FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Van Ness, B Crowley, J Blood, E Rasmussen, E Ramos, C Grindle, S Morgan, G Johnson, D Hoering, A Greipp, P Barlogie, B Durie, B AF Van Ness, B Crowley, J Blood, E Rasmussen, E Ramos, C Grindle, S Morgan, G Johnson, D Hoering, A Greipp, P Barlogie, B Durie, B TI SNP genotypes as prognostic factors associated with staging in myeloma: The first combined SNP association analysis of SWOG, ECOG, and MRC clinical trials from the bank on a cure. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Canc Res & Biostat, Seattle, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Royal Marsden Hosp, Inst Canc Res, Sutton, MN USA. Mayo Clin, Rochester, MN USA. Univ Arkansas, Myeloma Inst, Little Rock, AR 72204 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RI Johnson, David/A-3907-2011 OI Johnson, David/0000-0003-0887-3343 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3489 BP 974A EP 974A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006273 ER PT J AU Mulligan, G Mitsiades, C Bryant, B Zhan, F Cheng, W Eschrich, S Burrington, B Richardson, P Trepicchio, W Shaughnessy, J Bergsagel, L Damokosh, A Boral, A Esseltine, D Schenkein, D Anderson, K AF Mulligan, G Mitsiades, C Bryant, B Zhan, F Cheng, W Eschrich, S Burrington, B Richardson, P Trepicchio, W Shaughnessy, J Bergsagel, L Damokosh, A Boral, A Esseltine, D Schenkein, D Anderson, K TI Pharmacogenomics (PGx) research in the APEX randomized multicenter international phase 3 trial comparing bortezomib and high-dose dexamethasone (Dex). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA USA. Univ Arkansas, Fayetteville, AR 72701 USA. Mayo Clin, Rochester, MN 55905 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. RI Eschrich, Steven/K-6848-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3491 BP 975A EP 975A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006275 ER PT J AU Tefferi, A Lasho, TL Schwager, SM Steensma, DP Mesa, RA Li, CY Wadleigh, M Gilliland, DG AF Tefferi, A Lasho, TL Schwager, SM Steensma, DP Mesa, RA Li, CY Wadleigh, M Gilliland, DG TI The JAK2 V617F tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: Clinical correlates and prognostic relevance in 157 patients. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Mayo Clin, Rochester, MN USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3502 BP 978A EP 978A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006286 ER PT J AU Sattler, M Walz, C Crowley, BJ Gramlich, JL King, KL Podar, K Griffin, JD AF Sattler, M Walz, C Crowley, BJ Gramlich, JL King, KL Podar, K Griffin, JD TI The Jak2V617F oncogene associated with polycythemia vera regulates G1/S-phase transition. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3510 BP 980A EP 980A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006294 ER PT J AU Gazda, HT Kho, AT Sanoudou, D Zaucha, JM Sieff, CA Beggs, AH AF Gazda, HT Kho, AT Sanoudou, D Zaucha, JM Sieff, CA Beggs, AH TI Defective ribosomal protein gene expression alters transcription, translation and oncogenic pathways in Diamond-Blackfan anemia SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Genom Program, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. Acad Athens, Fdn Biomed Res, Athens, Greece. Childrens Hosp, Dept Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3546 BP 990A EP 990A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006330 ER PT J AU Josefsson, EC Bergmeier, W Wagner, DD Stossel, TP Hartwig, JH Hoffmeister, KM AF Josefsson, EC Bergmeier, W Wagner, DD Stossel, TP Hartwig, JH Hoffmeister, KM TI Differential changes in platelet VWF receptor following refrigeration for short or long periods SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Univ Gothenburg, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3564 BP 995A EP 995A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006348 ER PT J AU Montefusco, MC Fleming, JC Chick, G Neufeld, EJ AF Montefusco, MC Fleming, JC Chick, G Neufeld, EJ TI Thiamine deprivation induces reticulocytopenic anemia in Slc19A2 knockout marrow: Evidence for cell-intrinsic defect SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Neufeld, Ellis/F-9331-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3604 BP 1004A EP 1005A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006388 ER PT J AU Rhodes, J Amsterdam, A Ho, K Kanki, JP Hopkins, N Look, AT AF Rhodes, J Amsterdam, A Ho, K Kanki, JP Hopkins, N Look, AT TI A role for fbxo5 in zebrafish myelopoiesis SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3608 BP 1005A EP 1006A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006392 ER PT J AU Wang, ZZ Chen, T An, P Shao, Y Jain, R Scadden, DT AF Wang, ZZ Chen, T An, P Shao, Y Jain, R Scadden, DT TI A novel culture system of human ES cells for high efficient hematopoietic and endothelial differentiation SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Stem Cell Inst, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3616 BP 1007A EP 1008A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006400 ER PT J AU Wu, WS Heinrichs, S Xu, D Adams, JM Look, AT AF Wu, WS Heinrichs, S Xu, D Adams, JM Look, AT TI Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing Puma SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Walter & Eliza Hall Inst Med Res, Parkville, Vic, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3624 BP 1009A EP 1009A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006408 ER PT J AU Ebert, BL Mak, R Pretz, JL Peck, D Haggerty, S Tolliday, N Golub, TR AF Ebert, BL Mak, R Pretz, JL Peck, D Haggerty, S Tolliday, N Golub, TR TI High throughput screen to identify small molecules that differentially regulate expression of the globin genes SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat & Med Oncol, Boston, MA 02115 USA. Broad Inst, Canc Genom Grp, Cambridge, MA USA. Brigham & Womens Hosp, Dept Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3632 BP 1011A EP 1011A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006416 ER PT J AU Linden, E McAfee, SL Dey, BR Ballen, K Saidman, S Colby, C Sykes, M Spitzer, TR AF Linden, E McAfee, SL Dey, BR Ballen, K Saidman, S Colby, C Sykes, M Spitzer, TR TI Outcomes of patients with engraftment syndrome (ES) following nonmyeloablative hematopoietic stem cell transplant (SCT) for hematologic malignancy(HM). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3661 BP 1019A EP 1019A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006445 ER PT J AU Byrne, BJ Antin, JH Alyea, EP Choa, NJ Rizzieri, DA AF Byrne, BJ Antin, JH Alyea, EP Choa, NJ Rizzieri, DA TI Efficacy of performing a second non-myeloablative allogenic stem cell transplant. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Duke Univ, Med Ctr, Div Cellular Therapy, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3664 BP 1020A EP 1020A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006448 ER PT J AU Ting, DT Dey, B Chaudhary, A Colby, C Power, K McAfee, S Ballen, K Attar, E Saidman, S Preffer, F Sackstein, R Shaffer, J Sykes, M Spitzer, TR AF Ting, DT Dey, B Chaudhary, A Colby, C Power, K McAfee, S Ballen, K Attar, E Saidman, S Preffer, F Sackstein, R Shaffer, J Sykes, M Spitzer, TR TI Development of late over early full donor chimerism (FDC) results in improved progression-free and overall survival in patients with advanced malignant lymphomas receiving nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3665 BP 1020A EP 1020A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006449 ER PT J AU Yee, AJ Spitzer, TR Saidman, SL Shaffer, J Power, KA McAfee, SL Ballen, KK Attar, EC Preffer, FI Sykes, M Dey, BR AF Yee, AJ Spitzer, TR Saidman, SL Shaffer, J Power, KA McAfee, SL Ballen, KK Attar, EC Preffer, FI Sykes, M Dey, BR TI Minimal HLA disparity and KIR ligand compatibility in host versus graft direction may facilitate donor engraftment following in vivo and ex vivo T cell depleted (TCD) non-myeloablative haploidentical stem cell transplantation for hematologic malignancies. