmission: is arachidonic acid a nexus in the pathophysiology of schizophrenia? SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Review DE schizophrenia; phospholipid metabolism; polyunsaturated fatty acids; arachidonic acid signaling; eicosanoids; endocannabinoids; cytokines; neurotransmission; neurodevelopment; oxidative stress ID ESSENTIAL FATTY-ACIDS; MAGNETIC-RESONANCE-SPECTROSCOPY; POSITRON-EMISSION-TOMOGRAPHY; ETHYL-EICOSAPENTAENOIC ACID; POSTMORTEM HUMAN BRAIN; DRUG-FREE PATIENTS; NIACIN SKIN FLUSH; PROTEIN-KINASE-C; RED-BLOOD-CELLS; CANNABINOID RECEPTOR AB Schizophrenia (SZ) is a devastating neuropsychiatric disorder affecting 1% of the general population, and is characterized by symptoms such as delusions, hallucinations, and blunted affect. While many ideas regarding SZ pathogenesis have been put forth, the majority of research has focused on neurotransmitter function, particularly in relation to altered dopamine activity. However, treatments based on this paradigm have met with only modest success, and current medications fail to alleviate symptoms in 30-60% of patients. An alternative idea postulated a quarter of a century ago by Feldberg (Psychol. Med. 6 (1976) 359) and Horrobin (Lancet 1 (1977) 936) involves the theory that SZ is associated in part with phospholipid/fatty acid abnormalities. Since then, it has been repeatedly shown that in both central and peripheral tissue, SZ patients demonstrate increased phospholipid breakdown and decreased levels of various polyunsaturated fatty acids (PUFAs), particularly arachidonic acid (AA). Given the diverse physiological function of membrane phospholipids and PUFAs, an elucidation of their role in SZ pathophysiology may provide novel strategies in the treatment of this disorder. The purpose of this review is to summarize the relevant data on membrane phospholipid/PUFA defects in SZ, the physiological consequence of altered AA signaling, and how they relate to the neurobiological manifestations of SZ and therapeutic outcome. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, WPIC, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA. RP Yao, JK (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. NR 227 TC 47 Z9 50 U1 0 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 367 EP 384 DI 10.1016/j.plefa.2003.08.008 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500002 PM 14623490 ER PT J AU Reddy, RD Yao, JK AF Reddy, RD Yao, JK TI Environmental factors and membrane polyunsaturated fatty acids in schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE schizophrenia; smoking; polyunsaturated fatty acids; oxidative stress; diet; omega-3 fatty acids ID RED-BLOOD-CELLS; CIGARETTE-SMOKING; ERYTHROCYTE-MEMBRANES; LIPID-PEROXIDATION; SKIN FIBROBLASTS; PLASMA; SMOKERS; SUPPLEMENTATION; ANTIOXIDANTS; ASSOCIATION AB There is accumulating evidence of reductions in red blood cell membrane essential fatty acids in patients with schizophrenia. The mechanisms that may underlie these reductions have yet to be determined. It is possible that the observed membrane fatty acid deficits are associated with the development of schizophrenia. Alternatively, the membrane fatty acid deficits may be due to environmental factors, such as smoking and variations in diet, which may not be associated specifically with the pathophysiology of schizophrenia. Patients with schizophrenia smoke cigarettes at very high rates. Cigarette smoke contains many pro-oxidants that contribute directly to oxidative stress. Polyunsaturated fatty acids (PUFAs) are very susceptible to oxidative effects of free radicals. Thus, smoke-induced oxidative stress could plausibly account for reductions in membrane fatty acid in schizophrenia. Recent studies provide conflicting evidence for smoking effects on membrane fatty acid deficits. Likewise, the effects of diet on membrane PUFAs in schizophrenia are not entirely clear. Essential PUFAs need to be consumed in diet. Thus, differences in membrane PUFAs observed between patients and control subjects may be due to dietary variation. Few studies that have examined dietary effects differ in their interpretation of the effects of diet on membrane PUFAs. Thus, the jury is still out whether smoking or dietary effects are the primary causes of membrane PUFA deficits in patients with schizophrenia. Future studies will need to systematically examine the potential effects of smoking and diet, as well as other environmental factors such exercise, to definitively establish whether or not PUFA abnormalities are inherent to schizophrenia. