FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Damico, FM Xiong, J Gragoudas, ES Young, LHY AF Damico, FM Xiong, J Gragoudas, ES Young, LHY TI Destruction of pigmented choroidal melanoma using trans-scleral PDT SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4981 BP U687 EP U687 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002438 ER PT J AU de Boer, JF Cense, B Park, BH Pierce, MC Chen, TC AF de Boer, JF Cense, B Park, BH Pierce, MC Chen, TC TI In vivo depth resolved birefringence measurement of the human retinal nerve fiber layer by polarization sensitive OCT SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Wellman Labs, MGH, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3388 BP U239 EP U239 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000851 ER PT J AU DeAngelis, MM Shah, CP Lane, AM Gragoudas, ES Dryja, TP Miller, JW AF DeAngelis, MM Shah, CP Lane, AM Gragoudas, ES Dryja, TP Miller, JW TI Epidemiological study of extremely discordant sibpairs with neovascular age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 2 MA 3085 BP U110 EP U110 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000551 ER PT J AU Demers-Turco, P Stelmack, J Szlyk, JP Massof, RW Stelmack, TR Williams, T AF Demers-Turco, P Stelmack, J Szlyk, JP Massof, RW Stelmack, TR Williams, T TI Measuring visual ability with the VA LV VFQ-48 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Vis Rehab Ctr,Dept Ophthal, Boston, MA 02115 USA. Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60680 USA. Edward Hines Jr Vet Adm Hosp, Blind Rehab Ctr, Hines, IL USA. Illinois Coll Optometry, Chicago, IL USA. VA Chicago Hlth Care Syst W Div, Chicago, IL USA. Johns Hopkins Univ, Wilmer Eye Inst, Baltimore, MD 21218 USA. Deike Ctr Visual Rehab, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1283 BP U305 EP U305 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801234 ER PT J AU Dohlman, CH Nouri, M Barnes, S Ma, J Foster, C Durand, M AF Dohlman, CH Nouri, M Barnes, S Ma, J Foster, C Durand, M TI Prophylactic antibiotic regimens in keratoprosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1455 BP U343 EP U343 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801405 ER PT J AU Durrani, K Cunha, RNP Iaccheri, B Fiore, T Campos, M Dulley, FL Rojas, B Foster, CS AF Durrani, K Cunha, RNP Iaccheri, B Fiore, T Campos, M Dulley, FL Rojas, B Foster, CS TI Dry eyes in graft-versus-host disease: A clinical and immunohistochemical study of lacrimal gland and conjunctival tissue in patients undergoing bone marrow transplantation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI Dulley, Frederico/H-7063-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 1 MA 2481 BP U432 EP U432 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802409 ER PT J AU Ellis, DZ AF Ellis, DZ TI Hormone modulation of the membrane Na plus pump in mammalian trabecular meshwork SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Gen Hosp, Lab Membrane Bio Neurol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1155 BP U308 EP U308 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801105 ER PT J AU Evans, JE Green, KM Sullivan, RM Schaumberg, DA Dana, MR Sullivan, DA AF Evans, JE Green, KM Sullivan, RM Schaumberg, DA Dana, MR Sullivan, DA TI Proteomic analysis of human meibomian gland secretions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Brigham & Womens Hosp, Schepens Eye Res Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2478 BP U432 EP U432 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802405 ER PT J AU Fernandez-Suntay, JP Dryja, TP AF Fernandez-Suntay, JP Dryja, TP TI Immunohistochemical profiles of sebaceous, squamous and basal cell carcinoma using antibodies to epithelial membrane antigen (EMA) and anti-cytokeratin (CAM 5.2) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cogan Eye Pathol Lab, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2431 BP U422 EP U422 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802358 ER PT J AU Fiore, T Introini, U D'Amico, DJ Brancato, R AF Fiore, T Introini, U D'Amico, DJ Brancato, R TI Polypoidal choroidal vasculopathy: Clinical findings and angiographic, features SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Hosp San Raffaele, Dept Ophthalmol & Visual Sci, I-20132 Milan, Italy. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3160 BP U130 EP U130 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000627 ER PT J AU Friedman, E AF Friedman, E TI The role of blood pressure in the pathogenesis and management of diabetic retinopathy and age related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1704 BP U400 EP U400 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801656 ER PT J AU Fuhrmann, S Stark, MR Heller, S AF Fuhrmann, S Stark, MR Heller, S TI Expression of frizzled receptors during chick eye development SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Utah, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84112 USA. Brigham Young Univ, Dept Physiol & Dev Biol, Provo, UT 84602 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 646 BP U127 EP U127 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800621 ER PT J AU Fynn-Thompson, NA Henderson, BA Vavvas, D Hart, L Capaccioli, K AF Fynn-Thompson, NA Henderson, BA Vavvas, D Hart, L Capaccioli, K TI In vitro measurement of the anterior lens capsule without tissue dehydration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 248 BP U45 EP U45 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800222 ER PT J AU Gatinel, D Malet, J Azar, DT Hoang-Xuan, T AF Gatinel, D Malet, J Azar, DT Hoang-Xuan, T TI Effects of the pupil constriction on the wavefront Zernike terms SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Fdn Adolphe De Rothschild, Paris, France. Inst Stat Superieures, Paris, France. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 966 BP U265 EP U265 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800940 ER PT J AU Goddard, LE Clermont, AC Bursell, D Beaumont, P Strong, J Nuthi, A Wong, E Murtha, T Bursell, SE King, GL AF Goddard, LE Clermont, AC Bursell, D Beaumont, P Strong, J Nuthi, A Wong, E Murtha, T Bursell, SE King, GL TI The effect of topical administration of ET-1 inhibitor unoprostone isopropyl on retinal Hemodynamics in diabetic patients: Study design and baseline data SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Beetham Eye Inst, Joslin Diabet Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4020 BP U425 EP U425 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001481 ER PT J AU Goldstein, LE Moir, R Cherny, R Pineda, R Blakely, E Chang, P Bjornstad, K Tanzi, R Bush, A Chylack, LT AF Goldstein, LE Moir, R Cherny, R Pineda, R Blakely, E Chang, P Bjornstad, K Tanzi, R Bush, A Chylack, LT TI Expression and further characterization of Alzheimer's disease beta-amyloid (Abeta) in human aqueous humor and lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Brigham & Womens Hosp, Ctr Ophthalm Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Genet & Aging Res Unit, Boston, MA 02114 USA. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Lab Oxidat Biol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY PY 2003 VL 44 SU 2 MA 3488 BP U260 EP U260 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000950 ER PT J AU Grimsby, JL Sharon, D Stockton, DW Lewis, RA Berson, EL Dryja, TP AF Grimsby, JL Sharon, D Stockton, DW Lewis, RA Berson, EL Dryja, TP TI Mutation screening of the ESRRB gene in patients with Leber congenital amaurosis and autosomal recessive retinitis pigmentosa SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Grund Lab Study Retinal Degenerat, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2316 BP U399 EP U399 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802241 ER PT J AU Hauser, MA Abramson, KR Wiggs, JL del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL Allingham, RR AF Hauser, MA Abramson, KR Wiggs, JL del Bono, EA Graham, FL Pericak-Vance, MA Haines, JL Allingham, RR TI Primary open-angle glaucoma (POAG) candidate gene analysis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Duke Univ, Durham, NC 27706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1122 BP U301 EP U301 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801072 ER PT J AU Ho, C Walton, DS AF Ho, C Walton, DS TI Goniosurgery for glaucoma complicating chronic childhood uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Singapore Natl Eye Ctr, Singapore, Singapore. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1220 BP U319 EP U319 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801170 ER PT J AU Hong, JE Hatton, MP Fay, AM AF Hong, JE Hatton, MP Fay, AM TI Endocanalicular Nd : YAG laser dacryocystorhinostomy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2421 BP U421 EP U421 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802350 ER PT J AU Hunter, DD Zhang, M Koch, M Ferguson, JW Brunken, WJ AF Hunter, DD Zhang, M Koch, M Ferguson, JW Brunken, WJ TI WIF and Wnts modulate rod photoreceptor differentiation in vitro SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Tufts Univ, Sch Med, Medford, MA 02155 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, CBRC, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1650 BP U387 EP U387 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801601 ER PT J AU Iaccheri, B Fiore, T Papadaki, T Androudi, S Foster, C AF Iaccheri, B Fiore, T Papadaki, T Androudi, S Foster, C TI Adverse reactions with antitoxoplasma therapy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1415 BP U335 EP U335 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801365 ER PT J AU Ishida, S Usui, T Yamashiro, K Kaji, Y Ahmed, E Carrasquillo, KG Amano, S Hida, T Oguchi, Y Adamis, AP AF Ishida, S Usui, T Yamashiro, K Kaji, Y Ahmed, E Carrasquillo, KG Amano, S Hida, T Oguchi, Y Adamis, AP TI VEGF164 is pro-inflammatory in the diabetic retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Eyetech Res Ctr, Woburn, MA USA. Univ Tokyo, Tokyo, Japan. Kyorin Univ, Tokyo, Japan. Keio Univ, Tokyo, Japan. RI ISHIDA, SUSUMU/D-7067-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3895 BP U401 EP U401 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001357 ER PT J AU Jarade, EF Mian, SI Scally, A Azar, DT AF Jarade, EF Mian, SI Scally, A Azar, DT TI Combined ICRS and LASIK (IC-LASIK) for moderate to high myopia SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea & Refract Surg Dept, Boston, MA 02115 USA. Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02115 USA. Univ Michigan, Kellogg Eye Ctr, Cataract & Refract Surg Serv, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 967 BP U265 EP U265 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800943 ER PT J AU Javier, JD Davis, RP Oliveira, HB Jarade, EF Chang, JH Azar, DT AF Javier, JD Davis, RP Oliveira, HB Jarade, EF Chang, JH Azar, DT TI In vitro characterization of Mitomycin-C exposed bovine keratocytes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 916 BP U252 EP U252 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800891 ER PT J AU Jian-Seyed-Ahmadi, B Rivolta, C Keene, JA Berson, EL Dryja, TP AF Jian-Seyed-Ahmadi, B Rivolta, C Keene, JA Berson, EL Dryja, TP TI All-exon screen of the USH2A gene in recessive nonsyndromic retinitis pigmentosa and Usher syndrome type II SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2315 BP U399 EP U399 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802243 ER PT J AU Joussen, AM Poulaki, V Le, ML Koizumi, K Esser, C Janicki, H Fauser, S Kern, TS Kirchof, B Adamis, AP AF Joussen, AM Poulaki, V Le, ML Koizumi, K Esser, C Janicki, H Fauser, S Kern, TS Kirchof, B Adamis, AP TI Long-term leukocyte-mediated vascular pathology in the diabetic retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Eye Tech Pharmaceut, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3291 BP U221 EP U221 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000754 ER PT J AU Kaji, Y Amano, S Oshika, T Usui, T Yamashiro, K Ishida, S McMullen, T Moore, J Adamis, AP Horiuchi, S AF Kaji, Y Amano, S Oshika, T Usui, T Yamashiro, K Ishida, S McMullen, T Moore, J Adamis, AP Horiuchi, S TI Advanced glycation end products induce apoptosis in corneal endothelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Tsukuba, Inst Clin Sci, Dept Ophthalmol, Tsukuba, Ibaraki 305, Japan. Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol, Tsukuba, Ibaraki, Japan. Keio Univ, Sch Med, Dept Ophthalmol, Tsukuba, Ibaraki, Japan. Univ Ulster, Sch Biomed Sci, Tsukuba, Ireland. Queens Univ Belfast, Dept Ophthalmol, Belfast, Antrim, North Ireland. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Kumamoto Univ, Sch Med, Dept Biochem, Kumamoto 860, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 2 MA 4715 BP U631 EP U631 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002176 ER PT J AU Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES Miller, JW AF Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES Miller, JW TI Detection of Chlamydia pneumoniae in choroidal membranes isolated from patients with age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Retina Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 5023 BP U695 EP U695 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002482 ER PT J AU Kapadia, MK Koo, L Singh, RP Hatton, MP AF Kapadia, MK Koo, L Singh, RP Hatton, MP TI Seasonal variation in open globe injuries SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 819 BP U233 EP U233 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800795 ER PT J AU Khan, EA Sami, N Foster, C Ahmed, A AF Khan, EA Sami, N Foster, C Ahmed, A TI Intravenous immunoglobulin therapy in the treatment of refractory ocular cicatricial pemphigoid: A long-term follow-up SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2419 BP U420 EP U420 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802345 ER PT J AU Kim, EC Bernardino, CR Fay, AM Rubin, PAD AF Kim, EC Bernardino, CR Fay, AM Rubin, PAD TI Study of the expansile properties of a hydrogel implant within porcine scleral shells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 664 BP U203 EP U203 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800640 ER PT J AU Koh, S Gregory, MS Marshak-Rothstein, A Mukai, S Ksander, BR AF Koh, S Gregory, MS Marshak-Rothstein, A Mukai, S Ksander, BR TI A novel treatment for ocular tumors that terminates immune privilege and activates innate immunity SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 928 BP U255 EP U255 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800904 ER PT J AU Koo, L Kapadia, MK Singh, RP Hatton, MP AF Koo, L Kapadia, MK Singh, RP Hatton, MP TI Gender differences in open globe injuries SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 820 BP U234 EP U234 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800796 ER PT J AU Latina, MA Gulati, V AF Latina, MA Gulati, V TI The effect of corneal anatomical indices on measurements of intraocular pressure by applanation tonometry, pneumotonometer and TonoPen in patients with open-angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Reading Hlth Ctr, Reading, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4347 BP U507 EP U507 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001806 ER PT J AU Lawrence, MS AF Lawrence, MS TI Effects of bending, lifting and valsalva maneuver on intraocular pressure SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1297 BP U308 EP U308 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801247 ER PT J AU Le, LM Poulaki, V Koizumi, K Fauser, S Kirchhof, B Joussen, AM AF Le, LM Poulaki, V Koizumi, K Fauser, S Kirchhof, B Joussen, AM TI Reduced histopathological alterations in long-term diabetic TNF-R deficient mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Ctr Ophthalmol, Cologne, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3894 BP U401 EP U401 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001359 ER PT J AU Leahy, CD Ellis, EJ Ellis, JY Tchao, R AF Leahy, CD Ellis, EJ Ellis, JY Tchao, R TI Target validation of a treatment aimed at the common pathway of dry eye conditions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Contact Lens Serv, Boston, MA 02114 USA. Vista Sci LLC, Andover, MA USA. Univ Sci Philadelphia, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2480 BP U432 EP U432 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802406 ER PT J AU Letko, E Androudi, S Meniconi, M Papadaki, T Foster, CS AF Letko, E Androudi, S Meniconi, M Papadaki, T Foster, CS TI Safety and efficacy of intravitreal triamcinolone acetonide in patients with non-infectious uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2013 BP U331 EP U331 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801963 ER PT J AU Ling, CA Brockhurst, RJ Buzney, S Weiter, J AF Ling, CA Brockhurst, RJ Buzney, S Weiter, J TI Non-acquired unilateral deutan color deficiency in a child with normal ocular and retinal function SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Retina Specialists Boston, Cambridge, MA USA. Retina Specialists Boston, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 539 BP U107 EP U107 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800514 ER PT J AU Loewenstein, JI Montezuma, SR Waheed, N Rizzo, JF AF Loewenstein, JI Montezuma, SR Waheed, N Rizzo, JF TI Use of verteporfin photodynamic therapy to control choroidal bleeding for implantation of a retinal prosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol Retina, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 5065 BP U703 EP U703 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002524 ER PT J AU Lu, M Hansen, R Fulton, R AF Lu, M Hansen, R Fulton, R TI Effect of deferoxamine on the rod photoresponse SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1878 BP U433 EP U433 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801828 ER PT J AU MacNeil, MA Dacheux, RF Raviola, E Masland, RH AF MacNeil, MA Dacheux, RF Raviola, E Masland, RH TI The population of bipolar cells in a mammalian retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 CUNY York Coll, Jamaica, NY 11451 USA. Univ Alabama, Birmingham, AL USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 5161 BP U724 EP U724 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002622 ER PT J AU Martin, DF Bressler, NM Bressler, SB Chew, EY Clemons, TE Klein, R Seddon, JM AF Martin, DF Bressler, NM Bressler, SB Chew, EY Clemons, TE Klein, R Seddon, JM CA AREDS Res Grp TI Risk factors for the incidence of advanced age-related macular degeneration in the age-related eye disease study (AREDS) SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Emory Eye Ctr, Atlanta, GA USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. NEI, NIH, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3077 BP U109 EP U109 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000544 ER PT J AU Meniconi, ME Razzaque, MS Ahmed, RA Foster, CS AF Meniconi, ME Razzaque, MS Ahmed, RA Foster, CS TI Microarray study on conjunctiva from a patient with active ocular cicatricial pemphigoid SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med & Diagnost sci, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4612 BP U609 EP U609 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002070 ER PT J AU Montezuma, SR Rizzo, JF March, GA AF Montezuma, SR Rizzo, JF March, GA TI Meta-analysis of the dosage of corticosteroid therapy in giant cell arteritis: Attention to three clinically relevant questions SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 623 BP U123 EP U123 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800601 ER PT J AU Moulin, AP Della Pelle, P Dryja, TP Duncan, LM AF Moulin, AP Della Pelle, P Dryja, TP Duncan, LM TI Melastatin expression in ocular melanocytic proliferations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Dermatopathol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1539 BP U361 EP U361 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801491 ER PT J AU Nishiguchi, KM Berson, EL Dryja, TP AF Nishiguchi, KM Berson, EL Dryja, TP TI Mutation screening of the phosducin gene in patients with retinitis pigmentosa and other hereditary retinal diseases SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2323 BP U400 EP U400 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802250 ER PT J AU Nouri, M Dohlman, CH AF Nouri, M Dohlman, CH TI Sudden vitritis-presumed sterile-in patients with keratoprosthesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 1 MA 2396 BP U416 EP U416 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802323 ER PT J AU Oliveira, HB Javier, JD Jarade, EF Lee, JB Belsare, G Chang, JH Azar, DT AF Oliveira, HB Javier, JD Jarade, EF Lee, JB Belsare, G Chang, JH Azar, DT TI VEGF is involved in bFGF-induced murine corneal neovascularization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 1 MA 830 BP U236 EP U236 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800808 ER PT J AU Pantcheva, MB Hanninen, VA Poulin, NR Dobberfuhl, AP Grosskreutz, CL AF Pantcheva, MB Hanninen, VA Poulin, NR Dobberfuhl, AP Grosskreutz, CL TI Phosphorylation of Akt and activation of caspase 9 after optic nerve crush in rats SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3348 BP U232 EP U232 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000812 ER PT J AU Papadaki, TG Iaccheri, B Fiore, T Androudi, S Thadani, S Meniconi, M Christen, WG Foster, C AF Papadaki, TG Iaccheri, B Fiore, T Androudi, S Thadani, S Meniconi, M Christen, WG Foster, C TI Soluble interleukin 2 receptor (sIL-2R) levels in patients with ocular inflammation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med,Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 MAY PY 2003 VL 44 SU 2 MA 4603 BP U607 EP U607 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002062 ER PT J AU Papaliodis, GN Iaccheri, B Fiore, T Papadaki, T Androudi, S Foster, C AF Papaliodis, GN Iaccheri, B Fiore, T Papadaki, T Androudi, S Foster, C TI Cyclosporine and mycophenolate mofetil: The Massachusetts Eye and Ear Infirmary experience in the treatment of birdshot retinochoroidopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2009 BP U331 EP U331 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801961 ER PT J AU Pasquale, LK Kang, J Rosner, B Willett, W Hankinson, S AF Pasquale, LK Kang, J Rosner, B Willett, W Hankinson, S TI Age at menopause and primary open-angle glaucoma: A prospective study SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2003 VL 44 SU 1 MA 795 BP U229 EP U229 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800772 ER PT J AU Poulaki, V Joussen, A Iliaki, E Mitsiades, CS Fanourakis, G Mitsiades, N AF Poulaki, V Joussen, A Iliaki, E Mitsiades, CS Fanourakis, G Mitsiades, N TI The histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) induces growth arrest and apoptosis in human retinoblastoma cell lines SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Ctr Ophthalmol, Dept Vitreoretinal Surg, Cologne, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 931 BP U255 EP U255 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800908 ER PT J AU Ray, SK Carrasquillo, KG Rigas, I Calias, P Miller, JW Gragoudas, ES Adamis, AP AF Ray, SK Carrasquillo, KG Rigas, I Calias, P Miller, JW Gragoudas, ES Adamis, AP TI Encapsulation of anti-ICAM-1 antibodies into PLA-PEG microspheres: In vitro and in vivo characterization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Eyetech Res Ctr, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4450 BP U527 EP U527 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001908 ER PT J AU Razzaque, MS Khan, T Khan, EA Ahmed, B Foster, CS Ahmed, AR AF Razzaque, MS Khan, T Khan, EA Ahmed, B Foster, CS Ahmed, AR TI Connective tissue growth factor in ocular cicatricial pemphigoid: Possible role in conjunctival scarring SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol Immunol & Uveitis Serv, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3771 BP U319 EP U319 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001234 ER PT J AU Reichel, E Musch, DC Johnson, MW D'Amico, DJ Friberg, TR Landis, R Mainster, MA AF Reichel, E Musch, DC Johnson, MW D'Amico, DJ Friberg, TR Landis, R Mainster, MA TI Glaucoma as a possible factor for vision loss in the TTT4CNV clinical trial SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Tufts Univ, Sch Med, New England Eye Ctr, Boston, MA 02111 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Kansas, Kansas City, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 5043 BP U699 EP U699 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002504 ER PT J AU Rigas, IK Calias, P Karrasquillo, KG Gragoudas, ES Miller, JW Adamis, AP AF Rigas, IK Calias, P Karrasquillo, KG Gragoudas, ES Miller, JW Adamis, AP TI In vivo transscleral delivery of FITC-conjugated molecules to the rabbit choroid and retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Eyetech Res Ctr, Woburn, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4432 BP U524 EP U524 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001890 ER PT J AU Rivolta, C McGee, TL Stillberger, MA Berson, EL Dryja, TP AF Rivolta, C McGee, TL Stillberger, MA Berson, EL Dryja, TP TI RP11 transcripts with premature stop codons may escape nonsense-mediated decay; Possible role in explaining reduced penetrance SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2019 BP U333 EP U333 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801967 ER PT J AU Salti, HI Wong, E Nuthi, A Clermont, A Goddard, L Bursell, S Takahashi, J King, G Aiello, L AF Salti, HI Wong, E Nuthi, A Clermont, A Goddard, L Bursell, S Takahashi, J King, G Aiello, L TI Bacterial permeability increasing protein (rBPI21) inhibits VEGF and diabetes-induced retinal vascular leakage in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 2 MA 3909 BP U403 EP U403 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001370 ER PT J AU SanGiovanni, JP Chandra, SR Chew, EY Friberg, TR Klein, ML Kurinij, N Seddon, JM AF SanGiovanni, JP Chandra, SR Chew, EY Friberg, TR Klein, ML Kurinij, N Seddon, JM CA AREDS Res Grp TI Dietary omega-3 long-chain polyunsaturated fatty acids and risk for age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Devers Eye Inst, Portland, OR USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RI SanGiovanni, John Paul/A-7605-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2112 BP U353 EP U353 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802039 ER PT J AU Sato, M Kaji, Y Amano, S Oshika, T Usui, T Yamashiro, K Ishida, S Adamis, AP Nagai, R Horiuchi, S AF Sato, M Kaji, Y Amano, S Oshika, T Usui, T Yamashiro, K Ishida, S Adamis, AP Nagai, R Horiuchi, S TI Expression of advanced glycation end product (AGE) receptors in corneal endothelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Tsukuba, Dept Ophthalmol, Tsukuba, Ibaraki 305, Japan. Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol, Kyoto, Japan. Keio Univ, Sch Med, Dept Ophthalmol, Tokyo, Japan. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Kumamoto Univ, Sch Med, Dept Biochem, Kumamoto 860, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4716 BP U631 EP U631 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002174 ER PT J AU Schaumberg, DA Lyons, TJ Glynn, RJ Nathan, DM Manson, JE AF Schaumberg, DA Lyons, TJ Glynn, RJ Nathan, DM Manson, JE TI A prospective study of inflammatory biomarkers and diabetic retinopathy in type 1 diabetes mellitus SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2055 BP U341 EP U341 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801998 ER PT J AU Seddon, JM Book, K Chong, S Cote, J Santangelo, SL AF Seddon, JM Book, K Chong, S Cote, J Santangelo, SL TI A genome-wide scan for age-related macular degeneration SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Harvard Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Harvard Sch Publ Hlth,Psychiat & Neurodev Genet, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1781 BP U414 EP U414 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801729 ER PT J AU Sena, DRF Pasquale, L Allingham, R Santiago-Thurla, C Hauser, M DelBono, EA Pericak-Vance, M Haines, JL Wiggs, JL AF Sena, DRF Pasquale, L Allingham, R Santiago-Thurla, C Hauser, M DelBono, EA Pericak-Vance, M Haines, JL Wiggs, JL TI Distribution of p53 codon 72 polymorphism in primary open angle and low tension glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02115 USA. Duke Univ, Sch Med, Ctr Human Genet, Durham, NC 27706 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1119 BP U301 EP U301 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801068 ER PT J AU Sharon, D Sandberg, MA Rabe, VW Stilberger, M Dryja, TP Berson, EL AF Sharon, D Sandberg, MA Rabe, VW Stilberger, M Dryja, TP Berson, EL TI Mutation survey of the RP2 and RPGR genes (including ORF15) and evidence for genotype-phenotype correlations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Lab, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. RI Sharon, Dror/P-4539-2015 OI Sharon, Dror/0000-0002-1789-5811 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1481 BP U348 EP U348 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801431 ER PT J AU Shire, DB Gingerich, M Theogarajan, L Wyatt, J Loewenstein, J Montezuma, S Rizzo, J AF Shire, DB Gingerich, M Theogarajan, L Wyatt, J Loewenstein, J Montezuma, S Rizzo, J TI Packaging development for retinal prostheses SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Cornell Univ, Cornell Nanofabricat Facil, Ithaca, NY USA. Univ Michigan, Solid State Elect Lab, Ann Arbor, MI 48109 USA. MIT, Dept Elect Engn, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. VA Boston Healthcare Syst, Ctr Innovat Visual Rehabil, Jamaica Plain, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 2 MA 5084 BP U707 EP U707 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002543 ER PT J AU Singh, R Kapadia, MK Koo, L Hatton, M AF Singh, R Kapadia, MK Koo, L Hatton, M TI Characterization and causes of open globe injuries among different age groups presenting to a tertiary care facility SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Brookline, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2003 VL 44 SU 1 MA 784 BP U227 EP U227 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800758 ER PT J AU Sood, R Chen, TC AF Sood, R Chen, TC TI Evaluation of the diagnostic accuracy of scanning laser polarimetry in glaucomatous and ocular hypertensive eyes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 McMaster Univ, Fac Hlth Sci, Hamilton, ON, Canada. Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3416 BP U245 EP U245 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000881 ER PT J AU Suzuma, I Suzuma, K Takagi, H Aiello, LP Honda, Y AF Suzuma, I Suzuma, K Takagi, H Aiello, LP Honda, Y TI Cyclic stretch induced reactive oxygen species (ROS) enhances apoptosis in porcine retinal pericytes (PRPC) through JNK/SAPK activation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Vis Sci, Kyoto, Japan. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3888 BP U339 EP U339 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001349 ER PT J AU Takahashi, J Clermont, A Salti, H Bursell, D Horio, N Bursell, SE AF Takahashi, J Clermont, A Salti, H Bursell, D Horio, N Bursell, SE TI Angiotensin II modulates electroretinogram (ERG) amplitudes but not implicit times in vivo SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Nagoya Univ, Dept Ophthalmol, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1874 BP U433 EP U433 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801826 ER PT J AU Terada, Y Michaud, NA Connolly, EJ Lane, A Ohtsuki, H Gragoudas, ES Miller, JW AF Terada, Y Michaud, NA Connolly, EJ Lane, A Ohtsuki, H Gragoudas, ES Miller, JW TI Enhanced photodynamic therapy using angiostatin with verteporfin PDT in a laser-injury rat model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Angiogenesis & Laser Lab, Boston, MA 02114 USA. Okayama Univ, Sch Med, Okayama 700, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1749 BP U408 EP U408 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801699 ER PT J AU Thakker, MM D'Amico, DJ Ray, SK AF Thakker, MM D'Amico, DJ Ray, SK TI Ultrasonographic characteristics of eyes with endophthalmitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 1847 BP U427 EP U427 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606801797 ER PT J AU Tocyap, MD Azar, N Chen, T DelBono, EA Wiggs, JL AF Tocyap, MD Azar, N Chen, T DelBono, EA Wiggs, JL TI Molecular and clinical characterization of a patient with deletion of chromosome 12q21-22 and cornea plana SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3851 BP U333 EP U333 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001315 ER PT J AU Velez, G Weiter, JJ AF Velez, G Weiter, JJ TI Assessment and comparison of risk factors in subretinal hemorrhages associated with choroidal neovascularization and suprachoroidal hemorrhages SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4921 BP U674 EP U674 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607002381 ER PT J AU Wada, Y McGee, TL Stillberger, MA Sandberg, MA Berson, EL Dryja, TP AF Wada, Y McGee, TL Stillberger, MA Sandberg, MA Berson, EL Dryja, TP TI Mutation survey of the IMPDH1 gene in patients with autosomal dominant retinitis pigmentosa and review of the clinical findings associated with IMPDH1 mutations SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2306 BP U398 EP U398 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802233 ER PT J AU Walter, JW Allingham, RR Flor, JD Abramson, KR Graham, FL del Bono, EA Haines, JL Pericak-Vance, MA Hauser, MA Wiggs, JL AF Walter, JW Allingham, RR Flor, JD Abramson, KR Graham, FL del Bono, EA Haines, JL Pericak-Vance, MA Hauser, MA Wiggs, JL TI Optineurin sequence variants do not predispose to primary open angle glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Duke Univ, Med Ctr, Ctr Human Genet, Durham, NC USA. Vanderbilt Univ, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3227 BP U203 EP U203 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000695 ER PT J AU Walton, DS Ho, C AF Walton, DS Ho, C TI The clinical features of primary hereditary megalocornea SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 2200 BP U375 EP U375 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606802126 ER PT J AU Wang, Z Wen, XH Makino, C Lem, J AF Wang, Z Wen, XH Makino, C Lem, J TI Functional analysis of palmitoylation-defective rhodopsin in knock-in mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Tufts New England Med Ctr, Mol Cardiol Res Inst, Retina Res Lab, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4512 BP U541 EP U541 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001973 ER PT J AU Yamashiro, K Ishida, S Usui, T Kaji, Y Ogura, Y Adamis, AP AF Yamashiro, K Ishida, S Usui, T Kaji, Y Ogura, Y Adamis, AP TI VEGF dependent leukocyte infiltration and blood-retinal barrier breakdown in endotoxin-induced uveitis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Angiogenesis Retina Res Lab, Boston, MA 02114 USA. Nagoya City Univ, Sch Med, Nagoya, Aichi 467, Japan. Eyetech Res Ctr, Woburn, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 1 MA 719 BP U215 EP U215 PG 1 WC Ophthalmology SC Ophthalmology GA 709CH UT WOS:000184606800697 ER PT J AU Yates, PA O'Leary, DDM AF Yates, PA O'Leary, DDM TI Medial-lateral topography is established in the chick retinotectalprojection through topographic axon growth and topographically directed branch extension SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 4128 BP U447 EP U447 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001589 ER PT J AU Young, TA Pantcheva, MB Connolly, EJ Mandelcorn, MS Whiteside, CI Grosskreutz, CL Gragoudas, ES Miller, JW AF Young, TA Pantcheva, MB Connolly, EJ Mandelcorn, MS Whiteside, CI Grosskreutz, CL Gragoudas, ES Miller, JW TI Apoptosis in acute photodynamic therapy of choroidal neovascularization in the rat model SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Toronto, Vis Sci Res Program, Retina Serv, Toronto, ON, Canada. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Angiogenesis Lab,Retina Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Howe Lab, Boston, MA USA. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 SU 2 MA 3932 BP U409 EP U409 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607001394 ER PT J AU Zacks, DN Hanninen, V Pantcheva, M Grosskreutz, C Miller, JW AF Zacks, DN Hanninen, V Pantcheva, M Grosskreutz, C Miller, JW TI Caspase activation in an experimental model of retinal detachment SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04, 2003 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol C1 Univ Michigan, Kellogg Eye Ctr, Retina Serv, Ann Arbor, MI 48109 USA. Massachusetts Eye & Ear Infirm, Glaucoma Serv, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Retina Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 SU 2 MA 2951 BP U84 EP U84 PG 1 WC Ophthalmology SC Ophthalmology GA 709CK UT WOS:000184607000420 ER PT J AU Woody, TE Gallop, R Luborsky, L Blaine, J Frank, I Salloum, IM Gastfriend, B Crits-Christoph, P AF Woody, TE Gallop, R Luborsky, L Blaine, J Frank, I Salloum, IM Gastfriend, B Crits-Christoph, P CA Cocaine Psychotherapy Study Grp TI HIV risk reduction in the National Institute on Drug Abuse Cocaine Collaborative Treatment Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cocaine dependence; HIV risk ID ANTISOCIAL PERSONALITY-DISORDER; DEPENDENCE AB HIV risk was evaluated among 487 cocaine-dependent patients recruited from five treatment programs in a trial that examined the efficacy of four outpatient-based psychosocial treatments. Treatments were offered two to three times per week for 6 months and consisted of group drug counseling (GDC) or group counseling plus individual drug counseling (IDC), cognitive therapy (CT), or supportive-expressive therapy (SE). The average patient had used cocaine for 7 years, with 10 days of use in the last month. Crack smoking was the main route in 79%, and HIV risk was mainly due to multiple partners and unprotected sex. Treatment was associated with a decrease in cocaine use from an average of 10 days per month at baseline to 1 day per month at 6 months. Reduction in cocaine use was associated with an average 40% decrease in HIV risk across all treatment, gender, and ethnic groups, mainly as a result of fewer sexual partners and less unprotected sex. The combination of IDC and GDC was associated with an equal or even greater reduction in HIV risk than the other treatment conditions and thus shows promise as an effective HIV prevention strategy, at least for some patients. C1 Univ Penn, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. NIDA, Bethesda, MD 20892 USA. Brookside Hosp, Nashua, NH USA. Harvard Univ, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Woody, TE (reprint author), Treatment Res Inst, 600 Publ Ledger Bldg,150 S Independence Mall W, Philadelphia, PA 19106 USA. NR 19 TC 0 Z9 0 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAY 1 PY 2003 VL 33 IS 1 BP 82 EP 87 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 677KD UT WOS:000182805400012 ER PT J AU Berry, RB White, DP Roper, J Pillar, G Fogel, RB Stanchina, M Malhotra, A AF Berry, RB White, DP Roper, J Pillar, G Fogel, RB Stanchina, M Malhotra, A TI Awake negative pressure reflex response of the genioglossus in OSA patients and normal subjects SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE upper airway; sleep apnea syndrome; obstructive sleep apnea ID OBSTRUCTIVE SLEEP-APNEA; UPPER AIRWAY ANESTHESIA; EYE-MOVEMENT SLEEP; MUSCLE ACTIVATION; PATHOGENESIS; MECHANISMS; STIMULI; HUMANS AB We hypothesized that the response of the genioglossus to negative pressure during wakefulness should be intact in obstructive sleep apnea (OSA) patients despite published evidence showing impairment of the response of palatal muscles (Mortimore IL and Douglas NJ. Am J Respir Crit Care Med 156: 867-873, 1997). Thus the response of the genioglossus to brief nasal negative pressure applications (NPAs) in early inspiration was compared between OSA patients and an age-matched group of normal subjects at two study sites (n = 11 per group in Long Beach, n = 14 per group in Boston). Subjects were studied in the sitting ( Long Beach) or supine ( Boston) posture, and the genioglossus electromyogram (EMGgg) was measured with an intraoral surface electrode ( Long Beach) or intramuscular electrode ( Boston). The response of the EMGgg was expressed as the percent change from baseline where the baseline EMGgg was the value at the onset of the NPA. In Long Beach, the EMGgg response was significantly higher in the OSA patients at a lower suction pressure of similar to10 cmH(2)O (75.2 +/- 8.4 vs. 37.4 +/- 4.0% increase; P < 0.001) but not at a higher suction pressure of &SIM;20 cmH(2)O. In Boston, the response in the OSA patients was also greater (107.2 &PLUSMN; 25.9 vs. 46.3 &PLUSMN; 8.3%; P < 0.05) at a suction pressure of similar to13 cmH(2)O. We conclude that the response of the genioglossus to NPA during wakefulness is not impaired in OSA patients compared with normal subjects and is greater at low suction pressures. C1 Univ Calif Irvine, Long Beach Vet Affairs Med Ctr, Med Hlth Care Grp, Irvine, CA 90822 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care, Boston, MA 02115 USA. RP Berry, RB (reprint author), Univ Florida, Hlth Sci Ctr, Box 100225, Gainesville, FL 32610 USA. FU NCRR NIH HHS [MO1 RR-02635]; NHLBI NIH HHS [1 P50 HL-60292, HL-48531, T32 HL-07633] NR 28 TC 35 Z9 36 U1 0 U2 0 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 MAY PY 2003 VL 94 IS 5 BP 1875 EP 1882 DI 10.1152/japplphysiol.00324.2002 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 663BB UT WOS:000181984200025 PM 12533492 ER PT J AU Truong-Bolduc, QC Zhang, XM Hooper, DC AF Truong-Bolduc, QC Zhang, XM Hooper, DC TI Characterization of NorR protein, a multifunctional regulator of norA expression in Staphylococcus aureus SO JOURNAL OF BACTERIOLOGY LA English DT Article ID MULTIDRUG EFFLUX TRANSPORTER; MULTIPLE-ANTIBIOTIC-RESISTANCE; VIRULENCE-DETERMINANT EXPRESSION; ESCHERICHIA-COLI; QUINOLONE RESISTANCE; TOPOISOMERASE-IV; DNA GYRASE; FLUOROQUINOLONE RESISTANCE; TRANSCRIPTIONAL REGULATION; GENE REGULATOR AB We characterized a Staphylococcus aureus norA gene expression regulator, NorR, initially identified from its binding to the norA promoter. The norR gene was 444 bp in length, located similar to7 kb upstream from the norA gene, and encoded a predicted 17.6-kDa protein. Overexpression of norR in wild-type S. aureus strain ISP794 led to a fourfold decrease in sensitivity to quinolones and ethidium bromide and an increase in the level of norA transcripts, suggesting that NorR acts as a positive regulator of norA expression. Overexpression of norR in sarA and agr mutants did not alter quinolone sensitivity or levels of norA transcription, indicating that the presence of these two global regulatory systems is necessary for NorR to affect the expression of norA. Insertion and disruption of norR in ISP794 increased resistance to quinolones by 4- to 16-fold but had no effect on norA transcription, suggesting that NorR acts as a repressor for another unidentified efflux pump or pumps. These mutants also exhibited an exaggerated clumping phenotype in liquid media, which was complemented fully by a plasmid-encoded norR gene. Collectively, these results indicate that NorR is a multifunctional regulator, affecting cell surface properties as well as the expression of NorA and likely other multidrug resistance efflux pumps. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis & Med Serv, Boston, MA 02114 USA. RP Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [R01 AI023988, R01 AI23988] NR 55 TC 70 Z9 77 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 2003 VL 185 IS 10 BP 3127 EP 3138 DI 10.1128/JB.185.10.3127-3138.2003 PG 12 WC Microbiology SC Microbiology GA 675HA UT WOS:000182686900019 PM 12730173 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Operative release of complete ankylosis of the elbow due to heterotopic bone in patients without severe injury of the central nervous system SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID OSSIFICATION; EXCISION AB Background: Although uncommon, complete ankylosis of the elbow secondary to heterotopic ossification results in severe disability. The results of surgical management remain unclear. Methods: A single surgeon used a consistent operative technique to treat complete osseous ankylosis of the elbow in eleven limbs in seven patients after severe burns and in nine elbows in eight patients after trauma. The elbows in the burn cohort were more often ankylosed in extension (average, 47degrees of flexion) compared with those in the trauma cohort (66degrees of flexion), and they had more skin problems (three elbows required a free microvascular muscle transfer for coverage) and associated problems of the shoulder, wrist, and hand. Results: Four patients in the burn cohort and three patients in the trauma cohort failed to regain at least 80degrees of ulnohumeral motion. After a repeat release in three burn patients and three trauma patients, and at an average follow-up of forty months, the average arc of ulnohumeral motion was 81degrees in the burn cohort and 94degrees in the trauma cohort. Six of the eleven limbs in the burn cohort and five of the nine in the trauma cohort had a good result. The average score according to the American Shoulder and Elbow Surgeons elbow assessment form was 72 points for the burn cohort and 76 points for the trauma cohort. Conclusions: Osseous ankylosis of the elbow is a severely disabling problem, and attempts to regain mobility are both worthwhile and safe. The results are comparable when the ankylosis is caused by burns or trauma despite the greater complexity of osseous ankylosis in the burned arm. Patients and surgeons should be aware of the small risk of recurrent heterotopic ossification and the moderate risk of pain or recurrent contracture after operative release. Level of Evidence: Therapeutic study, Level I (case series [no, or historical, control group]). See Instructions to Authors for a complete description of levels of evidence. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, 11 Hancock St,Unit 4, Boston, MA 02114 USA. NR 22 TC 31 Z9 32 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAY PY 2003 VL 85A IS 5 BP 849 EP 857 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 675TP UT WOS:000182712100012 PM 12728035 ER PT J AU Wrobleski, D Houghtaling, C Josephson, ME Ruskin, JN Reddy, VY AF Wrobleski, D Houghtaling, C Josephson, ME Ruskin, JN Reddy, VY TI Use of electrogram characteristics during sinus rhythm to delineate the endocardial scar in a porcine model of healed myocardial infarction SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE substrate mapping; ventricular tachycardia; electroanatomic mapping; catheter ablation; arrhythmia ID RADIOFREQUENCY CATHETER ABLATION; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; VENTRICULAR-TACHYCARDIA; CARDIOMYOPATHY; REENTRY AB Substrate Mapping in a Porcine Model of Chronic MI. Introduction: Substrate-based catheter ablation of postmyocardial infarction (post-MI) ventricular tachycardia necessitates electroanatomic definition of the scarred endocardium. We sought to determine whether electrogram criteria during sinus rhythm could identify the location and extent of the myocardial scar by electroanatomic mapping. Methods and Results: A porcine model of healed MI was generated by injecting agarose microspheres into the mid left anterior descending coronary artery. At least 4 weeks post-MI, the animals (n = 24) underwent detailed left ventricular endocardial electroanatomic mapping using a 4-mm-tip catheter (BioSense-Webster, Inc.). Based upon mapping data in normal animals, infarcted tissue was defined as bipolar electrogram amplitude < 1.5 mV and electrogram duration greater than or equal to 50 msec. Radiofrequency ablation lesions (2-10 per animal) were placed to tag the endocardial borders of the electroanatomic mapping-defined scar. The area of the scar defined by abnormal voltage amplitude was 25.9 +/- 15.4 cm(2) (range 6.9-60.5). This area correlated well with that defined as scar by the electrogram duration criteria (26.4 +/- 16 cm(2)). Of those points remote from the infarct with falsely low voltage amplitude resulting from presumed poor catheter-tissue contact, 94% were correctly identified as normal when using the electrogram duration criteria. Late potentials were observed predominantly along the borders of the infarcted myocardium. The radiofrequency lesions placed to tag the scar borders were located along the scar periphery during gross pathologic examination. Conclusion: During normal sinus rhythm, both bipolar electrogram voltage amplitude and electrogram duration criteria are able to help differentiate normal from scarred myocardial tissue. Using these criteria, a detailed reconstruction of the endocardial scar can be rendered by electroanatomic mapping of the heart. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Cardiac Arrhythmia Serv, Boston, MA USA. RP Reddy, VY (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. FU NHLBI NIH HHS [K23 HL68064-01A1] NR 18 TC 39 Z9 41 U1 0 U2 0 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 MAY PY 2003 VL 14 IS 5 BP 524 EP 529 DI 10.1046/j.1540-8167.2003.02499.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 681WG UT WOS:000183058100016 PM 12776871 ER PT J AU Primack, JD Azar, DT AF Primack, JD Azar, DT TI Laser in situ keratomileusis and intrastromal corneal ring segments for high myopia - Three-step procedure SO JOURNAL OF CATARACT AND REFRACTIVE SURGERY LA English DT Article ID IATROGENIC KERATECTASIA; INTRACORNEAL RINGS; KERATOCONUS; DIOPTERS AB We describe a surgical procedure to correct relatively high myopia in patients with thin corneas. The technique combines laser in situ keratomileusis (LASIK) and intrastromal corneal ring segment (ICRS) implantation. The 3-step procedure comprises ICRS channel formation, LASIK, and segment insertion. The technique was used in 2 eyes of 2 patients with low pachymetry values and high myopia. One patient achieved an uncorrected visual acuity (UCVA) of 20/30 and a best spectacle-corrected visual acuity (BSCVA) of 20/25 with +0.50 -1.75 X 101. The other patient achieved a UCVA of 20/30 and a BSCVA of 20/20 with +0.75 -1.50 X 80. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Cornea & Refract Surg Serv, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Dept Ophthalmol, Cornea & Refract Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 2 Z9 2 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 MAY PY 2003 VL 29 IS 5 BP 869 EP 874 DI 10.1016/S0886-3350(02)01697-8 PG 6 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 681HN UT WOS:000183030900010 PM 12781268 ER PT J AU Pfander, D Cramer, T Schipan, E Johnson, RS AF Pfander, D Cramer, T Schipan, E Johnson, RS TI HIF-1 alpha controls extracellular matrix synthesis by epiphyseal chondrocytes SO JOURNAL OF CELL SCIENCE LA English DT Article DE chondrocytes; hypoxia; HIF-1 alpha; extracellular matrix ID ENDOTHELIAL GROWTH-FACTOR; ENDOCHONDRAL BONE-FORMATION; INDUCIBLE FACTOR 1-ALPHA; ARTICULAR-CARTILAGE; HYPERTROPHIC CHONDROCYTES; MONOLAYER-CULTURE; PLATE CARTILAGE; OXYGEN-TENSION; FACTOR VEGF; X COLLAGEN AB The transcription factor HIF-1alpha plays a crucial role in modifying gene expression during low oxygen tension. In a previous study, we demonstrated that HIF-1alpha is essential for chondrocyte growth arrest and survival in vivo. To explore further the role of HIF-1alpha in cartilage biology, we undertook studies with primary epiphyseal chondrocytes with a targeted deletion of HIF-1alpha. In this study, we show that HIF-1alpha is necessary for regulating glycolysis under aerobic and anaerobic conditions. HIF-1alpha-null chondrocytes were unable to maintain ATP levels in hypoxic microenvironments, indicating a fundamental requirement for this factor for the regulation of chondrocyte metabolism. Synthesis of the angiogenic factor vascular endothelial growth factor was also significantly induced by hypoxia, and this increase is lost in HIF-1alpha-null mutant cells. Under hypoxic conditions, aggrecan mRNA and protein levels were significantly reduced in chondrocytes lacking the HIF-1alpha transcription factor. Interestingly, strongly increased type-II collagen protein levels were detected in wild-type cells after 44 hours of hypoxia. In addition, type-H collagen mRNA and protein levels were strongly decreased under low oxygen in chondrocytes lacking HIF-1alpha. In summary, our results clearly demonstrate the importance of RIF-1alpha in maintenance of anaerobic glycolysis, and thereby extracellular matrix synthesis, of epiphyseal chondrocytes. C1 Univ Erlangen Nurnberg, Dept Orthoped Surg, Div Orthoped Rheumatol, D-91054 Erlangen, Germany. Univ Calif San Diego, Div Biol, Mol Biol Sect, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Johnson, RS (reprint author), Univ Erlangen Nurnberg, Dept Orthoped Surg, Div Orthoped Rheumatol, D-91054 Erlangen, Germany. RI Cramer, Thorsten/S-2479-2016 OI Cramer, Thorsten/0000-0002-6462-239X FU NCI NIH HHS [CA 082515] NR 31 TC 150 Z9 159 U1 0 U2 12 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD MAY 1 PY 2003 VL 116 IS 9 BP 1819 EP 1826 DI 10.1242/jcs.00385 PG 8 WC Cell Biology SC Cell Biology GA 679CN UT WOS:000182903600018 PM 12665562 ER PT J AU Moriarty, PJ Harvey, PD Mitropoulou, V Granholm, E Silverman, JM Siever, LJ AF Moriarty, PJ Harvey, PD Mitropoulou, V Granholm, E Silverman, JM Siever, LJ TI Reduced processing resource availability in schizotypal personality disorder: Evidence from a dual-task CPT study SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID VISUOSPATIAL WORKING-MEMORY; SCHIZOPHRENIC-PATIENTS; NONPSYCHOTIC RELATIVES; PERFORMANCE; RESPONSES; MARKER AB Performance on a dual-task information processing task was investigated in 23 schizotypal personality disorder patients (SPD), 29 patients with other noncluster A personality disorders (ORD) and 8 nonpsychiatric healthy controls (NC). All participants were assessed using a computer-based visual continuous performance test (CPT) and an auditory CPT individually, and administered again simultaneously in a dual-task condition. The SPD group showed a greater increase in the number of errors of omission than the OPD group or normal controls on the CPT tasks in the dual-task conditions. Performance operating characteristics indicated that the SPD patients did not allocate their attention in a manner different from the healthy controls, suggesting that poorer performance was due to resource limitations in the dual task condition and not strategic failures. These results are similar to previous studies of patients with schizophrenia, where performance deficits on information processing tests have been shown to be related to resource limitations more than failures in effective allocation of attention. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Hofstra Univ, Dept Psychol, Hempstead, NY 11550 USA. Bronx Vet Adm Med Ctr, Dept Psychiat, Bronx, NY USA. VA San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Harvey, PD (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1229, New York, NY 10029 USA. RI Granholm, Eric/P-7680-2014 FU NIMH NIH HHS [MH56140] NR 32 TC 17 Z9 17 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD MAY PY 2003 VL 25 IS 3 BP 335 EP 347 PG 13 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 683GX UT WOS:000183141200004 PM 12916647 ER PT J AU Chandrasekhar, S Peterfreund, RA AF Chandrasekhar, S Peterfreund, RA TI Horner's syndrome following very low concentration bupivacaine infusion for labor epidural analgesia SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Article DE Horner's syndrome; labor epidural analgesia; local anesthetics ID ANESTHESIA AB Homer's syndrome is a complication of epidural analgesia and anesthesia, encountered more commonly in pregnant women than in other patients. Previous reports described the appearance of Horner's syndrome following epidural injection of concentrated local anesthetic solutions. We report unilateral Homer's syndrome occurring in the setting of lumbar epidural analgesia for labor with a very low local anesthetic concentration (bupivacaine 0.04%) in an epidural infusion. We discuss the possible factors that could have contributed to this occurrence despite the extremely dilute concentration of local anesthetic used for analgesia. (C) 2003 by Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Chandrasekhar, S (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Clin 314D,55 Fruit St, Boston, MA 02114 USA. NR 12 TC 12 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD MAY PY 2003 VL 15 IS 3 BP 217 EP 219 DI 10.1016/S0952-8180(03)00017-5 PG 3 WC Anesthesiology SC Anesthesiology GA 687DH UT WOS:000183360400012 PM 12770660 ER PT J AU Yoon, KH Ko, SH Cho, JH Lee, JM Ahn, YB Song, KH Yoo, SJ Kang, MI Cha, BY Lee, KW Son, HY Kang, SK Kim, HS Lee, IK Bonner-Weir, S AF Yoon, KH Ko, SH Cho, JH Lee, JM Ahn, YB Song, KH Yoo, SJ Kang, MI Cha, BY Lee, KW Son, HY Kang, SK Kim, HS Lee, IK Bonner-Weir, S TI Selective beta-cell loss and beta-cell expansion in patients with type 2 diabetes mellitus in Korea SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE; ADULT-RATS; IN-VIVO; PANCREAS; ISLET; MASS; GROWTH; NEOGENESIS; LANGERHANS; APOPTOSIS AB In the presence of obesity, beta-cell mass needs to be increased to compensate for the accompanying demands and maintain euglycemia. However, in Korea, the majority of type 2 diabetic patients are nonobese. We determined the absolute masses, relative volumes, and ratio of alpha- and beta-cell in the pancreas and islets in normal and diabetic Korean subjects to correlate these findings with the clinical characteristics. Whole pancreases procured from organ donors were divided into 24 parts (control 1, n = 9). Tissue was also obtained by surgical resection after 35 partial pancreatectomies: in 25 diabetic patients, 10 age- and body mass index (BMI)-matched patients of benign or malignant pancreatic tumor without diabetes mellitus (DM) (control 2). Morphometric quantifications were performed. In control 1, the relative volume of beta-cells was 2.1 +/- 0.9%, and the total beta-cell mass was 1.3 +/- 0.3 g. The relative volume of beta-cells was found to be variable (control 1, 2.1 +/- 0.9%; control 2, 1.9 +/- 0.7%; DM, 1.4 +/- 1.0%; P < 0.05 DM vs. control 1 and 2) and showed good correlation with BMI (control 1, r(2) = 0.64; DM, r(2) = 0.55; all subjects, r(2) = 0.38; P < 0.05). Notably, in type 2 diabetic patients, the ratio of alpha-cell area to beta-cell area in the islet was higher than in control 1 and 2 (0.81 +/- 0.4 vs. 0.29 +/- 0.2, 0.20 +/- 0.1, P < 0.05). Additionally, significant beta-cell expansion and a decreased beta-cell fraction were predominantly observed in larger islets (islet area, > 6415 mum(2); P < 0.05) in control 1 and diabetic patients. The relative volume of beta-cell was found to be correlated with BMI in diabetic patients and normal organ donors. Moreover, decreased beta-cell but increased beta-cell proportion in the islets suggests for a selective beta-cell loss in the pathogenesis of Korean type 2 diabetes. C1 Catholic Univ Korea, Inst Med Sci, Dept Endocrinol & Metab, Immunol & Cell Biol Core Lab, Seoul 137701, South Korea. Catholic Univ Korea, Coll Nursing, Seoul 137701, South Korea. Keimyung Univ, Dongsan Med Ctr, Taegu 700712, South Korea. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Yoon, KH (reprint author), Catholic Univ Korea, Dept Internal Med, Div Endocrinol & Metab, Kangnam St Marys Hosp,Seocho Ku, 505 Banpo Dong, Seoul 137701, South Korea. EM yoonk@catholic.ac.kr NR 43 TC 314 Z9 337 U1 0 U2 4 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 MAY 1 PY 2003 VL 88 IS 5 BP 2300 EP 2308 DI 10.1210/jc.2002-020735 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 673TD UT WOS:000182595500057 PM 12727989 ER PT J AU Corbie-Smith, G St George, DMM Moody-Ayers, S Ransohoff, DF AF Corbie-Smith, G St George, DMM Moody-Ayers, S Ransohoff, DF TI Adequacy of reporting race/ethnicity in clinical trials in areas of health disparities SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE clinical research; inclusion of minorities; randomized clinical trials; health disparities ID RANDOMIZED CONTROLLED TRIALS; CANCER-TREATMENT TRIALS; WOMEN; REPRESENTATION; PARTICIPATION; MINORITIES; INCLUSION; INSTITUTE; RACE AB Although federal initiatives have mandated broader inclusion of minorities in clinical research on diseases that have disparities in health by race and ethnicity, it is not clear whether these initiatives have affected reporting of trial results. The objective of,this-study was to examine the reporting of race/ethnicity in clinical trials reports in areas of known disparities in health (i.e., diabetes, cardiovascular disease, HIV/AIDS, and cancer) and to determine what factors were associated with reporting of race/ethnicity in,results. We,performed a Medline search covering the period January 1989 to Oct 2000 to identify clinical trials of diabetes, cardiovascular disease, HIV/AIDS, and cancer published in the Annals of Internal Medicine, JAMA, and New England Journal of Medicine. The main outcome measure, was the reporting of participation and of results by race/ethnicity of trial participants. Of 253 : eligible trials, 40% (n = 102) were non race-focused yet did not report. race, while 2% (n = 4) were non gender-focused and did not report gender. Forty-six percent of trials' that reported the race/ethnicity of the sample reported only one or two racial/ethnic categories, and in 43% of these trials the total number of individuals reported in each race/ethnicity category, did not equal the total reported sample size. Analysis of results by race/ethnicity was reported in only two trials, and by gender in only three trials. In diseases With known racial and,ethnic disparities, many clinical trials do not report the race/ethnicity of the study participants, and almost none report analyses by race/ethnicity. Although federal initiatives mandate inclusion of minority groups in research, that inclusion has not translated to reporting of results that might. guide therapeutic decisions. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ N Carolina, Dept Social Med, Chapel Hill, NC 27599 USA. Walden Univ, Sch Hlth & Human Sci, Minneapolis, MN 55401 USA. San Francisco Vet Affairs Med Ctr, Dept Med, Div Geriatr, San Francisco, CA 94121 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27599 USA. RP Corbie-Smith, G (reprint author), Univ N Carolina, Dept Social Med, CB 7240, Chapel Hill, NC 27599 USA. FU NHLBI NIH HHS [HL04039] NR 24 TC 52 Z9 52 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD MAY PY 2003 VL 56 IS 5 BP 416 EP 420 DI 10.1016/S0895-4356(03)00031-3 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 691DH UT WOS:000183589200003 PM 12812814 ER PT J AU Lauwers, GY AF Lauwers, Gregory Y. TI Defining the Pathologic Diagnosis of Metaplasia, Atrophy, Dysplasia, and Gastric Adenocarcinoma SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE Stomach; Gastric cancer; Adenocarcinoma; Gastritis; Helicobacter pylori; Atrophy; Metaplasia; Dysplasia AB Epidemiologic and pathologic studies have confirmed that the development of gastric cancer spans over several decades starting with Helicobacter pylori chronic active gastritis followed, over time and only in a subset of patients, with the development of intestinal metaplasia and atrophy, dysplasia, and finally gastric adenocarcinoma. It has also been established that the pathogenesis of gastric cancer is a multifactorial process in which both environmental and host-related factors play significant role. Improvement in upper endoscopic techniques make possible the detection of not only early gastric cancers but also the mucosal alterations that predate malignant degeneration. A better understanding of the gastric carcinogenic sequence will allow us to better identify the patients at risk and to implement preventive strategies. We review the histopathologic steps that predate the development of gastric cancer and evaluate the risks of transformation that they confer. C1 [Lauwers, Gregory Y.] Massachusetts Gen Hosp, Dept Pathol, WRN 2, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. [Lauwers, Gregory Y.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 2, Gastrointestinal Pathol Serv, 55 Fruit St, Boston, MA 02114 USA. EM glauwers@partners.org NR 90 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY PY 2003 VL 36 BP S37 EP S43 DI 10.1097/00004836-200305001-00007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V16QJ UT WOS:000207883800007 PM 12702964 ER PT J AU Lauwers, GY AF Lauwers, GY TI Defining the pathologic diagnosis of metaplasia, atrophy, dysplasia, and gastric adenocarcinoma SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE stomach; gastric cancer; adenocarcinoma; gastritis; Helicobacter pylori; atrophy; metaplasia; dysplasia ID HELICOBACTER-PYLORI ERADICATION; HISTOLOGICAL FOLLOW-UP; LYMPH-NODE METASTASIS; INTESTINAL METAPLASIA; EPITHELIAL-DYSPLASIA; ADENOMATOUS POLYPOSIS; ENDOSCOPIC TREATMENT; NATURAL-HISTORY; CANCER; CARCINOMA AB Epidemiologic and pathologic studies have confirmed that the development of gastric cancer spans over several decades starting with Helicobacter pylori chronic active gastritis followed, over time and only in a subset of patients, with the development of intestinal metaplasia and atrophy, dysplasia, and finally gastric adenocarcinoma. It has also been established that the pathogenesis of gastric cancer is a multifactorial process in which both environmental and host-related factors play significant role. Improvement in upper endoscopic techniques make possible the detection of not only early gastric cancers but also the mucosal alterations that predate malignant degeneration. A better understanding of the gastric carcinogenic sequence will allow us to better identify the patients at risk and to implement preventive strategies. We review the histopathologic steps that predate the development of gastric cancer and evaluate the risks of transformation that they confer. C1 Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, WRN 2,55 Fruit St, Boston, MA 02114 USA. NR 90 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD MAY-JUN PY 2003 VL 36 IS 5 SU S BP S37 EP S43 DI 10.1097/00004836-200305001-00007 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 670XQ UT WOS:000182435700007 PM 12702964 ER PT J AU Vicent, D Ilany, J Kondo, T Naruse, K Fisher, SJ Kisanuki, YY Bursell, S Yanagisawa, M King, GL Kahn, CR AF Vicent, D Ilany, J Kondo, T Naruse, K Fisher, SJ Kisanuki, YY Bursell, S Yanagisawa, M King, GL Kahn, CR TI The role of endothelial insulin signaling in the regulation of vascular tone and insulin resistance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; ABNORMAL RETINAL HEMODYNAMICS; IN-VIVO; DIABETIC RATS; GLUCOSE-INTOLERANCE; GENE-EXPRESSION; ANGIOTENSIN-II; CELLS; TRANSPORT; RECEPTOR AB insulin receptors (IRs) on vascular endothelial cells have been suggested to participate in insulin-regulated glucose homeostasis. To directly address the role of insulin action in endothelial function, we have generated a vascular endothelial cell IR knockout (VENIRKO) mouse using the Cre-loxP system. Cultured endothelium of VENIRKO mice exhibited complete rearrangement of the IR gene and a more than 95% decrease in IR mRNA. VENIRKO mice were born at the expected Mendelian ratio, grew normally, were fertile, and exhibited normal patterns of vasculature in the retina and other tissues. Glucose homeostasis under basal condition was comparable in VENIRKO mice. Both eNOS and endothelin-1 mRNA levels, however, were reduced by approximately 30-60% in endothelial cells, aorta, and heart, while vascular EGF expression was maintained at normal levels. Arterial pressure tended to be lower in VENIRKO mice on both low- and high-salt diets, and on a low-salt diet VENIRKO mice showed insulin resistance. Thus, inactivation of the IR on endothelial cell has no major consequences on vascular development or glucose homeostasis under basal conditions, but alters expression of vasoactive mediators and may play a role in maintaining vascular tone and regulation of insulin sensitivity to dietary salt intake. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Kisanuki, Yasushi/E-3393-2011; Vicent, David/O-2255-2014 OI Vicent, David/0000-0002-6663-0350 FU NIDDK NIH HHS [DK-31036, DK-33201, R01 DK031036, R01 DK033201, R37 DK031036] NR 49 TC 189 Z9 203 U1 1 U2 10 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 MAY PY 2003 VL 111 IS 9 BP 1373 EP 1380 DI 10.1172/JCI200315211 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673XD UT WOS:000182605400016 PM 12727929 ER PT J AU Burcelin, R Crivelli, V Perrin, C Da Costa, A Mu, J Kahn, BB Birnbaum, MJ Kahn, CR Vollenweider, P Thorens, B AF Burcelin, R Crivelli, V Perrin, C Da Costa, A Mu, J Kahn, BB Birnbaum, MJ Kahn, CR Vollenweider, P Thorens, B TI GLUT4, AMP kinase, but not the insulin receptor, are required for hepatoportal glucose sensor-stimulated muscle glucose utilization SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; VENTROMEDIAL HYPOTHALAMUS; SYMPATHETIC RESPONSE; LIVER GLUCOSENSORS; SENSITIVE TISSUES; GLUT2-NULL MICE; NERVOUS-SYSTEM; TRANSPORT; LEPTIN AB Recent evidence suggests the existence of a hepatoportal vein glucose sensor, whose activation leads to enhanced glucose use in skeletal muscle, heart, and brown adipose tissue. The mechanism leading to this increase in whole body glucose clearance is not known, but previous data suggest that it is insulin independent. Here, we sought to further determine the portal sensor signaling pathway by selectively evaluating its dependence on muscle GLUT4, insulin receptor, and the evolutionarily conserved sensor of metabolic stress, AMP-activated protein kinase (AMPK). We demonstrate that the increase in muscle glucose use was suppressed in mice lacking the expression of GLUT4 in the organ muscle. In contrast, glucose use was stimulated normally in mice with muscle-specific inactivation of the insulin receptor gene, confirming independence from insulin-signaling pathways. Most importantly, the muscle glucose use in response to activation of the hepatoportal vein glucose sensor was completely dependent on the activity of AMPK, because enhanced hexose disposal was prevented by expression of a dominant negative AMPK in muscle. These data demonstrate that the portal sensor induces glucose use and development of hypoglycemia independently of insulin action, but by a mechanism that requires activation of the AMPK and the presence of GLUT4. C1 Univ Lausanne, Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. Hop Rangueil, Unite Mixte Rech 5018, F-5018 Toulouse, France. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Beth Israel Deaconess Med Ctr, Div Endocrinol & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr,Res Div, Boston, MA USA. Univ Lausanne, Inst Cell Biol & Morphol, Lausanne, Switzerland. RP Thorens, B (reprint author), Univ Lausanne, Inst Pharmacol & Toxicol, Rue Bugnon 27, CH-1005 Lausanne, Switzerland. RI burcelin, remy/M-6013-2014; OI Birnbaum, Morris/0000-0001-9972-8680 FU NIDDK NIH HHS [DK-4305] NR 36 TC 37 Z9 48 U1 0 U2 2 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 MAY PY 2003 VL 111 IS 10 BP 1555 EP 1562 DI 10.1172/JCI200316888 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 680KK UT WOS:000182976400016 PM 12750405 ER PT J AU Levi, MH Bartell, J Gandolfo, L Smole, SC Costa, SF Weiss, LM Johnson, LK Osterhout, G Herbst, LH AF Levi, MH Bartell, J Gandolfo, L Smole, SC Costa, SF Weiss, LM Johnson, LK Osterhout, G Herbst, LH TI Characterization of Mycobacterium montefiorense sp nov., a novel pathogenic mycobacterium from moray eels that is related to Mycobacterium triplex SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION ENZYME ANALYSIS; POLYMERASE-CHAIN-REACTION; IDENTIFICATION; HSP65; GENE; TUBERCULOSIS AB The characterization of a novel Mycobacterium sp. isolated from granulomatous skin lesions of moray eels is reported. Analysis of the hsp65 gene, small-subunit rRNA gene, rRNA spacer region, and phenotypic characteristics demonstrate that this organism is distinct from its closest genetic match, Mycobacterium triplex, and it has been named M. montefiorense sp. nov. C1 Montefiore Med Ctr, Dept Pathol, Bronx, NY 10461 USA. Montefiore Med Ctr, Inst Anim Studies, Bronx, NY 10461 USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. MIDI Inc, Newark, DE 19713 USA. MIDI Labs Inc, Newark, DE 19713 USA. Boston Univ, Sch Med, Dept Med, Infect Dis Sect, Boston, MA 02130 USA. VA Boston Healthcare Syst, Med Serv, Boston, MA 02130 USA. RP Levi, MH (reprint author), Montefiore Med Ctr, Microbiol Lab, 111 E 210th St, Bronx, NY 10467 USA. RI Johnson, Linda/B-1828-2014 OI Johnson, Linda/0000-0002-7574-7753 FU NIAID NIH HHS [AI31788, AI39454, R01 AI031788, R01 AI039454] NR 20 TC 36 Z9 37 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2003 VL 41 IS 5 BP 2147 EP 2152 DI 10.1128/JCM.41.5.2147-2152.2003 PG 6 WC Microbiology SC Microbiology GA 679QY UT WOS:000182934500055 PM 12734264 ER PT J AU Flaherty, JD Levett, PN Dewhirst, FE Troe, TE Warren, JR Johnson, S AF Flaherty, JD Levett, PN Dewhirst, FE Troe, TE Warren, JR Johnson, S TI Fatal case of endocarditis due to Weissella confusa SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LACTIC-ACID BACTERIA; LACTOBACILLUS ENDOCARDITIS; IDENTIFICATION; THERAPY AB This is the first reported case of endocarditis due to the Lactobacillus-like vancomycin-resistant grampositive bacillus Weissella confusa. Full identification and susceptibility testing of Lactobacillus-like organisms recovered in blood culture should be performed for patients with clinical presentations that suggest endocarditis. C1 Northwestern Univ, Dept Med, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. Northwestern Univ, Dept Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. Vet Affairs Chicago Hlth Care Syst, Lakeside Div, Chicago, IL USA. Ctr Dis Control & Prevent, Special Bacteriol Reference Lab, Meningitis & Special Pathogens Branch, Atlanta, GA USA. Forsyth Inst, Dept Mol Genet, Boston, MA USA. RP Warren, JR (reprint author), NW Mem Hosp, Galter Pavil 7-132A,251 E Huron St, Chicago, IL 60611 USA. NR 17 TC 29 Z9 33 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAY PY 2003 VL 41 IS 5 BP 2237 EP 2239 DI 10.1128/JCM.41.5.2237-2239.2003 PG 3 WC Microbiology SC Microbiology GA 679QY UT WOS:000182934500081 PM 12734290 ER PT J AU Chiou, YY Pitman, MB Hahn, PF Kim, YH Rhea, JT Mueller, PR AF Chiou, YY Pitman, MB Hahn, PF Kim, YH Rhea, JT Mueller, PR TI Rare benign and malignant appendiceal lesions: Spectrum of computed tomography findings with pathologic correlation SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE appendicitis; appendix; computed tomography (CT); appendix; neoplasms; carcinoid; lymphoma ID ULCERATIVE-COLITIS; VERMIFORM APPENDIX; CROHNS-DISEASE; CARCINOID-TUMORS; CT FINDINGS; MUCINOUS CYSTADENOCARCINOMA; GRANULOMATOUS APPENDICITIS; PRIMARY ADENOCARCINOMA; DIVERTICULAR-DISEASE; RADIOLOGIC FEATURES AB Although acute appendicitis is the most common disease of the appendix, the appendix can be involved by a wide range of diseases. Diseases other than acute appendicitis may produce signs and symptoms indistinguishable from those of acute appendicitis. Computed tomography (CT) can provide important information for diagnosis and evaluation of appendiceal diseases. The various CT and histologic features of appendiceal benign and neoplastic diseases are discussed, illustrated, and correlated in this article. Radiologists need to understand the full spectrum of appendiceal abnormalities, their underlying pathologic changes, and associated CT imaging findings. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Yang Ming Univ, Taipei 112, Taiwan. Vet Gen Hosp, Dept Radiol, Taipei, Taiwan. RP Hahn, PF (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. NR 53 TC 16 Z9 18 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2003 VL 27 IS 3 BP 297 EP 306 DI 10.1097/00004728-200305000-00001 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 693YP UT WOS:000183746200001 PM 12794590 ER PT J AU Prasad, SR Saini, S Sumner, JE Hahn, PF Sahani, D Boland, GW AF Prasad, SR Saini, S Sumner, JE Hahn, PF Sahani, D Boland, GW TI Radiological measurement of breast cancer metastases to lung and liver: Comparison between WHO (bidimensional) and RECIST (unidimensional) guidelines SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography; comparative studies; tumor measurements; treatment response ID SOLID TUMORS; CT AB Purpose: Radiologic assessment of "response-to-treatment" during clinical trials of anticancer drugs has been conventionally based on bidirectional tumor measurement. Recently, the revised guidelines were published, which recommended unidirectional tumor measurements. The purpose of this study was to compare response to treatment between the two measurement techniques in breast cancer patients with lung and liver metastases. Method: Contrast-enhanced computed tomography studies of 86 breast cancer patients who had lung (n = 27) and liver (n = 59) metastases and who were enrolled in a phase-III oncology trial were evaluated before initiation of treatment and at 6 months after treatment. Lesions were measured by subspecialist radiologists on digitized images using electronic calipers. The largest. diameter of the lesions was extracted from bidimensional measurements. Response to treatment was categorized into one of four categories: complete response indicating lesion disappearance, partial response indicating >30% decrease in tumor diameter, or >50% reduction in tumor area, disease progression indicating >20% increase in tumor diameter, or >25% increase in tumor area, and stable disease (neither complete response, partial response, nor disease progression). Response to treatment between the two measurement techniques was compared statistically using the chi(2) test. Results: Response to treatment was concordant in 76 patients between unidimensional and bidimensional measurement techniques. In 5 patients (2 lung and 3 liver metastases) the response assessment was improved using unidimensional criteria and in 5 patients (2 lung and 3 liver metastases) the response was worse using unidimensional guidelines. Thus, the overall response rate was 50% for both unidimensional and bidimensional measurement techniques. There was no statistical difference between the two techniques. Conclusion: Unidimensional measurements are appropriate for measuring the size of liver and lung metastases for determining response to treatment during clinical testing of oncologic drugs. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. WorldCare Inc, Cambridge, MA USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 12 TC 33 Z9 38 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2003 VL 27 IS 3 BP 380 EP 384 DI 10.1097/00004728-200305000-00014 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 693YP UT WOS:000183746200014 PM 12794603 ER PT J AU Wicky, S Rosol, M Hoffmann, U Graziano, M Yucel, KE Brady, TJ AF Wicky, S Rosol, M Hoffmann, U Graziano, M Yucel, KE Brady, TJ TI Comparative study with a moving heart phantom of the impact of temporal resolution on image quality with two multidetector electrocardiography-gated computed tomography units SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE computed tomography (CT) technology; computed tomography (CT) thin section; coronary vessels computed tomography (CT); heart computed tomography (CT) ID CORONARY-ARTERY STENOSES; ELECTRON-BEAM CT; ANGIOGRAPHY; EXPERIENCE; DIAMETER; MOTION AB Objective: The objective of this study was to compare the temporal resolution-related image quality of electrocardiography-gated images acquired with two multidetector computed tomography (CT) units with a moving heart phantom, at similar fixed heart rates, using half-scan and multisector acquisition modes. Methods: An adjustable moving heart phantom (Limbsandthings, Horfield, Bristol, UK) was used. Specific heart rates (47, 55, 64, 66, 69, and 73 beats per minute [bpm]) were chosen. On a General Electric CT unit (LightSpeed Plus; General Electric Medical Systems, Milwaukee, WI), retrospective half-scan and multisector mode protocols were performed. On a Siemens CT unit (Somatom Volume Zoom; Siemens, Forchheim, Germany), a retrospective half-scan mode was performed at 47, 55, and 64 bpm, and a two-sector mode was performed at 66, 69, and 73 bpm. Reformatted maximum intensity projection images were qualitatively compared and related to their temporal resolution. Results: Half-scan mode protocols provided similar good results with both CT units up to 55 bpm. The two-sector mode improved image quality compared with the half-scan mode. High temporal resolution with the multisector mode provided the best results. Conclusion: For coronary artery imaging, acquisition protocols that provide the highest temporal resolution are mandatory. The multisector mode is one technique that allows high temporal resolution but may be clinically inappropriate at heart rates below 65 bpm or when heart rate variation is observed during scan time. C1 Massachusetts Gen Hosp, Dept Radiol, CIMIT Div, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Wicky, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, CIMIT Div, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. NR 14 TC 16 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD MAY-JUN PY 2003 VL 27 IS 3 BP 392 EP 398 DI 10.1097/00004728-200305000-00016 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 693YP UT WOS:000183746200016 PM 12794605 ER PT J AU Zirwas, MJ Abell, E Ruben, A Silverman, AR Wolff, J Deng, JS AF Zirwas, MJ Abell, E Ruben, A Silverman, AR Wolff, J Deng, JS TI Immunofluorescence findings in granuloma faciale: report of two cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article AB Background: Immunofluorescence findings in granuloma faciale have been infrequently described. Reported findings include granular IgA, IgG, IgM, and C3 deposits in the dermoepidermal junction, in blood vessel walls, and on connective tissue fibers; IgG in the basement membrane zone, and IgG around blood vessels. Observations: We report two cases of granuloma faciale in which biopsy specimens were sent for routine pathology as well as immunofluorescence. Additional work-up included serologic testing for markers of lupus erythematosus (LE). Immunofluorescence in both cases revealed granular IgA, IgG, IgM, C3, and C5-9 deposits along the dermoepidermal junction only. Blood vessel walls and connective tissue fibers were spared. Serologic studies for markers of LE were negative. Conclusion: Immunofluorescence findings were essentially identical to those which would be expected in cutaneous LE; however, the combination of negative serologic studies for LE, histopathologic findings typical of granuloma faciale, and clinical findings most consistent with granuloma faciale allowed the diagnosis of granuloma faciale to be rendered with certainty. Interpretation of results of direct immunofluorescence of skin should be correlated with clinical presentation, histopathological findings and other laboratory results in order to render final diagnosis of a given patient. C1 VA Pittsburgh Healthcare Syst, Serv Dermatol, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Dermatol, Pittsburgh, PA 15261 USA. Dermatopathol Lab, Pittsburgh, PA USA. Westmorland Dermatol Assoc, Greensburg, PA USA. RP Deng, JS (reprint author), VA Pittsburgh Healthcare Syst, Serv Dermatol, Univ Dr, Pittsburgh, PA 15240 USA. NR 14 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD MAY PY 2003 VL 30 IS 5 BP 314 EP 317 DI 10.1034/j.1600-0560.2003.00051.x PG 4 WC Dermatology; Pathology SC Dermatology; Pathology GA 680ZQ UT WOS:000183010300005 PM 12753171 ER PT J AU Kumar, PS Griffen, AL Barton, JA Paster, BJ Moeschberger, ML Leys, EJ AF Kumar, PS Griffen, AL Barton, JA Paster, BJ Moeschberger, ML Leys, EJ TI New bacterial species associated with chronic periodontitis SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE 16S ribosomal identification; periodontal microbiology; periodontitis; human epidemiology; uncultivated bacteria ID SUBGINGIVAL PLAQUE; PORPHYROMONAS-GINGIVALIS; ADULT PERIODONTITIS; EIKENELLA-CORRODENS; SP-NOV.; HEALTH; MICROBIOTA; PREVALENCE; PCR; IDENTIFICATION AB Recent investigations of the human subgingival oral flora based on ribosomal 16S cloning and sequencing have shown many of the bacterial species present to be novel species or phylotypes. The purpose of the present investigation was to identify potential periodontal pathogens among these newly identified species and phylotypes. Species-specific ribosomal 16S primers for PCR amplification were developed for detection of new species. Associations With chronic. periodontitis were observed for several new species or phylotypes, including uncultivated clones D084 and BH017 from the Deferribacteres phylum, AU126 from the Bacteroidetes phylum, Megasphaera clone BB 166, clone X112 from the OP11 phylum, and clone I025 from the TM7 phylum, and the named species Eubacterium saphenum, Porphyromonas endodontalis, Prevotella denticola, and Cryptobacterium curtum. Species or phylotypes more prevalent in periodontal health included two uncultivated phylotypes clone W090 from the Deferribacteres phylum and clone BU063 from the Bacteroidetes, and named species Atopobium rimae and Atopobium parvulum. C1 Ohio State Univ, Dept Pediat Dent, Columbus, OH 43218 USA. Ohio State Univ, Dept Periodontol, Columbus, OH 43210 USA. Ohio State Univ, Coll Dent, Dept Oral Biol,Coll Med & Publ Hlth, Div Epidemiol & Biometr,Sch Publ Hlth, Columbus, OH 43210 USA. Harvard Univ, Sch Dent Med, Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Griffen, AL (reprint author), Ohio State Univ, Dept Pediat Dent, 305 W 12th Ave,POB 182357, Columbus, OH 43218 USA. RI Kumar, Purnima/F-6363-2013 OI Kumar, Purnima/0000-0001-5844-1341 FU NIDCR NIH HHS [DE10467] NR 33 TC 236 Z9 255 U1 1 U2 22 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 MAY PY 2003 VL 82 IS 5 BP 338 EP 344 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 671YQ UT WOS:000182493500003 PM 12709498 ER PT J AU Streja, D Cressey, P Rabkin, SW AF Streja, D Cressey, P Rabkin, SW TI Associations between inflammatory markers, traditional risk factors, and complications in patients with type 2 diabetes mellitus SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article DE diabetes mellitus; non-insulin-dependent; body mass index; C reactive protein; fibrinogen; microalbuminuria; hemoglobin A, C; hydroxymethylglutoryl Co A reductase inhibitor; post menopousal hormone replacement therapy ID C-REACTIVE PROTEIN; CORONARY-ARTERY DISEASE; INSULIN-RESISTANCE ATHEROSCLEROSIS; BEAM COMPUTED-TOMOGRAPHY; PLASMA-FIBRINOGEN; PRIMARY HYPERCHOLESTEROLEMIA; CAROTID ATHEROSCLEROSIS; ENDOTHELIAL DYSFUNCTION; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN AB Objective: Inflammatory markers predict cardiovascular events in a wide range of patients. Two factors, fibrinogen (FIB) and high-sensitivity C reactive protein (CRP), are currently entering clinical practice as cardiovascular risk predictors. In patients with type 2 diabetes mellitus, we sought to examine the relationship between macrovascular disease, urinary albumin/creatinine ratio (ACR), and FIB or CRP, as well as the relationship of FIB and CRP with traditional risk predictors of these complications of diabetes. Methods: In 202 consecutive patients with type 2 diabetes mellitus from a diabetes clinic, clinical and biochemical data were obtained and a cross-sectional analysis was performed. Results: Patients with macrovascular disease had higher FIB (P = .02) but not higher CRP. They were older, more likely to have retinopathy or elevated serum creatinine, had higher ACR and lower HDL cholesterol. They were more likely to be treated with statins, beta-blockers, and ASA. Adjustment for statin therapy did not result in significant differences in CRP levels according to macrovascular disease status. Both FIB (P = .01) and CRP (P = .02) were significantly higher in patients with ACR whose values were in the proteinuria range. In multivariate analysis, both FIB (P = .001) and CRP (P = .03) were positively correlated with ACR, but no association was seen between CRP and ACR when FIB was entered in the model. Other factors positively associated with ACR were age, diastolic blood pressure, retinopathy, and hemoglobin A1c (HbA1c). FIB and CRP were strongly correlated (R = .49, P < .001) and this effect was independent of statin therapy. CRP was positively associated with body mass index (BMI), serum triglycerides, and sulfonylurea therapy and negatively associated with metformin therapy. Patients on statin therapy had significantly higher FIB and lower CRP. Women on hormone replacement therapy (HRT) had significantly lower FIB and higher CRP. Conclusions: In patients with diabetes: (1) the two markers, FIB and CRP, are interrelated; (2) FIB is significantly associated with presence of microvascular disease, independent of CRP; (3) CRP is strongly associated with metabolic factors but not with complications of diabetes, independently of FIB; (4) statins and HRT were divergently associated with CRP and FIB as HRT was associated with lower FIB and higher CRP, while statins showed the reverse association; and (5) CRP and FIB provide different information about the characteristics and consequences of diabetes mellitus because of divergent associations with biological indicators and therapeutic agents. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Streja, D (reprint author), W Los Angeles Vet Affairs Med Ctr, Endocrinol Sect, 7345 Med Ctr Dr, Canoga Pk, CA 91307 USA. NR 53 TC 40 Z9 47 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD MAY-JUN PY 2003 VL 17 IS 3 BP 120 EP 127 DI 10.1016/S1056-8727(02)00204-0 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 679LQ UT WOS:000182924200002 PM 12738395 ER PT J AU Harris, NS Wenzel, RP Thomas, SH AF Harris, NS Wenzel, RP Thomas, SH TI High altitude headache: Efficacy of acetaminophen vs. ibuprofen in a randomized, controlled trial SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine (SAEM) CY MAY 23-25, 2000 CL SAN FRANCISCO, CA SP Soc Acad Emergency Med DE high altitude; headache; pulmonary edema; ibuprofen; acetaminophen ID ACUTE MOUNTAIN-SICKNESS; HYPOXIC PULMONARY VASOCONSTRICTION; CYCLOOXYGENASE INHIBITION; NITRIC-OXIDE; DOUBLE-BLIND; BLOOD-FLOW; EDEMA; INFLAMMATION; PROPHYLAXIS; DOGS AB Ibuprofen has been shown to be more effective than placebo in the treatment of high altitude headache (HAH), but nonsteroidal anti-inflammatory agents have been linked to increased incidence of gastrointestinal (GI) side effects and high-altitude pulmonary edema (HAPE). We postulated that acetaminophen, which does not share ibuprofen's theorized causal link to GI side effects or HAPE, could provide effective HAH therapy. We conducted a prospective, randomized, double-blind, clinical trial of ibuprofen vs. acetaminophen in the Solu Khumbu, Nepal: Mt. Everest Base Camp, Pheriche, Dingboche (4240 m to 5315 m). Seventy-four consecutive patients (ages 13 to 61 years) were randomized, were assessed with the Lake Louise Acute Mountain Sickness (AMS) criteria, and received a physical examination (which included vital signs, oxygen saturation as measured by pulse oximetry (SpO(2)), and assessment of clinical Lake Louise AMS criteria). Patients then received either 400 mg of ibuprofen (IBU) or 1000 mg of acetaminophen (ACET), and were asked to rate their cephalgia using a 10-cm visual analog scale (VAS). Thirty-nine patients received IBU, and 35 received ACET. Baseline Lake Louise AMS scores were identical in the two groups (mean = 5.9). No differences in mean VAS scores between IBU and ACET groups were noted at time 0 (presentation), 30, 60, or 120 min. No cases of HAPE or high altitude cerebral edema were noted during the study period. In this study population, acetaminophen was as effective as ibuprofen in relieving the pain of HAH. (C) 2003 Elsevier Inc. C1 Harvard Univ, Sch Med, Harvard Affiliated Emergency Med Residency, Boston, MA USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Internal Med, Richmond, VA 23298 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Harris, NS (reprint author), 62 Chestnut St, Brookline, MA 02445 USA. NR 62 TC 21 Z9 22 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2003 VL 24 IS 4 BP 383 EP 387 DI 10.1016/S0736-4679(03)00034-9 PG 5 WC Emergency Medicine SC Emergency Medicine GA 679CC UT WOS:000182902600005 PM 12745039 ER PT J AU Mick, N Brown, DFM Nadel, ES Masser, B Thomas, S Nagurney, T AF Mick, N Brown, DFM Nadel, ES Masser, B Thomas, S Nagurney, T TI Blunt multi-system trauma SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID TRANSESOPHAGEAL ECHOCARDIOGRAPHY; 10-YEAR EXPERIENCE; AORTIC INJURY; RUPTURE; DIAGNOSIS; REPAIR C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Affiliated Emergency Med Residency, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, CLN-115, Boston, MA 02114 USA. NR 12 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 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2003 VL 24 IS 4 BP 449 EP 454 DI 10.1016/S0736-4679(03)00045-3 PG 6 WC Emergency Medicine SC Emergency Medicine GA 679CC UT WOS:000182902600016 PM 12745050 ER PT J AU Fink, AS AF Fink, AS TI 2002 SSAT Annual Meeting - 2002 Consensus Conference on Management of Obesity - Introduction SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Editorial Material C1 Atlanta VA Med Ctr, Surg Serv, Atlanta, GA 30033 USA. Emory Univ, Sch Med, Dept Surg, Atlanta, GA 30322 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Washington Univ, St Louis, MO 63130 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. RP Fink, AS (reprint author), Atlanta VA Med Ctr, Surg Serv, 112,1670 Clairmont Rd, Atlanta, GA 30033 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1091-255X EI 1873-4626 J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2003 VL 7 IS 4 BP 433 EP 437 DI 10.1016/S1091-255X(03)00045-3 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 684LP UT WOS:000183209100001 ER PT J AU Kaplan, LA AF Kaplan, LA TI Body weight regulation and obesity SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT Conference on Management of Obesity CY MAY 19-23, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract, Amer Soc Bariatr Surg ID Y GASTRIC BYPASS; FOOD-INTAKE; UNITED-STATES; TRENDS; PREVALENCE; OVERWEIGHT; PHYSICIAN; OUTCOMES; SURGERY; BARRIER C1 Massachusetts Gen Hosp, MGH Weight Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Kaplan, LA (reprint author), Massachusetts Gen Hosp, MGH Weight Ctr, 50 Staniford St,4th Floor, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK99010, DK57478, DK43351] NR 50 TC 16 Z9 16 U1 3 U2 3 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 MAY-JUN PY 2003 VL 7 IS 4 BP 443 EP 451 DI 10.1016/S1091-255X(03)00047-7 PG 9 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 684LP UT WOS:000183209100003 PM 12763397 ER PT J AU Billingsley, KG Hur, K Henderson, WG Daley, J Khuri, SF Bell, RH AF Billingsley, KG Hur, K Henderson, WG Daley, J Khuri, SF Bell, RH TI Outcome after pancreaticoduodenectomy for periampullary cancer: An analysis from the veterans affairs national surgical quality improvement program SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract DE pancreatic neoplasms; surgery; adverse effects; postoperative complications ID PREOPERATIVE BILIARY DRAINAGE; RISK ADJUSTMENT; PROGNOSTIC PREDICTION; PANCREATIC RESECTION; OBSTRUCTIVE-JAUNDICE; OPERATIVE MORTALITY; HOSPITAL VOLUME; MORBIDITY; COMPLICATIONS; CARE AB The aim of this study is to define the risk factors that predict adverse outcomes for patients undergoing pancreaticoduodenectomy for periampullary cancer in the Department of Veterans Affairs Healthcare System (VA). The VA National Surgical Quality Improvement Program prospectively collected data on 462 patients undergoing pancreaticoduodenectomy in 123 VA medical centers from 1990 to 2000. Independent variables included 68 preoperative and 12 intraoperative variables. The main outcome measures were 30-day postoperative mortality and morbidity, as measured by a set of 20 pre-defined complications. Predictive models for 30-day morbidity and mortality were constructed using logistic regression analysis. The 30-day morbidity rate was 45.9% (212/462). The 30-day postoperative mortality rate was 9.3% (43/462 ). Significant predictors of mortality, included: preoperative serum albumin, American Society of Anesthesiologists classification, preoperative bilirubin >20mg/dl, and operative time. The use of preoperative biliary tract instrumentation did not predict postoperative death or septic complications. This study provides a set of preoperative risk factors that are predictive of adverse outcome following pancreaticoduodenectomy. These factors may assist in patient selection for this procedure and are likely to facilitate risk-adjusted comparison of pancreaticoduodenectomy outcomes between different health care systems. (C) 2003 The Society for Surgery of the Alimentary Tract, Inc. C1 VA Puget Sound Hlth Care Syst, Dept Surg, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. Hines VA Cooperat Studies Program, Coordinating Ctr, Hines, IL USA. Univ Colorado, Hlth Outcomes Program, Aurora, CO USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tenet Hlth Syst, Inst Hlth Policy, Ctr Hlth Syst Design & Evaluat, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. RP Billingsley, KG (reprint author), VA Puget Sound Hlth Care Syst, Dept Surg, 112,1660 Columbian Way, Seattle, WA 98108 USA. NR 39 TC 31 Z9 34 U1 0 U2 0 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 MAY-JUN PY 2003 VL 7 IS 4 BP 484 EP 491 DI 10.1016/S1091-255X(03)00067-2 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 684LP UT WOS:000183209100011 PM 12763405 ER PT J AU Stelzner, M Hoagland, VD Woolman, JD AF Stelzner, M Hoagland, VD Woolman, JD TI Identification of optimal harvest sites of ileal stem cells for treatment of bile acid malabsorption in a dog model SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Surg Alimentary Tract DE ileum; absorption; bile acid; dog ID MUCOSAL NUTRIENT TRANSPORT; ABSORPTION; ILEUM; EXPRESSION; MEMBRANE; RABBIT AB Ileal mucosal stein cells expressing the sodium-dependent ileal bile acid transporter (IBAT) have been successfully transplanted into the jejunum of rodents in projects aimed at creating a "neoileum" to treat bile acid malabsorption. To find optimal harvest sites for a dog model of stem cell transplantation, the ex,act location of peak IBAT expression in the donor ileum needs to be known. We therefore mapped MAT function, IBAT mRNA, and IBAT protein in the ileum of Beagle dogs (N = 3). Mucosal samples were taken every 5 cm in the ileum and every 20 cm in the jejunum of each dog. Sodium-dependent (active) and sodium-independent (passive) taurocholate uptake rates were measured using a standardized everted sleeve technique. IBAT mRNA concentrations were determined by semiquantitative reverse transcriptase-polymerase chain reaction and IBAT protein concentrations by fluorometric immunohistochemical analysis. The small bowel measured 208 +/- 17 cm (mean +/- standard error of the mean). Active and passive uptake rates were found to follow distinct distribution curves. Significant active uptake was seen only at the terminal 50 cm and peaked at 479 +/- 176 pM/mm(2). Depending on location, active uptake accounted for approximately half of the total uptake. IBAT in RNA and protein distributions corroborated uptake curves. The terminal 10 to 50 cm of ileum has the highest bile acid uptake capacity. This short segment appears to be the most promising donor site for ileal stem cell transplants to create a "neoileum" in dogs. (C) 2003 The Society for Surgery of the Alimentary Tract, Inc. C1 Univ Washington, Dept Surg, VAPSHCS Surg Serv 112, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Stelzner, M (reprint author), Univ Washington, Dept Surg, VAPSHCS Surg Serv 112, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 20 TC 4 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 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD MAY-JUN PY 2003 VL 7 IS 4 BP 516 EP 522 DI 10.1016/S1091-255X(03)00027-1 PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 684LP UT WOS:000183209100016 PM 12763409 ER PT J AU Tian, CR Bagley, J Kaye, J Iacomini, J AF Tian, CR Bagley, J Kaye, J Iacomini, J TI Induction of T cell tolerance to a protein expressed in the cytoplasm through retroviral-mediated gene transfer SO JOURNAL OF GENE MEDICINE LA English DT Article DE tolerance; T cells; gene therapy; GFP ID GREEN FLUORESCENT PROTEIN; CYTOTOXIC IMMUNE-RESPONSE; LONG-TERM EXPRESSION; TRANSGENE EXPRESSION; ADENOVIRAL VECTORS; HEMATOPOIETIC-CELLS; C57BL/6 MICE; HEMOPHILIA-A; FACTOR-VIII; STEM-CELLS AB Background Host immune responses to foreign gene products have been shown to lead to the elimination of genetically modified cells, and are a major barrier to successful therapeutic gene therapy. We have shown that immunological tolerance to retrovirally transduced cell surface proteins can be induced by expressing the gene encoding these products in bone marrow derived cells. Here, we investigate if expression of foreign gene products in bone marrow derived cells can be used to induce tolerance to cytoplasmic proteins. Methods Balb/c mice were reconstituted with syngeneic bone marrow cells transduced with retrovirus carrying the gene encoding enhanced green fluorescent protein (eGFP), or mock-transduced bone marrow cells. After mice were immunized with cells expressing eGFP, and T cells reconstitution, were tested for the ability to kill eGFP-expressing targets in in vitro cytotoxic T lymphocyte (CTL) assays. Results T cells from Balb/c mice reconstituted with mock-transduced bone marrow were able to kill target cells expressing eGFP. In contrast, T cells from mice reconstituted with eGFP-transduced bone marrow were unable to kill targets expressing eGFP. In addition, we observed that T cell responses to eGFP in C57BL/6 mice were minimal even under highly immunogenic conditions. Conclusions These data suggest that expression of foreign gene products in bone marrow derived cells is capable of inducing T cell tolerance to proteins expressed exclusively in the cytoplasm. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Iacomini, J (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, 149-5210,13th St,Bldg 149, Boston, MA 02129 USA. FU NIAID NIH HHS [R01 AI44268, R01 AI43619] NR 34 TC 24 Z9 24 U1 0 U2 0 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 MAY PY 2003 VL 5 IS 5 BP 359 EP 365 DI 10.1002/jgm.363 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 689KZ UT WOS:000183493100001 PM 12731084 ER PT J AU Linder, JA Singer, DE van den Ancker, M Atlas, SJ AF Linder, JA Singer, DE van den Ancker, M Atlas, SJ TI Measures of health-related quality of life for adults with acute sinusitis - A systematic review 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 sinusitis; outcome assessment (health care); health services research; antibiotics ID ACUTE MAXILLARY SINUSITIS; OF-LIFE; CONTROLLED TRIAL; CHRONIC RHINOSINUSITIS; ANTIBIOTIC-TREATMENT; NASAL IRRIGATION; PATIENT OUTCOMES; SURGERY; DISEASE; MULTICENTER AB Context: Symptoms suggestive of acute sinusitis are a common reason for patients to visit primary care providers. Since objective measures of outcome have not been shown to be related to patient reported outcomes, measures of treatment success have focused on symptom relief and improved health-related quality of life (HRQL). Assessing the appropriate role of treatment-for example, antibiotics for patients with acute sinusitis-requires valid, reliable, and responsive measures of outcome. We identified symptom scores and HRQL instruments for adults with sinusitis and assessed their performance characteristics. Data Sources: Articles identified through computer searches of the medline, premedline, and embase databases, the Cochrane Library, and internet documents; inquiries to experts in sinusitis and outcomes assessment; and review of reference lists. Study Selection: Studies that used HRQL instruments or evaluated the performance characteristics of symptom scores in adults with sinusitis, published in English after 1966. Data Extraction: Two reviewers independently extracted data on study design, setting, and patient characteristics; instrument length and format; and instrument validity, reliability, responsiveness to change, and interpretability. Study quality was assessed using a 10-point score. Data Synthesis: Of 1,340 articles in the original search, 29 articles using 16 HRQL instruments and 5 symptoms scores met inclusion and exclusion criteria. The overall quality of these studies was low; only 4 studies scored higher than 4 of 10 points. Four studies included patients with acute sinusitis, but only 2 included exclusively acute sinusitis patients. Three instruments have been shown to meet basic requirements for validity, reliability, and responsiveness: the Chronic Sinusitis Survey, the Rhinosinusitis Outcome Measure-31, and the Sinonasal Outcome Test-16. No instrument has been validated in a primary care setting or for patients with acute sinusitis. Conclusions: Few validated measures of sinusitis-specific HRQL are available. The 3 instruments shown to be valid, reliable, and responsive have been assessed in patients with chronic sinusitis. No measure has been validated in primary care settings or for patients with acute sinusitis. A lack of valid, responsive outcome measures may limit current treatment recommendations for patients with acute sinusitis. C1 Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. RP Linder, JA (reprint author), Brigham & Womens Hosp, Div Gen Med, 75 Francis St, Boston, MA 02115 USA. FU BHP HRSA HHS [5T32PE11001-12] NR 57 TC 28 Z9 29 U1 0 U2 4 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 MAY PY 2003 VL 18 IS 5 BP 390 EP 401 DI 10.1046/j.1525-1497.2003.20744.x PG 12 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 687EQ UT WOS:000183363500011 PM 12795739 ER PT J AU Samet, JH Freedberg, KA Savetsky, JB Sullivan, LM Padmanabhan, L Stein, MD AF Samet, JH Freedberg, KA Savetsky, JB Sullivan, LM Padmanabhan, L Stein, MD TI Discontinuation from HIV medical care: Squandering treatment opportunities SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE AIDS, primary care, HIV; access, linkage, injection drug user ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; PROTEASE INHIBITORS; HEALTH-CARE; INFECTION; DELAY; INSTRUMENT; ADULTS AB The purpose of this study was to assess HIV-infected patients' discontinuation of their primary care. One hundred ninety-eight consecutive outpatients were interviewed on initial HIV primary care presentation, assessed after six months about their discontinuation from primary care, and had characteristics associated with discontinuation determined. Primary care was not continued in 20 percent (401198) of the cases. Cohort characteristics included 25 percent women; 44 percent black, 28 percent white, 25 percent Hispanic; 69 percent with highest yearly income less than or equal to $16,000; 47 percent injection drug users; and median CD4 count 285/muL. Characteristics significantly associated (p less than or equal to 0.05) with discontinuation were higher CD4 count, less education, no history of victimization, previous jail time, and site of medical care. One-fifth of HIV-infected patients did not remain engaged in primary care after establishing this essential link to treatment. C1 Boston Med Ctr, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Coordinating Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rhode Isl Hosp, Providence, RI 02903 USA. RP Samet, JH (reprint author), Boston Med Ctr, Boston, MA 02118 USA. NR 28 TC 20 Z9 21 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD MAY PY 2003 VL 14 IS 2 BP 244 EP 255 DI 10.1177/1049208903251521 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 670UY UT WOS:000182428600008 PM 12739303 ER PT J AU Weninger, W Carlsen, HS Goodarzi, M Moazed, F Crowley, MA Baekkevold, ES Cavanagh, LL von Andrian, UH AF Weninger, W Carlsen, HS Goodarzi, M Moazed, F Crowley, MA Baekkevold, ES Cavanagh, LL von Andrian, UH TI Naive T cell recruitment to nonlymphoid tissues: A role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID L-SELECTIN; LYMPHOTOXIN-ALPHA; DISTINCT ROLES; CHRONIC INFLAMMATION; ECTOPIC EXPRESSION; HOMING CHEMOKINES; TRANSGENIC MICE; DEFICIENT MICE; P-SELECTIN; IN-VIVO AB Naive T cells are usually excluded from nonlymphoid tissues. Only when such tertiary tissues are subjected to chronic inflammation, such as in some (but not all) autoimmune diseases, are naive T cells recruited to these sites. We show that the CCR7 ligand CC chemokine ligand (CCL)21 is sufficient for attracting naive T cells into tertiary organs. We performed intravital microscopy of cremaster muscle venules in T-GFP mice, in which naive T cells express green fluorescent protein (GFP). GFP(+) cells underwent selectin-dependent rolling, but no firm adherence (sticking). Superfusion with CCL21, but not CXC chemokine ligand 12, induced integrin-dependent sticking of GFP(+) cells. Moreover, CCL21 rapidly elicited accumulation of naive T cells into sterile s.c. air pouches. Interestingly, a second CCR7 ligand, CCL19, triggered T cell sticking in cremaster muscle venules, but failed to induce extravasation in air pouches. Immunohistochemistry studies implicate ectopic expression of CCL21 as a mechanism for naive T cell traffic in human autoimmune diseases. Most blood vessels in tissue samples from patients with rheumatoid arthritis (85+/-10%) and ulcerative colitis (66+/-1%) expressed CCL21, and many perivascular CD45RA(+) naive T cells were found in these tissues, but not in psoriasis, where CCL21(+) vessels were rare (17+/-1%). These results identify endothelial CCL21 expression as an important determinant for naive T cell migration to tertiary tissues, and suggest the CCL21/CCR7 pathway as a therapeutic target in diseases that are associated with naive T cell recruitment. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Oslo, Rikshosp, Dept Surg, N-0316 Oslo, Norway. RP Weninger, W (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949, HL48675] NR 59 TC 139 Z9 144 U1 1 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 MAY 1 PY 2003 VL 170 IS 9 BP 4638 EP 4648 PG 11 WC Immunology SC Immunology GA 672NX UT WOS:000182528100029 PM 12707342 ER PT J AU deSchoolmeester, ML Little, MC Rollins, BJ Else, KJ AF deSchoolmeester, ML Little, MC Rollins, BJ Else, KJ TI Absence of CC chemokine ligand 2 results in an altered Th1/Th2 cytokine balance and failure to expel Trichuris muris infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTESTINAL NEMATODE INFECTION; CELLULAR IMMUNE-RESPONSES; CHEMOTACTIC PROTEIN-1; AUTOIMMUNE ENCEPHALOMYELITIS; TRICHINELLA-SPIRALIS; GRANULOMA-FORMATION; IL-12 PRODUCTION; TRANSGENIC MICE; IN-VIVO AB Despite a growing understanding of the role of cytokines in immunity to intestinal helminth infections, the importance of chemokines has been neglected. As a chemokine with both chemoattractive properties and an ability to shape the quality of the adaptive immune response, CC chemokine ligand 2 (CCL2) was investigated as an attractive candidate for controlling resistance to these types of infection, which require highly polarized Th cell responses. We show here for the first time that CCL2 plays an important role in the development of resistance to infection by the gastrointestinal nematode Trichuris muris. Thus, in the absence of CCL2, worm expulsion does not occur, and the lymph node draining the site of infection becomes a Th1-promoting environment. Elevated levels of IL-12 are produced by polarizing APCs, and the composition of the APC environment itself is perturbed, with reduced numbers of macrophages. C1 Univ Manchester, Sch Biol Sci, Dept Immunol Microbiol & Dev, Manchester M13 9PT, Lancs, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP deSchoolmeester, ML (reprint author), Univ Manchester, Sch Biol Sci, Dept Immunol Microbiol & Dev, 3-239 Stopford Bldg, Manchester M13 9PT, Lancs, England. NR 47 TC 29 Z9 29 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 MAY 1 PY 2003 VL 170 IS 9 BP 4693 EP 4700 PG 8 WC Immunology SC Immunology GA 672NX UT WOS:000182528100035 PM 12707348 ER PT J AU Ito, A Matejuk, A Hopke, C Drought, H Dwyer, J Zamora, A Subramanian, S Vandenbark, AA Offner, H AF Ito, A Matejuk, A Hopke, C Drought, H Dwyer, J Zamora, A Subramanian, S Vandenbark, AA Offner, H TI Transfer of severe experimental autoimmune encephalomyelitis by IL-12- and IL-18-potentiated T cells is estrogen sensitive SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GAMMA-INDUCING FACTOR; CHEMOKINE RECEPTOR EXPRESSION; CENTRAL-NERVOUS-SYSTEM; TNF-ALPHA PRODUCTION; IFN-GAMMA; INTERFERON-GAMMA; DENDRITIC CELLS; B-CELLS; MULTIPLE-SCLEROSIS; TH1 DEVELOPMENT AB The aim of this study was to evaluate the roles of IL-18 and IL-12 in potentiating the encephalitogenic activity of T cell lines specific for myelin oligodendrocyte glycoprotein (MOG(35-55)) MOG-specific T cells stimulated with anti-CD3 and anti-CD28 in the presence of IL-12 or IL-18 alone transferred only mild experimental autoimmune encephalomyelitis (EAE) into a low percentage of recipients. However, T cells cocultured with both cytokines transferred aggressive clinical and histological EAE into all recipients. Coculture of T cells with IL-12 enhanced the secretion of IFN-gamma, but not TNF-alpha, whereas coculture with IL-18 enhanced the secretion of TNF-alpha, but not INF-gamma. However, coculture with both IL-18 and IL-12 induced high levels of both TNF-alpha and IFN-gamma. Additionally, IL-12 selectively enhanced mRNA expression of CCR5, whereas IL-18 selectively enhanced the expression of CCR4 and CCR7, and CCR4 and CCR5 were coexpressed on the surface of T cells cocultured with IL-12 and IL-18. Finally, estrogen treatment, previously found to inhibit both TNF-alpha and IFN-gamma production, completely abrogated all signs of passive EAE. These data demonstrate that optimal potentiation of encephalitogenic activity can be achieved by conditioning MOG-specific T cells with the combination of IL-12 and IL-18, which, respectively, induce the secretion of IFN-gamma/CCR5 and TNF-alpha/CCR4/CCR7, and that estrogen treatment, which is known to inhibit both proinflammatory cytokines, can completely ablate this aggressive form of passive EAE. C1 Portland Vet Affairs Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Kyoto Univ, Inst Med Sci, Dept Expt Pathol, Kyoto, Japan. Polish Acad Sci, L Hirszfeld Inst Immunol & Expt Therapy, Wroclaw, Poland. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97201 USA. RP Offner, H (reprint author), Portland Vet Affairs Med Ctr, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU NIAID NIH HHS [AI42376]; NINDS NIH HHS [NS23221, NS23444] NR 52 TC 32 Z9 32 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 MAY 1 PY 2003 VL 170 IS 9 BP 4802 EP 4809 PG 8 WC Immunology SC Immunology GA 672NX UT WOS:000182528100049 PM 12707362 ER PT J AU Nolte, A Scheffold, C Slotty, J Huenefeld, C Schultze, JL Grabbe, S Berdel, WE Kienast, J AF Nolte, A Scheffold, C Slotty, J Huenefeld, C Schultze, JL Grabbe, S Berdel, WE Kienast, J TI Generation of melanoma-specific cytotoxic T lymphocytes for allogeneic immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE allogeneic immunotherapy; cytotoxic T lymphocytes; hematopoietic stem cell transplantation; melanoma; peptides ID TUMOR-INFILTRATING LYMPHOCYTES; STEM-CELL TRANSPLANTATION; PULSED DENDRITIC CELLS; GRAFT-VERSUS-LEUKEMIA; BONE-MARROW TRANSPLANTATION; METASTATIC MALIGNANT-MELANOMA; HIGH-DOSE INTERLEUKIN-2; PHASE-I TRIAL; PERIPHERAL-BLOOD; ANTIGEN GP100 AB To exploit alloreactive T-cell responses known as the graft-versus-tumor effect, allogeneic hematopoietic stem cell transplantation is being explored as experimental therapy in selected solid tumors, including metastatic melanoma. However, donor T-cell responses are often delayed and associated with severe graft-versus-host disease. Posttransplant adoptive immunotherapy using tumor-specific cytotoxic T lymphocytes (CTL) of donor origin might provide immediate graft-versus-tumor effects but not graft-versus-host disease. Therefore, the aim of the current study was to define in vitro conditions for the expansion of allogeneic major histocompatibility complex-matched CTLs targeting melanoma-associated antigens (MAA). The CTLs were generated from peripheral blood mononuclear cells (PBMCs) of HLA-A*0201+ healthy donors by repetitive stimulations with HLA-A*0201-restricted MAA-derived peptides. Melanoma reactivity, as determined by lysis of peptide-pulsed T2 cells and HLA-A2+/Ag+ melanoma cells, was detected using in vitro expanded CTL targeting MAA peptides AAGIGILTV(MT27-35), IMDQVPFSV(G(209-2M)), and YMDGTMSQV(T368-376). In contrast, FLWGPRALV(MAGE3(271-279),) and VLPDVFIRCV(GnT-Vnt38-67) induced peptide-specific recognition of T2 target cells only, whereas ITDQVPFSV(G(209-217)), KTWGQYWQV(G9(154)), MLLAVLYCL(T1-9), and tumor lysate could not induce specific CTLs. Specific cytolytic activity was accompanied by interferon-gamma secretion. Peptide-pulsed dendritic cells were required only for the initial stimulation of CTLs and could be substituted by PBMCs during restimulations. The median expansion rate of CTL was five to six times, regardless of whether dendritic cells or PBMCs were used after the initial stimulation. The results delineate the conditions for effective ex vivo expansion of melanoma-specific CTLs from PBMCs of healthy donors to be used as an adjunct in allogeneic cell therapy of metastatic melanoma. C1 Univ Munster, Dept Haematol & Med Oncol, D-48129 Munster, Germany. Univ Munster, Dept Dermatol, D-48129 Munster, Germany. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA 02115 USA. RP Kienast, J (reprint author), Univ Munster, Dept Haematol & Med Oncol, Albert Schweitzer Str 33, D-48129 Munster, Germany. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 70 TC 6 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAY-JUN PY 2003 VL 26 IS 3 BP 257 EP 269 DI 10.1097/00002371-200305000-00009 PG 13 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 682MM UT WOS:000183095800009 PM 12806279 ER PT J AU Stoffel, EM Garber, JE Grover, S Russo, L Johnson, J Syngal, S AF Stoffel, EM Garber, JE Grover, S Russo, L Johnson, J Syngal, S TI Cancer surveillance is often inadequate in people at high risk for colorectal cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; DIAGNOSIS; CARE C1 Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA. RP Syngal, S (reprint author), Brigham & Womens Hosp, Div Gastroenterol, Smith 209,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA85453] NR 13 TC 16 Z9 16 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD MAY PY 2003 VL 40 IS 5 AR e54 DI 10.1136/jmg.40.5.e54 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 677TK UT WOS:000182823500019 PM 12746408 ER PT J AU McConnell, KA Bohning, DE Nahas, Z Shastri, A Teneback, C Lorberbaum, JP Lomarev, MP Vincent, DJ George, MS AF McConnell, KA Bohning, DE Nahas, Z Shastri, A Teneback, C Lorberbaum, JP Lomarev, MP Vincent, DJ George, MS TI BOLD fMRI response to direct stimulation (transcranial magnetic stimulation) of the motor cortex shows no decline with age SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE transcranial magnetic stimulation; motor cortex; fMRI; blood flow; imaging; aging ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; HEMODYNAMIC-RESPONSE; NEURAL ACTIVITY; FUNCTIONAL MRI; BRAIN; METABOLISM; OXYGEN; TMS; PET AB Previous studies using BOLD fMRI to examine age-related changes in cortical activation used tasks that relied on peripheral systems to activate the brain. They were unable to distinguish between alterations due to age-related changes in the periphery and actual changes in cortical physiology. Transcranial magnetic stimulation (TMS), which allows direct, non-invasive stimulation of cortical neurons, was interleaved with BOLD fMRI to study 6 young and 5 old subjects. Three different tasks were compared: direct stimulation by TMS, indirect active stimulation produced by a motor task, and indirect passive stimulation produced by hearing the TMS coil discharge. Direct neuronal stimulation by TMS produced similar fMRI signal increases in both groups, suggesting that cortical physiology itself may not necessarily decline with age. C1 Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurobiol, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP George, MS (reprint author), Med Univ S Carolina, Dept Radiol, 171 Ashley Ave, Charleston, SC 29425 USA. FU NIAAA NIH HHS [AA10761-03] NR 39 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD MAY PY 2003 VL 110 IS 5 BP 495 EP 507 DI 10.1007/s00702-002-0804-6 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 675UW UT WOS:000182715400005 PM 12721811 ER PT J AU Nelson, AL Algon, SA Munasinghe, J Graves, O Goumnerova, L Burstein, D Pomeroy, SL Kim, JYH AF Nelson, AL Algon, SA Munasinghe, J Graves, O Goumnerova, L Burstein, D Pomeroy, SL Kim, JYH TI Magnetic resonance imaging of patched heterozygous and xenografted mouse brain tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brain tumor; medulloblastoma; mouse; MRI; patched; xenograft ID ANIMAL-MODEL; MEDULLOBLASTOMA; MRI; GLIOMA AB Experimental mouse models are emerging as useful systems for the study of human brain tumors. Nuclear magnetic resonance imaging (MRI) methods can noninvasively provide images of complex heterogeneous tissues such as experimental brain tumors. The current report demonstrates the feasibility of longitudinal high-resolution MRI in two mouse brain tumor models: patched heterozygous (ptc+/-) mice with spontaneously arising posterior fossa tumors that resemble human medulloblastoma, and homozygous nude mice implanted with intracerebral xenografts of human medulloblastoma cell lines. Methods were optimized to achieve favorable volumetric comparison with histologic methods and sub-millimeter resolution, improved by contrast enhancement with intravenous administration of a gadolinium-based agent. Results also show that experimental mice, even symptomatic mice, tolerate repeated serial imaging studies over weeks to months to follow tumor progression and to visualize placement of an intracerebral drug delivery system. C1 Childrens Hosp, Div Neurol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kim, JYH (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS35701, NS043517-01] NR 14 TC 18 Z9 19 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2003 VL 62 IS 3 BP 259 EP 267 DI 10.1023/A:1023339902812 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 668QF UT WOS:000182304100005 PM 12777077 ER PT J AU Kim, HA Zhang, D Mak, SK Stiles, CD AF Kim, HA Zhang, D Mak, SK Stiles, CD TI Conversation with the Schwann cell: growth factor signaling between axons and the myelinating glial cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 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 MAY PY 2003 VL 85 SU 1 BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800109 ER PT J AU Basilion, JP AF Basilion, JP TI Molecular imaging of transgene and endogenous gene expression SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 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 MAY PY 2003 VL 85 SU 1 BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800211 ER PT J AU Redwine, JM Kosofsky, BE Jacobs, RE Games, D Reilly, JF Morrison, JH Young, WG Bloom, FE AF Redwine, JM Kosofsky, BE Jacobs, RE Games, D Reilly, JF Morrison, JH Young, WG Bloom, FE TI Hippocampal volume reduction precedes plaque formation in a PDAPP mouse model of Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Neurome Inc, La Jolla, CA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. CALTECH, Pasadena, CA 91125 USA. Elan Pharmaceut, San Francisco, CA USA. Mt Sinai Sch Med, New York, NY USA. Scripps Res Inst, La Jolla, CA USA. RI Morrison, John/F-9229-2012 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 MAY PY 2003 VL 85 SU 1 BP 59 EP 59 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800208 ER PT J AU Bakalkin, G Yakovleva, T Usynin, I Pasikova, N Marinova, Z Cebers, G Gileva, I Matskevich, A Nikoshkov, A Haroutunian, V Hauser, KF Hurd, YL Terenius, L AF Bakalkin, G Yakovleva, T Usynin, I Pasikova, N Marinova, Z Cebers, G Gileva, I Matskevich, A Nikoshkov, A Haroutunian, V Hauser, KF Hurd, YL Terenius, L TI Biogenesis and secretion of dynorphins are regulated by the Ubiquitin Proteasome system: implications for Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Bronx Vet Adm Med Ctr, Bronx, NY USA. Univ Kentucky, Dept Anat, Lexington, KY 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 MAY PY 2003 VL 85 SU 1 BP 61 EP 61 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800217 ER PT J AU Rowitch, D Sun, T Ligon, K Hafler, B Lu, R Alberta, J Stiles, C AF Rowitch, D Sun, T Ligon, K Hafler, B Lu, R Alberta, J Stiles, C TI Olig2 regulation and function during CNS development and tumorigenesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 34th Annual Meeting of the American-Society-for-Neurochemistry CY MAY 03-07, 2003 CL NEWPORT BEACH, CALIFORNIA SP Amer Soc Neurochem C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 MAY PY 2003 VL 85 SU 1 BP 66 EP 66 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 677VJ UT WOS:000182828800234 ER PT J AU Dunah, AW Standaert, DG AF Dunah, AW Standaert, DG TI Subcellular segregation of distinct heteromeric NMDA glutamate receptors in the striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE biochemical fractionation; co-immunoprecipitation; glutamate receptor; NMDA receptor; striatum; subcellular compartment ID D-ASPARTATE RECEPTORS; PROTEIN-KINASE-C; RAT-BRAIN; SUBUNIT COMPOSITION; SURFACE EXPRESSION; POSTSYNAPTIC DENSITY; BIOCHEMICAL-EVIDENCE; REGIONAL EXPRESSION; NERVOUS-SYSTEM; AMPA RECEPTORS AB Functional N -methyl-d-aspartate (NMDA) glutamate receptors are composed of heteromeric complexes of NR1, the obligatory subunit for channel activity, and NR2 or NR3 family members, which confer variability in the properties of the receptors. Recent studies have provided evidence for the existence of both binary (containing NR1 and either NR2A or NR2B) and ternary (containing NR1, NR2A, and NR2B) receptor complexes in the adult mammalian brain. However, the mechanisms regulating subunit assembly and receptor localization are not well understood. In the CNS, NMDA subunits are present both at intracellular sites and the post-synaptic membrane of neurons. Using biochemical protein fractionation and co-immunoprecipitation approaches we have found that in rat striatum binary NMDA receptors are widely distributed, and can be identified in the light membrane, synaptosomal membrane, and synaptic vesicle-enriched subcellular compartments. In contrast, ternary receptors are found exclusively in the synaptosomal membranes. When striatal proteins are chemically cross-linked prior to subcellular fractionation, ternary NMDA receptors can be precipitated from the light membrane and synaptic vesicle-enriched fractions where this type of receptor complex is not detectable under normal conditions. These findings suggest differential targeting of distinct types of NMDA receptor assemblies between intracellular and post-synaptic sites based on subunit composition. This targeting may underlie important differences in the regulation of the transport pathways involved in both normal as well as pathological receptor functions. C1 Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA USA. RP Standaert, DG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Ctr Aging Genet & Neurodegenerat, B114-2004,114 16th St, Charlestown, MA 02129 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS 34361] NR 44 TC 60 Z9 60 U1 0 U2 6 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 MAY PY 2003 VL 85 IS 4 BP 935 EP 943 DI 10.1046/j.1471-4159.2003.01744.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 671QW UT WOS:000182476400011 PM 12716425 ER PT J AU Ligon, KL Alberto, JA Kwaan, M Louis, DN Stiles, CD Rowitch, DH AF Ligon, KL Alberto, JA Kwaan, M Louis, DN Stiles, CD Rowitch, DH TI OLIG2 is a general marker of gliomas. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 79th Annual Meeting of the American-Association-of-Neuropathologists CY JUN 19-22, 2003 CL ORLANDO, FLORIDA SP Amer Assoc Neuropatholgists C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2003 VL 62 IS 5 MA 26 BP 544 EP 544 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 680CQ UT WOS:000182959100037 ER PT J AU Hartung, D Petrov, A Kolodgie, F Narula, N Haider, N Gold, HK Vanderheyden, JL Virmani, R Narula, J AF Hartung, D Petrov, A Kolodgie, F Narula, N Haider, N Gold, HK Vanderheyden, JL Virmani, R Narula, J TI Preventing apoptosis should constitute the basis of management of atherosclerosis: Pan-caspase inhibitor simulate the effects of diet withdrawal and statin therapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Univ Penn, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Theseus Imaging Corp, Worcester, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1 BP 1P EP 1P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600002 ER PT J AU Van den Abbeele, AD Badawi, RD Tetrault, RJ Cliche, JP Manola, J Spangler, T Janicek, MJ Israel, DA Heinrich, MC Silberman, SS Dimitrijevic, S Demetri, GD AF Van den Abbeele, AD Badawi, RD Tetrault, RJ Cliche, JP Manola, J Spangler, T Janicek, MJ Israel, DA Heinrich, MC Silberman, SS Dimitrijevic, S Demetri, GD TI FDG-PET as a surrogate marker for response to Gleevec (TM) (imatinib mesylate) in patients with advanced gastrointestinal stromal tumors (GIST). SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Oshawa Nucl Med Clin, Oshawa, ON, Canada. Cape Cod Hosp, Hyannis, MA USA. Oregon Hlth Sci Univ, Inst Canc, Portland, OR 97201 USA. Novartis Oncol, Clin Res Oncol, Basel, Switzerland. Novartis Oncol, Clin Res Oncol, E Hanover, NJ USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 7 Z9 7 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 77 BP 24P EP 25P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600078 ER PT J AU El Fakhri, G Holdsworth, CH Badawi, RD Santos, PA Kijewski, MF Van den Abbeele, AD Moore, SC AF El Fakhri, G Holdsworth, CH Badawi, RD Santos, PA Kijewski, MF Van den Abbeele, AD Moore, SC TI Dependence of whole-body-FDG-PET lesion detection and activity estimation performance on patient size, randoms variance reduction, and acquisition geometry. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 MAY PY 2003 VL 44 IS 5 SU S MA 197 BP 61P EP 61P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600198 ER PT J AU Bonab, AA Alpert, NM Livni, E Dragotakes, SD Spencer, TJ Dougherty, DD Fischman, AJ AF Bonab, AA Alpert, NM Livni, E Dragotakes, SD Spencer, TJ Dougherty, DD Fischman, AJ TI Dopamine transporter density in patients with attention deficit hyperactivity disorder (ADHD) measured by PET with C-11-Atropane. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 217 BP 67P EP 67P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600218 ER PT J AU Rajendran, JG Meyer, J Schwartz, DL Kinahan, PE Cheng, PM Hummell, SM Phillips, M Krohn, KA AF Rajendran, JG Meyer, J Schwartz, DL Kinahan, PE Cheng, PM Hummell, SM Phillips, M Krohn, KA TI PET imaging with [F-18]FMISO permits hypoxia directed radiotherapy dose escalation in head and neck cancer. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 415 BP 127P EP 128P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600416 ER PT J AU Shoup, TM Elmaleh, DR Syed, S Martyn, S Fischman, AJ AF Shoup, TM Elmaleh, DR Syed, S Martyn, S Fischman, AJ TI Synthesis and biological evaluation of a new series of F-18-labeled modified fatty acids for detecting heart disease by PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 502 BP 154P EP 154P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600503 ER PT J AU Dougherty, DD Deckersbach, T Rauch, SL Fava, M Fischman, AJ AF Dougherty, DD Deckersbach, T Rauch, SL Fava, M Fischman, AJ TI PET studies of anger attacks in depressed patients with and without anger attacks SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 894 BP 248P EP 248P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600811 ER PT J AU El Fakhri, G Zimmerman, RE Kijewski, MF Moore, SC Maksud, P Fischman, AJ AF El Fakhri, G Zimmerman, RE Kijewski, MF Moore, SC Maksud, P Fischman, AJ TI Tc-99m/I-123 dynamic brain SPECT for simultaneous assessment of perfusion and dopamine transporter density: Feasibility of scatter, cross-talk and high-energy contamination correction in primates. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Hop La Pitie Salpetriere, INSERM, U494, Paris, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 973 BP 271P EP 271P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600890 ER PT J AU Fischman, AJ Bonab, AA Alpert, NM Elahi, D Tonpkins, RG AF Fischman, AJ Bonab, AA Alpert, NM Elahi, D Tonpkins, RG TI Adaptation of a Concord P4 microPET device for "small-parts", imaging in humans. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1012 BP 282P EP 282P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600929 ER PT J AU Smith, CJ Sieckman, GL Owen, NK Atkinson, LA Volkert, WA Hoffman, TJ AF Smith, CJ Sieckman, GL Owen, NK Atkinson, LA Volkert, WA Hoffman, TJ TI Design and development of Tc-99m-carbonyl-Bombesin analogs: A structure activity relationship study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Univ Missouri, Columbia, MO 65211 USA. US Dept Vet Affairs, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1066 BP 298P EP 298P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729600983 ER PT J AU Pellegrino, D Bonab, AA Carter, EA Syed, S Martyn, SF Fischman, AJ AF Pellegrino, D Bonab, AA Carter, EA Syed, S Martyn, SF Fischman, AJ TI Comparison of the localization properties of F-18- and In-111-labeled leukocytes in a rat model of focal infection: A microPET study. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 MAY PY 2003 VL 44 IS 5 SU S MA 1109 BP 310P EP 310P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601026 ER PT J AU Bonab, AA Weise, SW Syed, SZ Martyn, FS Carter, EA Fischman, AJ AF Bonab, AA Weise, SW Syed, SZ Martyn, FS Carter, EA Fischman, AJ TI Monitoring treatment with a CDK2 inhibitor by microPET with F-18-FLT in a nude mouse tumor model. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1313 BP 368P EP 368P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601230 ER PT J AU Rajendran, JG Ng, P Peterson, LM Schwartz, DL Scharnhorst, J Conrad, EU Grierson, JR Krohn, KA AF Rajendran, JG Ng, P Peterson, LM Schwartz, DL Scharnhorst, J Conrad, EU Grierson, JR Krohn, KA TI F-18 FMISO PET tumor hypoxia imaging: Investigating the tumor volume-hypoxia connection. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Orthoped, Seattle, WA 98195 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1340 BP 376P EP 376P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601257 ER PT J AU Charania, M Aquino, S Fischman, A AF Charania, M Aquino, S Fischman, A TI Clinical impact of whole-body vs. Thoracic PET for staging patients with lung cancer. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract CT 50th Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 21-25, 2003 CL NEW ORLEANS, LOUISIANA SP Soc Nucl Med C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Joint Program Nucl Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 SU S MA 1396 BP 392P EP 392P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 676AK UT WOS:000182729601313 ER PT J AU Donohoe, KJ Frey, KA Gerbaudo, VH Mariani, G Nagel, JS Shulkin, B AF Donohoe, KJ Frey, KA Gerbaudo, VH Mariani, G Nagel, JS Shulkin, B TI Procedure guideline for brain death scintigraphy SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE procedure guideline; scintigraphy; brain death C1 Beth Israel Deaconess Med Ctr, Dept Nucl Med, Boston, MA 02215 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Pisa, Sch Med, I-56100 Pisa, Italy. VA Boston Healthcare Syst, W Roxbury, MA USA. RP Donohoe, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Nucl Med, 330 Brookline Ave, Boston, MA 02215 USA. NR 0 TC 27 Z9 29 U1 0 U2 0 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 MAY PY 2003 VL 44 IS 5 BP 846 EP 851 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 675XZ UT WOS:000182724000030 PM 12732688 ER PT J AU August, M Faquin, W Troulis, M Kaban, L AF August, M Faquin, W Troulis, M Kaban, L TI Clear cell odontogenic carcinoma: Evaluation of reported cases SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID LYMPH-NODE METASTASIS; TUMORS; AMELOBLASTOMA; PULMONARY AB Purpose: We present the cases of 4 patients with clear cell odontogenic carcinoma and a contrasting case of a patient with a calcifying epithelial odontogenic tumor from Massachusetts General Hospital. Differential diagnosis, distinguishing characteristics, and data from 32 cases in the literature are also reported. Because this rare tumor behaves aggressively with both regional and distant spread, a better understanding of its biologic behavior is imperative. Patients and Methods: The 4 patients with clear cell odontogenic carcinoma were women and had an average age of 65 years (range, 40 to 77 years). Three tumors were in the posterior mandible and I was in the maxilla. Three patients complained of pain; bony expansion and tooth mobility were noted in isolated cases. A comparison is made with other reported cases, and factors associated with recurrence and survival are presented. Results: All patients were treated with resection, and 1 patient received postoperative radiotherapy. Two patients with positive surgical margins underwent further resection. All patients have been followed an average of 2 years (range, 0.5 to 4 years) and presently have no evident disease. Conclusions: Recognition of this unusual tumor and differentiating it from other clear cell neoplasms is critical in developing an appropriate treatment plan. Management should include wide en bloc resection and long-term follow-up. (C) 2003 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP August, M (reprint author), Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Warren 1201,55 Fruit St, Boston, MA 02114 USA. FU PHS HHS [K-231200209103] NR 21 TC 11 Z9 12 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD MAY PY 2003 VL 61 IS 5 BP 580 EP 586 DI 10.1053/joms.2003.50114 PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 675AB UT WOS:000182669800008 PM 12730837 ER PT J AU Wang, M Hays, T Balasa, V Bagatell, R Gruppo, R Grabowski, EF Valentino, LA Tsao-Wu, G Manco-Johnson, MJ AF Wang, M Hays, T Balasa, V Bagatell, R Gruppo, R Grabowski, EF Valentino, LA Tsao-Wu, G Manco-Johnson, MJ CA Pediat Coagulation Consortium TI Low-dose tissue plasminogen activator thrombolysis in children SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE arterial and venous thrombosis; post-thrombotic syndrome; thrombolysis in children; tissue plasminogen activator ID VENOUS THROMBOEMBOLIC COMPLICATIONS; FEMORAL-ARTERY THROMBOSIS; CARDIAC-CATHETERIZATION; ALTEPLASE TREATMENT; CANADIAN REGISTRY; THERAPY; HEPARIN; INFANTS; ADJUNCT; DISEASE AB Purpose: To compare results of low-dose tissue plasminogen activator (TPA) in children with arterial and venous thrombi relative to standard published dosing. Methods: Subjects consisted of all consecutive children with objectively confirmed thrombi for whom TPA thrombolysis was clinically ordered by the authors. Initial dosing used published standard dose (0.1-0.5 mg/kg per hour). With experience, a low-dose regimen (0.01-0.06 mg/kg per hour) was given in an attempt to derive a minimal effective dose. Results: Thirty-five children were treated with TPA. Either standard or low-dose infusions of TPA resulted in complete thrombolysis of 28 of 29 (97%) acute thrombi, while all 6 chronic thrombi had a partial response. In contrast to the recommended adult-derived dosages of 0.1 to 0.5 mg/kg per hour, the authors found that initial doses of less than 0.01 mg/kg per hour were effective in 12 of 17 patients with acute thrombosis. Neonates required 0.06 mg/kg per hour. Route of administration (local or systemic) did not affect efficacy. Major bleeding occurred in only one extremely preterm infant. Minor bleeding, primarily oozing at intravenous sites. occurred in 27% of children during TPA infusions. Prophylactic unfractionated or low-molecular-weight heparin was infused concomitant with TPA in 42% of the children and did not increase the risk of bleeding. Conclusions: TPA in very low doses appears to be safe and effective for thrombolysis of acute thromboses in most children, given appropriate patient selection. C1 Childrens Hosp, Dept Pediat, Denver, CO 80218 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Arizona, Tucson, AZ USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rush Childrens Hosp, Chicago, IL USA. Alaska Ctr Pediat, Anchorage, AK USA. RP Manco-Johnson, MJ (reprint author), Univ Colorado, Hlth Sci Ctr, Mt States Reg Hemophilia & Thrombosis Ctr, POB 6507,MS F416, Aurora, CO 80045 USA. NR 28 TC 79 Z9 79 U1 0 U2 1 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 MAY PY 2003 VL 25 IS 5 BP 379 EP 386 DI 10.1097/00043426-200305000-00006 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 677KC UT WOS:000182805300006 PM 12759624 ER PT J AU Sundgren, NC Giraud, GD Stork, PJS Maylie, JG Thornburg, KL AF Sundgren, NC Giraud, GD Stork, PJS Maylie, JG Thornburg, KL TI Angiotensin II stimulates hyperplasia but not hypertrophy in immature ovine cardiomyocytes SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID LEFT-VENTRICULAR HYPERTROPHY; CONVERTING ENZYME-INHIBITION; MYOCARDIAL-CELL HYPERTROPHY; INDUCED CARDIAC-HYPERTROPHY; EXPERIMENTAL HEART-FAILURE; ACTIVATED PROTEIN-KINASES; INDUCED GROWTH-RESPONSES; ADULT-RAT HEARTS; IN-VITRO; NEONATAL RAT AB Rat and sheep cardiac myocytes become binucleate as they complete the 'terminal differentiation' process soon after birth and are not able to divide thereafter. Angiotensin II (Ang II) is known to stimulate hypertrophic changes in rodent cardiomyocytes under both in vivo and in vitro conditions via the AT, receptor and intracellular extracellular regulated kinase (ERK) signalling cascade. We sought to develop culture methods for immature sheep cardiomyocytes in order to test the hypothesis that Ang II is a hypertrophic agent in the immature myocardium of the sheep. We isolated fetal sheep cardiomyocytes and cultured them for 96 h, added Ang II and phenylephrine (PE) for 48 h, and measured footprint area and proliferation (5-bromo-2'-deoxyuridine (BrdU) uptake) separately in mono- vs. binucleate myocytes. We found that neither Ang II nor PE changed the footprint area of mononucleated cells. PE stimulated an increase in footprint area of binucleate cells but Ang II did not. Ang II increased myocyte BrdU uptake compared to serum free conditions, but PE did not affect BrdU uptake. The MAP kinase kinase (MEK) inhibitor UO126 prevented BrdU uptake in Ang II-stimulated cells and prevented cell hypertrophy in PE-stimulated cells. This paper establishes culture methods for immature sheep cardiomyocytes and reports that: (1) Ang II is not a hypertrophic agent; (2) Ang II stimulates hyperplastic growth among mononucleate myocytes; (3) PE is a hypertrophic agent in binucleate myocytes; and (4) the ERK cascade is required for the proliferation effect of Ang H and the hypertrophic effect of PE. C1 Oregon Hlth Sci Univ, Sch Med, Heart Res Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Dept Physiol Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Dept Med Cardiol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Vollum Inst Adv Biomed Res, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Sch Med, Dept Obstet & Gynecol, Portland, OR 97239 USA. RP Thornburg, KL (reprint author), Oregon Hlth Sci Univ, Sch Med, Heart Res Ctr, L464, Portland, OR 97239 USA. FU NICHD NIH HHS [P01 HD034430, 2P01 HD34430] NR 67 TC 56 Z9 59 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD MAY 1 PY 2003 VL 548 IS 3 BP 881 EP 891 DI 10.1113/jphysiol.2003.038778 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VR UT WOS:000183571600024 PM 12626668 ER PT J AU Simon, NM Smoller, JW Fava, M Sachs, G Racette, SR Perlis, R Sonawalla, S Rosenbaum, JF AF Simon, NM Smoller, JW Fava, M Sachs, G Racette, SR Perlis, R Sonawalla, S Rosenbaum, JF TI Comparing anxiety disorders and anxiety-related traits in bipolar disorder and unipolar depression SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE bipolar; major depression; panic; generalized anxiety; comorbidity; neuroticism; anxiety sensitivity ID NATIONAL-COMORBIDITY-SURVEY; PANIC DISORDER; MAJOR DEPRESSION; I-DISORDER; PERSONALITY-TRAITS; PSYCHIATRIC-DISORDERS; GENERAL-POPULATION; UNITED-STATES; PREVALENCE; LIFETIME AB The frequent comorbidity of anxiety disorders and mood disorders has been documented in previous studies. However, it remains unclear whether specific anxiety traits or disorders are more closely associated with unipolar major depression (MDD) or bipolar disorder (BPD). We sought to examine whether MDD and BPD can be distinguished by their association with specific types of anxiety comorbidity. Individuals with a primary lifetime diagnosis of either bipolar disorder (N = 122) or major depressive disorder (N = 114) received diagnostic assessments of anxiety disorder comorbidity, and completed questionnaires assessing anxiety sensitivity and neuroticism. The differential association of these anxiety phenotypes with MDD versus BPD was examined with multivariate modeling. Panic disorder and generalized anxiety disorder (GAD) specifically emerged amongst all the anxiety disorders as significantly more common in patients with BPD than MDD. After controlling for current mood state, anxiety sensitivity and neuroticism did not differ by mood disorder type. This study supports prior research suggesting a specific panic disorder-bipolar disorder connection, and suggests GAD may also be differentially associated with BPD. Further research is needed to clarify the etiologic basis of anxiety disorder/BPD comorbidity and to optimize treatment strategies for patients with these co-occurring disorders. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, WACC 815, Boston, MA 02114 USA. RP Simon, NM (reprint author), Massachusetts Gen Hosp, WACC 815, 15 Parkman St, Boston, MA 02114 USA. NR 41 TC 80 Z9 81 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0022-3956 J9 J PSYCHIAT RES JI J. Psychiatr. Res. PD MAY-JUN PY 2003 VL 37 IS 3 BP 187 EP 192 DI 10.1016/S0022-3956(03)00021-9 PG 6 WC Psychiatry SC Psychiatry GA 664YG UT WOS:000182092000002 PM 12650739 ER PT J AU Taub, E Uswatte, G AF Taub, E Uswatte, G TI Constraint-induced movement therapy: Bridging from the primate laboratory to the stroke rehabilitation laboratory SO JOURNAL OF REHABILITATION MEDICINE LA English DT Article DE rehabilitation; physical therapy; cortical reorganization; learned nonuse; stroke; neurological injury ID MYOGRAPHIC BIOFEEDBACK APPLICATIONS; MOTOR CORTEX PLASTICITY; UPPER EXTREMITY; CORTICAL REORGANIZATION; FORCED-USE; PHYSICAL REHABILITATION; CEREBRAL-PALSY; OWL MONKEYS; RECOVERY; ARM AB In this laboratory we have developed a set of techniques that randomized controlled studies indicate can substantially reduce the motor deficit of patients with mild to moderately severe chronic strokes. The techniques, termed Constraint-Induced Movement therapy (CI therapy), involve motor restriction of the less-affected arm while at the same time intensively training the more-affected arm. The intervention was derived directly from basic research with monkeys. The primary difference between Cl therapy and conventional physical therapy is in the duration and intensity of the treatment. The greatly improved extremity function produced in the laboratory transfers to the activities of daily living outside the clinic. Treatment gains persisted for the two years tested. Converging data from seven experiments has shown that CI therapy produces massive alterations in brain organization and function correlated with the large improvements in motor ability that it produces. C1 Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Taub, E (reprint author), Univ Alabama, Dept Psychol, CPM 712,1530 3rd Ave S, Birmingham, AL 35294 USA. EM Etaub@uab.edu RI Uswatte, Gitendra/C-4913-2009 NR 71 TC 3 Z9 5 U1 0 U2 1 PU FOUNDATION REHABILITATION INFORMATION PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 1650-1977 J9 J REHABIL MED JI J. Rehabil. Med. PD MAY PY 2003 VL 35 SU 41 BP 34 EP 40 DI 10.1080/16501960310010124 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 686TD UT WOS:000183336300007 ER PT J AU Hatzakis, M Haselkorn, J Williams, R Turner, A Nichol, P AF Hatzakis, M Haselkorn, J Williams, R Turner, A Nichol, P TI Telemedicine and the delivery of health services to veterans with multiple sclerosis SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE cost-benefit analysis; health services; MS; multiple sclerosis; review; telemedicine; translation; veterans ID COLUMBIA-UNIVERSITY INFORMATICS; SPINAL-CORD INJURY; PARKINSONS-DISEASE; DIABETES EDUCATION; IDEATEL PROJECT; DEPRESSION; PRESSURE; PATIENT; TELEDERMATOLOGY; CONSULTATIONS AB Telemedicine involves the provision of health care and sharing of medical knowledge using telecommunications technologies. Preventive, diagnostic, and therapeutic services, as well as patient education and assistance with self-management of health, can be provided via telemedicine. The Veterans Health Administration (VHA) has a wide range of telemedicine capabilities. Given limitations on studying its effectiveness, telemedicine is often applied to new patient populations without explicit evaluation of efficacy. Evaluating the potential use of telemedicine services through supporting literature from other disorders may be possible. This paper discusses applying telemedicine to the care of individuals with multiple sclerosis (MS) when few published evaluations exist in MS. In this paper, we (1) provide a background on the use of telemedicine in the private sector and in the VHA, (2) discuss the use of current telemedicine literature to management of individuals with MS, and (3) review the strengths and limitations of telemedicine as a care delivery vehicle. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Rehabil Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. RP Hatzakis, M (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. OI Turner, Aaron/0000-0001-6897-8003 NR 56 TC 20 Z9 20 U1 2 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD MAY-JUN PY 2003 VL 40 IS 3 BP 265 EP 282 PG 18 WC Rehabilitation SC Rehabilitation GA 687KE UT WOS:000183374800008 PM 14582530 ER PT J AU Shito, M Tilles, AW Tompkins, RG Yarmush, ML Toner, M AF Shito, M Tilles, AW Tompkins, RG Yarmush, ML Toner, M TI Efficacy of an extracorporeal flat-plate bioartificial liver in treating fulminant hepatic failure SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE hepatocyte; bioartificial liver; bioreactor; animal model; liver failure; D-galactosamine ID PORCINE ENDOGENOUS RETROVIRUS; IN-VIVO EVALUATION; RAT HEPATOCYTES; ASSIST DEVICE; OXYGEN-TRANSPORT; SUPPORT SYSTEM; HUMAN-CELLS; BIOREACTOR; VIABILITY; VITRO AB Background. Fulminant hepatic failure is associated with a high mortality rate. Orthotopic liver transplantation is the only established treatment for patients who do not respond to medical management. A major limitation of this treatment is a shortage of donor organs, resulting in many patients dying while waiting for a transplant. An extracorporeal bioartificial liver (BAL) has the potential to provide temporary support for patients with fulminant hepatic failure (FHF) and for patients awaiting orthotopic liver transplantation. We developed a flat-plate BAL with an internal membrane oxygenator in which porcine hepatocytes were cultured as a monolayer. Materials and methods. Twenty-four hours after cannulation of the left carotid artery and right jugular vein, FHF was induced in rats by administering 2 intraperitoneal injections of D-galactosamine (GaIN) (1.2 g/kg) at a 12-h interval. The rats were connected to a BAL device 24 h after the first GaIN injection and underwent extracorporeal perfusion for a duration of 10 h. Liver histology, liver-specific markers, and animal survival up to 168 h (7 days) were examined. Results. Histologically, liver damage was reduced in the animal group treated with the hepatocyte-based BAL device. Significant reductions occurred in the plasma ammonia levels and prothrombin times in the group treated with the seeded BAL device. Animal survival in the group treated with the seeded BAL device was significantly higher (50.0%) than in the control animal group treated with an unseeded BAL device (11.1%). Conclusions. This flat-plate BAL with an internal membrane oxygenator and cultured porcine hepatocytes has yielded encouraging results in the treatment of rats with GaIN-induced FHF. (C) 2003 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Shriners Hosp Children, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Bigelow 1401,55 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK43371]; NIGMS NIH HHS [5T32GM07035-26] NR 44 TC 28 Z9 30 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD MAY 1 PY 2003 VL 111 IS 1 BP 53 EP 62 DI 10.1016/S0022-4804(03)00048-9 PG 10 WC Surgery SC Surgery GA 699BQ UT WOS:000184036400008 PM 12842448 ER PT J AU Shera, CA Guinan, JJ AF Shera, CA Guinan, JJ TI Stimulus-frequency-emission group delay: A test of coherent reflection filtering and a window on cochlear tuning SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; EVOKED OTOACOUSTIC EMISSIONS; GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; MIDDLE-EAR; RESPONSES; MECHANICS; MODEL; ORIGIN; PHASE AB This paper tests and applies a key prediction of the theory of coherent reflection filtering for the generation of reflection-source otoacoustic emissions. The theory predicts that reflection-source-emission group delay is determined by the group delay of the basilar-membrane (BM) transfer function at its peak. This prediction is tested over a seven-octave frequency range in cats and guinea pigs using measurements of stimulus-frequency-emission (SFOAE) group delay. A comparison with group delays calculated from published measurements of BM mechanical transfer functions supports the theory at the basal end of the cochlea. A comparison across the whole frequency range based on variations in the sharpness of neural tuning with characteristic frequency (CF) suggests that the predicted relation holds in the basal-most 60% of the cochlea. At the apical end of the cochlea, however, the measurements disagree with neural and mechanical group delays. This disagreement suggests that there are important differences in cochlear mechanics and/or mechanisms of emission generation between the base and apex of the cochlea. Measurements in humans over a four-octave range indicate that human SFOAE group delays are roughly a factor of 3 longer than their counterparts in cat and guinea pig but manifest similar trends across CF. The measurements thus reveal global deviations from scaling whose form appears quantitatively similar in all three species. Interpreted using the theory of coherent reflection filtering, the group delay measurements indicate that the wavelength at the peak of the traveling wave decreases with increasing CF at a rate of roughly 25% per octave in the base of the cochlea. The measurements and analysis reported here illustrate the rich potential inherent in OAE measurements for obtaining valuable information about basic cochlear properties such as tuning. (C) 2003 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [DC00235, DC03687, R01 DC003687] NR 72 TC 120 Z9 124 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2003 VL 113 IS 5 BP 2762 EP 2772 DI 10.1121/1.1557211 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 676LA UT WOS:000182752500039 PM 12765394 ER PT J AU Hicks, SP Swindells, KJ Middelkamp-Hup, MA Sifakis, MA Gonzalez, E Gonzalez, S AF Hicks, SP Swindells, KJ Middelkamp-Hup, MA Sifakis, MA Gonzalez, E Gonzalez, S TI Confocal histopathology of irritant contact dermatitis in vivo and the impact of skin color (black vs white) SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID SCANNING LASER MICROSCOPY; IN-VIVO; WATER-LOSS; HISTOLOGY; PHYSIOLOGY; DISEASE AB Background: The pathogenesis of irritant contact dermatitis and its modulation according to skin color is not well understood. Reflectance confocal microscopy (RCM) enables high-resolution, real-time, in-vivo imaging of human skin. Objective: The goal of our study was to use RCM to determine whether susceptibility to irritant contact dermatitis differs between black and white skin. Methods: Participants were placed in groups on the basis of skin color and the volar aspects of their forearnis exposed to 1% and 4% sodium lauryl sulfate using Finn Chambers (Allerderm Laboratories Inc, Petaluma, Calif). They were evaluated at 6, 24, and 48 hours by RCM, transepidermal water loss, laser Doppler velocimetry, and routine histology. Results: Participants with white skin had more severe clinical reactions than those with black skin. RCM revealed microscopic changes even without clinical evidence of irritation. Confocal features included parakeratosis, spongiosis, perivascular inflammatory infiltrate, and microvesicle formation, and these features were confirmed by routine histology. Also, participants with white skin had greater mean increases in transepidermal water loss after exposure to 4% sodium lauryl sulfate than did participants with black skin. Conclusion: In-vivo RCM can track early pathophysiologic events revealing differences between black and white skin during the development of irritant contact dermatitis, and may support the theory that those with black skin are more resistant to irritants. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Contact Dermatitis Unit, Boston, MA 02114 USA. RP Gonzalez, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Bartlett Hall 814, Boston, MA 02114 USA. FU NIOSH CDC HHS [R01 OH04029] NR 24 TC 28 Z9 33 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2003 VL 48 IS 5 BP 727 EP 734 DI 10.1067/mjd.2003.220 PG 8 WC Dermatology SC Dermatology GA 680KT UT WOS:000182977200011 PM 12734502 ER PT J AU Lindenberger, EC Landefeld, CS Sands, LP Counsell, SR Fortinsky, RH Palmer, RM Kresevic, DM Covinsky, KE AF Lindenberger, EC Landefeld, CS Sands, LP Counsell, SR Fortinsky, RH Palmer, RM Kresevic, DM Covinsky, KE TI Unsteadiness reported by older hospitalized patients predicts functional decline SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society CY MAY, 2002 CL WASHINGTON, D.C. SP Amer Geriatr Soc DE aged; hospitalization; activities of daily living; equilibrium; physical fitness ID ACUTE MEDICAL ILLNESS; PHYSICAL PERFORMANCE; ADULTS; RISK; OUTCOMES; VALIDATION; DEPENDENCE; MORBIDITY; ADMISSION; DISCHARGE AB OBJECTIVES: To determine whether a simple question about steadiness at admission predicts in-hospital functional decline and whether unsteadiness at admission predicts failure of in-hospital functional recovery of patients who have declined immediately before hospitalization. DESIGN: Prospective cohort study. SETTING: One university hospital and one community teaching hospital. PARTICIPANTS: One thousand five hundred fifty-seven hospitalized medical patients aged 70 and older. MEASUREMENTS: On admission, patients reported their steadiness with walking and whether they could perform independently each of five basic activities of daily living (ADLs) at admission and 2 weeks before admission (baseline). For the primary analysis, the outcome was decline in ADL function between admission and discharge. For the secondary analysis, the outcome was in-hospital recovery to baseline ADL function in patients who experienced ADL decline in the 2 weeks before admission. RESULTS: In the primary cohort (n = 1,557), 25% of patients were very unsteady at admission; 22% of very unsteady patients declined during hospitalization, compared with 17%, 18%, and 10% for slightly unsteady, slightly steady, and very steady patients, respectively (P for trend = .001). After adjusting for age; medical comorbidities; Acute Physiology, Age, and Chronic Health Evaluation II score; and admission ADL, unsteadiness remained significantly associated with ADL decline (odds for decline for very unsteady compared with very steady = 2.6, 95% confidence interval = 1.5-4.5). In the secondary analysis, predicting ADL recovery in patients who declined before hospitalization (n = 563), 46% of patients were very unsteady at admission. In this cohort, 44% of very unsteady patients failed to recover, compared with 35%, 36%, and 33% for each successively higher level of steadiness, respectively (P for trend = 0.06). After multivariate adjustment, greater unsteadiness independently predicted failure of recovery (P for trend = 0.02). CONCLUSION: A simple question about steadiness identified patients at increased risk for in-hospital ADL decline and, in patients who lost ADL function immediately before admission, failure to recover. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA 94121 USA. Indiana Univ, Sch Med, Ctr Aging Res, Div Gen Internal Med & Geriatr, Indianapolis, IN 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. Univ Hosp Cleveland, Cleveland, OH 44106 USA. RP Lindenberger, EC (reprint author), San Francisco VA Med Ctr, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. RI Sands, Laura/E-8919-2015 OI Sands, Laura/0000-0003-2446-4486 FU AHRQ HHS [K02HS00006-01]; PHS HHS [T-32] NR 27 TC 15 Z9 17 U1 2 U2 2 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 MAY PY 2003 VL 51 IS 5 BP 621 EP 626 DI 10.1034/j.1600-0579.2003.00205.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 673JU UT WOS:000182577900005 PM 12752836 ER PT J AU Roman, GC AF Roman, GC TI Vascular dementia: Distinguishing characteristics, treatment, and prevention SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE vascular dementia; poststroke dementia; multi-infarct dementia; strategic stroke dementia; subcortical ischemia dementia ID EXECUTIVE COGNITIVE IMPAIRMENT; CENTRAL-NERVOUS-SYSTEM; WHITE-MATTER LESIONS; BASE-LINE FREQUENCY; ALZHEIMERS-DISEASE; POSTSTROKE DEMENTIA; ANTIHYPERTENSIVE TREATMENT; MULTIINFARCT DEMENTIA; PHYSICAL-DISABILITY; RISK-FACTORS AB Vascular dementia (VaD) is the second-most-common cause of dementia in the elderly, after Alzheimer's disease (AD). VaD is defined as loss of cognitive function resulting from ischemic, hypoperfusive, or hemorrhagic brain lesions due to cerebrovascular disease or cardiovascular pathology. Diagnosis requires the following criteria: cognitive loss, often predominantly subcortical; vascular brain lesions demonstrated by imaging; a temporal link between stroke and dementia; and exclusion of other causes of dementia. Poststroke VaD may be caused by large-vessel disease with multiple strokes (multiinfarct dementia) or by a single stroke (strategic stroke VaD). A common form is sub. cortical ischemic VaD caused by small-vessel occlusions with multiple lacunas and by hypoperfusive lesions resulting from stenosis of medullary arterioles, as in Binswanger's disease. Unlike with AD, in VaD, executive dysfunction is commonly seen, but memory impairment is mild or may not even be present. The cholinesterase inhibitors used for AD are also useful in VaD. Prevention strategies should focus on reduction of stroke and cardiovascular disease, with attention to control of risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and hyperhomocysteinemia. C1 Univ Texas, Hlth Sci Ctr, Sch Med, Dept Med,Div Neurol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, Sch Med, Dept Med,Div Neurol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 70 TC 82 Z9 85 U1 0 U2 10 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 MAY PY 2003 VL 51 IS 5 SU 2 BP S296 EP S304 DI 10.1046/j.1532-5415.5155.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 675WG UT WOS:000182720100003 PM 12801386 ER PT J AU Kramer, HJM Grodstein, F Stampfer, MJ Curhan, GC AF Kramer, HJM Grodstein, F Stampfer, MJ Curhan, GC TI Menopause and postmenopausal hormone use and risk of incident kidney stones SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID BONE LOSS; REPLACEMENT THERAPY; SURGICAL MENOPAUSE; NATURAL MENOPAUSE; LUMBAR SPINE; URIC-ACID; WOMEN; CALCIUM; ESTROGEN; REPRODUCIBILITY AB Menopause is associated with increased urinary calcium excretion, which could increase the risk for the development of calcium-containing kidney stones. However, it is unknown whether menopause and postmenopausal hormone (PMH) use are independent risk factors for incident kidney stone disease in women. Data from 91,731 female Nurses' Health Study participants who provided information on diet, menopause status, and kidney stone disease were used to examine the independent association between menopause and PMH use and risk of incident kidney stones. No association was found between menopause and incident kidney stones in age-adjusted (relative risk [RR], 1.07; 95% CI, 0.85 to 1.34) or multivariate models (RR, 1.12; 95% CI, 0.89 to 1.41). However, when the association between the type of menopause and risk of incident kidney stones was examined, surgical menopause was associated with an increased risk in both the age-adjusted (RR, 1.37; 95% CI, 1.05 to 1.77) and multivariate models (RR, 1.39; 95% CI, 1.07 to 1.81), whereas natural menopause was not. Compared with never-use, past or current PMH use (including duration of PMH use) was not associated with incident kidney stones among postmenopausal women. In conclusion, no association was found between menopause and PMH use and incident kidney stones. Surgical menopause, however, may be associated with an increased risk. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Loyola Univ, Med Ctr, Dept Epidemiol & Prevent Med, Chicago, IL 60611 USA. Loyola Univ, Med Ctr, Dept Nephrol, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. NR 30 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2003 VL 14 IS 5 BP 1272 EP 1277 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 671YL UT WOS:000182492900018 ER PT J AU O'Hare, AM Feinglass, J Sidawy, AN Bacchetti, P Rodriguez, RA Daley, J Khuri, S Henderson, WG Johansen, KL AF O'Hare, AM Feinglass, J Sidawy, AN Bacchetti, P Rodriguez, RA Daley, J Khuri, S Henderson, WG Johansen, KL TI Impact of renal insufficiency on short-term morbidity and mortality after lower extremity revascularization: Data from the Department of Veterans Affairs' National Surgical Quality Improvement Program SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PERIPHERAL VASCULAR-DISEASE; GLOMERULAR-FILTRATION RATE; CRITICAL LEG ISCHEMIA; INFRAINGUINAL BYPASS; SERUM CREATININE; LIMB SALVAGE; NONCARDIAC SURGERY; FAILURE; OUTCOMES; RECONSTRUCTION AB Few data are available on the impact of renal insufficiency on short-term operative outcomes after lower extremity surgical revascularization. We used prospectively collected data from the Department of Veterans Affairs' National Surgical Quality Improvement Program (NSQIP) to explore the association with renal dysfunction of adverse outcomes occurring within 30 d of lower extremity surgical revascularization in a cohort of all patients undergoing at least one lower extremity surgical revascularization from 1/1/94 to 9/30/01 (n = 18,217). Even moderate renal insufficiency (estimated GFR 30-59cc/min/1.73m(2)) was associated with an increased incidence of postoperative death (adjusted odds ratio (OR) 1.44, 95% confidence interval (0), 1.17 to 1.77, P = 0.001), cardiac arrest (OR 1.43, CI 1.09 to 1.88, P = 0.011), myocardial infarction (OR 1.68, 1.39 to 2.16, P < 0.001), unplanned intubation (OR 1.69, CI 1.39 to 2.07, P < 0.001) and prolonged intubation (OR 1.57, CI 1.28 to 1.94, P < 0.001) within 30 d of lower extremity revascularization. However, the incidence of wound infection and graft failure requiring return to the operating room did not appear to be substantially higher in this group. Our data also show that patients with renal insufficiency undergoing revascularization were more likely to require distal procedures and to present with limb-threatening infection compared to those with normal renal function. Efforts to improve pre-and post-operative care in patients with renal insufficiency undergoing lower extremity revascularization should take into account the increased incidence of postoperative death and cardiopulmonary complications in this group in addition to more traditional concerns about operative site complications. Further studies are needed to explore reasons for the higher rate of limb-threatening infection in patients with renal insufficiency undergoing revascularization. C1 San Francisco VA Med Ctr, Div Nephrol, Dept Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Northwestern Univ, Sch Med, Div Gen Internal Med, Chicago, IL USA. Washington DC VA Med Ctr, Surg Serv, Washington, DC USA. George Washington Univ, Dept Surg, Washington, DC USA. Georgetown Univ, Dept Surg, Washington, DC USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA. Tenet Hlth Syst, Med Affairs, Clin Effectiveness, Dallas, TX USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA USA. VA Boston Healthcare Syst, Surg Serv, Boston, MA USA. Univ Colorado, Hlth Outcomes Program, Denver, CO 80202 USA. RP O'Hare, AM (reprint author), San Francisco VA Med Ctr, Div Nephrol, Dept Med, Box 111J,4150 Clement St, San Francisco, CA 94121 USA. NR 39 TC 62 Z9 64 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD MAY PY 2003 VL 14 IS 5 BP 1287 EP 1295 DI 10.1097/01.ASN.0000061776.60146.02 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 671YL UT WOS:000182492900020 PM 12707397 ER PT J AU Rentz, J Bull, D Harpole, D Bailey, S Neumayer, L Pappas, T Krasnicka, B Henderson, W Daley, J Khuri, S AF Rentz, J Bull, D Harpole, D Bailey, S Neumayer, L Pappas, T Krasnicka, B Henderson, W Daley, J Khuri, S TI Transthoracic versus transhiatal esophagectomy: A prospective study of 945 patients SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID AFFAIRS SURGICAL RISK; QUALITY; CARE; THORACOTOMY; ADJUSTMENT; CANCER; MANAGEMENT; RESECTION; CARCINOMA; MORBIDITY AB Objective: Debate continues as to whether transhiatal esophagectomy results in lower morbidity and mortality than transthoracic esophagectomy. Most data addressing this issue are derived from single-institution studies. To investigate this question from a nationwide multicenter perspective, we used the Veterans Administration National Surgical Quality Improvement Program to prospectively analyze risk factors for morbidity and mortality in patients undergoing transthoracic esophagectomy or transhiatal esophagectomy from 1991 to 2000. Methods: Univariate and multivariate analyses were performed on 945 patients (mean age, 63 +/- 10 years). There were 562 transthoracic esophagectomies and 383 transhiatal esophagectomies in 105 hospitals, with complete 30-day outcomes recorded. Results: There were no differences in recorded preoperative variables between the groups that might bias any comparisons. Overall mortality was 10.0% (56/562) for transthoracic esophagectomy and 9.9% (38/383) for transhiatal esophagectomy (P = .983). Morbidity occurred in 47% (266/562) of patients after transthoracic esophagectomy and in 49% (188/383) of patients after transhiatal esophagectomy (P = .596). Risk factors for mortality common to both groups included a serum albumin value of less than 3.5 g/dL, age greater than 65 years, and blood transfusion of greater than 4 units (P < .05). When comparing transthoracic esophagectomy with transhiatal esophagectomy, there was no difference in the incidence of respiratory failure, renal failure, bleeding, infection, sepsis, anastomotic complications, or mediastinitis. Wound dehiscence occurred in 5% (18/383) of patients undergoing transhiatal esophagectomy and only 2% (12/562) of patients undergoing transthoracic esophagectomy (P = .036). Conclusions: These data demonstrate no significant differences in preoperative variables and postoperative mortality or morbidity between transthoracic esophagectomy and transhiatal esophagectomy on the basis of a 10-year, prospective, multi-institutional, nationwide study. C1 Univ Utah, Sch Med, Vet Affairs Med Ctr, Salt Lake City, UT 84132 USA. Duke Univ, Sch Med, Vet Affairs Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Inst Hlth Policy, Partners Healthcare Syst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Vet Affairs Med Ctr, W Roxbury, MA USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Hines, IL USA. RP Bull, D (reprint author), Univ Utah, Hlth Sci Ctr, Div Cardiothorac Surg, 30 North 1900 East, Salt Lake City, UT 84132 USA. NR 18 TC 83 Z9 87 U1 0 U2 0 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 MAY PY 2003 VL 125 IS 5 BP 1114 EP 1120 DI 10.1067/mtc.2003.315 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 685MC UT WOS:000183266600020 PM 12771885 ER PT J AU Penson, DF Litwin, MS Aaronson, NK AF Penson, DF Litwin, MS Aaronson, NK TI Health related quality of life in men with prostate cancer SO JOURNAL OF UROLOGY LA English DT Review DE prostatic neoplasms; quality of life; research; follow-up studies; patient satisfaction ID EXTERNAL-BEAM RADIATION; OF-LIFE; RADICAL PROSTATECTOMY; FUNCTIONAL ASSESSMENT; PATIENT PREFERENCES; CAPSURE DATABASE; THERAPY; OUTCOMES; RADIOTHERAPY; INSTRUMENT AB Purpose: Quality of life is of great concern to patients considering treatment options for prostate cancer. In the absence of clinical trial data clearly demonstrating that a particular treatment is superior to another for localized prostate cancer, in terms of cause specific survival, patients may value quality of life as much as quantity of life. The goal of this review is to familiarize the reader with the methodology of quality of life research and to review the recent literature on quality of life outcomes in prostate cancer. Materials and Methods: A structured MEDLINE review of literature on health related quality of life in prostate cancer for the years 1995 to 2001 was performed, and was augmented with highly relevant articles from additional selected journals. Results: In the case of advanced or metastatic disease, where the goal of treatment is palliation and symptom-free survival, quality of life often becomes the primary desired outcome. In localized disease all treatments affect health related quality of life, although the impact of each therapy on sexual, urinary and bowel function is unique. Conclusions: Although a highly personal and subjective entity, health related quality of life can be assessed using rigorous and scientifically stringent methods from the field of psychometric test theory. A substantial amount of literature exists regarding the use of established and validated instruments for assessing the impact of prostate cancer and its treatment on health related quality of life. This information is of critical importance when counseling men with newly diagnosed prostate cancer regarding treatment choices and is also helpful in setting appropriate expectations for men with metastatic disease. C1 VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, Amsterdam, Netherlands. RP Penson, DF (reprint author), VA Puget Sound Hlth Care Syst, Urol Sect, Seattle, WA 98108 USA. NR 68 TC 108 Z9 110 U1 3 U2 5 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 MAY PY 2003 VL 169 IS 5 BP 1653 EP 1661 DI 10.1097/01.ju.0000061964.49961.55 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 667WM UT WOS:000182257600003 PM 12686803 ER PT J AU Beer, TM Garzotto, M Eilers, KM Lemmon, D AF Beer, TM Garzotto, M Eilers, KM Lemmon, D TI Phase II study of abarelix depot for androgen independent prostate cancer progression during gonadotropin-releasing hormone agonist therapy SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; gonadorelin; hormone antagonists ID FOLLICLE-STIMULATING-HORMONE; LUTEINIZING-HORMONE; ANTAGONIST CETRORELIX; CLINICAL-TRIALS; GNRH AGONIST; OPEN-LABEL; TESTOSTERONE; LEUPROLIDE; CARCINOMA; RECEPTOR AB Purpose: We determine the clinical efficacy of the gonadotropin-releasing hormone (Gn-RH) antagonist abarelix in patients with androgen independent prostate cancer, and measure its effect on serum follicle-stimulating hormone (FSH) and testosterone. Materials and Methods: A total of 20 patients with prostate cancer progression during Gn-RH agonist therapy received 100 mg. abarelix depot by intramuscular injection on days 1, 15 and 29, and then every 28 days for up to 24 weeks. Gn-RH agonist therapy was not continued. Patients who met criteria for prostate specific antigen (PSA) response after 24 weeks of therapy could receive treatment for up to 52 weeks. PSA response was the primary end point and was defined as a 50% decrease confirmed 4 weeks later. Secondary end points of this study were the effect of therapy on serum FSH and testosterone. Results: No patient met the criteria for PSA response. At the end of the 6 cycles of therapy 2 patients remained stable without PSA progression or other signs of disease progression. Median time to progression was 8 weeks (95% CI 5.7-10.3). Mean serum FSH decreased by more than 50% from a baseline of 5.7 IU/l. (95% Cl 4.2-7.1) and remained suppressed throughout the observation period. Mean serum testosterone did not change after 4 and 8 weeks of therapy and remained in the anorchid range. Treatment was well tolerated with no grade 3 or higher toxicity. Conclusions: Treatment of androgen independent prostate cancer with abarelix decreases circulating FSH. and maintains anorchid testosterone but does not result in clinical responses. C1 Oregon Hlth & Sci Univ, Div Hematol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Med Oncol, Portland, OR USA. Portland VA Med Ctr, Div Urol, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Div Hematol, Portland, OR 97201 USA. FU NCRR NIH HHS [5M01 RR 00334-33S2] NR 20 TC 20 Z9 20 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 MAY PY 2003 VL 169 IS 5 BP 1738 EP 1741 DI 10.1097/01.ju.0000059584.47272.9d PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 667WM UT WOS:000182257600021 PM 12686821 ER PT J AU Brewster, DC Cronenwett, JL Hallett, JW Johnston, KW Krupski, WC Matsumura, JS AF Brewster, DC Cronenwett, JL Hallett, JW Johnston, KW Krupski, WC Matsumura, JS TI Guidelines for the treatment of abdominal aortic aneurysms - Report of a subcommittee of the Joint Council of the American Association for Vascular Surgery and Society for Vascular Surgery SO JOURNAL OF VASCULAR SURGERY LA English DT Review ID POPULATION-BASED ANALYSIS; MECHANICAL WALL STRESS; IN-HOSPITAL MORTALITY; LIFE-TABLE ANALYSIS; HIGH-RISK PATIENTS; ENDOVASCULAR REPAIR; ENDOLUMINAL REPAIR; FOLLOW-UP; STENT-GRAFT; EUROSTAR EXPERIENCE AB Decision-making in regard to elective repair of abdominal aortic aneurysms (AAA) requires careful assessment of factors that influence rupture risk, operative mortality, and life expectancy. Individualized consideration of these factors in each patient is essential, and the role of patient preference is of increasing importance. It is not possible or appropriate to recommend a single threshold diameter for intervention which can be generalized to all patients. Based upon the best available current evidence, 5.5 cm is the best threshold for repair in an "average" patient. However, subsets of younger, good-risk patients or aneurysms at higher rupture risk may be identified in whom repair at smaller sizes is justified. Conversely, delay in repair until larger diameter may be best for older, higher-risk patients, especially if endovascular repair is not possible. Intervention at diameter <5.5 cm appears indicated in women with AAA. If a patient has suitable anatomy, endovascular repair may be considered, and it is most advantageous for older, higher-risk patients or patients with a hostile abdomen or other technical factors that may complicate standard open repair. With endovascular repair, perioperative morbidity and recovery time are clearly reduced; however, there is a higher reintervention rate, increased surveillance burden, and a small but ongoing risk of AAA rupture. There is no justification at present for different indications for endovascular repair, such as earlier treatment of smaller A-AA. Until long-term outcome of endoluminal repair is better defined and results of randomized trials available, the choice between endovascular and open repair will continue to rely heavily on patient preference. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Eastern Maine Med Ctr, Bangor, ME 04401 USA. Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Northwestern Univ, Chicago, IL 60611 USA. RP 1 Hawthorne Pl,Ste 111, Boston, MA 02114 USA. EM dcbrewster@partners.org NR 147 TC 342 Z9 373 U1 0 U2 20 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2003 VL 37 IS 5 BP 1106 EP 1117 DI 10.1067/mva.2003.363 PG 12 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 675YG UT WOS:000182724700038 PM 12756363 ER PT J AU Kaur, A Kassis, N Hale, CL Simon, M Elliott, M Gomez-Yafal, A Lifson, JD Desrosiers, RC Wang, F Barry, P Mach, M Johnson, RP AF Kaur, A Kassis, N Hale, CL Simon, M Elliott, M Gomez-Yafal, A Lifson, JD Desrosiers, RC Wang, F Barry, P Mach, M Johnson, RP TI Direct relationship between suppression of virus-specific immunity and emergence of cytomegalovirus disease in simian AIDS SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; INFECTED RHESUS-MACAQUES; ALLOGENEIC BONE-MARROW; LIVED PLASMA-CELLS; IMMUNODEFICIENCY-VIRUS; DIFFERENTIATION; INDIVIDUALS; ANTIBODIES; GENERATION; RECIPIENTS AB Although opportunistic infections like cytomegalovirus (CMV) are common sequelae of end-stage AIDS, the immune events leading to CMV reactivation in human immunodeficiency virus (HIV)-infected individuals are not well defined. The role of cellular and humoral CMV-specific immune responses in immune control of latent CMV infection was evaluated prospectively in a cohort of 11 simian immunodeficiency virus (SIV)-infected CMV-seropositive rhesus macaques, 6 of whom had histologic evidence of CMV disease at death. Macaques with CMV disease differed from macaques without CMV disease in having significantly higher levels of plasma SIV RNA and CMV DNA and significantly lower titers of anti-CMV binding antibodies (Abs) at the time of death. A significant decline in anti-CMV Abs and CMV-specific CD4(+) and CD8(+) T lymphocytes over time was observed in the macaques with CMV disease, but not in the macaques without CMV disease. Reduction in CMV-specific CD8(+) T lymphocytes and anti-CMV neutralizing Abs was significantly correlated with a decline in CMV-specific CD4(+) T lymphocytes. Although declines in CMV-specific T lymphocytes alone were sufficient for reactivation of low-level CMV viremia, high-level viremia (> 1,000 copies of CMV DNA per ml of plasma) was observed when anti-CMV neutralizing and binding Abs had also declined. Thus, the occurrence of CMV reactivation-associated disease in AIDS is associated with suppression of both cellular and humoral CMV-specific immune responses. The underlying mechanism may be a dysfunction of memory B and CD8(+) T lymphocytes associated with SIV-induced impairment of CMV-specific CD4(+) T-cell help. C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Div Pathol, Southborough, MA 01772 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Div Microbiol, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Infect Dis Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Therion Biol, Cambridge, MA 02142 USA. NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Univ Erlangen Nurnberg, Inst Klin & Mol Virol, D-91058 Erlangen, Germany. RP Kaur, A (reprint author), Harvard Univ, Sch Med, New England Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [P51 RR000168, K26 RR000168, RR00168]; NIAID NIH HHS [AI43890, AI45314, R01 AI043890] NR 31 TC 48 Z9 50 U1 0 U2 0 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 MAY PY 2003 VL 77 IS 10 BP 5749 EP 5758 DI 10.1128/JVI.77.10.5749-5758.2003 PG 10 WC Virology SC Virology GA 674HJ UT WOS:000182631100022 PM 12719568 ER PT J AU Bean-Mayberry, B AF Bean-Mayberry, B TI Influences on primary care achievement among women veterans SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. NR 0 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 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD MAY PY 2003 VL 12 IS 4 MA P16 BP 426 EP 426 PG 1 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 683JN UT WOS:000183145100058 ER PT J AU Ibrahim, SA Burant, CJ Mercer, MB Siminoff, LA Kwoh, CK AF Ibrahim, SA Burant, CJ Mercer, MB Siminoff, LA Kwoh, CK TI Older patients' perceptions of quality of chronic knee or hip pain: Differences by ethnicity and relationship to clinical variables SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID OF-LIFE; RHEUMATOID-ARTHRITIS; HEALTH-STATUS; OSTEO-ARTHRITIS; OSTEOARTHRITIS; ARTHROPLASTY; DETERMINANTS; VALIDATION; SEVERITY; WOMAC AB Background. There is marked ethnic or racial disparity in the utilization of joint replacement for osteoarthritis. The reasons are not known. Pain is the reason most patients with osteoarthritis seek care. Cultural and psychosocial factors influence how patients experience and express pain. We examined whether patient descriptions of chronic pain vary by ethnicity and if they correlate with important clinical measures used in arthritis care. Methods. Sample consisted of 300 male veterans who were greater than or equal to50 years of age with moderate to severe symptomatic knee or hip osteoarthritis. Structured surveys were used to assess patient descriptions of pain and to collect important demographic, clinical, and psychosocial variables. Factor analysis was used to assess patterns of pain description in a comparison of African-American and Caucasian patients. Pearson correlations were used to examine relationships between pain descriptions and clinical variables. Results. The two groups were similar with respect to age and other baseline clinical characteristics. A confirmatory factor analysis on quality of pain description showed that a four-factor model converged for Caucasian patients (chi square = 39.6, comparative fit index = 0.95, Tucker Lewis index = 0.93, and root mean square error of approximation = 0.047), but a three-factor model was supported by the data for African-American patients (chi square = 25.4, comparative fit index = 1.00, Tucker Lewis index = 1.05, and root mean square error of approximation less than or equal to 0.001). Chronic pain quality descriptions correlate significantly with Western Ontario and McMaster Universities Arthritis Index scores but not with radiologic stage of disease. Conclusions. African-American and Caucasian elderly patients with chronic knee or hip symptomatic osteoarthritis describe the quality of their pain differently. Patient descriptions of quality of chronic knee or hip pain do not correlate with radiologic stage of disease. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15240 USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Univ Dr C,11 East 130 A-U, Pittsburgh, PA 15240 USA. RI Siminoff, Laura /H-6277-2012 NR 40 TC 24 Z9 24 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAY PY 2003 VL 58 IS 5 BP 472 EP 477 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 675BP UT WOS:000182673400015 ER PT J AU Al-Nimri, MA Komers, R Oyama, TT Subramanya, AR Lindsley, JN Anderson, S AF Al-Nimri, MA Komers, R Oyama, TT Subramanya, AR Lindsley, JN Anderson, S TI Endothelial-derived vasoactive mediators in polycystic kidney disease SO KIDNEY INTERNATIONAL LA English DT Article DE polycystic kidney; nitric oxide; endothelin; cystic disease; glomerular filtration rate; proteinuria ID NITRIC-OXIDE SYNTHASE; RENAL HEMODYNAMIC-CHANGES; DEPENDENT RELAXATION; SYMPATHETIC ACTIVITY; VASCULAR-RESPONSES; RESISTANCE VESSELS; CONVERTING ENZYME; FAMILY MEMBERS; RATS; HYPERTENSION AB Background. Autosomal dominant polycystic kidney disease (ADPKD) is characterized by hypertension and renal vasoconstriction. Mediators of these hemodynamic changes are not well understood, but evidence suggests that endothelial-derived mediators may participate. Methods. Baseline measurements of blood pressure, proteinuria, and urinary nitrite/nitrate excretion were performed in control and cystic male Han:SPRD rats (6 weeks of age). They were then treated with the nitric oxide (NO), nitric oxide synthase (NOS) inhibitor, N-G-nitro-L-arginine methyl ester (L-NAME), or vehicle, for 6 weeks. After repeat systemic measurements, renal function was determined using inulin and para-aminohippurate (PAH) clearances. Levels of renal endothelin-1 (ET-1) and renal endothelial NOS (eNOS) proteins were determined, and immunohistochemistry localized renal eNOS and neuronal NOS (nNOS). Results. Administration of L-NAME aggravated systemic hypertension and renal vasoconstriction in the cystic rats, but did not affect the progression of proteinuria or cystic expansion. Cystic rats demonstrated marked increases in renal ET-1 and eNOS levels. L-NAME reduced eNOS expression in the membrane compartment, but increased eNOS in the cytosol. Localization studies indicated that renal eNOS was abundant in nonvascular compartments, but not in renal vascular and glomerular structures, whereas renal nNOS was diffusely diminished. Conclusion. These alterations of endothelial-derived mediators (up-regulation of ET-1, and dysfunction of the NO system) contribute to vasoconstriction, and thereby are likely to contribute to the progressive loss of renal function in polycystic kidney disease (PKD). C1 Oregon Hlth Sci Univ, Dept Hypertens & Nephrol, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. RP Anderson, S (reprint author), Oregon Hlth Sci Univ, Div Nephrol, PP262,3314 SW,US Vet Hosp Rd, Portland, OR 97201 USA. FU NIA NIH HHS [AG 14699] NR 42 TC 23 Z9 25 U1 1 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 MAY PY 2003 VL 63 IS 5 BP 1776 EP 1784 DI 10.1046/j.1523-1755.2003.00913.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400018 PM 12675853 ER PT J AU Salusky, IB Goodman, WG Kuizon, BD Lavigne, JR Zahranik, RJ Gales, B Wang, HJ Elashoff, RM Juppner, H AF Salusky, IB Goodman, WG Kuizon, BD Lavigne, JR Zahranik, RJ Gales, B Wang, HJ Elashoff, RM Juppner, H TI Similar predictive value of bone turnover using first- and second-generation immunometric PTH assays in pediatric patients treated with peritoneal dialysis SO KIDNEY INTERNATIONAL LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Nephrology CY NOV 03-06, 2002 CL PHILADELPHIA, PENNSYLVANIA SP American Soc Nephrol DE parathyroid hormone; immunometric PTH assay; peritoneal dialysis ID INTERMITTENT CALCITRIOL THERAPY; PARATHYROID-HORMONE; RENAL-FAILURE; IMMUNORADIOMETRIC ASSAY; PTH/PTHRP RECEPTOR; CALCIUM-CONCENTRATION; SKELETAL RESISTANCE; DIABETIC-PATIENTS; UREMIC RATS; INTACT AB Background. Accurate measurements of the concentration of parathyroid hormone (PTH) in serum or plasma are essential for the proper assessment of renal osteodystrophy. The first-generation immunometric PTH assay (1st PTH-IMA) not only detects the intact hormone, but also additional PTH fragments truncated at the amino N-terminally truncated PTH-derived fragments [ntPTH(1-84)]. A second-generation immunometric PTH assay (2nd PTH-IMA) recognizes only PTH(1-84) and possibly PTH fragments that are truncated at the carboxyl-terminus but not PTH(7-84). Whether estimates of the ratio between PTH(1-84) and ntPTH(1-84) fragments are a better predictor of bone turnover remains controversial. Methods. Thirty-three patients aged 12.8 +/- 4.4 years treated with continuous cycling peritoneal dialysis (CCPD) for 13 +/- 9 months underwent iliac crest bone biopsy. PTH levels were measured by two newly developed first-generation and second-generation PTH-IMA. The ntPTH(1-84) fragments were calculated by subtracting PTH values determined using the 2nd PTH-IMA from values obtained using 1st PTH-IMA that detects both PTH(1-84) and relatively large ntPTH(1-84). Results. Determinations of PTH levels by both assays were highly correlated (r = 0.89, P < 0.001). The relationships between first-generation and second-generation PTH-IMA and bone formation were similar (r = 0.67, P < 0.0001 and r = 0.64, P < 0.0001, respectively). When patients were grouped according to the presence or absence of secondary hyperparathyroidism, the ratio PTH(1-84) to ntPTH(1-84) did not differ between groups. Conclusion. PTH concentrations determined by either the first- or the second-generation PTH-IMA were found to be better predictors of bone formation than the PTH(1-84) to ntPTH(1-84) fragments ratio. C1 Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Dept Pediat,David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Div Nephrol, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biomath, David Geffen Sch Med, Los Angeles, CA 90095 USA. Immutop, San Clemente, CA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA USA. RP Salusky, IB (reprint author), Univ Calif Los Angeles, Med Ctr, Div Pediat Nephrol, Dept Pediat,David Geffen Sch Med, Box 951752, Los Angeles, CA 90095 USA. FU NIDDK NIH HHS [DK-35423] NR 42 TC 81 Z9 84 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1801 EP 1808 DI 10.1046/j.1523-1755.2003.00915.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400021 PM 12675856 ER PT J AU Stamatelou, KK Francis, ME Jones, CA Nyberg, LM Curhan, GC AF Stamatelou, KK Francis, ME Jones, CA Nyberg, LM Curhan, GC TI Time trends in reported prevalence of kidney stones in the United States: 1976-1994 SO KIDNEY INTERNATIONAL LA English DT Article DE kidney stones; prevalence; temporal trends ID DIETARY CALCIUM; GEOGRAPHIC VARIABILITY; NEPHROLITHIASIS; RISK; UROLITHIASIS; EPIDEMIOLOGY; POPULATION; HYPERCALCIURIA; HYPERTENSION; NUTRIENTS AB Background. A body of evidence establishes that the occurrence of kidney stone disease has increased in some communities of industrialized countries. Information on recent temporal trends in the United States is lacking and population-based data on epidemiologic patterns are limited. Study objective was to determine whether kidney stone disease prevalence increased in the United States over a 20-year period and the influence of region, race/ethnicity, and gender on stone disease risk. Methods. We measured the prevalence of kidney stone disease history from the United States National Health and Nutrition Examination Survey (II and III), population-based, cross-sectional studies, involving 15,364 adult United States residents in 1976 to 1980 and 16,115 adult United States residents in 1988 to 1994. Results. Disease prevalence among 20- to 74-year-old United States residents was greater in 1988 to 1994 than in 1976 to 1980 (5.2% vs. 3.8%, P < 0.05), greater in males than females, and increased with age in each time period. Among 1988 to 1994 adults, non-Hispanic African Americans had reduced risk of disease compared to non-Hispanic Caucasians (1.7% vs. 5.9%, P < 0.05), and Mexican Americans (1.7% vs. 2.6%, P < 0.05). Also, age-adjusted prevalence was highest in the South (6.6%) and lowest in the West (3.3%). Findings were consistent across gender and multivariate adjusted odds ratios for stone disease history, including all demographic variables, as well as diuretic use, tea or coffee consumption, and dietary intake of calcium, protein, and fat did not materially change the results. Conclusion. Prevalence of kidney stone disease history in the United States population increased between 1980 and 1994. A history of stone disease was strongly associated with race/ethnicity and region of residence. C1 Blue Cross Hosp, Renal Unit, Athens, Greece. Social & Sci Syst, Silver Spring, MD USA. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. NIDDKD, Urol Program, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Stamatelou, KK (reprint author), 40 E Adistasis Str Vrilissia, Athens 15235, Greece. NR 29 TC 629 Z9 653 U1 3 U2 23 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1817 EP 1823 DI 10.1046/j.1523-1755.2003.00917.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400023 PM 12675858 ER PT J AU Knight, EL Ofsthun, N Teng, M Lazarus, JM Curhan, GC AF Knight, EL Ofsthun, N Teng, M Lazarus, JM Curhan, GC TI The association between mental health, physical function, and hemodialysis mortality SO KIDNEY INTERNATIONAL LA English DT Article DE hemodialysis; mental health; physical function; functional status; depression; mortality; elderly ID STAGE RENAL-DISEASE; QUALITY-OF-LIFE; REHABILITATION PROGRAM; MYOCARDIAL-INFARCTION; DEPRESSION; SURVIVAL; DIALYSIS; HOSPITALIZATION; PERFORMANCE; PREDICTORS AB Background. Mortality rates for individuals on chronic hemodialysis remain very high; therefore, strategies are needed to identify individuals at greatest risk for mortality so preventive strategies can be implemented. One such approach is to stratify individuals by self-reported mental health and physical function. Examining these parameters at baseline, and over time, may help identify individuals at greater risk for mortality. Methods. We enrolled 14,815 individuals with end-stage renal disease (ESRD) and followed these individuals for up to 2 years. The mean age was 61.0 +/- 15.4 years (range, 20 to 96 years) and 31% were African Americans. The SF-36 Health Survey was administered 1 to 3 months after hemodialysis initiation and 6 months later. We examined the associations between the initial SF-36 Health Survey mental component summary (MCS) and physical component summary (PCS) scores and mortality during the follow-up period, and examined the associations between 6-month decline in PCS and MCS scores and subsequent mortality. We also examined the interactions between age and MCS and PCS scores. The general population-based mean of each of these scores was 50 with a standard deviation of 10. The main outcome measurement was death. Results. Self-reported baseline mental health (MCS score) and physical function (PCS score) were both independently associated with increased mortality, and 6-month decline in these parameters was also associated with increased mortality. The multivariate hazard ratios for 1-year mortality for MCS scores of less than 30, 30 to 39, and 40 to 49 were 1.48 (95% CI, 1.32 to 1.64), 1.23 (95% CI, 1.14 to 1.32) and 1.18 (95% CI, 1.10 to 1.26) compared with a MCS score of 50 or more. The hazard ratios for PCS scores of less than 20, 20 to 29, and 30 to 39 were 1.97 (95% CI, 1.64 to 2.36), 1.62 (95% CI, 1.36 to 1.92), and 1.32 (95% CI, 1.11 to 1.57) compared with a PCS score of 50 or more. Six-month decline in self-reported mental health (hazard ratio, 1.07; 95% CI, 1.02 to 1.12, per 10-point decline in MCS score) and physical function (hazard ratio, 1.25; 95% CI, 1.18 to 1.33, per 10-point decline in PCS score) were also both significantly associated with an additional increase in mortality beyond baseline risk. We also found a significant interaction between age and physical function (P = 0.02). Specifically, there was a graded response between the PCS score category and mortality in most age strata, but this relationship was not observed in the oldest age (85 years old or older). Conclusion. In individuals newly initiated on chronic hemodialysis, self-reported baseline mental health and physical function are important, independent predictors of mortality, and there is a graded relationship between these parameters and mortality risk. Following these parameters over time provides additional information on mortality risk. One must also consider age when interpreting the relationship between physical function and mortality. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gen Med Unit,Renal Unit, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Fresenius Med Care, Lexington, MA USA. RP Knight, EL (reprint author), Channing Labs, Nursing Hlth Study, 4th Floor,181 Longwood Ave, Boston, MA 02115 USA. FU NIDDK NIH HHS [T32DK07791, DK52866, T32 DK0740-16] NR 33 TC 124 Z9 138 U1 2 U2 7 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1843 EP 1851 DI 10.1046/j.1523-1755.2003.00931.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400027 PM 12675862 ER PT J AU Colvin, RB AF Colvin, RB TI Transplant Mac attack: Humor the macrophages SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE acute humoral rejection; peritubular capillary deposition; glomerular macrophage infiltration ID KIDNEY-TRANSPLANTATION; ALLOGRAFT-REJECTION; C4D; CAPILLARIES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Warren 225, Boston, MA 02114 USA. NR 10 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2003 VL 63 IS 5 BP 1953 EP 1954 DI 10.1046/j.1523-1755.2003.00943.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 664BG UT WOS:000182041400043 PM 12675878 ER PT J AU Folmer, RL Griest, SE AF Folmer, RL Griest, SE TI Chronic tinnitus resulting from head or neck injuries SO LARYNGOSCOPE LA English DT Article DE tinnitus; head-neck trauma; severity; whiplash; brain injury ID PERILYMPHATIC FISTULA; WHIPLASH; LITIGATION; SEVERITY; TRAUMA AB Objectives: The main objectives were 1) to determine the percentage of cases of chronic tinnitus in a specialized clinic that resulted from head or neck injuries; 2) to describe the characteristics of this population; and 3) to compare patients with head or neck trauma with patients whose tinnitus onset was not associated with head or neck injuries. Study Design: Retrospective analysis of tinnitus clinic patient data. Methods: Detailed questionnaires were mailed to 2400 patients before their initial appointment at the Oregon Health and Science University Tinnitus Clinic (Portland, OR). All of the patients experienced and received treatment for chronic tinnitus. Patient data were entered into a database and later analyzed. Results: Two hundred ninety-seven patients (214 male and 83 female patients) reported that their chronic tinnitus started as a result of head or neck injuries. Compared with patients whose tinnitus onset was not associated with trauma, patients with tinnitus associated with head or neck trauma were younger; had better hearing thresholds; experienced headaches more frequently, reported greater difficulties with concentration, memory, and thinking clearly; were more likely to experience current depression, but not lifetime depression; rated their tinnitus as louder on a 1-to-10 scale; matched their tinnitus to louder sounds on the right side; and had higher Tinnitus Severity Index scores. Conclusions: Tinnitus is a significant symptom that commonly occurs as a result of head or neck trauma. The fact that tinnitus resulting from head or neck injuries tends to be more severe (and is often accompanied by a greater number of co-symptoms) than tinnitus resulting from other causes should be taken into account by clinicians treating these patients. C1 Oregon Hlth Sci Univ, Oregon Hlth & Sci Univ Tinnitus Clin, Dept Otolaryngol, Oregon Hearing Res Ctr, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Natl Ctr Rehabilitat Auditory Res, Portland, OR USA. RP Folmer, RL (reprint author), Oregon Hlth Sci Univ, Oregon Hlth & Sci Univ Tinnitus Clin, Dept Otolaryngol, Oregon Hearing Res Ctr, 3181 SW Sam Jackson Pk Rd,Mail Code NRC04, Portland, OR 97239 USA. RI Folmer, Robert/E-3105-2010 NR 24 TC 27 Z9 29 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 MAY PY 2003 VL 113 IS 5 BP 821 EP 827 DI 10.1097/00005537-200305000-00010 PG 7 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 676AF UT WOS:000182729200010 PM 12792317 ER PT J AU Ishikawa, F Livingston, AG Minamiguchi, H Wingard, JR Ogawa, M AF Ishikawa, F Livingston, AG Minamiguchi, H Wingard, JR Ogawa, M TI Human cord blood long-term engrafting cells are CD34(+) CD38(-) SO LEUKEMIA LA English DT Article DE umbilical cord blood; hematopoietic stem cells; CD34; CD38; xenotransplantation ID HEMATOPOIETIC STEM-CELLS; REPOPULATING ACTIVITY; EXPRESSION; MICE; GENERATION AB There have been controversies about CD34 and CD38 expression by human cord blood (CB) stem cells. Using the newborn NOD/SCID/beta2-microglobulin-null mouse assay that we recently developed, we examined the in vivo engrafting capability of human CB cells. Almost all of the 4-5 months engrafting cells were found in CD34(+) population. The capability of secondary reconstitution was found only in the CD34(+) cells. When the CD34(+) CB cells were separated into CD38(-) and CD38(+) subpopulations and tested for engraftment, the majority of the engrafting cells were detected in the CD38(-) subpopulation. These findings are consistent with the results from studies of murine stem cells and strongly indicate that the phenotype of human CB stem cells is CD34(+) CD38(-). C1 Med Univ S Carolina, Dept Med, Dept Vet Affairs Med Ctr, Charleston, SC 29425 USA. Univ Florida, Div Hematol Oncol, Gainesville, FL USA. RP Ogawa, M (reprint author), Ralph H Johnson VA Med Ctr, 109 Bee St, Charleston, SC 29401 USA. RI 石川, 文彦/L-4488-2014 FU NCI NIH HHS [P01-CA78582]; NIDDK NIH HHS [R01-DK54197] NR 17 TC 36 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2003 VL 17 IS 5 BP 960 EP 964 DI 10.1038/sj.leu.2402878 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 679FN UT WOS:000182910200019 PM 12750710 ER PT J AU Fukushima, T Miyazaki, Y Tsushima, H Tsutsumi, C Taguchi, J Yoshida, S Kuriyama, K Scadden, D Nimer, S Tomonaga, M AF Fukushima, T Miyazaki, Y Tsushima, H Tsutsumi, C Taguchi, J Yoshida, S Kuriyama, K Scadden, D Nimer, S Tomonaga, M TI The level of MEF but not ELF-1 correlates with FAB subtype of acute myeloid leukemia and is low in good prognosis cases SO LEUKEMIA RESEARCH LA English DT Article DE ETS genes; gene expression; AML; transcription factor; MEF ID EWINGS-SARCOMA TRANSLOCATION; VIRUS TYPE-2 ENHANCER; DNA-BINDING DOMAIN; TRANSCRIPTION FACTOR; GENE-EXPRESSION; ETS-FAMILY; T-CELLS; REGULATORY ELEMENTS; EWS GENE; ACTIVATION AB ETS proteins (such as PU.1, Fli-1 and ETS-1) have been shown to play important roles in normal and abnormal hematopoiesis. We examined the expression of the ELF subfamily of ETS genes (ELF-1, MEF and NERF) in acute myeloid leukemia (AML) cells using Northern blot analysis. ELF-I and MEF were expressed in all samples, whereas NERF was not. The relative expression (RE) of MEF, but not ELF-1, was significantly lower (P < 0.0001) in AML with t(8;21) and t(15;17) compared with AML with normal karyotype. The pattern of MEF expression was not uniform among cells with CD34(+)/CD33(+). It is suggested that the low RE of MEF might be part of a gene expression profile characterizing AML with a good prognosis. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Hematol, Nagasaki 852, Japan. Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Mol Med Unit, Nagasaki 852, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MCH Canc Ctr, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Cambridge, MA 02138 USA. Sloan Kettering Inst Canc Res, New York, NY USA. RP Miyazaki, Y (reprint author), Nagasaki Univ, Sch Med, Atom Bomb Dis Inst, Dept Hematol, Nagasaki 852, Japan. EM y-miyaza@med.nagasaki-u.ac.jp NR 34 TC 15 Z9 15 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD MAY PY 2003 VL 27 IS 5 BP 387 EP 392 AR PII S0145-2126(02)00214-X DI 10.1016/S0145-2126(02)00214-X PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 656RT UT WOS:000181622800003 PM 12620289 ER PT J AU Saab, S Wang, V Ibrahim, AB Durazo, F Han, S Farmer, DG Yersiz, H Morrisey, M Goldstein, LI Ghobrial, RM Busuttil, RW AF Saab, S Wang, V Ibrahim, AB Durazo, F Han, S Farmer, DG Yersiz, H Morrisey, M Goldstein, LI Ghobrial, RM Busuttil, RW TI MELD score predicts 1-year patient survival post-orthotopic liver transplantation SO LIVER TRANSPLANTATION LA English DT Article ID PUGH SCORE; MODEL; ALLOCATION; SEVERITY; DISEASE AB The Model for End-Stage Liver Disease (MELD) is an important predictor in patients awaiting orthotopic liver transplantation (OLT). However, the model's association with posttransplant patient survival is unclear. We studied 1-year patient survival in 404 adult patients who underwent OLT at the University of California Los Angeles. The hazard rates of patient survival according to the MELD strata and United Network for Organ Sharing (UNOS) statuses were assessed by Proportional Hazard Cox regression analysis. The difference in survival for MELD strata and UNOS status were compared using the Cox model. There was a significant difference in 1-year patient (P =.0006) survival using different MELD strata, whereas there was a trend according to UNOS status (P =.051). Increased rate of death was observed in recipients of OLT with higher MELD scores (> 36, hazard ratio 3.9; 95% CI 1.55, 10.27) and more urgent UNOS status (2A, hazard ratio, 1.99; 95% CI 1.07, 3.7). The MELD stratum is better associated with 1-year patient survival in liver transplant recipients than UNOS statuses. Patient survival was worse with higher MELD scores. C1 Univ Calif Los Angeles, Ctr Med, Div Digest Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dumont Liver Transplant Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Biostat, Los Angeles, CA 90024 USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Ctr Med, Div Digest Dis, 44-138 CHS,MC 168417,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 15 TC 125 Z9 136 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD MAY PY 2003 VL 9 IS 5 BP 473 EP 476 DI 10.1053/jlts.2003.50090 PG 4 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 674MQ UT WOS:000182640900004 PM 12740789 ER PT J AU McGlynn, EA Kerr, EA Adams, J Keesey, J Asch, SM AF McGlynn, EA Kerr, EA Adams, J Keesey, J Asch, SM TI Quality of health care for women - A demonstration of the quality assessment tools system SO MEDICAL CARE LA English DT Article DE quality; women's health; quality measurement; managed care ID ARTERY BYPASS-SURGERY; DIABETES-MELLITUS; PERFORMANCE; CRITERIA; OUTCOMES; CONSUMERS; UNDERUSE; STATE AB BACKGROUND. Consumers, purchasers, and regulators are seeking information on quality for a variety of purposes. To address these demands, methods are required that are flexible in meeting the information needs of different audiences. OBJECTIVES. To test a new clinically detailed, comprehensive approach to quality measurement called Quality Assessment (QA) Tools. DESIGN. Quality measures were developed for women ages 18 to 50 years for preventive care and 17 clinical areas that included chronic and acute health problems. A stratified random sample of women enrolled in 1 of 2 health plans in 1996 to 1997 was drawn and data abstracted from the medical records of all their providers for a 2-year period. FINDINGS. We evaluated quality for 758 women in 2 managed care plans. Quality of care varied substantially depending on the dimension being examined. For example, acute care was significantly better than chronic or preventive care. Quality was highest for follow-up care and lowest for treatment in both plans. Quality by modality ranged from approximately 90% for referral or admission to 16% for education and counseling. We found significant differences between the plans in the quality of care for 7 of the 17 conditions studied. CONCLUSION. The QA Tools system offers an alternative approach to evaluating health system performance. Potential advantages include the richness of the information produced by the system, the ability to create summary scores for consumers and purchasers, and the system-level performance information for use in quality improvement activities. C1 RAND Hlth, Santa Monica, CA 90401 USA. Vet Affairs Ctr Practice Management & Outcomes Re, VA Ann Arbor Hlth Care Syst, Ann Arbor, MI USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP McGlynn, EA (reprint author), RAND Hlth, 1700 Main St, Santa Monica, CA 90401 USA. NR 47 TC 15 Z9 15 U1 1 U2 4 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 MAY PY 2003 VL 41 IS 5 BP 616 EP 625 DI 10.1097/00005650-200305000-00009 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 675LH UT WOS:000182695900010 PM 12719686 ER PT J AU Wittenberg, E Goldie, SJ Fischhoff, B Graham, JD AF Wittenberg, E Goldie, SJ Fischhoff, B Graham, JD TI Rationing decisions and individual responsibility for illness: Are all lives equal? SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 22nd Annual Meeting of the Society-for-Medical-Decision-Making CY SEP 25, 2000 CL CINCINNATI, OHIO SP Soc Med Decis Making DE rationing; personal responsibility; preferences ID WILLINGNESS-TO-PAY; ALLOCATION; RISK; TRANSPLANTATION; GRAFTS AB Objectives. This survey measured individuals' rationing allocation choices for situations in which patients are deemed to hold personal responsibility for their diseases and the influence of different arguments on such choices. Methods. The association between allocation decisions for liver disease and asthma and the belief that a patient was responsible for his or her illness was modeled using multivariable regression analysis, controlling for the effect of arguments on choices. Results. In data from 310 returned surveys (43% response rate), respondents were 10 to 17 times more likely to allocate liver transplants or asthma treatment to patients they deemed not responsible for their illnesses than to patients they deemed responsible for their conditions (liver transplants: odds ratio [OR]= 10.3, 95% confidence interval [CI] = 2.5-42.1; asthma: OR = 16.8, 95% CI = 2.1-136.6). Conclusions. Personal responsibility for illness was an important consideration in respondents' rationing allocation decisions. These choices appeared to be stable although possibly influenced by respondents' interpretations of the survey scenarios and decision tasks. Key words: rationing, personal responsibility; preferences. (Med Decis Making 2003;23:194-211). C1 Massachusetts Gen Hosp, MGH Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. RP Wittenberg, E (reprint author), Massachusetts Gen Hosp, MGH Inst Technol Assessment, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. NR 32 TC 12 Z9 12 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2003 VL 23 IS 3 BP 194 EP 211 DI 10.1177/0272989X03253647 PG 18 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 681UA UT WOS:000183052700001 PM 12809318 ER PT J AU King, JT Styn, MA Tsevat, J Roberts, MS AF King, JT Styn, MA Tsevat, J Roberts, MS TI "Perfect health" versus "disease free": The impact of anchor point choice on the measurement of preferences and the calculation of disease-specific disutilities SO MEDICAL DECISION MAKING LA English DT Article DE measurement; preferences; standard gamble; time tradeoff; utility; visual analogue scale; willingness to pay AB Background. During preference testing, some investigators use "perfect health " as the upper anchor point of their measurement scale ("Q scale "), whereas others use "disease free " ("q scale"), which can confound the interpretation and comparison of study results. Methods. We measured current health preferences among 74 patients with cervical spondyloticmyelopathy(CSM) on both the Q and q scales using the visual analogue scale (VAS), standard gamble (SG), time tradeoff (TTO), and willingness to pay (WTP). Results. There were significant differences in mean Q and q scale values for the VAS, SG, and WTP (for all, P < 0.011); there were no significant differences for mean TTO values (P = 0.592). CSM accounted for 63% to 82% of total disutility, whereas other comorbidities accounted for 28% to 37%. Conclusions. Preferences for CSM differ when measured on the Q and q scales. Caution should be used when comparing and interpreting health values measured on scales with different upper anchors. Key words: measurement; preferences; standard gamble; time tradeoff; utility; visual analogue scale; willingness to pay. (Med Decis Making 2003;23:212-225). C1 VA Pittsburgh Healthcare Syst, Neurosurg Sect, Surg Serv Line, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sect Decis Sci & Clin Syst Modeling, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Div Gen Internal Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Cincinnati, Med Ctr, Dept Internal Med, Div Gen Internal Med,Sect Outcomes Res, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Ctr Clin Effectiveness, Inst Hlth Policy & Hlth Serv Res, Cincinnati, OH 45267 USA. Vet Affairs Med Ctr, Cincinnati, OH 45267 USA. RP King, JT (reprint author), VA Connecticut Healthcare Syst, Surg Serv 112, 950 Campbell Ave, West Haven, CT 06516 USA. FU NINDS NIH HHS [1K23 NS02169-01] NR 13 TC 18 Z9 18 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD MAY-JUN PY 2003 VL 23 IS 3 BP 212 EP 225 DI 10.1177/0272989X03253652 PG 14 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 681UA UT WOS:000183052700002 PM 12809319 ER PT J AU Hacker, F Low, D AF Hacker, F Low, D TI Compared with inverse-planning, forward planning is preferred for IMRT stereotactic radiosurgery SO MEDICAL PHYSICS LA English DT Editorial Material ID LINEAR-ACCELERATOR; NONCOPLANAR ARCS; RADIOTHERAPY; OPTIMIZATION; IRRADIATION; THERAPY; SYSTEM C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp,Childrens, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biomed Engn, St Louis, MO 63110 USA. RP Hacker, F (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Brigham & Womens Hosp,Childrens, 44 Binney St, Boston, MA 02115 USA. OI Hacker, Fred/0000-0001-7535-7598 NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2003 VL 30 IS 5 BP 731 EP 734 DI 10.1118/1.1565114 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 680GK UT WOS:000182967800001 PM 12772977 ER PT J AU Graves, EE Ripoll, J Weissleder, R Ntziachristos, V AF Graves, EE Ripoll, J Weissleder, R Ntziachristos, V TI A submillimeter resolution fluorescence molecular imaging system for small animal imaging SO MEDICAL PHYSICS LA English DT Article DE fluorescence molecular tomography; diffuse optical tomography; small animal imaging ID DIFFUSE OPTICAL TOMOGRAPHY; CONTRAST AGENTS; TURBID MEDIA; BREAST-CANCER; TUMORS; PROBES; LIGHT; APPROXIMATION; LIFETIME; WAVES AB Most current imaging systems developed for tomographic investigations of intact tissues using diffuse photons suffer from a limited number of sources and detectors. In this paper we describe the construction and evaluation of a large dataset, low noise tomographic system for fluorescence imaging in small animals. The system consists of a parallel plate-imaging chamber and a lens coupled CCD camera, which enables conventional planar imaging as well as fluorescence tomography. The planar imaging data are used to guide the acquisition of a Fluorescence Molecular Tomography (FMT) dataset containing more than 106 measurements, and to superimpose anatomical features with tomographic results for improved visual representation. Experimental measurements exhibited good agreement with the diffusion theory models used to predict light propagation within the chamber. Tests of the instrument's capacity to quantitatively reconstruct fluorochrome distributions in three dimensions showed less than 5% errors between actual fluorochrome concentrations and FMT findings, and suggested a detection threshold of approximately 100 femptomoles for small localized objects. Experiments to assess the instrument's spatial resolution demonstrated the ability of the system to resolve objects placed at clear distances of less than 1 mm. This is a significant resolution increase over previously developed systems for animal imaging, and is primarily due to the large dataset employed and the use of inversion methods. Finally, the in vivo imaging capacity is showcased. It is expected that the large dataset collected can enable superior imaging of molecular probes in vivo and improve quantification of fluorescence signatures. (C) 2003 American Association of Physicists in Medicine. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Harvard Med Sch, Charlestown, MA 02129 USA. RP Graves, EE (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Harvard Med Sch, Charlestown, MA 02129 USA. RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [P50 CA 86355, R21 CA 91807, R24 CA 92782, T32 CA 79443]; NIBIB NIH HHS [R01 EB 000750-1] NR 30 TC 313 Z9 322 U1 1 U2 27 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAY PY 2003 VL 30 IS 5 BP 901 EP 911 DI 10.1118/1.1568977 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 680GK UT WOS:000182967800022 PM 12772999 ER PT J AU Kahn, T AF Kahn, T TI Reset osmostat and salt and water retention in the course of severe hyponatremia SO MEDICINE LA English DT Article ID INTOXICATION; POLYDIPSIA; HUMANS AB To evaluate whether a reset osmostat and salt and water retention may be features of the course of some patients with hyponatremia, we present the long-term course of 6 selected patients. Three patients had spinal cord injury, 3 had marked psychiatric problems, and 3 had alcoholism. Five developed severe hyponatremia superimposed on chronic hyponatremia consequent to a reset osmostat. In 5 patients marked salt and water retention of unclear etiology occurred during therapy on 11 occasions. In 4 of these 11 episodes hypernatremia developed. Knowledge of a patient's past history and the possibility of developing salt and water overload should influence therapy. C1 Bronx Vet Adm Med Ctr, Renal Sect, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RP Kahn, T (reprint author), Bronx Vet Adm Med Ctr, Renal Sect, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. NR 19 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2003 VL 82 IS 3 BP 170 EP 176 DI 10.1097/00005792-200305000-00003 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 679EC UT WOS:000182907000003 PM 12792303 ER PT J AU Cobb, KL Bachrach, LK Greendale, G Marcus, R Neer, RM Nieves, J Sowers, MF Brown, BW Gopalakrishnan, G Luetters, C Tanner, HK Ward, B Kelsey, JL AF Cobb, KL Bachrach, LK Greendale, G Marcus, R Neer, RM Nieves, J Sowers, MF Brown, BW Gopalakrishnan, G Luetters, C Tanner, HK Ward, B Kelsey, JL TI Disordered eating, menstrual irregularity, and bone mineral density in female runners SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE female athletes; long distance; osteopenia; osteoporosis; amenorrhea; oligomenorrhea; eating attitudes; eating disorder inventory; female athlete triad ID WOMEN DISTANCE RUNNERS; EXERCISE-INDUCED AMENORRHEA; ENERGY-BALANCE; STRESS-FRACTURES; COLLEGIATE WOMEN; WEIGHT-BEARING; SITES; DIET; OSTEOPOROSIS; DETERMINANTS AB Purpose: To examine the relationships between disordered eating, menstrual irregularity, and low bone mineral density (BMD) in young female runners. Methods: Subjects were 91 competitive female distance runners aged 18-26 yr. Disordered eating was measured by the Eating Disorder Inventory (EDI). Menstrual irregularity was defined as oligo/amenorrhea (0-9 menses per year). BMD was measured by dual x-ray absorptiometry. Results: An elevated score on the EDI (highest quartile) was associated with oligo/amenorrhea, after adjusting for percent body fat, age, miles run per week, age at menarche, and dietary fat, (OR [95% Cl]: 4.6 [1.1-18.6]). Oligo/amenorrheic runners had lower BMD than eumenorrheic runners at the spine (-5%), hip (-6%), and whole body (-3%), even after accounting for weight. percent body fat, EDI score, and age at menarche. Eumenorrheic runners with elevated EDI scores had lower BMD than eumenorrheic runners with normal EDI scores at the spine (-11%), with trends at the hip (-5%), and whole body (-5%), after adjusting for differences in weight and percent body fat. Runners with both an elevated EDI score and oligo/amenorrhea had no further reduction in BMD than runners with only one of these risk factors. Conclusion: In young competitive female distance runners, (i) disordered eating is strongly related to menstrual irregularity, (ii) menstrual irregularity is associated with low BMD, and (iii) disordered eating is associated with low BMD in the absence of menstrual irregularity. C1 Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Pediat, Sch Med, Stanford, CA 94305 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Stanford Univ, Sch Med, Vet Affairs Med Ctr, Palo Alto, CA 94304 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Helen Hayes Hosp, Clin Res Ctr, New York, NY USA. Columbia Univ, New York, NY USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. RP Cobb, KL (reprint author), Stanford Univ, Div Epidemiol, Dept Hlth Res & Policy, Sch Med, HRP Redwood Bldg, Stanford, CA 94305 USA. NR 50 TC 127 Z9 131 U1 3 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2003 VL 35 IS 5 BP 711 EP 719 DI 10.1249/01.MSS.0000064935.68277.E7 PG 9 WC Sport Sciences SC Sport Sciences GA 675UH UT WOS:000182714200001 PM 12750578 ER PT J AU Wakamatsu, MM AF Wakamatsu, MM TI What affects bladder function more: menopause or age? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. RP Wakamatsu, MM (reprint author), Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 6 TC 0 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD MAY-JUN PY 2003 VL 10 IS 3 BP 191 EP 192 DI 10.1097/01.GME.000006743.38349.2C PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 679EQ UT WOS:000182908100002 PM 12792287 ER PT J AU Yohrling, GJ Farrell, LA Hollenberg, AN Cha, JHJ AF Yohrling, GJ Farrell, LA Hollenberg, AN Cha, JHJ TI Mutant huntingtin increases nuclear corepressor function and enhances ligand-dependent nuclear hormone receptor activation SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID REPRESSES TRANSCRIPTION; MEDIATED TRANSCRIPTION; BINDING-PROTEIN; DISEASE PROTEIN; EXPRESSION; INTERACTS; DOMAIN; GENE; INHIBITION; MODEL AB There is increasing evidence that transcriptional dysregulation is important in Huntington's disease pathogenesis. The transcriptional protein, nuclear corepressor (NCoR), acts to repress transcription of nuclear hormone receptors, such as the thyroid hormone receptor (TR) and retinoic acid receptor, in the absence of their appropriate ligand. NCoR has been shown to bind to the mutated huntingtin protein in a yeast two-hybrid screen. This aberrant interaction may have profound effects on both the function of the NCoR protein and on its control of nuclear hormone receptor-mediated transcription. To test this hypothesis, reporter gene assays were performed in inducible PC 12 cell lines expressing exon 1 of the human huntingtin protein (Htt) with either a 25 or 103 polyglutamine (Q) repeat. Expression of mutant 103Q protein appears to enhance the ability of NCoR to repress TR-mediated transcription in the absence of ligand. Western analyses indicated that the expression of the mutant 103Q Htt protein did not change the endogenous NCoR levels in the HD103QPC12 cells when compared to uninduced cells. Interestingly, using GST pull-down assays we found that a mutant Htt exon 1 construct with 53 polyglutamine (HD53Q) did not bind to NCoR in a polyglutamine-dependent fashion. These findings suggest that an aberrant NCoR-Htt interaction does not exist in vitro. Expression of the mutant 103Q protein was also found to enhance ligand-dependent activation of TR and retinoic acid receptor. In vitro binding data shows that TR binds to HD53Q in the presence of ligand. Taken together these data suggest that Htt may function as a transcriptional coactivator of nuclear hormone receptors. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, Charlestown, MA 02129 USA. Beth Israel Deaconess Med Ctr, Thyroid Unit, Div Endocrinol, Boston, MA 02215 USA. RP Cha, JHJ (reprint author), Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Dept Neurol, 114 16th St,B114-2200, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01-DK-56123]; NINDS NIH HHS [R01-NS-38106] NR 29 TC 25 Z9 26 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2003 VL 23 IS 1 BP 28 EP 38 DI 10.1016/S1044-7431(03)00032-0 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 686VR UT WOS:000183342100003 PM 12799135 ER PT J AU Legesse-Miller, A Massol, RH Kirchhausen, T AF Legesse-Miller, A Massol, RH Kirchhausen, T TI Constriction and Dnm1p recruitment are distinct processes in mitochondrial fission SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID DYNAMIN-RELATED GTPASE; WD REPEAT PROTEIN; YEAST; DIVISION; IDENTIFICATION; FUSION; MORPHOLOGY; MEMBRANE; VPS1P; CELLS AB Mitochondria undergo cycles of fusion and fission crucial for organelle homeostasis. Fission is regulated partially by recruitment of the large GTPase Drun1p to the outer mitochondrial membrane. Using three-dimensional time-lapse fluorescence imaging of Saccharomyces cerevisiae cells, we found that Dnm1p-EGFP appears and disappears at "hot spots" along mitochondrial tubes. It forms patches that convert rapidly into different shapes regardless of whether mitochondrial fission ensues or not. Moreover, the thickness of the mitochondrial matrix displays frequent temporal fluctuations apparently unrelated to fission or to recruitment of Dnm1p-EGFP. These results suggest that mitochondrial fission requires coordination of at least two distinct processes. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIGMS NIH HHS [R01 GM036548, GM-036548] NR 26 TC 112 Z9 114 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2003 VL 14 IS 5 BP 1953 EP 1963 DI 10.1091/mbc.E02-10-0657 PG 11 WC Cell Biology SC Cell Biology GA 679ED UT WOS:000182907100019 PM 12802067 ER PT J AU Mahmood, U Weissleder, R AF Mahmood, U Weissleder, R TI Near-infrared optical imaging of proteases in cancer SO MOLECULAR CANCER THERAPEUTICS LA English DT Review ID TRANSFECTED CATHEPSIN-D; IN-SITU HYBRIDIZATION; MATRIX METALLOPROTEINASES; BREAST-CANCER; TUMOR PROGRESSION; MOLECULAR BEACONS; PROGNOSTIC-SIGNIFICANCE; COLORECTAL-CANCER; LUNG-CANCER; EXPRESSION AB Near-infrared optical imaging is a newer imaging technique that, coupled with sensitive enzymatically specific fluorescent beacons, shows much promise for earlier detection of many cancers and their in situ characterization. On the basis of animal studies demonstrating visualization of micrometastasis-sized tumors and the ability to evaluate therapeutic enzyme inhibition real-time, such imaging may be incorporated in the clinical imaging paradigm in the future, both to improve cancer screening as well as for monitoring therapy in individual patients. This review details some of the related biology, optical probe design, and required hardware, with in vivo cathepsin and matrix metalloprotinease imaging used as examples. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Boston, MA 02114 USA. NR 69 TC 206 Z9 210 U1 1 U2 34 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2003 VL 2 IS 5 BP 489 EP 496 PG 8 WC Oncology SC Oncology GA 679EG UT WOS:000182907400008 PM 12748311 ER PT J AU Settleman, J AF Settleman, J TI A nuclear MAL-Function links Rho to SRF SO MOLECULAR CELL LA English DT Editorial Material ID SERUM RESPONSE FACTOR; TRANSCRIPTION FACTORS; ACTIN DYNAMICS; ACTIVATION; MYOCARDIN; GTPASES; FAMILY; GENE AB The activation of SRF-mediated transcription in response to Rho GTPase-induced actin assembly involves the ability of SRF to sense changes in the cellular level of actin monomers. An article in the May 2 issue of Cell identifies the transcription factor MAL as an actin binding protein that functions as an SRF coactivator and whose translocation from cytoplasm to nucleus depends on its dissociation from actin monomers (Miralles et aL, 2003). C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. NR 9 TC 11 Z9 11 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY PY 2003 VL 11 IS 5 BP 1121 EP 1123 DI 10.1016/S1097-2765(03)00189-8 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 683GE UT WOS:000183139400001 PM 12769835 ER PT J AU Grad, Y Aach, J Hayes, GD Reinhart, BJ Church, GM Ruvkun, G Kim, J AF Grad, Y Aach, J Hayes, GD Reinhart, BJ Church, GM Ruvkun, G Kim, J TI Computational and experimental identification of C-elegans microRNAs SO MOLECULAR CELL LA English DT Article ID CAENORHABDITIS-ELEGANS; RNA-INTERFERENCE; REGULATORY RNA; POSTTRANSCRIPTIONAL REGULATION; GENE; EXPRESSION; LIN-14; SEQUENCE; INITIATION; ENCODES AB MicroRNAs (miRNAs) constitute an extensive class of noncoding RNAs that are thought to regulate the expression of target genes via complementary base-pair interactions. To date, cloning has identified over 200 miRNAs; from diverse eukaryotic organisms. Despite their success, such biochemical approaches are skewed toward identifying abundant miRNAs, unlike genome-wide, sequence-based computational predictions. We developed informatic methods to predict miRNAs in the C. elegans genome using sequence conservation and structural similarity to known miRNAs and generated 214 candidates. We confirmed the expression of four new miRNAs; by Northern blotting and used a more sensitive PCR approach to verify the expression of ten additional candidates. Based on hypotheses underlying our computational methods, we estimate that the C. elegans genome may encode between 140 and 300 miRNAs and potentially many more. C1 Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Lipper Ctr Computat Genet, Boston, MA 02115 USA. EM ruvkun@molbio.mgh.harvard.edu RI Hayes, Gabriel/B-9816-2012 FU NIGMS NIH HHS [GM44619] NR 36 TC 208 Z9 258 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY PY 2003 VL 11 IS 5 BP 1253 EP 1263 DI 10.1016/S1097-2765(03)00153-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 683GE UT WOS:000183139400015 PM 12769849 ER PT J AU Fan, HY He, X Kingston, RE Narlikar, GJ AF Fan, HY He, X Kingston, RE Narlikar, GJ TI Distinct strategies to make nucleosomal DNA accessible SO MOLECULAR CELL LA English DT Article ID CHROMATIN-REMODELING COMPLEX; YEAST SWI/SNF COMPLEX; HISTONE OCTAMER; ISWI; TRANSCRIPTION; HETEROCHROMATIN; MOBILIZATION; REPLICATION; EXPRESSION; DISRUPTION AB One hallmark of ATIP-dependent remodeling complexes is the ability to make nucleosomal DNA accessible to regulatory factors. We have compared two prominent human ATP-dependent remodelers, BRG1 from the SWI/SNF family and SNF2h from the ISWI family, for their abilities to make a spectrum of nucleosomal sites accessible. By measuring rates of remodeling at seven different sites on a mononucleosome and at six different sites on the central nucleosome of a trinucleosome, we have found that BRG1 opens centrally located sites more than an order of magnitude better than SNF2h. We provide evidence that this capability of BRG1 is caused by its ability to create DNA loops on the surface of a nucleosome, even when that nucleosome is constrained by adjacent nucleosomes. This specialized ability to make central sites accessible should allow SWI/SNF family complexes to facilitate binding of nuclear factors in chromatin environments where adjacent nucleosomes might otherwise constrain mobility. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Narlikar, GJ (reprint author), Univ Calif San Francisco, Dept Biochem & Biophys, 600 16th St,Genentech Hall, San Francisco, CA 94143 USA. FU NIGMS NIH HHS [GM 20209] NR 37 TC 119 Z9 122 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAY PY 2003 VL 11 IS 5 BP 1311 EP 1322 DI 10.1016/S1097-2765(03)00192-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 683GE UT WOS:000183139400020 PM 12769854 ER PT J AU Chau, KY Manfioletti, G Cheung-Chau, KW Fusco, A Dhomen, N Sowden, JC Sasabe, T Mukai, S Ono, SJ AF Chau, KY Manfioletti, G Cheung-Chau, KW Fusco, A Dhomen, N Sowden, JC Sasabe, T Mukai, S Ono, SJ TI Derepression of HMGA2 gene expression in retinoblastoma is associated with cell proliferation SO MOLECULAR MEDICINE LA English DT Article ID ARCHITECTURAL TRANSCRIPTION FACTOR; MOBILITY GROUP PROTEIN; I-C PROTEIN; NEOPLASTIC TRANSFORMATION; MESENCHYMAL TUMORS; GENOMIC STRUCTURE; THYROID-CELLS; CDNA CLONING; DNA; SEQUENCE AB To assess whether retinoblastoma formation is associated with the expression of high mobility group (HMG) A2 protein, a transcription factor that is highly expressed during embryogenesis and completely repressed in normal adult tissues, we performed Northern and Western blots and RT-PCR analyses, and immunohistochemistry to test for HMGA2 expression. We used established retinoblastoma cell lines in tumors grown in nude mice and clinical retinoblastoma specimens, and contrasted these tumors with normal embryonic and adult retina. Adenoviral-mediated antisense experiments were conducted on the retinoblastoma cell lines to suppress HMGA2 expression and determine if cell proliferation is HMGA2dependent. We also transfected a retinoblastoma cell line to identify cis-regulatory elements and transcription initiation sites on the HMGA2 gene promoter. HMGA2 gene expression was silenced in terminally differentiated retina of 6-wk-old mice, but it was detected in retina of a 13.5-d postcoitum embryo. Reactivation of HMGA2 gene expression was observed in the retinoblastoma cell lines Y79, WERI-Rb1, and TOTL-1, in tumors derived from some of these cells propagated in nude mice, and in a high frequency of retinoblastomas excised from human patients. This suggests that expression of HMGA2 gene in retinoblastoma cells involves a derepression process. By using an antisense approach to block HMGA2 expression, we observed a decrease in the number of proliferating retinoblastoma cells. As a 1 st step toward understanding HMGA2 gene reactivation in retinoblastoma, we mapped the 2 transcription initiation sites and associated positive regulatory elements within the WERI-Rb1 cells. Our discovery of derepression of HMGA2 gene expression in retinoblastoma provides the 1 st evidence that this protein might contribute to neoplastic transformation of retina cells. C1 UCL, Dept Immunol, Inst Ophthalmol, London, England. UCL, Dept Immunol, Inst Child Hlth, London, England. Univ Trieste, Dipartimento Biochim Biofis & Chim Macromol, Trieste, Italy. Univ Naples Federico 2, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy. UCL, Inst Child Hlth, Dev Biol Unit, London, England. Osaka Habikino Hosp, Dept Ophthalmol, Osaka, Japan. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Ono, SJ (reprint author), UCL, Dept Immunol, Inst Ophthalmol, Mortimer St, London, England. EM santa.ono@ucl.ac.uk RI Chau, Kai-Yin (David)/C-2845-2011; OI Fusco, Alfredo/0000-0003-3332-5197 FU NIGMS NIH HHS [R01 GM49661] NR 50 TC 13 Z9 17 U1 0 U2 1 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD MAY-AUG PY 2003 VL 9 IS 5-8 BP 154 EP 165 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 738ED UT WOS:000186273000004 PM 14571323 ER PT J AU Luthi-Carter, R AF Luthi-Carter, R TI Progress towards a vaccine for Huntington's disease SO MOLECULAR THERAPY LA English DT Article ID AGGREGATION C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Luthi-Carter, R (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 9 TC 9 Z9 12 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 BP 569 EP 570 DI 10.1006/mthe.2003.0942 PN 1 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 674PU UT WOS:000182645800002 PM 12718897 ER PT J AU Wade-Martins, R Saeki, Y Chiocca, EA AF Wade-Martins, R Saeki, Y Chiocca, EA TI Infectious delivery of a 135-kb LDLR genomic locus leads to regulated complementation of low-density lipoprotein receptor deficiency in human cells SO MOLECULAR THERAPY LA English DT Article DE gene transfer; gene expression regulation; genomic DNA; herpesvirus; amplicon; bacterial artificial chromosome; functional genomics; episomal vector; cardiovascular disease ID EPSTEIN-BARR-VIRUS; VIVO GENE-THERAPY; HERITABLE HYPERLIPIDEMIC RABBIT; ADENOVIRUS-MEDIATED TRANSFER; FAMILIAL HYPERCHOLESTEROLEMIA; IN-VIVO; AMPLICON VECTORS; DNA-SEQUENCE; EXPRESSION; SYSTEM AB The ability to deliver efficiently a complete genomic DNA locus to human and rodent cells will likely find widespread application in functional genomic studies and novel gene therapy protocols. In contrast to a cDNA expression cassette, the use of a complete genomic DNA locus delivers a transgene intact with its native promoter, the exons, all the intervening introns, and the regulatory regions. The presence of flanking, noncoding genomic DNA sequences could prove critical for prolonged and appropriate gene expression. We have recently developed a technology for the rapid conversion of bacterial artificial chromosome (BAC) clones into high-capacity herpes simplex virus-based amplicon vectors. Here, we express the human low-density lipoprotein receptor (LDLR), mutated in familial hypercholesterolemia (FH), from a 135-kb BAC insert. The infectious LDLR genomic locus vectors were shown to express at physiologically appropriate levels in three contexts. First, the LDLR locus was expressed appropriately in the ldl(-/-)a7 Chinese hamster ovary (CHO) cell line immediately following infectious delivery; second, the locus was maintained within a replicating episomal vector and expressed at broadly physiological levels in CHO cells for 3 months following infectious delivery; and third, the locus was efficiently expressed in human fibroblasts derived from FH patients. Finally, we show that the infectious LDLR locus retains classical expression regulation by sterol levels in human cells. This long-term expression and physiological regulation of LDLR prepares the way for in vivo functional studies of infectious delivery of BAC inserts. C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Neurosurg Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Wade-Martins, R (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. EM richard.wade-martins@well.ox.ac.uk; saeki@helix.mgh.harvard.edu FU NCI NIH HHS [CA692460] NR 45 TC 79 Z9 80 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 BP 604 EP 612 DI 10.1016/S1525-0016(03)00060-1 PN 1 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 674PU UT WOS:000182645800008 PM 12718903 ER PT J AU Baloglu, S Cucchiarini, M Francis, JW Terwilliger, EF AF Baloglu, S Cucchiarini, M Francis, JW Terwilliger, EF TI A gene therapy approach to spinal muscular atrophy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Harvard Univ, Inst Med, Div Expt Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Saarland, Ctr Med, Dept Orthopaed Surg, Lab Expt Orthopaed, Homburg, Germany. Massachusetts Gen Hosp, Cecil Day Neuromuscular Res Lab, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 488 BP S191 EP S191 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300487 ER PT J AU Goss, JR Tubio, AT Fetterolf, CM Mata, M Glorioso, JC Fink, DJ AF Goss, JR Tubio, AT Fetterolf, CM Mata, M Glorioso, JC Fink, DJ TI A non-replicating HSV vector expressing interleukin-4 reduces pain-related behavior in a mouse model of bone cancer pain SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 635 BP S248 EP S248 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300634 ER PT J AU Ino, Y Saeki, Y Chiocca, EA Martuza, RL Todo, T AF Ino, Y Saeki, Y Chiocca, EA Martuza, RL Todo, T TI Simultaneous administration of multiple oncolytic HSV-1 vectors expressing different immunostimulatory genes provides high antitumor efficacy in a poorly immunogenic tumor model SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurosurg Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab, Boston, MA USA. Univ Tokyo, Dept Neurosurg, Tokyo 113, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 957 BP S368 EP S369 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300956 ER PT J AU Inoue, R Moghaddam, KA Saeki, Y Chiocca, EA Wade-Martins, R Ranasinghe, M AF Inoue, R Moghaddam, KA Saeki, Y Chiocca, EA Wade-Martins, R Ranasinghe, M TI Infectious delivery of the 132 kb CDKN2A/CDKN2B genomic DNA region results in correctly spliced gene expression and growth suppression in glioma cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Mol Neurooncol Labs, Charlestown, MA USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1218 BP S471 EP S471 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301217 ER PT J AU Lawler, SE Ingelsson, M Augustinack, JC Saeki, Y Hyman, BT Chiocca, EA Wade-Martins, R AF Lawler, SE Ingelsson, M Augustinack, JC Saeki, Y Hyman, BT Chiocca, EA Wade-Martins, R TI Examination of the pathological mechanism of the microtubule associated protein tau using an HSV amplicon based neuronal gene delivery system SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Ctr Aging Genet & Neurodegenerat, Charlestown, MA USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 960 BP S369 EP S370 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300959 ER PT J AU Messerli, SM Tang, Y Giovannini, M Prabhakar, S Murthy, V Schuback, D Sena-Esteves, M Todo, T Rabkin, S Martuza, R Tung, C Weissleder, R Breakefield, XO AF Messerli, SM Tang, Y Giovannini, M Prabhakar, S Murthy, V Schuback, D Sena-Esteves, M Todo, T Rabkin, S Martuza, R Tung, C Weissleder, R Breakefield, XO TI Treatment of schwannomas in a transgenic murine model of neurofibromatosis type 2 (NF2) using both HSV recombinant and amplicon vectors SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Dept Radiol, Charlestown, MA USA. Harvard Univ, Sch Med, Program Neurosci, Charlestown, MA USA. INSERM, U434, CEPH, Fdn Jean Dausset, Paris, France. Childrens Hosp Philadelphia, Dept Gen Surg, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Mol Neurosurg Lab, Dept Neurosurg, Boston, MA 02114 USA. RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 230 BP S91 EP S91 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300231 ER PT J AU Monahan, PE Rabinowitz, JE Elia, JR Tang, Y Ntziachristo, V Sorg, BS Dewhirst, MW Weissleder, R Samulski, RJ AF Monahan, PE Rabinowitz, JE Elia, JR Tang, Y Ntziachristo, V Sorg, BS Dewhirst, MW Weissleder, R Samulski, RJ TI Serial real-time luminescence imaging profiles differential kinetics and biodistibution of transgene expression from AAV serotype 1-5 vectors following adult and neonatal gene transfer SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA. Massachusetts Gen Hosp, Charlestown, MA USA. Duke Univ, Ctr Med, Durham, NC USA. NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 401 BP S158 EP S159 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300401 ER PT J AU Mountz, JD Yang, PA Wu, Q Hsu, HC Zhang, HG AF Mountz, JD Yang, PA Wu, Q Hsu, HC Zhang, HG TI Identification of multiple genetic loci that regulate clearance of adenovirus gene therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 16 BP S7 EP S7 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300017 ER PT J AU Tsuji, T del Monte, F Hayase, M Guerrero, JL Abe, T Yoshikawa, Y Kobayashi, S Taniguchi, S Takaki, M Hajjar, RJ AF Tsuji, T del Monte, F Hayase, M Guerrero, JL Abe, T Yoshikawa, Y Kobayashi, S Taniguchi, S Takaki, M Hajjar, RJ TI Efficient cardiac gene transfer using percutaneous aortic occlusion technique in the rat SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Surg Res, Boston, MA USA. Nara Med Univ, Dept Surg 3, Kashihara, Nara, Japan. Nara Med Univ, Dept Physiol 2, Kashihara, Nara, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 612 BP S238 EP S238 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300611 ER PT J AU Tyminski, E Terada, K Hyatt, JL Danks, MK Potter, PM Saeki, Y Chiocca, EA AF Tyminski, E Terada, K Hyatt, JL Danks, MK Potter, PM Saeki, Y Chiocca, EA TI Augmentation of tumor cell oncolysis by HSV mutant expressing prod rug-activating enzymes, CYP2B1 and CE, in combination with cyclophosphamide and irinotecan chemotherapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RI Potter, Philip/J-4515-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 815 BP S314 EP S314 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300814 ER PT J AU Zerbini, LF Wang, YH Cho, JY Gu, XS Jones, J Inan, M Bailey, C Joseph, M Zhou, JR Libermann, TA AF Zerbini, LF Wang, YH Cho, JY Gu, XS Jones, J Inan, M Bailey, C Joseph, M Zhou, JR Libermann, TA TI Transcription factors NF-kB and AP-1 as targets for prostate cancer gene therapy SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Harvard Univ, Sch Med, BIDMC Genom Ctr, Boston, MA 02115 USA. RI Zerbini, Luiz /B-7720-2015 NR 0 TC 0 Z9 0 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 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1075 BP S415 EP S415 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301074 ER PT J AU Zhang, HG Hyde, K Page, GP Brand, JPL Hsu, HC Allison, DB Mountz, JD AF Zhang, HG Hyde, K Page, GP Brand, JPL Hsu, HC Allison, DB Mountz, JD TI AdlkB-DN specifically blocks a TNF-alpha-induced anti-apoptosis signaling resulting in significant downregulation of 350 genes that normally enhance adhesion or inflammation in RASF SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Alabama, Sect Stat Genet, Dept Stat, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 1048 BP S404 EP S404 PN 2 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740301047 ER PT J AU Zhang, HG Mountz, JM Wu, Q Yang, P Hsu, HC Mountz, JD AF Zhang, HG Mountz, JM Wu, Q Yang, P Hsu, HC Mountz, JD TI T cells transfected with Ad-hSSTR2 into T cells from hCARxTg71xGFP triple transgenic mice can be used to determine T-cell activation and AICD in vitro and in vivo SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 6th Annual Meeting of the American-Society-of-Gene-Therapy CY JUN 04-08, 2003 CL WASHINGTON, D.C. SP Amer Soc Gene Therapy C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD MAY PY 2003 VL 7 IS 5 MA 282 BP S111 EP S112 PN 2 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 676FH UT WOS:000182740300283 ER PT J AU Lee, JT AF Lee, JT TI Molecular biology: Complicity of gene and pseudogene SO NATURE LA English DT Editorial Material ID GENOME C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. RP Lee, JT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu NR 8 TC 26 Z9 28 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 1 PY 2003 VL 423 IS 6935 BP 26 EP 28 DI 10.1038/423026a PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673CG UT WOS:000182561600026 PM 12721611 ER PT J AU Reboul, J Vaglio, P Rual, JF Lamesch, P Martinez, M Armstrong, CM Li, SM Jacotot, L Bertin, N Janky, R Moore, T Hudson, JR Hartley, JL Brasch, MA Vandenhaute, J Boulton, S Endress, GA Jenna, S Chevet, E Papasotiropoulos, V Tolias, PP Ptacek, J Snyder, M Huang, R Chance, MR Lee, HM Doucette-Stamm, L Hill, DE Vidal, M AF Reboul, J Vaglio, P Rual, JF Lamesch, P Martinez, M Armstrong, CM Li, SM Jacotot, L Bertin, N Janky, R Moore, T Hudson, JR Hartley, JL Brasch, MA Vandenhaute, J Boulton, S Endress, GA Jenna, S Chevet, E Papasotiropoulos, V Tolias, PP Ptacek, J Snyder, M Huang, R Chance, MR Lee, HM Doucette-Stamm, L Hill, DE Vidal, M TI C-elegans ORFeome version 1.1: experimental verification of the genome annotation and resource for proteome-scale protein expression SO NATURE GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; FUNCTIONAL ANNOTATION; GENES; IDENTIFICATION; MICROARRAYS; BIOLOGY; CLONING; YEAST; CDNAS; MAPS AB To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Fac Univ Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Belgium. Res Genet Invitrogen, Huntsville, AL USA. Life Technol Invitrogen, Rockville, MD USA. Protedyne Crop, Windsor, CT 06095 USA. McGill Univ, Dept Surg, Montreal, PQ H3A 2T5, Canada. Publ Hlth Res Inst, Ctr Appl Genom, Newark, NJ 07103 USA. Yale Univ, New Haven, CT 06520 USA. Albert Einstein Coll Med, Ctr Synchrotron Biosci, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. Genome Therapeut, Waltham, MA 02453 USA. RP Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM marc_vidal@dfci.harvard.edu RI Bertin, Nicolas/C-3025-2008; Hill, David/B-6617-2011; Chevet, Eric/E-4992-2016; Reboul, Jerome/P-9103-2016; OI Bertin, Nicolas/0000-0002-9835-9606; Chevet, Eric/0000-0001-5855-4522; Reboul, Jerome/0000-0002-5513-4546; Vaglio, Philippe/0000-0003-2900-5596; Huang, Raymond/0000-0001-7661-797X; Rual, Jean-Francois/0000-0003-4465-8819 NR 30 TC 255 Z9 265 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD MAY PY 2003 VL 34 IS 1 BP 35 EP 41 DI 10.1038/ng1140 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 674ZK UT WOS:000182667900014 PM 12679813 ER PT J AU Paw, BH Davidson, AJ Zhou, Y Li, R Pratt, SJ Lee, C Trede, NS Brownlie, A Donovan, A Liao, EC Ziai, JM Drejer, AH Guo, W Kim, CH Gwynn, B Peters, LL Chernova, MN Alper, SL Zapata, A Wickramasinghe, SN Lee, MJ Lux, SE Fritz, A Postlethwait, JH Zon, LI AF Paw, BH Davidson, AJ Zhou, Y Li, R Pratt, SJ Lee, C Trede, NS Brownlie, A Donovan, A Liao, EC Ziai, JM Drejer, AH Guo, W Kim, CH Gwynn, B Peters, LL Chernova, MN Alper, SL Zapata, A Wickramasinghe, SN Lee, MJ Lux, SE Fritz, A Postlethwait, JH Zon, LI TI Cell-specific mitotic defect and dyserythropoiesis associated with erythroid band 3 deficiency SO NATURE GENETICS LA English DT Article ID ANEMIA TYPE-II; POLYMERASE CHAIN-REACTION; STRUCTURAL PROTEIN-4.1; MEMBRANE SKELETON; IDENTIFICATION; LOCALIZATION; BINDING; LINKAGE; GENE; AE1 AB Most eukaryotic cell types use a common program to regulate the process of cell division. During mitosis, successful partitioning of the genetic material depends on spatially coordinated chromosome movement and cell cleavage(1). Here we characterize a zebrafish mutant, retsina (ret), that exhibits an erythroid-specific defect in cell division with marked dyserythropoiesis similar to human congenital dyserythropoietic anemia. Erythroblasts from ret fish show binuclearity and undergo apoptosis due to a failure in the completion of chromosome segregation and cytokinesis. Through positional cloning, we show that the ret mutation is in a gene (slc4a1) encoding the anion exchanger 1 (also called band 3 and AE1), an erythroid-specific cytoskeletal protein. We further show an association between deficiency in Slc4a1 and mitotic defects in the mouse. Rescue experiments in ret zebrafish embryos expressing transgenic slc4a1 with a variety of mutations show that the requirement for band 3 in normal erythroid mitosis is mediated through its protein 4.1R-binding domains. Our report establishes an evolutionarily conserved role for band 3 in erythroid-specific cell division and illustrates the concept of cell-specific adaptation for mitosis. C1 Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME USA. Jackson Lab, Bar Harbor, ME 04609 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Mol Med Unit, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA USA. Univ Complutense, Dept Cell Biol, E-28040 Madrid, Spain. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England. Univ London Imperial Coll Sci Technol & Med, Dept Hematol, London, England. Emory Univ, Dept Biol, Atlanta, GA 30322 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. RP Zon, LI (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL064885] NR 29 TC 80 Z9 81 U1 2 U2 6 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 MAY PY 2003 VL 34 IS 1 BP 59 EP 64 DI 10.1038/ng1137 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 674ZK UT WOS:000182667900017 PM 12669066 ER PT J AU Opferman, JT Korsmeyer, SJ AF Opferman, JT Korsmeyer, SJ TI Apoptosis in the development and maintenance of the immune system SO NATURE IMMUNOLOGY LA English DT Review ID RECEPTOR-DEFICIENT MICE; PROGRAMMED CELL-DEATH; FAMILY MEMBER BIM; RESCUES T-LYMPHOPOIESIS; BCL-2 FAMILY; CYTOCHROME-C; MITOCHONDRIAL APOPTOSIS; TRANSGENIC MICE; NEGATIVE SELECTION; LACKING JAK3 AB Programmed cell death is essential for the development and maintenance of cellular homeostasis of the immune system. The Bcl-2 family of proteins comprises both pro-apoptotic and. anti-apoptotic members. A subset of pro-apoptotic members, called 'BH3-only' proteins, share sequence homology only in the minimal death domain, designated the Bcl-2 homology 3 (BH3) domain. BH3-only proteins operate as upstream sentinels, selectively sensing both intrinsic and extrinsic death stimuli. They communicate this information to the pro. apoptotic 'multidomain' members Bax or Bak-a process that is antagonized by anti-apoptotic members of the Bcl-2 family. The functional balance of pro-apoptotic versus anti-apoptotic influences, which operates at organelles, determines whether a lymphocyte will live or die. BH3-only molecules, often working in concert, compete for downstream multidomain pro-and anti-apoptotic BCL-2 members to control serial stages of lymphocyte development and homeostasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Korsmeyer, SJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst, 44 Binney St, Boston, MA 02115 USA. NR 101 TC 329 Z9 341 U1 1 U2 15 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 MAY PY 2003 VL 4 IS 5 BP 410 EP 415 DI 10.1038/ni0503-410 PG 6 WC Immunology SC Immunology GA 674YN UT WOS:000182665400004 PM 12719730 ER PT J AU Shinkura, R Tian, M Smith, M Chua, K Fujiwara, Y Alt, FW AF Shinkura, R Tian, M Smith, M Chua, K Fujiwara, Y Alt, FW TI The influence of transcriptional orientation on endogenous switch region function SO NATURE IMMUNOLOGY LA English DT Article ID CYTIDINE DEAMINASE AID; B-CELLS; SOMATIC HYPERMUTATION; ANTIBODY DIVERSIFICATION; DNA DEAMINATION; DEFICIENT MICE; IGH LOCI; RECOMBINATION; RNA; EXPRESSION AB Immunoglobulin heavy chain (IgH) class switch recombination (CSR) takes place between large switch (S) regions that precede exons of the constant region. The precise functions of the S region are controversial, although transcription of the S region targets CSR. We have tested the effects of deletion, inversion and replacement of the endogenous 12-kilobase S-gamma1 region on CSR in vivo. Here we show that S-gamma1 is required for CSR, that CSR is effected by a 1-kilobase sequence that generates a G-rich transcript, and that inversion of S-gamma1 or the G-rich sequence decreases CSR. We conclude that S-gamma1 function is dependent on orientation and lacks an absolute requirement for common S region motifs. We propose that single-stranded DNA stabilized by transcription-dependent, higher order structures is a primary substrate of CSR. C1 Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. FU NIAID NIH HHS [AI07512, AI31541] NR 58 TC 142 Z9 145 U1 0 U2 5 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 MAY PY 2003 VL 4 IS 5 BP 435 EP 441 DI 10.1038/ni918 PG 7 WC Immunology SC Immunology GA 674YN UT WOS:000182665400010 PM 12679811 ER PT J AU Golub, TR AF Golub, TR TI Mining the genome for combination therapies SO NATURE MEDICINE LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst, MIT, Ctr Genome Res, Cambridge, MA 02142 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Golub, TR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 4 TC 16 Z9 16 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 MAY PY 2003 VL 9 IS 5 BP 510 EP 511 DI 10.1038/nm0503-510 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 673ZD UT WOS:000182610600022 PM 12724758 ER PT J AU Dolmans, DEJGJ Fukumura, D Jain, RK AF Dolmans, DEJGJ Fukumura, D Jain, RK TI Photodynamic therapy for cancer SO NATURE REVIEWS CANCER LA English DT Editorial Material ID HUMAN BLADDER-CARCINOMA; PHOTORADIATION THERAPY; IN-VIVO; PHASE-I; LIGHT FRACTIONATION; TUMOR-MODEL; PORPHYRIN PHOTOSENSITIZATION; MACULAR DEGENERATION; MALIGNANT-TUMORS; ANIMAL TUMORS AB The therapeutic properties of light have been known for thousands of years, but it was only in the last century that photodynamic therapy (PDT) was developed. At present, PDT is being tested in the clinic for use in oncology-to treat cancers of the head and neck, brain, lung, pancreas, intraperitoneal cavity, breast, prostate and skin. How does PDT work, and how can it be used to treat cancer and other diseases?. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Fukumura, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol,Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. NR 127 TC 1970 Z9 2031 U1 129 U2 773 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD MAY PY 2003 VL 3 IS 5 BP 380 EP 387 DI 10.1038/nrc1071 PG 8 WC Oncology SC Oncology GA 680YP UT WOS:000183007900017 PM 12724736 ER PT J AU Lieberman, J AF Lieberman, J TI The ABCs of granule-mediated cytotoxicity: New weapons in the arsenal SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID PROTEASE GRANZYME-A; CYTOCHROME-C RELEASE; NATURAL-KILLER-CELLS; CYTOLYTIC T-CELLS; INDUCED APOPTOSIS; IMMUNOLOGICAL SYNAPSE; TARGET-CELLS; DNA FRAGMENTATION; IN-VITRO; MYCOBACTERIUM-TUBERCULOSIS AB Granule exocytosis is the main pathway for the immune elimination of virus-infected cells and tumour cells by cytotoxic T lymphocytes and natural killer cells. After target-cell recognition, release of the cytotoxic granule contents into the immunological synapse formed between the killer cell and its target induces apoptosis. The granules contain two membrane-perturbing proteins, perforin and granulysin, and a family of serine proteases known as granzymes, complexed with the proteoglycan serglycin. In this review, I discuss recent insights into the mechanisms of granule-mediated cytotoxicity, focusing on how granzymes A, Band C and granulysin activate cell death through caspase-independent pathways. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 106 TC 390 Z9 404 U1 2 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD MAY PY 2003 VL 3 IS 5 BP 361 EP 370 DI 10.1038/nri1083 PG 10 WC Immunology SC Immunology GA 679MC UT WOS:000182925400017 PM 12766758 ER PT J AU Davidson, BL Breakefield, XO AF Davidson, BL Breakefield, XO TI Viral vectors for gene delivery to the nervous system SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID HERPES-SIMPLEX-VIRUS; NEURAL STEM-CELLS; RETROGRADE AXONAL-TRANSPORT; GREEN FLUORESCENT PROTEIN; SITE-SPECIFIC INTEGRATION; SUSTAINED TRANSGENE EXPRESSION; AMYOTROPHIC-LATERAL-SCLEROSIS; LYSOSOMAL STORAGE DISEASE; BLOOD-BRAIN-BARRIER; IN-VIVO AB Our ability to manipulate the genetic constitution of the nervous system has come of age with various technologies, including virus vectors that can efficiently deliver genes to neurons and other neural cells in vitro and in vivo. These vectors allow us to monitor neurobiological functions, replace, correct, express or block expression of target genes, tag cells for fate determination, and change the physiological state of specific cell populations. The available vectors differ in their suitability for different applications, which depends on factors such as the size of the transgene, route of delivery, tropism, duration and regulation of gene expression, and side effects. C1 Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Program Gene Therapy, Iowa City, IA 52242 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02129 USA. RP Davidson, BL (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Program Gene Therapy, Iowa City, IA 52242 USA. NR 176 TC 187 Z9 192 U1 1 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2003 VL 4 IS 5 BP 353 EP 364 DI 10.1038/nrn1104 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 674YK UT WOS:000182665100012 PM 12728263 ER PT J AU Lo, EH Dalkara, T Moskowitz, MA AF Lo, EH Dalkara, T Moskowitz, MA TI Mechanisms, challenges and opportunities in stroke SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; TISSUE-PLASMINOGEN-ACTIVATOR; BLOOD-BRAIN-BARRIER; MATRIX-METALLOPROTEINASE EXPRESSION; CENTRAL-NERVOUS-SYSTEM; INTERCELLULAR-ADHESION MOLECULE-1; RANDOMIZED CONTROLLED TRIAL; OXYGEN-GLUCOSE DEPRIVATION; CUZN-SUPEROXIDE-DISMUTASE AB Over the past two decades, research has heavily emphasized basic mechanisms that irreversibly damage brain cells after stroke. Much attention has focused on what makes neurons die easily and what strategies render neurons resistant to ischaemic injury. In the past few years, clinical experience with clot-lysing drugs has confirmed expectations that early reperfusion improves clinical outcome. With recent research emphasizing ways to reduce tissue damage by both vascular and cell-based mechanisms, the spotlight is now shifting towards the study of how blood vessels and brain cells communicate with each other. This new research focus addresses an important need in stroke research, and provides challenges and opportunities that can be used to therapeutic advantage. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Hacettepe Univ, Fac Med, Dept Neurol, TR-06100 Ankara, Turkey. RP Moskowitz, MA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Neurosci, Stroke & Neurovasc Regulat Lab, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 NR 237 TC 815 Z9 877 U1 15 U2 113 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD MAY PY 2003 VL 4 IS 5 BP 399 EP 415 DI 10.1038/nrn1106 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 674YK UT WOS:000182665100016 PM 12728267 ER PT J AU Schellenberger, EA Bogdanov, A Petrovsky, A Ntziachristos, V Weissleder, R Josephson, L AF Schellenberger, EA Bogdanov, A Petrovsky, A Ntziachristos, V Weissleder, R Josephson, L TI Optical imaging of apoptosis as a biomarker of tumor response to chemotherapy SO NEOPLASIA LA English DT Article DE annexin V; optical imaging; apoptosis; tumor; chemotherapy ID PROGRAMMED CELL-DEATH; IN-VIVO DETECTION; ANNEXIN-V; FLOW-CYTOMETRY; GASTRIC-CANCER; REAL-TIME; PHOSPHATIDYLSERINE; NECROSIS; EXPOSURE; SYSTEM AB A rapid and accurate assessment of the antitumor efficacy of new therapeutic drugs could speed up drug discovery and improve clinical decision making. Based on the hypothesis that most effective antitumor agents induce apoptosis, we developed a near-infrared fluorescent (NIRF) annexin V to be used for optical sensing of tumor environments. To demonstrate probe specificity, we developed both an active (i.e., apoptosis-recognizing) and an inactive form of annexin V with very similar properties (to account for nonspecific tumor accumulation), and tested the agents in nude mice each bearing a cyclophosphamide (CPA) chemosensitive (LLC) and a chemoresistant LLC (CR-LLC). After injection with active annexin V, the tumor-annexin V ratio (TAR; tumor NIRF/background NIRF) for untreated mice was 1.22 +/- 0.34 for LLC and 1.43 +/- 0.53 for CR-LLC (n = 4). The LLC of CPA-treated mice had significant elevations of TAR (2.56 +/- 0.29, P = .001, n = 4), but only a moderate increase was obtained for the CR-LLC (TAR = 1.89 +/- 0.19, P = .183). The in vivo measurements correlated well with terminal deoxyribosyl transferase-mediated dUTP nick end labeling indexes. When inactive Cy-annexin V was used, with or without CPA treatment and in both CCL and CR-CCL tumors, tumor NIRF values ranged from 0.91 to 1.17 (i.e., tumor were equal to background). We conclude that active Cy-annexin V and surface reflectance fluorescence imaging provide a nonradioactive, semiquantitative method of determining chemosensitivity in LLC xenografts. The method maybe used to image pharmacologic responses in other animal models and, potentially, may permit the clinical imaging of apoptosis with non-invasive or minimally invasive instrumentation. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Josephson, L (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5403, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA91807, R33 CA091807, P50 CA086355, P50CA86355, R01 CA086782, R01CA86782, R21 CA091807, R24 CA092782, R24 CA92782] NR 31 TC 90 Z9 95 U1 2 U2 7 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2003 VL 5 IS 3 BP 187 EP 192 PG 6 WC Oncology SC Oncology GA 727AZ UT WOS:000185635000001 PM 12869301 ER PT J AU Allport, JR Weissleder, R AF Allport, JR Weissleder, R TI Murine lewis lung carcinoma-derived endothelium expresses markers of endothelial activation and requires tumor-specific extracellular matrix in vitro SO NEOPLASIA LA English DT Article DE endothelium; tumor; adhesion molecule; extracellular matrix; murine ID HEMATOPOIETIC PROGENITOR CELLS; ADHESION MOLECULES; E-SELECTIN; ANGIOGENESIS; GROWTH; CANCER; NEUTROPHILS; MICE; NEOVASCULARIZATION; IDENTIFICATION AB The purpose of the study was to identify characteristics specific to tumor-derived endothelium that may be important in tumor biology, or for the development of targeted therapeutics or imaging agents. Normal C57BI/6 murine heart or lung endothelium, or C57BI/6 murine Lewis lung carcinoma tumor-derived endothelium was isolated from excised tissues using specific antibodies. The endothelium was cultured using either native fibronectin, or the oncofetal form of fibronectin. Cell surface adhesion molecule expression was analyzed by flow cytometry, and the cellular distribution of specific molecules was examined using indirect immunofluorescence staining. Oncofetal fibronectin was critical for maintaining the phenotype of tumor-derived endothelium, which demonstrated an elongated morphology in vitro, with few cell-cell contacts. They expressed high levels of CD31, CD102, and vascular endothelial cadherin, and constitutively expressed CD62E, CD54, and CD106, indicating an "activated" phenotype. Moreover, they expressed significantly greater levels of Sca-1 and Flk-1 than normal murine endothelium. Cellular distribution of CD31, beta-catenin, and CD106 in tumor-derived endothelium was not continuous at cell borders, as observed in cultures of murine heart endothelium. In conclusion, Lewis lung carcinoma-derived tumor endothelium exhibits a specific phenotype in vitro, distinct from normal endothelium, and could be used as an in vitro tool for developing targeted agents. C1 Massachusetts Gen Hosp, Dept Radiol, CMIR, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Allport, JR (reprint author), Massachusetts Gen Hosp, Dept Radiol, CMIR, Room 5416,149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [R01 CA085240, CA85240-02, P50 CA086355, CA96978-01, CA79443-01A1, R01 CA096978, CA86355-02, T32 CA079443]; NIAID NIH HHS [AI86782-02] NR 38 TC 24 Z9 25 U1 0 U2 1 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD MAY-JUN PY 2003 VL 5 IS 3 BP 205 EP 217 PG 13 WC Oncology SC Oncology GA 727AZ UT WOS:000185635000004 PM 12869304 ER PT J AU Smith, AC Brown, EN AF Smith, AC Brown, EN TI Estimating a state-space model from point process observations SO NEURAL COMPUTATION LA English DT Article ID TIME; HIPPOCAMPUS; CODE; RAT AB A widely used signal processing paradigm is the state-space model. The state-space model is defined by two equations: an observation equation that describes how the hidden state or latent process is observed and a state equation that defines the evolution of the process through time. Inspired by neurophysiology experiments in which neural spiking activity is induced by an implicit (latent) stimulus, we develop an algorithm to estimate a state-space model observed through point process measurements. We represent the latent process modulating the neural spiking activity as a gaussian autoregressive model driven by an external stimulus. Given the latent process, neural spiking activity is characterized as a general point process defined by its conditional intensity function. We develop an approximate expectation-maximization (EM) algorithm to estimate the unobservable state-space process, its parameters, and the parameters of the point process. The EM algorithm combines a point process recursive nonlinear filter algorithm, the fixed interval smoothing algorithm, and the state-space covariance algorithm to compute the complete data log likelihood efficiently. We use a Kolmogorov-Smirnov test based on the time-rescaling theorem to evaluate agreement between the model and point process data. We illustrate the model with two simulated data examples: an ensemble of Poisson neurons driven by a common stimulus and a single neuron whose conditional intensity function is approximated as a local Bernoulli process. C1 Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Smith, AC (reprint author), Massachusetts Gen Hosp, Neurosci Stat Res Lab, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL 07901]; NIDA NIH HHS [DA 015644]; NIMH NIH HHS [MH 59733, MH 61637] NR 47 TC 136 Z9 136 U1 1 U2 6 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0899-7667 J9 NEURAL COMPUT JI Neural Comput. PD MAY PY 2003 VL 15 IS 5 BP 965 EP 991 DI 10.1162/089976603765202622 PG 27 WC Computer Science, Artificial Intelligence SC Computer Science GA 671XY UT WOS:000182491600001 PM 12803953 ER PT J AU Dhond, RP Marinkovic, K Dale, AM Witzel, T Halgren, E AF Dhond, RP Marinkovic, K Dale, AM Witzel, T Halgren, E TI Spatiotemporal maps of past-tense verb inflection SO NEUROIMAGE LA English DT Article DE magnetoencephalography; MEG; language; prefrontal; ventral temporal; occipitotemporal; dual route; past tense; connectionist; single route ID LEFT PREFRONTAL CORTEX; MORPHOLOGICALLY COMPLEX WORDS; DEPTH-RECORDED POTENTIALS; SURFACE-BASED ANALYSIS; TEMPORAL-LOBE ATROPHY; CORTICAL SURFACE; BRAIN ACTIVITY; COORDINATE SYSTEM; SEMANTIC DEMENTIA; NEUROIMAGING DATA AB Does the brain inflect verbs by applying rules, by associative retrieval of the inflected form, or both? We used whole-head magnetoencephalography to spatiotemporally map the brain response underlying verb past-tense inflection. Placing either regular or irregular verbs into the past tense sequentially modulates the bilateral visual, left inferotemporal, posterior superior temporal (Wernicke's area), left inferior prefrontal (Broca's area), and right prefrontal cortices. Although irregular and regular verb inflection evokes similar cortical response patterns, differences in specific frontotemporal regions are observed. At similar to340 ins, irregular verbs evoke greater response modulation in left occipitotemporal cortex. This modulation occurs when widespread areas are simultaneously active, suggesting that it reflects associative activation necessary for generation of past-tense forms. Subsequently, regular verbs show increased response at similar to470 ms within left inferior prefrontal regions associated with rule-based inflection. Increased right dorsolateral preftontal response at similar to570 ins may represent directed/effortful retrieval of irregular past-tense forms. Thus, the brain inflects verbs by dynamically modulating different functional divisions of an integrated language system. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Northeastern Univ, Coll Comp Sci, Boston, MA 02115 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84105 USA. Massachusetts Gen Hosp, NMR Ctr, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Dhond, RP (reprint author), Massachusetts Gen Hosp, NMR Ctr, Athinoula A Martinos Ctr, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010; Witzel, Thomas/P-1402-2014 FU NIBIB NIH HHS [EB00307, EB00790, R01 EB000790, R01 EB003070]; NINDS NIH HHS [NS18741, NS39581, R01 NS018741] NR 76 TC 37 Z9 38 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2003 VL 19 IS 1 BP 91 EP 100 DI 10.1016/S1053-8119(03)00047-8 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 684ZP UT WOS:000183236600007 PM 12781729 ER PT J AU Waters, G Caplan, D Alpert, N Stanczak, L AF Waters, G Caplan, D Alpert, N Stanczak, L TI Individual differences in rCBF correlates of syntactic processing in sentence comprehension: effects of working memory and speed of processing SO NEUROIMAGE LA English DT Article ID IMAGE REGISTRATION; BRAIN RESPONSE; ACTIVATION; LANGUAGE; PET; POTENTIALS; FMRI; FORM; DETERMINANTS; LOCALIZATION AB Positron emission tomography (PET) was used to determine the effect of working memory and speed of sentence processing on regional cerebral blood flow (rCBF) during syntactic processing in sentence comprehension. PET activity associated with making plausibility judgments about syntactically more complex subject-object (SO) sentences (e.g., The juice that the child spilled stained the rug) was compared to that associated with making judgments about synonymous syntactically simpler object-subject (OS) sentences (e.g., The child spilled the juice that stained the rug). Two groups of nine subjects differing in working memory and matched for speed of sentence processing both showed increases in rCBF in lateral posteroinferior frontal lobe bilaterally. The subjects were reclassified to form two groups of eight subjects who were matched for working memory but who differed in speed of sentence processing. Fast-performing subjects activated lateral posteroinferior frontal lobe bilaterally and slow-performing subjects showed activation of left superior temporal lobe. The results indicate that rCBF responses to syntactic comprehension tasks vary as a function of speed of sentence processing but not as a function of working memory. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Boston Univ, Dept Commun Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Neurol, Neuropsychol Lab, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Radiol, Div Nucl Med, Boston, MA 02215 USA. RP Waters, G (reprint author), Boston Univ, Dept Commun Disorders, 635 Commonwealth Ave, Boston, MA 02215 USA. EM gwaters@bu.edu FU NIA NIH HHS [AG0096610]; NIDCD NIH HHS [DC02146] NR 63 TC 34 Z9 35 U1 4 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD MAY PY 2003 VL 19 IS 1 BP 101 EP 112 DI 10.1016/S1053-8119(03)00007-7 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 684ZP UT WOS:000183236600008 PM 12781730 ER PT J AU Anzai, Y Yueh, B AF Anzai, Y Yueh, B TI Imaging evaluation of sinusitis: diagnostic performance and impact on health outcome SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID COMPUTED TOMOGRAPHIC FINDINGS; HIV-INFECTED PATIENTS; PARANASAL SINUSES; ENDOSCOPIC SURGERY; FRONTAL SINUSITIS; COCAINE ABUSE; CT FINDINGS; CORONAL CT; RHINOSINUSITIS; CHILDREN AB Sinusitis is a highly prevalent disease, with a significant impact on the health care economy. Sinus CT is the primary imaging modality for evaluation of acute and chronic sinusitis. The roles of CT for patients with sinusitis are to assist clinical diagnosis, to evaluate the extent of disease, and to provide detailed anatomy necessary for treatment planning. Although sinus CT has been criticized for lack of specificity and correlation with patients' clinical symptoms, sinus CT may provide pivotal objective information that affects treatment decisions for acute and chronic sinusitis. This article provides a clinical overview and reviews the role of imaging studies in diagnosis and treatment of sinusitis. C1 Univ Washington, Dept Radiol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98108 USA. RP Anzai, Y (reprint author), Univ Washington, Dept Radiol, 1959 NE Pacific St,Box 357115, Seattle, WA 98195 USA. EM anzai@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 NR 63 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2003 VL 13 IS 2 BP 251 EP + DI 10.1016/S1052-5149(03)00017-0 PG 14 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 694RY UT WOS:000183789100009 PM 13677805 ER PT J AU Jaramillo, D Poussaint, TY Grottkau, BE AF Jaramillo, D Poussaint, TY Grottkau, BE TI Scoliosis: evidence-based diagnostic evaluation SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Article ID ADOLESCENT IDIOPATHIC SCOLIOSIS; CONGENITAL SCOLIOSIS; DIGITAL RADIOGRAPHY; IONIZING-RADIATION; IMAGING EVALUATION; NATURAL-HISTORY; CLINICAL-VALUE; LIFETIME RISK; COBB ANGLE; CHILDREN AB This article summarizes the evidence behind the imaging evaluation of scoliosis, which is primarily performed with plain radiographs and MR imaging. Issues related to the radiographic evaluation of spinal curvature include interobserver variability of scoliosis measurements and the radiologist's detection of unexpected findings. The effects of radiation exposure during scoliosis evaluation and strategies to minimize radiation dose are summarized. The use of MR imaging in idiopathic scoliosis is discussed, with special attention to imaging groups at higher risk for underlying pathology of the neural axis. C1 Massachusetts Gen Hosp, Div Pediat Radiol, Dept Radiol, Boston, MA 02114 USA. Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Ped Orthopaed, Dept Orthopaed, Boston, MA 02114 USA. RP Jaramillo, D (reprint author), Massachusetts Gen Hosp, Div Pediat Radiol, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 43 TC 3 Z9 3 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 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD MAY PY 2003 VL 13 IS 2 BP 335 EP + DI 10.1016/S1052-5149(03)00023-6 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 694RY UT WOS:000183789100016 PM 13677811 ER PT J AU Murtha, T Stasheff, SF AF Murtha, T Stasheff, SF TI Visual dysfunction in retinal and optic nerve disease SO NEUROLOGIC CLINICS LA English DT Review ID BLIND SPOT ENLARGEMENT; MELANOMA-ASSOCIATED RETINOPATHY; NEURITIS TREATMENT TRIAL; RETINITIS-PIGMENTOSA; COLOR-VISION; ACUITY IMPAIRMENT; OCULAR TOXICITY; BRIGHT LIGHT; NEUROPATHY; THERAPY AB The authors review symptoms of visual dysfunction having its origin in the anterior visual pathways (anterior ocular elements, retina, and optic nerve), and contrast these with similar symptoms arising from disorders at or posterior to the chiasm. General principles that help distinguish among these include whether the visual phenomena are negative or positive, monocular or binocular, the presence and location of any pain, and the location and form of any deficits. A number of negative phenomena are discussed. Acute complete or partial visual field loss is more likely to arise from anterior disease if it is asymmetric, conforms to any of several particular field patterns or is accompanied by fundoscopic or anterior chamber signs. Dimming of images is commonly due to optic nerve disease, photosensitivity or decreased dark adaptation to that of the photoreceptors. Blurring and decreased acuity may arise from a plethora of etiologies, while particular patterns of color loss distinguish between anterior and posterior disease. Among positive symptoms, 'floaters and flashers' commonly arise from benign properties of the vitreous or retinal vasculature. Photopsias or phosphenes may be normal phenomena or herald significant disease of the retinea, choroid, or optic nerve; characteristic qualities help in the distinction. More complex hallucinations and illusions may arise from inflammatory or toxic disorders of these elements, or from vascular etiologies such as migraine. Distinctive alterations in color perception may be caused by specific toxins. The authors provide tables and charts to aid the reader in developing a differential diagnosis. C1 Childrens Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Stasheff, SF (reprint author), Childrens Hosp, Dept Neurol, 429 Wellman MGH,50 Blossom St, Boston, MA 02114 USA. NR 105 TC 13 Z9 13 U1 1 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD MAY PY 2003 VL 21 IS 2 BP 445 EP + DI 10.1016/S0733-8619(02)00108-1 PN 1 PG 38 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 683BV UT WOS:000183127800005 PM 12916487 ER PT J AU Barker, FG Amin-Hanjani, S Ogilvy, CS Carter, BS AF Barker, FG Amin-Hanjani, S Ogilvy, CS Carter, BS TI In-hospital mortality and morbidity after surgical treatment of unruptured intracranial aneurysms in the United States, 1996-2000: The effect of hospital and surgeon volume SO NEUROSURGERY LA English DT Article DE high-volume hospitals; high-volume surgeons; outcome; unruptured intracranial aneurysms; volume of care ID CEREBRAL ANEURYSMS; SUBARACHNOID HEMORRHAGE; CAROTID ENDARTERECTOMY; ADMINISTRATIVE DATA; PUBLICATION BIAS; OUTCOMES; CARE; COMPLICATIONS; QUALITY; ASSOCIATION AB OBJECTIVE: We sought to determine the risk of adverse outcome after contemporary surgical treatment of patients with unruptured intracranial aneurysms in the United States. Patient, surgeon, and hospital characteristics were tested as potential outcome predictors, with particular attention to the,surgeon's and hospital's volume of care. METHODS: We performed a retrospective cohort study with the Nationwide Inpatient, Sample, 1996 to 2000. Multivariate logistic and ordinal regression analyses were performed with endpoints of mortality, discharge other than to home, length of stay, and total hospital charges. RESULTS: We identified 3498 patients who were treated at 463 hospitals, and we identified 585 surgeons in the database. Of all patients, 2.1% died 3.3% were discharged to skilled-nursing facilities, and 12.8% were discharged to other facilities. The analysis adjusted for age, sex, race, primary payer, four variables measuring acuity of treatment and medical comorbidity, and five variables indicating symptoms and signs. The statistics for median annual number of unruptured aneurysms treated were eight per hospital and three per surgeon. High-volume hospitals had fewer adverse outcomes-than hospitals that handled comparatively fewer unruptured aneurysms: discharge other than to home occurred after 15.6% of operations at high-volume hospitals (20 or more cases/yr) compared with 23.8% at low-volume hospitals (fewer than 4 cases/yr) (P = 0.002). High surgeon volume had a similar effect (15.3 versus 20.6%, P = 0.004). Mortality was lower at high-volume hospitals (1.6 versus 2.2%) than at hospitals that handled comparatively fewer unruptured aneurysms, but not significantly so. Patients treated by high-Volume surgeons had fewer postoperative neurological complications (P = 0,04). Length of stay was not related to hospital volume. Charges were slightly higher at high-volume hospitals, partly because arteriography was performed more frequently than at hospitals that handled comparatively fewer unruptured aneurysms. CONCLUSION: For patients with unruptured aneurysms who were treated in the United States between 1996 and 2000 surgery performed at high-volume institutions or by high-volume surgeons was associated with significantly lower morbidity and modestly lower mortality. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Carter, BS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, Vincent Burnham 730,Fruit St, Boston, MA 02114 USA. NR 66 TC 103 Z9 106 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2003 VL 52 IS 5 BP 995 EP 1007 DI 10.1227/01.NEU.0000057743.56678.5F PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 675CU UT WOS:000182676100001 PM 12699540 ER PT J AU Quinones-Hinojosa, A Malek, JY Ames, A Ogilvy, CS Maynard, KI AF Quinones-Hinojosa, A Malek, JY Ames, A Ogilvy, CS Maynard, KI TI Metabolic effects of hypothermia and its neuroprotective effects on the recovery of metabolic and electrophysiological function in the ischemic retina in vitro SO NEUROSURGERY LA English DT Article DE cerebral ischemia; energy metabolism; neuroprotection; stroke; temperature-dependent ID TRANSIENT FOREBRAIN ISCHEMIA; CEREBRAL ENERGY-METABOLISM; TRAUMATIC BRAIN INJURY; MILD HYPOTHERMIA; FOCAL ISCHEMIA; RABBIT RETINA; MODERATE HYPOTHERMIA; MAGNETIC-RESONANCE; HYPOXIA-ISCHEMIA; HEAD-INJURY AB OBJECTIVE: Reduction in energy usage has been investigated as the mechanism by which hypothermia provides protection during ischemia. We describe, experiments using hypothermia in the rabbit retina in Vitro that show a correlation between energy usage and neuroprotection., hypothermia-induced reductions in METHODS: We examined energy metabolism and electrophysiological function under control/nonischemic conditions during I or 2 hours of "ischemia" (induced by, decreasing glucose from 6 to 1 mmol/L and oxygen from,95 to 15%) and during 3 to conditions. Glucose utilization and lactate production 4 hours of "return-to-control", were measured as indices of energy metabolism, and light-evoked compound action potentials were monitored to assess functional recovery. RESULTS: Nonischemic retinas subjected to both mild (33 +/- 0.5degreesC) hypothermia exhibited a decrease of 38% in the rate of glucose utilization and lactate production compared with normothermic retinas (36 +/- 0.5degreesC) (analysis,of variance, P < 0.001). In retinas that were made ischemic, mild or moderate hypothermia further reduced the rates of glucose utilization (18 and 39%, respectively) and lactate production (21 and 28%, respectively) (P < 0.001 for glucose, P < 0.01 for lactate). Retinas that had, been mildly or moderately hypothermic during ischemia exhibited improved recovery of glucose utilization (65 and 57%, respectively) and lactate production (72 and 74%, respectively) compared with normothermic retinas (18% for glucose and 54% for lactate; repeated-measures analysis of variance, P < 0.001). Recovery of compound action potentials for retinas kept at 36, 33, and 30degreesC was 15, 36, and 53%, respectively (repeated-measures analysis of variance, P < 0.001). CONCLUSION: Our studies in an avascular neuronal ischemia de that hypothermia protects against ischemic injury. We interpret the smaller reductions hypothermia energy generation and usage caused by ischemia when the retinas were mic as evidence that hypothermia had reduced energy requirements more than energy production, and we propose that this at least in part explains its protection. C1 Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv,Neurophysiol Lab, Boston, MA 02115 USA. RP Quinones-Hinojosa, A (reprint author), Univ Calif San Francisco, Dept Neurol Surg, 505 Parnassus Ave,M-779, San Francisco, CA 94143 USA. OI Mayberg, Marc/0000-0002-6718-7143 FU NINDS NIH HHS [NS-01732] NR 71 TC 18 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD MAY PY 2003 VL 52 IS 5 BP 1178 EP 1186 DI 10.1227/01.NEU.0000057836.64972.A0 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 675CU UT WOS:000182676100046 PM 12699563 ER PT J AU Zile, MR Gaasch, WH AF Zile, MR Gaasch, WH TI Heart failure in aortic stenosis - Improving diagnosis and treatment SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. Lahey Clin Fdn, Dept Cardiovasc Med, Burlington, MA USA. RP Zile, MR (reprint author), Med Univ S Carolina, Gazes Cardiac Res Inst, Dept Med, Div Cardiol, Charleston, SC 29425 USA. NR 0 TC 13 Z9 13 U1 0 U2 2 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 MAY 1 PY 2003 VL 348 IS 18 BP 1735 EP 1736 DI 10.1056/NEJMp030035 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 672VK UT WOS:000182543500001 PM 12724478 ER PT J AU Jackson, LA Neuzil, KM Yu, OC Benson, P Barlow, WE Adams, AL Hanson, CA Mahoney, LD Shay, DK Thompson, WW AF Jackson, LA Neuzil, KM Yu, OC Benson, P Barlow, WE Adams, AL Hanson, CA Mahoney, LD Shay, DK Thompson, WW CA Vaccine Safety Datalink TI Effectiveness of pneumococcal polysaccharide vaccine in older adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMMUNITY-ACQUIRED PNEUMONIA; STREPTOCOCCUS-PNEUMONIAE; REQUIRING HOSPITALIZATION; ELDERLY PEOPLE; UNITED-STATES; EFFICACY; DISEASE; TRIAL; INFECTION; METAANALYSIS AB BACKGROUND: Streptococcus pneumoniae is the chief cause of pneumonia in older adults, but it remains unclear whether use of the pneumococcal polysaccharide vaccine alters the overall risk of community-acquired pneumonia. In a large population of older adults, we assessed the effectiveness of the pneumococcal vaccine. METHODS: In this retrospective cohort study, 47,365 Group Health Cooperative members 65 years of age or older were assessed over a three-year period. The primary outcomes were hospitalization because of community-acquired pneumonia (validated by chart review), pneumonia in patients who were not hospitalized (``outpatient pneumonia,'' determined from administrative data sources), and pneumococcal bacteremia. The association between pneumococcal vaccination and the risk of each outcome was evaluated by means of multivariate Cox proportional-hazards models, with adjustment for age, sex, nursing-home residence or nonresidence, smoking status, medical conditions, and receipt or nonreceipt of influenza vaccine. RESULTS: During the study period, 1428 cohort members were hospitalized with community-acquired pneumonia, 3061 were assigned a diagnosis of outpatient pneumonia, and 61 had pneumococcal bacteremia. Receipt of the pneumococcal vaccine was associated with a significant reduction in the risk of pneumococcal bacteremia (hazard ratio, 0.56; 95 percent confidence interval, 0.33 to 0.93) but a slightly increased risk of hospitalization for pneumonia (hazard ratio, 1.14; 95 percent confidence interval, 1.02 to 1.28). Pneumococcal vaccination did not alter the risk of outpatient pneumonia (hazard ratio, 1.04; 95 percent confidence interval, 0.96 to 1.13) or of any case of community-acquired pneumonia, whether or not it required hospitalization (hazard ratio, 1.07; 95 percent confidence interval, 0.99 to 1.14). CONCLUSIONS: These findings support the effectiveness of the pneumococcal polysaccharide vaccine for the prevention of bacteremia, but they suggest that alternative strategies are needed to prevent nonbacteremic pneumonia, which is a more common manifestation of pneumococcal infection in elderly persons. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA USA. RP Jackson, LA (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. OI Shay, David/0000-0001-9619-4820 NR 39 TC 322 Z9 333 U1 1 U2 13 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 MAY 1 PY 2003 VL 348 IS 18 BP 1747 EP 1755 DI 10.1056/NEJMoa022678 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 672VK UT WOS:000182543500003 PM 12724480 ER PT J AU Hwang, JH Bluml, S Leaf, A Ross, BD AF Hwang, JH Bluml, S Leaf, A Ross, BD TI In vivo characterization of fatty acids in human adipose tissue using natural abundance H-1 clecoupled C-13 MRS at 1.5 T: Clinical applications to dietary therapy SO NMR IN BIOMEDICINE LA English DT Article DE adipose tissue; C-13NMR spectroscopy; fish oil diet; lipid composition; Lorenzo's oil diet; unsaturated fatty acids ID MAGNETIC-RESONANCE SPECTROSCOPY; ALPHA-LINOLENIC ACID; NONINVASIVE DETERMINATION; EICOSAPENTAENOIC ACID; LIPIDS; CHROMATOGRAPHY; PREVENTION; DISEASE AB Natural abundance proton-decoupled C-13 magnetic resonance spectroscopy was used to establish the in vivo lipid composition of normal adipose tissue and the corresponding effects of altered lipid diets. Experiments were performed on a standard 1.5 T clinical MR scanner using a double-tuned H-1-C-13 Coil. Peaks from double-bonded and methylene carbons were analyzed. Normal lipid composition was established in 20 control subjects. For comparison, five subjects on altered lipid diets were studied. Four subjects were on a fish oil supplement diet or predominantly seafood diet (polyunsaturated fatty acids), and one subject was on a Lorenzo's oil diet (monounsaturated fatty acids). Well-resolved C-13 spectra were obtained from the calf adipose tissue with a total acquisition time of 10 min. Model oil solutions were used to identify specific C-13 resonances. Subjects on lipid diets showed significantly elevated levels of monounsaturated and polyunsaturated fatty acids for Lorenzo's and fish oil diets, respectively. We conclude that C-13 MR spectroscopy can readily detect changes in lipid composition due to medium- and long-term therapeutic lipid diets. Since the examination is rapid, robust and noninvasive, opportunities arise for large clinical trials of preventive or therapeutic diets to be performed with C-13 MRS on a clinical MR scanner. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Huntington Med Res Inst, Pasadena, CA USA. Rudi Schulte Res Inst, Santa Barbara, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hwang, JH (reprint author), Albert Einstein Coll Med, Gruss MRRC, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 23 TC 27 Z9 28 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD MAY PY 2003 VL 16 IS 3 BP 160 EP 167 DI 10.1002/nbm.824 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 704FB UT WOS:000184327000006 PM 12884360 ER PT J AU Plais, DC Gardner-Thorpe, J Ito, H Ashley, SW Whang, EE AF Plais, DC Gardner-Thorpe, J Ito, H Ashley, SW Whang, EE TI Vitamin B6 inhibits the growth of human pancreatic carcinoma SO NUTRITION RESEARCH LA English DT Article DE vitamin B6; pyridoxal; pyridoxine; pancreatic cancer ID PYRIDOXAL 5'-PHOSPHATE; RAT-LIVER; POLYMERASES; EXPRESSION; CANCER; MICE; RNA AB Vitamin 136 serves as a coenzyme and is essential for the metabolism of amino acids. The human pancreatic carcinoma cell line PANC-1 was treated with pyridoxine (at concentrations of 0.1, 0.5, 1.0, 2.5, 5.0 and 10.0 mM) or pyridoxal (0.01, 0.05, 0.1, 0.5, 1.0 and 2.5 mM). The viable cell count was determined daily for six days using the MTT assay. The experiment was repeated three times. Each control and each concentration tested was performed in triplicate. All comparisons were analyzed by ANOVA with Tukey HSD. At doses of 2.5 mM and higher, PN significantly inhibited the growth in a dose-dependent manner (p < 0.05). Treatment with PL (0.5, 1.0 and 2.5 mM) significantly inhibited growth from the second day (p < 0.05). We have demonstrated the inhibitory effect of PL and PN on a human pancreatic cancer cell line. Further studies are needed to assess the impact of megadose vitamin treatment in vivo. (C) 2003 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Whang, EE (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD MAY PY 2003 VL 23 IS 5 BP 673 EP 679 DI 10.1016/S0271-5317(03)00029-0 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 680YK UT WOS:000183007500010 ER PT J AU Gulati, V Agarwal, HC Sihota, R Saxena, R AF Gulati, V Agarwal, HC Sihota, R Saxena, R TI Correlation analysis of visual field thresholds and scanning laser ophthalmoscopic optic nerve head measurements in glaucoma SO OPHTHALMIC AND PHYSIOLOGICAL OPTICS LA English DT Article DE glaucoma; HRT 11; Humphrey Visual Field Analyser; retinotopy; scanning laser ophthalmoscope; visual field ID NORMAL-TENSION GLAUCOMA; FIBER LAYER; RETINOTOPIC ORGANIZATION; FUNCTIONAL DAMAGE; DISK; VARIABLES; RETINA; EYES AB In a cross-sectional study of 50 consecutive primary open-angle glaucoma cases, full threshold 30-2 visual fields on Humphrey Visual Field Analyser were correlated to stereometric parameters obtained using a scanning laser ophthalmoscope (HRT II). The strength of linear correlation between the stereometric parameters and visual thresholds was used to generate a correspondence map between the optic disc and the visual field. Rim/disc area ratio and cup/disc area ratio correlated with the visual thresholds at the highest number of points in the visual fields. Thresholds at superior hemifield locations correlated best with the rim/disc area ratio and cup/disc area ratio in the inferonasal sector and the ones in the inferior hemifield correlated best with the rim/disc area ratio and cup/disc area ratio in the superotemporal sector. Optic disc parameters correlated better with inferior field locations and non-edge points than superior field locations and edge points. The data indicate that rim/disc area ratio and cup/disc area ratio measurements on HRT II have a good correlation with visual field damage seen on automated visual fields. C1 All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi 110029, India. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Agarwal, HC (reprint author), All India Inst Med Sci, Dr Rajendra Prasad Ctr Ophthalm Sci, New Delhi 110029, India. NR 22 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0275-5408 J9 OPHTHAL PHYSL OPT JI Ophthalmic Physiol. Opt. PD MAY PY 2003 VL 23 IS 3 BP 233 EP 242 DI 10.1046/j.1475-1313.2003.00111.x PG 10 WC Ophthalmology SC Ophthalmology GA 685AW UT WOS:000183239500005 PM 12753479 ER PT J AU Sarraf, D Schwartz, SD AF Sarraf, D Schwartz, SD TI Bilateral choroidal folds and optic neuropathy: a variant of the crowded disk syndrome.? SO OPHTHALMOLOGY LA English DT Article ID ACQUIRED HYPEROPIA; INTRACRANIAL HYPERTENSION; CHORIORETINAL FOLDS; RISK-FACTORS; PAPILLEDEMA; EYE AB Purpose: To describe the clinical features of the syndrome that includes bilateral choroidal folds and optic neuropathy and to propose a novel etiology to explain this presentation. Design: Observational small case series. Participants: Three patients. Methods: Three patients received an extensive clinical work-up including complete ocular examination, A and B scan ultrasonography, Humphrey visual field analysis, and imaging of the brain and orbit. Neurological consultation was obtained in each patient two of whom underwent lumbar puncture. The findings of this detailed investigation are reported. Results: Each patient demonstrated bilateral choroidal folds with optic disk congestion and leakage in one eye and optic atrophy in the fellow eye. Extensive ocular and extraocular investigation failed to uncover a specific etiology. Pseudotumor cerebri, a well-documented cause of papilledema and choroidal folds, was ruled out in each case. Each patient did demonstrate variable degrees of hyperopia and shortened axial lengths. Conclusions: The syndrome of bilateral choroidal folds and optic neuropathy may have various etiologies. Pseudotumor cerebri needs to be definitively ruled out. Normal neuro-ophthalmological investigation including lumbar puncture may indicate an alternative cause. Idiopathic acquired hyperopia in middle-aged patients who are hyperopic with shortened axial lengths may be associated with choroidal folds and a constricted scleral canal causing optic disk congestion and complicated by nonarteritic anterior ischemic optic neuropathy due to a crowded disk. C1 Univ Calif Los Angeles, Jules Stein Eye Inst, Sch Med, Dept Ophthalmol, Los Angeles, CA 90095 USA. Greater Los Angeles VA Healthcare Syst, Dept Ophthalmol, Los Angeles, CA USA. Martin L King Hosp, Dept Ophthalmol, Charles R Drew Sch Med, Los Angeles, CA USA. Kaiser Permanente, Dept Ophthalmol, Woodland Hills, CA USA. RP Sarraf, D (reprint author), Univ Calif Los Angeles, Jules Stein Eye Inst, Sch Med, Dept Ophthalmol, 100 Stein Plaza, Los Angeles, CA 90095 USA. NR 36 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2003 VL 110 IS 5 BP 1047 EP 1052 DI 10.1016/S0161-6420(03)00082-4 PG 6 WC Ophthalmology SC Ophthalmology GA 676LY UT WOS:000182754600043 PM 12750112 ER PT J AU Thakker, MM Perez, VL Moulin, A Cremers, SL Foster, CS AF Thakker, MM Perez, VL Moulin, A Cremers, SL Foster, CS TI Multifocal nodular episcleritis and scleritis with undiagnosed Hodgkin's lymphoma SO OPHTHALMOLOGY LA English DT Article ID WEGENERS GRANULOMATOSIS; POSTERIOR SCLERITIS; DISEASE; VASCULITIS AB Purpose: To report the case of a patient with undiagnosed Hodgkin's lymphoma who presented with coexistent unilateral nodular episcleritis and scleritis. Design: Interventional case report and literature review Methods: Review of clinical history, laboratory findings, histology of episcleral and cervical lymph node biopsies, and follow-up. Results: A 20-year-old female presented with a 5-month history of redness and pain in her left eye, with associated symptoms of dyspnea, malaise, and fever. The patient was found to have multifocal nodular episcleritis and scleritis that was not responsive to topical steroids or systemic nonsteroidal anti-inflammatory treatment. Laboratory tests subsequently revealed evidence of systemic inflammation, and radiologic studies showed extensive mediastinal and cervical adenopathy. A cervical lymph node biopsy showed Reed-Sternberg cells and a chronic lymphocytic infiltrate consistent with nodular sclerosing Hodgkin's lymphoma. Histopathologic analysis of an episcleral nodule revealed a necrotizing granuloma with vasculitis. Systemic chemotherapy was instituted for the Hodgkin's disease; this therapy abolished the nodular scleritis. Conclusions: This case raises the possibility of concurrent undiagnosed systemic vasculitis with only an ocular manifestation with Hodgkin's lymphoma, either as a coincidence or as a paraneoplastic syndrome. Moreover, it emphasizes the important role of tissue biopsy in establishing diagnosis and directing treatment. (C) 2003 by the American Academy of Ophthalmology. C1 Massachusetts Eye & Ear Infirm, Dept Immunol & Uveitis, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Ocular Pathol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Gen Eye Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Dept Immunol & Uveitis, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2003 VL 110 IS 5 BP 1057 EP 1060 DI 10.1016/S0161-6420(03)00090-3 PG 4 WC Ophthalmology SC Ophthalmology GA 676LY UT WOS:000182754600045 PM 12750114 ER PT J AU Baltatzis, S Tufail, F Yu, EN Vredeveld, CM Foster, CS AF Baltatzis, S Tufail, F Yu, EN Vredeveld, CM Foster, CS TI Mycophenolate mofetil as an immunomodulatory agent in the treatment of chronic ocular inflammatory disorders SO OPHTHALMOLOGY LA English DT Article ID TRANSPLANTATION; DISEASE AB Purpose: To evaluate the outcomes of patients with chronic ocular inflammatory disease treated with mycophenolate mofetil as an immunosuppressive and steroid-sparing agent. Design: Retrospective noncomparative interventional case series. Participants: All patients with ocular inflammatory disease treated with mycophenolate mofetil at a single institution between 1998 and 2001. Methods: Charts of patients seen on the Ocular Immunology and Uveitis Service at the Massachusetts Eye and Ear Infirmary were reviewed. Patients with chronic ocular inflammatory disease were included in the study. Main Outcome Measures: Control of inflammation, steroid-sparing effect, visual acuity, and adverse reactions were measured. Results: A total of 54 patients were evaluated. Control of ocular inflammation with mycophenolate mofetil as monotherapy was achieved in 35 patients (65%) and in 67 eyes (62%), and a steroid-sparing effect was achieved in 29 (54%) patients. Visual acuity was maintained or improved in 51 patients (94%) and in 97 eyes (90%). Side effects requiring discontinuation of medication occurred in 10 patients (18%). There was neither long-term morbidity nor mortality due to mycophenolate mofetil. Conclusions: Mycophenolate mofetil is effective in the treatment of patients with steroid-dependent or-resistant chronic ocular inflammatory disorders that fail to respond to conventional steroid treatment. It is a safe and effective steroid-sparing immunomodulatory agent and can be considered an important addition to our armamentarium in the care of patients with ocular inflammatory disease. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Serv Immunol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 62 Z9 70 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 MAY PY 2003 VL 110 IS 5 BP 1061 EP 1065 DI 10.1016/S0161-6420(03)00092-7 PG 5 WC Ophthalmology SC Ophthalmology GA 676LY UT WOS:000182754600046 PM 12750115 ER PT J AU Kufer, KH Scherrer, A Monz, M Alonso, F Trinkaus, H Bortfeld, T Thieke, C AF Kufer, KH Scherrer, A Monz, M Alonso, F Trinkaus, H Bortfeld, T Thieke, C TI Intensity-modulated radiotherapy a large scale multi-criteria programming problem SO OR SPECTRUM LA English DT Article DE multi-criteria optimization; representative pareto solutions; adaptive triangulation; clustering techniques; radiotherapy ID OPTIMIZATION AB Radiation therapy planning is often a tightrope walk between dangerous insufficient dose in the target volume and life threatening overdosing of organs at risk. Finding ideal balances between these inherently contradictory goals challenges dosimetrists and physicians in their daily practice. Todays inverse planning systems calculate treatment plans based on a single evaluation function that measures the quality of a radiation treatment plan. Unfortunately, such a one dimensional approach cannot satisfactorily map the different backgrounds of physicians and the patient dependent necessities. So, too often a time consuming iterative optimization process between evaluation of the dose distribution and redefinition of the evaluation function is needed. In this paper we propose a generic multi-criteria approach based on Pareto's solution concept. For each entity of interest - target volume or organ at risk - a structure dependent evaluation function is defined measuring deviations from ideal doses that are calculated from statistical functions. A reasonable bunch of clinically meaningful Pareto optimal solutions are stored in a data base, which can be interactively searched by physicians. The system guarantees dynamic planning as well as the discussion of tradeoffs between different entities. Mathematically, we model the inverse problem as a multi-criteria linear programming problem. Because of the large scale nature of the problem it is not possible to solve the problem in a 3D-setting without adaptive reduction by, appropriate approximation schemes. Our approach is twofold: First, the discretization of the continuous problem results from an adaptive hierarchical clustering process which is used for a local refinement of constraints during the optimization procedure. Second, the set of Pareto optimal solutions is approximated by an adaptive grid of representatives that are found by a hybrid process of calculating extreme compromises and interpolation methods. C1 Fraunhofer Inst Ind Math, Dept Optimizat, D-67663 Kaiserslautern, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. German Canc Res Ctr, Dept Phys Med, D-69120 Heidelberg, Germany. RP Kufer, KH (reprint author), Fraunhofer Inst Ind Math, Dept Optimizat, Gottlieb Daimler Str 49, D-67663 Kaiserslautern, Germany. NR 20 TC 57 Z9 58 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-6468 J9 OR SPECTRUM JI OR Spectrum PD MAY PY 2003 VL 25 IS 2 BP 223 EP 249 PG 27 WC Operations Research & Management Science SC Operations Research & Management Science GA 676LB UT WOS:000182752600006 ER PT J AU Lam, NP Donoff, RB Kaban, LB Dodson, TB AF Lam, NP Donoff, RB Kaban, LB Dodson, TB TI Patient satisfaction after trigeminal nerve repair SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the American-Association-of-Dental-Research CY MAR 08-10, 2001 CL CHICAGO, ILLINOIS SP Amer Assoc Dent Res ID 3RD MOLAR SURGERY; INFERIOR ALVEOLAR; LINGUAL NERVE; DEFECTS; REMOVAL AB Objective. The purpose of this study was to measure patient satisfaction and to evaluate the factors influencing patients' perceptions of the outcome of inferior alveolar nerve or lingual nerve repair. Study design. We used a retrospective cohort study design and a sample of patients who underwent repair of inferior alveolar nerve or lingual nerve injuries. The major outcome variable was the patient's overall satisfaction with treatment. The patient's satisfaction was rated as either good to excellent (group A) or fair to poor (group 13). Results. The study sample was composed of 46 patients with a mean age of 28 +/- 12 years; 76% were female. Fifty-five percent of the sample reported their overall satisfaction to be good to excellent. No individual predictor factors were statistically associated with patient satisfaction. Among the outcome variables, the measures of taste, pronunciation, self-consciousness, and function were statistically significantly different (P < .05) between the 2 groups. Conclusion. After nerve repair, more than half of the patients rated their overall satisfaction with the operative results to be good to excellent. C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, 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-DE00448] NR 23 TC 18 Z9 18 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD MAY PY 2003 VL 95 IS 5 BP 538 EP 543 DI 10.1067/moe.2003.163 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677TQ UT WOS:000182824000010 PM 12738944 ER PT J AU Biederman, J Faraone, SV Monuteaux, MC Plunkett, EA Gifford, J Spencer, T AF Biederman, J Faraone, SV Monuteaux, MC Plunkett, EA Gifford, J Spencer, T TI Growth deficits and attention-deficit/hyperactivity disorder revisited: Impact of gender, development, and treatment SO PEDIATRICS LA English DT Article DE ADHD; growth; stimulants ID HYPERACTIVITY DISORDER; NUTRITIONAL-STATUS; FAMILIAL SUBTYPE; STIMULANT-DRUGS; RENAL DISEASES; FOLLOW-UP; CHILDREN; GIRLS; ADHD; METHYLPHENIDATE AB Objective. Although the relationship between putative growth deficits and attention-deficit/hyperactivity disorder (ADHD) has been examined in boys, this issue has not been evaluated in girls. Methods. Height and weight were examined in 124 female ADHD children and 116 female controls using age and parental height corrections, attending to issues of pubertal stage and treatment. Also, we examined the interaction between ADHD status and gender on growth outcomes using data from 124 ADHD and 109 control males. Results. The ADHD-growth association was not moderated by gender. No deficits in age-adjusted height or age and height-adjusted weight were detected in ADHD girls. Also, we found no association between growth measurements and psychotropic treatment, malnutrition, short stature, pubertal development, family history of ADHD, or psychiatric comorbidity, except for major depression: ADHD girls with major depression were on average 7.6 kg heavier than ADHD girls without depression, adjusting for age and height. Conclusions. No growth deficits appear to be associated with ADHD or its treatment in females. These findings add to a growing literature supporting the notion that stimulant treatment does not have an adverse impact on ADHD children's growth and development. C1 Massachusetts Gen Hosp, Dept Psychiat, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Fruit St, Boston, MA 02114 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH-41314-01A2] NR 51 TC 62 Z9 63 U1 1 U2 3 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 MAY 1 PY 2003 VL 111 IS 5 BP 1010 EP 1016 DI 10.1542/peds.111.5.1010 PG 7 WC Pediatrics SC Pediatrics GA 673KC UT WOS:000182579300030 PM 12728081 ER PT J AU Boudreaux, ED Emond, SD Clark, S Camargo, CA AF Boudreaux, ED Emond, SD Clark, S Camargo, CA CA Multicenter Airway Res Collaborati TI Race/ethnicity and asthma among children presenting to the emergency department: Differences in disease severity and management SO PEDIATRICS LA English DT Article DE asthma; children; socioeconomic status; race; ethnicity; quality of care ID SMALL-AREA ANALYSIS; NEW-YORK-CITY; CHILDHOOD ASTHMA; HEALTH-CARE; SOCIOECONOMIC-STATUS; HOSPITALIZATION RATES; RACIAL-DIFFERENCES; PERSISTENT WHEEZE; UNITED-STATES; RISK-FACTORS AB Objective. To investigate racial/ethnic differences in acute asthma among children who present to the emergency department (ED). Method. We analyzed data from 2 prospective cohort studies performed during 1997-1998 as part of the Multicenter Airway Research Collaboration. Using a standardized protocol, researchers at 40 EDs in 18 US states provided 24-hour-per-day coverage for a median of 2 weeks per year. Children with acute asthma were interviewed in the ED and by telephone 2 weeks after discharge. Results. Among 1095 patients, 679 (62%) were black, 256 (23%) were Hispanic, and 160 (15%) were white. Black and Hispanic children had greater histories of lifetime (63%, 64%, 46%) and past- year (34%, 31%, 14%) hospitalization and more ED visits in the past year (medians: 2, 3, 1). Asthma severity at ED presentation, ED management and course, hospitalization during the index visit, discharge prescriptions, and postdischarge outcomes were equivalent among all race/ethnic groups. Conclusion. Despite pronounced race/ethnicity-based differences in chronic asthma, all racial/ethnic groups exhibited similar acute asthma severity, ED management, and course. However, given that black and Hispanic children exhibited much higher admission histories and past ED use, the equivalence in inhaled corticosteroid prescriptions on discharge is a disconcerting pattern that mirrors previous literature on outpatient prescription practices. In addition to barriers attributable to socioeconomic factors, health care providers and policy makers should target equalizing deficiencies in preventive medication prescription practices. C1 Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, Boston, MA 02114 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Emergency Med, Cooper Hosp, Camden, NJ 08103 USA. Santa Clara Valley Med Ctr, Emergency Dept, Santa Clara, CA USA. Harvard Univ, Sch Med, Channing Lab, Dept Med,Brigham & Womens Hosp, Boston, MA 02115 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, EMNet Coordinating Ctr, Dept Emergency Med, 55 Fruit St,Clin Bldg 397, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-63841, HL-63253] NR 42 TC 59 Z9 60 U1 2 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 MAY 1 PY 2003 VL 111 IS 5 BP E615 EP E621 DI 10.1542/peds.111.5.e615 PG 7 WC Pediatrics SC Pediatrics GA 673KC UT WOS:000182579300013 PM 12728120 ER PT J AU Gow, DW AF Gow, DW TI Feature parsing: Feature cue mapping in spoken word recognition SO PERCEPTION & PSYCHOPHYSICS LA English DT Article ID SPEECH-PERCEPTION; TRADING RELATIONS; HIERARCHICAL CATEGORIZATION; COARTICULATED PHONEMES; CONNECTIONIST MODEL; LEXICAL AMBIGUITY; STOP CONSONANTS; ACOUSTIC CUES; INFORMATION; REPRESENTATION AB For listeners to recognize words, they must map temporally distributed phonetic feature cues onto higher order phonological representations. Three experiments are reported that were performed to examine what information listeners extract from assimilated segments (e.g., place-assimilated tokens of cone that resemble comb) and how they interpret it. Experiment 1 employed form priming to demonstrate that listeners activate the underlying form Of CONE, but not of its neighbor (comB). Experiment 2 employed phoneme monitoring to show that the same assimilated tokens facilitate the perception of postassimilation context. Together, the results of these two experiments suggest that listeners recover both the underlying place of the modified item and information about the subsequent item from the same modified segment. Experiment 3 replicated Experiment 1, using different postassimilation contexts to demonstrate that context effects do not reflect familiarity with a given assimilation process. The results are discussed in the context of general auditory grouping mechanisms. C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Salem State Coll, Salem, MA 01970 USA. RP Gow, DW (reprint author), Massachusetts Gen Hosp, Neuropsychol Lab, VBK 821,55 Fruit St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R29DC03108] NR 77 TC 76 Z9 76 U1 0 U2 1 PU PSYCHONOMIC SOC INC PI AUSTIN PA 1710 FORTVIEW RD, AUSTIN, TX 78704 USA SN 0031-5117 J9 PERCEPT PSYCHOPHYS JI Percept. Psychophys. PD MAY PY 2003 VL 65 IS 4 BP 575 EP 590 DI 10.3758/BF03194584 PG 16 WC Psychology; Psychology, Experimental SC Psychology GA 683EJ UT WOS:000183134600007 PM 12812280 ER PT J AU Yaremchuk, MJ AF Yaremchuk, MJ TI Facial skeletal reconstruction using porous polyethylene implants SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID HIGH-DENSITY POLYETHYLENE; ORBITAL FLOOR IMPLANT; FRACTURE REPAIR; LATE COMPLICATION; TISSUE-RESPONSE; CHIN IMPLANTS; BONE; AUGMENTATION; PROPLAST; BIOMATERIALS AB A retrospective review of clinical outcomes was performed to determine the clinical utility and morbidity associated with the use of porous polyethylene facial implants. Three hundred seventy implants were placed in 162 consecutive patients, in 178 operations performed in 11 years. The number of patients, the number of implants used, and the average follow-up period were categorized according to the cause of the deformity. The resultant distribution was as follows: acquired (tumor-related), 17 patients, 39 implants, and 30 months; congenital, eight patients, 31 implants, and 92 months; aesthetic, 39 patients, 97 implants, and 24 months; secondary posttraumatic, 48 patients, 139 implants, and 37 months; and acute trauma (internal orbit reconstruction), 50 patients, 64 implants, and 9 months. The distribution of implants according to location was as follows: frontal, 21; temporal, 30; internal orbit, 145; infraorbital rim, 28; malar, 58; paranasal, 29; nasal, 13; mandible, 24; and chin, 22. The combined average follow-up period per patient was 27 months (range, immediate postoperative period to 11 years). All implants were placed in the subperiosteal plane, and the majority were fixed with titanium screws. Antibiotics were administered perioperatively. No implants were extruded or migrated, formed clinically apparent capsules, or caused symptoms attributable to bioincompatibility. The overall reoperation rate was 10 percent (n = 16), which included operations to remove implants because of acute infections (2 percent, n = 3) or a late infection (1 percent, n = 1), to remove implants causing displeasing contours (2 percent, n = 3), and to improve contours (6 percent, n = 9). Porous polyethylene implants have biomaterial properties favorable for facial skeletal augmentation. Screw application of the implants to the skeleton allows precise predictable contouring, thus limiting the need for revisional surgical procedures. C1 Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Plast Surg, 15 Parkman St,Suite 453, Boston, MA 02114 USA. NR 58 TC 92 Z9 96 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2003 VL 111 IS 6 BP 1818 EP 1827 DI 10.1097/01.PRS.0000056866.80665.7A PG 10 WC Surgery SC Surgery GA 674AM UT WOS:000182614200005 PM 12711941 ER PT J AU Maloney, CT Wages, D Upton, J Lee, WPA AF Maloney, CT Wages, D Upton, J Lee, WPA TI Free omental tissue transfer for extremity coverage and revascularization SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID ANGIOGENIC FACTOR; BUERGERS-DISEASE; INTACT OMENTUM; LIMB SALVAGE AB Microvascular transfer of the omentum has several unique advantages for the reconstruction and revascularization of extremity wounds. The omentum provides well-vascularized, malleable tissue for reconstruction of extensive soft-tissue defects and has a long vascular pedicle (35 to 40 cm) with sizable vessels, which reduces some of the potential technical challenges of microsurgery. It can also be used for flow-through revascularization of ischemic distal extremities. The unique properties of the omentum make it an ideal tissue for the reconstruction of difficult extremity defects, allowing simultaneous reconstruction and revascularization. Experience with six free omental tissue transfers for upper-extremity and lower-extremity reconstruction is described. Three of the cases involved distal anastomoses to take advantage of the flow-through characteristics of the flap, providing distal arterial augmentation. All flaps accomplished the reconstructive goals of wound coverage and extremity revascularization. The omentum is a valuable, often overlooked tissue for the treatment of difficult extremity wounds. C1 Inst Peripheral Nerve Surg SW, Tucson, AZ 85711 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. RP Maloney, CT (reprint author), Inst Peripheral Nerve Surg SW, 310 N Wilmot Rd,Suite 302, Tucson, AZ 85711 USA. NR 27 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2003 VL 111 IS 6 BP 1899 EP 1904 DI 10.1097/01.PRS.0000056874.31920.7D PG 6 WC Surgery SC Surgery GA 674AM UT WOS:000182614200014 PM 12711950 ER PT J AU Netscher, DT AF Netscher, DT TI The benefit of transverse carpal ligament reconstruction following open carpal tunnel release SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Editorial Material ID FLEXOR TENDON EXCURSION; DIVISION C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Plast Surg Serv, Houston, TX USA. RP Netscher, DT (reprint author), 6560 Fannin,Suite 800, Houston, TX 77030 USA. NR 19 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2003 VL 111 IS 6 BP 2020 EP 2022 DI 10.1097/01.PRS.0000056836.14559.09 PG 3 WC Surgery SC Surgery GA 674AM UT WOS:000182614200031 PM 12711966 ER PT J AU Thomson, CC Rigotti, NA AF Thomson, CC Rigotti, NA TI Hospital- and clinic-based smoking cessation interventions for smokers with cardiovascular disease SO PROGRESS IN CARDIOVASCULAR DISEASES LA English DT Review ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; NICOTINE REPLACEMENT THERAPY; SUSTAINED-RELEASE BUPROPION; RANDOMIZED CONTROLLED TRIAL; RISK FACTOR MODIFICATION; FOLLOW-UP; TRANSDERMAL NICOTINE; CIGARETTE-SMOKING; NASAL SPRAY C1 Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL61779, HLO7427, HL04440] NR 172 TC 27 Z9 27 U1 3 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0033-0620 J9 PROG CARDIOVASC DIS JI Prog. Cardiovasc. Dis. PD MAY-JUN PY 2003 VL 45 IS 6 BP 459 EP 479 DI 10.1053/pcad.2003.YPCAD15 PG 21 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 686XJ UT WOS:000183346000003 PM 12800128 ER PT J AU Zhu, JQ Li, PY Wu, TH Gao, F Ding, Y Zhang, CWH Rao, ZH Gao, GF Tien, P AF Zhu, JQ Li, PY Wu, TH Gao, F Ding, Y Zhang, CWH Rao, ZH Gao, GF Tien, P TI Design and analysis of post-fusion 6-helix bundle of heptad repeat regions from Newcastle disease virus F protein SO PROTEIN ENGINEERING LA English DT Article DE construct design; fusion; heptad repeat; 6-helix; Newcastle disease virus ID MEMBRANE-FUSION; PARAMYXOVIRUS FUSION; INFLUENZA HEMAGGLUTININ; COILED COILS; SENDAI VIRUS; GLYCOPROTEIN; HYPOTHESIS; SEQUENCES; CLEAVAGE; PEPTIDES AB Fusion of paramyxovirus to the cell involves receptor binding of the HN glycoprotein and a number of conformational changes of F glycoprotein. The F protein is expressed as a homotrimer on the virus surface. In the present model, there are at least three conformations of F protein, i.e. native form, pre-hairpin intermediate and the post-fusion state. In the post-fusion state, the two highly conserved heptad repeat (HR) regions of F protein form a stable 6-helix coiled-coil bundle. However, no crystal structure is known for this state for the Newcastle disease virus, although the crystal structure of the F protein native form has been solved recently. Here we deployed an Escherichia coli in vitro expression system to engineer this 6-helix bundle by fusion of either the two HR regions (HR1, linker and HR2) or linking the 6-helix [3 x (HR1, linker and HR2)] together as a single chain. Subsequently, both of them form a stable 6-helix bundle in vitro judging by gel filtration and chemical cross-linking and the proteins show salient features of an alpha-helix structure. Crystals diffracting X-rays have been obtained from both protein preparations and the structure determination is under way. This method could be used for crystallization of the post-fusion state HR structures of other viruses. C1 Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. Chinese Acad Sci, Inst Microbiol, Dept Mol Virol, Beijing 100080, Peoples R China. Tsing Hua Univ, Sch Life Sci & Bioengn, Struct Biol Lab, Beijing 100084, Peoples R China. Tsing Hua Univ, Sch Life Sci & Bioengn, MOE Lab Prot Sci, Beijing 100084, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Gao, GF (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. NR 23 TC 16 Z9 18 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0269-2139 J9 PROTEIN ENG JI Protein Eng. PD MAY PY 2003 VL 16 IS 5 BP 373 EP 379 DI 10.1093/protein/gzg041 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 695KU UT WOS:000183830300008 PM 12826729 ER PT J AU Liu, CF Hedrick, SC Caheny, EF Heagerty, P Felker, B Hasenberg, N Fihn, S Katon, W AF Liu, CF Hedrick, SC Caheny, EF Heagerty, P Felker, B Hasenberg, N Fihn, S Katon, W TI Cost-effectiveness of collaborative care for depression in a primary care veteran population SO PSYCHIATRIC SERVICES LA English DT Article; Proceedings Paper CT Annual Meeting of the VA-Health-Services-Research-and-Development-Service CY FEB 14-16, 2001 CL Washington, DC SP VA Hlth Serv Res Dev Serv ID RANDOMIZED CONTROLLED-TRIAL; TREATING MAJOR DEPRESSION; CHRONIC DISEASE SCORE; QUALITY IMPROVEMENT; MEDICAL PATIENTS; HIGH UTILIZERS; HEALTH-STATUS; OLDER-ADULTS; MANAGEMENT; SYMPTOMS AB Objective: This study examined the incremental cost-effectiveness of a Collaborative care intervention for depression compared with consult-liaison care. Methods: A total of 354 patients in a Department of Veterans Affairs (VA) primary care clinic who met the criteria for major depression or dysthymia were randomly assigned to one of the two care models. Under the collaborative care model, a mental health team provided a treatment plan to primary care providers, telephoned patients to encourage adherence, reviewed treatment results, and suggested modifications. Outcomes were assessed at three and nine months by telephone interviews. Health care greater number of use and costs were also assessed. Results: A significantly collaborative care patients were treated for depression and given prescriptions for antidepressants. The collaborative care patients experienced an average of 14.6 additional depression-free days over the nine months. The mean incremental Cost of the intervention per patient Was $237 for depression treatment and $519 for total outpatient costs. A majority of the additional expenditures were accounted for by the intervention. The incrementa-l cost-effectiveness ratio was $24 per depression-free day for depression treatment costs and $33 for total outpatient cost. Conclusions: Better coordination and communication under collaborative care was associated with a greater number of patients being treated for depression and with moderate increase's in days free of depression and in treatment cost. Additional resources are needed for effective collaborative care models for depression treatment in primary care. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Mental Hlth Serv, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Liu, CF (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res, HSRD 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM chuan-fen.liu@med.va.gov NR 58 TC 62 Z9 62 U1 1 U2 3 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 MAY PY 2003 VL 54 IS 5 BP 698 EP 704 DI 10.1176/appi.ps.54.5.698 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 839BK UT WOS:000222758100013 PM 12719501 ER PT J AU Papakostas, GI Petersen, T Denninger, J Sonawalla, SB Mahal, Y Alpert, JE Nierenberg, AA Fava, M AF Papakostas, GI Petersen, T Denninger, J Sonawalla, SB Mahal, Y Alpert, JE Nierenberg, AA Fava, M TI Somatic symptoms in treatment-resistant depression SO PSYCHIATRY RESEARCH LA English DT Article DE response prediction; antidepressants; symptom questionnaire; nortriptyline ID EFFICACY; COMPLAINTS; PREVALENCE; DISORDER; TRIAL; PAIN; CARE AB The purpose of this work was to study the prevalence of somatic symptoms in patients with treatment-resistant depression (TRD) and their impact on the response to antidepressant treatment. Somatic symptoms were assessed during the screen visit with the Symptom Questionnaire (SQ) somatic symptom (SQ-SS) and somatic well-being sub-scales (SQ-SWB) in 40 patients with TRD enrolled in a 6-week open trial of nortriptyline. A logistic regression was used to test whether SQ-SS or SQ-SWB scores predicted clinical response to nortriptyline. Ninety-five percent of patients reported at least one somatic symptom. Higher SQ-SS scores during the screen visit predicted poorer response to nortriptyline. There was a trend for lower SQ-SWB scores to predict poor response to nortriptyline. None of the patients with SQ-SS scores above the mean for the sample responded to nortriptyline. The overwhelming majority of patients with TRD presented with somatic symptoms. In addition, a greater number of somatic symptoms during the screen visit placed patients at risk for further treatment resistance. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. RP Papakostas, GI (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, WACC 812,15 Parkman St, Boston, MA 02114 USA. RI Papakostas, George/I-6905-2013; OI Papakostas, George/0000-0002-2465-5103; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R29 MH46952] NR 22 TC 30 Z9 30 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAY 1 PY 2003 VL 118 IS 1 BP 39 EP 45 DI 10.1016/S0165-1781(03)00063-5 PG 7 WC Psychiatry SC Psychiatry GA 682EK UT WOS:000183078200006 PM 12759160 ER PT J AU Huffman, JC Pollack, MH AF Huffman, JC Pollack, MH TI Predicting panic disorder among patients with chest pain: An analysis of the literature SO PSYCHOSOMATICS LA English DT Article ID NORMAL CORONARY-ARTERIES; GENERALIZED ANXIETY DISORDER; EPIDEMIOLOGIC CATCHMENT-AREA; PSYCHIATRIC-DISORDERS; SOCIAL MORBIDITY; EMERGENCY; DEPRESSION; COMORBIDITY; DISEASE; CARE AB As many as 25% of patients with chest pain who come to hospital emergency departments have panic disorder Rates of panic disorder are even higher among those who present for outpatient evaluation of their chest pain. Unfortunately, panic disorder remains largely undiagnosed and untreated in these settings. The authors reviewed studies published between 1970 and 2001 that addressed the prevalence of panic disorder among persons who seek treatment for chest pain in an emergency department or outpatient cardiology clinic. A meta-analysis of the findings revealed five variables that appear to correlate with higher rates of panic disorder among persons who present with chest pain: 1) absence of coronary artery disease, 2) atypical quality of chest pain, 3) female sex, 4) younger age, and 5) a high level of self-reported anxiety. Further studies of these and other variables associated with panic disorder should aid in the detection of this disabling but treatable cause of chest pain. C1 Massachusetts Gen Hosp, Dept Psychiat, Belmont, MA USA. Harvard Univ, Sch Med, Belmont, MA 02178 USA. McLean Hosp, Belmont, MA 02178 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Warren 605, Boston, MA 02114 USA. NR 65 TC 47 Z9 52 U1 5 U2 6 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2003 VL 44 IS 3 BP 222 EP 236 DI 10.1176/appi.psy.44.3.222 PG 15 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 673AL UT WOS:000182556300006 PM 12724504 ER PT J AU Lafayette, JM Pirl, WF Henderson, DC AF Lafayette, JM Pirl, WF Henderson, DC TI Low-dose clozapine and diabetic ketoacidosis SO PSYCHOSOMATICS LA English DT Article ID RISPERIDONE TREATMENT; GLUCOSE-METABOLISM; PC12 CELLS; MELLITUS; SCHIZOPHRENIA; ABNORMALITIES C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Lafayette, JM (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WACC 812,15 Parkman St, Boston, MA 02114 USA. NR 28 TC 10 Z9 10 U1 0 U2 1 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD MAY-JUN PY 2003 VL 44 IS 3 BP 249 EP 252 DI 10.1176/appi.psy.44.3.249 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 673AL UT WOS:000182556300009 PM 12724507 ER PT J AU Fava, M Evins, AE Dorer, DJ Schoenfeld, DA AF Fava, M Evins, AE Dorer, DJ Schoenfeld, DA TI The problem of the placebo response in clinical trials for psychiatric disorders: Culprits, possible remedies, and a novel study design approach SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE placebo; clinical trials; novel design; sequential ID DEPRESSION RATING-SCALE; SMOKING CESSATION; MAJOR DEPRESSION; NICOTINE PATCH; EFFICACY; ANTIDEPRESSANTS; SENSITIVITY AB The placebo response is a major issue in clinical trials for psychiatric disorders. Possible contributing factors to this problem include diagnostic misclassification, issues concerning inclusion/exclusion criteria, outcome measures' lack of sensitivity to change, measurement errors, poor quality of data entry and verification, waxing and waning of the natural course of illness, regression toward the mean phenomenon, patient and clinician expectations about the trial, study design issues, non-specific therapeutic effects, and high attrition. Over the past few decades, researchers have attempted to reduce the placebo effect in a variety of ways. Unfortunately, approaches with very little or no benefit have included restricting enrollment to selected populations, rater training, requirement of same rater, and placebo lead-in phases. Some benefits, although often marginal, have been derived from standardizing diagnostic procedures, managing clinicians' overestimation of change, simplification of study visits and assessments, minimizing nonspecific, therapeutic effects, extending trial duration, reducing number of sites, increasing the sensitivity of outcome measures, and reducing the number of treatment arms. Thus far, there has been no attempt to develop new study designs aimed at reducing the placebo effect. We are proposing a novel study design, called 'Sequential Parallel Comparison Design', suitable for double-blind, placebo-controlled trials in psychiatric disorders. This design is aimed at reducing both the overall placebo response rate and the sample size required for such trials. Its usefulness in clinical research needs to be tested empirically. If this study design were to be found to meet its stated goals, this could markedly facilitate the process of clinical development of new compounds for the treatment of psychiatric disorders. Copyright (C) 2003 S. Karger AG, Basel. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. RP Fava, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, WACC-812,15 Parkman St, Boston, MA 02114 USA. NR 37 TC 201 Z9 205 U1 1 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD MAY-JUN PY 2003 VL 72 IS 3 BP 115 EP 127 DI 10.1159/000069738 PG 13 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 678FK UT WOS:000182854300002 PM 12707478 ER PT J AU Herndon, B Asch, SM Kilbourne, AM Wang, MM Lee, M Wenzel, SL Andersen, R Gelberg, L AF Herndon, B Asch, SM Kilbourne, AM Wang, MM Lee, M Wenzel, SL Andersen, R Gelberg, L TI Prevalence and predictors of HIV testing among a probability sample of homeless women in Los Angeles county SO PUBLIC HEALTH REPORTS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED DISEASES; NEW-YORK-CITY; UNITED-STATES; MEDICAL-CARE; RISK BEHAVIORS; DRUG-USE; INFECTION; ADULTS; AIDS AB Objectives. To describe the prevalence and predictors of HIV testing in a probability cluster sample of urban homeless women. Methods. Analysis of data from the University of California Los Angeles-RAND Access to Health Care for Homeless Women of Reproductive Age Study, a survey conducted in six waves from January 1997 through November 1997 at shelters and soup kitchens in Los Angeles (LA) County, California. The sampling unit consists of homeless woman-visits, and data were collected using structured face-to-face interviews for which respondents were paid $10. Each sampling unit was weighted to take into account the frequency with which the respondent used shelters or meal programs. The main outcome measure was receipt of HIV test in the past year. Results. The response rate was 83%, and the final sample size was N=970. Sixty-eight percent of our sample reported receiving an HIV test in the past year, and 1.6% reported ever being diagnosed with HIV. HIV testing in the past year was most strongly associated with pregnancy in the past year (OR 2.99; p<.001) and having a regular source of care (OR 2.13; p<.001). Approximately 25% of homeless women with indications for HIV testing had not been tested in the past year. Conclusions. The reported HIV seroprevalence of greater than 1% suggests that providers should offer and encourage HIV testing for all homeless women in LA County. Our data, which show a high rate of testing and few statistically significant independent predictors, indicate that this may be what is happening in practice. C1 Dartmouth Coll, Hitchcock Med Ctr, Sect Gen Internal Med, Lebanon, NH 03756 USA. Vet Affairs Greater Los Angeles, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Pittsburgh, Vet Affairs Pittsburgh Ctr Hlth Equity Res & Prom, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. RP Herndon, B (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Sect Gen Internal Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. FU AHRQ HHS [HS08323]; NIAAA NIH HHS [1R21AA13398]; NIDA NIH HHS [1R01 DA14835] NR 54 TC 16 Z9 16 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2003 VL 118 IS 3 BP 261 EP 269 DI 10.1016/S0033-3549(04)50246-7 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 754AJ UT WOS:000187280300012 PM 12766220 ER PT J AU Dirks, SJ Paunovich, ED Terezhalmy, GT Chiodo, LK AF Dirks, SJ Paunovich, ED Terezhalmy, GT Chiodo, LK TI The patient with Parkinson's disease SO QUINTESSENCE INTERNATIONAL LA English DT Article ID ENDOGENOUS DOPAMINERGIC NEUROTOXIN; ALPHA-SYNUCLEIN; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE MPTP; ULTRASONIC TOOTHBRUSH; CLINICAL-EVALUATION; SURGICAL-TREATMENT; UNITED-STATES; PLAQUE; MORTALITY; GENE AB Parkinson's disease is an idiopathic, slowly progressive disorder of the central nervous system characterized by resting tremor, muscular rigidity, slow and decreased movement (bradykinesia), and postural instability. In the United States, Parkinson's disease is the fourth most common neurodegenerative disorder in the elderly, affecting an estimated half a million people. Oral health care providers can expect to be called upon to care for patients with this progressively debilitating disease. To provide competent care to patients with Parkinson's disease, clinicians must understand the disease, its treatment, and its impact on the patient's ability to undergo and respond to dental care. C1 Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, Div Oral Med,Dent Sch, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Geriatr Oral Hlth Clin Program, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Terezhalmy, GT (reprint author), Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, Div Oral Med,Dent Sch, Mail Code 7919,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 78 TC 9 Z9 11 U1 0 U2 3 PU QUINTESSENCE PUBL CO INC PI CAROL STREAM PA 551 NORTH KIMBERLY DR, CAROL STREAM, IL 60188-1881 USA SN 0033-6572 J9 QUINTESSENCE INT JI Quintessence Int. PD MAY PY 2003 VL 34 IS 5 BP 379 EP 393 PG 15 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 688UJ UT WOS:000183454700009 PM 12795358 ER PT J AU vanSonnenberg, E Goodacre, BW Wittich, GR Logrono, R Kennedy, PT Zwischenberger, JB AF vanSonnenberg, E Goodacre, BW Wittich, GR Logrono, R Kennedy, PT Zwischenberger, JB TI Image-guided 25-gauge needle biopsy for thoracic lesions: Diagnostic feasibility and safety SO RADIOLOGY LA English DT Article; Proceedings Paper CT 87th Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 25-30, 2001 CL CHICAGO, ILLINOIS SP Radiol Soc N Amer DE biopsies, complications; biopsies, technology; thorax, biopsy; thorax, neoplasms ID ASPIRATION BIOPSY; CUTTING NEEDLE; ULTRATHIN NEEDLE; LUNG-BIOPSY; PNEUMOTHORAX; RISK; PNEUMONIA; SPECIMENS; CYTOLOGY; DISEASE AB PURPOSE: To report our experience regarding the feasibility and safety of 25-gauge needles for biopsy of thoracic lesions. MATERIALS AND METHODS: Twenty-six patients with thoracic lesions, predominately pulmonary nodules, measuring 0.7-5.2 cm (mean, 1.6 cm) underwent biopsy with computed tomographic (n = 24), ultrasonographic (n = 1), or fluoroscopic (n = 1) guidance. Nineteen patients had severe chronic obstructive pulmonary disease (COPD), one had severe restrictive lung disease, and one had a coagulopathy; the other five patients had nonpulmonary primary tumors. Biopsy with an inner 25-gauge needle traversing an outer extrapleural coaxial cannula was performed in all patients. Cytologic quick staining was performed routinely to determine specimen adequacy and to establish a preliminary diagnosis. Complications, specimen adequacy, and need for larger specimens were evaluated. RESULTS: Adequate specimens (as determined by cytopathologists) were obtained in 24 (92%) of 26 patients, with a definitive diagnosis achieved in 23 (88%) patients during initial quick staining (17 malignant and six benign diagnoses). Two cases initially considered suspicious for malignancy were reclassified as benign (thymoma and histoplasmosis). At the request of cytopathologists, a larger needle was used to supplement the 25-gauge needle in six patients: In one patient, it provided further, diagnostic information; in four, it did not; and in one, it confirmed non-Hodgkin lymphoma. Five patients developed a small pneumothorax (<10%) with use of the 25-gauge needle alone; one other patient, in whom larger needles were placed, received a radiologic chest catheter to evacuate the pneumothorax, thereby allowing the biopsy to continue. CONCLUSION: Image-guided 25-gauge needle biopsy is both feasible and safe. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, Boston, MA 02115 USA. Univ British Columbia, Dept Radiol, Vancouver, BC, Canada. Bayshore Med, Alliance Radiol Consultants, Pasadena, CA USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77550 USA. Royal Victoria Hosp, Dept Radiol, Belfast BT12 6BA, Antrim, North Ireland. RP vanSonnenberg, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 10 Z9 12 U1 0 U2 0 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 MAY PY 2003 VL 227 IS 2 BP 414 EP 418 DI 10.1148/radiol.2272011416 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 672RH UT WOS:000182534900016 PM 12663819 ER PT J AU Ahmed, SU AF Ahmed, SU TI Complex regional pain syndrome type I after myocardial infarction treated with spinal cord stimulation SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Article DE myocardial infarction; complex regional pain syndrome; spinal cord stimulator ID REFLEX SYMPATHETIC DYSTROPHY; MANAGEMENT AB Objective: A rare case of Complex Regional Pain Syndrome (CRPS) type I after myocardial infarction (MI) and significant comorbid illness with few treatment options for pain control was successfully managed with the placement of a spinal cord stimulator (SCS). Case Report: A 44-year old man presented with left upper extremity burning pain after MI. His past medical history included insulin-dependent diabetes mellitus, oxygen-dependent idiopathic pulmonary fibrosis, and recent coronary revascularization surgery. His pain was presumed to be related to his MI and a clinical diagnosis of CRPS type I (or reflex sympathetic dystrophy) was made. Facing limited medical and less invasive options for his pain relief, he underwent a spinal cord stimulation trial with excellent response. He had more than 70% pain relief from the spinal cord stimulation at the last follow-up, 2 years later. Conclusion: CRPS type I after MI can be difficult to treat because of other comorbid illnesses. SCS can be a safe and effective mode of therapy for patients facing limited treatment options. C1 Massachusetts Gen Hosp, Pain Ctr, WACC 324, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ahmed, SU (reprint author), Massachusetts Gen Hosp, Pain Ctr, WACC 324, Dept Anesthesia & Crit Care, 15 Parkman St, Boston, MA 02114 USA. NR 16 TC 3 Z9 4 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 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD MAY-JUN PY 2003 VL 28 IS 3 BP 245 EP 247 DI 10.1053/rapm.2003.50051 PG 3 WC Anesthesiology SC Anesthesiology GA 683QQ UT WOS:000183161100013 PM 12772144 ER PT J AU Seliger, SL Stehman-Breen, CO AF Seliger, SL Stehman-Breen, CO TI Are HMG-CoA reductase inhibitors underutilized in dialysis patients? SO SEMINARS IN DIALYSIS LA English DT Editorial Material ID CORONARY-ARTERY DISEASE; CHRONIC-RENAL-FAILURE; CARDIOVASCULAR-DISEASE; HEMODIALYSIS-PATIENTS; DENSITY LIPOPROTEINS; FOLLOW-UP; CHOLESTEROL; MEN; PREVENTION; EVENTS AB Patients with end-stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this article we will first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologic mechanisms by which statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population. Finally, we will review how statins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population. C1 VA Puget Sound Hlth Care Syst, Div Nephrol, Seattle, WA 98108 USA. Univ Washington, Dept Med, Div Nephrol, Seattle, WA 98195 USA. RP Stehman-Breen, CO (reprint author), VA Puget Sound Hlth Care Syst, Div Nephrol, Mailstop 111A,1650 S Columbian Way, Seattle, WA 98108 USA. NR 81 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD MAY-JUN PY 2003 VL 16 IS 3 BP 179 EP 185 DI 10.1046/j.1525-139X.2003.16036.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 677AM UT WOS:000182784800001 PM 12753674 ER PT J AU Ancoli-Israel, S Cole, R Alessi, C Chambers, M Moorcroft, W Pollak, CP AF Ancoli-Israel, S Cole, R Alessi, C Chambers, M Moorcroft, W Pollak, CP TI The role of actigraphy in the study of sleep and circadian rhythms SO SLEEP LA English DT Review ID NURSING-HOME PATIENTS; REST-ACTIVITY RHYTHM; DEFICIT-HYPERACTIVITY DISORDER; DATA-ANALYSIS SOFTWARE; SCHOOL-AGE-CHILDREN; POSTTRAUMATIC-STRESS-DISORDER; AMBULATORY BLOOD-PRESSURE; STIMULATION TENS IMPROVES; PHYSICAL-ACTIVITY LEVEL; ARTERY BYPASS-SURGERY C1 VASDHS, Dept Psychiat, San Diego, CA 92161 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Synchrony Appl Hlth Sci, Del Mar, CA 92014 USA. VA Greater Los Angles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA 90024 USA. Colorado State Univ, Ft Collins, CO 80523 USA. Ohio State Univ, Dept Neurol, Columbus, OH 43210 USA. RP Ancoli-Israel, S (reprint author), VASDHS, Dept Psychiat, 3350 La Jolla Village Dr, San Diego, CA 92161 USA. FU NCI NIH HHS [CA85264]; NIA NIH HHS [AG08415, AG13885] NR 224 TC 906 Z9 913 U1 19 U2 114 PU AMER ACAD SLEEP MEDICINE PI ROCHESTER PA 6301 BANDEL RD, STE 101, ROCHESTER, MN 55901 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAY 1 PY 2003 VL 26 IS 3 BP 342 EP 392 PG 51 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670ZC UT WOS:000182439100020 PM 12749557 ER PT J AU Orces, CH Casas, C Lee, S Garcia-Cavazos, R White, W AF Orces, CH Casas, C Lee, S Garcia-Cavazos, R White, W TI Determinants of osteoporosis prevention in low-income Mexican-American women SO SOUTHERN MEDICAL JOURNAL LA English DT Article ID HORMONE REPLACEMENT THERAPY; BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; ESTROGEN REPLACEMENT; CALCIUM; HEALTH; EXERCISE; MANAGEMENT; PHYSICIANS; NUTRITION AB Background: Prevention is the most cost-effective means of managing osteoporosis. However, little is known about osteoporosis-related preventive practices in Mexican-American women. We examined factors that might influence women's decision to start preventive measures for osteoporosis. Methods: Information was gathered through a cross-sectional survey of low-income Mexican-American women who were seen at two clinics in southern Texas. Results: Of the 270 participants, 37% reported calcium supplementation, and 41% reported regular weight-bearing exercise to prevent osteoporosis. Fifty (41%) of the postmenopausal women were currently using hormone replacement therapy. Only 15% of the premenopausal and 13% of the postmenopausal women recalled that their health care provider had counseled them about prevention. Multivariate analysis showed that public education, bone densitometry evaluation, knowledge of osteoporosis, and counseling were determinants of prevention. Conclusion: Although osteoporosis is a preventable condition, our findings suggest that the majority of Mexican-American women do not receive adequate preventive measures or counseling about osteoporosis. Furthermore, we found that their health care provider's counseling about osteoporosis was a major determinant of osteoporosis prevention in these women. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Gateway Community Hlth Ctr, Laredo, Spain. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Orces, CH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 35 TC 18 Z9 21 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD MAY PY 2003 VL 96 IS 5 BP 458 EP 464 DI 10.1097/01.SMJ.0000051905.38128.B4 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 681XP UT WOS:000183061100009 PM 12911184 ER PT J AU Kurth, T Kase, CS Berger, K Schaeffner, ES Buring, JE Gaziano, JM AF Kurth, T Kase, CS Berger, K Schaeffner, ES Buring, JE Gaziano, JM TI Smoking and the risk of hemorrhagic stroke in men SO STROKE LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the American-Academy-of-Neurology CY APR 13-20, 2002 CL DENVER, COLORADO SP Amer Acad Neurol DE cigarette smoking; cohort study; intracerebral hemorrhage; risk factors; subarachnoid hemorrhage ID SPONTANEOUS INTRACEREBRAL HEMORRHAGE; ANEURYSMAL SUBARACHNOID HEMORRHAGE; MULTIPLE INTRACRANIAL ANEURYSMS; CIGARETTE-SMOKING; CARDIOVASCULAR-DISEASE; POPULATION; WOMEN; HYPERTENSION; CHOLESTEROL; PHYSICIANS AB Background and Purpose - Smoking is an established risk factor for ischemic stroke and subarachnoid hemorrhage (SAH), but the impact of smoking on intracerebral hemorrhage (ICH) is less clear. Methods - Prospective cohort study among 22 022 US male physicians participating in the Physicians' Health Study. Incidence of stroke was measured by self-report and confirmed by medical record review. We used Cox proportional-hazards models to evaluate the association of smoking with risk of total hemorrhagic stroke, ICH, and SAH. We categorized smoking into 4 groups: never, past, or current smokers of <20 or of &GE;20 cigarettes per day. Results - During 17.8 years of follow-up, 108 ICHs and 31 SAHs occurred. Never smokers and past smokers had equal rates of ICH and SAH. Current smokers of &GE;20 cigarettes per day had multivariable-adjusted relative risks of 1.65 (95% CI, 0.61 to 4.50) for total hemorrhagic stroke, 1.60 ( 95% CI, 0.50 to 5.07) for ICH, and 1.75 ( 95% CI, 0.24 to 13.09) for SAH when compared with never smokers. Current smokers of <20 cigarettes had relative risks of 2.36 ( 95% CI, 1.38 to 4.02) for total hemorrhagic stroke, 2.06 ( 95% CI, 1.08 to 3.96) for ICH, and 3.22 ( 95% CI, 1.26 to 8.18) for SAH when compared with never smokers. Conclusions - This prospective study suggests an increased risk of total hemorrhagic stroke, ICH, and SAH in current cigarette smokers with a graded increase in risk that depended on how many cigarettes were smoked. The effect of smoking on ICH is of about the same magnitude as the effect of smoking on ischemic stroke. Our results add to the multiple health benefits that can be accrued by abstaining from cigarette smoking. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. Univ Munster, Inst Epidemiol & Social Med, Munster, Germany. Univ Freiburg, Dept Nephrol, Freiburg, Germany. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Kurth, T (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 NR 43 TC 47 Z9 49 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD MAY PY 2003 VL 34 IS 5 BP 1151 EP 1155 DI 10.1161/01.STR.0000065200.93070.32 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 673NB UT WOS:000182586100011 ER PT J AU Atochin, DN Clark, J Demchenko, IT Moskowitz, MA Huang, PL AF Atochin, DN Clark, J Demchenko, IT Moskowitz, MA Huang, PL TI Rapid cerebral ischemic preconditioning in mice deficient in endothelial and neuronal nitric oxide synthases SO STROKE LA English DT Article DE cerebral ischemia; ischemic preconditioning; mice, knockout; models, animal ID HEAT-SHOCK-PROTEIN; BLOOD-FLOW; TOLERANCE; BRAIN; GENE; PATHWAY; HIPPOCAMPUS; SURVIVAL; RATS AB Background and Purpose-The purpose of this study was to test the hypothesis that nitric oxide is required for preconditioning in an intact animal model of focal ischemia using neuronal and endothelial nitric oxide synthase (nNOS and eNOS) knockout mice. Methods-Cerebral blood flow was measured in wild-type, nNOS knockout, and eNOS knockout mice by hydrogen clearance (absolute) and laser Doppler flowmetry (relative). Mice were preconditioned by three 5-minute episodes of transient middle cerebral artery occlusion (MCAO) and subjected to permanent MCAO. Neurological deficit and infarct size were determined 24 hours later. Results-Although wild-type mice showed protection from ischemic preconditioning, neither eNOS nor nNOS knockout mice showed protection. Laser Doppler measurements indicated that the relative blood flow decreases in core ischemic areas were the same in all groups. Conclusions-Neither eNOS nor nNOS knockout mice show protection from rapid ischemic preconditioning, suggesting that nitric oxide may play a role in the molecular mechanisms of protection. C1 Massachusetts Gen Hosp E, Cardiovasc Res Ctr, Div Cardiol, Charlestown, MA USA. Massachusetts Gen Hosp E, Ctr Neurosci, Dept Radiol, Charlestown, MA USA. Duke Univ, Ctr Hyperbar Med & Environm Physiol, Durham, NC USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Atochin, Dmitriy/Q-3150-2016 FU NINDS NIH HHS [2R01-NS33335, 5P50-NS10828] NR 23 TC 73 Z9 84 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 MAY PY 2003 VL 34 IS 5 BP 1299 EP 1303 DI 10.1161/01.STR.0000066870.70976.57 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 673NB UT WOS:000182586100038 PM 12677017 ER PT J AU Swaminathan, GJ Holloway, DE Colvin, RA Campanella, GK Papageorgiou, AC Luster, AD Acharya, KR AF Swaminathan, GJ Holloway, DE Colvin, RA Campanella, GK Papageorgiou, AC Luster, AD Acharya, KR TI Crystal structures of oligomeric forms of the IP-10/CXCL10 chemokine SO STRUCTURE LA English DT Article ID NEUTROPHIL-ACTIVATING PEPTIDE-2; HUMAN-PLATELET FACTOR-4; DIFFERENTIAL EXPRESSION; MONOMERIC INTERLEUKIN-8; INDUCIBLE PROTEIN-10; MULTIPLE-SCLEROSIS; IP-10 CHEMOKINE; NMR ASSIGNMENTS; BINDING; CHEMOATTRACTANT AB We have determined the structure of wild-type IP-10 from three crystal forms. The crystals provide eight separate models of the IP-10 chain, all differing substantially from a monomeric IP-10 variant examined previously by NMR spectroscopy. In each crystal form, IP-10 chains form conventional beta sheet dimers, which, in turn, form a distinct tetrameric assembly. The M form tetramer is reminiscent of platelet factor 4, whereas the T and H forms feature a novel twelve-stranded beta sheet. Analytical ultracentrifugation indicates that, in free solution, IP-10 exists in a monomer-dimer equilibrium with a dissociation constant of 9 muM. We propose that the tetrameric structures may represent species promoted by the binding of glycosaminoglycans. The binding sites for several IP-10-neutralizing mAbs have also been mapped. C1 Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Charlestown, MA 02129 USA. RP Acharya, KR (reprint author), Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. OI Swaminathan, Jawahar/0000-0002-0215-4084; Papageorgiou, Anastassios/0000-0002-7980-1120; Holloway, Daniel/0000-0003-0155-6978 FU NCI NIH HHS [R01-CA69212]; NIAID NIH HHS [K08-AI50147]; NIDDK NIH HHS [P01-DK5030] NR 59 TC 40 Z9 42 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2003 VL 11 IS 5 BP 521 EP 532 DI 10.1016/S0969-2126(03)00070-4 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 677ZC UT WOS:000182838900008 PM 12737818 ER PT J AU Stolt, PC Jeon, H Song, HK Herz, J Eck, MJ Blacklow, SC AF Stolt, PC Jeon, H Song, HK Herz, J Eck, MJ Blacklow, SC TI Origins of peptide selectivity and phosphoinositide binding revealed by structures of disabled-1 PTB domain complexes SO STRUCTURE LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; PLECKSTRIN HOMOLOGY DOMAINS; AMYLOID PRECURSOR PROTEIN; ABL TYROSINE KINASE; PHOSPHOTYROSINE-BINDING; INOSITOL PHOSPHATES; CYTOSOLIC ADAPTER; VLDL RECEPTOR; SHC; PHOSPHORYLATION AB Formation of the mammalian six-layered neocortex depends on a signaling pathway that involves Reelin, the very low-density lipoprotein receptor, the apolipoprotein E receptor-2 (ApoER2), and the adaptor protein Disabled-1 (Dab1). The 1.5 Angstrom crystal structure of a complex between the Dab1 phosphotyrosine binding (PTB) domain and a 14-residue peptide from the ApoER2 tall explains the unusual preference of Dab1 for unphosphorylated tyrosine within the NPxY motif of the peptide. Crystals of the complex soaked with the phosphoinositide PI-4,5P(2) (PI) show that PI binds to conserved basic residues on the PTB domain opposite the peptide binding groove. This finding explains how the Dab1 PTB domain can simultaneously bind PI and the ApoER2 tail. Recruitment of the Dab1 PTB domain to PI-rich regions of the plasma membrane may facilitate association with the Reelin receptor cytoplasmic tails to transduce a critical positional cue to migrating neurons. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dept Mol Genet, Dallas, TX 75390 USA. RP Blacklow, SC (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU NCRR NIH HHS [RR-01646]; NHLBI NIH HHS [HL20948, HL61001, HL63762, R37 HL063762]; NINDS NIH HHS [NS43408] NR 47 TC 79 Z9 88 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2003 VL 11 IS 5 BP 569 EP 579 DI 10.1016/S0969-2126(03)00068-6 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 677ZC UT WOS:000182838900012 PM 12737822 ER PT J AU Berger, DH O'Mahony, CA Sheng, HM Shao, JY Albo, D DuBois, RN Beauchamp, RD AF Berger, DH O'Mahony, CA Sheng, HM Shao, JY Albo, D DuBois, RN Beauchamp, RD TI Intestinal transformation results in transforming growth factor-beta-dependent alteration in tumor cell-cell matrix interactions SO SURGERY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; PRIMARY BREAST-CANCER; HUMAN-LUNG FIBROBLASTS; HUMAN COLON-CANCER; TGF-BETA; COLORECTAL-CANCER; DISEASE PROGRESSION; UROKINASE-RECEPTOR; MESSENGER-RNA; ENDOTHELIAL-CELLS AB Background. An alteration in the expression of and response to transforming growth fa(tor-beta I (TGF-beta1) appears to be an important event during colorectal carcinogenesis. However, the precise role of TGF-beta1 in colorectal carcinogenesis is not clear. We have previously described in detail the changes in cell proliferation and differentiation caused by chronic exposure to TGF-beta1. In this study we sought to better characterize, the changes in tumor cell-cell matrix interactions seen during TGF-beta1-mediated intestinal transformation. Methods. Rat intestinal epithelial cells (RIE) and RIE cells transformed by chroinic exposure to TGF-beta1 (RIE-Tr) were treated with TGF-beta1 and production of components of the plasmin/plasminogen system measured by ELISA and Western blotting. TGF-beta1 effects on invasion and adhesion were determined in vitro. The role of urokinase on TGF-beta1-mediated invasion and adhesion were determined using immunoneutralization. The role of COX-2 was determined suing a specific COS-2 inhibitor. Results. TGF-beta1 had no effect on RIE-1 adhesion to collagen types I and IV, fibronectin, and laminin, or invasion through collagen types I and IV However, 5 ng/mL TGF-beta1 significantly increased the invasiveness and decreased the adhesiveness of RIE-Tr. This effect of TGF-beta1 on RIE-Tr was associated with a significant increase in plasmin activity secondary to increased expression of muPA. TGF-beta1 had no effect on either uPA receptor or PAI-1 in this system. Antibodies to uPA completely blocked the TGF-beta1-mediated invasiveness of the RIE-Tr cells and returned their adhesiveness to basement membrane proteins to baseline. Addition of the selective Cox-2, inhibitor SG58125 resulted in a dose-dependent decrease in TGF-beta1-mediated invasion and uPA expression. Conclusion. This study provides additional evidence for TGF-beta1 as a tumor promoter during intestinal carcinogenesis and a possible new mechanism for Cox-2-related colon carcinogenesis. C1 Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Drexel Univ, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Vanderbilt Univ, Ctr Med, Vanderbilt Ingram Canc Ctr, Dept Surg, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA. Vet Affairs Med Ctr, Nashville, TN 37212 USA. RP Berger, DH (reprint author), Houston Vet Adm Med Ctr, Surg Serv 112, 2002 Holcombe Blvd, Houston, TX 77030 USA. OI Beauchamp, Robert Daniel/0000-0002-8446-4114 FU NCI NIH HHS [CA69457, CA68485, P01-CA 77839]; NIDDK NIH HHS [DK-52334, DK47297]; NIEHS NIH HHS [ES00267] NR 57 TC 5 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD MAY PY 2003 VL 133 IS 5 BP 568 EP 579 DI 10.1067/msy.2003.125 PG 12 WC Surgery SC Surgery GA 686RL UT WOS:000183334700014 PM 12773985 ER PT J AU Kamada, K Houkin, K Takeuchi, F Ishii, N Ikeda, J Sawamura, Y Kuriki, S Kawaguchi, H Iwasaki, Y AF Kamada, K Houkin, K Takeuchi, F Ishii, N Ikeda, J Sawamura, Y Kuriki, S Kawaguchi, H Iwasaki, Y TI Visualization of the eloquent motor system by integration of Meg, functional, and anisotropic diffusion-weighted MRI in functional neuronavigation SO SURGICAL NEUROLOGY LA English DT Article DE anisotropic diffusion-weighted imaging; functional neuronavigation; functional magnetic resonance imaging; magnetoencephalography; neuronavigation; corticospinal tract ID MAGNETOENCEPHALOGRAPHY; CORTEX; IMAGES; QUANTIFICATION; ACTIVATION; TUMORS; AREAS AB BACKGROUND In this study, we visualized the eloquent motor system including the somatosensory-motor cortex and corticospinal tract on a neuronavigation system, integrating magnetoencephalography (MEG), functional magnetic resonance imaging (fMRI), and anisotropic diffusion-weighted MRI (ADWI). METHODS Four patients with brain lesions adjacent to the eloquent motor system were studied. Motor-evoked responses (MER) by finger-tapping paradigm were acquired with a 1.5-Tesla MR scanner, and somatosensory-evoked magnetic fields (SEF) by median nerve stimulation were measured with a 204-channel MEG system. In the same fMRI examination, ADWI and anatomic three-dimensional T1-weighted imaging (3-D MRI) were obtained. Activated areas of MER, estimated SEF dipoles, and the corticospinal tract on ADWI were coregistered to 3-D MRI, and the combined MR data were transferred to a neuronavigation system (functional neuronavigation). Intraoperative recording of cortical somatosensory-evoked potentials was performed for confirmation of the central sulcus. RESULTS Combination of fMRI and MEG enabled firm identification of the central sulcus. Functional neuronavigation facilitated extensive tumor resection, having the advantage of sparing the motor cortex and corticospinal tract in all cases. CONCLUSIONS The proposed functional neuronavigation allows neuro-surgeons to perform effective and maximal resection of brain lesions, identifying and sparing eloquent cortical components and their subcortical connections. Potential clinical application of this technique is discussed. (C) 2003 Elsevier Inc. All rights reserved. C1 Hokkaido Univ, Sch Med, Dept Neurosurg, Kita Ku, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Res Inst Elect Sci, Sapporo, Hokkaido 0608638, Japan. Hokkaido Univ, Dept Lab Med, Sapporo, Hokkaido 0608638, Japan. Massachusetts Gen Hosp, Dept Neurol Sci, Boston, MA 02114 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Kamada, K (reprint author), Hokkaido Univ, Sch Med, Dept Neurosurg, Kita Ku, N-15 W-7, Sapporo, Hokkaido 0608638, Japan. RI Houkin, Kiyohiro/G-5364-2012 NR 15 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD MAY PY 2003 VL 59 IS 5 BP 353 EP 362 DI 10.1016/S0090-3019(03)00018-1 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 682JV UT WOS:000183089200005 ER PT J AU Ambati, J Ambati, BK Yoo, SH Ianchulev, S Adamis, AP AF Ambati, J Ambati, BK Yoo, SH Ianchulev, S Adamis, AP TI Age-related macular degeneration: Etiology, pathogenesis, and therapeutic strategies SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE age-related macular degeneration; choroidal neovascularization; drusen; macular dystrophies ID ENDOTHELIAL GROWTH-FACTOR; RETINAL-PIGMENT EPITHELIUM; CHOROIDAL NEOVASCULAR MEMBRANES; BEAVER-DAM-EYE; BLUE-MOUNTAINS EYE; VASCULAR-PERMEABILITY FACTOR; GLYCATION END-PRODUCTS; NITRIC-OXIDE SYNTHASE; EXTERNAL-BEAM RADIATION; STARGARDT-DISEASE GENE AB Age-related macular degeneration is the principal cause of registered legal blindness among those aged over 65 in the United States, western Europe, Australia, and Japan. Despite intensive research, the precise etiology of molecular events that underlie age-related macular degeneration is poorly understood. However, investigations on parallel fronts are addressing this prevalent public health problem. Sophisticated biochemical and biophysical techniques have refined our understanding of the pathobiology of drusen, geographic atrophy, and retinal pigment epithelial detachments. Epidemiological identification of risk factors has facilitated an intelligent search for underlying mechanisms and fueled clinical investigation of behavior modification. Gene searches have not only brought us to the cusp of identifying the culpable gene loci in age-related macular degeneration, but also localized genes responsible for other macular dystrophies. Recent and ongoing investigations, often cued by tumor biology, have revealed an important role for various growth factors, particularly in the neovascular form of the condition. Transgenic and knockout studies have provided important mechanistic insights into the development of choroidal neovascularization, the principal cause of vision loss in age-related macular degeneration. This in turn has culminated in preclinical and clinical trials of directed molecular interventions. C1 Eyetech Res Ctr, Woburn, MA 01801 USA. Univ Kentucky, Dept Ophthalmol, Ocular Angiogenesis Lab, Lexington, KY USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Miami, FL USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Eyetech Res Ctr, 42 Cummings Pk, Woburn, MA 01801 USA. NR 522 TC 505 Z9 568 U1 12 U2 73 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2003 VL 48 IS 3 BP 257 EP 293 DI 10.1016/S0039-6257(03)000304 PG 37 WC Ophthalmology SC Ophthalmology GA 680YC UT WOS:000183006800002 PM 12745003 ER PT J AU Rohde, LA Roman, T Szobot, C Cunha, RD Hutz, MH Biederman, J AF Rohde, LA Roman, T Szobot, C Cunha, RD Hutz, MH Biederman, J TI Dopamine transporter gene, response to methylphenidate and cerebral blood flow in attention-deficit/hyperactivity disorder: A pilot study SO SYNAPSE LA English DT Article DE ADHD; DAT1 gene; SPECT; methylphenidate ID DEFICIT HYPERACTIVITY DISORDER; ASSOCIATION AB The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH),in children with attention-deficit/hyperactivity disorder (ADHD). This pilot study aimed to simultaneously assess polymorphisms at DAT1, response to MPH, and neuroimaging. Only ADHD children with at least a moderate response to MPH were included. Significantly higher regional cerebral blood flows assessed by single photon emission computerized tomography (SPECT) were detected in medial frontal and left basal ganglia areas in children with homozygosity for the 10-repeat allele at DAT1 gene (n = 4) than in children without this genotype (n = 4) (P < 0.05). These findings provide a preliminary connection between pharmacogenetics and neurobiological investigations on stimulant treatment of ADHD. (C) 2003 Wiley-Liss, Inc. C1 Univ Fed Rio Grande Sul, Serv Psiquiat Infancia & Adolescencia, Hosp Clin Porto Alegre, ADHD Outpatient Clin, BR-90035003 Porto Alegre, RS, Brazil. Univ Fed Rio Grande Sul, Dept Genet, BR-90035003 Porto Alegre, RS, Brazil. Hosp Clin Porto Alegre, Nucl Med Serv, Porto Alegre, RS, Brazil. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA USA. RP Rohde, LA (reprint author), Univ Fed Rio Grande Sul, Serv Psiquiat Infancia & Adolescencia, Hosp Clin Porto Alegre, ADHD Outpatient Clin, Rua Ramiro Barcelos 2350, BR-90035003 Porto Alegre, RS, Brazil. RI Rohde, Luis Augusto/A-6426-2008; Roman, Tatiana/C-1300-2010; OI Rohde, Luis Augusto/0000-0002-4552-4188; Hutz, Mara/0000-0002-9146-1229 NR 10 TC 45 Z9 47 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 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2003 VL 48 IS 2 BP 87 EP 89 DI 10.1002/syn.10186 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 661MT UT WOS:000181894900004 PM 12619042 ER PT J AU Zubair, A Zahrieh, D Daley, H Schott, D Gribben, JG Freedman, A Ritz, J AF Zubair, A Zahrieh, D Daley, H Schott, D Gribben, JG Freedman, A Ritz, J TI Early neutrophil engraftment following autologous BMT provides a functional predictor of long-term hematopoletic reconstitution SO TRANSFUSION LA English DT Article ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; COLONY-STIMULATING FACTOR; BLOOD PROGENITOR CELLS; HIGH-DOSE THERAPY; PERIPHERAL-BLOOD; HEMATOPOIETIC STEM; MYELODYSPLASTIC SYNDROME; MONOCLONAL-ANTIBODIES AB BACKGROUND: Previous studies have demonstrated that the number of CD34+ progenitor cells in the stem cell graft is highly predictive of the rapidity of short-term hematopoietic engraftment. The aim of this study was to identify factors that predict long-term hematopoietic reconstitution (LHR) following autologous BMT. STUDY DESIGN AND METHODS: To identify predictors of LHR, peripheral blood counts and marrow biopsies were evaluated at 1 year after transplant in 81 patients with B-cell non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia who underwent autologous BMT. Results were correlated with CD34+ cell dose, granulocyte-monocyte colony-forming units (CFU-GM) infused, and time to neutrophil engraftment (TNE). RESULTS: Total MNC dose, CD34+ cell dose, and CFU-GM infused were significantly associated with TNE (p = 0.011, p < 0.0001, and p = 0.078, respectively). Patients with chronic lymphocytic leukemia were more likely to have received a low CD34+ cell dose than patients with B-cell non-Hodgkin's lymphoma (p 0.01). Among the four principal predictors, only TNE showed consistent significant correlation with WBC, absolute neutrophil, and platelet count at 1 year after transplant. Logistic regression model showed that TNE was a more sensitive predictor of LHR than either CD34+ cell dose or CFU-GM infused. CONCLUSION: TNE is an in vivo functional measure of LHR and is a more sensitive predictor of LHR at 1 year after BIMT than either CD34+ cell dose or CFU-GM infused. C1 Dana Farber Canc Inst, Connell O Reilly Cell Manipulat Core Facil, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol & Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Connell O Reilly Cell Manipulat Core Facil, 44 Binney St,M530, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996]; NHLBI NIH HHS [5T32-HL66987, HL04095] NR 36 TC 12 Z9 17 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2003 VL 43 IS 5 BP 614 EP 621 DI 10.1046/j.1537-2995.2003.00369.x PG 8 WC Hematology SC Hematology GA 670PV UT WOS:000182418300013 PM 12702183 ER PT J AU Wu, A Buhler, LH Cooper, DKC AF Wu, A Buhler, LH Cooper, DKC TI ABO-incompatible organ and bone marrow transplantation: current status SO TRANSPLANT INTERNATIONAL LA English DT Review DE ABO-incompatibility; accommodation; B-cell tolerance; bone marrow allotransplantation; organ allotransplantation; tolerance ID SINGLE-CENTER EXPERIENCE; DONOR KIDNEY-TRANSPLANTATION; ACCELERATED ACUTE REJECTION; BLOOD-GROUP INCOMPATIBILITY; VERSUS-HOST DISEASE; LIVER-TRANSPLANTATION; RENAL-TRANSPLANTATION; HEART-TRANSPLANTATION; O-RECIPIENTS; A(2) KIDNEYS AB Despite the presence of preformed antibodies against AB oligosaccharide epitopes on the donor vascular endothelium, approximately one-third of ABO-incompatible organ allografts are not rejected by a humoral mechanism. With the growing immune-manipulation of the recipient, survival rates can be raised considerably, although they remain significantly inferior to those of ABO-compatible transplantation. Data from the Collaborative Transplant Study indicate a 1-year graft survival rate of approximately 50-60% following cadaveric ABO-incompatible kidney, liver or heart transplantation, compared with 70-80% for an ABO-compatible organ. The results for infants and young children, however, are very much better than those of adults, particularly for liver and heart transplantations, and the data suggest that B-cell tolerance can develop in the infant age group. We here review clinical and experimental experience with ABO-incompatible organ and bone marrow allotransplantation and address the mechanisms by which organs or cells survive in the presence of natural anti-carbohydrate antibodies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Univ Hosp Geneva, Dept Surg, CH-1211 Geneva, Switzerland. RP Buhler, LH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. FU PHS HHS [1PO1 A145897] NR 96 TC 45 Z9 51 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-0874 J9 TRANSPLANT INT JI Transpl. Int. PD MAY PY 2003 VL 16 IS 5 BP 291 EP 299 DI 10.1007/s00147-003-0592-4 PG 9 WC Surgery; Transplantation SC Surgery; Transplantation GA 696AN UT WOS:000183862700001 PM 12719804 ER PT J AU Carvalho, P Tirnauer, JS Pellman, D AF Carvalho, P Tirnauer, JS Pellman, D TI Surfing on microtubule ends SO TRENDS IN CELL BIOLOGY LA English DT Review ID XENOPUS EGG EXTRACTS; POLYPOSIS-COLI PROTEIN; APC TUMOR-SUPPRESSOR; MITOTIC SPINDLE; DYNAMIC INSTABILITY; BINDING PROTEIN; SACCHAROMYCES-CEREVISIAE; CYTOPLASMIC DYNEIN; IN-VITRO; TRANSITION FREQUENCIES AB A crowd of proteins seems to have gathered around the plus-ends of microtubules. A rapidly expanding group of proteins known as plus-end tracking proteins (+TIPs) have been identified that seem to be able to 'surf' the dynamic ends of microtubules. Microtubule plus-ends exist in multiple conformational and chemical states. In principle, altering this plus-end microenvironment is an appealing way for regulators such as the +TIPS to control microtubule dynamics; however, specific mechanisms are poorly defined. Here, we focus on new findings addressing the underlying mechanisms of plus-end tracking and the mechanisms by which +TIPS control microtubule dynamics. We review the evidence that plus-end-binding and the control of microtubule dynamics are mechanistically linked. We also consider the possibility that, by studying +TIPs, we might learn more about the dynamic structural changes at the microtubule ends that are at the heart of dynamic instability. C1 Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Inst Biomed Sci Abel Salazar, Oporto, Portugal. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. OI Carvalho, Pedro/0000-0002-9691-5277 FU NIDDK NIH HHS [K08 DK-02578] NR 90 TC 181 Z9 185 U1 1 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD MAY PY 2003 VL 13 IS 5 BP 229 EP 237 DI 10.1016/S0962-8924(03)00074-6 PG 9 WC Cell Biology SC Cell Biology GA 683BN UT WOS:000183127000004 PM 12742166 ER PT J AU Ploghaus, A Becerra, L Borras, C Borsook, D AF Ploghaus, A Becerra, L Borras, C Borsook, D TI Neural circuitry underlying pain modulation: expectation, hypnosis, placebo SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID ANTERIOR CINGULATE CORTEX; ANTICIPATORY ANXIETY; CONDITIONAL ANALGESIA; SOMATOSENSORY CORTEX; PREFRONTAL CORTEX; HUMAN BRAIN; RESPONSES; SYSTEMS; FEAR; STIMULATION AB The ability to predict the likelihood of an aversive event is an important adaptive capacity. Certainty and uncertainty regarding pain cause different adaptive behavior, emotional states, attentional focus, and perceptual changes. Recent functional neuroimaging studies indicate that certain and uncertain expectation are mediated by different neural pathways-the former having been associated with activity in the rostral anterior cingulate cortex and posterior cerebellum, the latter with activation changes in the ventromedial prefrontal cortex, mid-cingulate cortex and hippocampus. Expectation plays an important role not only in its modulation of acute and chronic pain, but also in other disorders which are characterized by certain expectation (specific phobias) or uncertain expectation (generalized anxiety disorder) of aversive events. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos NMR Ctr, Charlestown, MA 02129 USA. RP Ploghaus, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos NMR Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 33 TC 181 Z9 185 U1 7 U2 44 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD MAY PY 2003 VL 7 IS 5 BP 197 EP 200 DI 10.1016/S1364-6613(03)00061-5 PG 4 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 683PL UT WOS:000183157900005 ER PT J AU Oh, WK AF Oh, WK TI Neoadjuvant therapy before radical prostatectomy in high-risk localized prostate cancer: defining appropriate endpoints SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE localized prostate cancer; chemotherapy; hormonal therapy; targeted therapy; neoadjuvant; endpoints ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; BREAST-CANCER; ANDROGEN ABLATION; HORMONAL-THERAPY; CHEMOTHERAPY; ANGIOGENESIS; DOCETAXEL; ESTRAMUSTINE; INHIBITION AB High-risk localized prostate cancer remains a vexing problem for clinicians. Definitive local treatments such as surgery and radiation therapy cure only a minority of these patients. As a result, efforts are being made to reduce the risk of recurrence by using chemotherapy and new agents before, during or after definitive local therapy. Neoadjuvant androgen deprivation therapy has yielded disappointing results when combined with surgery. Chemotherapy in the management of localized disease is evolving, and preliminary studies are just now being completed. Although these agents have established activity and acceptable toxicity in the hormone-refractory setting. more extensive use of them in patients with androgen-dependent disease will require data from randomized studies to determine overall efficacy. New molecular-targeted therapies are promising and hold the greatest hope that outcomes in early disease may be improved with early use of systemic therapy. The neoadjuvant surgical model also has promise in assessing the activity of new drugs, because it provides a means to determine molecular effects of specific agents, along with standard pathologic and clinical parameters of efficacy. (C) 2003 Elsevier Inc. All rights reserved. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 53 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 1078-1439 J9 UROL ONCOL-SEMIN O I JI Urol. Oncol.-Semin. Orig. Investig. PD MAY-JUN PY 2003 VL 21 IS 3 BP 229 EP 234 DI 10.1016/S1078-1439(03)00019-X PG 6 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 695YE UT WOS:000183857300010 PM 12810211 ER PT J AU Sykes, M d'Apice, A Sandrin, M AF Sykes, M d'Apice, A Sandrin, M CA IXA Ethics Comm TI The Ethics of Xenotransplantation - Position Paper of the Ethics Committee of the International Xenotransplantation Association SO XENOTRANSPLANTATION LA English DT Article DE ethics; guidelines; infectious risk; pig; porcine; religion; retrovirus; XTx ID PORCINE ENDOGENOUS RETROVIRUS; CROSS-SPECIES TRANSMISSION; NO EVIDENCE; LIVER-TRANSPLANTATION; HUMAN-CELLS; INFECTION; RECIPIENTS; SURVIVAL; FAILURE; ORGANS AB Xenotransplantation (XTx) provides a potential solution to the shortage of human organs and tissues, and has several advantages over other possible solutions to this problem. However, a number of scientific and ethical barriers exist, and need to be addressed in order to advance the field of XTx in a manner that optimizes its potential to benefit society and minimizes its risk. Some of the most pressing ethical issues are discussed, and the position of the Ethics Committee of the International Xenotransplantation Association is presented. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Head Bone Marrow Transplantat Sect,Transplantat B, Boston, MA 02129 USA. St Vincents Hosp, Dept Clin Immunol, Fitzroy, Vic 3065, Australia. Austin Res Inst, Austin, Australia. Repatriat Med Ctr, Heidelberg, Vic, Australia. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Head Bone Marrow Transplantat Sect,Transplantat B, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. NR 42 TC 53 Z9 53 U1 2 U2 13 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2003 VL 10 IS 3 BP 194 EP 203 DI 10.1034/j.1399-3089.2003.00067.x PG 10 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 667YK UT WOS:000182262300001 PM 12694539 ER PT J AU Omer, A Keegan, M Czismadia, E De Vos, P Van Rooijen, N Bonner-Weir, S Weir, GC AF Omer, A Keegan, M Czismadia, E De Vos, P Van Rooijen, N Bonner-Weir, S Weir, GC TI Macrophage depletion improves survival of porcine neonatal pancreatic cell clusters contained in alginate macrocapsules transplanted into rats SO XENOTRANSPLANTATION LA English DT Article DE biocompatibility; clodronate; encapsulation; insulin; islets; liposomes; rat; xenotransplantation ID ISLET XENOGRAFT REJECTION; PIG PROISLET XENOGRAFTS; NUDE-MICE; CYTOKINE PRODUCTION; XENOGENEIC ISLETS; GRAFT-SURVIVAL; IN-VITRO; MICROENCAPSULATION; IMMUNOSUPPRESSION; XENOTRANSPLANTATION AB Background: Macrophages can accumulate on the surface of empty and islet-containing alginate capsules, leading to loss of functional tissue. In this study, the effect of peritoneal macrophage depletion on the biocompatibility of alginate macrocapsules and function of macroencapsulated porcine neonatal pancreatic cell clusters (NPCCs) was investigated. Methods: Clodronate liposomes were injected into the peritoneal cavities of normoglycemic Lewis rats 5 and 2 days before the transplantation. Empty or NPCC-containing Ca-alginate poly L-lysine (PLL)-coated macrocapsules were transplanted into the peritoneal cavities of rats injected with either clodronate liposomes or saline. On days 7, 14 and 21, samples were evaluated by immunohistochemistry for cellular immune responses on the surface of the macrocapsules and for macrophage populations in omental tissue. To assess the function of macroencapsulated NPCCs, insulin secretory responses to glucose and theophylline were measured after capsule retrieval. Results: In saline-injected control groups, all of the empty and NPCC-containing macrocapsules were overgrown with macrophages, this being especially severe on NPCC-containing macrocapsules. In the clodronate liposomes-injected group, the majority of the empty macrocapsules were free of macrophage accumulation and the NPCC-containing macrocapsules were less overgrown than in control animals. Higher insulin responses to glucose and theophylline were observed in NPCCs retrieved from rats injected with clodronate liposomes. Conclusion: We conclude that depletion of peritoneal macrophages with clodronate liposomes improve the survival of macroencapsulated NPCCs. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Surg, Sch Med, Boston, MA 02215 USA. Univ Groningen, Groningen, Netherlands. Free Univ Amsterdam, Fac Med, Dept Cell Biol & Immunol, Amsterdam, Netherlands. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. RI de Vos, Paul/A-3170-2013 FU NIDDK NIH HHS [DK36836, P01 DK 053087, R01 DK 50657] NR 41 TC 38 Z9 38 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD MAY PY 2003 VL 10 IS 3 BP 240 EP 251 DI 10.1034/j.1399-3089.2003.01150.x PG 12 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 667YK UT WOS:000182262300006 PM 12694544 ER PT J AU Lalani, SR Stockton, DW Bacino, C Molinari, LM Glass, NL Fernbach, SD Towbin, JA Craigen, WJ Graham, JM Hefner, MA Lin, AE McBride, KL Davenport, SL Belmont, JW AF Lalani, SR Stockton, DW Bacino, C Molinari, LM Glass, NL Fernbach, SD Towbin, JA Craigen, WJ Graham, JM Hefner, MA Lin, AE McBride, KL Davenport, SL Belmont, JW TI Toward a genetic etiology of CHARGE syndrome: I. A systematic scan for submicroscopic deletions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE CHARGE syndrome; microsatellite markers; genotyping; loss of heterozygosity; submicroscopic deletion ID NEURAL CREST; ASSOCIATION; CHILD; MALFORMATION; EXPRESSION; EXCLUSION; FEATURES AB CHARGE syndrome is a distinctive subgroup within the more heterogeneous group of patients with CHARGE association. While significant progress has been made in the clinical delineation of this syndrome, the molecular basis of the disorder remains unknown. Based on the complex phenotype, some overlap with DiGeorge/velocardiofacial. syndrome (DGS/VCFS), and its estimated population incidence, we hypothesized that CHARGE syndrome could be caused by an unidentified genomic microdeletion. In order to address this hypothesis, we carried out a genome-wide screen for loss of expected heterozygosity using 811 microsatellite markers in ten CHARGE syndrome subjects and their unaffected parents. Eight markers gave results suggestive of failure to inherit one parental allele. These loci were tested with fluorescence in situ hybridization (FISH), but none showed evidence of deletion. This screen sets upper limits on the length of a CHARGE-related microdeletion, should that be the genetic mechanism underlying the phenotype. (C) 2003 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat Cardiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Univ Calif Los Angeles, Sch Med, Cedars Sinai Med Ctr, Ahmanson Pediat Dept,Med Genet Birth Defects Ctr, Los Angeles, CA USA. St Louis Univ, Sch Med, Dept Pediat, St Louis, MO 63103 USA. Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Sensory Genet Neuro Dev, St Paul, MN USA. RP Belmont, JW (reprint author), Baylor Coll Med, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA. RI McBride, Kim/A-5879-2008; OI McBride, Kim/0000-0002-8407-8942; Belmont, John/0000-0001-7409-3578 FU NICHD NIH HHS [HD22657-11, HD39056] NR 30 TC 21 Z9 21 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR 30 PY 2003 VL 118A IS 3 BP 260 EP 266 DI 10.1002/ajmg.a.20002 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 670HM UT WOS:000182401500010 PM 12673657 ER PT J AU Anikeeva, N Lebedeva, T Krogsgaard, M Tetin, SY Martinez-Hackert, E Kalams, SA Davis, MM Sykulev, Y AF Anikeeva, N Lebedeva, T Krogsgaard, M Tetin, SY Martinez-Hackert, E Kalams, SA Davis, MM Sykulev, Y TI Distinct molecular mechanisms account for the specificity of two different T-cell receptors SO BIOCHEMISTRY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; PEPTIDE-MHC; TRANSITION-STATES; WATER-MOLECULES; BINDING; THERMODYNAMICS; ANTIGEN; RECOGNITION; ANTIBODY; COMPLEX AB Analysis of the thermodynamics of the interactions between the D3 T-cell receptor (TCR) and its natural ligand, an HIV peptide bound to a HLA-A*0201 (HLA-A2) major histocompatibility complex (MHC) protein, shows both similarities and striking differences when compared with the 2134 TCR binding to its peptide-MHC ligand. The equilibrium thermodynamic parameters of both reactions are consistent with a conformational adjustment at the binding interface during the formation of specific TCR-peptide-MHC complexes. However, osmolytic reagents that dehydrate protein surfaces have profoundly different effects on the strength of the two reactions, indicating that water molecules make very different contributions-enhancing the binding of D3 TCR but weakening the binding of 2134 TCR. The use of these different mechanisms by TCRs to recognize ligands might be an important means augmenting their inherent cross-reactivity. C1 Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Abbott Labs, Abbott Diagnost Div, Abbott Pk, IL 60064 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Sykulev, Y (reprint author), Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Microbiol & Immunol, BLSB 650, Philadelphia, PA 19107 USA. OI Martinez-Hackert, Erik/0000-0002-6182-7023 FU NIAID NIH HHS [AI43254, AI39966, 5-T32-AI07523] NR 41 TC 40 Z9 40 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 29 PY 2003 VL 42 IS 16 BP 4709 EP 4716 DI 10.1021/bi026864+ PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 671JB UT WOS:000182460700012 PM 12705834 ER PT J AU Albert, CM Chae, CU Grodstein, F Rose, LM Rexrode, KM Ruskin, JN Stampfer, MJ Manson, JE AF Albert, CM Chae, CU Grodstein, F Rose, LM Rexrode, KM Ruskin, JN Stampfer, MJ Manson, JE TI Prospective study of sudden cardiac death among women in the United States SO CIRCULATION LA English DT Article DE death, sudden; women; arrhythmia; coronary disease; risk factors ID CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; ARREST; RISK; POPULATION; STROKE AB Background-There are few data regarding the determinants of sudden cardiac death (SCD) in women, primarily because of their markedly lower rate of SCD compared with men. Nonetheless, existing data, although sparse, suggest possible gender differences in risk factors for SCD. Methods and Results-In this prospective cohort of 121 701 women aged 30 to 55 years at baseline, SCD was defined as death within 1 hour of symptom onset. From 1976 to 1998, 244 SCDs were identified. Although the risk of SCD increased markedly with age, the percentage of cardiac deaths that were sudden decreased. Most (69%) women who suffered a SCD had no history of cardiac disease before their death. However, almost all of the women who died suddenly (94%) had reported at least 1 coronary heart disease risk factor. Smoking, hypertension, and diabetes conferred markedly elevated (2.5- to 4.0-fold) risk of SCD, similar to that conferred by a history of nonfatal myocardial infarction (relative risk, 4.1; 95% confidence interval, 2.9 to 6.7). Family history of myocardial infarction before age 60 years and obesity were associated with moderate (1.6-fold) elevations in risk. With regard to mechanism, 88% of SCDs were classified as arrhythmic. In 76% of these, the first rhythm documented was ventricular tachycardia or ventricular fibrillation. Conclusions-These prospective data suggest that, as in men, coronary heart disease risk factors predict risk of SCD in women and that SCD is usually an arrhythmic death. Therefore, prevention of atherosclerosis or ventricular arrhythmias may reduce the incidence of SCD in women. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Albert, CM (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA-87969]; NHLBI NIH HHS [HL-34594, 1-K08-HL-03783] NR 20 TC 183 Z9 190 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 29 PY 2003 VL 107 IS 16 BP 2096 EP 2101 DI 10.1161/01.CIR.0000065223.21530.11 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 672MU UT WOS:000182525300020 PM 12695299 ER PT J AU Albertson, RC Streelman, JT Kocher, TD AF Albertson, RC Streelman, JT Kocher, TD TI Directional selection has shaped the oral jaws of Lake Malawi cichlid fishes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID QUANTITATIVE TRAIT LOCI; SYMPATRIC SPECIATION; MORPHOLOGY; CONVERGENCE; EVOLUTION; PERCIFORMES; TANGANYIKA; TELEOSTEI; VICTORIA; PISCES AB East African cichlid fishes represent one of the most striking examples of rapid and convergent evolutionary radiation among vertebrates. Models of ecological speciation would suggest that functional divergence in feeding morphology has contributed to the origin and maintenance of cichlid species diversity. However, definitive evidence for the action of natural selection has been missing. Here we use quantitative genetics to identify regions of the cichlid genome responsible for functionally important shape differences in the oral jaw apparatus. The consistent direction of effects for individual quantitative trait loci suggest that cichlid jaws and teeth evolved in response to strong, divergent selection. Moreover, several chromosomal regions contain a disproportionate number of quantitative trait loci, indicating a prominent role for pleiotropy or genetic linkage in the divergence of this character complex. Of particular interest are genomic intervals with concerted effects on both the length and height of the lower jaw. Coordinated changes in this area of the oral jaw apparatus are predicted to have direct consequences for the speed and strength of jaw movement. Taken together, our results imply that the rapid and replicative nature of cichlid trophic evolution is the result of directional selection on chromosomal packages that encode functionally linked aspects of the craniofacial skeleton. C1 Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. RP Albertson, RC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 The Fenway, Boston, MA 02115 USA. RI Kocher, Thomas/B-3089-2013; OI Kocher, Thomas/0000-0002-7547-0133 FU NIDCR NIH HHS [R03 DE014446] NR 40 TC 191 Z9 194 U1 2 U2 57 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 APR 29 PY 2003 VL 100 IS 9 BP 5252 EP 5257 DI 10.1073/pnas.0930235100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600053 PM 12704237 ER PT J AU Prota, AE Campbell, JA Schelling, P Forrest, JC Watson, MJ Peters, TR Aurrand-Lions, M Imhof, BA Dermody, TS Stehle, T AF Prota, AE Campbell, JA Schelling, P Forrest, JC Watson, MJ Peters, TR Aurrand-Lions, M Imhof, BA Dermody, TS Stehle, T TI Crystal structure of human junctional adhesion molecule 1: Implications for reovirus binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATTACHMENT PROTEIN SIGMA-1; IMMUNOGLOBULIN SUPERFAMILY; CELL-ADHESION; SIALIC-ACID; ADENOVIRUS RECEPTOR; ENDOTHELIAL-CELLS; TIGHT JUNCTION; HUMAN CD4; COXSACKIEVIRUS; DOMAINS AB Reovirus attachment to cells is mediated by the binding of viral attachment protein sigma1 to junctional adhesion molecule 1 (JAM1). The crystal structure of the extracellular region of human JAM1 (hJAM1) reveals two concatenated Ig-type domains with a pronounced bend at the domain interface. Two hJAM1 molecules form a dimer that is stabilized by extensive ionic and hydrophobic contacts between the N-terminal domains. This dimeric arrangement is similar to that observed previously in the murine homolog of JAM1, indicating physiologic relevance. However, differences in the dimeric structures of hJAM1 and murine JAM1 suggest that the interface is dynamic, perhaps as a result of its ionic nature. We demonstrate that hJAM1, but not the related proteins hJAM2 and hJAM3, serves as a reovirus receptor, which provides insight into sites in hJAM1 that likely interact with sigma1. In addition, we present evidence that the previously reported structural homology between A and the adenovirus attachment protein, fiber, also extends to their respective receptors, which form similar dimeric structures. Because both receptors are located at regions of cell-cell contact, this similarity suggests that reovirus and adenovirus use conserved mechanisms of entry and pathways of infection. C1 Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Elizabeth B Lamb Ctr Pediat Res, Nashville, TN 37232 USA. Ctr Med Univ Geneva, Dept Pathol, CH-1211 Geneva, Switzerland. Massachusetts Gen Hosp, Lab Dev Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Dermody, TS (reprint author), Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, 221 Kirkland Hall, Nashville, TN 37232 USA. RI Aurrand-Lions, Michel/O-9953-2016 OI Aurrand-Lions, Michel/0000-0002-8361-3034 FU NCI NIH HHS [CA68485, P30 CA068485, T32 CA009385, T32 CA09385]; NIAID NIH HHS [R01 AI038296, R01 AI045716, R01 AI38296, R01 AI45716]; NIDDK NIH HHS [DK20593, P30 DK020593, P60 DK020593]; NIGMS NIH HHS [R01 GM067853, R01 GM67853] NR 50 TC 99 Z9 104 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 29 PY 2003 VL 100 IS 9 BP 5366 EP 5371 DI 10.1073/pnas.0937718100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673ZY UT WOS:000182612600073 PM 12697893 ER PT J AU Rosendale, JD Kauffman, HM McBride, MA Chabalewski, FL Zaroff, JG Garrity, ER Delmonico, FL Rosengard, BR AF Rosendale, JD Kauffman, HM McBride, MA Chabalewski, FL Zaroff, JG Garrity, ER Delmonico, FL Rosengard, BR TI Hormonal resuscitation yields more transplanted hearts, with improved early function SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 19th International Congress of the Transplantation-Society CY AUG 25-30, 2002 CL MIAMI, FLORIDA SP Transplantat Soc ID POTENTIAL ORGAN DONORS; BRAIN-DEATH; THERAPY; VASOPRESSIN; REPLACEMENT; ACTIVATION; REJECTION; REVERSAL; RAT AB Background. Brain death results in cardiovascular instability and poor organ perfusion in many brain-dead donors. Hormonal resuscitation stabilizes certain brain-dead donors and is associated with significant increases in the numbers of organs transplanted per donor. The goal of this study was to examine the quality of hearts recovered from donors treated with hormonal resuscitation. Methods. A retrospective analysis of 4,543 recipients of hearts recovered from brain-dead donors, reported to the United Network for Organ Sharing/Organ Procurement and Transplantation Network database between November 1, 1999, and December 31, 2001, was conducted. Hormonal resuscitation consisted of a methylprednisolone bolus and infusions of vasopressin and either triiodothyronine or L-thyroxine. Univariate and multivariate analyses were used to evaluate the quality of hearts from donors who received three-drug hormonal resuscitation (3HR) treatment versus donors who did not receive all three drugs (non-3HR). Death within 30 days and early graft dysfunction were used as endpoints. Results. Hearts from 3HR donors demonstrated a 1-month survival rate of 96.2%, compared with a 92.1% survival rate for non-3HR donor hearts (P<0.01). Early graft dysfunction occurred in 5.6% of 3HR donor hearts and 11.6% of non-3HR donor hearts (P<0.01). Multivariate results demonstrated a 46% reduced odds of death within 30 days and a 48% reduced odds of early graft dysfunction. Steroids alone and steroids plus triiodothyronine/L-thyroxine also significantly reduced prolonged graft dysfunction. Conclusions. This study suggests that 3HR treatment of brain-dead donors results in increased numbers of transplanted hearts, with improved short-term graft function. C1 United Network Organ Sharing, Dept Res, Richmond, VA 23219 USA. United Network Organ Sharing, Prof Serv Dept, Richmond, VA 23219 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Loyola Univ, Dept Med, Chicago, IL 60611 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Rosendale, JD (reprint author), United Network Organ Sharing, Dept Res, 700 N 4th St, Richmond, VA 23219 USA. FU PHS HHS [231-00-0115] NR 28 TC 99 Z9 103 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 APR 27 PY 2003 VL 75 IS 8 BP 1336 EP 1341 DI 10.1097/01.TP.0000062839.58826.6D PG 6 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 673GV UT WOS:000182573100055 PM 12717226 ER PT J AU Alonso, JL Goldmann, WH AF Alonso, JL Goldmann, WH TI Feeling the forces: atomic force microscopy in cell biology SO LIFE SCIENCES LA English DT Review DE atomic force microscopy; intramolecular forces; intermolecular forces; molecular forces; cellular forces ID PROTEIN SURFACES; PROBE MICROSCOPY; AFM; VISUALIZATION; ELASTICITY; MOLECULES; DOMAINS; TITIN; DNA AB Atomic force microscopy allows three-dimensional imaging and measurements of unstained and uncoated biological samples in air or fluid. Using this technology it offers resolution on the nanometer scale and detection of temporal changes in the mechanical properties, i.e. surface stiffness or elasticity in live cells and membranes. Various biological processes including ligand-receptor interactions, reorganization, and restructuring of the cytoskeleton associated with cell motility that are governed by intermolecular forces and their mode of detection will be discussed. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Dept Med, Renal Unit,Massachusetts Gen Hosp, Bldg 149,13th St,Room 8200, Charlestown, MA 02129 USA. RI Alonso, Jose Luis/G-7961-2012; Goldmann, Wolfgang/H-5572-2013 NR 41 TC 104 Z9 111 U1 7 U2 46 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 25 PY 2003 VL 72 IS 23 BP 2553 EP 2560 DI 10.1016/S0024-3205(03)00165-6 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 665YT UT WOS:000182149400001 PM 12672501 ER PT J AU Lee, SS Kennedy, S Tolonen, AC Ruvkun, G AF Lee, SS Kennedy, S Tolonen, AC Ruvkun, G TI DAF-16 target genes that control C-elegans life-span and metabolism SO SCIENCE LA English DT Article ID CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; OXIDATIVE STRESS; TRANSCRIPTION; LONGEVITY; EXPRESSION AB Signaling from the DAF-2/insulin receptor to the DAF-16/FOXO transcription factor controls longevity, metabolism, and development in disparate phyla. To identify genes that mediate the conserved biological outputs of daf-2/insulin-like signaling, we used comparative genomics to identify 17 orthologous genes from Caenorhabditis and Drosophila, each of which bears a DAF-16 binding site in the promoter region. One-third of these DAF-16 downstream candidate genes were regulated by daf-2/insulin-like signaling in C. elegans, and RNA interference inactivation of the candidates showed that many of these genes mediate distinct aspects of daf-16 function, including longevity, metabolism, and development. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, 50 Blossom St, Boston, MA 02114 USA. NR 32 TC 376 Z9 392 U1 1 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 APR 25 PY 2003 VL 300 IS 5619 BP 644 EP 647 DI 10.1126/science.1083614 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 671FB UT WOS:000182453700043 PM 12690206 ER PT J AU Rosowsky, A Forsch, RA Queener, SF AF Rosowsky, A Forsch, RA Queener, SF TI Further studies on 2,4-Diamino-5-(2 ',5 '-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII; MYCOBACTERIUM-AVIUM; ANALOGS; TRIMETHOPRIM; PIRITREXIM; TRIMETREXATE; DERIVATIVES; DESIGN; ENZYME AB As part of an ongoing effort to discover novel small-molecule antifolates combining the enzyme-binding species selectivity of trimethoprim (TMP) with the potency of piritrexim (PTX), 10 previously unreported 2,4-diamino-5-(2'-methoxy-5'-substituted)benzylpyrimidines (2-11) containing a carboxyl group at the distal end of the 5'-substituent were synthesized and tested as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii (Pc), Toxoplasma gondii (Tg), and Mycobacterium avium (Ma), three of the opportunistic pathogens frequently responsible for life-threatening illness in people with impaired immune systems as a result of HIV infection or immunosuppressive chemotherapy. The selectivity index of DHFR inhibition was evaluated by comparing the potency of each compound against the parasite enzymes with its potency against rat liver DHFR. 2,4-Diamino-5-[5'-(5-carboxy-1-pentynyl)-2'-methoxybenzyl]-pyrimidine (3) inhibited Pc DHFR with a selectivity index of 79 and was 430 times more potent than TMP. 2,4-Diamino-5-[5'-(4-carboxy-1-butynyl)-2'-methoxybenzyl]pyrimidine (2), with one less carbon than 3 in the side chain, had a selectivity index of 910 against Ma DHFR and was 43 times more potent than TMP. 2,4-Diamino-5-[5'-(5-carboxypentyl)-2'-methoxybenzyl]pyrimidine (6) had a selectivity index of 490 against Tg DHFR and was 320 times more potent than TMP. 2,4-Diamino-5-[5'-(6-carboxy-1-hexynyl)-2'-methoxybenzyl]pyrimidine (4), with one more carbon than 3, was less potent against all three of the parasite enzymes than either 3 or 6 and also had a lower selectivity index than 3 against the Pc enzyme. However, 4 was the only member of the series with a selectivity index of >300 against both Tg and Ma DHFR. Given that PTX is at least 10 times more potent against rat DHFR than against P. carinii or T. gondii DHFR and that the selectivity index of several of the compounds matches or exceeds that of TMP as well as PTX, our results suggest that it may be possible to develop clinically useful nonclassical antifolates that are both potent and selective against the major opportunistic pathogens of AIDS. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM andre_rosowsky@dfci.harvard.edu FU NIAID NIH HHS [R01-AI29904] NR 36 TC 32 Z9 32 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 24 PY 2003 VL 46 IS 9 BP 1726 EP 1736 DI 10.1021/jm020466n PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 671WR UT WOS:000182488300017 PM 12699390 ER PT J AU Woolf, CJ AF Woolf, CJ TI No Nogo: Now where to go? SO NEURON LA English DT Review ID MYELIN-ASSOCIATED GLYCOPROTEIN; SPINAL-CORD INJURY; AXONAL REGENERATION; NEURITE OUTGROWTH; RECEPTOR; INHIBITOR; IDENTIFICATION; RECOVERY; GROWTH; LIGAND AB Nogo-A, a reticulon protein expressed by oligodendrocytes, contributes to the axonal growth inhibitory action of central myelin in growth cone collapse and neurite outgrowth in vitro assays, and antibody and inhibitor studies have implicated a role for Nogo in regeneration in the adult CNS in vivo. Three independent labs have now produced Nogo knockout mice with, quite unexpectedly, three different regeneration phenotypes. C1 Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Boston, MA 02129 USA. NR 20 TC 77 Z9 82 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 24 PY 2003 VL 38 IS 2 BP 153 EP 156 DI 10.1016/S0896-6273(03)00233-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 672AM UT WOS:000182498300005 PM 12718850 ER PT J AU Bar, M Aminoff, E AF Bar, M Aminoff, E TI Cortical analysis of visual context SO NEURON LA English DT Article ID MEDIAL TEMPORAL-LOBE; POSITRON EMISSION TOMOGRAPHY; HUMAN OBJECT AREAS; EPISODIC MEMORY; RETROSPLENIAL AMNESIA; SEMANTIC MEMORY; BRAIN ACTIVITY; HIPPOCAMPAL; RECOGNITION; INFORMATION AB Objects in our environment tend to be grouped in typical contexts. How does the human brain analyze such associations between visual objects and their specific context? We addressed this question in four functional neuroimaging experiments and revealed the cortical mechanisms that are uniquely activated when people recognize highly contextual objects (e.g., a traffic light). Our findings indicate that a region in the parahippocampal cortex and a region in the retrosplenial cortex together comprise a system that mediates both spatial and nonspatial contextual processing. Interestingly, each of these regions has been identified in the past with two functions: the processing of spatial information and episodic memory. Attributing contextual analysis to these two areas, instead, provides a framework for bridging between previous reports. C1 NMR Ctr, Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA 02129 USA. RP Bar, M (reprint author), NMR Ctr, Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA 02129 USA. OI Aminoff, Elissa/0000-0002-6455-8930 NR 60 TC 311 Z9 312 U1 3 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR 24 PY 2003 VL 38 IS 2 BP 347 EP 358 DI 10.1016/S0896-6273(03)00167-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 672AM UT WOS:000182498300022 PM 12718867 ER PT J AU Jonsson, KB Zahradnik, R Larsson, T White, KE Sugimoto, T Imanishi, Y Yamamoto, T Hampson, G Koshiyama, H Ljunggren, O Oba, K Yang, IM Miyauchi, A Econs, MJ Lavigne, J Juppner, H AF Jonsson, KB Zahradnik, R Larsson, T White, KE Sugimoto, T Imanishi, Y Yamamoto, T Hampson, G Koshiyama, H Ljunggren, O Oba, K Yang, IM Miyauchi, A Econs, MJ Lavigne, J Juppner, H TI Fibroblast growth factor 23 in oncogenic osteomalacia and X-linked hypophosphatemia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TUMOR-INDUCED OSTEOMALACIA; RICKETS; FGF-23; GENE AB Background: Mutations in fibroblast growth factor 23 (FGF-23) cause autosomal dominant hypophosphatemic rickets. Clinical and laboratory findings in this disorder are similar to those in oncogenic osteomalacia, in which tumors abundantly express FGF-23 messenger RNA, and to those in X-linked hypophosphatemia, which is caused by inactivating mutations in a phosphate-regulating endopeptidase called PHEX. Recombinant FGF-23 induces phosphaturia and hypophosphatemia in vivo, suggesting that it has a role in phosphate regulation. To determine whether FGF-23 circulates in healthy persons and whether it is elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, an immunometric assay was developed to measure it. Methods: Using affinity-purified, polyclonal antibodies against [Tyr223]FGF-23(206-222)amide and [Tyr224]FGF-23(225-244)amide, we developed a two-site enzyme-linked immunosorbent assay that detects equivalently recombinant human FGF-23, the mutant form in which glutamine is substituted for arginine at position 179 (R179Q), and synthetic human FGF-23(207-244)amide. Plasma or serum samples from 147 healthy adults (mean [+/-SD] age, 48.4+/-19.6 years) and 26 healthy children (mean age, 10.9+/-5.5 years) and from 17 patients with oncogenic osteomalacia (mean age, 43.0+/-13.3 years) and 21 patients with X-linked hypophosphatemia (mean age, 34.9+/-17.2 years) were studied. Results: Mean FGF-23 concentrations in the healthy adults and children were 55+/-50 and 69+/-36 reference units (RU) per milliliter, respectively. Four patients with oncogenic osteomalacia had concentrations ranging from 426 to 7970 RU per milliliter, which normalized after tumor resection. FGF-23 concentrations were 481+/-528 RU per milliliter in those with suspected oncogenic osteomalacia and 353+/-510 RU per milliliter (range, 31 to 2335) in those with X-linked hypophosphatemia. Conclusions: FGF-23 is readily detectable in the plasma or serum of healthy persons and can be markedly elevated in those with oncogenic osteomalacia or X-linked hypophosphatemia, suggesting that this growth factor has a role in phosphate homeostasis. FGF-23 measurements might improve the management of phosphate-wasting disorders. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Hosp Children, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Uppsala Univ, Dept Surg Sci, Uppsala, Sweden. Uppsala Univ, Dept Med Sci, Uppsala, Sweden. Immutopics, San Clemente, CA USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Kobe Univ, Grad Sch Med, Dept Clin Mol Med, Div Endocrinol & Metab, Kobe, Hyogo 657, Japan. Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka 558, Japan. Minoh City Hosp, Dept Pediat, Osaka, Japan. Osaka Univ, Grad Sch Med, Dept Pediat, Osaka, Japan. St Thomas Hosp, Dept Chem Pathol, London, England. Hyogo Kenritsu Amagasaki Hosp, Dept Med, Div Endocrinol & Metab, Amagasaki, Hyogo, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan. Aso Iizuka Hosp, Fukuoka, Japan. Kuyunghee Univ, Dept Internal Med, Seoul, South Korea. Natl Hyogo Chuo Hosp, Sanda, Hyogo, Japan. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. RI Koshiyama, Hiroyuki/H-3877-2011 FU NIAMS NIH HHS [AR42228, K24-AR02095]; NIDDK NIH HHS [DK063934-01, DK46718] NR 15 TC 483 Z9 500 U1 2 U2 7 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 APR 24 PY 2003 VL 348 IS 17 BP 1656 EP 1663 DI 10.1056/NEJMoa020881 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 670PB UT WOS:000182416300005 PM 12711740 ER PT J AU Usmani, GN Westra, SJ Younes, S Russell, GJ Harris, NL Grabowski, EE Younes, S AF Usmani, GN Westra, SJ Younes, S Russell, GJ Harris, NL Grabowski, EE Younes, S TI A 14-month-old boy with hepatomegaly, perianal lesions, and a bony lump on the forehead - Langerhans'-cell histiocytosis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ORBITAL RHABDOMYOSARCOMA; MALIGNANT HISTIOCYTOSIS; CHILDREN; CLASSIFICATION; SARCOIDOSIS; LYMPHOMA; DISEASE C1 Univ Massachusetts, Sch Med, Dept Pediat, Div Pediat Hematol & Oncol, Worcester, MA 01605 USA. UMass Mem Healthcare, Childrens Med Ctr, Worcester, MA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Usmani, GN (reprint author), Univ Massachusetts, Sch Med, Dept Pediat, Div Pediat Hematol & Oncol, Worcester, MA 01605 USA. NR 26 TC 7 Z9 9 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 APR 24 PY 2003 VL 348 IS 17 BP 1692 EP 1701 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 670PB UT WOS:000182416300010 PM 12711745 ER PT J AU Black, HR Elliott, WJ Grandits, G Grambsch, P Lucente, T White, WB Neaton, JD Grimm, RH Hansson, L Lacourciere, Y Muller, J Sleight, P Weber, MA Williams, G Wittes, J Zanchetti, A Anders, RJ AF Black, HR Elliott, WJ Grandits, G Grambsch, P Lucente, T White, WB Neaton, JD Grimm, RH Hansson, L Lacourciere, Y Muller, J Sleight, P Weber, MA Williams, G Wittes, J Zanchetti, A Anders, RJ CA CONVINCE Res Grp TI Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) Trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CONVERTING-ENZYME-INHIBITOR; LIPID-LOWERING TREATMENT; BLOOD-PRESSURE; CALCIUM-ANTAGONISTS; PLATELET-FUNCTION; CLINICAL-TRIALS; HYPERTENSION; METAANALYSIS; OUTCOMES AB Context Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. Objective To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. Design, Setting, and Participants Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. Intervention Initially, 8241 participants received 180 mg of COER Verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. Main Outcome Measures First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. Results Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the ateholol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P=.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% Cl, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Non-stroke hemorrhage was more common with participants in the COER-verapamil group (n=118) compared with the atenolol or hydrochlorothiazide group (n=79) (HR, 1.54 [95% CI, 1.16-2.04]; P=.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; FIR, 1.15 (95% CI, 0.86-1.53). Conclusions The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. Univ Minnesota, Div Biostat, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Evidence Based Med, Minneapolis, MN USA. Univ Connecticut, Sch Med, Dept Med, Sect Hypertens & Clin Pharmacol, Farmington, CT USA. Uppsala Univ, Dept Geriatr, Uppsala, Sweden. Ctr Hosp Univ Quebec, Quebec City, PQ, Canada. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ Oxford, Dept Med, Oxford, England. John Radcliffe Hosp, Oxford OX3 9DU, England. SUNY, Dept Med, Brooklyn, NY USA. Brookdale Hosp, Brooklyn, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Stat Collaborat, Washington, DC USA. Osped Maggiore, I-20122 Milan, Italy. Ist Auxol Italiano, Milan, Italy. Univ Milan, Milan, Italy. Searle Labs, Clin Res, Skokie, IL USA. RP Black, HR (reprint author), Rush Univ, Rush Med Coll, 1700 W Van Buren St,Suite 470, Chicago, IL 60612 USA. EM hblack@rush.edu NR 30 TC 389 Z9 407 U1 1 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 23 PY 2003 VL 289 IS 16 BP 2073 EP 2082 DI 10.1001/jama.289.16.2073 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 669WW UT WOS:000182374300023 PM 12709465 ER PT J AU Tassone, P Tagliaferri, P Perricelli, A Blotta, S Quaresima, B Martelli, ML Goel, A Barbieri, V Costanzo, F Boland, CR Venuta, S AF Tassone, P Tagliaferri, P Perricelli, A Blotta, S Quaresima, B Martelli, ML Goel, A Barbieri, V Costanzo, F Boland, CR Venuta, S TI BRCA I expression modulates chemosensitivity of BRCA I-defective HCC1937 human breast cancer cells SO BRITISH JOURNAL OF CANCER LA English DT Article ID SUSCEPTIBILITY GENE BRCA1; APOPTOSIS; RESISTANCE; INHIBITION; ACTIVATION; CISPLATIN; REPAIR; DOMAIN; AGENTS; RAD51 AB Germline mutations of the tumour suppressor gene BRCA1 are involved in the predisposition and development of breast cancer and account for 20-45% of all hereditary cases. There is an increasing evidence that these tumours are characterised by a specific phenotype and pattern of gene expression. We have hypothesised that differences in chemosensitivity might parallel molecular heterogeneity of hereditary and sporadic breast tumours. To this end, we have investigated the chemosensitivity of the BRCA1-defective HCC1937 breast cancer cell line, and the BRCA1-competent MCF-7 (hormone-sensitive) and MDA-MB231 (hormone-insensitive) breast cancer cell lines using the MTT assay. The 50% inhibitory concentration (IC50) for the individual compounds were derived by interpolate plot analysis of the logarithmic scalar concentration curve after a 48 h exposure. HCC1937 cells were significantly (P<0.005) more sensitive to cisplatin (CDDP) (IC50: 30-40muM) compared with MCF-7 (IC50: 60-70 muM) and MDA-MB23 I (IC50 : 90-100 muM) cells. On the other hand, BRCA1-defective breast cancer cells were significantly less sensitive to doxorubicin (Dox) (IC50:45-50 muM) compared with MCF-7 (IC50: 1-5 muM) and MDA-MB231 (IC50: 5-10 muM) (P<0.02), as well as to paclitaxel (Tax) (IC50 : > 2 mum for HCC1937, 0.1 -0.2 mum for MCF-7 and 0.01-0.02 mum for MDA-MB231) (P<0.001). Full-length BRCA1 cDNA transfection of BRCA1-defective HCC1937 cells led to the reconstituted expression of BRCA1 protein in HCC1937/(WT)BRCA1-derived cell clone, but did not reduce tumour cell growth in soft agar. BRCA1 reconstitution reverted the hypersensitivity to CDDP (P<0.02), and restored the sensitivity to Dox (P<0.05) and Tax (P<0.001), compared with parental HCC1937 cells. Taken together, our findings suggest a specific chemosensitivity profile of BRCA1-defective cells in vitro, which is dependent on BRCA1 protein expression, and suggest prospective preclinical and clinical investigation for the development of tailored therapeutical approaches in this setting. (C) 2003 Cancer Research UK. C1 Magna Mraecia Univ, Dept Expt & Clin Med, Oncol Unit, I-88100 Catanzaro, Italy. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Comprehens Canc, La Jolla, CA 92093 USA. RP Martelli, ML (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Mayer Bldg,RM551,44 Binney St, Boston, MA 02115 USA. NR 28 TC 197 Z9 207 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR 22 PY 2003 VL 88 IS 8 BP 1285 EP 1291 DI 10.1038/sj.bjc.6600859 PG 7 WC Oncology SC Oncology GA 678XD UT WOS:000182891200023 PM 12698198 ER PT J AU Vallat, JM Hahn, AF Leger, JM Cros, DP Magy, L Tabaraud, F Bouche, P Preux, PM AF Vallat, JM Hahn, AF Leger, JM Cros, DP Magy, L Tabaraud, F Bouche, P Preux, PM TI Interferon beta-1a as an investigational treatment for CIDP SO NEUROLOGY LA English DT Article ID INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY; RELAPSING MULTIPLE-SCLEROSIS; SUPPRESSOR-CELL FUNCTION; GUILLAIN-BARRE-SYNDROME; PLASMA-EXCHANGE; DOUBLE-BLIND; T-CELLS; MS; POLYNEUROPATHY; NEUROPATHIES AB A prospective, multicenter, open-label study was conducted to determine the safety and efficacy of intramuscular (IM) interferon beta-1alpha (IFNbeta-1alpha) (Avonex) for treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Eligible patients received IM IFNbeta-1a 30 mug once weekly for 6 months. Safety and tolerability were evaluated by reporting of adverse events, measurement of vital signs, and results of blood chemistry, hematology, and urinalysis. The primary efficacy end points were changed from baseline to month 6 on a quantitative Neurologic Disability Score (NDS), a clinical grading (CG) scale, and grip strength (GS) measures. Electrophysiologic measurements were performed at baseline and month 6. A total of 20 treatment-resistant patients with CIDP were enrolled in the study. The tolerability of IFNbeta-1alpha in patients with CIDP was similar to that seen with its use in MS. There were no serious adverse events, and no patients discontinued treatment due to adverse events. Seven patients (35%) showed clinical improvement, 10 (50%) bad stable disease, and 3 (15%) continued to deteriorate. Significant improvements from baseline were observed in NDS in both the intent-to-treat and per protocol analyses (p=0.0005). For CG, significant improvement from baseline was observed in the per protocol analysis (p<0.05) but not in the intent-to-treat analysis. There was no significant effect of treatment on GS. Clinical improvement was not dependent on age, gender, clinical form of CIDP, or duration of symptoms. Electrophysiologic data showed improvements in mean median, ulnar, and tibial motor nerve potential areas. There was no correlation between clinical improvement and electrophysiologic data. The promising results of this study, especially given the refractory nature of the patient population, suggest that a larger placebo-controlled study should be performed to further evaluate the efficacy of IM IFNβ-1a for the treatment of CIDP. C1 Dupuytren Univ Hosp, Dept Neurol, Limoges, France. Dupuytren Univ Hosp, Fac Med, Biostat & Med Informat Dept, Limoges, France. Victoria Hosp, Dept Clin Neurol Sci, London, ON N6A 4G5, Canada. Salpetriere Hosp, Federat Neurol, Paris, France. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Vallat, JM (reprint author), CHU Dupuytren, Serv Neurol, Limoges, France. RI PREUX, Pierre-Marie/B-8393-2014 OI PREUX, Pierre-Marie/0000-0002-2171-2977 NR 32 TC 41 Z9 42 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 APR 22 PY 2003 VL 60 IS 8 SU 3 BP S23 EP S28 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 672HE UT WOS:000182514500005 PM 12707419 ER PT J AU Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML AF Lee, K Berthiaume, F Stephanopoulos, GN Yarmush, ML TI Profiling of dynamic changes in hypermetabolic livers SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE metabolic profiling; metabolic flux analysis; metabolic networks; clustering; oxidant stress; uncoupling protein-2 ID UNCOUPLING PROTEIN-2 EXPRESSION; PENTOSE-PHOSPHATE CYCLE; BURN INJURY; RAT-LIVER; AMINO-ACID; FLUX DISTRIBUTIONS; PERFUSED LIVER; METABOLISM; GLUCOSE; HEPATOCYTES AB The liver plays an important role in the overall negative nitrogen balance leading to muscle wasting commonly observed in patients following many conditions, including severe injury, cancer, and diabetes. In order to study changes in liver metabolism during the establishment of such catabolic states, we used a rat skin burn injury model that induces hypermetabolism and muscle wasting. At various times during the first week following the injury, livers were isolated and perfused in a recirculating system under well-defined conditions. We applied a steady-state metabolic flux analysis model of liver metabolism and then used k-means clustering to objectively group together reaction flux time profiles. We identified six distinct groups of reactions that were differentially responsive: (1) pentose phosphate pathway (PPP); (2) amino acid oxidation reactions leading to the formation of tricarboxylic acid (TCA) cycle intermediates; (3) gluconeogenesis; (4) TCA-cycle and mitochondrial oxidation; (5) lipolysis, beta-oxidation, and ketone body formation; and (6) urea-cycle. Burn injury sequentially upregulated the urea-cycle, the PPP, and the TCA-cycle, in order, while beta-oxidation and gluconeogenesis remained unchanged. The upregulation of the PPP was transient, whereas the rise in urea- and TCA-cycle fluxes was sustained. An ATP balance predicted an increased production of ATP and energy expenditure starting on day 3 post-burn, which correlated with the induction of the oxidative phosphorylation uncoupler uncoupling protein-2. We conclude that metabolic profiling using flux analysis and clustering analysis is a useful methodology to characterize the differential activation of metabolic pathways in perfused organs and to identify specific key pathways that are sensitive to a stimulus or insult without making a priori assumptions. (C) 2003 Wiley Periodicals, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Shriners Burns Hosp, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, GRB 1402, Boston, MA 02114 USA. RI Lee, Kyongbum/D-9230-2013 FU NIGMS NIH HHS [GM058125] NR 47 TC 44 Z9 45 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD APR 20 PY 2003 VL 83 IS 4 BP 400 EP 415 DI 10.1002/bit.10682 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 698HM UT WOS:000183993000005 PM 12800135 ER PT J AU Chandrasekar, B Colston, JT de la Rosa, SD Rao, PP Freeman, GL AF Chandrasekar, B Colston, JT de la Rosa, SD Rao, PP Freeman, GL TI TNF-alpha and H2O2 induce IL-18 and IL-18R beta expression in cardiomyocytes via NF-kappa B activation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE proinflammatory cytokines; oxidative stress; reperfusion injury; cardiomyocytes; NF-kappa B; PDTC ID TUMOR-NECROSIS-FACTOR; CXC CHEMOKINE; PROINFLAMMATORY CYTOKINE; INTERLEUKIN-18; CELLS; DYSFUNCTION; FAMILY; BRAIN AB Myocardial ischemia/reperfusion is characterized by oxidative stress and induction of proinflammatory cytokines. Interleukin (IL)-18, a member of the IL-1 family, acts as a proinflammatory cytokine, and is induced during various immune and inflammatory disorders. Therefore, in the present study we investigated whether IL-18 expression is regulated by cytokines and oxidative stress in cardiomyocytes. TNF-alpha induced rapid and sustained activation of NF-kappaB whereas H2O2 induced delayed and transient activation. Both TNF-alpha and H2O2 induced IL-18 mRNA and precursor protein in cardiornyocytes, and IL-18 release into culture supernatants. However, only TNF-alpha led to sustained expression. Expression of IL-18Rbeta, but not alpha, was induced by both agonists. TNF-alpha and H2O2 induced delayed expression of IL-18 BP. Pretreatment with PDTC attenuated TNF-alpha and H2O2 induced IL-18 and IL-18Rbeta, but not basal expression of IL-18Ralpha. These results indicate that adult cardiomyocytes express IL-18 and its receptors, and proinflammatory cytokines and oxidative stress regulate their expression via activation of NF-kappaB. Presence of both ligand and receptors suggests IL-18 impacts myocardial biology through an autocrine pathway. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. RP Chandrasekar, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM chandraseka@uthscsa.edu FU NHLBI NIH HHS [HL68020] NR 28 TC 62 Z9 74 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 18 PY 2003 VL 303 IS 4 BP 1152 EP 1158 DI 10.1016/S0006-291X(03)00496-0 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 672MN UT WOS:000182524600027 PM 12684057 ER PT J AU Patane, G Kaneto, H Toschi, E Sharma, A Gupta, S Weir, GC AF Patane, G Kaneto, H Toschi, E Sharma, A Gupta, S Weir, GC TI Induction of Mad expression leads to augmentation of insulin gene transcription SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Mad; insulin gene expression; PDX-1; rat pancreatic islets; c-Myc; insulin content; beta-cell; Glut-2; glucokinase ID PANCREATIC BETA-CELLS; C-MYC EXPRESSION; HOMEOBOX FACTOR; HIGH GLUCOSE; HOMEODOMAIN PROTEIN; HIT-T15 CELLS; FACTOR-I; PDX-1; DIFFERENTIATION; ACTIVATION AB Insulin gene transcription is critical for the maintenance of pancreatic beta-cell differentiation and insulin production. In this study, we found that the basic helix-loop-helix transcription factor Mad, which usually acts as a repressor to c-Myc, enhances insulin gene transcription. In isolated rat islets adenoviral overexpression of Mad augmented insulin mRNA expression and insulin protein content, as well as glucokinase and GLUT2 mRNA expression. Also, Mad overexpression upregulated insulin promoter activity in beta-cell-derived cell lines, MIN6 and betaTC1, as well as in non-insulin producing liver cell line, HepG2. Mad overexpression in rat islets enhanced PDX-1 expression and its DNA binding activity. We found that Mad mediated increased PDX-1 expression by an E-box dependent transcriptional regulation of the PDX-1 gene. That the effects of Mad on insulin expression were mediated through PDX-1 was further substantiated by studies showing inhibition of insulin promoter activation by Mad in the presence of mutated PDX-1 binding site. Although Mad functions as a negative regulatory factor for multiple target genes, these studies establish the fact that Mad can also function as a positive regulatory factor for insulin gene transcription. Such regulation of insulin expression by Mad with modulation of PDX-1 expression and DNA binding activity could offer useful therapeutic and/or experimental tools to promote insulin production in appropriate cell types. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [U19 DK61251-02, DK-36836, DK-35449, R01 DK46952] NR 56 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 18 PY 2003 VL 303 IS 4 BP 1199 EP 1208 DI 10.1016/S0006-291X(03)00493-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 672MN UT WOS:000182524600033 PM 12684063 ER PT J AU Sordella, R Jiang, W Chen, GC Curto, M Settleman, J AF Sordella, R Jiang, W Chen, GC Curto, M Settleman, J TI Modulation of rho GTPase signaling regulates a switch between adipogenesis and myogenesis SO CELL LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; AXON OUTGROWTH; P190 RHOGAP; DIFFERENTIATION; SHP-2; CELL; EXPRESSION; FAMILY; ACTIN; GENE AB Mature adipocytes and myocytes are derived from a common mesenchymal precursor. While IGF-1 promotes the differentiation of both cell types, the signaling pathways that specify the distinct cell fates are largely unknown. Here, we show that the Rho GTPase and its regulator, p190-B RhoGAP, are components of a critical switch in the adipogenesis-myogenesis "decision." Cells derived from embryos lacking p190-B RhoGAP exhibit excessive Rho activity, are defective for adipogenesis, but undergo myogenesis in response to IGF-1 exposure. In vitro, activation of Rhokinase by Rho inhibits adipogenesis and is required for myogenesis. The activation state of Rho following IGF-1 signaling is determined by the tyrosine-phosphorylation status of p190-B RhoGAP and its resulting subcellular relocalization. Moreover, adjusting Rho activity is sufficient to alter the differentiation program of adipocyte and myocyte precursors. Together, these results identify the Rho GTPase as an essential modulator of IGF-1 signals that direct the adipogenesis-myogenesis cell fate decision. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Med Sch, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69498] NR 32 TC 238 Z9 248 U1 1 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD APR 18 PY 2003 VL 113 IS 2 BP 147 EP 158 DI 10.1016/S0092-8674(03)00271-X PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 672EP UT WOS:000182508500005 PM 12705864 ER PT J AU Takagi, T Walker, AK Sawa, C Diehn, F Takase, Y Blackwell, TK Buratowski, S AF Takagi, T Walker, AK Sawa, C Diehn, F Takase, Y Blackwell, TK Buratowski, S TI The Caenorhabditis elegans mRNA 5 '-capping enzyme - In vitro and in vivo characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; PROTEIN-TYROSINE-PHOSPHATASE; CARBOXYL-TERMINAL DOMAIN; MAMMALIAN CAPPING ENZYME; MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; DIPHOSPHATASE ACTIVITIES; EMBRYONIC TRANSCRIPTION; TRANSITION-STATE; P-TEFB AB Eukaryotic mRNA capping enzymes are bifunctional, carrying both RNA triphosphatase (RTPase) and guanylyltransferase (GTase) activities. The Caenorhabditis elegans CEL-1 capping enzyme consists of an N-terminal region with RTPase activity and a C-terminal region that resembles known GTases, However, CEL-1 has not previously been shown to have GTase activity. Cloning of the cel-1 cDNA shows that the full-length protein has 623 amino acids, including an additional 38 residues at the C termini and 12 residues at the N termini not originally predicted from the genomic sequence. Full-length CEL-1 has RTPase and GTase activities, and the cDNA can functionally replace the capping enzyme genes in Saccharomyces cerevisiae. The CEL-1 RTPase domain is related by sequence to protein-tyrosine phosphatases; therefore, mutagenesis of residues predicted to be important for RTPase activity was carried out. CEL-1 uses a mechanism similar to protein-tyrosine phosphatases, except that there was not an absolute requirement for a conserved acidic residue that acts as a proton donor. CEL-1 shows a strong preference for RNA substrates of at least three nucleotides in length. RNA-mediated interference in C. elegans embryos shows that lack of CEL-1 causes development to arrest with a phenotype similar to that seen when RNA polymerase 11 elongation activity is disrupted. Therefore, capping is essential for gene expression in metazoans. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Buratowski, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. FU NIGMS NIH HHS [R01 GM062891, GM62891, GM56663] NR 84 TC 16 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 18 PY 2003 VL 278 IS 16 BP 14174 EP 14184 DI 10.1074/jbc.M212101200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 670JV UT WOS:000182405000079 PM 12576476 ER PT J AU Chaudhuri, J Tian, M Khuong, C Chua, K Pinaud, E Alt, FW AF Chaudhuri, J Tian, M Khuong, C Chua, K Pinaud, E Alt, FW TI Transcription-targeted DNA deamination by the AID antibody diversification enzyme SO NATURE LA English DT Article ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; MECHANISM; SEQUENCES; REGION; STRAND AB Activation-induced cytidine deaminase (AID), which is specific to B lymphocytes, is required for class switch recombination (CSR)-a process mediating isotype switching of immunoglobulin-and somatic hypermutation-the introduction of many point mutations into the immunoglobulin variable region genes(1,2). It has been suggested that AID may function as an RNA-editing enzyme(3) or as a cytidine deaminase on DNA(4),(5). However, the precise enzymatic activity of AID has not been assessed in previous studies. Similarly, although transcription of the target immunoglobulin locus sequences is required for both CSR and somatic hypermutation, the precise role of transcription has remained speculative(6-9). Here we use two different assays to demonstrate that AID can deaminate specifically cytidines on single-stranded (ss) DNA but not double-stranded (ds) DNA substrates in vitro. However, dsDNA can be deaminated by AID in vitro when the reaction is coupled to transcription. Moreover, a synthetic dsDNA sequence, which targets CSR in vivo in a manner dependent on transcriptional orientation(10), was deaminated by AID in vitro with the same transcriptional-orientation-dependence as observed for endogenous CSR. We conclude that transcription targets the DNA deamination activity of AID to dsDNA by generating secondary structures that provide ssDNA substrates. C1 Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. RI PINAUD, Eric/O-8443-2016 OI PINAUD, Eric/0000-0001-7405-9273 NR 31 TC 470 Z9 475 U1 1 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 APR 17 PY 2003 VL 422 IS 6933 BP 726 EP 730 DI 10.1038/nature01574 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668CG UT WOS:000182272300043 PM 12692563 ER PT J AU Shi, YJ Sawada, J Sui, GC Affar, EB Whetstine, JR Lan, F Ogawa, H Luke, MPS Nakatani, Y Shi, Y AF Shi, YJ Sawada, J Sui, GC Affar, EB Whetstine, JR Lan, F Ogawa, H Luke, MPS Nakatani, Y Shi, Y TI Coordinated histone modifications mediated by a CtBP co-repressor complex SO NATURE LA English DT Article ID COREPRESSOR CTBP; PROTEIN; TRANSCRIPTION; TRANSFORMATION; EXPRESSION; GENES; CELLS AB The transcriptional co-repressor CtBP (C-terminal binding protein) is implicated in tumorigenesis because it is targeted by the adenovirus E1A protein during oncogenic transformation(1). Genetic studies have also identified a crucial function for CtBP in animal development(2). CtBP is recruited to DNA by transcription factors that contain a PXDLS motif(3,4), but the detailed molecular events after the recruitment of CtBP to DNA and the mechanism of CtBP function in tumorigenesis are largely unknown. Here we report the identification of a CtBP complex that contains the essential components for both gene targeting and coordinated histone modifications, allowing for the effective repression of genes targeted by CtBP. Inhibiting the expression of CtBP and its associated histone-modifying activities by RNA-mediated interference resulted in alterations of histone modifications at the promoter of the tumour invasion suppressor gene E-cadherin and increased promoter activity in a reporter assay. These findings identify a molecular mechanism by which CtBP mediates transcriptional repression and provide insight into CtBP participation in oncogenesis. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shi, Y (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA. NR 24 TC 468 Z9 484 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 17 PY 2003 VL 422 IS 6933 BP 735 EP 738 DI 10.1038/nature01550 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668CG UT WOS:000182272300045 PM 12700765 ER PT J AU Ahveninen, J Jaaskelainen, IP Pennanen, S Liesivuori, J Ilmoniemi, RJ Kahkonen, S AF Ahveninen, J Jaaskelainen, IP Pennanen, S Liesivuori, J Ilmoniemi, RJ Kahkonen, S TI Auditory selective attention modulated by tryptophan depletion in humans SO NEUROSCIENCE LETTERS LA English DT Article DE attention; auditory cortex; event-related potentials; electroencephalography; magnetoencephalography; processing negativity; serotonin; tryptophan depletion ID BRAIN; MEG; POTENTIALS; CORTEX; MALES; EEG AB To elucidate serotonin modulation of selective attention, 13 volunteers (21-30 years) were studied in two sessions, 5 h after either acute tryptophan depletion (ATD) that decreases brain serotonin synthesis, or control-mixture ingestion (randomized, double-blind, cross-over design). Simultaneous electroencephalogram and magnetoencephalogram were measured during dichotic listening of two concurrent trains of standard and deviant tones, Subjects counted the deviants presented to one car and ignored those presented to the other ear. ATD lowered plasma total tryptophan by 75% and free tryptophan by 39%. ATD suppressed the amplitude enhancement of P50 and NI to selectively attended tones, but did not affect the later aspects of processing negativity. The P50 latencies were increased after ATD, irrespective of attention. In conclusion, serotonin may regulate attentional modulation of early cortical stimulus processing. (C) 2003 Published by Elsevier Science Ireland Ltd. C1 Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, FIN-00014 Helsinki, Finland. Univ Helsinki, BioMag Lab, Ctr Engn, FIN-00014 Helsinki, Finland. Univ Helsinki, Dept Neurol, FIN-00014 Helsinki, Finland. Helsinki Univ Technol, Lab Computat Engn, FIN-00014 Helsinki, Finland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA USA. Univ Helsinki, Dept Psychol, SF-00100 Helsinki, Finland. Kuopio Reg Inst Occupat Hlth, Occupat Hyg & Toxicol Sect, FIN-70701 Kuopio, Finland. Univ Kuopio, Dept Pharmacol & Toxicol, FIN-70211 Kuopio, Finland. Helsinki Brain Res Ctr, Helsinki, Finland. RP Ahveninen, J (reprint author), Univ Helsinki, Cognit Brain Res Unit, Dept Psychol, POB 9, FIN-00014 Helsinki, Finland. RI Jaaskelainen, Iiro/C-7392-2012; Liesivuori, Jyrki/O-2519-2013; Ilmoniemi, Risto/E-9704-2012 OI Jaaskelainen, Iiro/0000-0001-6001-6950; Ilmoniemi, Risto/0000-0002-3340-2618 NR 16 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 17 PY 2003 VL 340 IS 3 BP 181 EP 184 DI 10.1016/S0304-3940(03)00102-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 669JB UT WOS:000182347200006 PM 12672536 ER PT J AU Malhotra, A Muse, VV Mark, EJ Brown, R Hales, CA Bhan, I AF Malhotra, A Muse, VV Mark, EJ Brown, R Hales, CA Bhan, I TI Case 12-2003: An 82-year-old man with dyspnea and pulmonary abnormalities - Amiodarone-induced lung disease with bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID POSITIVE AIRWAY PRESSURE; ERYTHROCYTE SEDIMENTATION-RATE; HEART-FAILURE; SLEEP-APNEA; TOXICITY; CLASSIFICATION; PATHOGENESIS; FIBROSIS; SURVIVAL; THERAPY C1 Brigham & Womens Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Malhotra, A (reprint author), Brigham & Womens Hosp, Pulm & Crit Care Unit, 75 Francis St, Boston, MA 02115 USA. NR 45 TC 23 Z9 24 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 APR 17 PY 2003 VL 348 IS 16 BP 1574 EP 1585 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 667TT UT WOS:000182248900009 PM 12700378 ER PT J AU Yueh, B Shapiro, N MacLean, CH Shekelle, PG AF Yueh, B Shapiro, N MacLean, CH Shekelle, PG TI Screening and management of adult hearing loss in primary care - Scientific review SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID QUALITY-OF-LIFE; OLDER ADULTS; COST-UTILITY; COCHLEAR IMPLANT; OTITIS-MEDIA; COGNITIVE DYSFUNCTION; SYSTEMIC STEROIDS; RANDOMIZED TRIAL; ELDERLY PATIENTS; IMPAIRMENT AB Context Hearing loss is the third most prevalent chronic condition in older adults and has important effects on their physical and mental health. Despite these effects, most older patients are not assessed or treated for hearing loss. Objective To review the evidence on screening and management of hearing loss of older adults in the primary care setting. Data Sources and Study Selection We performed a search from 1985 to 2001 using MEDLINE, HealthSTAR, EMBASE, Ageline, and the National Guideline Clearinghouse for articles and practice guidelines about screening and management of hearing loss in older adults, as well as reviewed references in these articles and those suggested by experts in hearing impairment. Data Extraction We reviewed articles for the most clinically important information, emphasizing randomized clinical trials, where available, and identified 1595 articles. Data Synthesis Screening tests that reliably detect hearing loss are use of an audioscope, a hand-held combination otoscope and audiometer, and a self-administered questionnaire, the Hearing Handicap Inventory for the Elderly-Screening version. The value of routine screening for improving patient outcomes has not been evaluated in a randomized clinical trial. Screening is endorsed by most professional organizations, including the US Preventive Services Task Force. While most hearing loss in older adults is sensorineural and due to presbycusis, cerumen impaction and chronic otitis media may be present in up to 30% of elderly patients with hearing loss and can be treated by the primary care clinician. In randomized trials, hearing aids have been demonstrated to improve outcomes for patients with sensorineural hearing loss. Nonadherence to use of hearing aids is high. Prompt recognition of potentially reversible causes of hearing loss, such as sudden sensorineural hearing loss, is important to maximize the possibility of functional recovery. Conclusion While untested in a clinical trial, older adults can be screened for hearing loss using simple methods, and effective treatments exist and are available for many forms of hearing loss. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98108 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Hlth Serv, Seattle, WA 98108 USA. RAND Hlth, Santa Monica, CA USA. Univ Calif Los Angeles, Div Head & Neck Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Div Rheumatol, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Yueh, B (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Otolaryngol Head & Neck Surg, 1660 S Columbian Way,Surg Sect 112OTO, Seattle, WA 98108 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 88 TC 140 Z9 154 U1 6 U2 33 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 APR 16 PY 2003 VL 289 IS 15 BP 1976 EP 1985 DI 10.1001/jama.289.15.1976 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 667VC UT WOS:000182253900031 PM 12697801 ER PT J AU Bogardus, ST Yueh, B Shekelle, PG AF Bogardus, ST Yueh, B Shekelle, PG TI Screening and management of adult hearing loss in primary care - Clinical applications SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID QUALITY-OF-LIFE; OLDER ADULTS; ELDERLY PEOPLE; COGNITIVE DYSFUNCTION; RANDOMIZED TRIAL; IMPAIRMENT; PREVALENCE; AIDS; AMPLIFICATION; EPIDEMIOLOGY AB Hearing loss is one of the most common chronic health conditions and has important implications for patient quality of life. However, hearing loss is substantially underdetected and undertreated. We present clinical cases to illustrate common situations in which primary care physicians may be called on to identify or to manage hearing loss. With the data reported in the companion scientific review as a guide, we present potential answers to important questions pertaining to hearing loss and suggest ways in which primary care physicians can improve the detection, evaluation, and treatment of hearing loss. The cases focus on screening for chronic hearing loss, evaluation of hearing loss, and treatment of patients with presbycusis. C1 Yale Univ, Sch Med, Dept Med, New Haven, CT 06504 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Dev Serv, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, Surg Serv, Seattle, WA USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Hlth Serv, Seattle, WA 98195 USA. RAND Hlth, Los Angeles, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Bogardus, ST (reprint author), Yale Univ, Sch Med, Dept Med, 20 York St,Tompkins 15, New Haven, CT 06504 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 41 TC 39 Z9 42 U1 5 U2 9 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 APR 16 PY 2003 VL 289 IS 15 BP 1986 EP 1990 DI 10.1001/jama.289.15.1986 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 667VC UT WOS:000182253900032 PM 12697802 ER PT J AU Giugliano, RP Roe, MT Harrington, RA Gibson, M Zeymer, U Van de Werf, F Baran, KW Hobbach, HP Woodlief, LH Hannan, KL Greenberg, S Miller, J Kitt, MM Strony, J McCabe, CH Braunwald, E Califf, RM AF Giugliano, RP Roe, MT Harrington, RA Gibson, M Zeymer, U Van de Werf, F Baran, KW Hobbach, HP Woodlief, LH Hannan, KL Greenberg, S Miller, J Kitt, MM Strony, J McCabe, CH Braunwald, E Califf, RM CA INTEGRITI Invest TI Combination reperfusion therapy with eptifibatide and reduced-dose tenecteplase for ST-elevation myocardial infarction - Results of the integrilin and tenecteplase in acute myocardial infarction (INTEGRITI) phase II angiographic trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TISSUE-PLASMINOGEN-ACTIVATOR; THROMBOLYTIC THERAPY; FIBRINOLYTIC THERAPY; INHIBITION; ABCIXIMAB; FLOW; STREPTOKINASE; PLACEBO AB OBJECTIVES The goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI). BACKGROUND Glycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established. METHODS Patients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 mug/kg bolus, 2 mug/kg/min infusion, and 180 mug/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min. RESULTS In dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). 1mracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively. CONCLUSIONS Double-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use. (C) 2003 by the American College of Cardiology Foundation. C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Duke Univ, Clin Res Inst, Durham, NC USA. Klinikum Kassel, Kassel, Germany. Univ Ziekenhuis Gasthuisberg, Louvain, Belgium. St Paul Heart Clin, St Paul, MN USA. St Marienkrankenhaus Siegen, Siegen, Germany. Millenium Pharmaceut Inc, San Francisco, CA USA. Schering Plough Res Inst, Kenilworth, NJ USA. RP Giugliano, RP (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. OI Van de Werf, Frans/0000-0001-9479-7767 NR 25 TC 64 Z9 68 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR 16 PY 2003 VL 41 IS 8 BP 1251 EP 1260 DI 10.1016/S0735-1097(03)00123-2 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666KW UT WOS:000182177300003 PM 12706917 ER PT J AU Fried, LF Shlipak, MG Crump, C Bleyer, AJ Gottdiener, JS Kronmal, RA Kuller, LH Newman, AB AF Fried, LF Shlipak, MG Crump, C Bleyer, AJ Gottdiener, JS Kronmal, RA Kuller, LH Newman, AB TI Renal insufficiency as a predictor of cardiovascular outcomes and mortality in elderly individuals SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; CONGESTIVE-HEART-FAILURE; METABOLIC SYNDROME; RISK-FACTORS; CREATININE CLEARANCE; SERUM CREATININE; UNITED-STATES; DISEASE; HEALTH; INTERLEUKIN-6 AB OBJECTIVES This study was designed to evaluate the relationship between elevated creatinine levels and cardiovascular events. BACKGROUND End-stage renal disease is associated with high cardiovascular morbidity and mortality. The association of mild to moderate renal insufficiency with cardiovascular outcomes remains unclear. METHODS We analyzed data from the Cardiovascular Health Study, a prospective population-based study of subjects, aged >65 years, who had a serum creatinine measured at baseline (n = 5,808) and were followed for a median of 7.3 years. Proportional hazards models were used to examine the association of creatinine to all-cause mortality and incident cardiovascular mortality and morbidity. Renal insufficiency was defined as a creatinine level greater than or equal to1.5 mg/dl in men or greater than or equal to1.3 mg/dl in women. RESULTS An elevated creatinine level was present in 648 (11.2%) participants. Subjects with elevated creatinine had higher overall (76.7 vs. 29.5/1,000 years, p < 0.001) and cardiovascular (35.8 vs. 13.0/1,000 years, p < 0.001) mortality than those with normal creatinine levels. They were more likely to develop cardiovascular disease (54.0 vs. 31.8/1,000 years, p < 0.001), stroke (21.1 vs. 11.9/1,000 years, p < 0.001), congestive heart failure (38.7 vs. 17/1,000 years, p < 0.001), and symptomatic peripheral vascular disease (10.6 vs. 3.5/1,000 years, p < 0.001). After adjusting for cardiovascular risk factors and subclinical disease measures, elevated creatinine remained a significant predictor of all-cause and cardiovascular mortality, total cardiovascular disease (CVD), claudication, and congestive heart failure (CHF). A linear increase in risk was observed with increasing creatinine. CONCLUSIONS Elevated creatinine levels are common in older adults and are associated with increased risk of mortality, CVD, and CHF. The increased risk is apparent early in renal disease. (C) 2003 by the American College of Cardiology Foundation. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15260 USA. Vet Affairs Med Ctr, Med Serv, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Wake Forest Univ, Sch Med, Nephrol Sect, Winston Salem, NC 27109 USA. St Francis Hosp, Div Cardiol, Roslyn, NY USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15260 USA. RP Fried, LF (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, 111F-U,Univ Dr C, Pittsburgh, PA 15240 USA. RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086] NR 45 TC 325 Z9 338 U1 0 U2 9 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 APR 16 PY 2003 VL 41 IS 8 BP 1364 EP 1372 DI 10.1016/S0735-1097(03)00163-3 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666KW UT WOS:000182177300019 PM 12706933 ER PT J AU O'Connor, AM Mulley, AG Wennberg, JE AF O'Connor, AM Mulley, AG Wennberg, JE TI Standard consultations are not enough to ensure decision quality regarding preference-sensitive options SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER; RANDOMIZED TRIAL C1 Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH 03755 USA. Univ Ottawa, Ottawa, ON, Canada. Ottawa Hlth Res Inst, Ottawa, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Wennberg, JE (reprint author), Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH 03755 USA. NR 13 TC 29 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 16 PY 2003 VL 95 IS 8 BP 570 EP 571 PG 2 WC Oncology SC Oncology GA 667YM UT WOS:000182262500001 PM 12697842 ER PT J AU Pond, KK Martin, GV Every, N Lehmann, KG Anderson, R Caldwell, JH Kapadia, SR AF Pond, KK Martin, GV Every, N Lehmann, KG Anderson, R Caldwell, JH Kapadia, SR TI Predictors of progression of native coronary narrowing to total occlusion after coronary artery bypass grafting SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID STENOSIS C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Div Cardiol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Div Cardiothorac Surg, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Kapadia, SR (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. NR 9 TC 4 Z9 4 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 APR 15 PY 2003 VL 91 IS 8 BP 971 EP 974 DI 10.1016/S0002-9149(03)00115-2 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 667DH UT WOS:000182215300011 PM 12686339 ER PT J AU Ho, PM Maynard, C Starks, H Sun, H Sloan, K Sales, A AF Ho, PM Maynard, C Starks, H Sun, H Sloan, K Sales, A TI Outcomes in patients with coronary heart disease who do not undergo lipid testing SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ARTERY DISEASE; GUIDELINES; SECONDARY C1 VAMC, Cardiol & Hlth Serv Res, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. VA Puget Sound Hlth Care Syst, IHD QUERI, Hlth Serv Res & Dev, Seattle, WA USA. RP Ho, PM (reprint author), 1055 Clermont St,111B, Denver, CO 80220 USA. RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Sales, Anne/0000-0001-9360-3334 NR 8 TC 2 Z9 2 U1 0 U2 1 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 APR 15 PY 2003 VL 91 IS 8 BP 986 EP 988 DI 10.1016/S0002-9149(03)00120-6 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 667DH UT WOS:000182215300016 PM 12686344 ER PT J AU Pradhan, AD Manson, JE Meigs, JB Rifai, N Buring, JE Liu, SM Ridker, PM AF Pradhan, AD Manson, JE Meigs, JB Rifai, N Buring, JE Liu, SM Ridker, PM TI Insulin, proinsulin, proinsulin : insulin ratio, and the risk of developing type 2 diabetes mellitus in women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; FASTING PROINSULIN; MEXICAN-AMERICANS; LIFE-STYLE; NIDDM; PREDICT; HYPERPROINSULINEMIA; RESISTANCE; MODEL; POPULATIONS AB PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin: insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin: insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (less than or equal to4.0 pmol/L, 4.01 to 6.99 pmol/L, greater than or equal to7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass, index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (greater than or equal to7.0 pmol/L vs. less than or equal to4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin: insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A,. level less than or equal to6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin: insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women. Am J Med. 2003;114:438-444. (C) 2003 by Excerpta Medica Inc. C1 Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA 02215 USA. Brigham & Womens Hosp, Leducq Ctr Mol & Genet Epidemiol Cardiovasc Disor, Boston, MA USA. Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Childrens Hosp Med Ctr, Dept Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Pradhan, AD (reprint author), Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, 900 Commonwealth Ave E, Boston, MA 02215 USA. RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA47988]; NHLBI NIH HHS [HL43851, HL58755, HL63293] NR 37 TC 29 Z9 32 U1 0 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 APR 15 PY 2003 VL 114 IS 6 BP 438 EP 444 DI 10.1016/S0002-9343(03)00061-5 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 672YR UT WOS:000182551900002 PM 12727576 ER PT J AU Crowley, WF AF Crowley, WF TI Translation of basic research into useful treatments: How often does it occur? SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; CLINICAL-RESEARCH; ESCHERICHIA-COLI; CHALLENGES; INHIBITOR; FRACTURES; SEQUENCE; HORMONE; WOMEN C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Clin Res Program, Boston, MA 02114 USA. RP Crowley, WF (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Clin Res Program, 55 Fruit St,Bartlett Hall Extens Room 511, Boston, MA 02114 USA. EM crowley.william@mgh.harvard.edu NR 13 TC 29 Z9 29 U1 2 U2 6 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 APR 15 PY 2003 VL 114 IS 6 BP 503 EP 505 DI 10.1016/S0002-9343(03)00119-0 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 672YR UT WOS:000182551900012 PM 12727585 ER PT J AU Morrison, ED Brandhagen, DJ Phatak, PD Barton, JC Krawitt, EL El-Serag, HB Gordon, SC Galan, MV Tung, BY Ioannou, GN Kowdley, KV AF Morrison, ED Brandhagen, DJ Phatak, PD Barton, JC Krawitt, EL El-Serag, HB Gordon, SC Galan, MV Tung, BY Ioannou, GN Kowdley, KV TI Serum ferritin level predicts advanced hepatic fibrosis among US patients with phenotypic hemochromatosis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; HOMOZYGOUS HEMOCHROMATOSIS; DIAGNOSIS; SURVIVAL AB Background: DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. Objective: To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. Design: Cross-sectional study. Setting: Six tertiary care referral clinics. Patients: 182 patients with phenotypically defined hemochromatosis. Measurements: Liver histopathology and serum ferritin, aspartate arninotransferase, and alanine arninotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). Results: Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 mug/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 mug/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 mug/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 mug/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 mug/L compared with 72% among patients with serum ferritin levels greater than 1000 mug/L after adjustment for age and elevated serum liver enzyme levels. Conclusions: Patients with hemochromatosis and serum ferritin levels less than 1000 mug/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels. C1 Univ Washington, Div Gastroenterol Hepatol, Seattle, WA 98195 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA USA. Baylor Coll Med, Vet Adm Med Ctr, Houston, TX 77030 USA. Univ Vermont, Burlington, VT USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Rochester, Rochester, NY USA. Rochester Gen Hosp, Rochester, NY 14621 USA. Mayo Clin, Rochester, MN USA. RP Kowdley, KV (reprint author), Univ Washington, Div Gastroenterol Hepatol, 1959 NE Pacific St,Box 356174, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK 38215, DK02957] NR 12 TC 110 Z9 113 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 15 PY 2003 VL 138 IS 8 BP 627 EP 633 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 666JH UT WOS:000182173800003 PM 12693884 ER PT J AU Vassilopoulos, D Niles, JL Villa-Forte, A Arroliga, AC Sullivan, EJ Merkel, PA Hoffman, GS AF Vassilopoulos, D Niles, JL Villa-Forte, A Arroliga, AC Sullivan, EJ Merkel, PA Hoffman, GS TI Prevalence of antineutrophil cytoplasmic antibodies in patients with various pulmonary diseases or multiorgan dysfunction SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE systemic vasculitis; antineutrophil cytoplasmic antibodies; multiorgan dysfunction ID WEGENER GRANULOMATOSIS; DIFFERENTIAL-DIAGNOSIS; ANCA; VASCULITIS; GLOMERULONEPHRITIS; AUTOANTIBODIES; ENDOCARDITIS AB Objective. To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with diseases that may mimic systemic vasculitides, such as severe multiorgan dysfunction (MOD) and parenchymal pulmonary disorders. Methods. We conducted a prospective study of patients with MOD admitted to the medical intensive care unit and patients with various lung diseases seen at the outpatient pulmonary clinic of a tertiary care hospital. Patients with a documented diagnosis of Wegener's granulomatosis (WG) served as positive controls. ANCA were determined in serum samples from each patient by a combination of indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assays (ELISAs) for antibodies to proteinase-3 and myeloperoxidase (anti-MPO). Results. Ninety-nine patients with MOD, 29 outpatients with various lung disorders, and 18 patients with WG were included in the study. ANCA were detected by IIF alone in 16% (15/96) of patients with nonvasculitic MOD and 17% (5/29) of outpatients with various pulmonary disorders. The majority of the positive IIF specimens from each group displayed an atypical IIF pattern (73% and 80%, respectively). Only 1 specimen from patients with nonvasculitic disorders was positive for anti-MPO. ANCA by both IIF and ELISA were detected in 78% (12/14) of control patients with WG. Conclusion. Detection of ANCA by the combination of IIF and antigen-specific assays for proteinase 3 and myeloperoxidase in diseases that mimic systemic vasculitides is highly specific for WG, microscopic polyangiitis, and Churg-Strauss syndrome. C1 Cleveland Clin Fdn, Harold C Schott Chair Rheumat & Immunol Dis, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Hoffman, GS (reprint author), Cleveland Clin Fdn, Harold C Schott Chair Rheumat & Immunol Dis, A50,9500 Euclid Ave, Cleveland, OH 44195 USA. NR 21 TC 21 Z9 25 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 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2003 VL 49 IS 2 BP 151 EP 155 DI 10.1002/art.10997 PG 5 WC Rheumatology SC Rheumatology GA 666HM UT WOS:000182171700002 PM 12687504 ER PT J AU Del Rincon, I Battafarano, DF Arroyo, RA Murphy, FT Fischbach, M Escalante, A AF Del Rincon, I Battafarano, DF Arroyo, RA Murphy, FT Fischbach, M Escalante, A TI Ethnic variation in the clinical manifestations of rheumatoid arthritis: Role of HLA-DRB1 Alleles SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE rheumatoid arthritis; African Americans; Hispanic Americans; ethnic groups; HLA-DRB1; shared epitope ID SHARED-EPITOPE HYPOTHESIS; AMERICAN PATIENTS; DISEASE SEVERITY; SUSCEPTIBILITY; ASSOCIATION; RA; EXPRESSION; DISABILITY; REVEALS; INDIANS AB Objective. To assess the extent of ethnic variation in the clinical expression of rheumatoid arthritis (RA) and the role of HLA-DRB1 alleles in this variation. Methods. We assessed consecutive RA patients for joint findings, subcutaneous nodules, laboratory and radiographic findings, and treatment. We typed HLA-DRB1 alleles to identify those that contain the shared epitope (SE). We adjusted ethnic comparisons for age and sex, and tested for ethnic heterogeneity in the effect of the SE. Results. We studied 777 RA patients, 498 of whom were women (64%), 432 were Hispanic (56%), 2 72 were non-Hispanic white (NHW; 35%), 53 were African American (AA; 7%), and 20 were Asian (3%). Compared with NHW, Hispanics had significantly more tender joints (17 versus 11), more swollen joints (8 versus 7), more frequent rheumatoid factor (RF) positivity (93% versus 84%), higher erythrocyte sedimentation rate (ESR; 45 versus 36 mm/hr), and a lower number of lifetime disease-modifying antirheumatic drugs (1.9 versus 2.5). AA were older at onset (46 versus 44 years), had less frequent subcutaneous nodules (18% versus 28%). and higher ESR (42 versus 36 mm/hour) than did NHW. Hispanics and AA were more likely than NHW to be null for the SE (odds ratio, [OR] = 4.59 for AA; and OR = 1.61 for Hispanics), and less likely to have 2 SE-carrying alleles (OR = 0.59 for Hispanics and OR = 0.25 for AA). The number of SE copies was associated with subcutaneous nodules, ESR, RF, and radiographic changes. Ethnic heterogeneity in the effect of the SE was modest. Conclusions. There is ethnic variation in the clinical expression of RA and in both the frequency and types of SE-carrying HLA-DRB1 alleles. Some ethnic variation in clinical findings is associated with differences in SE frequency. However, we found that the effect of the SE on the clinical features of RA varies little between ethnic groups. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Brooke Army Med Ctr, San Antonio, TX USA. Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. S Texas Vet Adm Hlth Syst, San Antonio, TX USA. RP Escalante, A (reprint author), Univ Texas, Hlth Sci Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCRR NIH HHS [M01-RR1346]; NHLBI NIH HHS [K23-HL004481]; NIAMS NIH HHS [K24-AR47530]; NICHD NIH HHS [R01-HD37151] NR 37 TC 35 Z9 35 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 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2003 VL 49 IS 2 BP 200 EP 208 DI 10.1002/art.11000 PG 9 WC Rheumatology SC Rheumatology GA 666HM UT WOS:000182171700009 PM 12687511 ER PT J AU McGibbon, CA Krebs, DE Scarborough, DM AF McGibbon, CA Krebs, DE Scarborough, DM TI Rehabilitation effects on compensatory gait mechanics in people with arthritis and strength impairment SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID SENIORS TRIAL FAST; KNEE OSTEOARTHRITIS; PHYSICAL THERAPY; OLDER ADULTS; DISABLEMENT CONCEPTS; EXERCISE THERAPY; DISABILITY; PROGRAM; PERFORMANCE; FITNESS C1 Massachusetts Gen Hosp, Biomot Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Biomot Lab, RSL 010,40 Parkman St, Boston, MA 02114 USA. FU NIA NIH HHS [R01-AG12561]; NIAMS NIH HHS [R01-AR45278] NR 57 TC 19 Z9 19 U1 3 U2 5 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 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2003 VL 49 IS 2 BP 248 EP 254 DI 10.1002/art.11005 PG 7 WC Rheumatology SC Rheumatology GA 666HM UT WOS:000182171700016 PM 12687518 ER PT J AU Krebs, D Herzog, W McGibbon, CA Sharma, L AF Krebs, D Herzog, W McGibbon, CA Sharma, L TI Work group recommendations: 2002 Exercise and Physical Activity Conference, St. Louis, Missouri - Session III, biomechanical considerations for exercise SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calgary, Calgary, AB T2N 1N4, Canada. Northwestern Univ, Evanston, IL USA. RP Krebs, D (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 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 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2003 VL 49 IS 2 BP 261 EP 262 DI 10.1002/art.11007 PG 2 WC Rheumatology SC Rheumatology GA 666HM UT WOS:000182171700018 PM 12687520 ER PT J AU McCarley, RW Salisbury, D Wible, C Shenton, ME AF McCarley, RW Salisbury, D Wible, C Shenton, ME TI Matching the mismatch in EEG, fMRI and structural MRI data SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry ID SCHIZOPHRENIA C1 Harvard Univ, VA Boston Healthcare, Brockton, MA 02401 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 18 BP 6S EP 7S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000015 ER PT J AU Wright, CI AF Wright, CI TI Functional neuroimaging of the amygdala and related stuctures SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Dept Psychiat, Pschiat Neuroimaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol,Brigham Behav Neurol Grp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 19 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000016 ER PT J AU Wirshing, DA Smith, RA Wirshing, WC Pierre, JM Kisicki, MD AF Wirshing, DA Smith, RA Wirshing, WC Pierre, JM Kisicki, MD TI The metabolic syndrome and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 82 BP 29S EP 30S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000079 ER PT J AU Wirshing, WC Wirshing, DA Champion, KM Pierre, JM Erhart, SM Kisicki, MD AF Wirshing, WC Wirshing, DA Champion, KM Pierre, JM Erhart, SM Kisicki, MD TI Switchover from clozapine to quetiapine: Mixed results SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Greater Los Angeles VA Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 83 BP 30S EP 30S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000080 ER PT J AU Casada, JH Roache, JD AF Casada, JH Roache, JD TI The stop-signal task in PTSD: Behavioral and physiological responses SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp Div, S Texas Vet Hlth Care Syst, Psychiat Serv, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 108 BP 38S EP 39S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000105 ER PT J AU Albers, L Ozdemir, V Aravagiri, M Marder, S Raggi, M Reist, C AF Albers, L Ozdemir, V Aravagiri, M Marder, S Raggi, M Reist, C TI A prospective dose-controlled interaction between olanzapine and fluvoxamine: Application to pharmacoeconomic optimization of olanzapine treatment in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 VA Long Beach Healthcare Syst, Mental Healthcare Grp, Long Beach, CA USA. Univ Calif Irvine, Long Beach, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Toronto, Toronto, ON, Canada. Univ Bologna, Bologna, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 133 BP 47S EP 48S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000130 ER PT J AU Koenigsberg, HW Buchsbaum, M Harvey, PD Tang, C New, AS Goodman, M Siever, LJ AF Koenigsberg, HW Buchsbaum, M Harvey, PD Tang, C New, AS Goodman, M Siever, LJ TI Fmri in schizotypal personality disorder patients during a visuospatial working memory task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Bronx Vet Affairs Med Ctr, Dept Psychiat, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 157 BP 56S EP 56S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000154 ER PT J AU Yamanaka, K Nahas, Z Mu, Q Mishory, A Hill, SA Horner, MD Bedwell, JS Bohning, DE George, MS AF Yamanaka, K Nahas, Z Mu, Q Mishory, A Hill, SA Horner, MD Bedwell, JS Bohning, DE George, MS TI The effect of sleep deprivation on functional circuits involved in working memory SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 160 BP 57S EP 57S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000157 ER PT J AU Yao, JK Magan, SJ Thomas, EA Gurklis, JA Sanders, R Sonel, AF Reddy, RD AF Yao, JK Magan, SJ Thomas, EA Gurklis, JA Sanders, R Sonel, AF Reddy, RD TI Biochemical and treatment effects of ethyl eicosapentaenoate supplementation in neuroleptic-treated schizophrenic patients with a high risk for coronary artery disease SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 VA Pittsburgh Healthcare Syst, Med Res Serv, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA USA. Univ Pittsburgh, Sch Nursing, Hlth & Community Syst, Pittsburgh, PA USA. Scripps Res Inst, Dept Biol Mol, La Jolla, CA USA. VA Med Ctr, Dept Psychiat, Dayton, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 185 BP 65S EP 66S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000182 ER PT J AU Papakostas, GL Petersen, T Losifescu, DV Roffi, PA Alpert, JE Fava, M Nierenberg, AA AF Papakostas, GL Petersen, T Losifescu, DV Roffi, PA Alpert, JE Fava, M Nierenberg, AA TI Axis III disorders in treatment-resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Depress Clin & Res Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 200 BP 71S EP 71S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000197 ER PT J AU Gurrera, RJ Simpson, JC AF Gurrera, RJ Simpson, JC TI Evidence of publication bias in studies of neuroleptic malignant syndrome incidence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Dept Vet Affairs, VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 239 BP 85S EP 85S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000236 ER PT J AU Perlis, RH Wan, YJY Smoller, JW Mischoulon, D Fava, M AF Perlis, RH Wan, YJY Smoller, JW Mischoulon, D Fava, M TI Serotonin transporter polymorphisms and adverse effects with fluoxetine treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Harbor Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 243 BP 86S EP 86S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000240 ER PT J AU Leverenz, JB Tsuang, DW AF Leverenz, JB Tsuang, DW TI Psychosis in dementia - Biology to treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Washington, Clin & Educ Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 280 BP 99S EP 100S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000272 ER PT J AU Breiter, H AF Breiter, H TI Neural circuitry of reward and decision-making process in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 284 BP 101S EP 101S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000276 ER PT J AU Frazier, JA Chiu, S Kennedy, D Bent, E Stein, N Rauch, S Dietrich, M Makris, N Biederman, J Caviness, V AF Frazier, JA Chiu, S Kennedy, D Bent, E Stein, N Rauch, S Dietrich, M Makris, N Biederman, J Caviness, V TI Brain anatomic magnetic resonance imaging in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, McLean Hosp, Sch Med, Dept Child Psychiat, Belmont, MA 02178 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. RI Kennedy, David/H-3627-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 287 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000279 ER PT J AU New, AS Hazlett, EA Buchsbaum, MS Goodman, M Koenigsberg, HW Iskander, L Lo, J Mitropoulou, V Siever, LJ AF New, AS Hazlett, EA Buchsbaum, MS Goodman, M Koenigsberg, HW Iskander, L Lo, J Mitropoulou, V Siever, LJ TI M-CPP PET and impulsive aggression in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. NR 0 TC 4 Z9 4 U1 1 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 292 BP 104S EP 104S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000284 ER PT J AU Siever, LJ Frankle, WG Laruelle, M New, AS Buchsbaum, M Hazlett, E Goodman, M O'Flynn, K Miller, K Abi-Dargham, A AF Siever, LJ Frankle, WG Laruelle, M New, AS Buchsbaum, M Hazlett, E Goodman, M O'Flynn, K Miller, K Abi-Dargham, A TI The serotonergic system in personality disordered patients with impulsive aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 306 BP 108S EP 109S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000298 ER PT J AU Levitt, JJ McCarley, RW Westin, CF Nestor, PG Estepar, RSJ Kikinis, R Jolesz, FA Shenton, ME AF Levitt, JJ McCarley, RW Westin, CF Nestor, PG Estepar, RSJ Kikinis, R Jolesz, FA Shenton, ME TI Shape of the caudate nucleus in schizotypal personality disorder: An MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. 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NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 335 BP 119S EP 119S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000327 ER PT J AU Pekary, AE Faull, KF Sattin, A AF Pekary, AE Faull, KF Sattin, A TI A novel peptide, pyroglutamyltyrosylproline amide, in rat brain, structurally related to thyrotropin-releasing hormone SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 VA Greater Los Angeles Healthcare Syst, Res Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 374 BP 132S EP 132S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000366 ER PT J AU Bartzokis, G Freeman, T Roca, V Kimbrell, T Brown, SJ Lu, PH Turner, J Mintz, J Saunders, S AF Bartzokis, G Freeman, T Roca, V Kimbrell, T Brown, SJ Lu, PH Turner, J Mintz, J Saunders, S TI Risperidone in the treatment of chronic combat-related posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Calif Los Angeles, Los Angeles, CA USA. Cent Arkansas Vet Heath Care Syst, Little Rock, AR USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RI Bartzokis, George/K-2409-2013; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 384 BP 135S EP 135S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000376 ER PT J AU Zatzick, D Russo, J Pittman, R Roy-Byrne, P AF Zatzick, D Russo, J Pittman, R Roy-Byrne, P TI The association between emergency department heart rate and the development of PTSD symptoms in a representative sample of acutely injured trauma survivors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 386 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000378 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 BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Childrens Hosp, Sch Med, Psychopharmacol Program, Boston, MA 02115 USA. Organon Inc, Med Serv, W Orange, NJ USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 390 BP 137S EP 137S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000382 ER PT J AU Biederman, J Faraone, S Mick, E van Patten, S Pandina, G Gharabawi, G AF Biederman, J Faraone, S Mick, E van Patten, S Pandina, G Gharabawi, G TI Risperidone and affective symptoms in children with disruptive behavior disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, S Easton, MA USA. Janssen Pharmaceut Prod LP, CNS Med Affairs, Titusville, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 392 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000384 ER PT J AU Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL Cohen, LS AF Soares, CN Poitras, JR Prouty, J Alexander, AB Shifren, JL Cohen, LS TI Treatment of menopausal depression: Impact of SSRIs on symptoms of depression, anxiety, and quality of life SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 MGH, Ctr Womens Mental Hlth, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Mem Obstet & Gynecol Serv, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 408 BP 144S EP 144S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000400 ER PT J AU Mishory, A Yamanaka, K Nahas, Z Mu, Q Hill, S Horner, MD Li, X Bohning, D George, MS AF Mishory, A Yamanaka, K Nahas, Z Mu, Q Hill, S Horner, MD Li, X Bohning, D George, MS TI Can within-individual image-guided repetitive transcranial magnetic stimulation (rTMS) improve cognitive performance in sleep deprived men? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Brain Stimulat Lab, CAIR, Dept Psychiat Radiol & Neurol, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs, Med Ctr, Charleston, SC USA. NR 2 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 414 BP 146S EP 146S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000406 ER PT J AU Valera, EM Seidman, LJ Biederman, J Faraone, SV AF Valera, EM Seidman, LJ Biederman, J Faraone, SV TI An fMRI study of working memory in adults with ADHD: Age differences SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp,Psychopharmacol Unit, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 430 BP 152S EP 152S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000422 ER PT J AU Kose, S Lorberbaum, JP Horwitz, AR Dubno, JR Newman, JD Lester, BM Hamner, MB George, MS AF Kose, S Lorberbaum, JP Horwitz, AR Dubno, JR Newman, JD Lester, BM Hamner, MB George, MS TI A method of inducing an infant cry that parents can easily identify as their own infant's cry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Otolaryngol, Charleston, SC 29425 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. Brown Univ, Infant Dev Ctr, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 439 BP 155S EP 156S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000431 ER PT J AU Goodman, M Frankle, WG Laurelle, A New, A Koenigsberg, H Miller, K Iskander, E Abi-Dargham, A Siever, L AF Goodman, M Frankle, WG Laurelle, A New, A Koenigsberg, H Miller, K Iskander, E Abi-Dargham, A Siever, L TI Pet imaging of 5-HT 2A and 5-HT transporter receptors in personality disordered subjects with impulsive aggression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Mt Sinai Sch Med, New York, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. New York State Psychiat Inst Columbia, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 440 BP 156S EP 156S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000432 ER PT J AU Green, MF Marder, SR Fenton, W Davis, KL AF Green, MF Marder, SR Fenton, W Davis, KL TI Overcoming obstacles in treating cognitive deficits in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Psychiat Serv, Los Angeles, CA USA. NIMH, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 449 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000436 ER PT J AU Pitman, RK Marmar, CR Bremner, JD Carrion, VG Gilbertson, MW Teicher, MH AF Pitman, RK Marmar, CR Bremner, JD Carrion, VG Gilbertson, MW Teicher, MH TI Does psychological stress really damage the human brain? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Stanford Univ, Stanford, CA 94305 USA. VA Med Ctr, Manchester, NH USA. McLean Hosp, Belmont, MA 02178 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 451 BP 159S EP 159S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000438 ER PT J AU Spencer, KM McCarley, RW AF Spencer, KM McCarley, RW TI 40-Hz EEG phase synchrony abnormalities in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Brockton, MA 02401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 510 BP 180S EP 180S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000497 ER PT J AU Pierre, JM Wirshing, DA Cannell, J Marks, J Sheppard, K Saunders, D Wirshing, WC AF Pierre, JM Wirshing, DA Cannell, J Marks, J Sheppard, K Saunders, D Wirshing, WC TI High dose quetiapine in treatment refractory schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles VA Healthcare Ctr, Dept Psychiat, Los Angeles, CA USA. Atascadero State Hosp, Dept Psychiat, Atascadero, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 532 BP 188S EP 188S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000519 ER PT J AU Dougherty, DD Deckersbach, T Loh, R Rauch, SL Fischman, AJ Fava, M AF Dougherty, DD Deckersbach, T Loh, R Rauch, SL Fischman, AJ Fava, M TI PET studies of anger in depressed patients with and without anger attacks SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 540 BP 191S EP 191S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000527 ER PT J AU Li, X Nahas, Z Anderson, B Kozel, AF Yamanaka, K Bohning, DE George, MS AF Li, X Nahas, Z Anderson, B Kozel, AF Yamanaka, K Bohning, DE George, MS TI Transcranial magnetic stimulation delivered over the left prefrontal cortex of depressed patients increases local cortical activity as well as in the right orbitofrontal cortex, hippocampus, insula and thalamus SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 541 BP 191S EP 192S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000528 ER PT J AU Murck, H Alpert, J Nierenberg, AA Mischoulon, D Otto, MW Zajecka, J Rosenbaum, JF Fava, M AF Murck, H Alpert, J Nierenberg, AA Mischoulon, D Otto, MW Zajecka, J Rosenbaum, JF Fava, M TI Favorable response with hypericum extract in patients with depression with reversed vegetative signs - Reanalysis from data of a double-blind, randomized trial of hypericum extract, fluoxetine, and placebo in major depressive disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Lichtwer Pharma AG, Res & Dev, Berlin, Germany. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 549 BP 194S EP 194S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000536 ER PT J AU Deckersbach, T McMurrich, S Ogutha, JO Savage, CR Dougherty, DD Rauch, SL Sachs, GS AF Deckersbach, T McMurrich, S Ogutha, JO Savage, CR Dougherty, DD Rauch, SL Sachs, GS TI Characteristics of nonverbal memory impairment in bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 555 BP 197S EP 197S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000542 ER PT J AU Martin, LF Olincy, A Hall, MH Freedman, R AF Martin, LF Olincy, A Hall, MH Freedman, R TI Abnormalities of antisaccade task performance in schizophrenia and bipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 554 BP 197S EP 197S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000541 ER PT J AU Gurrera, RJ Salisbury, DF O'Donnell, BF Nestor, PG McCarley, RW AF Gurrera, RJ Salisbury, DF O'Donnell, BF Nestor, PG McCarley, RW TI Auditory P3 correlates with major personality traits and cognitive performance in healthy individuals SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Dept Vet Affairs, VA Boston Healthcare Syst, Boston, MA USA. Dept Vet Affairs, VA Boston Healthcare Syst, Brockton, MA USA. McLean Hosp, Belmont, MA 02178 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR 15 PY 2003 VL 53 IS 8 SU S MA 590 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000576 ER PT J AU Lorberbaum, JP Kose, S Hamner, MB George, MS AF Lorberbaum, JP Kose, S Hamner, MB George, MS TI Women prefer cradling infants on the left side in late pregnancy and the early postpartum period SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 58th Annual Convention and Scientific Program of the Society-of-Biological-Psychiatry CY MAY 15-17, 2003 CL SAN FRANCISCO, CALIFORNIA SP Soc Bio Psychiatry C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2003 VL 53 IS 8 SU S MA 607 BP 215S EP 215S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 670XU UT WOS:000182436000593 ER PT J AU Fava, M AF Fava, M TI Diagnosis and definition of treatment-resistant depression SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Difficult-to-Treat Depression CY APR 21-22, 2002 CL SAN FRANCISCO, CALIFORNIA SP Soc Biol Psychiat DE depression; resistance; treatment; diagnosis; definition ID MAJOR DEPRESSION; TREATMENT RESPONSE; ANTIDEPRESSANT TREATMENT; PERSONALITY-DISORDERS; UNIPOLAR DEPRESSION; TREATMENT OUTCOMES; DRUG RESPONSE; PRIMARY-CARE; DOUBLE-BLIND; FOLLOW-UP AB Treatment-resistant depression (TRD) typically refers to inadequate response to at least one antidepressant trial of adequate doses and duration. TRD is a relatively common occurrence in clinical practice, with up to 50% to 60% of the patients not achieving adequate response following antidepressant treatment. A diagnostic re-evaluation is essential to the proper management of these patients. In particular, the potential role of several contributing factors, such as medical and psychiatric comorbidity, needs to be taken into account. An accurate and systematic assessment of TRD is a challenge to both clinicians and researchers, with the use of clinician-rated or self-rated instruments being perhaps quite helpful. It is apparent that there may be varying degrees of treatment resistance. Some staging methods to assess levels of treatment resistance in depression are being developed, but need to be tested empirically. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, Boston, MA 02114 USA. RP Fava, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Depress Clin & Res Program, 15 Parkman St ACC 812, Boston, MA 02114 USA. NR 74 TC 483 Z9 502 U1 11 U2 36 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 APR 15 PY 2003 VL 53 IS 8 BP 649 EP 659 DI 10.1016/S0006-3223(03)00231-2 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 669PV UT WOS:000182360400004 PM 12706951 ER PT J AU Schmidt, VA Scudder, L Devoe, CE Bernards, A Cupit, LD Bahou, WF AF Schmidt, VA Scudder, L Devoe, CE Bernards, A Cupit, LD Bahou, WF TI IQGAP2 functions as a GTP dependent effector protein in thrombin-induced platelet cytoskeletal reorganization SO BLOOD LA English DT Article ID HUMAN ARP2/3 COMPLEX; ACTIVATED RECEPTOR-3; SMALL GTPASES; HUMAN GENOME; N-WASP; RAC; CDC42; DOMAIN; IDENTIFICATION; SEQUENCE AB Human blood platelets are anucleate cells whose response to extracellular stimuli results in actin cytoskeleton rearrangements, thereby providing the critical initial step in the regulation of hemostasis. The serine protease alpha-thrombin, known, to activate platelets by cleavage I of a family of protease-activated receptors (PARs), is the most potent physiologic activator of human platelets, though downstream effector proteins uniquely linked to platelet cytoskeletal actin polymerization remain largely uncharacterized. The gene encoding the putative rac1/cdc42 effector protein IQGAP2 was identified within the PAR gene cluster at 5q13, flanked telomeric by PAR1 and encompassing PAR3. Immunofluorescence microscopy demonstrated IQGAP2 expression in filopodial extensions of activated platelets and colocalized with F-actin in lamellipodia and filopodia of IQGAP2-transfected COS1 cells. Platelet activation by alpha-thrombin, but not saturating concentrations of fibrillar collagen or adenosine 5'-diphosphate, uniquely assemble an lQGAP2/arp2/3-actin cytoplasmic complex, an association regulated by guanosine triphosphate rac1 ([GTP]rac1) but not by [GTP]cdc42. Likewise, only thrombin-activated platelets resulted in rapid translocation of IQGAP2 to the platelet cytoskeleton. These observations identify a physiologic scaffolding function for IQGAP2 and establish the presence of a functional genomic unit in humans uniquely evolved to regulate thrombin-induced platelet cytoskeletal actin reorganization. (C) 2003 by The American Society of Hematology. C1 SUNY Stony Brook, Div Hematol, Dept Med, Stony Brook, NY 11794 USA. SUNY Stony Brook, Genet Program, Stony Brook, NY 11794 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Vet Adm Med Ctr, Dept Med, Northport, NY 11768 USA. RP Bahou, WF (reprint author), SUNY Stony Brook, Div Hematol, Dept Med, HSCT15-040, Stony Brook, NY 11794 USA. EM wbahou@notes.cc.sunysb.edu FU NHLBI NIH HHS [HL53665, HL49141]; NIDDK NIH HHS [DDK62040] NR 47 TC 32 Z9 33 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2003 VL 101 IS 8 BP 3021 EP 3028 DI 10.1182/blood-2002-09-2807 PG 8 WC Hematology SC Hematology GA 665CE UT WOS:000182101400024 PM 12515716 ER PT J AU Johnson, H Scorrano, L Korsmeyer, SJ Ley, TJ AF Johnson, H Scorrano, L Korsmeyer, SJ Ley, TJ TI Cell death induced by granzyme C SO BLOOD LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; GRANULE-MEDIATED APOPTOSIS; SERINE PROTEASE GENES; CYTOCHROME-C; TARGET-CELLS; CYTOTOXIC LYMPHOCYTES; CASPASE ACTIVATION; DNA FRAGMENTATION; RAPID INDUCTION; DIRECT CLEAVAGE AB Although the functions of granzymei A and B have been defined, the functions of the other highly expressed granzymes (Gzms) of murine cytotoxic lymphocytes (C, D, and F) have not yet been evaluated. In this report, we describe the ability of murine GzmC (which is most closely related to human geanzyme H) to cause cell death. The induction of death requires its protease activity and is characterized. by the rapid externalization of phospoatidyl-serine, nuclear condensation and collapse, and single-stranded DNA nicking. The kinetics of these events are similar to those caused by granzyme B, and its potency (defined on molar basis) is also equivalent. The induction of death did not involve the activation of caspases, the cleavage of BID, or the activation of the CAD nuclease. However, granzyme C did cause rapid mitochondrial swelling and depolarization in intact cells or in isolated mitochondria, and this mitochondrial damage was not prevented by cycldsporin A pretreatment. These results suggest that granzyme C rapidly induces target cell death by attacking nuclear and mitochondrial targets and that these tar gets are distinct from those, used by granzyme B to cause classical apoptosis. (C) 2003 by The American Society of Hematology. C1 Washington Univ, Sch Med, Div Oncol, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Oncol, Dept Genet, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Oncol, Siternan Canc Ctr, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pathol & Med,Howard Huges Med Inst, Boston, MA USA. RP Ley, TJ (reprint author), Washington Univ, Sch Med, Div Oncol, Dept Med, Campus Box 8007,660 S Euclid Ave, St Louis, MO 63110 USA. RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [CA50239]; NIDDK NIH HHS [DK49786] NR 51 TC 84 Z9 84 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 APR 15 PY 2003 VL 101 IS 8 BP 3093 EP 3101 DI 10.1182/blood-2002-08-2485 PG 9 WC Hematology SC Hematology GA 665CE UT WOS:000182101400035 PM 12515723 ER PT J AU Hu, LP Shi, YJ Hsu, JH Gera, J Van Ness, B Lichtenstein, A AF Hu, LP Shi, YJ Hsu, JH Gera, J Van Ness, B Lichtenstein, A TI Downstream effectors of oncogenic ras in multiple myeloma cells SO BLOOD LA English DT Article ID NF-KAPPA-B; P70 S6 KINASE; K-RAS; FARNESYLTRANSFERASE INHIBITORS; TRANSCRIPTIONAL ACTIVITY; ACTIVATING MUTATIONS; PROTEIN-KINASES; TUMOR-CELLS; LINE ANBL6; AKT KINASE AB Ectopic expression of mutated K-ras or N-ras in the interleukin 6 (IL-6)-dependent ANBL6 multiple myeloma cell line induces cytokine-independent growth. To investigate the signaling pathways activated by oncogenic ras that may stimulate IL-6-independent growth, we compared ANBL6. cells stably transfected with mutated K or N-ras genes with wild-type ras-expressing control cells identically transfected with an empty vector. Upon depletion of IL-6, both mutated rascontaining myeloma lines demonstrated constitutive activation of mitogen-activated extracellular kinase 2(MEK)/extracellular signal-regulated kinase (ERK), phosphatidylinositol-3 kinase (PI3-kinase)/AKT, mammalian target of rapamycin (mTOR)/p70S6-kinase, and nuclear factor kippaB (NF-kB) pathways. In contrast, signal transducer and activator of transcription-3 (STAT-3) was not constitutively tyrosine phosphorylated in mutant ras-expressing cells. We used several maneuvers in attempts to selectively target these constitutively active pathways. The mTOR inhibitors rapamycin and CCI-779, the PI3-kinase inhibitor LY294002, and the MEK inhibitor PD98059 all significantly curtailed growth of mutant. rascontaining cells. Farnesyl transferase inhibitors, used to target ras itself, had modest effects only against mutant N-ras-containing cells. Growth of mutant N-ras-containing myeloma cells was also inhibited by acute expression of the IKB superrepressor gene, which abrogated NF-kB activation. These results indicate that several pathways contributing to stimulation of cytokine-independent growth are activated downstream of oncogenic ras in myeloma cells. They also suggest that therapeutic strategies that target these pathways may be particularly efficacious in patients whose myeloma clones contain ras mutations. (C) 2003 by The American Society of Hematology. C1 Univ Calif Berkeley, Ctr Med, Hematol Oncol Div, W Los Angeles Vet Adm, Los Angeles, CA USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Lichtenstein, A (reprint author), VA W LA Med Ctr, W111H,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA 62242, CA 96920] NR 46 TC 101 Z9 106 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 APR 15 PY 2003 VL 101 IS 8 BP 3126 EP 3135 DI 10.1182/blood-2002-08-2640 PG 10 WC Hematology SC Hematology GA 665CE UT WOS:000182101400040 PM 12515720 ER PT J AU Hinton, S Catalano, PJ Einhorn, LH Nichols, CR Crawford, ED Vogelzang, N Trump, D Loehrer, PJ AF Hinton, S Catalano, PJ Einhorn, LH Nichols, CR Crawford, ED Vogelzang, N Trump, D Loehrer, PJ TI Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors - Final analysis of an intergroup trial SO CANCER LA English DT Article DE germ cell tumors; BEP (bleomycin, etoposide, cisplatin); VIP (etoposide, ifosfamide, cisplatin); International Germ Cell Cancer Collaborative Group Toxicity ID NONSEMINOMATOUS TESTICULAR CANCER; COOPERATIVE-ONCOLOGY-GROUP; PROGNOSTIC FACTORS; MULTIVARIATE-ANALYSIS; LEUKEMIA; CHEMOTHERAPY; VINBLASTINE; THERAPY AB BACKGROUND. Various staging systems have been proposed for disseminated germ cell neoplasms. The Indiana University staging system was based on clinical and radiographic findings only, whereas the newly created International Germ Cell Cancer Collaborative Group (IGCCCG) staging system also utilized serum markers as a prognostic factor. This study updated the intergroup trial that compared the standard therapy of bleomycin, etoposide, and cisplatin (BEP) with etoposide, ifosfamide, and cisplatin (VIP) in advanced germ cell tumors and reanalyzed the results using the IGCCCG staging system. METHODS. From October 1987 to April 1992, 304 patients with advanced-stage germ cell tumors (using the Indiana University staging system) were randomized to receive four cycles of BEP or VIP. Two hundred and eighty-six patients were eligible and fully evaluable. With a median follow-up of 7.3 years, 283 of the 286 evaluable patients from the Eastern Cooperative Oncology Group protocol, E3887, were reclassified using the IGCCCG staging system. Progression-free survival (PFS), overall survival (OS), and toxicity were assessed for the treatment arms. RESULTS. With a longer follow-up of 7.3 years and using the Indiana University staging system, the PFS rates were 64% versus 58% and the OS rates were 69% versus 67% in the VIP and BEP arms, respectively. For patients reclassified with the IGCCCG staging system, the PFS rates were 81%, 72%, and 54% and the OS rates were 89%, 81%, and 60% for good, intermediate, and poor-risk patients, respectively. Differences in OS (VIP, 62%; BEP, 57%) and PFS (VIP, 56%; BEP, 49%) for the subset of patients reclassified as poor risk by the IGCCCG staging system were not significantly different. More toxicity, primarily hematologic ioxicity, occurred on the VIP arm. CONCLUSIONS. With a median follow-up of 7.3 years and with a reclassification based on the IGCCCG, OS and PFS rates were comparable between BEP and VIP. Toxicity, primarily hematologic, was modestly greater with the ifosfamide-containing arm. The VIP regimen may be considered a treatment alternative for patients with underlying pulmonary disease. In most patients with poor and intermediate risk germ cell tumors, four cycles of BEP remain the standard therapy. (C) 2003 American Cancer Society. C1 Indiana Univ, Dept Med, Med Ctr, Indianapolis, IN USA. Walther Canc Inst, Indianapolis, IN USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Univ Colorado, Denver, CO 80202 USA. Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. Lewis A Weiss Mem Hosp, Dept Urol, Chicago, IL USA. Univ Chicago, Ctr Canc, Chicago, IL USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Loehrer, PJ (reprint author), Indiana Canc Pavil,535 Barnhill Dr,RT 473, Indianapolis, IN 46202 USA. FU NCI NIH HHS [CA66636, CA23318, CA32102, CA42777, CA39229, CA52651, CA18653, CA38926, CA49883, CA21115] NR 22 TC 69 Z9 76 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 APR 15 PY 2003 VL 97 IS 8 BP 1869 EP 1875 DI 10.1002/cncr.11271 PG 7 WC Oncology SC Oncology GA 663HH UT WOS:000181999800007 PM 12673712 ER PT J AU Okuno, S Ryan, LM Edmonson, JH Priebat, DA Blum, RH AF Okuno, S Ryan, LM Edmonson, JH Priebat, DA Blum, RH TI Phase II trial of gemcitabine in patients with advanced sarcomas (E1797) - A trial of the Eastern Cooperative Oncology Group SO CANCER LA English DT Article DE sarcoma; chemotherapy; gemcitabine; antitumor activity; toxicity ID ADVANCED SOFT-TISSUE; DOXORUBICIN; IFOSFAMIDE; CHEMOTHERAPY AB BACKGROUND. The current study was conducted to evaluate the antitumor activity 2 and toxicity of gemcitabine in patients with advanced sarcoma. METHODS. Twenty-five patients with advanced sarcomas, who previously were untreated for metastatic disease, were treated on an Eastern Cooperative Oncology Group Phase II study. Patients ranged in age from 27 to 79 years, with a median age of 59 years. The most common histology was leiomyosarcoma (54%). The grades of the tumors were high in 40%, moderate in 24% and low in 12%. Gemcitabine was given at a dose of 1250 mg/m(2) as a 30-minute infusion weekly for 3 weeks followed by 1 week of rest. RESULTS. One of the 25 patients (4%) (90% confidence interval [90% CI], 0-18%) achieved a partial response lasting 8 months. The estimated overall median survival was 15 months. The 1-year estimated survival rate was 63% (90% CI, 47-84%). The estimated median progression-free survival (PFS) was 13 months with a 1-year PFS rate of 56% (90% CI, 41-76%). Grade 3-4 toxicities (by CTC criteria) were observed in all 25 patients. No lethal toxicity (Grade 5) related to treatment was found. CONCLUSIONS. The results of the current study demonstrated that gemcitabine given at this schedule and dose in this population of patients with advanced sarcoma had limited activity. (C) 2003 American Cancer Society. C1 Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Washington Hosp Ctr, Hematol Oncol Sect, Washington Canc Inst, Washington, DC 20010 USA. Beth Israel Med Ctr, Div Hematol Oncol, New York, NY 10003 USA. RP Okuno, S (reprint author), Mayo Clin, Div Med Oncol, 200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA21115, CA13650, CA59307, CA66636, CA23318] NR 18 TC 44 Z9 46 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2003 VL 97 IS 8 BP 1969 EP 1973 DI 10.1002/cncr.11290 PG 5 WC Oncology SC Oncology GA 663HH UT WOS:000181999800020 PM 12673725 ER PT J AU Shipley, WU Kaufman, DS Tester, WJ Pilepich, MV Sandler, HM AF Shipley, WU Kaufman, DS Tester, WJ Pilepich, MV Sandler, HM TI Overview of bladder cancer trials in the Radiation Therapy Oncology Group SO CANCER LA English DT Article DE bladder conservation; radiation therapy; overall survival; Radiation Therapy Oncology Group protocols; chemotherapy ID PHASE-II TRIAL; GEMCITABINE PLUS CISPLATIN; COMBINED-MODALITY PROGRAM; ORGAN PRESERVATION; UROTHELIAL CANCER; PACLITAXEL; CARCINOMA AB In the United States, radical cystectomy is viewed as the gold standard and, with few exceptions, is the only treatment recommended for patients with invasive bladder cancer. In many areas of cancer treatment, however, the trend in the 1990s has been toward organ conservation using combined chemotherapy and radiation with or without conservative local surgery. For patients with breast, esophageal, anal, and laryngeal cancers as well as limb sarcomas, conservative therapy often is recommended. However, invasive bladder cancer has not been viewed generally as a condition that allows for conservative management. In the past 15 years, the Radiation Therapy Oncology Group (RTOG) has completed six prospective protocols of combined-modality therapy for patients with muscle-invasive cancer who were candidates for cystectomy. Bladder preservation with intravesical surgery, chemotherapy, and radiation therapy were combined as initial treatment, with radical cystectomy recommended for incomplete responders. Five of the RTOG protocols were Phase I-II trials of concurrent chemotherapy and radiation therapy, and one protocol was a Phase III trial that tested the efficacy of adjuvant chemotherapy with methotrexate, cisplatin, and vinblastine. A total of 415 patients were entered on these trials. The 5-year overall survival rate was approximately 50%, with three-quarters of those patients achieving a cure for their bladder cancer while maintaining a functioning bladder. The current RTOG protocol and its successor are directed toward better tolerated and potentially more effective chemotherapy regimens that may result in a high protocol compliance rate and, possibly, a higher overall survival rate. The trimodality therapeutic approach used in all of these RTOG protocols was more effective compared with the radiation monotherapy offered in the 1970s and with protocols that used only chemotherapy. Trimodality therapy with selective bladder preservation is not designed to take the place of radical cystectomy; however, it may be offered as a reasonable alternative to patients with invasive bladder cancer who are not willing to undergo radical cystectomy and urinary diversion. A bladder-sparing strategy may be offered appropriately to highly selected patients with the understanding that radical cystectomy is an available option in those who fail combined radiation and chemotherapy with no diminution in survival related to the delay in cystectomy. (C) 2003 American Cancer Society. C1 Amer Coll Radiol, Radiat Therapy Oncol Grp, Genitourinary Oncol Comm, Philadelphia, PA USA. RP Shipley, WU (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 32 Fruit St, Boston, MA 02114 USA. NR 19 TC 59 Z9 62 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 APR 15 PY 2003 VL 97 IS 8 SU S BP 2115 EP 2119 DI 10.1002/cncr.11282 PG 5 WC Oncology SC Oncology GA 664TU UT WOS:000182078000010 PM 12673704 ER PT J AU Petrovsky, A Schellenberger, E Josephson, L Weissleder, R Bogdanov, A AF Petrovsky, A Schellenberger, E Josephson, L Weissleder, R Bogdanov, A TI Near-infrared fluorescent imaging of tumor apoptosis SO CANCER RESEARCH LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; CARDIAC ALLOGRAFT-REJECTION; IN-VIVO DETECTION; ANNEXIN-V; CELL-DEATH; PHOSPHATIDYLSERINE EXPOSURE; NONINVASIVE DETECTION; CANCER; EXPRESSION; THERAPY AB Noninvasive imaging using radioactive annexin V is an emerging strategy for the assessment of cell death in vivo (F. G. Blankenberg, and H. W. Strauss. Apoptosis, 6: 117-123, 2001.). Therefore, we investigated whether annexin V labeled with the fluorophore Cy5.5 (Cy) could serve as a probe for imaging of tumor apoptosis using near infrared fluorescence (NIRF). We prepared active Cy-annexin (an equimolar dye:protein ratio) that bound to apoptotic Jurkat T cells and an inactive Cy-annexin probe (>2 dyes/mol protein) that did not. Active Cy annexin was used to image a 9L gliosarcoma, constitutively expressing green fluorescent protein marker, and the CR8 variant of Lewis lung carcinoma, stably transfected to express DsRed2. The expression of transfected fluorescent protein provided an indication of tumor margins and a means of defining tumor-associated NIRF signal intensity with both tumor models. Tumors were imaged with and without cyclophosphamide treatment. In both tumor models active Cy-annexin V tumor NIRF signal increased two to three times after the treatment. Tumor NIRF signal developed by 75 min after active Cy-annexin injection and remained for a 20-h observation period. Inactive annexin V was used as a control in the CR8 carcinoma experiments and resulted in a low nonspecific signal. With the 9L gliomosacrcoma model, active Cy-annexin V bound to both tumor cells (Cy-annexin V staining only) and endothelial cells (costained with Cy-annexin V and antibody to the endothelial marker CD31). Our results demonstrate that active Cy-annexin can be used as a NIRF probe to image apoptosis from outside an intact living animal and may provide nonradioactive method of measuring the antiproliferative effects of cancer chemotherapeutic regimens. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Room 5420,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [1P50CA86355-01, 5R01CA74424-01] NR 44 TC 172 Z9 176 U1 6 U2 40 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2003 VL 63 IS 8 BP 1936 EP 1942 PG 7 WC Oncology SC Oncology GA 668TE UT WOS:000182308600036 PM 12702586 ER PT J AU Hu, FB Cho, EY Rexrode, KM Albert, CM Manson, JE AF Hu, FB Cho, EY Rexrode, KM Albert, CM Manson, JE TI Fish and long-chain omega-3 fatty acid intake and risk of coronary heart disease and total mortality in diabetic women SO CIRCULATION LA English DT Article DE coronary disease; nutrition; fish; fatty acids; women ID FOOD FREQUENCY QUESTIONNAIRE; POLYUNSATURATED FATTY-ACIDS; MYOCARDIAL-INFARCTION; SUDDEN-DEATH; DIETARY SUPPLEMENTATION; ENDOTHELIAL FUNCTION; GLYCEMIC CONTROL; MELLITUS; CONSUMPTION; OIL AB Background-Although several prospective cohort studies have found an inverse association between fish consumption and risk of coronary heart disease (CHD) or sudden cardiac death in the general population, limited data are available among diabetic patients. Methods and Results-We examined prospectively the association between intake of fish and omega-3 fatty acids and risk of CHD and total mortality among 5103 female nurses with diagnosed type 2 diabetes but free of cardiovascular disease or cancer at baseline. Between 1980 and 1996 (45 845 person-years of follow-up), we documented 362 incident cases of CHD (141 CHD deaths and 221 nonfatal myocardial infarctions) and 468 deaths from all causes. Compared with women who seldom consumed fish (<1 serving/mo), the relative risks (RRs) (95% CI) of CHD adjusted for age, smoking, and other established coronary risk factors were 0.70 (0.48 to 1.03) for fish consumption 1 to 3 times per month, 0.60 (0.42 to 0.85) for once per week, 0.64 (0.42 to 0.99) for 2 to 4 times per week, and 0.36 (0.20 to 0.66) for 5 or more times per week (P for trend=0.002). Higher consumption of fish was also associated with a significantly lower total mortality (multivariate RR=0.48 [0.29 to 0.80] for >= 5 times per week [P for trend=0.005]). Higher consumption of long-chain omega-3 fatty acids was associated with a trend toward lower incidence of CHD (RR=0.69 [95% CI 0.47 to 1.03], P for trend=0.10) and total mortality (RR=0.63 [95% CI, 0.45 to 0.88], P for trend=0.02). Conclusions-A higher consumption of fish and long-chain omega-3 fatty acids was associated with a lower CHD incidence and total mortality among diabetic women. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Hu, FB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM frank.hu@channing.harvard.edu OI Rexrode, Kathryn/0000-0003-3387-8429 FU NCI NIH HHS [CA-87969]; NHLBI NIH HHS [HL-65582]; NIDDK NIH HHS [DK-58845] NR 37 TC 168 Z9 178 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 15 PY 2003 VL 107 IS 14 BP 1852 EP 1857 DI 10.1161/01.CIR.0000062644.42133.5F PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 667FZ UT WOS:000182221800007 PM 12668520 ER PT J AU Miller, SM Beattie, MM Butt, AA AF Miller, SM Beattie, MM Butt, AA TI Personal digital assistant infectious diseases applications for health care professionals SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PRACTICE GUIDELINES; INTERVENTIONS AB Personal digital assistants (PDAs; also known as "handheld computers," "pocket personal computers," and Palm Pilots) provide immediate access to vital and clinically relevant infectious diseases information at the point of care. Several infectious diseases applications are available that provide information on pathogens, diagnosis, medication, and treatment. In this article, 4 infectious diseases PDA applications are reviewed: ePocrates ID (part of ePocrates Rx Pro), the Johns Hopkins Division of Infectious Diseases Antibiotic Guide, the 2002 Sanford Guide to Antimicrobial Therapy, and Infectious Diseases and Antimicrobials Notes. Drug information, including clinical pharmacology, dosing in patients with renal insufficiency, adverse reactions, and drug interactions, is evaluated for completeness and accuracy by comparison of each application with the package insert. Treatment recommendations for 6 diseases are compared with current practice guidelines. Each PDA infectious diseases application reviewed has unique advantages and disadvantages. This critical review will help health care professionals select the infectious diseases PDA application best tailored to meet their individual information needs. C1 Univ Missouri, Sch Med, Clin Pharmacol Sect, Kansas City, MO 64108 USA. Univ Missouri, Hlth Sci Lib, Kansas City, MO 64110 USA. Univ Pittsburgh, Ctr Hlth Equity Res & Promot, Pittsburgh, PA 15260 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Miller, SM (reprint author), Univ Missouri, Sch Med, Clin Pharmacol Sect, M4-207 Med Sch,2411 Holmes St, Kansas City, MO 64108 USA. NR 22 TC 24 Z9 24 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR 15 PY 2003 VL 36 IS 8 BP 1018 EP 1029 DI 10.1086/368198 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MK UT WOS:000182124700014 PM 12684915 ER PT J AU Fultz, SL Justice, AC Butt, AA Rabeneck, L Weissman, S Rodriguez-Barradas, M AF Fultz, SL Justice, AC Butt, AA Rabeneck, L Weissman, S Rodriguez-Barradas, M CA VACS-3 Project Team TI Testing, referral, and treatment patterns for hepatitis C virus coinfection in a cohort of veterans with human immunodeficiency virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; RISK; HEPATOTOXICITY; HCV AB We examined testing, referral, and treatment of patients with hepatitis C among HIV-infected patients in the Veterans Aging 3-Site Cohort Study by using patient- and provider-completed surveys and laboratory, pharmacy, and administrative records from the Department of Veterans Affairs electronic medical record. Of 881 human immunodeficiency virus-positive patients, 43% were coinfected with hepatitis C virus. Of these, 88 (30%) reported current alcohol consumption. Only one-third were counseled to reduce or stop alcohol consumption. Coinfected patients with indications for hepatitis C treatment had a high rate of contraindications, including both medical and psychiatric comorbidities. Of the 65 patients with indications for hepatitis C therapy and free of contraindications for treatment, only 18% underwent liver biopsy and 3% received IFN. Although treatment indications are common in this population, contraindications are also common. Health care providers are often unaware of alcohol consumption that may accelerate the course of hepatitis C, increase the risk of hepatocellular carcinoma, and reduce treatment efficacy. C1 Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. Baylor Coll Med, Houston, TX 77030 USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. Vet Affairs Ctr Excellence, Houston, TX USA. Hosp St Raphael, New Haven, CT USA. RP Justice, AC (reprint author), Univ Pittsburgh, Sch Med, Vet Affairs Pittsburgh Healthcare Syst, Univ Dr C,11 E 124 130-U, Pittsburgh, PA 15240 USA. FU NIA NIH HHS [AG-00826]; NIAAA NIH HHS [AA-13566]; NIDDK NIH HHS [DK-59318] NR 21 TC 62 Z9 63 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 APR 15 PY 2003 VL 36 IS 8 BP 1039 EP 1046 DI 10.1086/374049 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MK UT WOS:000182124700016 PM 12684917 ER PT J AU Steere, AC McHugh, G Suarez, C Hoitt, J Damle, N Sikand, VK AF Steere, AC McHugh, G Suarez, C Hoitt, J Damle, N Sikand, VK TI Prospective study of coinfection in patients with erythema migrans SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN GRANULOCYTIC EHRLICHIOSIS; LYME-DISEASE; BABESIA-MICROTI; DIAGNOSIS; AGENT AB The frequency of coinfection with Borrelia burgdorferi and either Anaplasma phagocytophila or Babesia microti among patients with erythema migrans, the initial skin lesion of Lyme disease, was assessed in 2 mainland locations in Rhode Island and Connecticut in a 4-year prospective study. Of the 93 patients with culture-proven erythema migrans, 2 (2%) patients had coinfection with A. phagocytophila and 2 (2%) had coinfection with B. microti. We concluded that the frequency of coinfection with these agents was low among patients with erythema migrans in the study areas. C1 Tufts Univ, Sch Med, New England Med Ctr, Div Rheumatol & Immunol, Boston, MA 02111 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, Bldg 149 13th St,Rm 8301, Charlestown, MA 02129 USA. FU ODCDC CDC HHS [CCU110291] NR 15 TC 44 Z9 46 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 APR 15 PY 2003 VL 36 IS 8 BP 1078 EP 1081 DI 10.1086/368187 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 665MK UT WOS:000182124700023 PM 12684924 ER PT J AU Elkin, SK Matthews, AG Oettinger, MA AF Elkin, SK Matthews, AG Oettinger, MA TI The C-terminal portion of RAG2 protects against transposition in vitro SO EMBO JOURNAL LA English DT Article DE hybrid joining; RAG1; RAG2; transposition; V(D)J recombination ID V(D)J RECOMBINATION ACTIVITY; SIGNAL SEQUENCES; PROTEINS; CLEAVAGE; DNA; COMPLEX; REARRANGEMENT; 12/23-RULE; EVOLUTION; MUTATIONS AB The assembly of antigen receptor genes by V(D)J recombination is initiated by the RAG1/RAG2 protein complex, which introduces double-strand breaks between recombination signal sequences and their coding DNA. Truncated forms of RAG1 and RAG2 are functional in vivo and have been used to study V(D)J cleavage, hybrid joint formation and transposition in vitro. Here we have characterized the activities of the full-length proteins. Unlike core RAG2, which supports robust transposition in vitro, full-length RAG2 blocks transposition of signal ends following V(D)J cleavage. Thus, one role of this non-catalytic domain may be to prevent transposition in developing lymphoid cells. Although full-length RAG1 and RAG2 proteins rarely form hybrid joints in vivo in the absence of non-homologous end-joining factors, we show that the full-length proteins alone can catalyze this reaction in vitro. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Oettinger, MA (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. FU NIGMS NIH HHS [R01 GM048026, R01 GM48026] NR 39 TC 51 Z9 51 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD APR 15 PY 2003 VL 22 IS 8 BP 1931 EP 1938 DI 10.1093/emboj/cdg184 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 666CW UT WOS:000182159900021 PM 12682025 ER PT J AU Citron, ML Berry, DA Cirrincione, C Hudis, C Winer, EP Gradishar, WJ Davidson, NE Martino, S Livingston, R Ingle, JN Perez, EA Carpenter, J Hurd, D Holland, JF Smith, BL Sartor, CI Leung, EH Abrams, J Schilsky, RL Muss, HB Norton, L AF Citron, ML Berry, DA Cirrincione, C Hudis, C Winer, EP Gradishar, WJ Davidson, NE Martino, S Livingston, R Ingle, JN Perez, EA Carpenter, J Hurd, D Holland, JF Smith, BL Sartor, CI Leung, EH Abrams, J Schilsky, RL Muss, HB Norton, L TI Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: First report of intergroup trial C9741/cancer and leukemia group B trial 9741 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CYCLOPHOSPHAMIDE; DOXORUBICIN; GROWTH AB Purpose: Using a 2 X 2 factorial design, we studied the adjuvant chemotherapy of women with axillary node-positive breast cancer to compare sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) with concurrent doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) for disease-free (DFS) and overall survival (OS); to determine whether the dose density of the agents improves DFS and OS; and to compare toxicities. Patients and Methods: A total of 2,005 female patients were randomly assigned to receive one of the following regimens: (I) sequential A x 4 (doses) --> T x 4 --> C x 4 with doses every 3 weeks, (11) sequential A x 4 T x 4 --> C x 4 every 2 weeks with filgrastim, (111) concurrent AC x 4 T x 4 every 3 weeks, or (IV) concurrent AC x 4 --> T x 4 every 2 weeks with filgrastim. Results: A protocol-specified analysis was performed at a median follow-up of 36 months: 315 patients had experienced relapse or died, compared with 515 expected treatment failures. Dose-dense treatment improved the primary end point, DFS (risk ratio [RR] = 0.74; P = .010), and OS (RR = 0.69; P = .013). Four-year DFS was 82% for the dose-dense regimens and 75% for the others. There was no difference in either DFS or OS between the concurrent and sequential schedules. There was no interaction between density and sequence. Severe neutropenia was less frequent in patients who received the dose-dense regimens. Conclusion: Dose density improves clinical outcomes significantly, despite the lower than expected number of events at this time. Sequential chemotherapy is as effective as concurrent chemotherapy. (C) 2003 by American Society of Clinical Oncology. C1 ProHlth Care Associates, LLP, Lake Success, NY 11042 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27109 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. Cent Off, Canc & Leukemia Grp B, Chicago, IL 60611 USA. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Alabama, Birmingham, AL USA. Univ Vermont, Burlington, VT USA. RP Citron, ML (reprint author), ProHlth Care Associates, LLP, 2800 Marcus Ave, Lake Success, NY 11042 USA. NR 21 TC 831 Z9 871 U1 2 U2 13 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 APR 15 PY 2003 VL 21 IS 8 BP 1431 EP 1439 DI 10.1200/JCO.2003.09.081 PG 9 WC Oncology SC Oncology GA 668NN UT WOS:000182300200003 PM 12668651 ER PT J AU Earle, CC Burstein, HJ Winer, EP Weeks, JC AF Earle, CC Burstein, HJ Winer, EP Weeks, JC TI Quality of non-breast cancer health maintenance among elderly breast cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Clin Oncol ID ROUTINE FOLLOW-UP; PRIMARY-CARE; COMORBIDITY INDEX; LUNG-CANCER; CHEMOTHERAPY AB Purpose: To assess the quality of preventive health care, the role of health care participation, and the patient and provider characteristics associated with high-quality care for breast cancer survivors. Methods: We analyzed the 1997 to 1998 Medicare data of elderly women who were diagnosed with nonmetastatic breast cancer in 1991 or 1992 while living in a Survival, Epidemiology, and End Results (SEER) tumor registry area and who survived to the end of 1998 without evidence of cancer recurrence. Controls were matched for age, race, and geographic location: Results: The 5,965 breast cancer survivors received more preventive services (influenza vaccination, lipid testing, cervical and colon screening, and bone densitometry) than matched controls: Among both groups, those who were younger, non-African-American, of higher socioeconomic status, living in urban areas, and receiving care in a teaching center were most likely to receive high-quality health maintenance. Those survivors who continued to see oncology specialists were more likely to receive appropriate follow-up mammography for their cancer, but those who were monitored by primary care physicians were more likely to receive all other non-cancer-related preventive services. Those who saw. both types of practitioners received more of both types of services. When the control group was restricted only to women actively undergoing mammographic screening before the study period, receipt of preventive services was similar. Conclusion: Breast cancer survivors receive high-quality preventive services, but disparities on the basis of nonmedical factors still exist. Cancer follow-up may provide regular contact with the health system, maximizing the likelihood of receiving appropriate general medical care. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Breast Oncol Ctr, Dept Med Oncol,Div Populat Sci, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 167 Z9 170 U1 0 U2 2 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 APR 15 PY 2003 VL 21 IS 8 BP 1447 EP 1451 DI 10.1200/JCO.2003.03.060 PG 5 WC Oncology SC Oncology GA 668NN UT WOS:000182300200005 PM 12697865 ER PT J AU Grossman, SA O'Neill, A Grunnet, M Mehta, M Pearlman, JL Wagner, H Gilbert, M Newton, HB Hellman, R AF Grossman, SA O'Neill, A Grunnet, M Mehta, M Pearlman, JL Wagner, H Gilbert, M Newton, HB Hellman, R TI Phase III study comparing three cycles of infusional carmustine and cisplatin followed by radiation therapy with radiation therapy and concurrent carmustine in patients with newly diagnosed supratentorial glioblastoma multiforme: Eastern Cooperative Oncology Group Trial 2394 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-GRADE ASTROCYTOMA; MALIGNANT BRAIN-TUMORS; PREIRRADIATION CHEMOTHERAPY; MYELOABLATIVE CHEMOTHERAPY; GLIOMA; RADIOTHERAPY; CARBOPLATIN; ETOPOSIDE; BCNU; TEMOZOLOMIDE AB Purpose: This phase III Eastern Cooperative Oncology Group-Southwest Oncology Group intergroup study was conducted to determine whether three 72-hour infusions of carmustine (BiCNU) and cisplatin administered monthly before external-beam radiotherapy would improve the survival of patients with newly diagnosed glioblastoma multiforme. The control arm consisted of radiation with standard adjuvant BiCNU. Patients and Methods: A total of 223 patients were accrued from 1996 to 1999. Of these, 219 patients were eligible; 109 were randomly assigned to the experimental arm, and 110 were randomly assigned to the control arm. Randomization was stratified by age, performance status, and extent of resection. Results: The median age of the patients was 55 years; 55% were male, 93% were white, 26% had a biopsy only, and 84% were ambulatory. Treatment arms were well balanced with respect to baseline characteristics. Median follow-up time of the 15 patients still alive at the time of analysis was 3.3 years (range, 2 to 5 years). Median survival times for the standard and experimental arms were 11.2 and 11.0 months (P = .33, two-sided log-rank test), and survival at 1 year was 45% versus 44%, respectively. Fifty-six percent of patients received all three cycles of BiCNU/cisplatin, 12% received two cycles, and 31% received only one cycle. Toxicity was primarily hematologic and was more common in the experimental arm (P < .01). Conclusion: This study demonstrates that 72-hour infusions of BiCNU and cisplatin followed by radiation do not improve median survival, survival at 1 year, or time to progression. Furthermore, this treatment requires more time in the hospital and is associated with more serious toxicities than standard therapy. (C) 2003 by American Society of Clinical Oncology. C1 Sydney Kimmel Canc Ctr, Baltimore, MD 21231 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Farmington, CT USA. Lawrence Mem Hosp, New London, CT USA. Univ Wisconsin, Madison, WI USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Ohio State Univ, Columbus, OH 43210 USA. RP Grossman, SA (reprint author), Sydney Kimmel Canc Ctr, 1650 Orleans St,Room G93, Baltimore, MD 21231 USA. OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA73590, CA04920, CA16116, CA21076, CA21115, CA23318, CA66636] NR 41 TC 81 Z9 84 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 APR 15 PY 2003 VL 21 IS 8 BP 1485 EP 1491 DI 10.1200/JCO.2003.10.035 PG 7 WC Oncology SC Oncology GA 668NN UT WOS:000182300200011 PM 12697871 ER PT J AU Videtic, GMM Stitt, LW Dar, AR Kocha, WI Tomiak, AT Truong, PT Vincent, MD Yu, EW AF Videtic, GMM Stitt, LW Dar, AR Kocha, WI Tomiak, AT Truong, PT Vincent, MD Yu, EW TI Continued cigarette smoking by patients receiving concurrent chemoradiotherapy for limited-stage small-cell lung cancer is associated with decreased survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROGNOSTIC FACTORS; CARCINOMA CELLS; GLOTTIC CANCER; LOCAL-CONTROL; RADIATION; NICOTINE; THERAPY AB Purpose: To determine the impact of continued smoking by patients receiving chemotherapy (CHT) and radiotherapy (RT) for limited-stage small-cell lung cancer (LSCLC) on toxicity and survival. Patients and Methods: A retrospective review was carried out on 215 patients with LSCLC treated between 1989 and 1999. Treatment consisted of six cycles of alternating cyclophosphamide, doxorubicin, vincristine and etoposide, cisplatin (EP). Thoracic RT was concurrent with EP (cycle 2 or 3) only. Patients were known smokers, with their smoking status recorded at the start of chemoradiotherapy (CHT/RT). RT interruption during concurrent CHT/RT was used as the marker for treatment toxicity. Results: Of 215 patients, smoking status was recorded for 186 patients (86.5%), with 79 (42%) continuing to smoke and 107 (58%) abstaining during CHT/RT. RT interruptions were recorded in 38 patients (20.5%), with a median duration of 5 days (range, 1 to 18 days). Median survival for former smokers was greater than for continuing smokers (18 v 13.6 months), with 5-year actuarial overall survival of 8.9% versus 4%, respectively (log-rank P = .0017). Proportion of noncancer deaths was comparable between the two cohorts. Continuing smokers did not have a greater incidence of toxicity-related treatment breaks (P = .49), but those who continued to smoke and also experienced a treatment break had the poorest overall survival (median, 13.4 months; log-rank P = .0014). Conclusion: LSCLC patients who continue to smoke during CHT/RT have poorer survival rates than those who do not. Smoking did not have an impact on the rate of treatment interruptions attributed to toxicity. J Clin Oncol 21:1544-1549. (C) 2003 by American Society of Clinical Oncology. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. London Reg Canc Ctr, Dept Biometry, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Radiat Oncol, London, ON N6A 4L6, Canada. London Reg Canc Ctr, Dept Med Oncol, London, ON N6A 4L6, Canada. Kingston Reg Canc Ctr, Dept Med Oncol, Kingston, ON, Canada. British Columbia Canc Agcy, Dept Radiat Oncol, Victoria, BC, Canada. Vancouver Isl Canc Ctr, Victoria, BC, Canada. RP Videtic, GMM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St,ASBI L2, Boston, MA 02115 USA. NR 25 TC 128 Z9 129 U1 0 U2 6 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 APR 15 PY 2003 VL 21 IS 8 BP 1544 EP 1549 DI 10.1200/JCO.2003.10.089 PG 6 WC Oncology SC Oncology GA 668NN UT WOS:000182300200019 PM 12697879 ER PT J AU Scagliotti, GV Shin, DM Kindler, HL Vasconcelles, MJ Keppler, U Manegold, C Burris, H Gatzemeier, U Blatter, J Symanowski, JT Rusthoven, JJ AF Scagliotti, GV Shin, DM Kindler, HL Vasconcelles, MJ Keppler, U Manegold, C Burris, H Gatzemeier, U Blatter, J Symanowski, JT Rusthoven, JJ TI Phase II study of pemetrexed with and without folic acid and vitamin B-12 as front-line therapy in malignant pleural mesothelioma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MULTITARGETED ANTIFOLATE LY231514; CELL LUNG-CANCER; LEUKEMIA GROUP-B; CLINICAL-TRIALS; DISODIUM; CHEMOTHERAPY; MTA AB Purpose: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). Patients and Methods: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m(2)) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B-12 supplementation to improve safety. Results: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. Conclusion: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation. J Clin Oncol 21:1556-1561. (C) 2003 by American Society of Clinical Oncology. C1 Univ Turin, Dept Clin & Biol Sci, Turin, Italy. Univ Chicago, Chicago, IL 60637 USA. Univ Pittsburgh, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Thorax Klin, Heidelberg, Germany. Krankenhaus Grosshansdorf, Grosshansdorf, Germany. Eli Lilly & Co, Bad Homburg, Germany. Sarah Cannon Canc Ctr, Nashville, TN USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Scagliotti, GV (reprint author), Univ Turin, Azienda Osped S Luigi, Dept Clin & Biol Sci, Reg Gonzole 10, I-10124 Turin, Italy. RI Ray, Dana/C-3470-2013; Shin, Dong Moon/G-9649-2013 NR 32 TC 169 Z9 174 U1 2 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2003 VL 21 IS 8 BP 1556 EP 1561 DI 10.1200/JCO.2003.06.122 PG 6 WC Oncology SC Oncology GA 668NN UT WOS:000182300200021 PM 12697881 ER PT J AU Goorin, AM Schwartzentruber, DJ Devidas, M Gebhardt, MC Ayala, AG Harris, MB Helman, LJ Grier, HE Link, MP AF Goorin, AM Schwartzentruber, DJ Devidas, M Gebhardt, MC Ayala, AG Harris, MB Helman, LJ Grier, HE Link, MP TI Presurgical chemotherapy compared with immediate surgery and adjuvant chemotherapy for nonmetastatic osteosarcoma: Pediatric oncology group study POG-8651 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HIGH-DOSE METHOTREXATE; PRIMARY OSTEOGENIC-SARCOMA; NEOADJUVANT CHEMOTHERAPY; DELAYED SURGERY; INTERGROUP RHABDOMYOSARCOMA; PREOPERATIVE CHEMOTHERAPY; OPERABLE OSTEOSARCOMA; PROGNOSTIC FACTORS; RADIATION-THERAPY; CANCER AB Purpose: Successful therapeutic interventions to prevent disease progression in patients with nonmetastatic osteosarcoma have included surgery with adjuvant chemotherapy. Presurgical chemotherapy has been advocated for these patients because of putative improvement in event-free survival (EFS). The advantages of presurgical chemotherapy include early administration of systemic chemotherapy, shrinkage of primary tumor, and pathologic identification of risk groups. The theoretic disadvantage is that it exposes a large tumor burden to marginally effective chemotherapy. The contribution of chemotherapy and surgery timing has not been tested rigorously. Patients and Methods: Between 1986 and 1993, we conducted a prospective trial in patients with nonmetastatic osteosarcoma who were assigned randomly to immediate surgery or presurgical chemotherapy. Except for the timing of surgery (week 0 or 10), patients received 44 weeks of identical combination chemotherapy that included high-dose methotrexate with leucovorin rescue, doxorubicin, cisplatin, bleomycin, cyclophosphamide, and dactinomycin. Results: One hundred six patients were enrolled onto this study. Six were excluded from analysis. Of the remaining 100 patients, 45 were randomly assigned to immediate chemotherapy, and 55 were randomly assigned to immediate surgery. Sixty-seven patients remain disease-free. At 5 years, the projected EFS +/- SE is 65% +/- 6% (69% +/- 8% for immediate surgery and 61% +/- 8% for presurgical chemotherapy; P = .8). The treatment arms had similar incidence of limb salvage (55% for immediate surgery and 50% for presurgical chemotherapy). Conclusion: Chemotherapy was effective in both treatment groups. There was no advantage in EFS for patients given presurgical chemotherapy. J Clin Oncol 21:1574-1580. (C) 2003 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, Surg Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Pediat Oncol Grp, Stat Off, Gainesville, FL USA. Univ Texas, Dept Surg Pathol, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Tomorrows Childrens Inst, Hackensack, NJ USA. Univ Med Ctr, Newark, NJ USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. RP Goorin, AM (reprint author), Dana Farber Canc Inst, Dept Pediat, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA-15525, CA-03161, CA-05587, CA-11233, CA-15898, CA-20549, CA-25408, CA-28383, CA-28439, CA-28476, CA-29139, CA-29293, CA-30969, CA-32053, CA-33587, CA-33603, CA-33625, CA-41573, CA-69177, CA-69478] NR 34 TC 156 Z9 171 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 15 PY 2003 VL 21 IS 8 BP 1574 EP 1580 DI 10.1200/JCO.2003.08.165 PG 7 WC Oncology SC Oncology GA 668NN UT WOS:000182300200023 PM 12697883 ER PT J AU Gu, XG Laouar, A Wan, JM Daheshia, M Lieberman, J Yokoyama, WM Katz, HR Manjunath, N AF Gu, XG Laouar, A Wan, JM Daheshia, M Lieberman, J Yokoyama, WM Katz, HR Manjunath, N TI The gp49B1 inhibitory receptor regulates the IFN-gamma responses of T cells and NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTIC CHORIOMENINGITIS VIRUS; IG-LIKE RECEPTOR; IN-VIVO; IMMUNOGLOBULIN SUPERFAMILY; DIFFERENTIAL EXPRESSION; HIV-1 INFECTION; CD8(+); ACTIVATION; MEMORY; EFFECTOR AB The magnitude and diversity of Ag-specific T cell effector activity have been proposed to be controlled by an integration of positive signals transduced by the TCR and negative signals originating from inhibitory cell surface molecules. Although the lectin family, of NK cell-associated inhibitory receptors has been reported to regulate the function of murine CTLs, gp49B1, the Ig superfamily member is not known to be expressed on T cells. Moreover, the consequences of the lack of an endogenously expressed NK cell-associated inhibitory receptor on T cell functions are not known. We report that gp49B1 is expressed by nearly all activated CD8 and CD4 T cells in addition to NK cells during an immune response to viral, bacterial, or tumor challenge. Kinetics of gp49B1 expression parallel functional capability and subside in the memory phase. Following vaccinia viral infection, IFN-gamma production by both subsets of T cells and NK cells is enhanced in gp49B1-deficient mice compared with gp49B1(+/+) mice. The stimulation threshold for IFN-gamma production is also lower in gp49B1-deficient T cells. In contrast, no significant differences were observed in the cytotoxic responses. We conclude that gp49B1 is a unique inhibitory receptor that is induced in multiple lineages of innate and adaptive immune cells during an infection and controls their IFN-gamma, but not cytotoxic responses. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. RP Manjunath, N (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 NR 44 TC 23 Z9 23 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 APR 15 PY 2003 VL 170 IS 8 BP 4095 EP 4101 PG 7 WC Immunology SC Immunology GA 666HG UT WOS:000182171100020 PM 12682239 ER PT J AU Meyer-Olson, D Brady, KW Blackard, JT Allen, TM Islam, S Shoukry, NH Hartman, K Walker, CM Kalams, SA AF Meyer-Olson, D Brady, KW Blackard, JT Allen, TM Islam, S Shoukry, NH Hartman, K Walker, CM Kalams, SA TI Analysis of the TCR beta variable gene repertoire in chimpanzees: Identification of functional homologs to human pseudogenes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEPATITIS-C VIRUS; T-LYMPHOCYTE RESPONSES; DISEASE PROGRESSION; IMMUNE-RESPONSE; INFECTION; DIVERSITY; EVOLUTION; SEQUENCE; ESCAPE; CHAIN AB Chimpanzees are used for a variety of disease models such as hepatitis C virus (HCV) infection, where Ag-specific T cells are thought to be critical for resolution of infection. The variable segments of the TCR alphabeta genes are polymorphic and contain putative binding sites for MHC class I and II molecules. In this study, we performed a comprehensive analysis of genes that comprise the TCR beta variable gene (TCRBV) repertoire of the common chimpanzee Pan troglodytes. We identified 42 P. troglodytes TCRBV sequences representative,of 25 known human TCRBV families. BV5, BV6, and BV7 are multigene TCRBV families in humans and homologs of most family members were found in the chimpanzee TCRBV repertoire. Some of the chimpanzee TCRBV sequences were identical with their human counterparts at the amino acid level. Notably four successfully rearranged TCRBV sequences in the chimpanzees corresponded to human pseudogenes. One of these TCR sequences was used by a cell line directed against a viral CTL epitope in an HCV-infected animal indicating the functionality of this V region in the context of immune defense against pathogens. These data indicate that some TCRBV genes maintained in the chimpanzee have been lost in humans within a brief evolutionary time frame despite remarkable conservation of the chimpanzee and human TCRBV repertoires. Our results predict that the diversity of TCR clonotypes responding to pathogens like HCV will be very similar in both species and will facilitate a molecular dissection of the immune response in chimpanzee models of human diseases. C1 Vanderbilt Univ, Med Ctr, Dept Med, Infect Dis Unit, Nashville, TN 37232 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit 3, Boston, MA 02114 USA. Childrens Res Inst, Div Mol Med, Columbus, OH 43205 USA. RP Kalams, SA (reprint author), Vanderbilt Univ, Med Ctr, Dept Med, Infect Dis Unit, Med Ctr N A4103, Nashville, TN 37232 USA. RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [AI-R01-A1-47367, U19AI48231] NR 43 TC 18 Z9 18 U1 1 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 APR 15 PY 2003 VL 170 IS 8 BP 4161 EP 4169 PG 9 WC Immunology SC Immunology GA 666HG UT WOS:000182171100029 PM 12682248 ER PT J AU Peltomaa, M McHugh, G Steere, AC AF Peltomaa, M McHugh, G Steere, AC TI Persistence of the antibody response to the VlsE sixth invariant region (IR6) peptide of Borrelia burgdorferi after successful antibiotic treatment of Lyme disease SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 9th International Conference on Lyme Brreliosis and Other Tick-Borne Diseases CY AUG 18-22, 2002 CL NEW YORK, NEW YORK ID IMMUNODOMINANT CONSERVED REGION; FACIAL PARALYSIS; ERYTHEMA MIGRANS; ARTHRITIS; MANIFESTATIONS; SERODIAGNOSIS; INFECTION; SYPHILIS AB It has been suggested that a <4-fold decline in the immunoglobulin G (IgG) antibody response to the VlsE sixth invariant region peptide of Borrelia burgdorferi within 6 months after antibiotic treatment may indicate spirochetal persistence in Lyme disease. We studied the response to this peptide in 77 patients with early or late disease, for whom archival samples were available at the time of antibiotic treatment and &SIM;6 months or years later. Eight (33%) of the 24 patients with early manifestations and 18 (86%) of the 21 patients with late manifestations had a &SIM;4-fold decline in IgG anti-VlsE titers &SIM;6 months after successful antibiotic treatment. Of 32 additional patients, 13 (50%) with early manifestations and 5 (83%) with late manifestations still had positive anti-VlsE titers 8-15 years after successful antibiotic treatment. We conclude that persistence of the anti-VlsE antibody response for months or years after antibiotic treatment cannot be equated with spirochetal persistence in Lyme disease. C1 Tufts New England Med Ctr, Div Rheumatol & Immunol, Boston, MA USA. Univ Helsinki, Cent Hosp, Dept Otolaryngol, Helsinki, Finland. RP Peltomaa, M (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 149 13th St,Rm 8301, Boston, MA 02129 USA. FU ODCDC CDC HHS [CCU110291] NR 26 TC 41 Z9 42 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 APR 15 PY 2003 VL 187 IS 8 BP 1178 EP 1186 DI 10.1086/374376 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 662WL UT WOS:000181972000002 PM 12695996 ER PT J AU Jones, SR Mulloney, B Kaper, TJ Kopell, N AF Jones, SR Mulloney, B Kaper, TJ Kopell, N TI Coordination of cellular pattern-generating circuits that control limb movements: The sources of stable differences in intersegmental phases SO JOURNAL OF NEUROSCIENCE LA English DT Article DE central pattern generators; crayfish swimmeret; coupled oscillator theory; phase lags; frequency regulation; phase-response curves ID WEAKLY COUPLED OSCILLATORS; CRAYFISH SWIMMERET SYSTEM; INTERNEURONS; NEURONS; RHYTHMS; CHAINS; MODELS AB Neuronal mechanisms in nervous systems that keep intersegmental phase lags the same at different frequencies are not well understood. We investigated biophysical mechanisms that permit local pattern-generating circuits in neighboring segments to maintain stable phase differences. We use a modified version of an existing model of the crayfish swimmeret system that is based on three known coordinating neurons and hypothesized intersegmental synaptic connections. Weakly coupled oscillator theory was used to derive coupling functions that predict phase differences between neurons in neighboring segments. We show how features controlling the size of the lag under simplified network configurations combine to create realistic lags in the full network. Using insights from the coupled oscillator theory analysis, we identify an alternative intersegmental connection pattern producing realistic stable phase differences. We show that the persistence of a stable phase lag to changes in frequency can arise from complementary effects on the network with ascending-only or descending-only intersegmental connections. To corroborate the numerical results, we experimentally constructed phase-response curves (PRCs) for two different coordinating interneurons in the swimmeret system by perturbing the firing of individual interneurons at different points in the cycle of swimmeret movement. These curves provide information about the contribution of individual intersegmental connections to the stable phase lag. We also numerically constructed PRCs for individual connections in the model. Similarities between the experimental and numerical PRCs confirm the plausibility of the network configuration that has been proposed and suggest that the same stabilizing balance present in the model underlies the normal phase-constant behavior of the swimmeret system. C1 Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Ctr BioDynam, Boston, MA 02215 USA. Univ Calif Davis, Sect Neurobiol Physiol & Behav, Davis, CA 95616 USA. RP Jones, SR (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIMH NIH HHS [R01 MH47150] NR 29 TC 31 Z9 31 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 2003 VL 23 IS 8 BP 3457 EP 3468 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 671QH UT WOS:000182475200041 PM 12716954 ER PT J AU Hewett, J Ziefer, P Bergeron, D Naismith, T Boston, H Slater, D Wilbur, J Schuback, D Kamm, C Smith, N Camp, S Ozelius, LJ Ramesh, V Hanson, PI Breakefield, XO AF Hewett, J Ziefer, P Bergeron, D Naismith, T Boston, H Slater, D Wilbur, J Schuback, D Kamm, C Smith, N Camp, S Ozelius, LJ Ramesh, V Hanson, PI Breakefield, XO TI TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE dystonia; oxidative stress; endoplasmic reticulum; movement disorders; cell morphology ID DYSTONIA GENE DYT1; OXIDATIVE STRESS; HUMAN BRAIN; HEAT-SHOCK; IN-VITRO; PROTEINS; DOPAMINE; ALPHA; DIFFERENTIATION; ACETYLCHOLINE AB Most cases of early-onset torsion dystonia are caused by deletion of GAG in the coding region of the DYT1 gene encoding torsinA. This autosomal dominant neurologic disorder is characterized by abnormal movements, believed to originate from neuronal dysfunction in the basal ganglia of the human brain. The torsins (torsinA and torsinB) are members of the "ATPases associated with a variety of cellular activities" (AAA(+)) superfamily of proteins that mediate chaperone and other functions involved in conformational modeling of proteins, protection from stress, and targeting of proteins to cellular organelles. In this study, the intracellular localization and levels of endogenous torsin were evaluated in rat pheochromocytoma PC12 cells following differentiation and stress. TorsinA, apparent MW 37 kDa, cofractionates with markers for the microsomal/endoplasmic reticulum (ER) compartment and appears to reside primarily within the ER lumen based on protease resistance. TorsinA immunoreactivity colocalizes with the lumenal ER protein protein disulfide isomerase (PHI) and extends throughout neurites. Levels of torsinA did not increase notably in response to nerve growth factor-induced differentiation. None of the stress conditions tested, including-heat shock and the unfolded protein response, affected torsinA, except for oxidative stress, which resulted in an increase in the apparent MW of torsinA and redistribution to protrusions from the cell surface. These findings are consistent with a relatively rapid covalent modification of torsinA in response to oxidative stress causing a change in state. Mutant torsinA may interfere with and/or compromise ER functions, especially in dopaminergic neurons, which have high levels of torsinA and are intrinsically vulnerable to oxidative stress. (C) 2003 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. RI Hanson, Phyllis/E-9420-2012 FU NINDS NIH HHS [NS28384, NS37409, NS38142] NR 54 TC 73 Z9 76 U1 0 U2 5 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD APR 15 PY 2003 VL 72 IS 2 BP 158 EP 168 DI 10.1002/jnr.10567 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 665HC UT WOS:000182113000003 PM 12671990 ER PT J AU John, J Wu, MF Kodama, T Siegel, JM AF John, J Wu, MF Kodama, T Siegel, JM TI Intravenously administered hypocretin-1 alters brain amino acid release: an in vivo microdialysis study in rats SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID OREXIN-A; LOCUS-COERULEUS; GABA RELEASE; SPINAL-CORD; NEURONS; NARCOLEPSY; GLUTAMATE; SLEEP; STIMULATION; EXPRESSION AB We have reported that intravenous administration of hypocretin (Hcrt or orexin) reverses the symptoms of narcolepsy in genetically narcoleptic dogs. We have also reported that the onset of symptoms in canine genetic narcolepsy is accompanied by degenerative changes in forebrain regions, particularly the septal nucleus and amygdala. In the present in vivo microdialysis study we have investigated the effect of intravenous administration of Hcrt-1 (orexin-A) to anaesthetized rats on glutamate and GABA release in the amygdala, a region with moderate Hcrt innervation, and in the cerebellar cortex, a region with sparse or no Hcrt innervation. We found that intravenous Hcrt administration caused a marked (> 60%) and sustained (> 50 min) increase in glutamate release within the amygdala, but no change in release in the cerebellar cortex. We did not detect a significant change in GABA release. When calcium-free artificial cerebrospinal fluid was used as the microdialysis perfusate, Hcrt-1 no longer produced an increase in glutamate release. Hcrt may act via the calcium-dependent regulation of glutamate release in certain nuclei of the central nervous system. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 91020 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 91020 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Sepulveda VAMC, Neurobiol Res 151A3,16111 Plummer St, North Hills, CA 91343 USA. FU NHLBI NIH HHS [HL41370, HL60296, R37 HL041370, P50 HL060296, R01 HL041370]; NINDS NIH HHS [R01 NS014610, NS14610, R37 NS014610] NR 36 TC 32 Z9 33 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 15 PY 2003 VL 548 IS 2 BP 557 EP 562 DI 10.1113/jphysiol.2002.038729 PG 6 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 690VL UT WOS:000183571100025 PM 12626669 ER PT J AU Stone, ME AF Stone, ME TI The Yale guide to women's reproductive health: From menarche to menopause. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 15 PY 2003 VL 128 IS 7 BP 114 EP 115 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 672MA UT WOS:000182523400170 ER PT J AU Wilhelmi, BJ Mowlavi, A Neumeister, MW Bueno, R Ketchum, J Lee, WPA AF Wilhelmi, BJ Mowlavi, A Neumeister, MW Bueno, R Ketchum, J Lee, WPA TI Surface landmarks to locate the thenar branch of the median nerve: An anatomical study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-for-Hand-Surgery CY JAN 10, 2002 CL CANCUN, MEXICO SP Amer Assoc Hand Surg ID CARPAL-TUNNEL; HYPOTHENAR MUSCLES; MUSCULAR BRANCH; HAND AB The thenar branch of the median nerve can be injured during carpal tunnel release. The purpose of this study was to identify surface landmarks to consistently predict the location of the thenar branch of the median nerve. Surface landmarks were marked and incised in 28 cadaveric hands. The incisions were made along the longitudinal line of the third web space and the horizontal cardinal line from the hamate hook to the ulnar border of the thumb. The origin of the thenar branch was determined in relation to these longitudinal and horizontal vectors. The origin of the thenar nerve branch was consistently observed in the radial proximal quadrant formed by the aforementioned longitudinal and horizontal vectors. The thenar branch origin was observed to be an average of 8.6 +/- 1.9 mm radial to the longitudinal axis along the third web space. The origin of the thenar branch was observed to be an average of 6.3 +/- 2.0 mm proximal to the horizontal axis between the hamate hook and the ulnar border of the thumb. The thenar branch was observed precisely at the intersection of the longitudinal vector from the second web space to the scaphoid tubercle and the horizontal vector from the hamate hook to the radial edge of the proximal metacarpophalangeal crease in all 28 cadaveric hands. On the basis of these 28 cadaveric dissections, the location of the thenar branch of the median nerve can be predicted by the intersection of the longitudinal vector from the second web space to the scaphoid tubercle and the horizontal vector from the hamate hook to the radial aspect of the metacarpophalangeal crease. C1 So Illinois Univ, Sch Med, Plast Surg Inst, Springfield, IL 62794 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilhelmi, BJ (reprint author), So Illinois Univ, Sch Med, Plast Surg Inst, POB 19653, Springfield, IL 62794 USA. NR 16 TC 8 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD APR 15 PY 2003 VL 111 IS 5 BP 1612 EP 1615 DI 10.1097/01.PRS.0000057969.87632.a8 PG 4 WC Surgery SC Surgery GA 662RQ UT WOS:000181962300004 PM 12655205 ER PT J AU Chestukhin, A Pfeffer, C Milligan, S DeCaprio, JA Pellman, D AF Chestukhin, A Pfeffer, C Milligan, S DeCaprio, JA Pellman, D TI Processing, localization, and requirement of human separase for normal anaphase progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SISTER-CHROMATID SEPARATION; COHESIN SUBUNIT SCC1; SACCHAROMYCES-CEREVISIAE; HUMAN-CELLS; YEAST; CLEAVAGE; DEGRADATION; PROTEOLYSIS; CHROMOSOME; METAPHASE AB In all eukaryotes, anaphase is triggered by the activation of a protease called separase. Once activated, separase cleaves a subunit of cohesin, a complex that links replicated chromatids before anaphase. Separase and cohesin are conserved from yeasts to humans. Although the machinery for dissolving sister cohesion is conserved, the regulation of this process appears to be more complex in higher eukaryotes than in yeast. Here we report the cloning of full-length human separase cDNA and the characterization of the encoded protein. Human separase was observed at the poles of the mitotic spindle until anaphase, at which time its association with the mitotic spindle was abruptly lost. The dynamic pattern of localization of human separase during cell cycle progression differs from that of fungal separases. Human separase also appears to undergo an autocatalytic processing on anaphase entry. The processed forms of human separase were isolated and the identity of the cleavage sites was determined by N-terminal sequencing and site-directed mutagenesis. The processed catalytic domain was found to be stably associated with the processed N-terminal fragment. Finally, by depletion of endogenous separase with antisense oligonucleotides, we report direct evidence that separase is required for high-fidelity chromosome separation in human cells. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [1 F32 CA84752, R01-CA63113, F32 CA084752, R01 CA063113, R01 CA55772] NR 46 TC 50 Z9 54 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4574 EP 4579 DI 10.1073/pnas.0730733100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100044 PM 12672959 ER PT J AU Haq, S Michael, A Andreucci, M Bhattacharya, K Dotto, P Walters, B Woodgett, J Kilter, H Force, T AF Haq, S Michael, A Andreucci, M Bhattacharya, K Dotto, P Walters, B Woodgett, J Kilter, H Force, T TI Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYNTHASE KINASE 3-BETA; HYPERTROPHY IN-VIVO; CARDIAC-HYPERTROPHY; SUBSTRATE-SPECIFICITY; PATHWAY; ACTIVATION; CELLS; PHOSPHORYLATION; KINASE-3-BETA; INACTIVATION AB beta-Catenin is a transcriptional activator that regulates embryonic development as part of the Wnt pathway and also plays a role in tumorigenesis. The mechanisms leading to Wnt-induced stabilization of beta-catenin, which results in its translocation to the nucleus and activation of transcription, have been an area of intense interest. However, it is not clear whether stimuli other than Writs can lead to important stabilization of beta-catenin and, if so, what factors mediate that stabilization and what biologic processes might be regulated. Herein we report that beta-catenin is stabilized in cardiomyocytes after these cells have been exposed to hypertrophic stimuli in culture or in vivo. The mechanism by which beta-catenin is stabilized is distinctly different from that used by Wnt signaling. Although, as with Wnt signaling, inhibition of glycogen synthase kinase-3 remains central to hypertrophic stimulus-induced stabilization of beta-catenin, the mechanism by which this occurs involves the recruitment of activated PKB to the beta-catenin-clegraclation complex. PKB stabilizes the complex and phosphorylates glycogen synthase kinase-3 within the complex, inhibiting its activity directed at beta-catenin. Finally, we demonstrate via adenoviral gene transfer that beta-catenin is both sufficient to induce growth in cardiomyocytes in culture and in vivo and necessary for hypertrophic stimulus-induced growth. Thus, in these terminally differentiated cells, beta-catenin is stabilized by hypertrophic stimuli acting via heterotrimeric G protein-coupled receptors. The stabilization occurs via a unique Wnt-independent mechanism and results in cellular growth. C1 Tufts Univ, New England Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Toronto, Toronto, ON M5S 1A1, Canada. RP Haq, S (reprint author), Tufts Univ, New England Med Ctr, Mol Cardiol Res Inst, 750 Washington St,Box 8486, Boston, MA 02111 USA. RI Woodgett, Jim/F-1087-2010; OI Woodgett, Jim/0000-0003-3731-5797; Force, Thomas/0000-0002-0450-8659 FU Canadian Institutes of Health Research [12043]; NHLBI NIH HHS [R01 HL067371, HL61688, HL67371, R01 HL061688] NR 33 TC 149 Z9 155 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4610 EP 4615 DI 10.1073/pnas.0835895100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100050 PM 12668767 ER PT J AU Sanoudou, D Haslett, JN Kho, AT Guo, SQ Gazda, HT Greenberg, SA Lidov, HGW Kohane, IS Kunkel, LM Beggs, AH AF Sanoudou, D Haslett, JN Kho, AT Guo, SQ Gazda, HT Greenberg, SA Lidov, HGW Kohane, IS Kunkel, LM Beggs, AH TI Expression profiling reveals altered satellite cell numbers and glycolytic enzyme transcription in nemaline myopathy muscle SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYPE-2 DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; GROWTH-FACTOR-BETA; INTRACELLULAR CALCIUM; MUSCULAR-DYSTROPHY; INSULIN-RESISTANCE; GENE-EXPRESSION; MDX MICE; DIFFERENTIATION; MECHANISM AB The nemaline myopathies (NMs) are a clinically and genetically heterogeneous group of disorders characterized by nemaline rods and skeletal muscle weakness. Mutations in five sarcomeric thin filament genes have been identified. However, the molecular consequences of these mutations are unknown. Using Affymetrix oligonucleotide microarrays, we have analyzed the expression patterns of >21,000 genes and expressed sequence tags in skeletal muscles of 12 NM patients and 21 controls. Multiple complementary approaches were used for data analysis, including geometric fold analysis, two-tailed unequal variance t test, hierarchical clustering, relevance network, and nearest-neighbor analysis. We report the identification of high satellite cell populations in NM and the significant down-regulation of transcripts for key enzymes of glucose and glycogen metabolism as well as a possible regulator of fatty acid metabolism, UCP3. Interestingly, transcript level changes of multiple genes suggest possible changes in Ca2+ homeostasis. The increased expression of multiple structural proteins was consistent with increased fibrosis. This comprehensive study of downstream molecular consequences of NM gene mutations provides insights in the cellular events leading to the NM phenotype. C1 Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Div Neuromuscular Dis, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Beggs, AH (reprint author), Childrens Hosp, Div Genet, 300 Longwood Ave, Boston, MA 02115 USA. RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Sanoudou, Despina/0000-0003-3704-1941; Beggs, Alan/0000-0001-8818-0568 FU NIAMS NIH HHS [R01 AR044345, R01 AR44345]; NINDS NIH HHS [P01 NS040828, P01 NS40828] NR 44 TC 50 Z9 50 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 APR 15 PY 2003 VL 100 IS 8 BP 4666 EP 4671 DI 10.1073/pnas.0330960100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100060 PM 12677001 ER PT J AU State, MW Greally, JM Cuker, A Bowers, PN Henegariu, O Morgan, TM Gunel, M DiLuna, M King, RA Nelson, C Donovan, A Anderson, GM Leckman, JF Hawkins, T Pauls, DL Lifton, RP Ward, DC AF State, MW Greally, JM Cuker, A Bowers, PN Henegariu, O Morgan, TM Gunel, M DiLuna, M King, RA Nelson, C Donovan, A Anderson, GM Leckman, JF Hawkins, T Pauls, DL Lifton, RP Ward, DC TI Epigenetic abnormalities associated with a chromosome 18(q21-q22) inversion and a Gilles de la Tourette syndrome phenotype SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LA-TOURETTE-SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; SEGREGATION ANALYSIS; REPLICATION; FAMILY; GENE; BREAKPOINT; DNA; TRANSLOCATION; INACTIVATION AB Gilles de la Tourette syndrome (GTS) is a potentially debilitating neuropsychiatric disorder defined by the presence of both vocal and motor tics. Despite evidence that this and a related phenotypic spectrum, including chronic tics (CT) and Obsessive Compulsive Disorder (OCD), are genetically mediated, no gene involved in disease etiology has been identified. Chromosomal abnormalities have long been proposed to play a causative role in isolated cases of GTS spectrum phenomena, but confirmation of this hypothesis has yet to be forthcoming. We describe an i(18q21.1-q22.2) inversion in a patient with CT and OCD. We have fine mapped the telomeric aspect of the rearrangement to within 1 Mb of a previously reported 18q22 breakpoint that cosegregated in a family with GTS and related phenotypes. A comprehensive characterization of this genomic interval led to the identification of two transcripts, neither of which was found to be structurally disrupted. Analysis of the epigenetic characteristics of the region demonstrated a significant increase in replication asynchrony in the patient compared to controls, with the inverted chromosome showing delayed replication timing across at least a 500-kb interval. These findings are consistent with long-range functional dys-regulation of one or more genes in the region. Our data support a link between chromosomal aberrations and epigenetic mechanisms in GTS and suggest that the study of the functional consequences of balanced chromosomal rearrangements is warranted in patients with phenotypes of interest, irrespective of the findings regarding structurally disrupted transcripts. C1 Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Biochem & Mol Biophys, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06511 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06511 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Charlestown, MA 02129 USA. US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. RP State, MW (reprint author), Yale Univ, Sch Med, Ctr Child Study, 333 Cedar St, New Haven, CT 06511 USA. RI Morgan, Tom/C-3478-2012 FU NCRR NIH HHS [K23 RR016118, RR16118]; NICHD NIH HHS [HD35497]; NIDDK NIH HHS [DK02467, DK56768]; NIMH NIH HHS [P01 MH049351, MH18268, MH49351, T32 MH018268]; NINDS NIH HHS [NS43520, R01 NS043520] NR 30 TC 49 Z9 55 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 15 PY 2003 VL 100 IS 8 BP 4684 EP 4689 DI 10.1073/pnas.0730775100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100063 PM 12682296 ER PT J AU Hodi, FS Mihm, MC Soiffer, RJ Haluska, FG Butler, M Seiden, MV Davis, T Henry-Spires, R MacRae, S Willman, A Padera, R Jaklitsch, MT Shankar, S Chen, TC Korman, A Allison, JP Dranoff, G AF Hodi, FS Mihm, MC Soiffer, RJ Haluska, FG Butler, M Seiden, MV Davis, T Henry-Spires, R MacRae, S Willman, A Padera, R Jaklitsch, MT Shankar, S Chen, TC Korman, A Allison, JP Dranoff, G TI Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; TUMOR-INFILTRATING LYMPHOCYTES; PULSED DENDRITIC CELLS; MHC CLASS-I; ANTITUMOR IMMUNITY; CTLA-4 BLOCKADE; COMBINATION IMMUNOTHERAPY; IMMUNOLOGICAL SYNAPSE; PROGNOSTIC FACTOR; PROSTATE-CANCER AB A large number of cancer-associated gene products evoke immune recognition, but host reactions rarely impede disease progression. The weak immunogenicity of nascent tumors contributes to this failure in host defense. Therapeutic vaccines that enhance dendritic cell presentation of cancer antigens increase specific cellular and humoral responses, thereby effectuating tumor destruction in some cases. The attenuation of T cell activation by cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) further limits the potency of tumor immunity. In murine systems, the administration of antibodies that block CTLA-4 function inhibits the growth of moderately immunogenic tumors and, in combination with cancer vaccines, increases the rejection of poorly immunogenic tumors, albeit with a loss of tolerance to normal differentiation antigens. To gain a preliminary assessment of the biologic activity of antagonizing CTLA-4 function in humans, we infused a CTLA-4 blocking antibody (MDX-CTLA4) into nine previously immunized advanced cancer patients. MDX-CTLA4 stimulated extensive tumor necrosis with lymphocyte and granulocyte infiltrates in three of three metastatic melanoma patients and the reduction or stabilization of CA-125 levels in two of two metastatic ovarian carcinoma patients previously vaccinated with irradiated, autologous granulocyte-macrophage colony-stimulating factor-secreting tumor cells. MDX-CTLA4 did not elicit tumor necrosis in four of four metastatic melanoma patients previously immunized with defined melanosomal antigens. No serious toxicities directly attributable to the antibody were observed, although five of seven melanoma patients developed T cell reactivity to normal melanocytes. These findings suggest that CTLA-4 antibody blockade increases tumor immunity in some previously vaccinated cancer patients. C1 Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Medarex Inc, Annandale, NJ 08801 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. RP Dranoff, G (reprint author), Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NCI NIH HHS [CA74886, CA39542, CA78880, P01 CA039542, R01 CA074886] NR 56 TC 552 Z9 576 U1 4 U2 27 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 APR 15 PY 2003 VL 100 IS 8 BP 4712 EP 4717 DI 10.1073/pnas.0830997100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 668RC UT WOS:000182306100068 PM 12682289 ER PT J AU Yang, Q Tofler, GH Cupples, LA Larson, MG Feng, DL Lindpaintner, K Levy, D D'Agostino, RB O'Donnell, CJ AF Yang, Q Tofler, GH Cupples, LA Larson, MG Feng, DL Lindpaintner, K Levy, D D'Agostino, RB O'Donnell, CJ TI A genome-wide search for genes affecting-circulating fibrinogen levels in the Framingham Heart Study SO THROMBOSIS RESEARCH LA English DT Article DE genome-wide scan; genetic linkage; fibrinogen; HindIII beta-148; cardiovascular disease; variance component analysis; Framingham Heart Study ID TRAIT LINKAGE ANALYSIS; PLASMA-FIBRINOGEN; BETA-FIBRINOGEN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; POLYMORPHISMS; ASSOCIATION; LOCI; ATHEROSCLEROSIS AB Introduction: Circulating levels of fibrinogen are associated with atherosclerosis and predict future coronary heart disease and stroke. Levels of fibrinogen are correlated among family members, suggesting a heritable component. Variants of the beta-fibrinogen gene subunit on 4q28 are associated with fibrinogen levels but explain only a small proportion of the total genetic variability. It remains unknown what role, if any, is played by other genetic variants in the inter-individual variability in levels of fibrinogen in the general population. Materials and methods: We conducted a 10-cM spaced genome-wide scan using 402 original cohort subjects and 1193 offspring subjects from 330 extended families of the Framingham Heart Study. Heritability and linkage analyses were carried out using variance component methods. Regression analyses were performed to adjust for traditional risk factors and HindIII beta-148 genotypes. Results and Discussions: The total heritability was estimated as 0.24. The highest and second highest LOD scores of linkage were found on chromosomes 2 (LOD= 1.5 at 243 cM) and 10 (LOD = 2.4 at 87 cM) using only offspring subjects in the analysis, and on chromosomes 2 (LOD = 2.1 at 242 cM) and 10(LOD = 1.4 at 86 cM), 17 (LOD = 1.4 at 96 cM) and 20 (LOD = 1.4 at 80 cM) using both original cohort and offspring. These results suggest that there may be influential genetic regions on these chromosomes. While no linkage with genome-wide significance was detected, further research to confirm our findings is warranted. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Max Delbruck Ctr Mol Med, Berlin, Germany. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Yang, Q (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 715 Albany St,T-4E, Boston, MA 02118 USA. RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254 NR 29 TC 21 Z9 22 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. PD APR 15 PY 2003 VL 110 IS 1 BP 57 EP 64 DI 10.1016/S0049-3848(03)00288-3 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 708WV UT WOS:000184593900010 PM 12877910 ER PT J AU Bradley, KA Bush, KR Epler, AJ Dobie, DJ Davis, TM Sporleder, JL Maynard, C Burman, ML Kivlahan, DR AF Bradley, KA Bush, KR Epler, AJ Dobie, DJ Davis, TM Sporleder, JL Maynard, C Burman, ML Kivlahan, DR TI Two brief alcohol-screening tests from the Alcohol Use Disorders Identification Test (AUDIT) - Validation in a female veterans affairs patient population SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID BRIEF PHYSICIAN ADVICE; RANDOMIZED CONTROLLED TRIAL; PRIMARY-CARE; PROBLEM DRINKING; BINGE-DRINKING; PROBLEM DRINKERS; LIKELIHOOD RATIOS; DIAGNOSTIC-TEST; DRUG MODULES; AUDADIS-ADR AB Background: Primary care physicians need a brief alcohol questionnaire that identifies hazardous drinking and alcohol use disorders. The Alcohol Use Disorders identification Test (AUDIT) questions 1 through 3 (AUDIT-C), and AUDIT question 3 alone are effective alcohol-screening tests in male Veterans Affairs (VA) patients, but have not been validated in women. Methods: Female VA patients (n = 393) completed self-administered questionnaires, including the 10-item AUDIT and a previously proposed modification to AUDIT question 3 with a sex-specific threshold for binge drinking (greater than or equal to 4 drinks/occasion), and in-person interviews with the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The AUDIT-C, AUDIT question 3 alone, and the 10-item AUDIT were each evaluated with and without the sex-specific binge question and compared with past-year hazardous drinking (> 7 drinks/week or :4 drinks/occasion) and/or active Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol abuse or dependence, based on interviews. Results: Eighty-nine women (22.6%) met interview criteria for past-year hazardous drinking and/or active alcohol abuse or dependence. Standard and sex-specific AUDIT-Cs were sensitive (0.81 and 0.84, respectively) and specific (0.86 and 0.85, respectively). Their areas under the receiver operating characteristic curves were equivalent (0.91, and 0.92, respectively) and slightly higher than for the standard 10-item AUDIT (0.87). A single, sex-specific question about binge drinking (modified AUDIT question 3) had a sensitivity of 0.69 and specificity of 0.94, whereas the standard AUDIT question 3 was specific (0.96) but relatively insensitive (0.45). Conclusions: The standard and sex-specific AUDIT-Cs are effective screening tests for past-year hazardous drinking and/or active alcohol abuse or dependence in female patients in a VA study. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv,Vet Hlth Adm, Dept Vet Affairs,Vet Womens Alcohol Problems Stud, Seattle, WA 98108 USA. Univ Washington, Primary & Specialty Med Care Serv, Seattle, WA 98108 USA. Univ Washington, Ctr Excellence Subst Abuse Treatment & Educ, Seattle, WA 98108 USA. Univ Washington, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98108 USA. RP Bradley, KA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv,Vet Hlth Adm, Dept Vet Affairs,Vet Womens Alcohol Problems Stud, Mail Stop 152,1660 S Columbian Way, Seattle, WA 98108 USA. RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 FU NIAAA NIH HHS [K23 AA00313] NR 59 TC 256 Z9 258 U1 4 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 14 PY 2003 VL 163 IS 7 BP 821 EP 829 DI 10.1001/archinte.163.7.821 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 669EZ UT WOS:000182340100008 PM 12695273 ER PT J AU Strate, LL Orav, EJ Syngal, S AF Strate, LL Orav, EJ Syngal, S TI Early predictors of severity in acute lower intestinal tract bleeding SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-College-of-Gastroenterology CY OCT 16-18, 2000 CL NEW YORK, NEW YORK SP Amer Coll Gastroenterol ID UPPER-GASTROINTESTINAL HEMORRHAGE; URGENT COLONOSCOPY; DIAGNOSIS; VALIDATION; MANAGEMENT; GUIDELINES; MORTALITY; PATIENT; SIGNS; CARE AB Background: Identification of high-risk patients with lower intestinal tract bleeding (LIB) is challenging, and prognostic factors have not been clearly defined. The aim of this study was to determine risk factors for severe acute LIB. Methods: A total of 252 consecutive patients admitted with acute LIB were identified. Data were collected on 24 clinical factors available in the first 4 hours of evaluation. The outcome was severe bleeding, which was defined as continued bleeding within the first 24 hours of hospitalization (transfusion of greater than or equal to2 units of blood and/or hematocrit decrease of greater than or equal to20%) and/or recurrent bleeding after 24 hours of stability (additional transfusions, further hematocrit decrease of greater than or equal to20%, or readmission for LIB within 1 week of discharge). Results: Severe LIB occurred in 123 patients (49%). Independent correlates of severe bleeding were as follows: heart rate, greater than or equal to100/min (odds ratio [OR], 3.67; 95% confidence interval [CI], 1.78-7.57); systolic blood pressure, less than or equal to115 mm Hg (OR, 3.45; 95% CI, 1.54-7.72); syncope (OR, 2.82; 95% CI, 1.06-7.46); nontender abdominal examination (OR, 2.43; 95% CI, 1.22-4.85); bleeding per rectum during the first 4 hours of evaluation (OR, 2.32; 95% CI, 1.28-4.20); aspirin use (OR, 2.07; 95% CI, 1.12-3.82); and more than 2 active comorbid conditions (OR, 1.93; 95% CI, 1.08-3.44). Conclusion: Clinical data available on initial evalua tion can be used to identify patients at risk for severe LIB, who may benefit most from urgent intervention. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Dept Gen Med, Boston, MA 02115 USA. RP Strate, LL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med, Div Gastroenterol, 44 Binney St, Boston, MA 02115 USA. FU AHRQ HHS [HS00020]; NIDDK NIH HHS [5T32DK0753315] NR 34 TC 67 Z9 70 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 14 PY 2003 VL 163 IS 7 BP 838 EP 843 DI 10.1001/archinte.163.7.838 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 669EZ UT WOS:000182340100010 PM 12695275 ER PT J AU Akiyama, Y Caucheteux, S Iwamoto, Y Guimezanes, A Kanellopoulos-Langevin, C Benichou, G AF Akiyama, Y Caucheteux, S Iwamoto, Y Guimezanes, A Kanellopoulos-Langevin, C Benichou, G TI Evidence for transplantation tolerance to non-inherited maternal antigens using a MHC class I transgenic mouse model SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Paris 06, Paris, France. Univ Paris 07, Paris, France. CNRS, Inst Jacques Monod, Paris, France. CIML, Marseille, France. CNRS, INSERM, Marseille, France. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C62 EP C62 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000289 ER PT J AU Barrington, RA Pozdnyakova, O Zafari, M Benjamin, C Carroll, MC AF Barrington, RA Pozdnyakova, O Zafari, M Benjamin, C Carroll, MC TI Importance of CD21/CD35 and Fc gamma RIIB in B lymphocyte memory SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Ctr Blood Res, Boston, MA 02115 USA. Biogen Inc, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C79 EP C79 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000363 ER PT J AU Caucheteux, SM Akiyama, Y Vernochet, C Gendron, MC Guimezanes, A Benichou, G Kanellopoulos-Langevin, C AF Caucheteux, SM Akiyama, Y Vernochet, C Gendron, MC Guimezanes, A Benichou, G Kanellopoulos-Langevin, C TI Exposure to Non-Inherited Maternal Antigens affects mouse fetal and neonatal T cell development, in an MHC class I transgenic mouse model SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 CNRS, Inst Jacques Monod, F-75005 Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. CIML, Marseille, France. NR 0 TC 0 Z9 0 U1 2 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C63 EP C63 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000290 ER PT J AU Das, S Husain, Z Alper, CA Dubey, DP AF Das, S Husain, Z Alper, CA Dubey, DP TI Differential regulation of cytokine production and cytotoxic activity of NK cells by crosslinking of inhibitory and activation receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C83 EP C83 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000383 ER PT J AU Eastcott, JW Smith, DJ Taubman, MA AF Eastcott, JW Smith, DJ Taubman, MA TI Development of T-like cells in nude rats: flow cytometry and proliferation SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C5 EP C6 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000026 ER PT J AU Gruber, A Chalmers, AS Popov, S Ruprecht, RM AF Gruber, A Chalmers, AS Popov, S Ruprecht, RM TI Functional aspects of binding of monoclonal antibody DCN46 to DC-SIGN on Dendritic Cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C201 EP C201 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000931 ER PT J AU Husain, Z Holodick, N Day, C Szymanski, I Alper, CA AF Husain, Z Holodick, N Day, C Szymanski, I Alper, CA TI Overexpression of caspase-1 gene and increased apoptosis of CD19+B cells in IgA-deficient patients SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Ctr Blood Res, Boston, MA 02115 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C210 EP C210 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000971 ER PT J AU Montfort, MJ Bouwer, HGA Hinrichs, DJ AF Montfort, MJ Bouwer, HGA Hinrichs, DJ TI CD40 deficiency impacts the quality of memory CD8 T cells generated in response to infection with Listeria monocytogenes SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C257 EP C258 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001200 ER PT J AU Niess, JH Brand, S Gu, XB Jung, S Littman, DR Reinecker, HC AF Niess, JH Brand, S Gu, XB Jung, S Littman, DR Reinecker, HC TI Intestinal antigen sampling dendritic cells are characterized by the expression of the fractalkine receptor CX3CR1 SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NYU, Sch Med, HHMI, Skirball Inst, New York, NY USA. RI Niess, Jan /E-8361-2017 OI Niess, Jan /0000-0001-6902-5650 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C231 EP C231 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001073 ER PT J AU Noso, S Hattori, K Wakeland, EK Flavell, RA Barbour, G Haskins, K Lund, T Hattori, M AF Noso, S Hattori, K Wakeland, EK Flavell, RA Barbour, G Haskins, K Lund, T Hattori, M TI Transfer of BDC2.5 T cell clones into neonatal NOD mice show that type 1 diabetogenic genes, Idd1a, b and c, control the onset of diabetes in time-dependent manner SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Texas, Dallas, TX 75230 USA. Yale Univ, New Haven, CT USA. Barbara Davis Ctr, Denver, CO USA. UCL, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C182 EP C182 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000841 ER PT J AU Schmidt-Supprian, M Pasparakis, M Rajewsky, K AF Schmidt-Supprian, M Pasparakis, M Rajewsky, K TI Analysis of the function of the classical NF-kappa B activation pathway in T cells by conditional gene targeting of IKK2 and NEMO SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. EMBL, Mouse Biol Programme, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C222 EP C222 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001029 ER PT J AU Seedhom, M Garcea, RL Carroll, MC Szomolanyi-Tsuda, E AF Seedhom, M Garcea, RL Carroll, MC Szomolanyi-Tsuda, E TI Impaired T cell-dependent and T cell-independent antibody responses to polyomavirus by CR1/CR2-deficient B cells SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Massachusetts, Worcester, MA 01655 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C160 EP C160 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000741 ER PT J AU Shepley, BAM Prabhala, R AF Shepley, BAM Prabhala, R TI You are the doctor SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Avon Middle High Sch, Avon, MA 02322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C280 EP C280 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001307 ER PT J AU Tzachanis, D Lafuente, EM Li, LQ Berezovskaya, A Freeman, GJ Nadler, LM Boussiotis, VA AF Tzachanis, D Lafuente, EM Li, LQ Berezovskaya, A Freeman, GJ Nadler, LM Boussiotis, VA TI The evolutionarily conserved, secreted protein Twisted Gastrulation (TSG) is an inducible selective inhibitor of preactivated T lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C229 EP C230 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001067 ER PT J AU Verschoor, A Brockman, MA Gadjeva, M Knipe, DM Carroll, MC AF Verschoor, A Brockman, MA Gadjeva, M Knipe, DM Carroll, MC TI Myeloid cells are the critical source of complement C3 in adaptive immunity to peripheral HSV infection SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C162 EP C163 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000750 ER PT J AU Wang, XH Yang, PA Wu, Q Zhou, JL Li, LN Powell, JK Zhang, HG Mountz, JD Hsu, HC AF Wang, XH Yang, PA Wu, Q Zhou, JL Li, LN Powell, JK Zhang, HG Mountz, JD Hsu, HC TI Defective activation-induced cell death (AICD) in T cells from aged mice is associated with altered PI-3 kinase/Akt signaling pathway SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C225 EP C225 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367001045 ER PT J AU Zhang, HG Liu, ZY Hsu, HC Grizzle, WE Yang, PA Wu, Q Mountz, JD AF Zhang, HG Liu, ZY Hsu, HC Grizzle, WE Yang, PA Wu, Q Mountz, JD TI Establishment of a novel tumor cell line (2299) derived from a tumor in IRF-1(-/-) and CD95LP-Luc transgene mouse SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C76 EP C76 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000350 ER PT J AU Zhang, M Austin, WA Verna, N Chiu, I Hung, R Reid, R Xu, M Alicot, EM Kobzik, L Hechtman, HB Moore, JD Carroll, MC AF Zhang, M Austin, WA Verna, N Chiu, I Hung, R Reid, R Xu, M Alicot, EM Kobzik, L Hechtman, HB Moore, JD Carroll, MC TI Complement receptors CD21/CD35 are important in shaping the natural antibody repertoire SO FASEB JOURNAL LA English DT Meeting Abstract CT 90th Annual Meeting of the American-Association-for-Immunologists CY MAY 06-10, 2003 CL DENVER, COLORADO SP American Assoc Immunologists C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 14 PY 2003 VL 17 IS 7 SU S BP C110 EP C111 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 669TR UT WOS:000182367000512 ER PT J AU Ho, A Lievore, A Patierno, S Kohlmeier, SE Tonini, M Sternini, C AF Ho, A Lievore, A Patierno, S Kohlmeier, SE Tonini, M Sternini, C TI Neurochemically distinct classes of myenteric neurons express the mu-opioid receptor in the guinea pig ileum SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE ascending excitatory neurons; interneurons; descending neurons; motor neurons; interstitial cells of Cajal ID PRIMARY AFFERENT NEURONS; SMALL-INTESTINE; INTERSTITIAL-CELLS; GASTROINTESTINAL-TRACT; ENDOGENOUS OPIOIDS; MOLECULAR-BIOLOGY; ENTERIC NEURONS; CAJAL; MOTILITY; PEPTIDES AB The mu-opioid receptor ( LOR), which mediates many of the opioid effects in the nervous system, is expressed by enteric neurons. The aims of this study were to determine whether 1) different classes of myenteric neurons in the guinea pig ileum contain muOR immunoreactivity by using double- and triple-labeling immunofluorescence and confocal microscopy, 2) muOR immunoreactivity is localized to enteric neurons immunoreactive for the endogenous opioid enkephalin, and 3) muOR immunoreactivity is localized to interstitial cells of Cajal visualized by c-kit. In the myenteric plexus, 50% of muOR-immunoreactive neurons contained choline acetyltransferase (ChAT) immunoreactivity, whereas about 43% of ChAT-immunoreactive neurons were LOR immunoreactive. Approximately 46% of muOR myenteric neurons were immunoreactive for vasoactive intestinal polypeptide (VIP), and about 31% were immunoreactive for nitric oxide synthase (NOS). muOR immunoreactivity was found in about 68% of VIP-containing neurons and 60% of NOS-immunoreactive neurons. Triple labeling showed that about 32% of muOR neurons contained VIP and ChAT immunoreactivities. The endogenous opioid enkephalin (ENK) was observed in about 30% of muOR neurons; conversely, 48% of ENK neurons contained muOR immunoreactivity. muOR was not detected in neurons containing calbindin, nor in interstitial cells of Cajal. muOR-immunoreactive fibers formed a dense network around interstitial cells of Cajal in the deep muscular plexus. This study demonstrates that muOR is expressed by neurochemically distinct classes of myenteric neurons that are likely to differ functionally, is colocalized with the endogenous opioid ENK, and is not expressed by interstitial cells of Cajal. (C) 2003 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Pavia, Inst Pharmacol, I-27100 Pavia, Italy. Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. CURE Digest Dis Res Ctr, Div Digest Dis, Los Angeles, CA 90073 USA. RP Sternini, C (reprint author), CURE Digest Dis Res Ctr, Div Digest Dis, Bldg 115,Room 224,11301 Wilshire Blvd,VAGLAHS, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK 35740, DK 41301, DK 54155] NR 58 TC 25 Z9 25 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 14 PY 2003 VL 458 IS 4 BP 404 EP 411 DI 10.1002/cne.10606 PG 8 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 657BF UT WOS:000181645000008 PM 12619074 ER PT J AU Goldstein, LE Muffat, JA Cherny, RA Moir, RD Ericsson, MH Huang, XD Mavros, C Coccia, JA Faget, KY Fitch, KA Masters, CL Tanzi, RE Chylack, LT Bush, AI AF Goldstein, LE Muffat, JA Cherny, RA Moir, RD Ericsson, MH Huang, XD Mavros, C Coccia, JA Faget, KY Fitch, KA Masters, CL Tanzi, RE Chylack, LT Bush, AI TI Cytosolic beta-amyloid deposition and supranuclear cataracts in lenses from people with Alzheimer's disease SO LANCET LA English DT Article ID ALPHA-B-CRYSTALLIN; A-BETA; OXIDATIVE STRESS; PROTEIN; PRECURSOR; BRAIN; NEUROTOXICITY; TRANSPARENCY; ACCUMULATION; PEPTIDE AB Background Pathological hallmarks of Alzheimer's disease include cerebral beta-amyloid (Abeta) deposition, amyloid accumulation, and neuritic plaque formation. We aimed to investigate the hypothesis that molecular pathological findings associated with Alzheimer's disease overlap in the lens and brain. Methods We obtained postmortem specimens of eyes and brain from nine individuals with Alzheimer's disease and eight controls without the disorder, and samples of primary aqueous humour from three people without the disorder who were undergoing cataract surgery. Dissected lenses were analysed by slit-lamp stereophotomicroscopy, western blot, tryptic-digest/mass spectrometry electrospray ionisation, and anti-Abeta surface-enhanced laser desorption ionisation (SELDI) mass spectrometry, immunohistochemistry, and immunogold electron microscopy. Aqueous humour was analysed by anti-Abeta SELDI mass spectrometry. We did binding and aggregation studies to investigate Abeta-lens protein interactions. Findings We identified Abeta1-40 and Abeta1-42 in lenses from people with and without Alzheimer's disease at concentrations comparable with brain, and Abeta1-40 in primary aqueous humour at concentrations comparable with cerebrospinal fluid. Abeta accumulated in lenses from individuals with Alzheimer's disease as electron-dense deposits located exclusively in the cytoplasm of supranuclear/cleep cortical lens fibre cells (n=4). We consistently saw equatorial supranuclear cataracts in lenses from people with Alzheimer's disease (n=9) but not in controls (n = 8). These supranuclear cataracts colocalised with enhanced Abeta immunoreactivity and birefringent Congo Red staining. Synthetic Abeta bound alphaB-crystallin, an abundant cytosolic lens protein. Abeta promoted lens protein aggregation that showed protofibrils, birefringent Congo Red staining, and Abeta/alphaB-crystallin coimmunoreactivity. Interpretation Abeta is present in the cytosol of lens fibre cells of people with Alzheimer's disease. Lens Abeta might promote regionally-specific lens protein aggregation, extracerebral amyloid formation, and supranuclear cataracts. C1 Massachusetts Gen Hosp, Genet & Aging Res Univ, Lab Oxidat Biol, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Ctr Ophthalm Res, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Ecole Normale Super, Dept Bioengn, Cachan, France. Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Univ Melbourne, Mental Hlth Res Inst Victoria, Parkville, Vic 3052, Australia. Harvard Univ, Sch Med, Electron Microscope Facil, Boston, MA 02115 USA. RP Bush, AI (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Univ, Lab Oxidat Biol, Bldg 114,16th St, Charlestown, MA 02129 USA. RI Muffat, Julien/P-2298-2014; Bush, Ashley/A-1186-2007 OI Bush, Ashley/0000-0001-8259-9069 FU NIA NIH HHS [AG005134-19, AG12686] NR 30 TC 164 Z9 170 U1 0 U2 17 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 12 PY 2003 VL 361 IS 9365 BP 1258 EP 1265 DI 10.1016/S0140-6736(03)12981-9 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 666DM UT WOS:000182161600010 PM 12699953 ER PT J AU Sugimoto, H Hamano, Y Charytan, D Cosgrove, D Kieran, M Sudhakar, A Kalluri, R AF Sugimoto, H Hamano, Y Charytan, D Cosgrove, D Kieran, M Sudhakar, A Kalluri, R TI Neutralization of circulating vascular endothelial growth factor (VEGF) by anti-VEGF antibodies and soluble VEGF receptor 1 (sFlt-1) induces proteinuria SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CONGENITAL NEPHROTIC SYNDROME; GLOMERULAR SLIT DIAPHRAGM; REMNANT KIDNEY MODEL; IMPAIRED ANGIOGENESIS; GRADED DEXTRANS; AMNIOTIC-FLUID; FACTOR FAMILY; PERMEABILITY; PREECLAMPSIA; NEPHRIN AB There are about 2.5 million glomeruli in the kidneys each consisting of a barrel of glomerular basement membrane surrounded by glomerular endothelial cells on the inside and glomerular epithelial cells with established foot processes (podocytes) on the outside. Defects in this filtration apparatus lead to glomerular vascular leak or proteinuria. The role of vascular endothelial growth factor (VEGF) in the regulation of glomerular vascular permeability is still unclear. Recent studies indicate that patients receiving anti-VEGF antibody therapy may have an increased incidence of proteinuria. In a different setting, pregnancies complicated by preeclampsia are associated with elevated soluble VEGF receptor 1 protein (sFIt-1), endothelial cell dysfunction and proteinuria. These studies suggest that neutralization of physiologic levels of VEGF, a key endothelial survival factor, may lead to proteinuria. In the present study, we evaluated the potential of anti-VEGF neutralizing antibodies and sFlt-1 in the induction of proteinuria. Our studies demonstrate that anti-VEGF antibodies and sFIt-1 cause rapid glomerular endothelial cell detachment and hypertrophy, in association with down-regulation of nephrin, a key epithelial protein in the glomerular filtration apparatus. These studies suggest that down-regulation or neutralization of circulating VEGF may play an important role in the induction of proteinuria in various kidney diseases, some forms of cancer therapy and also in women with preeclampsia. C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Program Matrix Biol, Div Gastroenterol, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Program Matrix Biol, Div Nephrol, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Program Matrix Biol, Div Nephrol, Ctr Canc, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Program Matrix Biol, Div Gastroenterol, Ctr Canc, Boston, MA 02215 USA. Boys Town Natl Res Hosp, Gene Express Lab, Omaha, NE 68131 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. RP Kalluri, R (reprint author), Harvard Univ, Sch Med, DANA 514,330 Brookline Ave, Boston, MA 02215 USA. RI Kalluri, Raghu/E-2677-2015; OI Kalluri, Raghu/0000-0002-2190-547X; Kieran, Mark/0000-0003-2184-7692 FU NIDDK NIH HHS [DK 55001, DK-51711, T32DK07199-25] NR 56 TC 347 Z9 365 U1 2 U2 10 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 APR 11 PY 2003 VL 278 IS 15 BP 12605 EP 12608 DI 10.1074/jbc.C300012200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500003 PM 12538598 ER PT J AU Cao, C Leng, YM Li, CF Kufe, D AF Cao, C Leng, YM Li, CF Kufe, D TI Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the oxidative stress response SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-DAMAGE; APOPTOTIC RESPONSE; SIGNAL-TRANSDUCTION; CELLULAR-RESPONSE; DROSOPHILA-ABL; ACTIVATION; NUCLEAR; BINDING; GENE; 1-BETA-D-ARABINOFURANOSYLCYTOSINE AB The AbI family of mammalian nonreceptor tyrosine kinases consists of c-Abl and Arg. Recent work has shown that c-Abl and Arg are activated in the cellular response to oxidative stress. The present studies demonstrate that reactive oxygen species (ROS) induce the formation of c-Abl and Arg heterodimers. The results show that the c-Abl SH3 domain binds directly to a proline-rich site (amino acids 567-576) in the Arg C-terminal region. Formation of c-Abl(.)Arg heterodimers also involves direct binding of the Arg Src homology 3 domain to the C-terminal region of c-Abl. The results further demonstrate that the interaction between c-Abl and Arg involves c-Abl-mediated phosphorylation of Arg. The functional significance of the c-Abl-Arg interaction is supported by the demonstration that both c-Abl and Arg are required for ROS-induced apoptosis. These findings indicate that ROS induce c-Abl(.)Arg heterodinters and that both c-Abl and Arg are necessary as effectors in the apoptotic response to oxidative stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beijing Inst Biotechnol, Beijing 100850, Peoples R China. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 48 TC 29 Z9 32 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 2003 VL 278 IS 15 BP 12961 EP 12967 DI 10.1074/jbc.M300058200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500048 PM 12569093 ER PT J AU Medley, QG Buchbinder, EG Tachibana, K Ngo, H Serra-Pages, C Streuli, M AF Medley, QG Buchbinder, EG Tachibana, K Ngo, H Serra-Pages, C Streuli, M TI Signaling between focal adhesion kinase and trio SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEOTIDE EXCHANGE FACTOR; HIGH-AFFINITY BINDING; SRC FAMILY KINASES; TYROSINE PHOSPHORYLATION; CELL-MIGRATION; PROTEIN-KINASE; SERINE/THREONINE KINASE; SERINE PHOSPHORYLATION; SUBSTRATE P130(CAS); NEURITE OUTGROWTH AB The Trio guanine nucleotide exchange factor functions in neural development in Caenorhabditis elegans and Drosophila and in the development of neural tissues and skeletal muscle in mouse. The association of Trio with the Lar tyrosine phosphatase led us to study the role of tyrosine phosphorylation in Trio function using focal adhesion kinase (FAK). The Lar-interacting domain of Trio is constitutively tyrosine-phosphorylated when expressed in COS-7 cells and was highly phosphorylated when it was co-transfected with FAK. Co-precipitation. studies indicated that Trio binds to the FAK amino-terminal domain and to the FAK kinase domain via its SH3 and kinase domains, respectively. Tyrosine-phosphorylated FAK and Trio were present mainly in the detergent-insoluble fraction of cell lysates, and co-expression of Trio and FAK resulted in increased amounts of Trio present in the detergent-insoluble fraction. Immunofluorescence of cells co-transfected with FAK and Trio revealed significant co-localization. of the proteins at the cell periphery, indicating that they form a stable complex in vivo. A FAK phosphorylation site, tyrosine residue 2737, was identified in subdomain I of the Trio kinase domain. Additionally, in vitro phosphorylation assays and in vivo co-expression studies indicated that Trio enhances FAK kinase activity. These results suggest Trio may be involved in the regulation of focal adhesion dynamics in addition to effecting changes in the actin cytoskeleton. through the activation of Rho family GTPases. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Medley, QG (reprint author), UCB Res, 840 Mem Dr, Cambridge, MA 02139 USA. FU NCI NIH HHS [CA55547, CA75091] NR 51 TC 41 Z9 42 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 APR 11 PY 2003 VL 278 IS 15 BP 13265 EP 13270 DI 10.1074/jbc.M300277200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500085 PM 12551902 ER PT J AU Freedman, SJ Song, HK Xu, YW Sun, ZYJ Eck, MJ AF Freedman, SJ Song, HK Xu, YW Sun, ZYJ Eck, MJ TI Homotetrameric structure of the SNAP-23 N-terminal coiled-coil domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNAPTIC SNARE COMPLEX; CRYSTAL-STRUCTURE; MEMBRANE-FUSION; SYNTAXIN 1A; PROTEIN; EXOCYTOSIS; IDENTIFICATION; ASSOCIATION; RECEPTORS; INSIGHTS AB SNARE proteins mediate intracellular membrane fusion by forming a coiled-coil complex to merge opposing membranes. A "fusion-active" neuronal SNARE complex is a parallel four-helix bundle containing two coiled-coil domains from SNAP-25 and one coiled-coil domain each from syntaxin-1a and VAMP-2. "Prefusion" assembly intermediate complexes can also form from these SNAREs. We studied the N-terminal coiled-coil domain of SNAP-23 (SNAP-23N), a non-neuronal homologue of SNAP-25, and its interaction with other coiled-coil domains. SNAP-23N can assemble spontaneously with the coiled-coil domains from SNAP-23C, syntaxiln-4. and VAMP-3 to form a heterotetrameric complex. Unexpectedly, pure SNAP-23N crystallizes as a coiled-coil homotetrameric complex. The four helices have a parallel orientation and are symmetrical about the long axis. The complex is stabilized through the interaction of conserved hydrophobic residues comprising the a and d positions of the coiled-coil heptad repeats. In addition, a central, highly conserved glutamine residue (Gln-48) is buried within the interface by hydrogen bonding between glutamine side chains derived from adjacent subunits and to solvent molecules. A comparison of the SNAP-23N structure to other SNARE complex structures reveals how a simple coiled-coil motif can form diverse SNARE complexes. C1 Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02115 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. RP Freedman, SJ (reprint author), Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, 41 Ave Louis Pasteur, Boston, MA 02115 USA. RI Song, Hyun Kyu/D-6763-2016 OI Song, Hyun Kyu/0000-0001-5684-4059 FU PHS HHS [K08] NR 33 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 11 PY 2003 VL 278 IS 15 BP 13462 EP 13467 DI 10.1074/jbc.M210483200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 666RD UT WOS:000182189500109 PM 12556468 ER PT J AU Moore, B Zhou, L Rolland, F Hall, Q Cheng, WH Liu, YX Hwang, I Jones, T Sheen, J AF Moore, B Zhou, L Rolland, F Hall, Q Cheng, WH Liu, YX Hwang, I Jones, T Sheen, J TI Role of the Arabidopsis glucose sensor HXK1 in nutrient, light, and hormonal signaling SO SCIENCE LA English DT Article ID GENE-EXPRESSION; SACCHAROMYCES-CEREVISIAE; CATABOLITE REPRESSION; HIGHER-PLANTS; TRANSDUCTION; RESTRICTION; HEXOKINASE; GENOME AB Glucose modulates many vital processes in photosynthetic plants. Analyses of Arabidopsis glucose insensitive2 (gin2) mutants de. ne the physiological functions of a specific hexokinase (HXK1) in the plant glucose-signaling network. HXK1 coordinates intrinsic signals with extrinsic light intensity. HXK1 mutants lacking catalytic activity still support various signaling functions in gene expression, cell proliferation, root and in florescence growth, and leaf expansion and senescence, thus demonstrating the uncoupling of glucose signaling from glucose metabolism. The gin2 mutants are also insensitive to auxin and hypersensitive to cytokinin. Plants use HXK as a glucose sensor to interrelate nutrient, light, and hormone signaling networks for controlling growth and development in response to the changing environment. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu NR 26 TC 511 Z9 541 U1 11 U2 104 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 APR 11 PY 2003 VL 300 IS 5617 BP 332 EP 336 DI 10.1126/science.1080585 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665RQ UT WOS:000182135400058 PM 12690200 ER PT J AU Grossman, SR Deato, ME Brignone, C Chan, HM Kung, AL Tagami, H Nakatani, Y Livingston, DM AF Grossman, SR Deato, ME Brignone, C Chan, HM Kung, AL Tagami, H Nakatani, Y Livingston, DM TI Polyubiquitination of p53 by a ubiquitin ligase activity of p300 SO SCIENCE LA English DT Article ID PROTEASOME-MEDIATED DEGRADATION; PROTEIN; BINDING; MDM2; COMPLEXES; PROMOTES AB Rapid turnover of the tumor suppressor protein p53 requires the MDM2 ubiquitin ligase, and both interact with p300-CREB-binding protein transcriptional coactivator proteins. p53 is stabilized by the binding of p300 to the oncoprotein E1A, suggesting that p300 regulates p53 degradation. Purified p300 exhibited intrinsic ubiquitin ligase activity that was inhibited by E1A. In vitro, p300 with MDM2 catalyzed p53 polyubiquitination, whereas MDM2 catalyzed p53 monoubiquitination. E1A expression caused a decrease in polyubiquitinated but not monoubiquitinated p53 in cells. Thus, generation of the polyubiquitinated forms of p53 that are targeted for proteasome degradation requires the intrinsic ubiquitin ligase activities of MDM2 and p300. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. OI Kung, Andrew/0000-0002-9091-488X FU NCI NIH HHS [CA15751] NR 20 TC 335 Z9 342 U1 0 U2 8 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 APR 11 PY 2003 VL 300 IS 5617 BP 342 EP 344 DI 10.1126/science.1080386 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665RQ UT WOS:000182135400061 PM 12690203 ER PT J AU Ross, AM Anupindi, SA Kleinman, RE Ryan, DP Balis, UJ AF Ross, AM Anupindi, SA Kleinman, RE Ryan, DP Balis, UJ TI A 14-year-old boy with ulcerative colitis, primary sclerosing cholangitis, and partial duodenal obstruction - Cholangiocarcinoma, with duodenal stricture SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHRONIC-PANCREATITIS; SURGICAL-TREATMENT; DISEASE; CHILDREN; COMPLICATION; POPULATION; CARCINOMA; SURVIVAL; RISK C1 Hasbro Childrens Hosp, Dept Pediat, Providence, RI USA. Brown Univ, Sch Med, Dept Pediat, Providence, RI USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ross, AM (reprint author), Hasbro Childrens Hosp, Dept Pediat, Providence, RI USA. NR 35 TC 5 Z9 5 U1 1 U2 2 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 APR 10 PY 2003 VL 348 IS 15 BP 1464 EP 1476 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 665CU UT WOS:000182102700008 PM 12686704 ER PT J AU Wolkowitz, OM Kramer, JH Reus, VI Costa, MM Yaffe, K Walton, P Raskind, M Peskind, E Newhouse, P Sack, D De Souza, E Sadowsky, C Roberts, E AF Wolkowitz, OM Kramer, JH Reus, VI Costa, MM Yaffe, K Walton, P Raskind, M Peskind, E Newhouse, P Sack, D De Souza, E Sadowsky, C Roberts, E CA DHEA-Alzheimer's Dis Collborative TI DHEA treatment of Alzheimer's disease - A randomized, double-blind, placebo-controlled study SO NEUROLOGY LA English DT Article ID DEHYDROEPIANDROSTERONE DHEA; SENILE DEMENTIA; SULFATE DHEAS; DIFFERENTIATION; ASSOCIATION; WOMEN AB Objective: To compare the efficacy and tolerability of dehydroepiandrosterone (DHEA) vs placebo in AD. Method: Fifty-eight subjects with AD were randomized to 6 month's treatment with DHEA (50 mg per os twice a day; n 28) or placebo (n = 30) in a multi-site, double-blind pilot trial. Primary efficacy measures assessed cognitive functioning (the AD Assessment Scale-Cognitive [ADAS-Cog]) and observer-based ratings of overall changes in severity (the Clinician's Interview-Based Impression of Change with Caregiver Input [CIBIC-Plus]). At baseline, 3 months, and 6 months, the ADAS-Cog was administered, and at 3 and 6 months, the CIBIC-Plus was administered. The 6-month time point was the primary endpoint. Results: Nineteen DHEA-treated subjects and 14 placebo-treated subjects completed the trial. DHEA was relatively well-tolerated. DHEA treatment, relative to placebo, was not associated with improvement in ADAS-Cog scores at month 6 (last observation carried forward; p = 0.10); transient improvement was noted at month 3 (p = 0.014; cutoff for Bonferroni significance = 0.0125). No difference between treatments was seen on the CIBIC-Plus at either the 6-month or the 3-month time points. Conclusions: DHEA did not significantly improve cognitive performance or overall ratings of change in severity in this small-scale pilot study. A transient effect on cognitive performance may have been seen at month 3, but narrowly missed significance. C1 Univ Calif San Francisco, Sch Med, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Ctr Neurobiol & Psychiat, San Francisco, CA 94143 USA. Univ Washington, Sch Med, Alzheimers Dis Res Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Vermont, Coll Med, Dept Psychiat, Burlington, VT 05405 USA. Inst Psychopharmacol Res, Cerritos, CA USA. Neurocrine Biosci Inc, San Diego, CA USA. Premier Res Inst, W Palm Beach, FL USA. City Hope Natl Med Ctr, Beckman Res Inst, Dept Neurobiochem, Duarte, CA 91010 USA. Clin Studies Ltd, Ft Myers, FL USA. Clin Studies Ltd, Boynton Beach, FL USA. So New Jersey Med Inst, Stratford, NJ USA. RP Wolkowitz, OM (reprint author), 401 Parnassus Ave,Box F-0984, San Francisco, CA 94143 USA. RI Wolkowitz, Owen/J-6649-2013; Newhouse, Paul/J-4597-2014; reus, victor/I-7923-2015 OI Wolkowitz, Owen/0000-0003-0655-5042; reus, victor/0000-0002-8193-5697 FU NIA NIH HHS [1R4 1AG NS13334-01] NR 29 TC 61 Z9 63 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 APR 8 PY 2003 VL 60 IS 7 BP 1071 EP 1076 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 675EP UT WOS:000182680300004 PM 12682308 ER PT J AU Bretsky, P Guralnik, JM Launer, L Albert, M Seeman, TE AF Bretsky, P Guralnik, JM Launer, L Albert, M Seeman, TE TI The role of APOE-epsilon 4 in longitudinal cognitive decline - MacArthur studies of successful aging SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E EPSILON-4; SPORADIC ALZHEIMERS-DISEASE; APOE GENOTYPE; COMMUNITY RESIDENTS; FOLLOW-UP; ALLELE; DEMENTIA; POPULATION; PERFORMANCE; RISK AB Background: While a genetic risk factor for late-onset AD, the effects of the is an element of4 allele of the APOE gene on cognitive functioning more generally remain unclear. Objective: To assess the role of the is an element of4 allele of the APOE gene in longitudinal cognitive decline. Methods: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. Results: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-is an element of4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-is an element of4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-is an element of4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. Conclusions: APOE-is an element of4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the is an element of4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory. C1 Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ Calif Los Angeles, Div Geriatr, Dept Med, Los Angeles, CA USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat Gerontol, Boston, MA USA. RP Bretsky, P (reprint author), Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. FU NIA NIH HHS [AG-17265, AG-17056] NR 47 TC 150 Z9 155 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR 8 PY 2003 VL 60 IS 7 BP 1077 EP 1081 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 675EP UT WOS:000182680300005 PM 12682309 ER PT J AU Park, BH Pierce, MC Cense, B de Boer, JF AF Park, BH Pierce, MC Cense, B de Boer, JF TI Real-time multi-functional optical coherence tomography SO OPTICS EXPRESS LA English DT Article ID VIVO HUMAN SKIN; DOPPLER TOMOGRAPHY; BIOLOGICAL TISSUE; BLOOD-FLOW; POLARIZATION; SPEED; VELOCITY; BIREFRINGENCE AB We demonstrate real-time acquisition, processing, and display of tissue structure, birefringence, and blood flow in a multi-functional optical coherence tomography (MF-OCT) system. This is accomplished by efficient data processing of the phase-resolved inteference patterns without dedicated hardware or extensive modification to the high-speed fiber-based OCT system. The system acquires images of 2048 depth scans per second, covering an area of 5 mm in width x 1.2 mm in depth with real-time display updating images in a rolling manner 32 times each second. We present a video of the system display as images from the proximal nail fold of a human volunteer are taken. (C) 2003 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Park, BH (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. EM hylepark@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012 OI de Boer, Johannes/0000-0003-1253-4950 NR 27 TC 91 Z9 92 U1 1 U2 8 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 APR 7 PY 2003 VL 11 IS 7 BP 782 EP 793 DI 10.1364/OE.11.000782 PG 12 WC Optics SC Optics GA 665EE UT WOS:000182106000017 PM 19461791 ER PT J AU Weng, XJ Yan, YL Shu, HZ Wang, JW Jiang, SB Luo, LM AF Weng, XJ Yan, YL Shu, HZ Wang, JW Jiang, SB Luo, LM TI A vectorized Monte Carlo code for radiotherapy treatment planning dose calculation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CALCULATION ALGORITHM; BEAM; PHOTON; SIMULATION; VMC AB How to speed up Monte Carlo (MC) simulation in dose calculation without losing its intrinsic accuracy is one of the key issues of making a clinical MC dose engine. In this study we intensively investigated a special parallel computation technique, the vectorization technique, to boost simulation efficiency on a personal computer (PC) without extra hardware investment. A MC code, dose planning method (DPM), was extensively modified into a vectorized code, V-DPM, using the streaming single-instruction-multiple-data extension (SSE) parallel computation model. Comparative simulations were conducted for typical simulation cases in both DPM and V-DPM codes. We found that in every case the V-DPM code runs 1.5 times faster than the DPM code with variance of 0.6%. C1 SE Univ, Dept Biol & Med Engn, Lab Image Sci & Technol, Nanjing 210096, Peoples R China. Univ Arkansas Med Sci, Dept Radiat Oncol, Little Rock, AR 72205 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Weng, XJ (reprint author), SE Univ, Dept Biol & Med Engn, Lab Image Sci & Technol, Nanjing 210096, Peoples R China. NR 20 TC 3 Z9 3 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD APR 7 PY 2003 VL 48 IS 7 BP N111 EP N120 AR PII S0031-9155(03)56040-7 DI 10.1088/0031-9155/48/7/401 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 669YL UT WOS:000182379200011 PM 12701898 ER PT J AU Soncin, F Zhang, XF Chu, BY Wang, XZ Asea, A Stevenson, MA Sacks, DB Calderwood, SK AF Soncin, F Zhang, XF Chu, BY Wang, XZ Asea, A Stevenson, MA Sacks, DB Calderwood, SK TI Transcriptional activity and DNA binding of heat shock factor-1 involve phosphorylation on threonine 142 by CK2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HSF-1; CK2; transcriptional regulation; heat shock ID CASEIN KINASE-II; PROTEIN-KINASE; ACTIVATION; EXPRESSION; GENE; CALMODULIN; STRESS; CELLS AB Heat shock factor-1 (HSF-1) is the regulator of hsp molecular chaperone transcription, although the intracellular mechanisms involved in HSF-1 activation have not been fully elucidated, As HSF1 is activated by heat shock simultaneously with the nuclear translocation of the protein kinase CK2, we have investigated the role of CK2 in HSF1 activation. We demonstrate that HSF-1 is phosphorylated by CK2 on both serine and threonine residues and has characterized a phosphorylation site at threonine 142. Mutation of Thr-142 to alanine (T142A) inhibits trans-activation of the HSP70 gene by HSF1 and in addition inhibits the accumulation of HSF-1 competent to bind heat shock elements in the nucleus. HSF1 activation by heat is correlated with the thermal activation of nuclear CK2 and overexpression of CK2 activates HSF1. Phosphorylation by CK2 on threonine 142 may therefore be an essential step in the thermal activation of latent HSF1 by stresses. (C) 2003 Elsevier Science (USA). All rights reserved. C1 Inst Pasteur, CNRS, F-59021 Lille, France. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Boston Med Ctr, Ctr Mol Stress Response, Dept Med, 88 E Newton St, Boston, MA 02115 USA. RI SONCIN, Fabrice/A-1475-2009; Asea, Alexzander/I-4112-2013; OI Asea, Alexzander/0000-0003-3592-3481; Soncin, Fabrice/0000-0001-6312-0673; Sacks, David/0000-0003-3100-0735 NR 22 TC 42 Z9 55 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 4 PY 2003 VL 303 IS 2 BP 700 EP 706 DI 10.1016/S0006-291X(03)00398-X PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 666LB UT WOS:000182177800047 PM 12659875 ER PT J AU Scorrano, L Oakes, SA Opferman, JT Cheng, EH Sorcinelli, MD Pozzan, T Korsmeyer, SJ AF Scorrano, L Oakes, SA Opferman, JT Cheng, EH Sorcinelli, MD Pozzan, T Korsmeyer, SJ TI BAX and BAK regulation of endoplasmic reticulum Ca2+: A control point for apoptosis SO SCIENCE LA English DT Article ID CYTOCHROME-C; CELL-DEATH; MITOCHONDRIAL DYSFUNCTION; PERMEABILITY TRANSITION; BCL-2; CALCIUM; EXPRESSION; ACTIVATION; MOLECULES; CHANNELS AB BAX and BAK are "multidomain" proapoptotic proteins that initiate mitochondrial dysfunction but also localize to the endoplasmic reticulum (ER). Mouse embryonic. broblasts deficient for BAX and BAK (DKO cells) were found to have a reduced resting concentration of calcium in the ER ([Ca2+](er)) that results in decreased uptake of Ca2+ by mitochondria after Ca2+ release from the ER. Expression of SERCA (sarcoplasmic-endoplasmic reticulum Ca2+ adenosine triphosphatase) corrected [Ca2+](er) and mitochondrial Ca2+ uptake in DKO cells, restoring apoptotic death in response to agents that release Ca2+ from intracellular stores (such as arachidonic acid, C-2-ceramide, and oxidative stress). In contrast, targeting of BAX to mitochondria selectively restored apoptosis to "BH3-only" signals. A third set of stimuli, including many intrinsic signals, required both ER-released Ca2+ and the presence of mitochondrial BAX or BAK to fully restore apoptosis. Thus, BAX and BAK operate in both the ER and mitochondria as an essential gateway for selected apoptotic signals. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol & Med, Boston, MA 02115 USA. Venetian Inst Mol Med, I-35121 Padua, Italy. Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy. RP Korsmeyer, SJ (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Howard Hughes Med Inst, Dana Farber Canc Inst,Dept Pathol & Med, Boston, MA 02115 USA. EM stanley_korsmeyer@dfci.harvard.edu RI Scorrano, Luca/A-6652-2008 OI Scorrano, Luca/0000-0002-8515-8928 FU NCI NIH HHS [R37CA50239]; NHLBI NIH HHS [T32HL07627]; Telethon [TCP02016] NR 31 TC 958 Z9 1004 U1 7 U2 74 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 APR 4 PY 2003 VL 300 IS 5616 BP 135 EP 139 DI 10.1126/science.1081208 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663CP UT WOS:000181988900050 PM 12624178 ER PT J AU Gasic, GP Nicotera, P AF Gasic, GP Nicotera, P TI To die or to sleep, perhaps to dream SO TOXICOLOGY LETTERS LA English DT Article; Proceedings Paper CT 6th Workshop on Apoptosis in Biology and Medicine CY MAY 25-29, 2002 CL VIBO VALENTIA, ITALY DE apoptosis; excitotoxicity; neurodegenerative and psychiatric diseases; synaptic loss; neuronal dysfunction ID APOPTOTIC CELL-DEATH; EXCITATORY AMINO-ACIDS; NEURONAL DEATH; GLUTAMATE ANTAGONISTS; INTRACELLULAR CALCIUM; HIPPOCAMPAL-NEURONS; NITRIC-OXIDE; SCHIZOPHRENIA; INJURY; RAT AB Establishing social contacts is the raison d'(e) over cap tre of neurons throughout their entire life span. To form and retain functional connections, neuronal differentiation and death are ruthlessly regulated in development and kept strictly under control in post-mitotic systems. Derangements in neural networks affect neuronal populations at large. Therefore, failure to retain synaptic connectivity is linked to dysfunction and often followed by neuronal death. Loss of neurons is a predominant feature of neurodegenerative disease. Nevertheless, neuronal cell death is not an obligate requirement for neural dysfunction at the level of distributed circuits or local circuits. Although more or less wide spread neuronal loss can occur after acute insults such as brain ischemia or invasion of the brain by pathogens, neuronal death is a hallmark of end-stage neurodegenerative and psychiatric disease. The relative contributions made by loss of synaptic connectivity versus cell death for these diseases are still debated. Here these processes are discussed in relation to acute and chronic CNS disorders. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Leicester, MRC, Toxicol Unit, Leicester LE1 911N, Leics, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,Athinoula Martinos Ctr Biomed Imaging, Boston, MA USA. RP Nicotera, P (reprint author), Univ Leicester, MRC, Toxicol Unit, POB 138,Lancaster Rd, Leicester LE1 911N, Leics, England. NR 50 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD APR 4 PY 2003 VL 139 IS 2-3 BP 221 EP 227 DI 10.1016/S0378-4274(02)00487-3 PG 7 WC Toxicology SC Toxicology GA 666WA UT WOS:000182198400018 PM 12628758 ER PT J AU Knopp, RH Retzlaff, B Aikawa, K Kahn, SE AF Knopp, RH Retzlaff, B Aikawa, K Kahn, SE TI Management of patients with diabetic hyperlipidemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on High-Density Lipoprotein Cholesterol esterol CY OCT 11-12, 2001 CL NEW YORK, NEW YORK ID CORONARY HEART-DISEASE; INSULIN-RESISTANCE; CHOLESTEROL CONCENTRATIONS; ARTERY DISEASE; RISK-FACTORS; LIPOPROTEIN; TRIGLYCERIDE; HYPERTRIGLYCERIDEMIA; ATHEROSCLEROSIS; FRAMINGHAM AB Hyperlipidemia is commonly observed in patients with type 2 diabetes and is also characteristic of the metabolic syndrome. We discuss the lipoprotein abnormalities in type 2 diabetes and the relation of triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol to insulin resistance and diabetes. We also present a case study of a diabetic woman with hyperlipidemia and coronary artery disease. (C) 2003 by Excerpta Medica, Inc. C1 Univ Washington, Sch Med, NW Lipid Res Clin, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98104 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Sch Med, Div Cardiol, Seattle, WA 98104 USA. RP Knopp, RH (reprint author), Univ Washington, Sch Med, NW Lipid Res Clin, 325 9th Ave,UW Box 359720, Seattle, WA 98104 USA. OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR37 DK 358616]; NIDDK NIH HHS [K24 DK 02654] NR 32 TC 12 Z9 14 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 APR 3 PY 2003 VL 91 IS 7A SU S BP 24E EP 28E DI 10.1016/S0002-9149(02)03385-4 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 664TT UT WOS:000182077800005 PM 12679200 ER PT J AU Petzer, JP Steyn, S Castagnoli, KP Chen, JF Schwarzschild, MA Van der Schyf, CJ Castagnoli, N AF Petzer, JP Steyn, S Castagnoli, KP Chen, JF Schwarzschild, MA Van der Schyf, CJ Castagnoli, N TI Inhibition of monoamine oxidase B by selective adenosine A(2A) receptor antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID MPTP-TREATED MONKEYS; PARKINSONS-DISEASE; CATALYZED OXIDATION; 1,2,3,6-TETRAHYDROPYRIDINE DERIVATIVES; DOPAMINERGIC NEUROTOXICITY; MOUSE MODEL; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE; NEUROPROTECTION; 7-NITROINDAZOLE AB Adenosine receptor antagonists that are selective for the A(2A) receptor subtype (A(2A) antagonists) are under investigation as possible therapeutic agents for the symptomatic treatment of the motor deficits associated with Parkinson's disease (PD). Results of recent studies in the MPTP mouse model of PD suggest that A(2A) antagonists may possess neuroprotective properties. Since monoamine oxidase B (MAO-B) inhibitors also enhance motor function and reduce MPTP neurotoxicity, we have examined the MAO-B inhibiting properties of several A(2A) antagonists and structurally related compounds in an effort to determine if inhibition of MAO-B may contribute to the observed neuroprotection. The results of these studies have established that all of the (E)-8-styryl-xanthinyl derived A(2A) antagonists examined display significant MAO-B inhibitory properties in vitro with K-i values in the low muM to nM range. Included in this series is (E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7-methylxanthine (KW-6002), a potent A(2A) antagonist and neuroprotective agent that is in clinical trials. The results of these studies suggest that MAO-B inhibition may contribute to the neuroprotective potential of A(2A) receptor antagonists such as KW-6002 and open the possibility of designing dual targeting drugs that may have enhanced therapeutic potential in the treatment of PD. (C) 2003 Elsevier Science Ltd. All rights reserved. C1 Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA. EM ncastagn@vt.edu OI Petzer, Jacobus/0000-0002-7114-8120 FU NIEHS NIH HHS [ES10804]; NINDS NIH HHS [NS411083] NR 49 TC 70 Z9 73 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 EI 1464-3391 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR 3 PY 2003 VL 11 IS 7 BP 1299 EP 1310 DI 10.1016/S0968-0896(02)00648-X PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 658HG UT WOS:000181715100016 PM 12628657 ER PT J AU Salzman, NH Ghosh, D Huttner, KM Paterson, Y Bevins, CL AF Salzman, NH Ghosh, D Huttner, KM Paterson, Y Bevins, CL TI Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin SO NATURE LA English DT Article ID INNATE HOST-DEFENSE; PANETH CELL; ANTIMICROBIAL PEPTIDE; EPITHELIAL-CELLS; ALPHA-DEFENSINS; GENE; LOCALIZATION; MACROPHAGES; SECRETION; GROWTH AB Genetically encoded antibiotic peptides are evolutionarily ancient and widespread effector molecules of immune defence(1-3). Mammalian defensins, one subset of such peptides, have been implicated in the antimicrobial defence capacity of phagocytic leukocytes and various epithelial cells(4), but direct evidence of the magnitude of their in vivo effects have not been clearly demonstrated. Paneth cells, specialized epithelia of the small intestinal crypt, secrete abundant alpha-defensins and other antimicrobial polypeptides(5,6) including human defensin 5 (HD-5; also known as DEFA5)(7-9). Although antibiotic activity of HD-5 has been demonstrated in vitro(9,10), functional studies of HD-5 biology have been limited by the lack of in vivo models. To study the in vivo role of HD-5, we developed a transgenic mouse model using a 2.9-kilobase HD-5 minigene containing two HD-5 exons and 1.4 kilobases of 5'-flanking sequence. Here we show that HD-5 expression in these mice is specific to Paneth cells and reflects endogenous enteric defensin gene expression. The storage and processing of transgenic HD-5 also matches that observed in humans. HD-5 transgenic mice were markedly resistant to oral challenge with virulent Salmonella typhimurium. These findings provide support for a critical in vivo role of epithelial-derived defensins in mammalian host defence. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. Med Coll Wisconsin, Dept Pediat, Div Gastroenterol, Milwaukee, WI 53226 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neonatol, Boston, MA 02114 USA. Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Bevins, CL (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bevinsc@ccf.org OI Salzman, Nita/0000-0003-0939-6139 FU NIAID NIH HHS [K08 AI001525, K08 AI001525-03] NR 30 TC 444 Z9 473 U1 2 U2 23 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 3 PY 2003 VL 422 IS 6931 BP 522 EP 526 DI 10.1038/nature01520 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 662TW UT WOS:000181965400038 PM 12660734 ER PT J AU Doong, ML Yang, H AF Doong, ML Yang, H TI Intravenous glucose infusion decreases intracisternal thyrotropin-releasing hormone induced vagal stimulation of gastric acid secretion in anesthetized rats SO NEUROSCIENCE LETTERS LA English DT Article DE autonomic disorders; diabetes; glucose; medullary vagal regulation ID TRH ANALOG; CONSCIOUS RATS; VAGUS NERVE; COMPLEX; NEURONS; HYPERGLYCEMIA; NUCLEUS; LOCALIZATION; EXPRESSION; MOTILITY AB Gastroparesis is a common complication of diabetes attributed to autonomic neuropathy. This study investigated whether acute hyperglycemia influences central thyrotropin-releasing hormone (TRH), a well-established brain medullary vagal stimulus, induced gastric acid secretion in overnight fasted, urethane-anesthetized rats. Intravenous infusion of D-glucose (20%, 30% and 40%) dose dependently reduced intracisternal TRH-induced gastric acid secretion (71 +/- 28 mumol/90,min) by 39%, 90% and 100% respectively. Pretreatment with cholecystokinin(A) (CCKA) receptor antagonist devazepide (1 mg/kg) did not influence the inhibitory effect of intravenous glucose (30%). These results indicate that hyperglycemia may have a central effect to antagonize medullary TRH stimulation of vagal outflow to the stomach. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Great Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, VA Great Los Angeles Healthcare Syst, Dept Med,Div Digest Dis, W Los Angeles Campus,Bldg 115,Room 203,11301 Wils, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-50255] NR 20 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 3 PY 2003 VL 340 IS 1 BP 49 EP 52 DI 10.1016/S0304-3940(03)00068-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 661QR UT WOS:000181901700013 PM 12648756 ER PT J AU Mozaffarian, D Kumanyika, SK Lemaitre, RN Olson, JL Burke, GL Siscovick, DS AF Mozaffarian, D Kumanyika, SK Lemaitre, RN Olson, JL Burke, GL Siscovick, DS TI Cereal, fruit, and vegetable fiber intake and the risk of cardiovascular disease in elderly individuals SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Heart-Associations-Epidemiology-Council CY APR 24, 2002 CL HONOLULU, HAWAII SP Amer Heart Assoc Epidemiol Council ID CORONARY HEART-DISEASE; FOOD FREQUENCY QUESTIONNAIRE; DIETARY FIBER; HEALTH; MEN; MORTALITY; WOMEN; CANCER; REDUCE; DEATH AB Context People older than 65 years are the fastest-growing segment of the population and account for the majority of cardiovascular disease (CVD) morbidity, mortality, and health care expenditures. Additionally, the influence of dietary habits on risk may be less pronounced in elderly persons, when atherosclerosis is more advanced. However, few data address the influence of diet on CVD risk in this population. Objective To determine whether fiber consumption from fruit, vegetable, and cereal sources (including whole grains and bran) is associated with incident CVD in elderly persons. Design Prospective cohort study conducted from 1989 to June 2000. Setting and Participants Population-based, multicenter study among 3588 men and women aged 65 years or older and free of known CVD at baseline in 1989-1990. Usual dietary fiber consumption was assessed at baseline (mean participant age, 72 years) using a 99-item food frequency questionnaire. Main Outcome Measure Incident CVD (combined stroke, ischemic heart disease death, and nonfatal myocardial infarction). Results During 8.6 years mean follow-up, there were 811 incident CVD events. After adjustment for age, sex, education, diabetes, ever smoking, pack-years of smoking, daily physical activity, exercise intensity, alcohol intake, and fruit and vegetable fiber consumption, cereal fiber consumption was inversely associated with incident CVD (P for trend=.02), with 21% lower risk (hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.62-0.99) in the highest quintile of intake, compared with the lowest quintile. In similar analyses, neither fruit fiber intake (P for trend=.98) nor vegetable fiber intake (P for trend=.95) were associated with incident CVD. When CVD events were separately evaluated, higher cereal fiber intake was associated with lower risk of total stroke and ischemic stroke and a trend toward lower risk of ischemic heart disease death. In a post hoc analysis, dark breads such as wheat, rye, or pumpernickel were associated with a lower risk of incident CVD (HR, 0.76; 95% CI, 0.64-0.90) rather than cereal fiber from other sources. Conclusions Cereal fiber consumption late in life is associated with lower risk of incident CVD, supporting recommendations for elderly individuals to increase consumption of dietary cereal fiber. C1 Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98101 USA. Univ Washington, Div Cardiol, Seattle, WA 98101 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Mozaffarian, D (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, 1730 Minor Ave,Suite 1360, Seattle, WA 98101 USA. EM darymd@hotmail.com RI Mozaffarian, Dariush/B-2276-2008 FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086, N01-HC-15103, N01-HC-35129] NR 39 TC 155 Z9 172 U1 0 U2 13 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 APR 2 PY 2003 VL 289 IS 13 BP 1659 EP 1666 DI 10.1001/jama.289.13.1659 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 662JX UT WOS:000181944500029 PM 12672734 ER PT J AU Ramani, S Orlander, JD Strunin, L Barber, TW AF Ramani, S Orlander, JD Strunin, L Barber, TW TI Whither bedside teaching? A focus-group study of clinical teachers SO ACADEMIC MEDICINE LA English DT Article ID CASE PRESENTATIONS; ATTENDING ROUNDS; EXPERIENCE; PHYSICIAN; PATIENT; WARDS AB Purpose. Previous reports document diminishing time spent on bedside teaching, with a shift towards conference rooms and corridors. This study explored faculty's perceptions of the barriers to and their strategies for increasing and improving bedside teaching. Method. Four focus groups consisting of (1) chief residents, (2) residency program directors, (3) skilled bedside teachers, and (4) a convenience group of other Department of Medicine faculty from the Boston University School of Medicine's affiliated hospitals were held in May 1998. Each session lasted 60-90 minutes. Sessions were audiotaped, transcribed, and analyzed using qualitative methods. Results. The most significant barriers reported were (1) declining bedside teaching skills; (2) the aura of bedside teaching, a belief that bedside teachers should possess an almost unattainable level of diagnostic skill that creates intense performance pressure; (3) that teaching is not valued; and (4) erosion of teaching ethic. Focus-group participants suggested the following strategies for addressing these barriers: improve bedside teaching skills through faculty training in clinical skills and teaching methods; reassure clinical faculty that they possess more than adequate bedside skills to educate trainees; establish a learning climate that allows teachers to admit their limitations; and address the undervaluing of teaching on a department level with adequate recognition and rewards for teaching efforts. Skilled teachers, in particular, stated that a bedside teaching ethic could be reestablished by emphasizing its importance and challenging learners to think clinically. Conclusions. Bedside teaching is regarded as valuable. Some barriers may be overcome by setting realistic faculty expectations, providing incentives for teaching faculty, and establishing ongoing faculty development programs. C1 Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, Boston, MA 02118 USA. Boston Med Ctr, Boston, MA USA. Quincy Med Ctr, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP Ramani, S (reprint author), Boston Univ, Sch Med, Gen Internal Med Sect, Dept Med, 720 Harrison Ave,Suite 1108, Boston, MA 02118 USA. NR 26 TC 71 Z9 72 U1 0 U2 10 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD APR PY 2003 VL 78 IS 4 BP 384 EP 390 DI 10.1097/00001888-200304000-00014 PG 7 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 711LC UT WOS:000184741200008 PM 12691971 ER PT J AU Kampman, K Majewska, MD Tourian, K Dackis, C Cornish, J Poole, S O'Brien, C AF Kampman, K Majewska, MD Tourian, K Dackis, C Cornish, J Poole, S O'Brien, C TI A pilot trial of piracetam and ginkgo biloba for the treatment of cocaine dependence SO ADDICTIVE BEHAVIORS LA English DT Article DE cocaine; piracetam; ginkgo biloba; clinical trial ID NEUROPSYCHOLOGICAL DEFICITS; CEREBRAL PERFUSION; MEMORY IMPAIRMENT; DOUBLE-BLIND; EXTRACT; ABUSERS; DEMENTIA; ABNORMALITIES; OUTPATIENTS; VOLUNTEERS AB Background: Chronic cocaine use is associated with cognitive deficits that may reduce the effectiveness of psychosocial treatment and promote relapse in newly abstinent cocaine-dependent patients. Nootropic agents, such as piracetam. and ginkgo biloba, may improve cognitive function and reduce the incidence of relapse in these patients. Methods: This was a 10-week, double-blind, placebo-controlled pilot trial involving 44 cocaine-dependent subjects. Subjects received either piracetam (4.8 g/day), ginkgo biloba (120 mg/day), or placebo. Subjects were required to attain abstinence from cocaine during a 2-week baseline phase demonstrated by providing at least one benzoylecgonine (BE)-negative urine toxicology screen. Outcome measures included treatment retention, urine toxicology screens, Clinical Global Impression (CGI) scores, and results from the Addiction Severity Index (ASI). Results: Ginkgo biloba was not superior to placebo in any outcome measure. Piracetam was associated with more cocaine use and lower CGI scores compared to placebo. Conclusions: Neither piracetam nor ginkgo biloba appears to be a promising medication for the treatment of cocaine dependence. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Univ Penn, Treatment Res Ctr, Dept Psychiat, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Natl Inst Drug Abuse, Bethesda, MD USA. Belmont Ctr, Philadelphia, PA USA. RP Kampman, K (reprint author), Univ Penn, Treatment Res Ctr, Dept Psychiat, Sch Med, 2900 Chestnut St, Philadelphia, PA 19104 USA. EM kampman_k@mail.trc.upenn.edu FU NIDA NIH HHS [K20 DA00238, YO1 DA30012] NR 42 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD APR PY 2003 VL 28 IS 3 BP 437 EP 448 DI 10.1016/S0306-4603(02)00226-5 PG 12 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 658DK UT WOS:000181706200003 PM 12628617 ER PT J AU Schutzer, WE Mader, SL AF Schutzer, WE Mader, SL TI Age-related changes in vascular adrenergic signaling: clinical and mechanistic implications SO AGEING RESEARCH REVIEWS LA English DT Review DE aging; aorta; beta-adrenergic receptors; blood pressure; cyclic AMP; G proteins; G protein receptor kinase; hypertension; isoproterenol; vascular smooth muscle cell; vasorelaxation ID DEPENDENT PROTEIN-KINASE; COUPLED RECEPTOR KINASES; SMOOTH-MUSCLE-CELLS; AGONIST-INDUCED DESENSITIZATION; CYCLIC-AMP METABOLISM; BETA-GAMMA-SUBUNITS; RAT ISOLATED AORTA; ADENYLYL-CYCLASE; BETA(2)-ADRENERGIC RECEPTOR; ANGIOTENSIN-II AB A large and growing segment of the general population are age 65 or older, and this percentage will continue to rise. Primary care of this population has, and is becoming a priority for clinicians. Hypertension, orthostatic hypotension, arterial insufficiency, and atherosclerosis are common disorders in the elderly that lead to significant morbidity and mortality. One common factor to these conditions is an age-related decline in beta-adrenergic receptor (beta-AR)-mediated function and subsequent cAMP generation. Presently, there is no single cellular factor that can explain this age-related decline, and thus the primary cause of this homeostatic imbalance is yet to be identified. However, the etiology is clearly associated with an age-related change in the ability of beta-AR receptor to respond to agonist at the cellular level. This article will review what is presently understood regarding the molecular and biochemical basis of age-impaired beta-AR receptor-mediated signaling. A fundamental understanding of why beta-AR-mediated vasorelaxation is impaired with age will provide new insights and innovative strategies for the management of the multiple clinical disorders that effect older people. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Res Serv, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Sch Med, Portland, OR 97201 USA. RP Mader, SL (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, Res Serv, POB 1034, Portland, OR 97201 USA. NR 146 TC 26 Z9 28 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD APR PY 2003 VL 2 IS 2 BP 169 EP 190 AR PII S1568-1637(02)00063-6 DI 10.1016/S1568-1637(02)00063-6 PG 22 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 691HG UT WOS:000183599600004 PM 12605959 ER PT J AU Malcolm, SE Ng, JJ Rosen, RK Stone, VE AF Malcolm, SE Ng, JJ Rosen, RK Stone, VE TI An examination of HIV/AIDS patients who have excellent adherence to HAART SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the Society-for-General-Internal-Medicine CY MAY 02-06, 2000 CL BOSTON, MASSACHUSETTS SP Soc Gen Internal Med ID ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; REPORTED ADHERENCE; HIV DISEASE; PERSPECTIVES AB This paper examines the attitudes and beliefs of HIV/AIDS patients with excellent adherence to highly active antiretroviral therapy (HAART) and how they differ from those with suboptimal adherence. Forty-four persons with HIV/AIDS, 28 men and 16 women, participated in a qualitative semi-structured interview which was based on the Health Belief Model. The main outcomes were themes consistent with several dimensions of this model, reflecting differences in the health-related attitudes and beliefs of the excellent adherers compared to the suboptimal adherers. Patients with excellent adherence voiced the following themes when compared to less adherent patients: (1) believed adherence rates needed to be 90-100% for medication efficacy; (2) trusted their primary providers greatly; (3) took medications even when actively using substances of abuse; (4) were open about their HIV status and received substantial social support; (5) cited staying healthy as their key motivator; (6) were not actively depressed; all had normal CESD scores. Our study suggests that patients with excellent adherence to HAART differ from their less adherent counterparts in terms of key health-related attitudes and beliefs. Identifying and studying excellent adherers provides new insights and strategies for enhancing adherence to HAART. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Internal Med Unit, Boston, MA 02114 USA. Mem Hosp Rhode Isl, Dept Med, Pawtucket, RI 02860 USA. Rhode Isl Hosp, Providence, RI 02903 USA. Brown Med Sch, Providence, RI USA. RP Stone, VE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gen Internal Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. NR 26 TC 76 Z9 79 U1 0 U2 6 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 APR PY 2003 VL 15 IS 2 BP 251 EP 261 DI 10.1080/0954012031000068399 PG 11 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 671NK UT WOS:000182470800011 PM 12856346 ER PT J AU Gittens, MV Roth, WW Roach, T Stringer, HG Pieniazek, D Bond, VC Levett, PN AF Gittens, MV Roth, WW Roach, T Stringer, HG Pieniazek, D Bond, VC Levett, PN TI The molecular epidemiology and drug resistance determination of HIV type 1 subtype B infection in Barbados SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; BRAZIL; PROGRESSION; SEQUENCES; STRAINS AB To better understand the emergence of HIV-1 variants in Barbados and the association with transmission modes, we analyzed phylogenetic relationships and genetic variability among HIV-1 strains collected in 1996 from 36 antiretroviral therapy-naive patients. Only subtype B variants were present in this sampling, based on analysis of HIV-1 envelope (env) C2V3, protease (PR), and reverse transcriptase (RT) sequences. The genetic diversity of env sequences was broad (13.9%; range, 5.9-24.9%), suggesting multiple introductions of distinct HIV-1 strains to the island. The frequency of subtype B HIV-1 variants with similar env V3 features, including the tetrameric tips, GPGR and GPGK, the threonine. deletion at position 23, and the substitution of threonine to arginine at position 22, was comparable in heterosexual, bisexual, and homosexual patients. Analyses of amino acid variations in PR sequences revealed a lack of major drug resistance-conferring mutations and a high (90%) prevalence of secondary mutations at positions 36, 63, 71, and 77. While the occurrence of 36I, 63P, and 71T mutations in Barbadian strains was similar to the global prevalence for subtype B variants, the frequency (64%) of the V77I mutation was more than three times that seen worldwide. Only two RT antiretroviral resistance mutations (M41L and T215Y) were observed, both from a single patient. This comprehensive genetic analysis documents a broad diversity within HIV-1 subtype B in Barbados and suggests a lack of association between particular subtype B variants and transmission modes. C1 Univ W Indies, Sch Clin Med & Res, Bridgetown, Barbados. Morehouse Sch Med, Atlanta, GA 30310 USA. Ctr Dis Control & Prevent, Div AIDS STD, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, TB Res Lab, Atlanta, GA 30333 USA. RP Gittens, MV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Room 6001,5th Floor,13th St, Charlestown, MA 02119 USA. FU NCRR NIH HHS [G12-RR03034, G12 RR003034]; NIGMS NIH HHS [S06-GM08248-12, S06 GM008248] NR 23 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2003 VL 19 IS 4 BP 313 EP 319 DI 10.1089/088922203764969519 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 672EW UT WOS:000182509100007 PM 12816080 ER PT J AU Barton, C Miller, B Yaffe, K AF Barton, C Miller, B Yaffe, K TI Evaluation of the diagnosis and management of cognitive impairment in long-term care SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; long-term care ID MINIMUM DATA SET; QUALITY STANDARDS SUBCOMMITTEE; NURSING-HOME PLACEMENT; ACADEMY-OF-NEUROLOGY; ALZHEIMERS-DISEASE; DOUBLE-BLIND; INTERNATIONAL WORKSHOP; RESIDENT ASSESSMENT; PRACTICE PARAMETER; MENTAL-STATE AB The objective was to determine the prevalence of screening for cognitive impairment and its effect on diagnosis and management of cognitive impairment in a long-term care setting, especially in comparison to depressive and behavioral symptoms. The study was a prospective cohort study of medical records of 60 patients admitted to the 120 bed Veterans Administration Nursing Home in San Francisco. Screening was determined by documented results on the Mini-Mental Status Examination, Geriatric Depression Scale, and Minimum Data Set. Diagnosis and management were determined by review of medical records for provider documentation. Strategies for management were broad, including interventions such as pharmacological therapy, education, behavioral strategies, or caregiver interventions. Screening was conducted routinely for cognitive impairment (95%), depressive symptoms (95%), and behavioral symptoms (85%). Cognitive status was uncertain in 8 patients; 23 (44%) met criteria for cognitive impairment. Twelve (52%) had a differential diagnosis of cognitive impairment and 11 (48%) had evidence of strategies for management. Depressive and behavioral symptoms were equally or almost as common as cognitive impairment (44% and 25%, respectively), but evidence of a management plan was more frequently present (80% and 100%; p = 0.002 vs. with cognitive impairment). Although depressive and behavioral symptoms were frequently diagnosed and interventions initiated, the diagnosis and management of cognitive impairment were often imprecise or absent. Further research is needed to identify barriers to diagnosis and management so that greater numbers of patients can benefit from recommended strategies. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Barton, C (reprint author), Univ Calif San Francisco, Dept Neurol, Box 111G,4150 Clement St, San Francisco, CA 94121 USA. FU NIA NIH HHS [K23-AG00888, P50 AG023501] NR 33 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2003 VL 17 IS 2 BP 72 EP 76 DI 10.1097/00002093-200304000-00004 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 693QP UT WOS:000183730100004 PM 12794383 ER PT J AU Albert, MS AF Albert, MS TI Detection of very early Alzheimer disease through neuroimaging SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article; Proceedings Paper CT 3rd Leonard Berg Symposium on Neurobiology of the Aging Nervous System CY FEB 15-16, 2002 CL ST LOUIS, MISSOURI SP Alzheimer Disease Res Ctr, Washington Univ Sch Med ID EMISSION COMPUTED-TOMOGRAPHY; ENTORHINAL CORTEX; MRI MEASURES; HIPPOCAMPUS; DEMENTIA; SPECT; AD C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. RP Albert, MS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Psych Geron 149-9124,149 13th St, Charlestown, MA 02129 USA. EM albert@psych.mgh.harvard.edu NR 9 TC 4 Z9 5 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD APR-JUN PY 2003 VL 17 SU 2 BP S63 EP S65 PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 769LE UT WOS:000188650900010 PM 12813213 ER PT J AU Fox, ER Picard, MH Chow, CM Levine, RA Schwamm, L Kerr, AJ AF Fox, ER Picard, MH Chow, CM Levine, RA Schwamm, L Kerr, AJ TI Interatrial septal mobility predicts larger shunts across patent foramen ovales: An analysis with transmitral Doppler scanning SO AMERICAN HEART JOURNAL LA English DT Article ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; RECURRENT CEREBROVASCULAR EVENTS; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CRYPTOGENIC STROKE; ISCHEMIC STROKE; ADULT PATIENTS; ANEURYSM; RISK; MULTICENTER; SIZE AB Background The association of patent foramen ovale (PFO) with cryptogenic stroke is strongest in patients with larger shunts and patients with atrial septal aneurysms (ASAs). We postulated that the potency of ASA as a risk factor for stroke relates to the size of shunt across PFOs associated with mobile atrial septae. The purpose of this study was to investigate the relationship between atrial septal mobility and the degree of right-to-left shunting with a transthoracic transmitral Doppler scanning (TMD) contrast technique. Methods In 165 consecutive patients, transthoracic TMD recordings were made during a saline contrast study with the patient at rest and after a maneuver to increase right atrial pressure. Bubble transit corresponded to high intensity signals in the velocity envelope of the mitral inflow profile and was quantified by a bubble score. Results A PFO was diagnosed in 59 patients (36%). In 50 patients with PFO and adequate echocardiography images, the incidence of ASA was 52%. In this group, both total septal mobility and leftward deviation predicted the TMD bubble score at rest (Spearman rho 0.6,4, 0.64, respectively, P < .001) and after the maneuver (Spearman rho 0.74, 0.73, P < .001). In 28 patients with cerebral ischemic events, the maneuver bubble score was predictive for cryptogenic stroke (P = .02, odds ratio 7.58). There was a trend toward significance between total septal motion and cryptogenic stroke (P = .06). Conclusion Atrial septal mobility predicts the degree of right-to-left shunts across PFOs. The role of excessive septal mobility in the etiology of stroke may therefore be caused by the greater opportunity,for paradoxical embolism because of the size of the associated trans-PFO shunt. C1 Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Picard, MH (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Div Cardiol, Dept Med, 55 Fruit St, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145; Picard, Michael/0000-0002-9264-3243 NR 27 TC 40 Z9 45 U1 0 U2 0 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 APR PY 2003 VL 145 IS 4 BP 730 EP 736 DI 10.1067/mhj.2003.5 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666TH UT WOS:000182192200028 PM 12679772 ER PT J AU Raitt, MH Klein, RC Wyse, DG Wilkoff, BL Beckman, K Epstein, AE Coromilas, J Friedman, PL Martins, J Ledingham, RB Greene, HL AF Raitt, MH Klein, RC Wyse, DG Wilkoff, BL Beckman, K Epstein, AE Coromilas, J Friedman, PL Martins, J Ledingham, RB Greene, HL CA AVID Invest TI Comparison of arrhythmia recurrence in patients presenting with ventricular fibrillation versus ventricular tachycardia in the antiarrhythmics versus implantable defibrillators (AVID) trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC-ARREST; SURVIVORS AB Because many episodes of ventricular fibrillation (VF) are believed to be triggered by ventricular tachycardia (VT), patients who present with VT or VF are usually grouped together in discussions of natural history and treatment. However, there are significant differences in the clinical profiles of these 2 patient groups, and some studies have suggested differences in their response to therapy. We examined arrhythmias occurring spontaneously in 449 patients assigned to implantable cardioverter-defibrillator (ICD) therapy in the Antiarrhythmics Versus Implantable Defibrillators (AVID) trial to determine whether patients who receive an ICD after VT have arrhythmias during follow-up that are different from patients who present with VF. ICD printouts were analyzed both by a committee blinded to the patients' original presenting arrhythmia and by the local investigator, During 31 +/- 14 months of follow-up, 2,673 therapies were reported. Patients who were enrolled in the AVID trial after an episode of VT were more likely to have an episode of VT (73.5% vs 30.1%, p <0.001), and were less likely to have an episode of VF (18.3% vs 28.0%, p = 0.013) than patients enrolled after an episode of VF. Adjustment for differences in ejection fraction, previous infarction, and β-blocker and antiarrhythmic therapy did not appreciably c hange the results. Ventricular arrhythmia recurrence during follow-up is different in patients who originally present with VT than in those who originally present with VF. These findings suggest there are important differences in the electrophysiologic characteristics of these 2 patient populations. (C) 2003 by Excerpta Medica, Inc. C1 Oregon Hlth & Sci Univ, Portland VA Med Ctr, Portland, OR USA. Univ Utah, Salt Lake City, UT USA. Univ Calgary, Calgary, AB, Canada. Cleveland Clin, Cleveland, OH 44106 USA. Univ Oklahoma, Oklahoma City, OK USA. Univ Alabama, Birmingham, AL USA. Columbia Univ, New York, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. Univ Washington, Seattle, WA 98195 USA. RP Raitt, MH (reprint author), AVID Clin Trial Ctr, 1107 NE 45th St,Room 505, Seattle, WA 98105 USA. OI Raitt, Merritt/0000-0001-5638-7732; Wilkoff, Bruce/0000-0001-8905-9233 FU NHLBI NIH HHS [N01-HC-25117] NR 10 TC 20 Z9 21 U1 0 U2 2 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 APR 1 PY 2003 VL 91 IS 7 BP 812 EP 816 DI 10.1016/S0002-9149(03)00015-8 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 663EY UT WOS:000181994300006 PM 12667566 ER PT J AU Refaai, MA Van Cott, EM Laposata, M AF Refaai, MA Van Cott, EM Laposata, M TI The timing of a positive test result for heparin-induced thrombocytopenia relative to the platelet count and anticoagulant therapy in 43 consecutive cases SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE heparin; heparin-induced thrombocytopenia; platelet count; thrombosis; thrombocytopenia ID SEROTONIN RELEASE; DIAGNOSIS; THROMBOSIS; ARGATROBAN; HIRUDIN; SAFE AB We studied the timing of a positive heparin-induced thrombocytopenia (HIT) test result relative to changes in platelet count and anticoagulant use. We obtained platelet counts in 100 consecutive HIT+ cases before, during, and after heparin therapy; 43 cases met study criteria and were included in study part 1. In part 2, platelet counts at the time of the HIT test in 2 groups (100 each HIT+ and HIT- cases) were compared. In part 1, cases could be divided into 4 groups based on the diagnosis of HIT relative to platelet counts (1, within 1-2 days of a major drop in platelet count [11.6%]; 2, after > 2 days of a major fall in platelet count [41.9%]; 3, in patients with already low platelet counts [27.9%]; 4, after platelet count was rising [18.6%]). In study part 2, the mean platelet counts for the HIT+ and HIT- groups were almost identical. HIT should be suspected in any thrombotic patient who had a previous decline in platelet count, has a low platelet count, or has a rising platelet count after a previous decline in association with heparin exposure. In study, part 2, 1 platelet count value at the time of the HIT test did not provide useful information. C1 Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Div Lab Med, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Room 235,Gray Bldg, Boston, MA 02114 USA. NR 30 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 2003 VL 119 IS 4 BP 497 EP 504 DI 10.1309/KM2Y9H9TP6DA59MT PG 8 WC Pathology SC Pathology GA 661BZ UT WOS:000181872500003 PM 12710122 ER PT J AU Saab, S DeRosa, V Nieto, J Durazo, F Han, S Roth, B AF Saab, S DeRosa, V Nieto, J Durazo, F Han, S Roth, B TI Costs and clinical outcomes of primary prophylaxis of variceal bleeding in patients with hepatic cirrhosis: A decision analytic model SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID RANDOMIZED CONTROLLED TRIAL; ESOPHAGEAL-VARICES; COMPENSATED CIRRHOSIS; PROGNOSTIC INDICATORS; PORTAL-HYPERTENSION; NATURAL-HISTORY; LIVER-DISEASE; PROPRANOLOL; PREVENTION; HEMORRHAGE AB OBJECTIVE: Current guidelines recommend upper endoscopic screening for patients with hepatic cirrhosis and primary prophylaxis with a nonselective beta-blocker for those with large varices. However, only 25% of cirrhotics develop large varices. Thus. the aim of this study is to evaluate the most cost-effective approach for primary prophylaxis of variceal hemorrhage. METHODS: Using a Markov model, we compared the costs and clinical outcomes of three strategies for primary prophylaxis of variceal bleeding. In the first strategy, patients were given a beta-blocker without undergoing upper endoscopy. In the second strategy, patients underwent upper endoscopic screening: those found to have large varices were treated with a beta-blocker. In the third strategy, no prophylaxis was used. Selected sensitivity analyses were performed to Validate outcomes. RESULTS: Our results show screening prophylaxis was associated with a cost of $37,300 and 5.72 quality-adjusted life yr (QALYs). Universal prophylaxis was associated with a cost of $34.100 and 6.65 QALYs. The no prophylaxis strategy was associated with a cost of $36,600 and 4.84 QALYs. The incremental cost-effectiveness ratio was $800/QALY for the endoscopic strategy relative to the no prophylaxis strategy. Screening endoscopy was cost saving when the compliance, bleed risk without beta-blocker, and variceal bleed costs were increased, and when the discount rate. bleed risk on beta-blockers, and cost of upper endoscopy were decreased. In contrast, the universal prophylaxis strategy was persistently cost saving relative to the no prophylaxis strategy. In comparing the strategies, sensitivity analysis on the death rates from variceal hemorrhage did not alter outcomes. CONCLUSIONS: Our results provide economic and clinical support for primary prophylaxis of esophageal variceal bleeding in patients with hepatic cirrhosis. Universal prophylaxis with beta-blocker is preferred because it is consistently associated with the lowest costs and highest QALYs. C1 Dumont UCLA Liver Transplant Ctr, Dept Med, Div Digest Dis, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. RP Saab, S (reprint author), Univ Calif Los Angeles, Med Ctr, Div Digest Dis, 44-138 CHS,MC 168417,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 55 TC 45 Z9 45 U1 0 U2 1 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 APR PY 2003 VL 98 IS 4 BP 763 EP 770 DI 10.1016/S0002-9270(03)00056-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 676LW UT WOS:000182754400010 PM 12738453 ER PT J AU Chitkara, DK Nurko, S Shoffner, JM Buie, T Flores, A AF Chitkara, DK Nurko, S Shoffner, JM Buie, T Flores, A TI Abnormalities in gastrointestinal motility are associated with diseases of oxidative phosphorylation in children SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID MITOCHONDRIAL NEUROGASTROINTESTINAL ENCEPHALOMYOPATHY; CHRONIC INTESTINAL PSEUDOOBSTRUCTION; DISORDER; DNA; MUTATIONS; MYOPATHY; MNGIE; OPHTHALMOPLEGIA; INHERITANCE; MEDICINE AB OBJECTIVE: Disorders of the mitochondrial electron transport chain enzymes of oxidative phosphorylation (OXPHOS) have neurologic. musculoskeletal, ophthalmologic, cardiac, and GI manifestations. Many adult and pediatric patients with disorders of OXPHOS have abnormalities in intestinal motility. The purpose of this study was to describe pediatric patients who initially presented with signs of GI dysmotility and were later evaluated and found to have a disorder of OXPHOS. METHODS: Data were collected on six patients, including initial GI and neurologic symptoms, histology of skeletal muscle biopsies, mitochondrial DNA mutational analysis, OXPHOS enzyme assay, upper GI barium imaging, technetium-99M liquid gastric emptying scan, upper GI endoscopy, esophageal manometry, and antroduodenal manometry. RESULTS: All six children presented with symptoms of GI dysmotility within 2 wk of life. Patients later developed symptoms of neurologic disorders. All patients had abnormalities in OXPHOS enzyme analysis. Muscle histology showed nonspecific changes with no ragged red fibers. Sequencing of the mitochondrial DNA showed no recognized mutations. No patient had any evidence of intestinal obstruction or malrotation by upper GI barium imaging. Four patients had delayed gastric emptying. Three patients had endoscopic and histologic evidence of esophagitis. All six had demonstrable neuropathic abnormalities by antroduodenal manometry, including the following: nonpropagated antral bursts, absent migrating motor complexes, postprandial antral hypomotility, retrograde migrating motor complexes, and tonic contractions with the migrating motor complex. CONCLUSION: Abnormalities in GI motility may be an early presenting sign of disorders of OXPHOS in children. C1 Childrens Hosp, Div Gastroenterol & Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Floating Hosp Children, Div Pediat Gastroenterol & Nutr, Boston, MA USA. Georgia State Univ, Dept Biol, Horizon Mol Med Lab, Norcross, GA USA. RP Chitkara, DK (reprint author), Mayo Clin, Charlton 8-100,200 1st St SW, Rochester, MN 55905 USA. FU NIDDK NIH HHS [T32 DK07471-19] NR 20 TC 15 Z9 17 U1 0 U2 0 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 APR PY 2003 VL 98 IS 4 BP 871 EP 877 DI 10.1016/S0002-0270(03)00049-2 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 676LW UT WOS:000182754400027 PM 12738470 ER PT J AU Chen, DH Brkanac, Z Verlinde, CLMJ Tan, XJ Bylenok, L Nochlin, D Matsushita, M Lipe, H Wolff, J Fernandez, M Cimino, PJ Bird, TD Raskind, WH AF Chen, DH Brkanac, Z Verlinde, CLMJ Tan, XJ Bylenok, L Nochlin, D Matsushita, M Lipe, H Wolff, J Fernandez, M Cimino, PJ Bird, TD Raskind, WH TI Missense mutations in the regulatory domain of PKC gamma: A new mechanism for dominant nonepisodic cerebellar ataxia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEIN-KINASE-C; SCA1 TRANSGENIC MICE; PHORBOL ESTER BINDING; CHROMOSOME 19Q13.4-QTER; MOLECULAR-DYNAMICS; PURKINJE-CELLS; MUTANT MICE; FAMILIES; MULTIPLE; SPINOCEREBELLAR AB We report a nonepisodic autosomal dominant (AD) spinocerebellar ataxia (SCA) not caused by a nucleotide repeat expansion that is, to our knowledge, the first such SCA. The AD SCAs currently comprise a group of greater than or equal to16 genetically distinct neurodegenerative conditions, all characterized by progressive incoordination of gait and limbs and by speech and eye-movement disturbances. Six of the nine SCAs for which the genes are known result from CAG expansions that encode polyglutamine tracts. Noncoding CAG, CTG, and ATTCT expansions are responsible for three other SCAs. Approximately 30% of families with SCA do not have linkage to the known loci. We recently mapped the locus for an AD SCA in a family (AT08) to chromosome 19q13.4-qter. A particularly compelling candidate gene, PRKCG, encodes protein kinase C gamma (PKCgamma), a member of a family of serine/threonine kinases. The entire coding region of PRKCG was sequenced in an affected member of family AT08 and in a group of 39 unrelated patients with ataxia not attributable to trinucleotide expansions. Three different nonconservative missense mutations in highly conserved residues in C1, the cysteine-rich region of the protein, were found in family AT08, another familial case, and a sporadic case. The mutations cosegregated with disease in both families. Structural modeling predicts that two of these amino acid substitutions would severely abrogate the zinc-binding or phorbol ester-binding capabilities of the protein. Immunohistochemical studies on cerebellar tissue from an affected member of family AT08 demonstrated reduced staining for both PKCg and ataxin 1 in Purkinje cells, whereas staining for calbindin was preserved. These results strongly support a new mechanism for neuronal cell dysfunction and death in hereditary ataxias and suggest that there may be a common pathway for PKCgamma-related and polyglutamine-related neurodegeneration. C1 Univ Washington, Dept Med, Sch Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Biol Struct, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res, Educ & Clin Ctr, Seattle, WA USA. Vet Affairs Puget Sound Hlth Care Syst, VISN 20 Mental Illness Res, Educ & Clin Ctr, Seattle, WA USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. RP Raskind, WH (reprint author), Univ Washington, Dept Med, Sch Med, Box 35-7720, Seattle, WA 98195 USA. RI VERLINDE, CHRISTOPHE/J-5796-2013 FU NIEHS NIH HHS [P30 ES007033, P30ES07033] NR 33 TC 137 Z9 145 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2003 VL 72 IS 4 BP 839 EP 849 DI 10.1086/373883 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 662WT UT WOS:000181972600006 PM 12644968 ER PT J AU Lin, JP Cupples, A Wilson, PWF Heard-Costa, N O'Donnell, CJ AF Lin, JP Cupples, A Wilson, PWF Heard-Costa, N O'Donnell, CJ TI Evidence for a gene influencing serum bilirubin on chromosome 2q telomere: A genomewide scan in the Framingham Study SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CORONARY-ARTERY DISEASE; HEART-DISEASE; GILBERTS-SYNDROME; LINKAGE ANALYSIS; RISK; ASSOCIATION; TRAIT; UDP-GLUCURONOSYLTRANSFERASE-1; LIPOPROTEIN; PEDIGREES AB There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 families with 1,394 sibling pairs, 681 cousin pairs, and 89 avuncular pairs. Using variance-component methods, the heritability was estimated to be 49% +/- 6%, and the genome scan demonstrated significant evidence of linkage of serum bilirubin to chromosome 2q, with a LOD score of 3.8 at location 243 cM. The peak multipoint LOD score is located 1 cM away from the uridine diphosphate glycosyltransferase 1 (UGT1A1) gene. UGT1A1 catalyzes the conjugation of bilirubin with glucuronic acid and thus enhances bilirubin elimination; therefore, it is an important candidate gene for serum bilirubin. Gilbert syndrome, a hyperbilirubinemic syndrome, has a population frequency of 2%-19% and is mainly due to a TA insertion at the promoter region of UGT1A1. Only one other region in the genome produced a multipoint LOD score >1 (LOD = 1.3). Our findings suggest that UGT1A1 may be a major gene controlling serum bilirubin levels in the population. C1 NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Lin, JP (reprint author), NHLBI, Div Epidemiol & Clin Applicat, NIH, 6701 Rockledge Dr,Suite 8217, Bethesda, MD 20892 USA. NR 27 TC 34 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2003 VL 72 IS 4 BP 1029 EP 1034 DI 10.1086/373964 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 662WT UT WOS:000181972600024 PM 12618960 ER PT J AU Arar, N Lee, S Chun, C Plaetke, R Abboud, H AF Arar, N Lee, S Chun, C Plaetke, R Abboud, H TI Gender differences in progression to end stage renal disease among diabetic Mexican-Americans SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 02-06, 2003 CL DALLAS, TEXAS SP Natl Kidney Fdn C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 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 APR PY 2003 VL 41 IS 4 MA 8 BP A13 EP A13 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675EG UT WOS:000182679600038 ER PT J AU Bastepe, M Kerachian, MA Berlach, DM Hendy, GN Juppner, H AF Bastepe, M Kerachian, MA Berlach, DM Hendy, GN Juppner, H TI Study of different Gs alpha-variants through the use of cells homozygous for disruption of Gnas exon 2. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 02-06, 2003 CL DALLAS, TEXAS SP Natl Kidney Fdn C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. NR 0 TC 0 Z9 0 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 APR PY 2003 VL 41 IS 4 MA 12 BP A14 EP A14 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 675EG UT WOS:000182679600042 ER PT J AU Skol, AD Young, KA Tsuang, DW Faraone, SV Haverstock, SL Bingham, S Prabhudesai, S Mena, F Menon, AS Yu, CE Rudell, P Pepple, J Sauter, F Baldwin, C Weiss, D Collins, J Keith, T Boehnke, M Schellenberg, GD Tsuang, MT AF Skol, AD Young, KA Tsuang, DW Faraone, SV Haverstock, SL Bingham, S Prabhudesai, S Mena, F Menon, AS Yu, CE Rudell, P Pepple, J Sauter, F Baldwin, C Weiss, D Collins, J Keith, T Boehnke, M Schellenberg, GD Tsuang, MT TI Modest evidence for linkage and possible confirmation of association between NOTCH4 and schizophrenia in a large veterans affairs cooperative study sample SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE NOTCH4; chromosome 6; schizophrenia; association; linkage; genetics ID PEDIGREE DISEQUILIBRIUM TEST; SIB-PAIR LINKAGE; CHROMOSOME 6P; SUSCEPTIBILITY LOCUS; DIAGNOSTIC INTERVIEW; GENETIC-LINKAGE; POLYMORPHISM; FAMILIES; SUPPORT; PROGRAM AB Wei and Hemmings [2000: Nat Genet 25:376-377], using 80 British parent-offspring trios, identified a number of NOTCH4 variants and haplotypes that showed statistically significant evidence of association to schizophrenia. Specifically, the 10 repeat allele of a (CTG)(n) marker and the 8 repeat allele of a (TAA)(n) marker demonstrated excess transmission to affected individuals; SNP2(1) and haplotypes SNP2-(CTG) and SNP1(2)-SNP2-(CTG)(n) also showed significant associations. In an attempt to replicate these findings, we tested for linkage and association between the same five markers used by Wei and Hemmings in 166 families collected from a multi-center study conducted by the Department of Veterans Affairs (DVA) Cooperative Study Program (CSP). The families include 392 affected subjects (schizophrenia or schizoaffective disorder, depressed) and 216 affected sibling pairs. The families represent a mix of European Americans (n=62, 37%), African Americans (n=60, 36%), and racially mixed or other races (n=44, 27%). We identified moderate evidence for linkage in the pooled race sample (LOD=1.25) and found excess transmission of the 8 (P=0.06) and 13 (P=0.04) repeat alleles of the (TAA)(n) marker to African American schizophrenic subjects. The 8 and 13 repeat alleles were previously identified to be positively associated with schizophrenia by Wei and Hemmings [2000: Nat Genet 25:376-377] and Sklar et al. [2001: Nat Genet 28:126-128], respectively. (C) 2003 Wiley-Liss, Inc. C1 VAPSHCS, GRECC 182, Seattle, WA 98108 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Vet Affairs Med Ctr, Waco, TX USA. Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Med Ctr, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA. Vet Affairs Med Ctr, Danville, IL USA. Vet Affairs Med Ctr, Tuskegee, AL USA. Univ Washington, Dept Gerontol, Seattle, WA 98195 USA. Univ Washington, Dept Geriatr Med, Seattle, WA 98195 USA. Vet Affairs Med Ctr, New Orleans, LA USA. Vet Affairs Med Ctr, Northport, NY USA. RP Schellenberg, GD (reprint author), VAPSHCS, GRECC 182, 1660 S Columbian Way, Seattle, WA 98108 USA. RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 NR 42 TC 26 Z9 27 U1 1 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 1 PY 2003 VL 118B IS 1 BP 8 EP 15 DI 10.1002/ajmg.b.10055 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670HQ UT WOS:000182401800002 PM 12627457 ER PT J AU Qian, QJ Wang, YF Zhou, RL Li, J Wang, B Glatt, S Faraone, SV AF Qian, QJ Wang, YF Zhou, RL Li, J Wang, B Glatt, S Faraone, SV TI Family-based and case-control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE attention deficit hyperactivity disorder; catechol-O-methyltransferase; association; genetics; gender differences ID CARDIO-FACIAL SYNDROME; OBSESSIVE-COMPULSIVE DISORDER; HAPLOTYPE RELATIVE RISK; NO ASSOCIATION; VAL ALLELE; COMT; SCHIZOPHRENIA; POLYMORPHISM; ADHD; BEHAVIOR AB Attention deficit hyperactivity disorder (ADHD) is the most common childhood-onset behavioral disorder. Boys are more often affected than girls. Family, twin, and adoption studies have supported a strong genetic basis. Some studies show that a catechol-O-methyltransferase (COMT) polymorphism affecting enzyme activity was associated with personality characteristics and diseases, such as novelty-seeking personality, substance abuse, and heroin addiction, whose features are similar to ADHD or are associated with ADHD. These findings suggest that the COMT gene may be a candidate gene for ADHD. TDT, HHRR, and case-control association studies were conducted within a sample of 202 nuclear ADHD families, 340 ADHD cases, and 226 controls in the Han Chinese population. Diagnoses and ADHD subtypes were ascertained according to DSM-IV criteria using American Clinical Diagnostic Interviewing Scales. The HHRR analysis suggested that the low enzyme-activity COMT Met allele was preferentially transmitted to ADHD boys (160 trios, chi(2) = 3.858, P = 0.05, df =1) but not girls. This association is particularly pronounced among male ADHD probands without any comorbidity (50 trios, HHRR: chi(2) = 5.128, P = 0.024, df =1; TDT: chi(2) = 4.558, P = 0.033, df = 1), especially the ADHD-I subtype (32 trios, HHRR: chi(2) = 5.792, P = 0.016, df =1; TDT: chi(2) = 5.333, P = 0.021, df =1). The case-control study revealed that the Val allele was more frequent in females meeting ICD-10 or DSM-IV criteria for ADHD than in female controls (86 and 79.5%, respectively, chi(2) = 4.059, P = 0.044, df =1). Although these results suggest the COMT gene exerts some influence on the risk for ADHD in the Han Chinese population, given the potential for Type I error, these findings require replication before drawing definitive conclusions. (C) 2003 Wiley-Liss, Inc. C1 Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Wang, YF (reprint author), Peking Univ, Inst Mental Hlth, Beijing 100083, Peoples R China. OI Glatt, Stephen/0000-0002-0360-7567; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R25 MH 60485] NR 38 TC 83 Z9 99 U1 2 U2 9 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 1 PY 2003 VL 118B IS 1 BP 103 EP 109 DI 10.1002/ajmg.b.10064 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 670HQ UT WOS:000182401800020 PM 12627475 ER PT J AU Cornia, PB Amory, JK Fraser, S Saint, S Lipsky, BA AF Cornia, PB Amory, JK Fraser, S Saint, S Lipsky, BA TI Computer-based order entry decreases duration of indwelling urinary catheterization in hospitalized patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID DECISION-SUPPORT SYSTEMS; PREVENTIVE CARE; TRACT INFECTION; RISK-FACTORS; BACTERIURIA; PERFORMANCE; PHYSICIANS C1 Univ Washington, Sch Med, Primary & Specialty Med Serv, Seattle, WA 98195 USA. Univ Washington, Sch Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Ann Arbor VA Med Ctr, Ann Arbor, MI USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Patient Safety Enhancement Program, Ann Arbor, MI 48109 USA. RP Cornia, PB (reprint author), Gen Internal Med Clin, S-111,1660 S Columbian Way, Seattle, WA 98108 USA. OI Lipsky, Benjamin A./0000-0001-9886-5114 FU AHRQ HHS [P20-HS11540] NR 20 TC 67 Z9 68 U1 0 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 APR 1 PY 2003 VL 114 IS 5 BP 404 EP 407 DI 10.1016/S0002-9343(02)01568-1 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 670XY UT WOS:000182436400010 PM 12714131 ER PT J AU Egan, RA Nguyen, TH Gass, JDM Rizzo, JF Tivnan, J Susac, JO AF Egan, RA Nguyen, TH Gass, JDM Rizzo, JF Tivnan, J Susac, JO TI Retinal arterial wall plaques in Susac syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID MICROANGIOPATHY; BRAIN; OCCLUSION AB PURPOSE: To demonstrate retinal arterial wall plaques (RAWPs) in patients with Susac syndrome, a disorder that consists of the triad of branch retinal artery occlu sion, encephalopathy, and hearing loss. The clinician may misinterpret these RAWPs as emboli. DESIGN: Observational case series. METHODS: Four patients (one man and three women, aged 21-38 years) were examined and followed. RESULTS: Four patients with Susac syndrome had AWPs in association with branch retinal artery occlu, sions. They were present in six of eight eyes. The plaques were yellow to yellow-white and located usually away from retinal bifurcations. Retinal arterial wall plaques occur at the midarteriolar segments, whereas Hollenhorst plaques occur at vascular bifurcations. Four of six eyes had resolution of the plaques. CONCLUSIONS: Retinal arterial wall plaques may occur with branch retinal artery occlusions in Susac syndrome. This finding should help the clinician who is struggling to make a diagnosis in a patient with an enigmatic encephalopathy and/or hearing loss. These plaques may resolve over time. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Casey Eye Inst, Portland, OR 97201 USA. Vanderbilt Univ, Med Ctr, Dept Ophthalmol, Nashville, TN USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Eye Specialists Mid Florida, Winter Haven, FL USA. Neurol & Neurosurg Associates, Winter Haven, FL USA. RP Egan, RA (reprint author), Oregon Hlth Sci Univ, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. NR 11 TC 45 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 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2003 VL 135 IS 4 BP 483 EP 486 DI 10.1016/S0002-9394(02)02085-8 PG 4 WC Ophthalmology SC Ophthalmology GA 657AE UT WOS:000181642600009 PM 12654364 ER PT J AU Hartnett, ME Laposata, M Van Cott, E AF Hartnett, ME Laposata, M Van Cott, E TI Antiphospholipid antibody syndrome in a six-year-old female patient SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB PURPOSE: To report the first instance of primary antiphos. pholipid antibody (APA) syndrome in an otherwise healthy 6-year old female patient with retinal venous thromboses. DESIGN: Observational case report. METHODS: A 6-year-old girl with poor vision in the left eye and preretinal hemorrhage underwent testing for infectious, autoimmune and embolic disease, diabetes, and hypertension. Testing for factor V Leiden and prothrombin G20210A mutations, homocysteine, anti, cardiolipin antibodies (ACAs), lupus anticoagulant, and functional assays for protein S, protein C, and antithrom bin III were performed to detect a hypercoagulable state. No IRB approval was necessary. RESULTS: Only a positive lupus anticoagulant and moderately elevated ACA IgG were found. The ACA IgG was moderately elevated on repeat testing 18 months later. Laser to nonperfused retina caused some regression of retinal neovascularization. Aspirin was recommended to reduce the risk of future thromboses. CONCLUSION: Although uncommon, retinovascular thrombosis in children can occur in APA syndrome. Testing for ACA and lupus anticoagulant should be considered. (C) 2003 by Elsevier Science Inc. All rights reserved. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Louisiana State Univ, Hlth Sci Ctr, Eye Ctr, Dept Ophthalmol, New Orleans, LA USA. RP Hartnett, ME (reprint author), Louisiana State Univ, Eye Ctr, 2020 Gravier St,Suite B, New Orleans, LA 70112 USA. FU NEI NIH HHS [P30EY02377] NR 6 TC 11 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD APR PY 2003 VL 135 IS 4 BP 542 EP 544 DI 10.1016/S0002-9394(02)02078-0 PG 3 WC Ophthalmology SC Ophthalmology GA 657AE UT WOS:000181642600021 PM 12654376 ER PT J AU French, CA Alexander, EK Cibas, ES Nose, V Laguette, J Faquin, W Garber, J Moore, F Fletcher, JA Larsen, PR Kroll, TG AF French, CA Alexander, EK Cibas, ES Nose, V Laguette, J Faquin, W Garber, J Moore, F Fletcher, JA Larsen, PR Kroll, TG TI Genetic and biological subgroups of low-stage follicular thyroid cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RET/PTC ONCOGENE ACTIVATION; COMPARATIVE GENOMIC HYBRIDIZATION; ACUTE PROMYELOCYTIC LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; PAPILLARY CARCINOMAS; MOLECULAR-GENETICS; COLORECTAL TUMORIGENESIS; CYTOGENETIC FINDINGS; OBSERVER VARIATION AB Investigations of cancer-specific gene rearrangements have increased our understanding of human neoplasia and led to the use of the rearrangements in pathological diagnosis of blood cell and connective tissue malignancies. Here, we have investigated 3p25 rearrangements of the peroxisome proliferator-activated receptor gamma (PPAR gamma) gene in follicular epithelial tumors of the human thyroid gland. Eleven of 42 (26%) low-stage follicular carcinomas, 0 of 40 follicular adenomas, 1 of 30 Hurthle cell carcinomas, 1 of 90 papillary carcinomas, and 0 of 10 nodular goiters had 3p25 rearrangements by interphase fluorescence in situ hybridization. All 11 follicular carcinomas with 3p25 rearrangement exhibited strong, diffuse nuclear immunoreactivity for PPARgamma, consistent with expression of PPARgamma fusion protein. Twelve of 42 (29%) low-stage follicular carcinomas had 3p25 aneusomy without PPARgamma rearrangement (P = 0.01), suggesting that PPARgamma rearrangement and aneuploidy are independent early events in follicular cancer. Eleven of 12 follicular carcinomas with 3p25 aneusomy exhibited no PPARgamma immunoreactivity, supporting the existence of two independent pathways. Follicular carcinoma patients with PPARgamma rearrangement more frequently had vascular invasion (P = 0.01), areas of solid/nested tumor histology (P < 0.001), and previous nonthyroid cancers (P < 0.01) compared with follicular carcinoma patients without PPARgamma rearrangement. Our experiments identify genetic subgroups of low-stage follicular thyroid cancer and provide evidence that follicular carcinomas with PPARgamma rearrangement are a distinct biological entity. The findings support a model in which separate genetic alterations initiate distinct pathways of oncogenesis in thyroid carcinoma subtypes. C1 Emory Univ, Sch Med, Dept Pathol & Lab Med, Winship Canc Inst, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Hematol & Oncol, Winship Canc Inst, Atlanta, GA 30322 USA. Brigham & Womens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Div Endocrinol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Vanguard Med Associates, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kroll, TG (reprint author), Emory Univ, Sch Med, Dept Pathol & Lab Med, Winship Canc Inst, 146 Whitehead Bldg,615 Michael St, Atlanta, GA 30322 USA. EM tkroll@emory.edu FU NCI NIH HHS [K08 CA075425, CA75425] NR 78 TC 94 Z9 99 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2003 VL 162 IS 4 BP 1053 EP 1060 DI 10.1016/S0002-9440(10)63902-8 PG 8 WC Pathology SC Pathology GA 658YH UT WOS:000181748300004 PM 12651598 ER PT J AU Clow, KA Giraud, GD Ogden, BE Brooks, VL AF Clow, KA Giraud, GD Ogden, BE Brooks, VL TI Pregnancy alters hemodynamic responses to hemorrhage in conscious rabbits SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE cardiac output; stroke volume; total peripheral resistance; mean arterial pressure; femoral conductance ID PRESSURE AB Pregnant animals are less able to maintain mean arterial pressure (MAP) during hemorrhage compared with nonpregnant animals, but the hemodynamic basis of this difference is unknown. The hypothesis that pregnancy attenuates responses of cardiac output, as well as total peripheral resistance (TPR) and femoral conductance, to hemorrhage was tested in conscious rabbits in both the pregnant and nonpregnant state (n = 10). During continuous slow blood loss (2% of the initial blood volume per minute), MAP was maintained initially in both groups. However, MAP then abruptly decreased to <45 mmHg in all animals after a smaller percentage of the initial blood volume was removed in pregnant compared with nonpregnant rabbits (43.6 +/- 1.7%, nonpregnant; 29.6 +/- 2.2%, pregnant; P < 0.005). The more rapid transition to hypotension exhibited by pregnant rabbits was associated with greater initial falls in cardiac output (-56 +/- 10 ml/min, nonpregnant; -216 +/- 33 ml/min, pregnant; P < 0.005) and stroke volume (0.8 +/- 0.1 ml/beat, nonpregnant; -1.3 +/- 0.1 ml/beat, pregnant; P < 0.05). In addition, the increase in TPR as a function of the decrease in cardiac output was markedly attenuated (P < 0.0001) during pregnancy. Whereas femoral conductance decreased in nonpregnant rabbits, it did not change significantly in pregnant animals. In conclusion, the lesser ability of conscious pregnant rabbits to maintain MAP during hemorrhage is due largely to a greater decrease in cardiac output but also to inadequate reflex increases in TPR, possibly in part in the femoral vascular bed. C1 Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Comparat Med, Portland, OR 97239 USA. Portland VA Med Ctr, Dept Med, Div Cardiol, Portland, OR 97207 USA. RP Brooks, VL (reprint author), Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, L-334,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM brooksv@ohsu.edu FU NHLBI NIH HHS [HL-35872, HL-39923] NR 21 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD APR PY 2003 VL 284 IS 4 BP H1110 EP H1118 DI 10.1152/ajpheart.00626.2002 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 653GB UT WOS:000181425900010 PM 12595295 ER PT J AU Figlewicz, DP AF Figlewicz, DP TI Adiposity signals and food reward: expanding the CNS roles of insulin and leptin SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Review DE central nervous system; dopamine; food intake ID BLOOD-BRAIN-BARRIER; CENTRAL-NERVOUS-SYSTEM; OBESE ZUCKER RATS; CONDITIONED PLACE PREFERENCE; CULTURED FETAL NEURONS; BODY-WEIGHT; ENERGY-BALANCE; INTRAVENTRICULAR INSULIN; NUCLEUS-ACCUMBENS; GENE-EXPRESSION AB The hormones insulin and leptin have been proposed to act in the central nervous system (CNS) as adiposity signals as part of a theoretical negative feedback loop that senses the caloric stores of an animal and orchestrates adjustments in energy balance and food intake. Much research has provided support for both the existence of such a feedback loop and the specific roles that insulin and leptin may play. Most studies have focused on hypothalamic sites, which historically are implicated in the regulation of energy balance, and on the brain stem, which is a target for neural and humoral signals relating to ingestive acts. More recent lines of research, including studies from our lab, suggest that in addition to these CNS sites, brain reward circuitry may be a target for insulin and leptin action. These studies are reviewed together here with the goals of providing a historical overview of the findings that have substantiated the originally hypothesized negative feedback model and of opening up new lines of investigation that will build on these findings and allow further refinement of the model of adiposity signal/CNS feedback loop. The understanding of how motivational circuitry and its endocrine or neuroendocrine modulation contributes to normal energy balance regulation should expand possibilities for future therapeutic approaches to obesity and may lead to important insights into mental illnesses such as substance abuse or eating disorders. C1 VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. Univ Washington, Dept Psychol, Seattle, WA 98195 USA. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 So Columbian Way, Seattle, WA 98108 USA. EM latte@u.washington.edu FU NIDDK NIH HHS [DK-40963] NR 132 TC 132 Z9 137 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 2003 VL 284 IS 4 BP R882 EP R892 DI 10.1152/ajpregu.00602.2002 PG 11 WC Physiology SC Physiology GA 653GA UT WOS:000181425800002 PM 12626355 ER PT J AU Alam, J Killeen, E Gong, PF Naquin, R Hu, B Stewart, D Ingelfinger Jr Nath, KA AF Alam, J Killeen, E Gong, PF Naquin, R Hu, B Stewart, D Ingelfinger, JR Nath, KA TI Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2 SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE Nrf2 transcription factor; stress-response element; protein stabilization ID ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR; OXIDATIVE STRESS; MEDIATED EXPRESSION; HEAVY-METALS; IN-VIVO; INDUCTION; PROTEIN; BINDING; MAF AB The mechanism of heme oxygenase-1 gene (ho-1) activation by heme in immortalized rat proximal tubular epithelial cells was examined. Analysis of the ho-1 promoter identified the heme-responsive sequences as the stress-response element (StRE), multiple copies of which are present in two enhancer regions, E1 and E2. Electrophoretic mobility shift assays identified Nrf2, MafG, ATF3, and Jun and Fos family members as StRE-binding proteins; binding of Nrf2, MafG, and ATF3 was increased in response to heme. Dominant-negative mutants of Nrf2 and Maf, but not of c-Fos and c-Jun, inhibited basal and heme-induced expression of an E1-controlled luciferase gene. Heme did not affect the transcription activity of Nrf2, dimerization between Nrf2 and MafG, or the level of MafG, but did stimulate expression of Nrf2. Heme did not influence the level of Nrf2 mRNA but increased the half-life of Nrf2 protein from similar to10 min to nearly 110 min. These results indicate that heme promotes stabilization of Nrf2, leading to accumulation of Nrf2.MafG dimers that bind to StREs to activate the ho-1 gene. C1 Alton Ochsner Med Fdn & Ochsner Clin, Dept Mol Genet, New Orleans, LA 70121 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Div Nephrol, Rochester, MN 55905 USA. RP Alam, J (reprint author), Alton Ochsner Med Fdn & Ochsner Clin, Dept Mol Genet, 1516 Jefferson Highway, New Orleans, LA 70121 USA. EM jalam@ochsner.org RI Alam, Jawed/F-2596-2010 OI Alam, Jawed/0000-0001-6520-482X FU NHLBI NIH HHS [HL-48455, HL-55552]; NIDDK NIH HHS [DK-43135, DK-47060, DK-58950] NR 55 TC 107 Z9 108 U1 1 U2 3 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 APR PY 2003 VL 284 IS 4 BP F743 EP F752 DI 10.1152/ajprenal.00376.2002 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 652JW UT WOS:000181376900015 PM 12453873 ER PT J AU Titton, RL Gryzenia, PC Gervais, DA Arellano, RS Boland, GW Mueller, PR AF Titton, RL Gryzenia, PC Gervais, DA Arellano, RS Boland, GW Mueller, PR TI Continuous high-output drainage of hepatic abscess 3 months after radiofrequency ablation of hepatocellular carcinoma SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID LIVER METASTASES; TISSUE ABLATION; FOLLOW-UP; BILIARY OBSTRUCTION; TUMOR ABLATION; THERAPY; CANCER; CT; OPPORTUNITIES; CHALLENGES C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging & Intervent, White 270,55 Fruit St, Boston, MA 02114 USA. NR 34 TC 2 Z9 2 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 APR PY 2003 VL 180 IS 4 BP 1079 EP 1084 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XC UT WOS:000181745500034 PM 12646459 ER PT J AU Torriani, M Kattapuram, SV AF Torriani, M Kattapuram, SV TI Dynamic sonography of the forefoot: The sonographic mulder sign SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID NEUROMAS C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Torriani, M (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 15 Parkman St,WACC515, Boston, MA 02114 USA. NR 8 TC 14 Z9 14 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 APR PY 2003 VL 180 IS 4 BP 1121 EP 1123 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 658XC UT WOS:000181745500041 PM 12646466 ER PT J AU Deshpande, V Selig, MK Nielsen, GP Fernandez-del Castillo, C Lauwers, GY AF Deshpande, V Selig, MK Nielsen, GP Fernandez-del Castillo, C Lauwers, GY TI Ductulo-insular pancreatic endocrine neoplasms - Clinicopathologic analysis of a unique subtype of pancreatic endocrine neoplasms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pancreas; endocrine neoplasm; tumor; associated ductules; ductulo-insular complex ID ISLET CELL TUMOR; CARCINOMA; METASTASIS; EXOCRINE AB Pancreatic neoplasms with mixed ductal and endocrine components are a heterogeneous group of tumors. The least recognized of these are pancreatic endocrine tumors (PETs) displaying benign-appearing tumor-associated ductules. To characterize these ductulo-insular pancreatic endocrine tumors (DI-PETs), we reviewed a series of 92 resected PETs. To be considered as a DI-PET we required the presence and tight intermingling of ductules with the dominant endocrine component (including the presence of ductulo-insular units). A total of 15 PETs fulfilled our criteria (16.3%). The average age of the DI-PET patients was similar to typical PETS (54 years vs 56 years). These tumors were smaller and more often insulin positive than typical PETs (p <0.05). Diffuse stromal fibrosis was more frequent in DI-PETs (I I of 15; 73.3.7%) compared with PETs (8 of 72; 11.1%) (p <0.05). The tumor-associated ductules were composed of cuboidal cells with dense eosinophilic cytoplasm and round nuclei without atypia or mitoses. They were positive for cytokeratin 7 and cytokeratin 19 and lacked any neuroendocrine markers. Reversibly, the endocrine component was negative for cytokeratin 7 and cytokeratin 19 and positive for neuroendocrine markers. Ultrastructural examination of ductulo-insular units confirmed a dual ductal and endocrine differentiation with amphicrine differentiation in one case. Follow-up was available in 12 cases with an average follow-up of 70.1 months (range 25-203 months). Ten patients are currently alive, and two patients died 81 and 158 months after surgery. We conclude that DI-PETs are not uncommon and that they are biologically similar to other PETs. We also hypothesize that the ductal cells develop by transdifferentiation of the endocrine cells. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Lauwers, GY (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 17 Z9 19 U1 0 U2 1 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 APR PY 2003 VL 27 IS 4 BP 461 EP 468 DI 10.1097/00000478-200304000-00005 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 661DP UT WOS:000181876200005 PM 12657930 ER PT J AU Yantiss, RK Nielsen, GP Lauwers, GY Rosenberg, AE AF Yantiss, RK Nielsen, GP Lauwers, GY Rosenberg, AE TI Reactive nodular fibrous pseudotumor of the gastrointestinal tract and mesentery - A clinicopathologic study of five cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE reactive nodular fibrous pseudotumor; fibroinflammatory tumor; fibromatosis; sclerosing mesenteritis; mesentery; gastrointestinal tract; differential diagnosis ID INFLAMMATORY MYOFIBROBLASTIC TUMOR; STROMAL TUMORS; DIFFERENTIAL-DIAGNOSIS; INTRAABDOMINAL FIBROMATOSIS; ENTITY; FIBROSARCOMA; WALL; CD34; KIT AB Although the majority of mesenchymal lesions of the gastrointestinal tract are neoplastic in nature, nonneoplastic reactive processes may involve the gastrointestinal tract and mesentery, causing diagnostic confusion with more aggressive neoplasms, such as fibromatosis or gastrointestinal stromal tumors. In this study, we report a series of fibroinflammatory lesions of the gastrointestinal tract that we think represent a relatively cohesive group of tumors and describe the clinical and pathologic features of this entity, which we have termed "reactive nodular fibrous pseudotumor." The tumors affected five patients (four male and one female patient) who ranged in age from 48 to 71 years (mean 56 years). Two patients presented with acute abdominal pain without a significant past medical history, two had incidental lesions discovered during evaluation for other medical conditions, and one was found to have an abdominal mass. Three patients had a history of abdominal surgery. The tumors were multiple in three patients and solitary in two patients. In four cases, at least one of the tumors involved the small intestine or colon, and the lesion was confined to the peripancreatic soft tissue in one case. The tumors were firm, tan-white, ranged in size from 4.3 to 6.5 cm in greatest dimension, and were grossly well circumscribed. All of the lesions were of low to moderate cellularity and composed of stellate or spindled fibroblasts arranged haphazardly or in intersecting fascicles. Three cases had microscopically infiltrative borders. The stroma was rich in collagen, which was wire-like, keloidal, or hyalinized. Intralesional mononuclear cells were sparse but were more numerous peripherally and frequently arranged in lymphoid aggregates. Immunohistochemical stains demonstrated that all of the tumors stained for vimentin, 80% stained for CD 117 or muscle specific actin, 60% stained for smooth muscle actin or desmin, and none of the tumors stained for CD34, S-100 protein, or anaplastic lymphoma kinase-1. Follow-up information was available in all cases: four patients had no residual disease following surgical resection (mean follow-up 16.3 months) and one patient who had an incomplete surgical resection had stable disease at 26 months. In summary, we report a series of distinct intraabdominal fibroinflammatory pseudotumors that we have collectively termed "reactive nodular fibrous pseudotumors." These lesions are uncommon and may infiltrate the bowel wall, thereby mimicking primary bowel neoplasms or intraabdominal fibromatosis. Recognition of these nonneoplastic lesions is important, as they pursue a benign clinical course, but may be confused with other mesenchymal neoplasms that require more aggressive treatment. C1 Univ Massachusetts, Dept Pathol, Mem Med Ctr, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Yantiss, RK (reprint author), Univ Massachusetts, Dept Pathol, Mem Med Ctr, 55 Lake Ave N, Worcester, MA 01655 USA. NR 41 TC 27 Z9 30 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 2003 VL 27 IS 4 BP 532 EP 540 DI 10.1097/00000478-200304000-00015 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 661DP UT WOS:000181876200015 PM 12657940 ER PT J AU Patenaude, AF Guttmacher, AE Collins, FS AF Patenaude, AF Guttmacher, AE Collins, FS TI Psychologists' contributions to the genetic revolution SO AMERICAN PSYCHOLOGIST LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NHGRI, Bethesda, MD 20892 USA. RP Patenaude, AF (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2003 VL 58 IS 4 BP 319 EP 320 DI 10.1037/0003-066X.58.4.319b PG 2 WC Psychology, Multidisciplinary SC Psychology GA 694QV UT WOS:000183786200013 PM 12866400 ER PT J AU Huang, Z Szostak, JW AF Huang, Z Szostak, JW TI Selective labeling and detection of specific RNAs in an RNA mixture SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE RNA selective labeling; direct detection and quantification of viral RNA; DNA template; DNA polymerase ID RIBOSOMAL-RNA; ESCHERICHIA-COLI; MESSENGER-RNA; POLYMERASE-I; VIRUS-RNA; RT-PCR; DNA; EXPRESSION; GROWTH; SYSTEM AB We report here a unique approach to selectively label and detect specific RNA in an RNA mixture (without separation or purification) using DNA polymerase, dNTP labels, and a short synthetic DNA template complementary to the 3'-terminus of the RNA. The detection sensitivity is high, at attomole level (10-18 mole). The selective principle was demonstrated by individually labeling and detecting RNAs in a RNA mixture when different templates were provided. By taking advantage of the template-directed selectivity, poly(A) tail-containing mRNA in total RNA was detected and labeled at the 3'-terminal on a poly(T) template. Nonradioactive labels, such as fluorophore and antigen labels, may also be used; this method can be applied in methodology for direct detection and quantification of viral RNAs. (C) 2003 Elsevier Science (USA). All rights reserved. C1 CUNY Brooklyn Coll, Grad Sch, Dept Chem, PhD Programs Biochem & Chem, Brooklyn, NY 11210 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Huang, Z (reprint author), CUNY Brooklyn Coll, Grad Sch, Dept Chem, PhD Programs Biochem & Chem, Brooklyn, NY 11210 USA. NR 21 TC 5 Z9 5 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 1 PY 2003 VL 315 IS 1 BP 129 EP 133 DI 10.1016/S0003-2697(02)00701-7 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 669BH UT WOS:000182331700015 PM 12672421 ER PT J AU Maratea, A Ecker, J Leffert, L Pian-Smith, MCM AF Maratea, A Ecker, J Leffert, L Pian-Smith, MCM TI Altered vasoactivity as a marker for preeclampsia SO ANESTHESIOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Society-for-Obstetric-Anesthesia-and-Perinatology CY MAY 14-17, 2003 CL PHOENIX, ARIZONA SP Soc Obstetric Anesthesia Perinatol C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2003 VL 98 SU S MA A14 BP 7 EP 7 PG 1 WC Anesthesiology SC Anesthesiology GA 662VQ UT WOS:000181969900015 ER PT J AU Kakinohana, M Marsala, M Carter, C Davison, K Yaksh, TL AF Kakinohana, M Marsala, M Carter, C Davison, K Yaksh, TL TI Neuraxial morphine may trigger transient motor dysfunction after a noninjurious interval of spinal cord ischemia - A clinical and experimental study SO ANESTHESIOLOGY LA English DT Article ID FOCAL CEREBRAL-ISCHEMIA; INTRATHECAL MORPHINE; NALOXONE REVERSAL; AMINO-ACID; BLOOD-FLOW; RAT; PHARMACOLOGY; OCCLUSION; NEURONS; STROKE AB Background: A patient underwent repair of a thoracoabdominal aortic aneurysm. Epidural morphine, 4 mg, was given for pain relief. After anesthesia, the patient displayed lower extremity paraparesis. This effect was reversed by naloxone. The authors sought to confirm these observations using a rat spinal ischemia model to define the effects of intrathecal morphine administered at various times after reflow on behavior and spinal histopathology. Methods: Spinal cord ischemia was induced for 6 min using an intraaortic balloon. Morphine or saline, 30 mug, was injected intrathecally at 0.5, 2, or 24 h after reflow. in a separate group, spinal cord temperature was decreased to 27degreesC before ischemia. After ischemia, recovery of motor function was assessed periodically using the motor deficit index (0 = complete recovery; 6 = complete paraplegia). Results: After ischemia, all rats showed near-complete recovery of function by 4-6 h. intrathecal injection of morphine at 0.5 or 2 h of reflow (but not at 24 h) but not saline caused a development of hind limb dysfunction and lasted for 4.5 h (motor deficit index score = 4-6). This effect was reversed by intrathecal naloxone (30 mug). Intrathecal morphine administered after hypothermic ischemia was without effect. Histopathological analysis in animals that received intrathecal morphine at 0.5 or 2 h after ischemia (but not at 24 h) revealed dark-staining a motoneurons and interneurons. Intrathecal saline or spinal hypothermia plus morphine was without effect. Conclusions: These data indicate that during the immediate reflow following a noninjurious interval of spinal ischemia, intrathecal morphine potentiates motor dysfunction. Reversal by naloxone suggests that this effect results from an opioid receptor-mediated potentiation of a transient block of inhibitory neurons initiated by spinal ischemia. C1 Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Boston, MA 02114 USA. RP Marsala, M (reprint author), Univ Calif San Diego, Dept Anesthesiol, 9500 Gilman Dr,0818, La Jolla, CA 92093 USA. RI Yaksh, Tony/D-4119-2009 FU NINDS NIH HHS [NS32794] NR 37 TC 26 Z9 28 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD APR PY 2003 VL 98 IS 4 BP 862 EP 870 DI 10.1097/00000542-200304000-00012 PG 9 WC Anesthesiology SC Anesthesiology GA 660ZG UT WOS:000181865500011 PM 12657847 ER PT J AU Tilly, JL AF Tilly, JL TI Oocyte apoptosis: prevention strategies, and implications for female aging and the menopause SO ANNALES D ENDOCRINOLOGIE LA English DT Article; Proceedings Paper CT 46th International Henri Pierre Klotz Conference on Clinical Endocrinology - Endocrinology of Menopause and Andropause CY 2003 CL PARIS, FRANCE ID PROGRAMMED CELL-DEATH; HYDROCARBON RECEPTOR; TRANSCRIPTION FACTOR; GENE-EXPRESSION; OVARIAN FAILURE; GERM-CELLS; MOUSE; MICE; CYCLOPHOSPHAMIDE; CHEMOTHERAPY C1 Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vinent Obstet & Gynecol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vinent Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 39 TC 8 Z9 9 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD APR PY 2003 VL 64 IS 2 BP 82 EP 84 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 677RT UT WOS:000182821900003 PM 12773936 ER PT J AU Houmard, BS Hansen, KA Woodruff, TK Sluss, PM Bremner, WJ Soules, MR Klein, NA AF Houmard, BS Hansen, KA Woodruff, TK Sluss, PM Bremner, WJ Soules, MR Klein, NA TI Age-related analysis of inhibin A and B relative to the intercycle monotropic FSH rise in normal ovulatory women SO ANNALES D ENDOCRINOLOGIE LA English DT Article; Proceedings Paper CT 46th International Henri Pierre Klotz Conference on Clinical Endocrinology - Endocrinology of Menopause and Andropause CY 2003 CL PARIS, FRANCE C1 Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL USA. RP Houmard, BS (reprint author), Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSON EDITEUR PI PARIS 06 PA 120 BLVD SAINT-GERMAIN, 75280 PARIS 06, FRANCE SN 0003-4266 J9 ANN ENDOCRINOL-PARIS JI Ann Endocrinol. PD APR PY 2003 VL 64 IS 2 BP 86 EP 86 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 677RT UT WOS:000182821900005 PM 12773938 ER PT J AU Tgavalekos, NT Venegas, JG Suki, B Lutchen, KR AF Tgavalekos, NT Venegas, JG Suki, B Lutchen, KR TI Relation between structure, function, and imaging in a three-dimensional model of the lung SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE asthma; airway hyperresponsiveness; ventilation distribution; PET ID INPUT IMPEDANCE; VENTILATION DISTRIBUTION; 3-DIMENSIONAL MODEL; AIRWAY; BRONCHOCONSTRICTION; ASTHMA; TREE AB Previous studies have reported morphometric models to predict function relations in the lung. These models, however, are not anatomically explicit. We have advanced a three-dimensional airway tree model to relate dynamic lung function to alterations in structure, particularly when constriction patterns are imposed heterogeneously in specific anatomic locations. First, we predicted the sensitivity of dynamic lung resistance and elastance (R-L and E-L) to explicit forms of potential constriction patterns. Simulations show that severe and heterogeneous peripheral airway constriction confined to a single region in the lung (apex, mid, or base) will not produce substantial alterations in whole lung properties as measured from the airway opening. Conversely, when measured R-L and E-L are abnormal, it is likely that significant (but not necessarily homogeneous) constriction has occurred throughout the entire airway tree. We also introduce the concept of image-assisted modeling. Here positron emission tomographic imaging data sensitive to ventilation heterogeneity is synthesized with R-L and E-L data to help identify which airway constriction conditions could be consistent with both data sets. An ultimate goal would be personalized predictions. (C) 2003 Biomedical Engineering Society. C1 Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Lutchen, KR (reprint author), Boston Univ, Dept Biomed Engn, 44 Cummington St, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL68011-01, HL62269-02] NR 21 TC 33 Z9 37 U1 1 U2 4 PU BIOMEDICAL ENGINEERING SOC AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD APR PY 2003 VL 31 IS 4 BP 363 EP 373 DI 10.1114/1.1557972 PG 11 WC Engineering, Biomedical SC Engineering GA 686RV UT WOS:000183335500001 PM 12723678 ER PT J AU Chung, DC Rustgi, AK AF Chung, DC Rustgi, AK TI The hereditary nonpolyposis colorectal cancer syndrome: Genetics and clinical implications SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID DNA-MISMATCH-REPAIR; TUMOR MICROSATELLITE INSTABILITY; COLON-CANCER; GERMLINE MUTATIONS; TURCOTS-SYNDROME; LYNCH SYNDROME; FAMILIES; CARCINOMA; RISK; MSH6 AB Basic studies of DNA replication and repair have provided surprising and pivotal insights into a novel pathway of tumorigenesis. Defects in the DNA mismatch repair process dramatically increase the risk for specific types of cancer because of instability in microsatellite DNA sequences. A germline mutation in either the hMSH2 or hMLH1 mismatch repair gene results in the hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch, syndrome. The lifetime risk for colon cancer is 80% in affected persons, and an aggressive cancer surveillance program is essential not only for these individuals but also for at-risk family members. The diagnosis of HNPCC can be made by fulfillment of the Amsterdam clinical criteria or through genetic testing for germline mutations in hMSH2 or hMLH1. Genetic testing is particularly useful in families with atypical clinical features and also for cancer risk assessment within an established HNPCC kindred. Microsatellite instability (MSI) of DNA is a hallmark feature of HNPCC-associated tumors, and as many as 15% of cases of sporadic colorectal cancer also display MSI. The biological behavior of colorectal tumors with MSI is distinctive; the most intriguing feature is their favorable natural history. The study of HNPCC has provided an example of the powerful interplay between molecular genetics and clinical care. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, GI Canc Genet Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GI Canc Genet Serv, GRJ 825,50 Blossom St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA92594]; NIDDK NIH HHS [DK56645] NR 67 TC 160 Z9 173 U1 0 U2 7 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 2003 VL 138 IS 7 BP 560 EP 570 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 661BV UT WOS:000181872100005 PM 12667026 ER PT J AU Gazelle, GS Hunink, MGM Kuntz, KM McMahon, PM Halpern, EF Beinfeld, M Lester, JS Tanabe, KK Weinstein, MC AF Gazelle, GS Hunink, MGM Kuntz, KM McMahon, PM Halpern, EF Beinfeld, M Lester, JS Tanabe, KK Weinstein, MC TI Cost-effectiveness of hepatic metastasectomy in patients with metastatic colorectal carcinoma - A state-transition Monte Carlo decision analysis SO ANNALS OF SURGERY LA English DT Article ID PERIOPERATIVE BLOOD-TRANSFUSION; FACTORS INFLUENCING SURVIVAL; QUALITY-OF-LIFE; LIVER METASTASES; ARTERIAL PORTOGRAPHY; NATURAL-HISTORY; INTRAOPERATIVE ULTRASOUND; OPERATIVE ULTRASOUND; CONVENIENT APPROXIMATION; HELICAL CT AB Objective To evaluate the cost-effectiveness of hepatic resection ("metastasectomy") in patients with metachronous liver metastases from colorectal carcinoma (CRC), and to investigate the impact of operative and follow-up strategies on outcomes, cost, and cost-effectiveness. Summary Background Data There is substantial evidence that resection of CRC liver metastases can result in long-term survival in some patients. However, several unresolved issues are difficult to address using currently available clinical data. These include the appropriate threshold for resection, whether to perform repeat resection, and the relative cost-effectiveness of the procedure(s). Methods The authors developed a state-transition Monte Carlo decision model to evaluate the (societal) cost-effectiveness of hepatic metastasectomy in patients with metachronous CRC liver metastases. The model tracks the presence, number, size, location, growth, detection, and removal of up to 15 individual metastases in each patient. Survival, quality of life, and cost are predicted on the basis of disease extent. Imaging and surgery affect outcomes via detection and removal of individual metastases. Several patient management strategies were developed and compared with respect to cost, effectiveness, and incremental cost-effectiveness ($/quality-adjusted life year [QALY]). A reference strategy in which metastasectomy is not offered and imaging is not performed for the purpose of assessing resectability or operative planning ("no-surgery" strategy) was included for comparison. Extensive sensitivity analysis was performed to evaluate the impact of alternative model assumptions on results. Results A strategy permitting resection of up to six metastases and one repeat resection, with CT follow-up every 6 months, resulted in a gain of 2.63 QALYs relative to the no-test/no-treat strategy, at an incremental cost of $18,100/QALY. When additional surgical strategies were considered, the incremental cost-effectiveness ratio (ICER; relative to the next least effective strategy) of the six metastases, one repeat, 6-month strategy was $31,700/QALY. Across a range of model assumptions, more aggressive treatment strategies (i.e., resection of more metastases, resection of recurrent metastases) were superior to less aggressive strategies and had ICERs below $35,000/QALY. Findings were insensitive to changes in most model parameters but somewhat sensitive to changes in surgery and treatment costs. Conclusions Hepatic metastasectomy is a cost-effective option for selected patients with metachronous CRC metastases limited to the liver. When considering metastasectomy, more aggressive approaches are generally preferred to less aggressive approaches. Overall, surgeons should be encouraged to consider resection for all patients whose metastases can technically be removed. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Inst Technol Assessment, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Erasmus Univ, Sch Med, Dept Epidemiol & Biostat, ART Program, NL-3000 DR Rotterdam, Netherlands. Erasmus Univ, Sch Med, Dept Radiol, Rotterdam, Netherlands. RP Gazelle, GS (reprint author), Inst Technol Assessment, Zero Emerson Pl,Suite 2H, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA/HS 83960] NR 88 TC 35 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD APR PY 2003 VL 237 IS 4 BP 544 EP 555 DI 10.1097/00000658-200304000-00017 PG 12 WC Surgery SC Surgery GA 730MK UT WOS:000185834400017 PM 12677152 ER PT J AU Joseph, NE Sigurdson, ER Hanlon, AL Wang, H Mayer, RJ MacDonald, JS Catalano, PJ Haller, DG AF Joseph, NE Sigurdson, ER Hanlon, AL Wang, H Mayer, RJ MacDonald, JS Catalano, PJ Haller, DG TI Accuracy of determining nodal negativity in colorectal cancer on the basis of the number of nodes retrieved on resection SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE lymph node status; colon cancer; survival; 5-fluorouracil chemotherapy; prognostic factors ID SMALL LYMPH-NODES; COLON-CANCER; ADJUVANT THERAPY; RECTAL-CANCER; METASTASES; CARCINOMA; ADENOCARCINOMA AB Background: Correct determination of nodal status is pivotal to accurate staging and predicting survival. Methods: This is a secondary analysis of INT0089, an intergroup trial of adjuvant chemotherapy for high-risk stage II and III colon cancer. A subset of patients was studied who underwent right or left hemicolectomy and from whom at least 10 lymph nodes were examined. A mathematical model was created to estimate the probability of a true negative result on the basis of the number of nodes examined. The number of nodes needed to predict nodal negativity with 85%, 50%, and 25% probability on the basis of tumor stage was calculated. Results: In this analysis, 1585 patients were studied. The average number of nodes removed at surgery was comparable between treatment groups at 18.5 (median of 16 in all groups). With this model, when 18 nodes are removed at resection, there is a <25% probability of true node negativity in T1/T2 tumors, whereas <10 nodes need to be examined in T3 and T4 tumors to achieve the same probability. Conclusions: Tumor stage and the number of nodes retrieved at resection influence the accuracy of determining nodal status in colon cancer. Most patients are understaged. Underestimating nodal stage may influence decisions regarding adjuvant therapy, as well as overall prognosis. C1 Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Biostat, Philadelphia, PA 19111 USA. Canc & Leukemia Grp B, Boston, MA USA. SW Oncol Grp, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Eastern Cooperat Oncol Grp, Philadelphia, PA USA. RP Sigurdson, ER (reprint author), Fox Chase Canc Ctr, Dept Surg Oncol, 7701 Burholme Ave, Philadelphia, PA 19111 USA. NR 24 TC 163 Z9 170 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD APR PY 2003 VL 10 IS 3 BP 213 EP 218 DI 10.1245/ASO.2003.03.059 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 665AY UT WOS:000182098500005 PM 12679304 ER PT J AU Hoerbelt, R Keunecke, L Grimm, H Schwemmle, K Padberg, W AF Hoerbelt, R Keunecke, L Grimm, H Schwemmle, K Padberg, W TI The value of a noninvasive diagnostic approach to mediastinal masses SO ANNALS OF THORACIC SURGERY LA English DT Article ID NEEDLE-BIOPSY; TUMORS AB Background. Mediastinal tumors show a wide variability, and therefore, a standardized diagnostic and therapeutic workup is instrumental. We subdivided mediastinal tumors into nonlymphatic mediastinal tumors (NLMTs), most of which require surgical resection without need of preoperative histology, and mediastinal lymphadenopathy (MLA), requiring surgical biopsy for exact histologic classification. We investigated the accuracy of noninvasive diagnostic studies distinguishing between the two groups of MLA and NLMT. Methods. A retrospective analysis was performed on patients who had previously undergone surgery on mediastinal tumors. Their data were statistically analyzed (X-2 test, logistic regression analysis), and the values of medical history, physical examination, laboratory tests, and computerized tomography scan discriminating between MLA and NLMT were assessed. Results. Out of 299 patients included in the study, 242 (80.9%) had MLA and 57 (19.1%) had NLMT. Sensitivity and specificity of noninvasive investigations for differentiation of MLA and NLMT were 98.2% and 86.0%, respectively. Whereas the prevalence of thoracic symptoms such as shortness of breath, cough, or chest pain was similar in both groups (MLA, 165 [69.3%]; NLMT, 41 169.5%]; p = 0.98), systemic symptoms, including fever, night sweats, or weight loss (MLA, 110 [49.8%]; NLMT, 17 [29.3%]; p < 0.01), and signs of inflammation, such as c-reactive protein, erythrocyte sedimentation rate, and leukocytosis (MLA, 202 [85.6%]; NLMT, 34 [57.6%]; p < 0.001), were significantly more common in MLA. Conclusions. Noninvasive diagnostic procedures, including medical history, physical examination, laboratory tests, and computerized tomographic scan, are highly sensitive in detecting MLAs that should undergo surgical biopsy. Our data suggest confirming all suspected NLMTs by fine needle aspiration (FNA) biopsy before surgery. (C) 2003 by The Society of Thoracic Surgeons. C1 Univ Giessen, Dept Gen & Thorac Surg, Giessen, Germany. RP Hoerbelt, R (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 15 TC 8 Z9 9 U1 1 U2 2 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 APR PY 2003 VL 75 IS 4 BP 1086 EP 1090 AR PII S0003-4975(02)04726-4 DI 10.1016/S0003-4975(02)04726-4 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 662KX UT WOS:000181946800004 PM 12683542 ER PT J AU Thatte, HS Biswas, KS Najjar, SF Birjiniuk, V Crittenden, MD Michel, T Khuri, SF AF Thatte, HS Biswas, KS Najjar, SF Birjiniuk, V Crittenden, MD Michel, T Khuri, SF TI Multi-photon microscopic evaluation of saphenous vein endothelium and its preservation with a new solution, GALA SO ANNALS OF THORACIC SURGERY LA English DT Article ID SCANNING FLUORESCENCE MICROSCOPY; NITRIC-OXIDE SYNTHASE; GRAFT FAILURE; CELLS; PATHOPHYSIOLOGY; STORAGE; SURGERY; INJURY AB Background. Injury to endothelium can compromise the patency of bypass grafts harvested during coronary artery bypass graft (CABC) surgery. Maintaining structural and functional viability of endothelium in grafts may lead to improved long-term patency. The information gained from the application of multi-photon microscopy in transmission and epifluorescence mode was used to assess the structural and functional integrity of human saphenous vein segments stored in multiple preservation solutions, and to design a superior storage solution. Methods. Multi-photon microscopy was used to image deep within saphenous vein tissue harvested from patients undergoing CABG for analysis of endothelial structure and function. Endothelial cell structural viability, calcium mobilization, and nitric oxide generation were determined using specific fluorescence markers. Results. Within 60 minutes of harvest and storage in standard preservation solutions, calcium mobilization and nitric oxide generation were markedly diminished with more than 90% of endothelial cells no longer viable in the vein. In contrast, veins could be stored for 24 hours without substantial loss in cell viability in a newly formulated heparinized physiologic buffered salt solution containing glutathione, ascorbic acid, and L-arginine (GALA). Conclusions. Standard solutions in clinical use today led to a profound decline in saphenous vein endothelial cell viability, whereas the newly designed physiologic salt solution (GALA) maintained endothelial function and structural viability for up to 24 hours. The improvements seen from using GALA as a vessel storage medium may lead to greater long-term vein graft patency following CABG surgery. (C) 2003 by The Society of Thoracic Surgeons. C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, VA Boston Healthcare Syst, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Dept Surg 112, 1400 VF W Pkwy, Boston, MA 02132 USA. NR 25 TC 24 Z9 25 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 APR PY 2003 VL 75 IS 4 BP 1145 EP 1152 AR PII S0003-4975(02)04705-7 DI 10.1016/S0003-4975(02)04705-7 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 662KX UT WOS:000181946800017 PM 12683553 ER PT J AU Wallace, A Ratcliffe, M AF Wallace, A Ratcliffe, M TI Ventricular energetics in endoventricular circular patch plasty for dyskinetic anterior left ventricular aneurysm - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, San Francisco, CA 94121 USA. RP Wallace, A (reprint author), San Francisco Vet Affairs Med Ctr, VAMC Surg 112D, 4150 Clement St, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2003 VL 75 IS 4 BP 1208 EP 1209 AR PII S0003-4975(03)00122-X DI 10.1016/S0003-4975(03)00122-X PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 662KX UT WOS:000181946800030 ER PT J AU Hilgenberg, AD Mora, BN AF Hilgenberg, AD Mora, BN TI Composite aortic root replacement with a bovine pericardial valve conduit SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material AB In order to offer selected patients undergoing composite aortic root replacement the advantages of a tissue valve, we have constructed conduits intraoperatively by suturing a stented bovine pericardial valve (Edwards Life-sciences LLC, Irvine, CA) inside of a Dacron tube graft (Boston Scientific Corp, Natick, MA). The conduit is quickly made from readily available materials, is easily implanted, and can accommodate any of the anatomic situations encountered in repair of aortic root aneurysms. It is particularly suitable for patients 65 years of age and older. (C) 2003 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. RP Hilgenberg, AD (reprint author), Massachusetts Gen Hosp, Cardiac Surg Div, Warren 735, Boston, MA 02114 USA. EM ahilgenberg@partners.org NR 3 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 2003 VL 75 IS 4 BP 1338 EP 1339 AR PII S0003-4975(02)04510-1 DI 10.1016/S0003-4975(02)04510-1 PG 2 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 662KX UT WOS:000181946800066 PM 12683599 ER PT J AU Andes, D Marchillo, K Lowther, J Bryskier, A Stamstad, T Conklin, R AF Andes, D Marchillo, K Lowther, J Bryskier, A Stamstad, T Conklin, R TI In vivo pharmacodynamics of HMR 3270, a glucan synthase inhibitor, in a murine candidiasis model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BLOOD-STREAM INFECTIONS; ANTIFUNGAL AGENTS; STREPTOCOCCUS-PNEUMONIAE; UNITED-STATES; MOUSE MODELS; OTITIS-MEDIA; ECHINOCANDIN; ALBICANS; FLUCONAZOLE; ASPERGILLOSIS AB In vivo pharmacokinetic/pharmacodynamic characterization for numerous antibacterial compounds has had a significant impact upon optimal dosing regimen design and the development of in vivo susceptibility breakpoints. More recently, similar characterization has been undertaken for antifungal drug classes. Very little is known of these pharmacodynamic relationships for the new echinocandin class of compounds. We utilized a neutropenic murine model of disseminated candidiasis to describe the time course antifungal activity of HMR 3270, a new glucan synthase inhibitor. Single-dose in vivo time kill studies with four 16-fold escalating doses demonstrated concentration-dependent killing when drug levels in serum were more than four times the MIC. Postantifungal effects were dose dependent, ranging from 8 to 80 h duration. Multiple dosing regimen studies utilized six total doses, four dosing intervals, and a treatment duration of 6 days. Shortening the dosing interval from every 144 h (q144h) to q36h resulted in a fourfold rise in the dose necessary to achieve a net fungistatic effect. The peak/MIC ratio most strongly correlated with treatment outcomes (peak/MIC ratio, R 2 = 98%; ratio of the area under the concentration-time curve from 0 to 24 h to the MIC, R-2 = 79%, percentage of time above the MIC, R-2 = 61%). Studies were also conducted with five additional Candida albicans isolates to determine if a similar peak/MIC ratio was associated with efficacy. In vivo concentration-dependent killing was similarly observed in studies with each of the additional isolates. The peak/MIC ratio necessary to produce efficacy was relatively similar among the strains studied (P = 0.42). The peak/MIC ratio (mean standard deviation) necessary to achieve a fungistatic effect was 3.72 +/- 1.84, and the ratio necessary to achieve maximal killing was near 10. C1 Univ Wisconsin, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Aventis Pharmaceut, Romainville, France. RP Andes, D (reprint author), Univ Wisconsin, 600 Highland Ave,Room H4-572, Madison, WI 53792 USA. NR 31 TC 68 Z9 76 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2003 VL 47 IS 4 BP 1187 EP 1192 DI 10.1128/AAC.47.4.1187-1192.2003 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 660PR UT WOS:000181842000002 PM 12654645 ER PT J AU Andes, D Marchillo, K Stamstad, T Conklin, R AF Andes, D Marchillo, K Stamstad, T Conklin, R TI In vivo pharmacodynamics of a new triazole, ravulconazole, in a murine candidiasis model SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO; STREPTOCOCCUS-PNEUMONIAE; ANTIFUNGAL AGENTS; PROTEIN-BINDING; AMPHOTERICIN-B; OTITIS-MEDIA; FLUCONAZOLE; ALBICANS; ITRACONAZOLE; INFECTIONS AB In vivo studies have characterized the pharmacodynamic characteristics of the triazole fluconazole. These investigations demonstrated that the ratio of the area under the concentration-time curve from 0 to 24 h to the MIC (24-h AUC/MIC ratio) is the critical pharmacokinetic/pharmacodynamic (PK/PD) parameter associated with treatment efficacy. Further analysis demonstrated that a fluconazole 24-h AUC/MIC ratio of 20 to 25 was predictive of treatment success in both experimental models and clinical trials. We used a neutropenic murine model of disseminated Candida albicans infection to similarly characterize the time course activity of the new triazole ravuconazole. The PK/PD parameters (percent time above the MIC, AUC/MIC ratio, and peak level in serum/MIC ratio) were correlated with in vivo efficacy, as measured by organism number in kidney cultures after 24 and 72 h of therapy. Ravuconazole kinetics and protein binding were performed in neutropenic infected mice. Peak/dose and AUC/dose values ranged from 0.03 to 0.04 and 0.30 to 0.34, respectively. Serum elimination half-life ranged from 3.9 to 4.8 h. Protein binding was 95.8%. Single-dose postantifungal effect studies demonstrated prolonged suppression of organism regrowth after serum ravuconazole levels had fallen below the MIC. Treatment efficacies with the five dosing intervals studied were similar, supporting the argument for the AUC/MIC ratio as the PK/PD parameter predictive of efficacy. Nonlinear regression analysis also suggested that the AUC/MIC ratio was strongly predictive of treatment outcomes (AUC/MIC ratio, R-2 = 91%; peak/MIC ratio, R-2 = 85%; percent time above the MIC, R-2 = 47 to 65%). Similar studies were conducted with seven additional C. albicans isolates with various ravuconazole susceptibilities (MIC, 0.016 to 0.12 mug/ml) to determine if a similar 24-h AUC/MIC ratio was associated with efficacy. The ravuconazole free-drug AUC/MIC ration were similar for all of the organisms studied (10 to 36; mean +/- SD = 20.3 +/- 8.2; P = 0.43). These free-drug AUC/MIC ratios are similar to those observed for fluconazole in this model. C1 Univ Wisconsin, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Andes, D (reprint author), Univ Wisconsin, 600 Highland Ave,Room H4-572, Madison, WI 53792 USA. NR 30 TC 67 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2003 VL 47 IS 4 BP 1193 EP 1199 DI 10.1128/AAC.47.4.1193-1199.2003 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 660PR UT WOS:000181842000003 PM 12654646 ER PT J AU Ince, D Zhang, XM Hooper, DC AF Ince, D Zhang, XM Hooper, DC TI Activity of and resistance to moxifloxacin in Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID IN-VITRO ACTIVITY; STREPTOCOCCUS-PNEUMONIAE; TOPOISOMERASE-IV; DNA GYRASE; ANTIBACTERIAL ACTIVITIES; TARGET INTERACTIONS; COUMARIN ACTIVITY; QUINOLONE; FLUOROQUINOLONES; CIPROFLOXACIN AB Moxifloxacin has enhanced potency against Staphylococcus aureus, lower propensity to select for resistant mutants, and higher bactericidal activity against highly resistant strains than ciprofloxacin. Despite similar activity against purified S. aureus topoisomerase IV and DNA gyrase, it selects for topoisomerase IV mutants, making topoisomerase IV the preferred target in vivo. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Med Serv, 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 33 TC 35 Z9 35 U1 0 U2 1 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 APR PY 2003 VL 47 IS 4 BP 1410 EP 1415 DI 10.1128/AAC.47.4.1410-1415.2003 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 660PR UT WOS:000181842000037 PM 12654680 ER PT J AU Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Rinaldi, MG Loebenberg, D Graybill, JR AF Gonzalez, GM Tijerina, R Najvar, LK Bocanegra, R Rinaldi, MG Loebenberg, D Graybill, JR TI Activity of posaconazole against Pseudallescheria boydii: In vitro and in vivo assays SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INFECTION; SCH56592; MODEL AB Thirty isolates of Pseudallescheria boydii were tested to compare the in vitro activity of posaconazole with those of fluconazole and itraconazole, using NCCLS methods. Posaconazole was evaluated in an immunosuppressed mouse model of disseminated pseudallescheriasis. Posaconazole was more effective than itraconazole and as effective as fluconazole in preventing death and significantly reducing the CFU of P. boydii from tissues. C1 Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Monterrey 64460, Nuevo Leon, Mexico. Univ Texas, Hlth Sci Ctr, Div Infect Dis 7881, Dept Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Schering Plough Corp, Inst Res, Kenilworth, NJ 07033 USA. RP Gonzalez, GM (reprint author), Univ Autonoma Nuevo Leon, Dept Microbiol, Fac Med, Madero & Dr Eduardo A Pequeno S-N,Colonia Mitras, Monterrey 64460, Nuevo Leon, Mexico. NR 14 TC 31 Z9 33 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2003 VL 47 IS 4 BP 1436 EP 1438 DI 10.1128/AAC.47.4.1436-1438.2003 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 660PR UT WOS:000181842000044 PM 12654687 ER PT J AU Baer, JS Sampson, PD Barr, HM Connor, PD Streissguth, AP AF Baer, JS Sampson, PD Barr, HM Connor, PD Streissguth, AP TI A 21-year longitudinal analysis of the effects of prenatal alcohol exposure on young adult drinking SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the Research-Society-on-Alcoholism CY JUN 23-28, 2001 CL MONTREAL, CANADA SP Res Soc Alcoholism ID MATERNAL SMOKING; PREGNANCY; RATS; ETHANOL; DRUG; RESPONSIVENESS; DEPENDENCE; DISORDER; INUTERO; SENSITIVITY AB Background: Prenatal alcohol exposure may be a risk factor for the development of alcohol problems in humans. Methods: We use data beginning with interviews of women in prenatal care at midpregnancy to predict alcohol use and alcohol-related problems in their offspring now aged 21 years. Maternal drinking during pregnancy was assessed from November 4, 1974, through October 2, 1975, along with measures of maternal smoking, use of caffeine and other drugs, and demographic factors. Family history of alcohol problems was assessed from interviews with parents when offspring were 14 years of age and updated when offspring were 21 years of age. Measures of parental use of alcohol and other drugs and many aspects of the family environment were assessed at 7 different ages, prenatally through 21 years. Young adult offspring (age, 21 years [N = 433]) provided self-reports of drinking quantity and frequency and completed the Alcohol Dependence Scale as a measure of alcohol-related problems and dependence. Results: Univariate, partial least squares, and regression analyses indicate that prenatal alcohol exposure is significantly associated with alcohol problems at 21 years of age. The relationship persists independent of the effects of family history of alcohol problems, nicotine exposure, other prenatal exposures, and postnatal environmental factors including parental use of other drugs. Prenatal nicotine exposure was not associated with alcohol problems by offspring at 21 years of age. Conclusions: Prenatal alcohol exposure is a risk factor for the development of drinking problems in humans. Potential mechanisms for the role of fetal exposure and the development of alcohol problems deserve study. C1 Univ Washington, Dept Psychol, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Stat, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Streissguth, AP (reprint author), Fetal Alcohol & Drug Unit, 180 Nickerson St, Seattle, WA 98109 USA. FU PHS HHS [R3701455-01-25] NR 48 TC 165 Z9 169 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2003 VL 60 IS 4 BP 377 EP 385 DI 10.1001/archpsyc.60.4.377 PG 9 WC Psychiatry SC Psychiatry GA 664ZW UT WOS:000182096000007 PM 12695315 ER PT J AU Bowden, CL Calabrese, JR Sachs, G Yatham, LN Asghar, SA Hompland, M Montgomery, P Earl, N Smoot, TM DeVeaugh-Geiss, J AF Bowden, CL Calabrese, JR Sachs, G Yatham, LN Asghar, SA Hompland, M Montgomery, P Earl, N Smoot, TM DeVeaugh-Geiss, J CA Lamictal 606 Study Grp TI A placebo-controlled 18-month trial of lamotrigine and lithium maintenance treatment in recently manic or hypomanic patients with bipolar I disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 4th International Conference on Bipolar Disorder CY JUN 14-16, 2001 CL PITTSBURGH, PENNSYLVANIA ID COMPARATIVE PROPHYLACTIC EFFICACY; MOOD DISORDERS; DOUBLE-BLIND; CARBAMAZEPINE; PREVALENCE; OUTPATIENTS; MONOTHERAPY; DEPRESSION; ILLNESS AB Background: Lamotrigine has been shown to be an effective treatment for bipolar depression and rapid cycling in placebo-controlled clinical trials. This double-blind, placebo-controlled study was conducted to assess the efficacy and tolerability of lamotrigine and lithium compared with placebo for the prevention of relapse or recurrence of mood episodes in recently manic or hypomanic patients with bipolar I disorder. Methods: After an 8- to 16-week open-label phase during which treatment with lamotrigine was initiated and other psychotropic drug regimens were discontinued, patients were randomized to lamotrigine (100-400 mg daily), lithium (0.8-1.1 mEq/L), or placebo as double-blind maintenance treatment for as long as 18 months. Results: Of 349 patients who met screening criteria and entered the open-label phase, 175 met stabilization criteria and were randomized to double-blind maintenance treatment (lamotrigine, 59 patients; lithium, 46 patients; and placebo, 70 patients). Both lamotrigine and lithium were superior to placebo at prolonging the time to intervention for any mood episode (lamotrigine vs placebo, P = .02; lithium vs placebo, P = .006). Lamotrigine was superior to placebo at prolonging the time to a depressive episode (P = .02). Lithium was superior to placebo at prolonging the time to a manic, hypomanic, or mixed episode (P = .006). The most common adverse event reported for lamotrigine was headache. Conclusions: Both lamotrigine and lithium were superior to placebo for the prevention of relapse or recurrence of mood episodes in patients with bipolar I disorder who had recently experienced a manic or hypomanic episode. The results indicate that lamotrigine is an effective, well-tolerated maintenance treatment for bipolar disorder, particularly for prophylaxis of depression. C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pharmacol, San Antonio, TX 78229 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Psychiat, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada. Ullevaal Univ Hosp, Oslo, Norway. Affective Disorders Clin, Bergen, Norway. GlaxoSmithKline, Res & Dev, Res Triangle Pk, NC USA. RP Bowden, CL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Psychiat, 7703 Floyd Curl Dr,Mail Code 7792, San Antonio, TX 78229 USA. NR 42 TC 421 Z9 433 U1 2 U2 15 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 2003 VL 60 IS 4 BP 392 EP 400 DI 10.1001/archpsyc.60.4.392 PG 9 WC Psychiatry SC Psychiatry GA 664ZW UT WOS:000182096000009 PM 12695317 ER PT J AU Graham, SH Hickey, RW AF Graham, SH Hickey, RW TI Cyclooxygenases in central nervous system diseases - A special role for cyclooxygenase 2 in neuronal cell death SO ARCHIVES OF NEUROLOGY LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; MITOGEN-INDUCIBLE CYCLOOXYGENASE; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); ALZHEIMERS-DISEASE; PPAR-GAMMA; BRAIN; EXPRESSION; LIGAND; DIFFERENTIATION; CONTRIBUTES C1 Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA. RP Graham, SH (reprint author), Vet Affairs Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Univ Dr C, Pittsburgh, PA 15240 USA. FU NICHD NIH HHS [K08 HD040848, K08 HD40848]; NINDS NIH HHS [R01 NS037459, R01 NS037459-06, R01 NS37459] NR 24 TC 30 Z9 33 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 2003 VL 60 IS 4 BP 628 EP 630 DI 10.1001/archneur.60.4.628 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 667CV UT WOS:000182214000024 PM 12707081 ER PT J AU Foster, CS Tufail, F Waheed, NK Chu, D Miserocchi, E Baltatzis, S Vredeveld, CM AF Foster, CS Tufail, F Waheed, NK Chu, D Miserocchi, E Baltatzis, S Vredeveld, CM TI Efficacy of etanercept in preventing relapse of uveitis controlled by methotrexate SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RHEUMATOID-ARTHRITIS; FUSION PROTEIN; THERAPY; MANAGEMENT; DISEASE AB Objective: To evaluate the efficacy of etanercept vs placebo in preventing relapses of uveitis in patients taking methotrexate with control of uveitis and whose methotrexate dosage was being tapered. Methods: Patients with chronic or recur-rent noninfectious uveitis with inflammation controlled by low-dose methotrexate were randomized to either the drug or placebo group in a double-masked manner, given a methotrexate taper schedule, and followed for 24 weeks. The main outcome measures were control of inflammation, visual acuity, and adverse reactions. Data were analyzed both as an attempt-to-treat analysis and an analysis only of those patients who completed the study. Results: A total of 20 patients were randomized to the drug and placebo groups. Relapse of uveitis occurred in 3 of 10 patients in the treatment group and 5 of 10 patients in the control group. Two patients in the treatment group withdrew prematurely from the study due to adverse effects. There was no significant difference between the treatment and placebo groups with regard to the rate of relapse and the final visual acuity. No patient suffered from any irreversible, long-term morbidity or mortality. Conclusion: Etanercept has no significant efficacy over placebo in preventing relapses of uveitis in patients being tapered from methotrexate. Arch Ophthalmol, 2003;121:437-440. C1 Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Foster, CS (reprint author), Massachusetts Eye & Ear Infirm, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 16 TC 100 Z9 104 U1 1 U2 3 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 APR PY 2003 VL 121 IS 4 BP 437 EP 440 DI 10.1001/archopht.121.4.437 PG 4 WC Ophthalmology SC Ophthalmology GA 664QM UT WOS:000182071800001 PM 12695239 ER PT J AU Kalayoglu, MV Galvan, C Mahdi, OS Byrne, GI Mansour, S AF Kalayoglu, MV Galvan, C Mahdi, OS Byrne, GI Mansour, S TI Serological association between Chlamydia pneumoniae infection and age-related macular degeneration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 05-10, 2002 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID ENDOTHELIAL GROWTH-FACTOR; LOW-DENSITY-LIPOPROTEIN; FOAM CELL-FORMATION; CARDIOVASCULAR-DISEASE; MONOCLONAL-ANTIBODIES; TRACHOMATIS HSP10; APOLIPOPROTEIN-E; BRUCHS MEMBRANE; ATHEROSCLEROSIS; PURIFICATION AB Background: Age-related macular degeneration (ARMD) is a leading cause of blindness in the United States, but the mechanisms that initiate and promote the disease remain ill defined. There are several risk factors that ARMD shares with atherosclerosis, and these diseases may have similar pathogenic mechanisms that involve inflammation. Chlamydia pneumoniae, a prokaryotic pathogen that causes chronic inflammation is now emerging as a risk factor in the development of cardiovascular diseases. It is therefore plausible that this microorganism also contributes to the pathogenesis of ARMD. Methods: To examine if C pneumonia infection is associated with ARMD, serum samples from 25 consecutive patients with ARMD and from 18 without the disease were collected and assayed for the presence of the antibodies to C pneumoniae elementary bodies, Chlamydia trachomatis heat shock protein 60 (cHsp60), C trachomatis heat shock protein 10 (cHsp 10), Escherichia coli GroEL, and E coli GroES. Results: A serological association was found between ARMD and anti-C pneumoniae antibodies (P=.047) but not between ARMD and the anti-C trachomatis or anti-E coli heat shock protein antibodies. The association remained statistically significant after adjusting for age and smoking, both established risk factors for ARMD. Conclusions: These data indicate that C pneumoniae infection may be associated with ARMD. Further studies on larger cohorts of individuals arc necessary to determine if this pathogen plays a role in the Pathogenesis of ARMD. Arch Ophihaltnol. 2003;121:478-482. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Educ Ctr, Boston, MA 02114 USA. Stanford Univ, Sch Med, Dept Ophthalmol, Palo Alto, CA 94304 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. RP Kalayoglu, MV (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ophthalm Educ Ctr, 8th Floor,243 Charles St, Boston, MA 02114 USA. EM Murat_Kalayoglu@meei.harvard.edu FU NIAID NIH HHS [R01 AI019782, R01 AI042790]; PHS HHS [A1 42790, A1 19782] NR 38 TC 57 Z9 61 U1 0 U2 1 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 APR PY 2003 VL 121 IS 4 BP 478 EP 482 DI 10.1001/archopht.121.4.478 PG 5 WC Ophthalmology SC Ophthalmology GA 664QM UT WOS:000182071800006 PM 12695244 ER PT J AU Banks, MC Robe-Collignon, NJ Rizzo, JF Pasquale, LR AF Banks, MC Robe-Collignon, NJ Rizzo, JF Pasquale, LR TI Scanning laser polarimetry of edematous and atrophic optic nerve heads SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol ID FIBER LAYER THICKNESS; CORNEAL POLARIZATION AXIS; GLAUCOMATOUS EYES; NEUROPATHY; NEURITIS; BIREFRINGENCE; DIAGNOSIS; PRESSURE AB Objective: To determine if scanning laser polarimetry (SLP) measures form birefringence of the retinal nerve fiber layer (RNFL). Methods: Consecutive patients with either acute unilateral disc edema or chronic diffuse unilateral disc atrophy underwent SLP using the GDx Nerve Fiber Analyzer (Laser Diagnostic Technologies Inc, San Diego, Calif). The former group had peripapillary RNFL edema, presumably with no change in form birefringence elements, while the latter had optic nerve atrophy, presumably with a loss of birefringence elements in the RNFL. A subset of patients with acute unilateral disc edema who subsequently developed disc atrophy had repeated SLP at 6 months. Intereye and intertest comparisons of 6 SLP parameters representative of RNFL thickness were performed using the paired t test. Results: In the acute unilateral disc edema group (n = 28), none of the SLP parameters were significantly increased in affected vs fellow eyes. In the chronic unilateral disc atrophy group (n=30), all SLP parameters were significantly decreased in affected vs fellow eyes (P<.001). Patients with disc edema who had a follow-up SLP demonstrated significant declines of all parameters in the affected eyes (P<.007) but no change in SLP parameters in unaffected eyes. Conclusion: Scanning laser polarimetry measures form birefringence properties of the RNFL, but not necessarily the RNFL thickness. Arch Ophthalmol. 2003 121:484-490. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Martin Luther King Hosp, Los Angeles, CA USA. Ctr Hosp Liege, Dept Ophthalmol, Liege, Belgium. RP Pasquale, LR (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 35 TC 22 Z9 24 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 APR PY 2003 VL 121 IS 4 BP 484 EP 490 DI 10.1001/archopht.121.4.484 PG 7 WC Ophthalmology SC Ophthalmology GA 664QM UT WOS:000182071800007 PM 12695245 ER PT J AU Yuen, SJA Rubin, PAD AF Yuen, SJA Rubin, PAD TI Idiopathic orbital inflammation - Distribution, clinical features, and treatment outcome SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BONE DESTRUCTION; PSEUDOTUMOR; MYOSITIS; DISEASE; RADIOTHERAPY; THERAPY; SARCOIDOSIS; CHILDHOOD; ENTITY AB Objective: To evaluate the distribution and clinical as well as treatment outcome characteristics of idiopathic orbital inflammation with the aim of delineating a more systematic approach to diagnosis and treatment. Methods: A 10-year retrospective review of patients with idiopathic orbital inflammation treated at one institution. Results: Ninety eyes in 65 patients (22 men and 43 women) were studied. Diagnoses were isolated dacryoadenitis (n = 21), isolated myositis (n = 19), concurrent dacryoadenitis and myositis (n = 5), orbital apex syndrome (n = 6) and idiopathic inflammation involving the preseptal region, supraorbital region, sclera, Tenon capsule, orbital fat, or optic nerve (n = 14). The mean age at presentation was 45 years. Pain and periorbital swelling were the most common clinical features and were observed in 45 (69%) and 49 (75%) patients, respectively. Seventeen patients (26%) had bilateral involvement. Biopsy was performed in 19 patients (29%) with atypical presentations or who failed to respond to the initial therapy. Patients were treated with steroids alone (n = 45), steroids and subsequent radiation therapy (n = 8), steroids and nonsteroidal anti-inflammatory agents (n = 6), nonsteroidal anti-inflammatory agents alone in mild cases (n = 2), and, rarely, radiation therapy without steroids (n = 1) or surgical debulking alone (n = 1). Of 65 patients, 41 (63% represented treatment successes, with complete symptom relief at the time of the last follow-up, and 24 (37%) represented treatment failures, with partial or no relief of symptoms. Treatment failures were often characterized by recurrence of inflammation after a period of quiescence (58%) and unremitting, recalcitrant inflammation (38%); 1 patient ultimately required an exenteration. Conclusion: Systemic steroid with a slow taper has been the established first-line treatment for idiopathic orbital inflammation, but refractory cases accounted for a significant portion of treatment failures in our study, reflecting the need for a more systematic approach to the study of this multifaceted disease and for therapeutic alternatives to systemic steroids. Arch Ophthalmol. 2003;121:491-499. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Orbital & Cosmet Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Rubin, PAD (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Orbital & Cosmet Surg Serv, 243 Charles St, Boston, MA 02114 USA. NR 57 TC 128 Z9 139 U1 1 U2 3 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 APR PY 2003 VL 121 IS 4 BP 491 EP 499 DI 10.1001/archopht.121.4.491 PG 9 WC Ophthalmology SC Ophthalmology GA 664QM UT WOS:000182071800008 PM 12695246 ER PT J AU Yueh, B Piccirillo, JF AF Yueh, B Piccirillo, JF TI On equivalence trials and alternative medicine SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID SURGERY; ISSUES C1 VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Yueh, B (reprint author), VA Puget Sound Hlth Care Syst, 112OTO,1660 S Columbian Way, Seattle, WA 98108 USA. OI Yueh, Bevan/0000-0003-1380-1053 NR 11 TC 3 Z9 4 U1 2 U2 2 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 APR PY 2003 VL 129 IS 4 BP 403 EP 404 DI 10.1001/archotol.129.4.403 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 665TK UT WOS:000182137200002 PM 12707185 ER PT J AU Davis, GE Murphy, MP Yueh, B Weymuller, EA AF Davis, GE Murphy, MP Yueh, B Weymuller, EA TI A complication from neurocranial restructuring - Nasal septum fracture SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article AB We report a case of nasal septum fracture after a complementary and alternative medicine procedure called neurocranial restructuring (NCR) that was used to treat a patient with chronic sinusitis. We initially evaluated this patient, obtained a computed tomographic scan, and recommended frontal sinus obliteration. The patient opted to see an alternative medicine practitioner, who performed NCR. This treatment involves the expansion of endonasal balloons in the nasopharynx that are used to "alter the skeletal structure." During the NCR procedure, the patient experienced severe midface pain and a crunching sound. Because of persisting pain, she presented to the emergency department, at which time another computed tomographic scan showed new septal fractures. The patient ultimately received a frontal sinus obliteration, bilateral revision antrostomies, and repositioning of her nasal septum. To our knowledge, this is the first published case report of a complication from NCR. C1 Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Hlth Serv, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. RP Davis, GE (reprint author), Univ Washington, Dept Otolaryngol Head & Neck Surg, Box 356515, Seattle, WA 98195 USA. OI Yueh, Bevan/0000-0003-1380-1053 FU NIDCD NIH HHS [DC-00018] NR 7 TC 2 Z9 2 U1 1 U2 1 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 APR PY 2003 VL 129 IS 4 BP 472 EP 474 DI 10.1001/archotol.129.4.472 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 665TK UT WOS:000182137200014 PM 12707197 ER PT J AU Covin, R O'Brien, M Grunwald, G Brimhall, B Sethi, G Walczak, S Reiquam, W Rajagopalan, C Shroyer, AL AF Covin, R O'Brien, M Grunwald, G Brimhall, B Sethi, G Walczak, S Reiquam, W Rajagopalan, C Shroyer, AL TI Factors affecting transfusion of fresh frozen plasma, platelets, and red blood cells during elective coronary artery bypass graft surgery SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID MULTIVARIATE-ANALYSIS; CONSERVATION; ASPIRIN; REQUIREMENTS; DETERMINANTS; VARIABILITY; OPERATIONS; REDUCTION; PRODUCTS; MODEL AB Context.-The ability to predict the use of blood components during surgery will improve the blood bank's ability to provide. efficient service. Objective.-Develop prediction models using preoperative risk factors to assess blood component usage during elective coronary artery bypass graft surgery (CABG). Design.-Eighty-three preoperative, multidimensional risk variables were evaluated for patients undergoing elective CARG-only surgery. Main Outcome Measures.-The study endpoints included transfusion of fresh frozen plasma (FFP), platelets, and red blood cells (RBC). Multivariate logistic regression models were built to assess the predictors related to each of these endpoints. Setting.-Department of Veterans Affairs (VA) health care system. Patients.-Records for 3034 patients undergoing elective CARG-only procedures; 1033 patients received a blood component transfusion during CABG. Results.-Previous heart surgery and decreased ejection fraction were significant predictors of transfusion for all blood components. Platelet count was predictive of platelet transfusion and FFP utilization. Baseline hemoglobin was a predictive factor for more than 2 units of RBC. Some significant hospital variation was noted beyond that predicted by patient risk factors alone. Conclusions.-Prediction models based on preoperative variables may facilitate blood component management for patients undergoing elective CABG. Algorithms are available to predict transfusion resources to assist blood banks in improving responsiveness to clinical needs. Predictors for use of each blood component may be identified prior to elective CABG for VA patients. C1 Denver Vet Affairs Med Ctr, Dept Cardiac Res, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Dept Pathol, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Pathol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Univ Arizona, Hlth Sci Ctr, Dept Cardiothorac Surg, Tucson, AZ USA. Tucson Vet Affairs Med Ctr, Tucson, AZ USA. Univ Colorado, Coll Business & Adm, Denver, CO 80202 USA. RP Shroyer, AL (reprint author), Denver Vet Affairs Med Ctr, Dept Cardiac Res, 1055 Clermont St, Denver, CO 80220 USA. RI Shroyer, Annie Laurie/B-8836-2016 OI Shroyer, Annie Laurie/0000-0001-6461-0623 NR 32 TC 33 Z9 33 U1 0 U2 0 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 APR PY 2003 VL 127 IS 4 BP 415 EP 423 PG 9 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 667YE UT WOS:000182261800008 PM 12683868 ER PT J AU Lee-Lewandrowski, E Corboy, D Lewandrowski, K Sinclair, J McDermot, S Benzer, TI AF Lee-Lewandrowski, E Corboy, D Lewandrowski, K Sinclair, J McDermot, S Benzer, TI TI Implementation of a point-of-care satellite laboratory in the emergency department of an academic medical center - Impact on test turnaround time and patient emergency department length of stay SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT SAEM Annual Meeting CY MAY 08, 2001 CL ATLANTA, GEORGIA SP SAEM ID SATISFACTION AB Context.-Emergency department (ED) overcrowding has reached crisis proportions in the United States. Many hospitals are seeking to identify process reengineering efforts to reduce crowding and ED patient length of stay (LOS). Objectives.-To investigate the impact of a point-of-care testing (POCT) satellite laboratory in the ED of a large academic medical center. Setting.-The ED of the Massachusetts General Hospital, Boston, Mass. Design and Outcome Measures.-Evaluation of physician satisfaction, turnaround time (TAT), and ED LOS before and after implementation of a POCT laboratory. ED LOS was measured by patient chart audits. TAT was assessed by manual and computer audits. Clinician satisfaction surveys measured satisfaction with test TAT and test accuracy. Results.-Blood glucose, urine human chorionic gonadotropin, urine dipstick, creatine kinase-MB, and troponin tests were performed in the ED POCT laboratory. Test TAT declined an average of 87% after the institution of POCT. The ED LOS decreased for patients who received pregnancy testing, urine dipstick, and cardiac markers. Although these differences were not significant for individual tests, when the tests were combined, the decreased LOS was, on average, 41.3 minutes (P =.006). Clinician satisfaction surveys documented equivalent satisfaction with test accuracy between the central laboratory and the POCT laboratory. These surveys also documented dissatisfaction with central laboratory TAT and increased satisfaction with TAT of the POCT program (P <.001). Conclusions.-The POCT satellite laboratory decreased test TAT and decreased ED LOS. There was excellent satisfaction with test accuracy and TAT. C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Benzer, TI (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 115, 55 Fruit St, Boston, MA 02114 USA. NR 8 TC 86 Z9 89 U1 0 U2 4 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 APR PY 2003 VL 127 IS 4 BP 456 EP 460 PG 5 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 667YE UT WOS:000182261800014 PM 12683874 ER PT J AU Hastings, JD Fanucchi, ER Burns, SP AF Hastings, JD Fanucchi, ER Burns, SP TI Wheelchair configuration and postural alignment in persons with spinal cord injury SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Spinal-Injury-Association CY MAY 18, 2001 CL LONG BEACH, CALIFORNIA SP Amer Spinal Injury Assoc DE rehabilitation; shoulder; spinal cord injuries; spine; wheelchairs ID BALANCE CONTROL; INDIVIDUALS; PAIN; TETRAPLEGIA; POSITION; PRESSURE AB Objective: To determine whether postural alignment and shoulder flexion range differ for persons with spinal cord injury (SCI) seated in wheelchairs with standard configurations versus wheelchairs with posterior seat inclination and a low backrest set perpendicular to the floor. Design: Prospective repeated-measures study. Setting: Outpatient SCI clinic. Participants: Fourteen subjects with C6-T10 motor-complete SCI. Interventions: Subjects sat in 3 manual wheelchairs: standard setup E&J Premier (S1), standard setup Quickie Breezy (S2), and test configuration Quickie TNT (T) with posterior seat inclination and a low backrest set perpendicular to the floor. Main Outcome Measures: Shoulder and neck alignment and pelvic tilt were determined from sagittal plane digital photographs at rest and with maximal vertical reach. Results: At rest, T produced less shoulder protraction than either standard configuration (difference between the mean values, S1: 1.6cm, P=.048; S2: 1.2cm, P=.013). SI and S2 showed a greater head-forward position than T (differences between the mean values, S1: 6.5degrees, P=.008; S2: 6.3degrees, P=.013). T allowed greater humeral flexion than S2 (difference between the mean values: 3.7degrees, P=.036) and greater vertical reach above the seat plane than either conventional configuration (differences between the mean values, S1: 4.7cm, P=.005; S2: 4.1cm, P=.002). The indirect pelvic tilt measurement showed a trend (P=.06) toward greater posterior pelvic tilt with S1 and S2. Conclusion: The alternate configuration produces more vertical postural alignment and greater reach ability versus the standard factory setup wheelchairs. C1 Univ Puget Sound, Phys Therapy Dept, Tacoma, WA 98416 USA. Vet Affairs Puget Sound Hlth Care Syst, Spinal Cord Injury Serv, Seattle, WA USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. RP Hastings, JD (reprint author), Univ Puget Sound, Phys Therapy Dept, 1500 N Warner, Tacoma, WA 98416 USA. NR 24 TC 20 Z9 21 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 APR PY 2003 VL 84 IS 4 BP 528 EP 534 DI 10.1053/apmr.2003.50036 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 664QL UT WOS:000182071700010 PM 12690591 ER PT J AU Livingston, EH Fink, AS AF Livingston, EH Fink, AS TI Quality of life - Cost and future of bariatric surgery SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the New-England-Surgical-Society CY SEP 27-29, 2002 CL DIXVILLE NOTCH, NEW HAMPSHIRE SP New England Surg Soc ID GASTRIC BYPASS-SURGERY; MORBIDLY OBESE PATIENTS; INDUCED WEIGHT-LOSS; HEALTH-CARE COSTS; BODY-MASS INDEX; OF-LIFE; UNITED-STATES; US ADULTS; OVERWEIGHT; MORTALITY AB Obesity is increasing in epidemic proportions internationally.(1) Health care costs for the teatment of obesity and its complications have also increased. Recent estimates are about $70 billion or 9.4% of all health care costs are attributable to treating obesity and obesity-related complications.(2,3) As the population's weight has become heavier,(46) the prevalence of morbid obesity has dramatically increased.(7) Morbid obesity is associated with significant medical complications such as sleep apnea, hypertension, osteoarthritis, diabetes mellitus, and other degenerative conditions.(8-18) Although these disorders respond to weight loss, individuals who have morbid obesity rarely achieve long-term weight loss with dietary interventions.(19) Bariatric surgery remains the only method that culminates in sustained weight loss with. subsequent control of obesity-related complications.(20) Bariatric surgery effectively treats obesity-induced diabetes mellitus,(21,22) hypertension,(23-26) hyperlipidemia.(27-32) osteoarthritis, pulmonary hypertension,(33) and sleep apnea.(34-36) The effects of obesity on health and, similarly, the effectiveness of bariatric surgery in treating obesity-related comorbid conditions is well documented. C1 Vet Affairs Greater Los Angeles Hlth Care Syst, Dept Surg, Los Angeles, CA USA. Emory Univ, Atlanta, GA 30322 USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. RP Livingston, EH (reprint author), Univ Texas, SW Med Ctr, Dept Gastrointestinal & Endocrine Surg, 5323 Harry Hines Blvd,Room E7-126, Dallas, TX 75390 USA. NR 62 TC 34 Z9 35 U1 2 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2003 VL 138 IS 4 BP 383 EP 388 DI 10.1001/archsurg.138.4.383 PG 6 WC Surgery SC Surgery GA 663WV UT WOS:000182030500006 PM 12686524 ER PT J AU Cummings, DE Shannon, MH AF Cummings, DE Shannon, MH TI Roles for ghrelin in the regulation of appetite and body weight SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the New-England-Surgical-Society CY SEP 27-29, 2002 CL DIXVILLE NOTCH, NEW HAMPSHIRE SP New England Surg Soc ID VERTICAL BANDED GASTROPLASTY; GROWTH-HORMONE SECRETAGOGUE; QUALITY-OF-LIFE; ROUX-EN-Y; AGOUTI-RELATED PROTEIN; PRADER-WILLI-SYNDROME; FOOD-INTAKE; GASTRIC BYPASS; MORBID-OBESITY; MESSENGER-RNA AB Obesity is a global epidemic that has proven daunting to prevent and treat. The prevalences of obesity (body mass index [BMI] > 30) and morbid obesity (BMI > 40) among American adults are about 30% and 5%, respectively.(1) Obesity is so strongly associated with medical comorbidities and mortality that it has begun to overtake infectious diseases as the most significant contributor to ill health worldwide.(2,3) Overweight persons are also frequently stigmatized and consequently suffer from low self-esteem. Their motivation to achieve and maintain weight loss is often Herculean. In 1 study of 47 patients who had durably lost 45 kg or more after bariatric surgery, 100% preferred to be deaf, dyslexic, diabetic, or have heart disease rather than be obese again; leg amputation and blindness were preferred by 91.5% and 89.4%, respectively.(4) The traditional treatment paradigm of diet, exercise, and medication generally achieves no more than a 5% to 10% reduction in body weight,5,6 and recidivism after such weight loss exceeds 90% within 5 years. 1,8 This failure arises because a robust homeostatic system of body weight regulation compensates for weight loss with increased hunger and decreased energy expenditure.(9-11) The molecular mediators of these compensatory responses to weight loss are potential targets for antiobesity treatments. Ghrelin is a potent orexigenic (appetite-stimulating) peptide that seems to participate in the adaptive response to weight loss. Therefore, ghrelin holds promise as a target for both medical and surgical approaches to obesity. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. RP Cummings, DE (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 1660 S Columbian Way,S-111 Endo, Seattle, WA 98108 USA. NR 111 TC 155 Z9 164 U1 3 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2003 VL 138 IS 4 BP 389 EP 396 DI 10.1001/archsurg.138.4.389 PG 8 WC Surgery SC Surgery GA 663WV UT WOS:000182030500007 PM 12686525 ER PT J AU Fernandez-del Castillo, C Targarona, J Thayer, SP Rattner, DW Brugge, WR Warshaw, AL AF Fernandez-del Castillo, C Targarona, J Thayer, SP Rattner, DW Brugge, WR Warshaw, AL TI Incidental pancreatic cysts - Clinicopathologic characteristics and comparison with symptomatic patients SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the New-England-Surgical-Society CY SEP 27-29, 2002 CL DIXVILLE NOTCH, NEW HAMPSHIRE SP New England Surg Soc ID FLUID ANALYSIS; MUCINOUS CYSTADENOCARCINOMA; DIFFERENTIAL-DIAGNOSIS; SEROUS CYSTADENOMA; TUMORS; NEOPLASMS; PSEUDOCYSTS; ULTRASOUND; SPECTRUM AB Hypothesis: Widespread use of computed tomography and ultrasound has led to the identification of increasing numbers of patients with asymptomatic cystic lesions of the pancreas. Design: Retrospective case series of patients with pancreatic cystic lesions. Setting: University-affiliated tertiary care referral center. Patients: Two hundred twelve patients with pancreatic cystic lesions seen in our surgical practice during 5 years (April 1997-March 2002). Main Outcome Measures: Presence or absence of symptoms, cyst size and location, cytologic or pathologic diagnosis, surgical treatment, and outcome. Results: Seventy-eight (36.7%) of 212 patients were asymptomatic. Incidental cysts were smaller (3.3 +/- 1.9 vs 4.6 +/- 2.7 cm; P<.001) and were found in older patients (65 +/- 13 vs 56 +/- 15 years; P<.001). Seventy-eight percent of the asymptomatic patients and 87% of those with symptoms underwent surgery, with a single operative death in the entire group (0.5%). Seventeen percent of asymptomatic cysts were serous cystadenomas; 28%, mucinous cystic neoplasms; 27%, intraductal papillary mucinous neoplasms; and 2.5%, ductal adenocarcinomas. The respective numbers for symptomatic cysts were 7%, 16%, 40%, and 9%. Ten percent of asymptomatic patients had a variety of other cystic lesions, and in 12%, no definitive cytologic or pathologic diagnosis was obtained. Overall, 17% of asymptomatic patients had in situ or invasive cancer, and 42% had a premalignant lesion. When evaluated as a function of size, only 1 (3.5%) of 28 asymptomatic cysts smaller than 2 cm had cancer compared with 13 (26%) of 50 cysts larger,than 2 cm (P=.04). The proportion of premalignant lesions, however, remained high in both groups (46% and 38%, respectively). Pseudocysts comprised only 3.8% of asymptomatic cysts compared with 19.4% of symptomatic cysts (P=.003). Conclusions: Incidental pancreatic cysts are common, occur in older patients, are smaller than symptomatic cysts, and are unlikely to be pseudocysts. More than half of them are either malignant or premalignant lesions and therefore cannot be dismissed. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, ACC-336,15 Parkman St, Boston, MA 02114 USA. FU NIDDK NIH HHS [K08 DK071329] NR 23 TC 262 Z9 269 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2003 VL 138 IS 4 BP 427 EP 433 PG 7 WC Surgery SC Surgery GA 663WV UT WOS:000182030500013 PM 12686529 ER PT J AU Matsumoto, I Lee, DM Goldbach-Mansky, R Sumida, T Hitchon, CA Schur, PH Anderson, RJ Coblyn, JS Weinblatt, ME Brenner, M Duclos, B Pasquali, JL El-Gabalawy, H Mathis, D Benoist, C AF Matsumoto, I Lee, DM Goldbach-Mansky, R Sumida, T Hitchon, CA Schur, PH Anderson, RJ Coblyn, JS Weinblatt, ME Brenner, M Duclos, B Pasquali, JL El-Gabalawy, H Mathis, D Benoist, C TI Low prevalence of antibodies to glucose-6-phosphate isomerase in patients with rheumatoid arthritis and a spectrum of other chronic autoimmune disorders SO ARTHRITIS AND RHEUMATISM LA English DT Article ID T-CELL; AUTOANTIBODIES; CLASSIFICATION; DISEASE; CRITERIA; ENZYME; GPI; RECOGNITION; SYSTEM; SERA AB Objective. Arthritis in the K/BxN mouse model results from pathogenic immunoglobulins that recognize glucose-6-phosphate isomerase (GPI), a glycolytic enzyme residing in the cytoplasm of all cells. Antibodies directed against GPI can, alone, transfer arthritis to healthy recipients. Previous experiments have revealed significant titers of anti-GPI antibodies in the serum of many patients with rheumatoid arthritis (RA). We evaluated the generality of these observations in cohorts of patients with 12 different arthritic and chronic autoimmune diseases and in population-matched healthy control subjects. Methods. Anti-GPI antibodies were assayed in 811 individual serum samples by enzyme-linked immunosorbent assay with 2 forms of GPI, recombinant and native. Results were confirmed by immunoblotting. Results. Several patients had significantly elevated anti-GPI antibody titers, but without the prevalence or the specificity reported previously. Only 15% of RA patients had anti-GPI antibodies (range 12-29% in different cohorts), with a higher prevalence in patients with active disease. Psoriatic arthritis, undifferentiated arthritis, and spondylarthropathy patients also displayed anti-GPI antibodies at similar frequencies (12-25%). Similar titers were detected in a proportion (5-10%) of control subjects or patients with Crohn's disease or sarcoidosis. Very high titers were found in rare cases of RA and systemic lupus erythematosus. Conclusion. No disease-specific pattern of antibody positivity to GPI was apparent. While the antibody-mediated mechanism at play in the mouse model may exemplify a generic mechanism for some forms of arthritis in humans, GPI itself does not appear to be a target common to the majority of RA patients. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Tsukuba, Ibaraki, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Tsukuba, Ibaraki, Japan. Univ Manitoba, Winnipeg, MB, Canada. Hop Hautepierre, Hop Univ Strasbourg, Strasbourg, France. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Manitoba, Winnipeg, MB, Canada. RP Benoist, C (reprint author), Joslin Diabet Ctr, 1 Joslin Pl,Room 475, Boston, MA 02215 USA. FU NIAMS NIH HHS [K08-AR-0221401] NR 26 TC 86 Z9 96 U1 2 U2 4 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 APR PY 2003 VL 48 IS 4 BP 944 EP 954 DI 10.1002/art.10898 PG 11 WC Rheumatology SC Rheumatology GA 665HZ UT WOS:000182115300010 PM 12687536 ER PT J AU Lehtinen, JT Tetreault, P Warner, JJP AF Lehtinen, JT Tetreault, P Warner, JJP TI Arthroscopic management of painful and stiff scapulothoracic articulation SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE scapulothoracic articulation; scapulothoracic bursitis; shoulder stiffness; arthroscopy ID SNAPPING SCAPULA AB We present the case of a patient who had chronic refractory scapulothoracic pain accompanied by the loss of scapulothoracic motion. Despite intensive physical therapy, the insidious onset of scapulothoracic pain and stiffness progressed. A wide range of diagnostic tests did not show a systemic, anatomic, or neurologic cause for the disorder. Finally, the patient elected to undergo an arthroscopic release and decompression of the scapulothoracic articulation. The patient had a dramatic response to surgery; the pain was gone immediately, and by 4 months after surgery, her scapulothoracic motion was evaluated as symmetric. One year after the surgery, she maintained an active lifestyle and was extremely satisfied with the result. Progressive and painful loss of shoulder motion in the case reported was due to a rare adhesive inflammation of the scapulothoracic bursa, which was successfully treated using arthroscopic resection. Arthroscopy of the scapulothoracic articulation is an option to treat scapulothoracic abnormalities, especially bursitis, but long-term clinical studies are needed to strongly recommend this emerging treatment option. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shoulder Serv, 275 Cambridge St,Suite 403, Boston, MA 02114 USA. NR 16 TC 3 Z9 3 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD APR PY 2003 VL 19 IS 4 DI 10.1053/jars.2003.50117 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 666RV UT WOS:000182191000017 ER PT J AU Lefler, D Mukhin, YV Pettus, T Leeb-Lundberg, LMF Garnovskaya, MN Raymond, JR AF Lefler, D Mukhin, YV Pettus, T Leeb-Lundberg, LMF Garnovskaya, MN Raymond, JR TI Jak2 and Ca2+/calmodulin are key intermediates for bradykinin B-2 receptor-mediated activation of Na+/H+ exchange in KNRK and CHO cells SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES LA English DT Article ID SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE; ISOFORM-1 NHE1; PHOSPHORYLATION; CALCIUM; TRANSDUCTION; INHIBITION; EXPRESSION; P90(RSK) AB Na+/H+ exchangers are ubiquitous in mammalian cells, carrying out key functions, such as cell volume defense, acid-base homeostasis, and regulation of the cytoskeleton. We used two screening technologies (FLIPR and microphysiometry) to characterize the signal transduction pathway used by the bradykinin beta(2) receptor to activate Na+/H+ exchange in two cell lines, KNRK and CHO. In both cell types, beta(2) receptor activation resulted in rapid increases in the rate of proton extrusion that were sodium-dependent and could be blocked by the Na+/H+ exchange inhibitors EIPA and MIA or by replacing extracellular sodium with TMA. Activation of Na+/H+ exchange by bradykinin was concentration-dependent and could be blocked by the selective beta(2) receptor antagonist HOE140, but not by the beta(1) receptor antagonist des-Arg(10)-HOE140. Inhibitors of Jak2 tyrosine kinase (genistein and AG490) and of CAM (W-7 and calmidazolium) attenuated bradykinin-induced activation of Na+/H+ exchange. Bradykinin induced formation of a complex between CAM and Jak2, supporting a regulatory role for Jak2 and CAM in the activation of Na+/H+ exchange in KNRK and CHO cells. We propose that this pathway (beta(2) receptor --> Jak2 --> CAM --> Na+/H+ exchanger) is a fundamental regulator of Na+/H+ exchange activity. C1 Med Univ S Carolina, Dept Med, Div Nephrol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Med Serv, Charleston, SC USA. Ralph H Johnson Vet Adm Med Ctr, Res Serv, Charleston, SC USA. Lund Univ, Wallenberg Neurosci Ctr, Div Mol Neurobiol, S-22100 Lund, Sweden. RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, Div Nephrol, Room 200,Adm Bldg,POB 250002,171 Ashley Ave, Charleston, SC 29425 USA. RI Pettus, Thomas/B-4352-2008 FU NCRR NIH HHS [S10RR13656]; NIDDK NIH HHS [DK02694, DK52448] NR 34 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 1540-658X J9 ASSAY DRUG DEV TECHN JI ASSAY DRUG DEV. TECHNOL. PD APR PY 2003 VL 1 IS 2 BP 281 EP 289 DI 10.1089/15406580360545099 PG 9 WC Biochemical Research Methods; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 738WK UT WOS:000186310700007 PM 15090193 ER PT J AU Lee, SJ Vogelsang, G Flowers, MED AF Lee, SJ Vogelsang, G Flowers, MED TI Chronic graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic stem cell transplantation ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; QUALITY-OF-LIFE; TERM FOLLOW-UP; HLA-IDENTICAL SIBLINGS; BLOOD PROGENITOR-CELL; TREATMENT-RELATED MORTALITY; TOTAL-LYMPHOID IRRADIATION; RANDOMIZED CLINICAL-TRIAL; OBSTRUCTIVE LUNG-DISEASE AB Chronic graft-versus-host disease (GVHD) remains a vexing and dangerous complication of allogeneic stem cell transplantation. Mild forms of chronic GVHD are often manageable with local or low-dose systemic immunosuppression and do not affect long-term survival. In contrast, more severe forms of chronic GVHD require intensive medical management and adversely affect survival. This report reviews current concepts of the pathogenesis, clinical risk factors, classification systems, organ manifestations, and available treatments for chronic GVHD. It also provides a comprehensive listing of the published clinical trials aimed at prevention and primary treatment of chronic GVHD. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lee, SJ (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. FU NCI NIH HHS [CA18029, CA18221, CA75267-05]; NHLBI NIH HHS [HL36444] NR 163 TC 336 Z9 347 U1 1 U2 8 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 APR PY 2003 VL 9 IS 4 BP 215 EP 233 DI 10.1053/bbmt.2003.50026 PG 19 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 675GZ UT WOS:000182686800001 PM 12720215 ER PT J AU Feinstein, LC Sandmaier, BM Maloney, DG Maris, MB Gooley, TA Chauncey, TR Hegenbart, U McSweeney, PA Stuart, MJ Forman, SJ Agura, EA Pulsipher, MA Blume, KG Niedervieser, DW Storb, RF AF Feinstein, LC Sandmaier, BM Maloney, DG Maris, MB Gooley, TA Chauncey, TR Hegenbart, U McSweeney, PA Stuart, MJ Forman, SJ Agura, EA Pulsipher, MA Blume, KG Niedervieser, DW Storb, RF TI Allografting after nonmyeloablative conditioning as a treatment after a failed conventional hematopoietic cell transplant SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE second hematopoietic cell allografts nonmyeloablative conditioning ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; NON-HODGKINS-LYMPHOMA; ALLOGENEIC TRANSPLANTATION; AUTOLOGOUS TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; 2ND AUTOGRAFT; DOUBLE-BLIND; BLOOD; FLUDARABINE AB Outcomes with conventional allogeneic hematopoietic cell transplantation (HCT) after failed HCT are typically poor. To reduce transplantation-related mortality (TRM), 55 patients (median age, 43 years; range, 18-69 years) who had failed conventional autologous (n = 49), allogeneic (n = 4), or syngeneic (n = 2) HCT received human leukocyte antigen-matched related (n 31) or unrelated (n = 24) donor allografts after nomnyeloablative conditioning with 2 Gy of total body irradiation or 2 Gy of total body irradiation and 90 mg/m(2) of fludarabine. Postgrafting inununosuppression consisted of cyclosporine and mycophenolate mofetil. One rejection occurred. Thirty-three patients died a median of 127 days (range, 7-834 days) after HCT: 21 of relapse, 11 of TRM, and 1 of suicide. The TRM rate on day 100 was 11 % with an estimated 1-year TRM rate of 20% (95% confidence interval [CI], 9% to 3 1 %). The median follow-up among the 22 survivors is 368 days (range, 173-796 days). Seventeen of 22 survivors are progression-free. One-year estimates of overall and progression-free survival rates are 49% (95% CI, 35% to 62%) and 28% (95% CI, 16% to 41%), respectively. Untreated disease at the time of allografting after nomnyeloablative conditioning increased the risk of death (hazard ratio = 2.4; P = .04). Although the length of follow-up is still short, it appears that encouraging outcomes can be achieved with nomnyeloablative conditioning in patients expected to have poor outcomes with conventional allografting. (C) 2003 American Society for Blood and Marrow Transplantation. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Leipzig, Leipzig, Germany. Univ Colorado, Denver, CO 80202 USA. Stanford Univ, Stanford, CA 94305 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Baylor Univ, Dallas, TX USA. Univ Utah, Salt Lake City, UT USA. RP Storb, RF (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM rstorb@fhcrc.org FU NCI NIH HHS [K23CA92058, CA18221, CA15704, P01 CA078902, CA78902]; NHLBI NIH HHS [HL36444] NR 34 TC 20 Z9 20 U1 0 U2 0 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 APR PY 2003 VL 9 IS 4 BP 266 EP 272 DI 10.1053/bbmt.2003.50014 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 675GZ UT WOS:000182686800005 PM 12720219 ER PT J AU Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Harris, WH Gul, R McGarry, F AF Muratoglu, OK Bragdon, CR O'Connor, DO Jasty, M Harris, WH Gul, R McGarry, F TI Unified wear model for highly crosslinked ultra-high molecular weight polyethylenes (UHMWPE) (vol 20, pg 1463, 1999) SO BIOMATERIALS LA English DT Correction C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. MIT, Dept Mat Sci & Engn, Cambridge, MA 02141 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GRJ 1206, Boston, MA 02114 USA. NR 1 TC 7 Z9 7 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2003 VL 24 IS 8 BP 1527 EP 1527 AR PII S0142-9612(02)00535-5 DI 10.1016/S0142-9612(02)00535-5 PG 1 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 638ZY UT WOS:000180604200021 ER PT J AU Schmidt, H Brown, EB Schwaller, B Eilers, J AF Schmidt, H Brown, EB Schwaller, B Eilers, J TI Diffusional mobility of parvalbumin in spiny dendrites of cerebellar purkinje neurons quantified by fluorescence recovery after photobleaching SO BIOPHYSICAL JOURNAL LA English DT Article ID SMOOTH-MUSCLE CELLS; BUFFERING PROPERTIES; 3-DIMENSIONAL ANALYSIS; CALCIUM DIFFUSION; CHROMAFFIN CELLS; CA2+ BUFFERS; RAT; BINDING; KINETICS; RELEASE AB Ca2+-binding proteins (CaBPs) represent key factors for the modulation of cellular Ca2+ dynamics. Especially in thin extensions of nerve cells, Ca2+ binding and buffered diffusion of Ca2+ by CaBPs is assumed to effectively control the spatio-temporal extend of Ca2+ signals. However, no quantitative data about the mobility of specific CaBPs in the neuronal cytosol are available. We quantified the diffusion of the endogenous CaPB parvalbumin (PV) in spiny dendrites of cerebellar Purkinje neurons with two-photon fluorescence recovery after photobleaching. Fluorescently labeled PV diffused readily between spines and dendrites with a median time constant of 49 ms (37-61 ms, interquartile range). Based on published data on spine geometry, this value corresponds to an apparent diffusion coefficient of 43 mum(2) s(-1) (34-56 mum(2) s(-1)). The absence of large or immobile binding partners for PV was confirmed in PV null-mutant mice. Our data validate the common but so far unproven assumption that PV is highly mobile in neurons and will facilitate simulations of neuronal Ca2+ buffering. Our experimental approach represents a versatile tool for quantifying the mobility of proteins in neuronal dendrites. C1 Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Fribourg, Dept Med, Div Histol, CH-1705 Fribourg, Switzerland. RP Schmidt, H (reprint author), Max Planck Inst Brain Res, Dept Neurophysiol, D-60528 Frankfurt, Germany. RI Schmidt, Hartmut/F-7058-2010; Eilers, Jens/E-6251-2012 OI Eilers, Jens/0000-0003-0497-5625 NR 48 TC 49 Z9 51 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2003 VL 84 IS 4 BP 2599 EP 2608 DI 10.1016/S0006-3495(03)75065-6 PG 10 WC Biophysics SC Biophysics GA 682ZZ UT WOS:000183123100046 PM 12668468 ER PT J AU Betensky, RA Louis, DN Cairncross, JG AF Betensky, RA Louis, DN Cairncross, JG TI Analysis of a molecular genetic neuro-oncology study with partially biased selection SO BIOSTATISTICS LA English DT Article DE missing covariate; omitted covariate; selection bias ID SURVIVAL; OLIGODENDROGLIOMAS; REGRESSION; GLIOMA; TRIALS AB Oligodendrogliomas are a common variant of malignant brain tumors, and are unique for their relative sensitivity to chemotherapy and better prognosis. For these reasons, the identification of an objective oligodendroglial marker has been a long sought-after goal in the field of neuro-oncology. To this end, 75 patients who received chemotherapy at the London Regional Cancer Centre between 1984 and 1999 were studied (Ino et al., Clinical Cancer Research, 7, 839-845, 2001). Of these 75 patients, 50 were initially treated with chemotherapy (the current practice) and comprise a population-based sample. The remaining 25 patients were initially treated with radiation and were included in the study only because their tumor recurred, at which time they received chemotherapy. Because this group of 25 patients included neither those radiation patients whose tumors never recurred nor those radiation patients whose tumors recurred but were not treated with chemotherapy, issues of selection bias were of concern. For this reason, the initial analysis of these data included only the 50 population-based patients. This was unsatisfying given the rarity of this disease and of genetic information on this disease and led us to question whether we could undertake an analysis that includes all of the patients. Here we examine approaches for utilizing the entire study population, as well as the assumptions required for doing so. We illustrate that there are both costs and benefits to using the 25 selected patients. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Western Ontario, Dept Oncol & Clin Neurol Sci, London, ON, Canada. London Reg Canc Ctr, London, ON N6A 4L6, Canada. RP Betensky, RA (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA75971, CA57683] NR 16 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2003 VL 4 IS 2 BP 167 EP 178 DI 10.1093/biostatistics/4.2.167 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 678YU UT WOS:000182894900001 PM 12925514 ER PT J AU Baldessarini, RJ AF Baldessarini, RJ TI Assessment of treatment response in mania: commentary and new findings SO BIPOLAR DISORDERS LA English DT Editorial Material DE bipolar disorder; drug/placebo differences; mania; outcome; rating scales; treatment response ID BIPOLAR DISORDER; DOUBLE-BLIND; PLACEBO; OLANZAPINE; VALPROATE; EFFICACY; LITHIUM; SCALE AB Background: Assessment of therapeutic interventions in bipolar disorder is complicated by rapid, complex clinical changes, high placebo-response rates, and varying times to specific levels of clinical recovery that may not be adequately reflected in averaged rating-scale scores particularly in acute mania, calling for improved methods to evaluate treatment responses. Chengappa et al. (1) propose operational criteria for specific outcomes based on rating-scale data from two placebo-controlled trials of olanzapine in mania. Methods: These trials and other recent research were considered in commenting on the design, conduct, analysis and interpretation of experimental therapeutic trials in mania and to optimize olanzapine versus placebo contrasts by systematically varying end-point criteria for mania (YMRS) and depression (HDRS) ratings. Results: Olanzapine versus placebo responses were optimally separated at scores of 10 for final paired mania and depression ratings, or 5 for each rating scale considered separately. Conclusions: Use of empirically determined end-points derived from standard rating scales used in experimental therapeutics research in mood disorders can improve both outcome-assessment and separation of active treatment from placebo responses in acute mania. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Bipolar & Psychot Disorders Program, Belmont, MA USA. Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Int Consortium Bipolar Disorder Res, Belmont, MA USA. RP Baldessarini, RJ (reprint author), McLean Hosp, Mailman Res Ctr 306, 115 Mill St, Belmont, MA 02478 USA. NR 25 TC 9 Z9 9 U1 2 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD APR PY 2003 VL 5 IS 2 BP 79 EP 84 DI 10.1034/j.1399-5618.2003.00020.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 665CB UT WOS:000182101100002 PM 12680896 ER PT J AU Nemeth, E Valore, EV Territo, M Schiller, G Lichtenstein, A Ganz, T AF Nemeth, E Valore, EV Territo, M Schiller, G Lichtenstein, A Ganz, T TI Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein SO BLOOD LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; ANTIMICROBIAL ACTIVITY; PEPTIDE HEPCIDIN; IRON OVERLOAD; LIVER; GENE; HORMONE; DISEASE; MICE AB Hepcidin is a liver-made peptide proposed to be a central regulator of intestinal iron absorption and iron recycling by macrophages. In animal models, hepcidin is induced by inflammation and iron loading, but its regulation in humans has not been studied. We report that urinary excretion of hepcidin was greatly increased in patients with iron overload, infections, or inflammatory diseases. Hepcidin excretion correlated well with serum ferritin levels, which are regulated by similar pathologic stimuli. In vitro iron loading of primary human hepatocytes, however, unexpectedly down-regulated hepcidin mRNA, suggesting that in vivo regulation of hepcidin expression by iron stores involves complex indirect effects. Hepcidin mRNA was dramatically induced by interleukin-6 (IL-6) in vitro, but not by IL-1 or tumor necrosis factor a (TNF-alpha), demonstrating that human hepcidin is a type II acute-phase reactant. The linkage of hepcidin induction to inflammation in humans supports its proposed role as a key mediator of anemia of inflammation. C1 Univ Calif Los Angeles, Dept Med, David Gelfen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Pathol, David Gelfen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, W Los Angeles Vet Adm Hosp, Los Angeles, CA 90095 USA. RP Ganz, T (reprint author), Univ Calif Los Angeles, Dept Med, David Gelfen Sch Med, 37-055 CHS, Los Angeles, CA 90095 USA. NR 13 TC 777 Z9 825 U1 7 U2 28 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 APR 1 PY 2003 VL 101 IS 7 BP 2461 EP 2463 DI 10.1182/blood-2002-10-3235 PG 3 WC Hematology SC Hematology GA 660FR UT WOS:000181823600010 PM 12433676 ER PT J AU Fleming, MD Pinkus, JL Alexander, SW Tam, C Loda, M Sallan, SE Nichols, KE Carpentieri, DF Pinkus, GS Rollins, BJ AF Fleming, MD Pinkus, JL Alexander, SW Tam, C Loda, M Sallan, SE Nichols, KE Carpentieri, DF Pinkus, GS Rollins, BJ TI Coincident expression of the chemokine receptors CCR6 and CCR7 by pathologic Langerhans cells in Langerhans cell histiocytosis SO BLOOD LA English DT Article ID MATURE DENDRITIC CELLS; ADHESION MOLECULES; B-CELLS; MATURATION; DIFFERENTIATION AB It has been suggested that a switch in chemokine receptor expression underlies Langerhans cell migration from skin to lymphoid tissue. Activated cells are thought to down-regulate CCR6, whose ligand macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 is expressed in skin, and up-regulate CCR7, whose ligands are in lymphoid tissues. In Langerhans cell histiocytosis (LCH), pathologic Langerhans cells (LCs) accumulate in several tissues, including skin, bone, and lymphoid organs. We have examined 24 LCH cases and find that pathologic LCs expressed CCR6 and CCR7 coincidentally in all cases. Furthermore, MIP-3alpha/CCL20 is expressed by keratinocytes in involved skin and by macrophages and osteoblasts in involved bone. Expression of CCR6 by pathologic LCs may contribute to their accumulation in nonlymphoid organs such as skin and bone, whereas CCR7 expression may direct them to lymphoid tissue. Histiocytes in Rosai-Dorfman disease and hemophagocytic syndrome also coexpressed CCR6 and CCR7, suggesting that this may be a general attribute of abnormal histiocytes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Div Hematol Oncol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Dept Pathol, Sch Med, Boston, MA 02115 USA. Univ Penn, Dept Pediat Oncol, Childrens Hosp Penn, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol, Childrens Hosp Penn, Philadelphia, PA 19104 USA. RP Rollins, BJ (reprint author), Dana Farber Canc Inst, Dept Med Oncol, M430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA53091]; NIAID NIH HHS [AI50225] NR 18 TC 47 Z9 49 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 APR 1 PY 2003 VL 101 IS 7 BP 2473 EP 2475 DI 10.1182/blood.V101.7.2473 PG 3 WC Hematology SC Hematology GA 660FR UT WOS:000181823600012 PM 12642342 ER PT J AU Gallagher, RE Yeap, BY Bi, WL Livak, KJ Beaubier, N Rao, S Bloomfield, CD Appelbaum, FR Tallman, MS Slack, JL Willman, CL AF Gallagher, RE Yeap, BY Bi, WL Livak, KJ Beaubier, N Rao, S Bloomfield, CD Appelbaum, FR Tallman, MS Slack, JL Willman, CL TI Quantitative real-time RT-PCR analysis of PML-RAR alpha-mRNA in acute promyelocytic leukemia: assessment of prognostic significance in adult patients from intergroup protocol 0129 SO BLOOD LA English DT Article ID TRANS-RETINOIC ACID; POLYMERASE-CHAIN-REACTION; MINIMAL RESIDUAL DISEASE; FUSION MESSENGER-RNA; MOLECULAR REMISSION; LIMITING DILUTION; CELL-LINE; RELAPSE; THERAPY; CONSOLIDATION AB The potential prognostic value of quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR [qrt-PCR]) measurements of PML-RARalpha mRNA in acute promyelocytic leukemia was retrospectively assessed before treatment and at 3 posttreatment intervals in 123 patients on intergroup protocol 0129. The primary measure was the PML-RARalpha(GAPDH) normalized quotient (NQ), that is, PML-RARalpha mRNA copies divided by glyceralclehyde-3'-phosphate dehydrogenase (GAPDH) mRNA copies. Only samples with more than 2.5 x 10(5) copies of the housekeeping gene GAPDH mRNA (detection sensitivity exceeding 10(4)) were considered NQ evaluable. With RNA from low-density selected cells, paired peripheral blood (PB) and bone marrow samples (n = 140) had comparable NQs (P < .001). Before treatment, high NQ was associated with short-form PML-RARα, (P < .001), but not with white blood cell count or clinical outcome. Following treatment, NQ was lower in all-trans retinoic acid-induced complete remission (CR) than chemotherapy-induced CR (P = .018) and at first test after consolidation chemotherapy (P = .037). After consolidation chemotherapy, patients with NQ exceeding 10(-5) had 4.1-fold increased relapse risk (P = .008); however, 73% of patients who experienced relapse had NQ lower than 10(-5). In the follow-up period (FUP), any NQ exceeding 10(-5) and 10(-6) had 17.5-fold and 7.6-fold increased relapse risk, respectively (P < .001), while no gradation of relapse risk (approximately 18%) could be identified at NQ lower than 10(-6), including NQ(-). These results indicate that qrtPCR monitoring of PML-RARα NQ can identify patients at high risk of relapse and suggest that clinically practical PB NQ monitoring at more frequent FUP intervals may improve predictive accuracy for relapse or continuing CR in patients with persistent, fluctuating minimal residual disease levels. C1 Montefiore Med Ctr, Dept Oncol, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Albert Einstein Canc Ctr, Bronx, NY USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Appl Biosyst Inc, Foster City, CA 94404 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Northwestern Univ, Sch Med, Dept Med, Div Hematol Oncol, Chicago, IL 60611 USA. Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. Univ New Mexico, Dept Pathol, Ctr Canc, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Cell Biol, Ctr Canc, Albuquerque, NM 87131 USA. RP Gallagher, RE (reprint author), Montefiore Med Ctr, Dept Oncol, Rm 601,Hofheimer Bldg,111 E 210th St, Bronx, NY 10467 USA. FU NCI NIH HHS [CA31946, CA56771, CA21115] NR 35 TC 100 Z9 108 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 APR 1 PY 2003 VL 101 IS 7 BP 2521 EP 2528 DI 10.1182/blood-2002-05-1357 PG 8 WC Hematology SC Hematology GA 660FR UT WOS:000181823600019 PM 12468436 ER PT J AU Shi, JL Gilbert, GE AF Shi, JL Gilbert, GE TI Lactadherin inhibits enzyme complexes of blood coagulation by competing for phospholipid-binding sites SO BLOOD LA English DT Article ID PHOSPHATIDYL-L-SERINE; ACTIVATED PROTEIN-C; HUMAN-FACTOR-VIII; HUMAN FACTOR-V; MEMBRANE-BINDING; ANNEXIN-V; HUMAN-MILK; PROTHROMBINASE COMPLEX; LIPOCORTIN FAMILY; HUMAN-PLATELETS AB Lactadherin, a glycoprotein of the milk-fat globule membrane, contains tandem C domains with homology to discoidin-type lectins and to membrane-binding domains of blood-clotting factors V and VIII. We asked whether the structural homology confers the capacity to compete for the membrane-binding sites of factor VIII and factor V and to function as an anticoagulant. Our results indicate that lactadherin competes efficiently with factor VIII and factor V for binding sites on synthetic phosphatidylserine-containing membranes with half-maximal displacement at lactadherin concentrations of 1 to 4 nM. Binding competition correlated to functional inhibition of factor VIIIa-factor IXa (factor Xase) enzyme complex. In contrast to annexin V, lactadherin was an efficient inhibitor of the prothrombinase and the factor Xase complexes regardless of the degree of membrane curvature and the phosphatidylserine content. Lactadherin also inhibited the factor Vila-tissue factor complex efficiently whereas annexin V was less effective. Because the inhibitory concentration of lactadherin was proportional to the phospholipid concentration, and because lactadherin was not an efficient inhibitor in the absence of phospholipid, the major inhibitory effect of lactadherin relates to blocking phospholipid sites rather than forming inhibitory protein-protein complexes. Lactadherin was also an effective inhibitor of a modified whole blood prothrombin time assay in which clotting was initiated by dilute tissue factor; 60 nM lactadherin prolonged the prothrombin time 150% versus 20% for 60 nM annexin V. These results indicate that lactadherin can function as a potent phospholipid-blocking anticoagulant. C1 VA Boston Healthcare Syst, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gilbert, GE (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NHLBI NIH HHS [R01 HL57867] NR 57 TC 96 Z9 104 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 APR 1 PY 2003 VL 101 IS 7 BP 2628 EP 2636 DI 10.1182/blood-2002-07-1951 PG 9 WC Hematology SC Hematology GA 660FR UT WOS:000181823600035 PM 12517809 ER PT J AU Burger, PC Wagner, DD AF Burger, PC Wagner, DD TI Platelet P-selectin facilitates atherosclerotic lesion development SO BLOOD LA English DT Article ID E-DEFICIENT MICE; CIRCULATING PLASMA-PROTEIN; ENDOTHELIAL-CELL; APOLIPOPROTEIN-E; ACTIVATED PLATELETS; IN-VIVO; INTIMAL HYPERPLASIA; ADHESION MOLECULES; UNSTABLE ANGINA; HEART-DISEASE AB P-selectin is an adhesion molecule expressed on activated platelets and endothelium. It is known to play an important role in atherosclerosis. P-selectin also circulates in plasma in a soluble form (sP-selectin), which induces procoagulant microparticle formation. We investigated the role of platelet versus endothelial P-selectin in generating sP-selectin and in the formation of atherosclerotic lesions in the apolipoprotein E (apoE)deficient mouse model. For this we transplanted apoE(-/-)P-selectin(-/-) and apoE(-/-)P-selectin(+/+) lethally irradiated mice with bone marrow of either genotype. Seven months after transplantation, we determined from the chimeric animals that the majority of circulating sP-selectin was of endothelial origin. Thus, in atherosclerosis, the procoagulant sP-selectin reflects endothelial rather than platelet activation. We found that endothelial P-selectin was crucial for the promotion of atherosclerotic lesion growth because in its absence only relatively small lesions developed. However, platelet P-selectin also contributed to the lesion development because lesions in wild-type recipients receiving transplants with wild-type platelets were 30% larger than those receiving P-selectin-deficient platelets (P <.008) and were more frequently calcified (80% versus 44%). In comparison with P-selectin wild-type animals, absence of either endothelial or platelet P-selectin inhibited migration of smooth muscle cells into the lesion. Thus, in addition to endothelium, platelets and their P-selectin also actively promote advanced atherosclerotic lesion development. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL 53756, R01 HL053756] NR 47 TC 249 Z9 259 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 APR 1 PY 2003 VL 101 IS 7 BP 2661 EP 2666 DI 10.1182/blood-2002-07-2209 PG 6 WC Hematology SC Hematology GA 660FR UT WOS:000181823600039 PM 12480714 ER PT J AU Tai, YT Podar, K Mitsiades, N Lin, B Mitsiades, C Gupta, D Akiyama, M Catley, L Hideshima, T Munshi, NC Treon, SP Anderson, KC AF Tai, YT Podar, K Mitsiades, N Lin, B Mitsiades, C Gupta, D Akiyama, M Catley, L Hideshima, T Munshi, NC Treon, SP Anderson, KC TI CD40 induces human multiple myeloma. cell migration via phosphatidylinositol 3-kinase/AKT/NF-kappa B signaling SO BLOOD LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; ACTIVATED PROTEIN-KINASE; UROKINASE PLASMINOGEN-ACTIVATOR; CROSS-LINKING CD40; BIOLOGIC SEQUELAE; CANCER CELLS; PLASMA-CELLS; IN-VIVO; EXPRESSION AB Multiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow and their egress into peripheral blood with progression to plasma cell leukemia. Our previous study defined a functional role of CD40 activation in MM cell homing and migration. In this study, we examine signaling events mediating CD40-induced MM cell migration. We show that cross-linking CD40, using either soluble CD40L (sCD40L) or anti-CD40 monoclonal antibody (mAb), induces phosphatidylinositol 3-kinase (PI3K) activity and activates its downstream effector AKT in MMAS cells. CD40 activation also activates the MAP kinase (MEK) pathway, evidenced by phosphorylation of extracellular signal-regulated mitogen-activated protein kinase (ERK), but not c-jun amino-terminal kinase (JNK) or p38, in a dose- and time-dependent manner. Using pharmacologic inhibitors of PI3K and MEK, as well, as adenoviruses expressing dominant-negative and constitutively expressed AKT, we demonstrate that PI3K and AKT activities are required for CD40-induced MM cell migration. In contrast, inhibition of ERK/MEK phosphorylation only partially (10%-15%) prevents migration, suggesting only a minor role in regulation of CD40-mediated MM migration. We further demonstrate that CD40 induces nuclear factor (NF)-kappaB activation as a downstream target of PI3K/ AKT signaling, and that inhibition of NF-kappaB signaling using specific inhibitors PS1145 and SN50 completely abrogates CD40-induced MM migration. Finally, we demonstrate that urokinase plasminogen activator (uPA), an NF-kappaB target gene, is induced by CD40; and conversely, that uPA induction via CD40 is blocked by PI3K and NF-kappaB inhibitors. Our data therefore indicate that CD40-induced MM cell migration is primarily mediated via activation of PI3K/AKT/NF-kappaB signaling, and further suggest that novel therapies targeting this pathway may inhibit MM cell migration associated with progressive MM. C1 Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Jerome Lipper Multiple Myeloma Ctr, M557,44 Binney St, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 FU PHS HHS [P01-78378, R0-1 50947] NR 49 TC 75 Z9 77 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 APR 1 PY 2003 VL 101 IS 7 BP 2762 EP 2769 DI 10.1182/blood-2002-09-2813 PG 8 WC Hematology SC Hematology GA 660FR UT WOS:000181823600053 PM 12433678 ER PT J AU Blaha, P Bigenzahn, S Koporc, Z Schmid, M Langer, F Selzer, E Bergmeister, H Wrba, F Kurtz, J Kiss, C Roth, E Muehlbacher, F Sykes, M Wekerle, T AF Blaha, P Bigenzahn, S Koporc, Z Schmid, M Langer, F Selzer, E Bergmeister, H Wrba, F Kurtz, J Kiss, C Roth, E Muehlbacher, F Sykes, M Wekerle, T TI The influence of immunosuppressive drugs on tolerance induction through bone marrow transplantation with costimulation blockade SO BLOOD LA English DT Article ID MIXED HEMATOPOIETIC CHIMERISM; CD8(+) T-CELLS; SKIN ALLOGRAFT TOLERANCE; DONOR-SPECIFIC TOLERANCE; TOTAL-BODY IRRADIATION; ALLOGENEIC CHIMERISM; MONOCLONAL-ANTIBODY; CYCLOSPORINE-A; PHARMACOLOGICAL IMMUNOSUPPRESSION; ANTI-CD154 ANTIBODY AB We recently developed a murine protocol for the induction of allogeneic mixed chimerism and tolerance employing nonmyeloablative total body irradiation (TBI), standard-dose bone marrow transplantation (BMT), and costimulation blockade (cobl) with an anti-CD154 monoclonal antibody (mAb) plus CTLA4Ig. We now evaluated whether a short course (1 month) of immunosuppressive drugs, which would be ethically required in the clinical setting of organ transplantation to prevent graft loss in case tolerance is not achieved, interferes with tolerance induced with this regimen. Our results show that calcineurin inhibitors (cyclosporin A [CyA] or tacrolimus [FK]) inhibit development of long-term chimerism and abrogate tolerance induction in this model. Rapamycin (rapa), methylprednisolone (MP), FTY720, and mycophenolate mofetil (MMF), in contrast, have no negative effect on chimerism or tolerance development. Peripheral deletion of donor-reactive T cells, which usually occurs in the weeks following BMT in this model, is blocked by CyA and FK, but not by the other drugs tested. Furthermore, we found that the additional use of compatible immunosuppressive drugs (rapa plus MMF plus MP) allows the dose of TBI to be reduced, so that mixed chimerism and donor skin-graft acceptance can be achieved with 1 Gy using clinically feasible cell numbers. Thus, this protocol of BMT with costimulation blockade can be safely combined with a clinically tested immunosuppressive regimen to permit success with a lower dose of irradiation. These results should facilitate clinical application of this tolerance strategy. C1 Univ Vienna, Vienna Gen Hosp, Dept Surg 21A, Div Transplantat, A-1010 Vienna, Austria. Univ Vienna, Vienna Gen Hosp, Dept Radiotherapy & Radiobiol, A-1010 Vienna, Austria. Univ Vienna, Vienna Gen Hosp, Inst Biomed Res, A-1010 Vienna, Austria. Univ Vienna, Vienna Gen Hosp, Inst Clin Pathol, A-1010 Vienna, Austria. Univ Vienna, Vienna Gen Hosp, Surg Res Labs, A-1010 Vienna, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Wekerle, T (reprint author), Univ Vienna, Vienna Gen Hosp, Dept Surg 21A, Div Transplantat, Waehringer Guertel 18, A-1010 Vienna, Austria. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL44-9915] NR 51 TC 130 Z9 137 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 APR 1 PY 2003 VL 101 IS 7 BP 2886 EP 2893 DI 10.1182/blood-2002-10-3014 PG 8 WC Hematology SC Hematology GA 660FR UT WOS:000181823600070 PM 12433677 ER EF