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3668 BP 1021A EP 1021A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006452 ER PT J AU Zhang, XF Wang, JF Maor, Y Kunos, G Groopman, JE AF Zhang, XF Wang, JF Maor, Y Kunos, G Groopman, JE TI Endogenous cannabinoid-like arachidonoyl serine induces angiogenesis through novel pathways. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, BIDMC, Boston, MA USA. Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Jerusalem, Israel. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3690 BP 1027A EP 1027A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006474 ER PT J AU Appel, LJ Sacks, FM Carey, VJ Obarzanek, E Swain, JF Miller, ER Conlin, PR Erlinger, TP Rosner, BA Laranjo, NM Charleston, J McCarron, P Bishop, LM AF Appel, LJ Sacks, FM Carey, VJ Obarzanek, E Swain, JF Miller, ER Conlin, PR Erlinger, TP Rosner, BA Laranjo, NM Charleston, J McCarron, P Bishop, LM CA OmniHeart Collaborative Res Grp TI Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids - Results of the OmniHeart randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; DIETARY-PROTEIN; HYPERTENSION PREVENTION; MEDITERRANEAN DIET; EDUCATION-PROGRAM; GLYCEMIC INDEX; WEIGHT-LOSS; OLIVE OIL; RISK; CHOLESTEROL AB Context Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. Objective To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. Design, Setting, and Participants Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. Interventions A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. Main Outcome Measures Systolic blood pressure and low-density lipoprotein cholesterol. Results Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P=.002) and by 3.5 mm Hg (P=.006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P=.01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P=.02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P=.005) and by 2.9 mm Hg among those with hypertension (P=.02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P=.03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P=.02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. Conclusion In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00051350. C1 Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD 21205 USA. Bloomberg Sch Publ Hlth, Baltimore, MD USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Gen Clin Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. VA Boston Healthcare Syst, Div Endocrinol, Boston, MA USA. RP Appel, LJ (reprint author), Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-618, Baltimore, MD 21205 USA. EM lappel@jhmi.edu FU NCRR NIH HHS [RR02635]; NHLBI NIH HHS [HL67098, HL68712]; NIDDK NIH HHS [DK63214] NR 47 TC 487 Z9 500 U1 11 U2 61 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 16 PY 2005 VL 294 IS 19 BP 2455 EP 2464 DI 10.1001/jama.294.19.2455 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 984BL UT WOS:000233277400024 PM 16287956 ER PT J AU Cannon, CP AF Cannon, CP TI The IDEAL cholesterol - Lower is better SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CORONARY-HEART-DISEASE; PLACEBO-CONTROLLED TRIAL; SCANDINAVIAN SIMVASTATIN SURVIVAL; LOW-DENSITY-LIPOPROTEIN; TREATMENT PANEL-III; C-REACTIVE PROTEIN; STATIN THERAPY; PRIMARY PREVENTION; CLINICAL-TRIALS; ARTERY-DISEASE C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 29 TC 31 Z9 32 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 16 PY 2005 VL 294 IS 19 BP 2492 EP 2494 DI 10.1001/jama.294.19.2492 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 984BL UT WOS:000233277400029 PM 16287961 ER PT J AU Magavi, SSP Mitchell, BD Szentirmai, O Carter, BS Macklis, JD AF Magavi, SSP Mitchell, BD Szentirmai, O Carter, BS Macklis, JD TI Adult-born and preexisting olfactory granule neurons undergo distinct experience-dependent modifications of their olfactory responses in vivo SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurogenesis; plasticity; neuronal survival; integration; olfaction; granule cell ID C-FOS; SYNAPTIC PLASTICITY; SUBVENTRICULAR ZONE; GENERATED NEURONS; NEWBORN NEURONS; MAMMALIAN BRAIN; MESSENGER-RNA; YOUNG-RATS; CELL-DEATH; BULB AB Neurogenesis continues throughout adulthood in the mammalian olfactory bulb and hippocampal dentate gyrus, suggesting the hypothesis that recently generated, adult-born neurons contribute to neural plasticity and learning. To explore this hypothesis, we examined whether olfactory experience modifies the responses of adult-born neurons to odorants, using immediate early genes (IEGs) to assay the response of olfactory granule neurons. We find that, shortly after they differentiate and synaptically integrate, the population of adultborn olfactory granule neurons has a greater population IEG response to novel odors than mature, preexisting neurons. Familiarizing mice with test odors increases the response of the recently incorporated adult-born neuron population to the test odors, and this increased responsiveness is long lasting, demonstrating that the response of the adult-born neuron population is altered by experience. In contrast, familiarizing mice with test odors decreases the IEG response of developmentally generated neurons, suggesting that recently generated adult- born neurons play a distinct role in olfactory processing. The increased IEG response is stimulus specific; familiarizing mice with a set of different, "distractor" odors does not increase the adult-born neuron population response to the test odors. Odor familiarization does not influence the survival of adult-born neurons, indicating that the changes in the population response of adultborn neurons are not attributable to increased survival of odor-stimulated neurons. These results demonstrate that recently generated adult- born olfactory granule neurons and older, preexisting granule neurons undergo contrasting experience-dependent modifications in vivo and support the hypothesis that adult-born neurons are involved in olfactory learning. C1 Harvard Univ, Sch Med, Ctr Nervous Syst Repair, Massachusetts Gen Hosp,Dept Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Nervous Syst Repair, Massachusetts Gen Hosp,Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Stem Cell Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Macklis, JD (reprint author), Harvard Univ, Sch Med, Ctr Nervous Syst Repair, Massachusetts Gen Hosp,Dept Neurosurg, Edwards Res Bldg,Mail Code EDR 410,50 Blossom St, Boston, MA 02114 USA. EM jeffrey_macklis@hms.harvard.edu FU NICHD NIH HHS [HD18655]; NINDS NIH HHS [NS41590, NS45523, NS49553] NR 55 TC 137 Z9 145 U1 3 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 16 PY 2005 VL 25 IS 46 BP 10729 EP 10739 DI 10.1523/JNEUROSCI.2250-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 984QJ UT WOS:000233319100017 PM 16291946 ER PT J AU Wei, EK Giovannucci, E Fuchs, CS Willett, WC Mantzoros, CS AF Wei, EK Giovannucci, E Fuchs, CS Willett, WC Mantzoros, CS TI Low plasma adiponectin levels and risk of colorectal cancer in men: A prospective study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GROWTH-FACTOR-I; FOOD FREQUENCY QUESTIONNAIRE; BODY-FAT DISTRIBUTION; INSULIN SENSITIVITY; COLON-CANCER; PHYSICAL-ACTIVITY; IGF-I; ENDOMETRIAL CANCER; METABOLIC SYNDROME; DIABETES-MELLITUS AB Background. Adiponectin is an insulin-sensitizing hormone secreted by adipocytes. Levels of adiponectin are inversely associated with adiposity and insulin resistance. Because both adiposity and insulin resistance have been associated with risk of colorectal cancer, we hypothesized that adiponectin is associated with colorectal carcinogenesis. Methods: We evaluated the association between adiponectin and colorectal cancer among 18 225 men in the Health Professionals Follow-up Study who provided blood samples in 1994. Between blood collection and January 31, 2002, 179 incident colorectal cancer cases occurred. Each case patient was matched to