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. RP Reddy, RD (reprint author), Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH43742, MH 64118, MH58141] NR 67 TC 21 Z9 23 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 385 EP 391 DI 10.1016/j.plefa.2003.08.009 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500003 PM 14623491 ER PT J AU Reddy, R Keshavan, MS AF Reddy, R Keshavan, MS TI Phosphorus magnetic resonance spectroscopy: its utility in examining the membrane hypothesis of schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE magnetic resonance spectroscopy; phosphorus; schizophrenia; polyunsaturated fatty acids; membranes ID FATTY-ACID COMPOSITION; HIGH-ENERGY PHOSPHATE; IN-VIVO; PHOSPHOLIPID-METABOLISM; PREFRONTAL CORTEX; TEMPORAL LOBES; METHODOLOGICAL ISSUES; DOCOSAHEXAENOIC ACID; FRONTAL LOBES; FED PIGLETS AB A novel approach to understanding the pathophysiology of schizophrenia has been the investigation of membrane composition and functional perturbations, referred to as the "Membrane Hypothesis of Schizophrenia." The evidence in support of this hypothesis has been accumulating in findings in patients with schizophrenia of reductions in phospholipids and essential fatty acids various peripheral tissues. Postmortem studies indicate similar reductions in essential fatty acids in the brain. However, the use of magnetic resonance spectroscopy (MRS) has provided an opportunity to examine aspects of membrane biochemistry in vivo in the living brain. MRS is a powerful, albeit complex, noninvasive quantitative imaging tool that offers several advantages over other methods of in vivo biochemical investigations. It has been used extensively in investigating brain biochemistry in schizophrenia. Phosphorus MRS (P-31 MRS) can provide important information about neuronal membranes, such as levels of phosphomonoesters that reflect the building blocks of neuronal membranes and phosphodiesters that reflect breakdown products. P-31 MRS can also provide information about bioenergetics. Studies in patients with chronic schizophrenia as well as at first episode prior to treatment show a variety of alterations in neuronal membrane biochemistry, supportive of the membrane hypothesis of schizophrenia. Below, we will briefly review the principles underlying P-31 MRS and findings to date. Magnetic resonance spectroscopy (MRS) is a powerful, albeit complex, imaging tool that permits investigation of brain biochemistry in vivo. It utilizes the magnetic resonance imaging hardware. It offers several advantages over other methods of in vivo biochemical investigations. MRS is noninvasive, there is no radiation exposure, does not require the use of tracer ligands or contrast media. Because of it is relatively benign, repeated measures are possible. It has been used extensively in investigating brain biochemistry in schizophrenia. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. RP Reddy, R (reprint author), Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Dept Psychiat, 3811 OHara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH-45203, MH-64118] NR 45 TC 22 Z9 24 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 401 EP 405 DI 10.1016/j.plefa.2003.08.011 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500005 PM 14623493 ER PT J AU Yao, JK Sistilli, CG van Kammen, DP AF Yao, JK Sistilli, CG van Kammen, DP TI Membrane polyunsaturated fatty acids and CSF cytokines in patients with schizophrenia SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article DE schizophrenia; red blood cells; cerebrospinal fluid; polyunsaturated fatty acids; interleukin 6; interleukin 10 ID MAGNETIC-RESONANCE SPECTROSCOPY; DIETARY SUPPLEMENTATION; PHOSPHOLIPASE-A2 ACTIVITY; ARACHIDONIC-ACID; INTERLEUKIN-2 PRODUCTION; DRUG-FREE; ERYTHROCYTE-MEMBRANES; SERUM INTERLEUKIN-6; SIGNAL TRANSDUCTION; LIPID PEROXIDES AB Findings to date provide evidence that altered membrane structure and function are present in patients with either first-episode or chronic schizophrenia, suggesting defects in phospholipid metabolism and cell signaling in schizophrenia. The purpose of this investigation is to test whether decreased membrane polyunsaturated fatty acids (PUFAs) were associated with an increased secretion of proinflammatory cytokines. Thus, we measured interleukin 6 (IL-6) and interleukin 10 (IL-10) in cerebrospinal fluid (CSF) of patients with chronic schizophrenia as well as PUFAs of red blood cell (RBC) membranes from the same individuals. A significant and inverse correlation was found between CSF IL-6 (not IL-10) and RBC membrane PUFAs levels in both haloperidol-treated and medication-free patients with schizophrenia. Specifically, such an association was found in the n-6 (18:2, 20:4, and 22:4) and, to a lesser extent, the n-3 fatty acids. Taken together, the present findings suggest that decreased membrane PUFAs may be related to an immune disturbance in schizophrenia, possibly resulting from an increased phospholipase A, activity mediated through the proinflammatory cytokines. (C) 2003 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15206 USA. Aventis Inc, Bridgewater, NJ 08807 USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Yao, JK (reprint author), Univ Pittsburgh, Med Ctr, VA Pittsburgh Healthcare Syst, 7180 Highland Dr,Bldg 13, Pittsburgh, PA 15206 USA. FU NIMH NIH HHS [MH44841, MH58141, MH43742] NR 91 TC 17 Z9 18 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD DEC PY 2003 VL 69 IS 6 BP 429 EP 436 DI 10.1016/j.plefa.2003.08.015 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 747QV UT WOS:000186816500009 PM 14623497 ER PT J AU Shetty, RP de Bakker, PIW DePristo, MA Blundell, TL AF Shetty, RP de Bakker, PIW DePristo, MA Blundell, TL TI Advantages of fine-grained side chain conformer libraries SO PROTEIN ENGINEERING LA English DT Article DE all-atom modelling; conformational sampling; side chain conformations; RAPPER; rotamers ID PROTEIN-STRUCTURE PREDICTION; DEPENDENT ROTAMER LIBRARY; AB-INITIO CONSTRUCTION; POLYPEPTIDE FRAGMENTS; CONFORMATIONS; MODEL; ACCURACY; PACKING AB We compare the modelling accuracy of two common rotamer libraries, the Dunbrack-Cohen and the 'Penultimate' rotamer libraries, with that of a novel library of discrete side chain conformations extracted from the Protein Data Bank. These side chain conformer libraries are extracted automatically from high-quality protein structures using stringent filters and maintain crystallographic bond lengths and angles. This contrasts with traditional rotamer libraries defined in terms of chi angles under the assumption of idealized covalent geometry. We demonstrate that side chain modelling onto native and near-native main chain conformations is significantly more successful with the conformer libraries than with the rotamer libraries when solely considering excluded-volume interactions. The rotamer libraries are inadequate to model side chains without atomic clashes on over 20% of targets if the backbone is held fixed in the native conformation. An algorithm is described for simultaneously modelling both main chain and side chain atoms during discrete ab initio sampling. The resulting models have equivalent root mean square deviations from the experimentally determined protein loops as models from backbone-only ensembles, indicating that all-atom modelling does not detract from the accuracy of conformational sampling. C1 Univ Cambridge, Dept Biochem, Cambridge CB2 1GA, England. RP de Bakker, PIW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM debakker@molbio.mgh.harvard.edu RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 25 TC 19 Z9 19 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD DEC PY 2003 VL 16 IS 12 BP 963 EP 969 DI 10.1093/protein/gzg143 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 807SE UT WOS:000220520400014 PM 14983076 ER PT J AU Monnier, J Knapp, RG Frueh, BC AF Monnier, J Knapp, RG Frueh, BC TI Recent advances in telepsychiatry: An updated review SO PSYCHIATRIC SERVICES LA English DT Article ID MENTAL-HEALTH-SERVICE; COGNITIVE-BEHAVIORAL THERAPY; FACE-TO-FACE; CONTROLLED-TRIAL; COST-ANALYSIS; TELEMEDICINE; CARE; CHILD; PROGRAM; SATISFACTION AB Objective: In response to new developments and interest in the area of telepsychiatry, literature on this topic has greatly increased over the past three years. Because of this increase, the authors conducted a literature review of telepsychiatry to update a previously published review that covered the years 1970 to 2000. Methods: A search was conducted on the MEDLINE, PsycINFO, and Telemedicine