two control subjects on year of birth and date of blood draw. Information on lifestyle factors and diet was collected using biennial questionnaires and food frequency questionnaires. Logistic regression models were used to estimate relative risks (RRs) and confidence intervals (CIs). All statistical tests were two-sided. Results: We observed a statistically significant inverse association between plasma adiponectin levels and risk of colorectal cancer (for the highest quintile [Q5] versus the lowest quintile [Q1], RR = 0.42, 95% CI = 0.23 to 0.78; P-trend = .01). The association was only slightly attenuated after adjustment for body mass index (Q5 versus Q1, RR = 0.48, 95% CI = 0.25 to 0-90; P-trend = .04) or for body mass index and other major risk factors for colorectal cancer (family history, physical activity, multivitamin use, smoking, alcohol, aspirin use, history of endoscopy, dietary calcium, folate, vitamin E, and vitamin D; Q5 versus Q1, multivariable RR = 0.50, 95% CI = 0.26 to 0.97; P-trend = .08). Relative risks were not linear in any of the analyses; the second quintile had a lower relative risk than the lowest quintile, but further decreases in risk were not evident with increasing levels of adiponectin. Conclusions: In this prospective nested case-control study, men with low plasma adiponectin levels had a higher risk of colorectal cancer than men with higher levels. More prospective observational studies, particularly in women, and mechanistic studies are required to fully understand the relationship between adiponectin and carcinogenesis. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Wei, EK (reprint author), Channing Labs, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM esther.wei@channing.harvard.edu FU NCI NIH HHS [CA 055075, CA 58785, T32 CA 090001] NR 41 TC 286 Z9 299 U1 5 U2 15 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 NOV 16 PY 2005 VL 97 IS 22 BP 1688 EP 1694 DI 10.1093/jnci/dji376 PG 7 WC Oncology SC Oncology GA 985DM UT WOS:000233356300012 PM 16288122 ER PT J AU Kaufman, ES Gorodeski, EZ Dettmer, MM Dikshteyn, M AF Kaufman, ES Gorodeski, EZ Dettmer, MM Dikshteyn, M TI Use of autonomic maneuvers to probe phenotype/genotype discordance in congenital long QT syndrome SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EXERCISE STRESS TEST; T-WAVE; VENTRICULAR REPOLARIZATION; INTERVAL PROLONGATION; POTASSIUM CHANNEL; GENOTYPE; GENE; LQT1; RISK; CARRIERS AB Patients with congenital long QT syndrome due to potassium channel mutations (LQT1 and LQT2) may elude diagnosis due to normal electrocardiographic findings at rest, yet remain at risk of sudden death during bradycardia or sympathetic stimulation. To test the hypothesis that autonomic maneuvers can unmask long QT syndrome in genetically abnormal subjects with a normal phenotype (QTc <= 450 ms), we exposed 13 controls (33 +/- 9 years; 5 men), 5 patients with LQT1 (32 -t 12 years; 3 men), and 5 patients with LQT2 (30 11 years; 5 men) to phenylephrine bolus, exercise, and epinephrine infusion. The QT interval was measured at baseline and after each intervention. A substantial overlap was found in QTc among the groups at baseline and after phenylephrine. In contrast, QTc was significantly and consistently longer in subjects with LQT1 compared with controls during and after exercise (492 +/- 40 vs 407 +/- 14 ms, p < 0.0001, at peak exercise; 498 +/- 30 vs 399 +/- 20 ms, p < 0.0001, at 1 minute into recovery) or epinephrine (623 +/- 51 vs: 499 +/- 51 ms, p < 0.001, at peak epinephrine; 604 +/- 36 vs 507 +/- 54 ms, p < 0.01, at I minute into recovery) but not in subjects with LQT2. In conclusion, sympathetic stimulation can reveal the LQT1 phenotype even in subjects with normal baseline electrocardiographic findings. (c) 2005 Elsevier Inc. All rights reserved. C1 Case Western Reserve Univ, Heart & Vasc Res Ctr, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Kaufman, ES (reprint author), Case Western Reserve Univ, Heart & Vasc Res Ctr, MetroHlth Campus, Cleveland, OH 44106 USA. EM ekaufman@metrohealth.org RI Gorodeski, Eiran/D-5384-2009; OI Gorodeski, Eiran/0000-0003-3756-8831 FU NCRR NIH HHS [M01 RR 00080] NR 30 TC 12 Z9 12 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 NOV 15 PY 2005 VL 96 IS 10 BP 1425 EP 1430 DI 10.1016/j.amjcard.2005.07.046 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 987HV UT WOS:000233509900017 PM 16275192 ER PT J AU Poorkaj, P Nutt, JG James, D Gancher, S Bird, TD Steinbart, E Schellenberg, GD Payami, H AF Poorkaj, P Nutt, JG James, D Gancher, S Bird, TD Steinbart, E Schellenberg, GD Payami, H TI Parkin mutation analysis in clinic patients with early-onset Parkinson's disease (vol 129, pg 44, 2004) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Correction C1 Vet Affairs Puget Sound Hlth Care Syst, Seattle Div, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Washington, Div Gerontol & Geriat Med, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Kaiser Permanente, Portland, OR USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Univ Washington, Dept Neurol & Pharmacol, Seattle, WA 98195 USA. RP Payami, H (reprint author), New York State Dept Hlth, Wadsworth Ctr, Genom Inst, Div Genet Disorders, 120 New Scotland Ave, Albany, NY 12208 USA. EM hpayami@wadsworth.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 EI 1552-4833 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 15 PY 2005 VL 139A IS 1 BP 56 EP 56 DI 10.1002/ajmg.a.30937 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 981AL UT WOS:000233059300016 ER PT J AU Hager, DN Krishnan, JA Hayden, DL Brower, RG AF Hager, DN Krishnan, JA Hayden, DL Brower, RG CA ARDS Clinical Trials Network TI Tidal volume reduction in patients with acute lung injury when plateau pressures are not high SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; acute lung injury; plateau; mechanical ventilation ID RESPIRATORY-DISTRESS-SYNDROME; END-EXPIRATORY PRESSURE; EVIDENCE-BASED MEDICINE; MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; PULMONARY-EDEMA; HOSPITAL MORTALITY; AIRWAY PRESSURES; SYNDROME TRIALS; ARDS AB Use of a volume- and pressure-limited mechanical ventilation strategy improves clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). However, the extent to which tidal volumes and inspiratory airway pressures should be reduced to optimize clinical outcomes is a controversial topic. This article addresses the question, "Is there a safe upper limit to inspiratory plateau pressure in patients with ALI/ARDS?' We reviewed data from animal models with and without preexisting lung injury, studies of normal human respiratory system mechanics, and the results of five clinical trials of lung-protective mechanical ventilation strategies. We also present an original analysis of data from the largest of the five clinical trials. The available data from each of these assessments do not support the commonly held view that inspiratory plateau pressures of 30 to 35 cm H2O are safe. We could not identify a safe upper limit for plateau pressures in patients with ALI/ARDS. C1 Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA USA. RP Hager, DN (reprint author), 1830 E Monument St,Room 549, Baltimore, MD 21205 USA. EM dhager1@jhmi.edu FU NHLBI NIH HHS [F32-HL078132, K23-HL67850, N01-HR46063, N01-HR46064, P50-HL073944] NR 47 TC 239 Z9 253 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD NOV 15 PY 2005 VL 172 IS 10 BP 1241 EP 1245 DI 10.1164/rccm.200501-048CP PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 982SP UT WOS:000233182200003 PM 16081547 ER PT J AU Nishimura, W Salameh, T Kondo, T Sharma, A AF Nishimura, W Salameh, T Kondo, T Sharma, A TI Regulation of insulin gene expression by overlapping DNA-binding elements SO BIOCHEMICAL JOURNAL LA English DT Article DE insulin gene transcription; MafA; Maf-response element; overlapping element; RIPE3b; transcription factors ID TRANSCRIPTION FACTOR; BETA-CELLS; DIABETES-MELLITUS; LENS