Information Exchange (TIE) databases for literature published from March 2000 to March 2003 on telepsychiatry applications, using the following terms: telepsychiatry, telepsychology, telemental health, videoconferencing, and video conferencing. Results: Sixty-eight publications were identified over this three-year period, exceeding the 63 publications identified in the previous literature review. The authors summarize the results of findings in six areas: novel clinical demonstrations and current program descriptions; the reliability of clinical assessments; clinical outcomes; satisfaction of patients and clinicians; cost and cost-effectiveness; and legal, regulatory, and ethical issues. Studies describing existing programs and novel clinical applications support the belief that the use of telepsychiatry is expanding. Overall, studies continued to support the notion that telepsychiatry assessments can produce reliable results, telepsychiatric services can lead to improved clinical status, and patients and clinicians are satisfied with treatment delivered via telepsychiatry. Evidence supported the notion that telepsychiatry is a cost-effective means of delivering mental health services; however, this conclusion was based on limited studies of economic models of telepsychiatry programs. Also limited were papers on the topics of legal, regulatory, and ethical issues. Conclusions: Despite the rapid increase in information on telepsychiatry, methodologically sound studies in the area of telepsychiatry are still infrequent. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC USA. RP Monnier, J (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 171 Ashley Ave,POB 250681, Charleston, SC 29425 USA. EM monnierj@musc.edu NR 67 TC 103 Z9 104 U1 0 U2 9 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2003 VL 54 IS 12 BP 1604 EP 1609 DI 10.1176/appi.ps.54.12.1604 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BV UT WOS:000222759200012 PM 14645799 ER PT J AU Lafayette, JM Frankle, WG Pollock, A Dyer, K Goff, DC AF Lafayette, JM Frankle, WG Pollock, A Dyer, K Goff, DC TI Clinical characteristics, cognitive functioning, and criminal histories of outpatients with schizophrenia SO PSYCHIATRIC SERVICES LA English DT Article ID VIOLENCE; CLOZAPINE; BEHAVIOR; OLANZAPINE; DEFICITS; RISPERIDONE; INPATIENTS; COMMUNITY; DISORDER; VALIDITY AB Objective. The authors examined the relationships between clinical characteristics, cognitive functioning, and history of violent behavior and substance use among outpatients with schizophrenia. Methods: Ninety-six patients with a diagnosis of schizophrenia or schizoaffective disorder completed a clinical and neuropsychiatric battery that included tests of general intelligence, executive. and frontal lobe function, visual-motor processing, and motor function. Violent behavior was defined on the basis of arrest records. Self-reported violent behavior and substance use were recorded. The study participants were separated into three groups: history of violent arrest (N = 34), nonviolent arrest.(N = 23), and no arrest (N = 39). The three groups were compared for differences in demographic characteristics, clinical symptoms, and scores on neuropsychological tests. Results: Fifty-seven (59 percent) of the 96 participants had a history of arrest. Persons who were arrested for nonviolent crimes had a significantly lower meant +/- SD number of arrests (3.39 +/- 3.7) than those arrested for violent crimes (9.24 +/- 8.9). No significant differences in neuropsychological test scores or clinical ratings were found between the three groups. The prevalence of substance use disorders was 65 percent, 57 percent, and 36 percent among patients with a history of violent, nonviolent,and no arrest, respectively. Only 47 percent of participants with a criminal history accurately reported this history, and 11 percent of participants, with a history of drug-related arrests acknowledged, previous substance use. Conclusions: Performance on neuropsychiatric tests does not distinguish stable outpatients with schizophrenia who have a history of violent behavior from those who do not have such a history. Two established predictors of violence, a history of arrests and substance abuse, are unreliable when assessed by self-report. C1 Massachusetts Gen Hosp, Schizophrenia Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA USA. RP Lafayette, JM (reprint author), Massachusetts Gen Hosp, Schizophrenia Res Program, Warren 605,33 Fruit St, Boston, MA 02114 USA. EM jlafayette@partners.org NR 29 TC 29 Z9 30 U1 0 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2003 VL 54 IS 12 BP 1635 EP 1640 DI 10.1176/appi.ps.54.12.1635 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BV UT WOS:000222759200017 PM 14645804 ER PT J AU Weissman, EM Kushner, M Marcus, SM Davis, DF AF Weissman, EM Kushner, M Marcus, SM Davis, DF TI Volume of VA patients with posttraumatic stress disorder in the New York metropolitan area after september 11 SO PSYCHIATRIC SERVICES LA English DT Article ID TERRORIST ATTACKS; PSYCHOLOGICAL SEQUELAE AB The authors examined data from the Veterans Integrated Service Network of New York and New Jersey to determine whether the number of veterans who were treated for posttraumatic stress disorder (PTSD) increased significantly after the terrorist attacks of September 11, 2001. They analyzed the number of veterans treated for PTSD at Veterans Healthcare Administration facilities in New York and New Jersey from September 1999 through June 2002. The number of veterans treated for PTSD in these facilities after September 11 exceeded projections based on secular trends, and the increase was more pronounced than for other, diagnostic groups. The results highlight the need to ensure adequate availability of services in the! wake of traumatic events. C1 MIRECC, Dept Vet Affairs Med Ctr, Bronx, NY USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. VISN 3, Mental Hlth Care Line, Bronx, NY USA. RP Weissman, EM (reprint author), Bronx Vet Adm Med Ctr, OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM ellen.weissman@med.va.gov NR 9 TC 9 Z9 9 U1 2 U2 2 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD DEC PY 2003 VL 54 IS 12 BP 1641 EP 1643 DI 10.1176/appi.ps.54.12.1641 PG 3 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BV UT WOS:000222759200018 PM 14645805 ER PT J AU Garb, HN AF Garb, HN TI Incremental validity and the assessment of psychopathology in adults SO PSYCHOLOGICAL ASSESSMENT LA English DT Review ID BORDERLINE PERSONALITY-DISORDER; NONCLINICAL YOUNG-ADULTS; RATING DEPRESSION SCALE; EGO IMPAIRMENT INDEX; ANXIETY SENSITIVITY; COMPREHENSIVE SYSTEM; PERCEIVED CONTROL; INTERPERSONAL PROBLEMS; SCHIZOPHRENIC-PATIENTS; PSYCHIATRIC-PATIENT AB Results from studies on incremental validity are described for (a) interviews, (b) personality inventories, (c) projective techniques, and (d) brief self-rated and clinician-rated measures. In some of the studies (clinical judgment studies), psychologists were given increasing amounts of information. In other studies (statistical prediction studies), increasing amounts of assessment information were entered into a statistical prediction rule. Although relatively little research has been conducted on incremental validity, results that have been obtained tend to favor the use of interviews, personality inventories (e.g., the Minnesota Multiphasic Personality Inventory-2; J. N. Butcher, W. G. Dahlstrom, J. R., Graham, A. Tellegen, & B. Kaemmer, 1989), and brief self-rated measures (e.g., the Anxiety Sensitivity Index, S. Reiss, R. A. Peterson, D. M. Gursky, & R. M. McNally, 1986). Results are generally less encouraging for projective techniques. C1 Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat & Psychol, Pittsburgh, PA 15260 USA. RP Garb, HN (reprint author), Wilford Hall USAF Med Ctr, Psychol Res Serv, 59 MDOS MMCPR,2200 Bergquist Dr,Suite 1, Lackland AFB, TX 78236 USA. NR 156 TC 30 Z9 31 U1 5 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1040-3590 J9 PSYCHOL ASSESSMENT JI Psychol. Assess. PD DEC PY 2003 VL 15 IS 4 BP 508 EP 520 DI 10.1037/1040-3590.15.4.508 PG 13 WC Psychology, Clinical SC Psychology GA 754VH UT WOS:000187352200007 PM 14692846 ER PT J AU Koski, G AF Koski, G TI Imagination and attention: protecting participants in psychopharmacological research SO PSYCHOPHARMACOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. RP Koski, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 56 EP 57 DI 10.1007/s00213-003-1631-7 PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900008 PM 14598015 ER PT J AU Beresin, EV Baldessarini, RJ Alpert, J Rosenbaum, J AF Beresin, EV Baldessarini, RJ Alpert, J Rosenbaum, J TI Teaching ethics of psychopharmacology research in psychiatric residency training programs SO PSYCHOPHARMACOLOGY LA English DT Review DE education; ethics; psychiatry; psychopharmacology; research; residency ID MENTAL-ILLNESS; ISSUES; DISORDERS; CAPACITY; CONSENT AB Rationale. American psychiatric residency training programs are now required to teach principles of research ethics. This task is especially pressing in light of evolving guidelines pertaining to human subjects, including psychiatric patients, especially when psychopharmacology is involved. Residents need to understand principles of research ethics and implications of roles of psychiatrists as investigators and clinicians. Objectives. We consider major contemporary ethical issues in clinical psychiatric research, with an emphasis on psychopharmacology, and implications of addressing them within residency training programs. Methods. We reviewed recent literature on ethical issues in clinical research and on medical education in bioethics. Results. This report considers: (1) an overview of current training; (2) perceived needs and rationales for training in research ethics, (3) recommended educational content and methods; (4) issues that require further study (including demonstration of acquired knowledge, practice issues, and the treatment versus-investigation misconception); and (5) conclusions. Recommended components of residency training programs include basic ethical principles; scientific merit and research design; assessment of risks and benefits; selection and informed consent of patient-subjects; and integrity of the clinical investigator, including definition of roles, conflicts-of-interest, and accountability. Evaluation of educational effectiveness for both trainees and faculty is a recommended component of such programs. Conclusions. We recommend that psychiatric training include education about ethical aspects of clinical research, with a particular emphasis on psychopharmacology. These activities can efficiently be incorporated into teaching of other aspects of bioethics, research methods, and psychopharmacology. Such education early in professional development should help to clarify roles of clinicians and investigators, improve the planning, conduct and reporting of research, and facilitate career development of much-needed clinical investigators in psychiatry. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, McLean Hosp, Sch Med, Mailman Res Ctr 306,Dept Psychiat, Belmont, MA 02478 USA. RP Beresin, EV (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bullfinch 449, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X NR 31 TC 8 Z9 8 U1 3 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD DEC PY 2003 VL 171 IS 1 BP 105 EP 111 DI 10.1007/s00213-003-1434-x PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 750ET UT WOS:000186978900016 PM 12677357 ER PT J AU Hasenfeld, R Shekelle, PG AF Hasenfeld, R Shekelle, PG TI Is the methodological quality of guidelines declining in the US? Comparison of the quality of US Agency for Health Care Policy and Research (AHCPR) guidelines with those published subsequently SO QUALITY & SAFETY IN HEALTH CARE LA English DT Article ID SPECIALTY; APPRAISAL; REVIEWS AB Objective: To determine whether North American guidelines published subsequent to and in the same topic areas as those developed by the US Agency for Health Care Policy and Research (AHCPR) meet the same methodological criteria. Study design: A guideline appraisal instrument containing 30 criteria was used to evaluate the methodological quality of the AHCPR guidelines, "updates" of the AHCPR guidelines authored by others, and guidelines that referenced or were adapted from the AHCPR guidelines. The frequency with which the criteria appeared in each guideline was compared and an analysis was performed to determine guidelines with two key features of the ACHPR guidelines - multidisciplinary guideline development panels and systematic reviews of the literature. Data were extracted from the guidelines by one investigator and then checked for accuracy by the other. Results: Fifty two guidelines identified by broad based searches were evaluated. 