DIFFERENTIATION; L-MAF; GLUCOSE; ENHANCER; RIPE3B1; REDUCTION; PROTEINS AB The transcription factor MafA/RIPE3b I is an important regulator of insulin gene expression. MafA binds to the insulin enhancer element RIPE3b (C1-A2), now designated as insulin MARE (Maf response element). The insulin MARE element shares an overlapping DNA-binding region with another insulin enhancer element A2.A2.2, a beta-cell-specific activator, like the MARE-binding factor MafA, binds to the overlapping A2 element. Our previous results demonstrated that two nucleotides in the overlapping region are required for the binding of both factors. Surprisingly, instead of interfering with each other's binding activity, the MafA and the A2-binding factors co-operatively activated insulin gene expression. To understand the molecular mechanisms responsible for this functional co-operation, we have determined the nucleotides essential for the binding of the A2.2 factor. Using this information, we have constructed non-overlapping DNA-binding elements and their derivatives, and subsequently analysed the effect of these modifications on insulin gene expression. Our results demonstrate that the overlapping binding site is essential for maximal insulin gene expression. Furthermore, the overlapping organization is critical for MafA-mediated transcriptional activation, but has a minor effect on the activity of A2-binding factors. Interestingly, the binding affinities of both Mafa and A2.2 to the overlapping or non-overlapping binding sites were not significantly different, implying that the overlapping binding organization may increase the activation potential of MafA by physical/functional interactions with A2-binding factors. Thus our results demonstrate a novel mechanism for the regulation of MafA activity, and in turn beta-cell function, by altering expression and/or binding of the A2.2 factor. Our results further suggest that the major downstream targets of MafA will in addition to the MARE element have a binding site for the A2.2 factor.. C1 Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Sect Islet Transplantat & Cell, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Sharma, A (reprint author), Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr,Sect Islet Transplantat & Cell, 1 Joslin Pl, Boston, MA 02215 USA. EM arun.sharma@joslin.harvard.edu OI Nishimura, Wataru/0000-0002-8068-1277 FU NIDDK NIH HHS [R01 DK060127-01A2, DK-36836, P30 DK036836, R01 DK060127, R01 DK060127-02, R01 DK060127-03, R01 DK060127-04, R01 DK060127-05, R01DK060127] NR 49 TC 5 Z9 5 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 15 PY 2005 VL 392 BP 181 EP 189 DI 10.1042/BJ20050970 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 987UM UT WOS:000233542800020 PM 16050808 ER PT J AU Alter, G Teigen, N T Davis, B Addo, MM Suscovich, TJ Waring, MT Streeck, H Johnston, MN Staller, KD Zaman, MT Yu, XG Lichterfeld, M Basgoz, N Rosenberg, ES Altfeld, M AF Alter, G Teigen, N T Davis, B Addo, MM Suscovich, TJ Waring, MT Streeck, H Johnston, MN Staller, KD Zaman, MT Yu, XG Lichterfeld, M Basgoz, N Rosenberg, ES Altfeld, M TI Sequential deregulation of NK cell subset distribution and function starting in acute HIV-1 infection SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; INDIVIDUALS; IMMUNODEFICIENCY; CYTOTOXICITY; CHEMOKINES; RECEPTORS; VIREMIA AB Natural killer (NK) cells are critical in the first-line defense against viral infections. Chronic HIV-1 infection leads to a perturbation in the NK cell compartment, yet the kinetics of this deregulation and the functional consequences are unclear. Here, we characterized changes in the NK cell compartment longitudinally by multiparameter flow cytometry, starting in acute HIV-1 infection. Acute HIV-1 infection was associated with elevated INK cell numbers, with an expansion of CD3(neg)CD56(dim)CD16(pos) NK cells and an early depletion of CD3(neg)CD56(bright)CD16(neg) NK cells. Ongoing viral replication resulted in a depletion of CD3(neg)CD56(dim)CD16(pos) NK cells with a paralleled increase in functionally anergic CD3(neg)CD56(neg)CD16(pos) NK cells, accompanied by reduced functional activity, as measured by CD107a expression and cytokine secretion. Taken together, these studies demonstrate a sequential impairment of NK cell function with persistent viral replication resulting from a progressive deregulation of NK cell subsets with distinct functional properties. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Div Aids, Cambridge, MA 02138 USA. RP Altfeld, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr,Infect Dis Unit, Cambridge, MA 02138 USA. EM maltfeld@partners.org OI Staller, Kyle/0000-0003-4925-4290 NR 20 TC 166 Z9 171 U1 1 U2 10 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3366 EP 3369 DI 10.1182/blood-2005-03-1100 PG 4 WC Hematology SC Hematology GA 982US UT WOS:000233187700015 PM 16002429 ER PT J AU Levine, RL Loriaux, M Huntly, BJP Loh, ML Beran, M Stoffregen, E Berger, R Clark, JJ Willis, SG Nguyen, KT Flores, NJ Estey, E Gattermann, N Armstrong, S Look, AT Griffin, JD Bernard, OA Heinrich, MC Gilliland, DG Druker, B Deininger, MWN AF Levine, RL Loriaux, M Huntly, BJP Loh, ML Beran, M Stoffregen, E Berger, R Clark, JJ Willis, SG Nguyen, KT Flores, NJ Estey, E Gattermann, N Armstrong, S Look, AT Griffin, JD Bernard, OA Heinrich, MC Gilliland, DG Druker, B Deininger, MWN TI The JAK2V617F activating mutation occurs in chronic myelomonocytic leukemia and acute myeloid leukemia, but not in acute lymphoblastic leukemia or chronic lymphocytic leukemia SO BLOOD LA English DT Article ID TYROSINE KINASE JAK2; MYELOPROLIFERATIVE-DISORDERS; POLYCYTHEMIA-VERA; RECEPTOR-BETA; FUSION; GENE; IDENTIFICATION; TRANSLOCATION; LYMPHOMA; IMATINIB AB Activating mutations in tyrosine kinases have been identified in hematopoietic and nonhematopoietic malignancies. Recently, we and others identified a single recurrent somatic activating mutation (JAK2V617F) in the Janus kinase 2 (JAK2) tyrosine kinase in the myeloproliferative disorders (MPDs) polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. We used direct sequence analysis to determine if the JAK2V617F mutation was present in acute myeloid leukemia (AML), chronic myelomonocytic leukemia (CMML/atypical chronic myelogenous leukemia (aCML), myelodysplastic syndrome (MDS), B-lineage acute lymphoblastic leukemia (ALL), T-cell ALL, and chronic lymphocytic leukemia (CLL). Analysis of 222 patients with AML identified JAK2V617F mutations in 4 patients with AML, 3 of whom had a preceding MPD. JAK2V617F mutations were identified in 9 (7.8%) of 116 CMML/a CIVIL samples, and in 2 (4.2%) of 48 MDS samples. We did not identify the JAK2V617F disease allele in B-lineage ALL (n = 83), T-cell ALL (n = 93), or CLL (n = 45). These data indicate that the JAK2V617F allele is present in acute and chronic myeloid malignancies but not in lymphoid malignancies. C1 Oregon Hlth Sci Univ, Inst Canc, Leukemia Ctr, BMT, Portland, OR 97239 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Howard Hughes Med Inst, Ctr Canc, Portland, OR USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Rochester, MN 55905 USA. Hop Necker Enfants Malad, INSERM, E0210, Inst Federat Rech Necker Enfants Malad, Paris, France. Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-4000 Dusseldorf, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Deininger, MWN (reprint author), Oregon Hlth Sci Univ, Inst Canc, Leukemia Ctr, BMT, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM deininge@ohsu.edu RI huntly, brian/E-6725-2014; Bernard, Olivier/E-5721-2016 OI huntly, brian/0000-0003-0312-161X; FU NCI NIH HHS [1P01-CA108631-01A1, CA66996]; NIDDK NIH HHS [DK50654] NR 22 TC 227 Z9 244 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3377 EP 3379 DI 10.1182/blood-2005-05-1898 PG 3 WC Hematology SC Hematology GA 982US UT WOS:000233187700018 PM 16081687 ER PT J AU Sundrud, MS VanCompernolle, SE Eger, KA Bruno, TC Subramaniam, A Mummidi, S Ahuja, SK Unutmaz, D AF Sundrud, MS VanCompernolle, SE Eger, KA Bruno, TC Subramaniam, A Mummidi, S Ahuja, SK Unutmaz, D TI Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTORS; ERYTHROID-CELLS; GENE-EXPRESSION; MAST-CELLS; TH2 CELLS; IN-VITRO; INFECTION; DIFFERENTIATION; PROMOTER AB CC chemokine receptor 5 (CCR5) is the major HIV-1 coreceptor and its expression levels are a critical determinant of HIV-1 infection. However, the molecular mechanisms of CCR5 regulation in primary targets of HIV-1 remain unknown. Despite binding to conserved DNA elements, we show that the transcription factors GATA binding protein 1 (GATA-1) and GATA-3 differentially suppress the expression of CCR5 in stem-cell-derived dendritic cells and primary human T-cell subsets. In addition, GATA-1 expression was also more potent than GATA-3 in suppressing T helper 1 (Th1)-associated genes, interferon-gamma (IFN gamma), and CXC chemokine receptor-3 (CXCR3). GATA-1, but not GATA-3, potently suppressed CCR5 transcription, thereby rendering human T cells resistant to CCR5-tropic HIV-1 infection. However, GATA-1 could also serve as a surrogate for GATA-3 in its canonic role of programming Th2 gene expression. These findings provide insight into GATA-3-mediated gene regulation during T-cell differentiation. Importantly, decoding the mechanisms of GATA-1-mediated repression of CCR5 may offer an opportunity to develop novel approaches to inhibit CCR5 expression in T cells. C1 Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Vet Adm Ctr AIDS & HIV Infect, San Antonio, TX USA. Sanofi Aventis Pharmaceut, Dept Internal Med, Bridgewater, NJ USA. RP Unutmaz, D (reprint author), Vanderbilt Univ, Med Ctr, Dept Microbiol & Immunol, 21st Ave S,MCN-AA5206, Nashville, TN 37232 USA. EM AHUJAS@uthscsa.edu RI Mummidi, Srinivas/C-1004-2008 OI Mummidi, Srinivas/0000-0002-4068-6380 FU NIAID NIH HHS [R01-AI054206, R01-AI043279] NR 52 TC 11 Z9 11 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3440 EP 3448 DI 10.1182/blood-2005-03-0857 PG 9 WC Hematology SC Hematology GA 982US UT WOS:000233187700028 PM 16091457 ER PT J AU Goemans, BF Zwaan, CM Harlow, A Loonen, AH Gibson, BES Hahlen, K Reinhardt, D Creutzig, U Heinrich, MC Kaspers, GJL AF Goemans, BF Zwaan, CM Harlow, A Loonen, AH Gibson, BES Hahlen, K Reinhardt, D Creutzig, U Heinrich, MC Kaspers, GJL TI In vitro profiling of the sensitivity of pediatric leukemia cells to tipifarnib: identification of T-cell ALL and FAB M5 AML as the most sensitive subsets SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; RAS GENE-MUTATIONS; FARNESYL TRANSFERASE INHIBITORS; ACUTE MYELOGENOUS LEUKEMIA; N-RAS; DRUG-RESISTANCE; FARNESYLTRANSFERASE INHIBITORS; MYELODYSPLASTIC SYNDROME; PROTEIN TRANSFERASE AB Although the prognosis of pediatric leukemias has improved considerably, many patients still have relapses. Tipifarnib, a farnesyl transferase inhibitor (FTI), was developed to target malignancies with activated RAS, including leukemia. We tested 52 pediatric acute myeloid leukemia (AML) and 36 pediatric acute lymphoblastic leukemia (ALL) samples for in vitro sensitivity to tipifarnib using a total cell-kill assay and compared these results to those obtained with normal bone marrow (N BM) samples (n = 25). AML samples were significantly more sensitive to tipifarnib compared to B-cell precursor ALL (BCP ALL) or IN BM samples. Within AML, French-American-British (FAB) M5 samples were most sensitive to tipifarnib. T-cell ALL samples were significantly more sensitive than BCP ALL and N BM samples. In AML there was a marked correlation between tipifarnib resistance and daunorubicin or etoposide resistance, but not to cytarabine or 6-thioguanine. RAS mutations were present in 32% of AML and 18% of ALL samples, but there was no correlation between RAS mutational status and sensitivity to tipifarnib. Future studies are needed to identify biomarkers predictive of tipifarnib sensitivity. In addition, clinical studies, especially in T-cell ALL, seem warranted. C1 VU Univ, Med Ctr, Dept Pediat Oncol Hematol, NL-1007 MB Amsterdam, Netherlands. Sophia Childrens Univ Hosp, Erasmus MC, Dept Pediat Hematol Oncol, Rotterdam, Netherlands. Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Med Oncol, Dept Med, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. MRC, Childhood Leukaemia Working Party, Glasgow, Lanark, Scotland. Dutch Childhood Oncol Grp, The Hague, Netherlands. AML BFM Study Grp, Munster, Germany. RP Goemans, BF (reprint author), VU Univ, Med Ctr, Dept Pediat Oncol Hematol, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM bf.goemans@vumc.nl RI Reinhardt, Dirk/D-3939-2011 OI Reinhardt, Dirk/0000-0003-4313-9056 NR 39 TC 22 Z9 22 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3532 EP 3537 DI 10.1182/blood-2005-04-1640 PG 6 WC Hematology SC Hematology GA 982US UT WOS:000233187700039 PM 16051737 ER PT J AU Wu, CJ Krishnamurti, L Kutok, JL Biernacki, M Rogers, S Zhang, WD Antin, JH Ritz, J AF Wu, CJ Krishnamurti, L Kutok, JL Biernacki, M Rogers, S Zhang, WD Antin, JH Ritz, J TI Evidence for ineffective erythropoiesis in severe sickle cell disease SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGENS; VERSUS-HOST-DISEASE; RED-BLOOD-CELLS; STEM-CELL; HEMATOPOIETIC CHIMERISM; ERYTHROID LINEAGE; ANEMIA; SURVIVAL; THERAPY AB Peripheral destruction of sickled erythrocytes is a cardinal feature of sickle cell disease (SCD). Less well established is the potential contribution of ineffective erythropoiesis to the pathophysiology of this hemoglobinopathy. Since patients with SCD frequently develop mixed hematopoietic chimerism after allogeneic nonmyeloablative stem cell transplantation, we used this opportunity to directly compare the differentiation and survival of SCD and donor-derived erythropoiesis in vivo. Donor and recipient erythropoiesis was compared in 4 patients with SCD and 4 without SCD who developed stable mixed hematopoietic chimerism following transplant. Molecular analysis of chimerism in peripheral blood and bone marrow demonstrated higher expression of donor-derived P-globin RNA relative to the level of donor-derived genomic DNA in patients with SCD. Analysis of chimerism in immature (glycophorin A-positive [GYPA(+)], CD71(hi)) and mature (GYPA(+), CD71(neg)) erythroblasts confirmed the intramedullary loss of SS erythroblasts with progressive maturation. In patients with SCD, relative enrichment of donor erythroid precursors began to appear at the onset of hemoglobinization. Ineffective erythropoiesis of homozygous hemoglobin S (SS) progenitors thus provides a maturation advantage for homozygous hemoglobin A (AA) or heterozygous hemoglobin S/hemoglobin A (SA) donor erythroid precursor cells that results in greater donor contribution to overall erythropoiesis following stem-cell transplantation and improvement of clinical disease. C1 Dana Farber Canc Inst, Div Hematol Malignancies, 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. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. RP Wu, CJ (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM cwu@partners.org RI Krishnamurti, Lakshmanan/F-7637-2011; Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NHLBI NIH HHS [HL070149, K08 HL04293]; NIAID NIH HHS [AI29530] NR 43 TC 30 Z9 31 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3639 EP 3645 DI 10.1182/blood-2005-04-1376 PG 7 WC Hematology SC Hematology GA 982US UT WOS:000233187700054 PM 16091448 ER PT J AU Savoy, RL AF Savoy, RL TI Experimental design in brain activation MR: Cautionary tales SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT 2nd Conference on NeuroEconomics CY MAY 25-27, 2004 CL Munster, GERMANY SP Stift Neuromed, Med Fdn, Gesell Forder Westfal Wilhelms Univ Munster eV, German Minist Educ & Res, Wilhelm Lorch Stift, Philips Med Syst, HMK comp Technologies GmbH, Covilex, Medres Med Res GmbH DE functional MRI (fMRI); experimental design; error correction in science ID BOLD HEMODYNAMIC-RESPONSES; FMRI; VARIABILITY; ANXIETY AB The use of functional magnetic resonance imaging (fMRI) in cognitive neuroscience has expanded at an amazing rate in the past 10 years. Cur-rent research includes increasingly subtle and specific attempts to dissect the cognitive and emotional mechanisms called into play when humans make decisions. The present essay will briefly review some of the general considerations and domains of information needed when one designs fMRI-based experiments. However, the main theme will be the difficulties associated with designing, conducting, analyzing and interpreting such research. Functional MRI is an unusually complicated technique, and there are numerous ways for experiments to go wrong. As well as demanding exceptional care in maintaining the quality of one's own research, this makes the universal problem of evaluating other peoples' research particularly challenging. (c) 2005 Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,HyperVis, Lexington, MA 02420 USA. RP Savoy, RL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,HyperVis, US POB 158, Lexington, MA 02420 USA. EM savoy@rowland.org NR 16 TC 23 Z9 24 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD NOV 15 PY 2005 VL 67 IS 5 SI SI BP 361 EP 367 DI 10.1016/j.brainresbull.2005.06.008 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 978GZ UT WOS:000232862900004 PM 16216682 ER PT J AU Ganz, PA Farmer, MM Belman, MJ Garcia, CA Streja, L Dietrich, AJ Winchell, C Bastani, R Kahn, KL AF Ganz, PA Farmer, MM Belman, MJ Garcia, CA Streja, L Dietrich, AJ Winchell, C Bastani, R Kahn, KL TI Results of a randomized controlled Trial to increase Colorectal cancer screening in a managed care health plan SO CANCER LA English DT Article DE quality improvement; randomized clinical trial; provider organizations; colorectal cancer screening; managed care ID PHYSICIAN PERFORMANCE; MEDICAL GROUPS; PREVENTION; CALIFORNIA; ADHERENCE; RECOMMENDATIONS; ORGANIZATIONS; INTERVENTIONS; SERVICES; COVERAGE AB BACKGROUND. Colorectal cancer (CRC) is the third most common cause of cancer deaths; however, rates Of regular screening for this cancer are low. A quality improvement (QI) program to increase CRC screening was developed for use in a managed care health plan. METHODS. Thirty-six provider organizations (POs) contracting with the health plan were recruited for a randomized controlled effectiveness trial testing the QI program. The intervention was delivered over a 2-year period, and its effectiveness was assessed by chart review of a random sample of patients from each PO. RESULTS. Thirty-two of the 36 POs were evaluable for outcome assessment. During the 2-year intervention period, only 26% of the eligible patients received any CRC screening test. Twenty-nine percent of patients had any CRC screening test within guidelines, with no differences between the intervention or control POs. Significant predictors of having received CRC screening within guidelines were older age (P = 0.0004), receiving care in an integrated medical group (P < 0.0001) and having had a physical examination within the past 2 years (P < 0.0001). CONCLUSIONS. A facilitated QI intervention program for CRC screening that focused on the PO did not increase rates of CRC screening. Overall CRC screening rates are low and are in need of improvement. (c) 2005 American Cancer Society. C1 Univ Calif Los Angeles, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory & Nursing Home Ctr, VA Ctr Study Healthcare Provider Behav, Sepulveda, CA USA. Blue Cross Calif, Woodland Hills, CA USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. RAND Corp, Santa Monica, CA USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Div Canc Prevent & Control Res, Jonsson Comprehens Canc Ctr, 650 Charles Young Dr S,CHS A2-125, Los Angeles, CA 90095 USA. EM pganz@ucla.edu FU NCI NIH HHS [R01 CA75544] NR 48 TC 21 Z9 22 U1 2 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 15 PY 2005 VL 104 IS 10 BP 2072 EP 2083 DI 10.1002/cncr.21434 PG 12 WC Oncology SC Oncology GA 981QL UT WOS:000233103000005 PM 16216030 ER PT J AU Berenson, JR Jagannath, S Barlogie, B Siegel, DT Alexanian, R Richardson, PG Irwin, D Alsina, M Rajkumar, SV Srkalovic, G Singhal, S Limentani, S Niesvizky, R Esseltine, DL Trehu, E Schenkein, DP Anderson, K AF Berenson, JR Jagannath, S Barlogie, B Siegel, DT Alexanian, R Richardson, PG Irwin, D Alsina, M Rajkumar, SV Srkalovic, G Singhal, S Limentani, S Niesvizky, R Esseltine, DL Trehu, E Schenkein, DP Anderson, K TI Safety of prolonged therapy with bortezomib in relapsed or refractory multiple myeloma SO CANCER LA English DT Article DE bortezomib; CREST; extension; myelomas; proteasome; SUMMIT ID PHASE-2 AB BACKGROUND. Bortezomib, a first-in-class proteasome inhibitor, is active with manageable toxicities in relapsed and/or refractory myeloma, METHODS. Bortezomib 1.0 or 1.3 mg/m(2) was administered Days 1, 4, 8, and 11 every 21 days for tip to 8 cycles to patients with relapsed and/or refractory myeloma participating in two Phase II trials. Dexamethasone IIcould be added because of progressive disease after 2 cycles or stable disease after 4 cycles. Continuation of or retreatment with bortezomib was offered to patients who, in the investigator's opinion, would benefit from extended treatment. RESULTS. Sixty-three patients with relapsed/refractory myeloma treated in this extension trial received a median of 7 additional cycles of therapy, for a total of 14 cycles (range, 7-32) over a median duration of therapy of 45.1 weeks in the parent and extension studies. Seventy-eight percent of patients completed this study at the same or higher bortezomib dose than they started on during this study, and the treatment schedule of twice-weekly administration remained unchanged in 89%. Overall, 75% of patients received dexamethasone in combination with bortezomib for a median of 5 cycles starting either in the parent or extension study. The safety profile was similar between the extension mid parent trials, with no evidence of new cumulative toxicity. The most commonly reported Grade 3/4 toxicities were thrombocytopenia (29%), with a consistent pattern of recovery during the rest period of each cycle, diarrhea (11%), anemia (11%), and neutropenia (10%). Neuropathy was reported less frequently. CONCLUSIONS. Retreatment with or continuation of bortezomib +/- dexamethasone beyond 6 months was safe, and toxicities were manageable, in patients with relapsed and/or refractory myeloma. (c) 2005 American Cancer Society. C1 Inst Myeloma & Bone Canc Res, W Hollywood, CA 90069 USA. St Vincents Comprehans Canc Ctr, New York, NY USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Hackensack Univ, Med Ctr, Div Hematol Oncol, Hackensack, NJ USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Adult Oncol Dept, Boston, MA USA. Alta Bates Canc Ctr, Berkeley, CA USA. H Lee Moffitt Canc Ctr & Res Inst, Malignant Hematol Program, Tampa, FL USA. Mayo Clin Rochester, Div Hematol, Rochester, MN USA. Northwestern Univ, Div Hematol Oncol, Evanston, IL USA. Carolinas Hematol Oncol Assoc, Charlotte, NC USA. Cornell Univ, Weill Med Coll, Div Hematol & Med Oncol, Ithaca, NY USA. RP Berenson, JR (reprint author), Inst Myeloma & Bone Canc Res, 9201 Sunset Blvd,Suite 300, W Hollywood, CA 90069 USA. EM jberenson@myelomasource.org OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 5 TC 70 Z9 73 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 NOV 15 PY 2005 VL 104 IS 10 BP 2141 EP 2148 DI 10.1002/cncr.21427 PG 8 WC Oncology SC Oncology GA 981QL UT WOS:000233103000013 PM 16206291 ER PT J AU Seftor, EA Brown, KM Chin, L Kirschmann, DA Wheaton, WW Protopopov, A Feng, B Balagurunathan, Y Trent, JM Nickoloff, BJ Seftor, REB Hendrix, MJC AF Seftor, EA Brown, KM Chin, L Kirschmann, DA Wheaton, WW Protopopov, A Feng, B Balagurunathan, Y Trent, JM Nickoloff, BJ Seftor, REB Hendrix, MJC TI Epigenetic transdifferentiation of normal melanocytes by a metastatic melanoma microenvironment