50% of the criteria were present in every AHCPR guideline. The AHCPR guidelines scored 80% or more on 24 of the 30 criteria compared with 14 for the "updates" and 11 for those that referenced/adapted the AHCPR guidelines. All of the 17 AHCPR guidelines had both multidisciplinary development panels and systematic reviews of the literature compared with five from the other two categories (p < 0.05). Conclusions: North American guidelines developed subsequent to and in the same topic areas as the AHCPR guidelines are of substantially worse methodological quality and ignore key features important to guideline development. This finding contrasts with previously published conclusions that guideline methodological quality is improving over time. C1 RAND Hlth, So Calif Evidence Based Practice Ctr, Santa Monica, CA 90406 USA. Greater Los Angeles VA Med Ctr, Dept Gen Internal Med, Los Angeles, CA USA. RP Hasenfeld, R (reprint author), RAND Corp, 1700 Main St,POB 2138, Santa Monica, CA 90407 USA. FU PHS HHS [290-97-0001] NR 18 TC 30 Z9 31 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1475-3898 J9 QUAL SAF HEALTH CARE JI Qual. Saf. Health Care PD DEC PY 2003 VL 12 IS 6 BP 428 EP 434 DI 10.1136/qhc.12.6.428 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 754NY UT WOS:000187324300011 PM 14645758 ER PT J AU Ptak, T Rhea, JT Novelline, RA AF Ptak, T Rhea, JT Novelline, RA TI Radiation dose is reduced with a single-pass whole-body multi-detector row CT trauma protocol compared with a conventional segmented method: Initial experience SO RADIOLOGY LA English DT Article; Proceedings Paper CT 88th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY DEC 01-06, 2002 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE computed tomography (CT), image processing; computed tomography (CT), radiation exposure; radiations, exposure to patients and personnel; trauma AB Radiation dose data were collected from a calibrated multi-detector row computed tomographic (CT) scanner during trauma CT. One protocol (used with 10 case subjects) involved a single-pass continuous whole-body acquisition from cranial vertex to symphysis pubis, while the other, conventional protocol (used with 10 control subjects) involved scouting and scanning body segments (head, cervical spine, chest, abdomen, and pelvis) individually. Technical factors were kept constant within each body segment for the single-pass and the segmented protocols. Statistics included univariate analysis, two-tailed t testing to evaluate statistical significance of the summary statistic, and power and subject population contingency tables. The mean dose length product (DLP) with the single-pass protocol was 17% lower than the sum of the DLPs of each of the individual body segment scans (P < .001). Analysis of power and subject population by using a difference in mean of 500 mGy . cm and an ot of .05 revealed a (1 - beta) of higher than 0.90 for a sample of 10 patients. Thus, a whole-body single-pass trauma protocol, compared with a typical segmented acquisition protocol matched for imaging technique, resulted in reduced total radiation dose. The reduction in radiation dose is thought to represent a reduction in redundant imaging at overlap zones between body segments scanned in the segmental protocol but not in the continuous acquisition. - RSNA, 2003. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Emergency Radiol,Dept Radiol, Boston, MA 02114 USA. RP Ptak, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Emergency Radiol,Dept Radiol, 55 Fruit St,FND-210, Boston, MA 02114 USA. NR 4 TC 61 Z9 62 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD DEC PY 2003 VL 229 IS 3 BP 902 EP 905 DI 10.1148/radiol.2293021651 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745XZ UT WOS:000186717700039 PM 14657320 ER PT J AU Steppel, JH Horton, ES AF Steppel, JH Horton, ES TI Exercise in the management of type 1 diabetes mellitus SO REVIEWS IN ENDOCRINE & METABOLIC DISORDERS LA English DT Article DE physical exercise; type 1 diabetes mellitus ID CARDIOVASCULAR RISK-FACTORS; AUTONOMIC NEUROPATHY; PROLONGED EXERCISE; PHYSICAL-ACTIVITY; HEART-RATE; INSULIN; GLUCOSE; METABOLISM; IDDM; LIPOPROTEINS C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. RP Horton, ES (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 33 TC 21 Z9 22 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1389-9155 J9 REV ENDOCR METAB DIS JI Rev. Endocr. Metab. Disord. PD DEC PY 2003 VL 4 IS 4 BP 355 EP 360 DI 10.1023/A:1027302112655 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 756HX UT WOS:000187460600005 PM 14618020 ER EF