SO CANCER RESEARCH LA English DT Article ID MALIGNANT-MELANOMA; VASCULOGENIC MIMICRY; EXPRESSION; DIFFERENTIATION AB The clinical management of cutaneous melanoma would benefit significantly from a better understanding of the molecular changes that occur during melanocytic progression to a melanoma phenotype. To gain unique insights into this process, we developed a three-dimensional in vitro model that allows observations of normal human melanocytes interacting with a metastatic melanoma matrix to determine whether these normal cells could be reprogrammed by inductive cues in the tumor cell microenvironment. The results show the epigenetic transdifferentiation of the normal metanocytic phenotype to that of an aggressive melanoma-like cell with commensurate increased migratory and invasive ability with no detectable genomic alterations. Removal of the trans-differentiated melanocytes from the inductive metastatic melanoma microenvironment results in a reversion to their normal phenotype. However, a normal melanocyte microenvironment had no epigenetic influence on the phenotype of metastatic melanoma cells. This novel approach identifies specific genes involved in the transdifferentiation of melanocytes to a more aggressive phenotype, which may offer significant therapeutic value. C1 Northwestern Univ, Childrens Mem Res Ctr, Chicago, IL 60614 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60614 USA. Loyola Univ, Med Ctr, Dept Pathol, Chicago, IL USA. Translat Gen Res Inst, Phoenix, AZ USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Boston, MA 02115 USA. RP Hendrix, MJC (reprint author), Northwestern Univ, Childrens Mem Res Ctr, 2300 Childrens Pl,Box 222, Chicago, IL 60614 USA. EM mjchendrix@childrensmemorial.org FU NCI NIH HHS [CA59702, CA93947, CA59327, CA27502] NR 20 TC 38 Z9 39 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10164 EP 10169 DI 10.1158/0008-5472.CAN-05-2497 PG 6 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900008 PM 16288000 ER PT J AU Chen, ZY Wang, XS Zhou, YH Offner, G Tseng, CC AF Chen, ZY Wang, XS Zhou, YH Offner, G Tseng, CC TI Destabilization of Kruppel-like factor 4 protein in response to serum stimulation involves the ubiquitin-proteasome pathway SO CANCER RESEARCH LA English DT Article ID ZINC-FINGER PROTEIN; MEDIATED DEGRADATION; DOWN-REGULATION; CELL-CYCLE; C-JUN; EXPRESSION; GENE; PROLIFERATION; PROGRESSION; P27(KIP1) AB Although the zinc finger transcription factor Kruppel-like factor 4 (KLF4) has been shown to be a negative regulator of cell proliferation, the mechanisms underlying the posttranslational modification of KLF4, especially at the level of protein degradation, are poorly understood. Here, we show that KLF4 protein levels in quiescent cells were high, but decreased rapidly as cells entered the proliferating stage following serum stimulation. This decrease was partially reversed by pretreatment with MG132, a proteasome inhibitor. Moreover, KLF4 was an unstable protein that underwent rapid turnover, and exhibited a relatively short half-life (t(1/2) similar to 120 minutes). To investigate the involvement of the ubiquitin-proteasome pathway in the regulation of the stability of KLF4, HCT116 cells were treated with proteasome inhibitors. Our results showed that, following lactacystin treatment, levels of endogenous KLF4 increased in a time- and dose-dependent manners. Using a cell-free system, in vitro -translated S-35-labeled KLF4 protein was degraded by protein extracts prepared from exponentially growing HCT116 cells in the presence of ATP. These effects were prevented by pretreatment with MG132 or replacement of ATP with ATP-gamma-S, a nonhydrolyzable analogue of ATP, suggesting that ATP is required for KLF4 degradation by the 263 proteasome. In addition, KLF4 was subject to ubiquitination when cells were treated with the proteasome inhibitor or transfected with exogenous ubiquitin. Collectively, these results indicate that destabilization of KLF4 following serum stimulation is mediated, at least in part, through a ubiquitin-proteasome pathway. C1 Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA USA. RP Chen, ZY (reprint author), Boston Univ, Sch Med, Gastroenterol Sect, EBRC X-513,650 Albany St, Boston, MA 02118 USA. EM zhiyi.chen@bmc.org OI Offner, Gwynneth/0000-0002-3687-9809 FU NCI NIH HHS [CA82593]; NIDDK NIH HHS [DK061376] NR 40 TC 59 Z9 64 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10394 EP 10400 DI 10.1158/0008-5472.CAN-05-2059 PG 7 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900038 PM 16288030 ER PT J AU Huang, L Chen, DS Liu, D Yin, L Kharbanda, S Kufe, D AF Huang, L Chen, DS Liu, D Yin, L Kharbanda, S Kufe, D TI MUC1 oncoprotein blocks glycogen synthase kinase 3 beta-mediated phosphorylation and degradation of beta-catenin SO CANCER RESEARCH LA English DT Article ID CARCINOMA-ASSOCIATED ANTIGEN; TUMOR-SUPPRESSOR PROTEIN; GROWTH-FACTOR RECEPTOR; MONOCLONAL-ANTIBODY; GENE-TRANSCRIPTION; CRYSTAL-STRUCTURE; CYTOPLASMIC TAIL; MYELOMA CELLS; BREAST-CANCER; E-CADHERIN AB Dysregulation of beta-catenin is of importance to the development of diverse human malignancies. The MUC1 oncoprotein is aberrantly overexpressed by most human carcinomas and associates with beta-catenin. However, the functional significance of the MUC1-beta-catenin interaction is not known. Here, we show that MUC1 increases beta-catenin levels in the cytoplasm and nucleus of carcinoma cells. Previous studies have shown that glycogen synthase kinase 3 beta (GSK3 beta) phosphorylates beta-catenin and thereby targets it for proteosomal degradation. Consistent with the up-regulation of beta-catenin levels, our results show that MUC1 blocks GSK3 beta-mediated phosphorylation and degradation of beta-catenin. To further define the interaction between MUC1 and beta-catenin, we identified a serine-rich motif (SRM) in the MUCI cytoplasmic domain that binds directly to beta-catenin Armadillo repeats. Mutation of the SRM attenuated binding of MUCI to beta-catenin and MUC1-mediated inhibition of beta-catenin degradation. Importantly, disruption of the MUC1-beta-catenin interaction with the SRM mutant also attenuated MUC1-induced anchorage-dependent and -independent growth and delayed MUC1-mediated tumorigenicity. These findings indicate that MUCI promotes transformation, at least in part, by blocking GSK3 beta-mediated phosphorylation and thereby degradation of beta-catenin. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kufe, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM donald_kufe@dfci.harvard.edu FU NCI NIH HHS [CA29431, CA97098] NR 50 TC 143 Z9 149 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10413 EP 10422 DI 10.1158/0008-5472.CAN-05-2474 PG 10 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900040 PM 16288032 ER PT J AU Ahmad, F Arad, M Musi, N He, HM Wolf, C Branco, D Perez-Atayde, AR Stapleton, D Bali, D Xing, YQ Tian, R Goodyear, LJ Berul, CI Ingwall, JS Seidman, CE Seidman, JG AF Ahmad, F Arad, M Musi, N He, HM Wolf, C Branco, D Perez-Atayde, AR Stapleton, D Bali, D Xing, YQ Tian, R Goodyear, LJ Berul, CI Ingwall, JS Seidman, CE Seidman, JG TI Increased alpha 2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy SO CIRCULATION LA English DT Article DE cardiomyopathy; exercise; genetics; metabolism; Wolff-Parkinson-White syndrome ID ACTIVATED PROTEIN-KINASE; PARKINSON-WHITE-SYNDROME; GLYCOGEN-STORAGE-DISEASE; FAMILIAL HYPERTROPHIC CARDIOMYOPATHY; VENTRICULAR PREEXCITATION; CARDIAC-HYPERTROPHY; MOUSE MODEL; GAMMA(2) SUBUNIT; TRANSGENIC MICE; MUTATION AB Background: AMP-activated protein kinase (AMPK) regulatory gamma 2 subunit (PRKAG2) mutations cause a human cardiomyopathy with cardiac hypertrophy, preexcitation, and glycogen deposition. PRKAG2 cardiomyopathy is recapitulated in transgenic mice overexpressing mutant PRKAG2 N488I in the heart (TG gamma 2(N488I)). AMPK is a heterotrimeric kinase consisting of 1 catalytic (alpha) and 2 regulatory (beta and gamma) subunits. Two alpha-subunit isoforms, alpha 1 and alpha 2, are expressed in the heart; however, the contribution of AMPK utilization of these subunits to PRKAG2 cardiomyopathy is unknown. Mice overexpressing a dominant-negative alpha 2 subunit of AMPK (TG alpha 2(DN)) provide a tool for selectively inhibiting alpha 2, but not alpha 1, subunit-associated AMPK activity. Methods and Results: In compound-heterozygous TG gamma 2(N488I)/TG alpha 2(DN) mice, AMPK activity associated with alpha 2 but not alpha 1 was decreased compared with TG gamma 2N(488I). The TG alpha 2DN transgene reduced the disease phenotype of TG gamma 2(N488I), partially or completely normalizing the ECG, cardiac function, cardiac morphology, and exercise capacity in compound-heterozygous mice. TG gamma 2(N488I) hearts had normal resting levels of high-energy phosphates and could improve cardiac performance during exercise. Cardiac glycogen content decreased in TG gamma 2(N488I) mice after exercise stress, indicating availability of the stored glycogen for metabolic utilization. No differences in glycogen-metabolizing enzymes were observed. Conclusions: The PRKAG2 N488I mutation causes inappropriate AMPK activation, which leads to glycogen accumulation and conduction system disease. The accumulated glycogen can serve as an energy source, and the animals have contractile reserve during exercise. Because the dominant-negative alpha 2 subunit attenuates the mutant PRKAG2 phenotype, AMPK complexes containing the alpha 2 rather than the alpha 1 subunit are the primary mediators of the effects of PRKAG2 mutations. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Pittsburgh, Cardiovasc Inst, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Tel Aviv Univ, Inst Heart, Tel Aviv, Israel. Tel Aviv Univ, Sheba Med Ctr, Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, NMR Lab Physiol Chem, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Melbourne, Mol Sci & Biotechnol Inst Bio21, Melbourne, Vic, Australia. Duke Univ, Med Ctr, Res Triangle Pk, NC USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Seidman, JG (reprint author), Harvard Univ, Sch Med, Dept Genet, 77 Ave Louis Pasteur,NRB 256, Boston, MA 02115 USA. EM seidman@genetics.med.harvard.edu OI Tian, Rong/0000-0002-3676-3830 FU NHLBI NIH HHS [HL 52320, HL 67970, HL 63985] NR 31 TC 54 Z9 56 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 2005 VL 112 IS 20 BP 3140 EP 3148 DI 10.1161/CIRCULATIONAHA.105.550806 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 983TN UT WOS:000233255100017 PM 16275868 ER PT J AU Su, HL Spinale, FG Dobrucki, LW Song, J Hua, J Sweterlitsch, S Dione, DP Cavaliere, P Chow, C Bourke, BN Hu, XY Azure, M Yalamanchili, P Liu, R Cheesman, EH Robinson, S Edwards, S Sinusas, AJ AF Su, HL Spinale, FG Dobrucki, LW Song, J Hua, J Sweterlitsch, S Dione, DP Cavaliere, P Chow, C Bourke, BN Hu, XY Azure, M Yalamanchili, P Liu, R Cheesman, EH Robinson, S Edwards, S Sinusas, AJ TI Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling SO CIRCULATION LA English DT Article DE myocardial infarction; metalloproteinases; remodeling; radionuclide imaging ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR ENLARGEMENT; HEART-FAILURE; POSTMYOCARDIAL INFARCTION; CLINICAL-IMPLICATIONS; IN-VIVO; INHIBITION; EXPRESSION; MICE; RAT AB Background: Time-dependent activation of matrix metalloproteinases (MMPs) after myocardial infarction (MI) contributes to adverse left ventricular (LV) remodeling; however, noninvasive methods to monitor this process serially are needed. Methods and Results: MMP-targeted radiotracers were developed that displayed selective binding kinetics to the active MMP catalytic domain. Initial nonimaging studies were performed with a In-111-labeled MMP-targeted radiotracer (In-111-RP782) and negative control compound (In-111-RP788) in control mice (Ctrl) and in mice 1 week after surgically induced MI. Localization of In-111-RP782 was demonstrated within the MI by microautoradiography. A 334 +/- 44% increase (P < 0.001 versus Ctrl) in relative retention of In-111-RP782 was confirmed by gamma well counting of myocardium. Subsequent high-resolution dual-isotope planar and hybrid micro-single-photon emission computed tomography/CT imaging studies with an analogous Tc-99m-labeled MMP-targeted radiotracer (Tc-99m-RP805) and Tl-201 demonstrated favorable biodistribution and clearance kinetics of Tc-99m-RP805 for in vivo cardiac imaging, with robust retention 1 to 3 weeks after MI in regions of decreased 201Tl perfusion. Gamma well counting yielded a similar approximate to 300% increase in relative myocardial retention of Tc-99m-RP805 in MI regions (Ctrl, 102 +/- 9%; 1 week, 351 +/- 77%; 2 weeks, 291 +/- 45%; 3 weeks, 292 +/- 41%; P < 0.05 versus Ctrl). Myocardial uptake in the MI region was also significantly increased approximate to 5-fold when expressed as percentage injected dose per gram tissue. There was also a significant 2-fold increase in myocardial activity in remote regions relative to control mice, suggesting activation of MMPs in regions remote from the MI. Conclusions: This novel noninvasive targeted MMP radiotracer imaging approach holds significant diagnostic potential for in vivo localization of MMP activation and tracking of MMP-mediated post-MI remodeling. C1 Yale Univ, Sch Med, Expt Nucl Cardiol Lab, Div Cardiovasc Med,Dept Internal Med, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Bristol Myers Squibb Med Imaging, N Billerica, MA USA. RP Sinusas, AJ (reprint author), Yale Univ, Sch Med, Expt Nucl Cardiol Lab, Div Cardiovasc Med,Dept Internal Med, 3FMP,POB 208017, New Haven, CT 06520 USA. EM albert.sinusas@yale.edu RI Sinusas, Albert/A-7235-2009 FU NHLBI NIH HHS [R01 HL078650-04, R01-HL-65662, R01 HL078650, P01-HL-48788, R01-HL-59165] NR 26 TC 115 Z9 117 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 2005 VL 112 IS 20 BP 3157 EP 3167 DI 10.1161/CIRCULATIONAHA.105.583021 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 983TN UT WOS:000233255100019 PM 16275862 ER PT J AU Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J AF Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J TI The progress and promise of molecular imaging probes in oncologic drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-BRAIN-BARRIER; METASTATIC PROSTATE-CANCER; STEROID-HORMONE RECEPTORS; P-GLYCOPROTEIN TRANSPORT; ADVANCED BREAST-CANCER; NON-HODGKINS-LYMPHOMA; IN-VIVO; ESTROGEN-RECEPTOR; ANNEXIN-V AB As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency and cost effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have a great potential as oncological drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmocokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analysis may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. this article outlines the scientific basis for oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes. C1 NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. Mol Tracer LLC, Bethesda, MD USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. CCS Associates, Mountain View, CA USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Off Drug Evaluat, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Kelloff, GJ (reprint author), NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, EPN 6130 Execut Blvd,Suite 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov RI Mankoff, David/F-9576-2010 FU NCI NIH HHS [P01 CA042045] NR 182 TC 160 Z9 162 U1 2 U2 17 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 7967 EP 7985 DI 10.1158/1078-0432.CCR-05-1302 PG 19 WC Oncology SC Oncology GA 987HI UT WOS:000233508600003 PM 16299226 ER PT J AU Cohen, EEW Lingen, MW Martin, LE Harris, PL Brannigan, BW Haserlat, SM Okimoto, RA Sgroi, DC Dahiya, S Muir, B Clark, JR Rocco, JW Vokes, EE Haber, DA Bell, DW AF Cohen, EEW Lingen, MW Martin, LE Harris, PL Brannigan, BW Haserlat, SM Okimoto, RA Sgroi, DC Dahiya, S Muir, B Clark, JR Rocco, JW Vokes, EE Haber, DA Bell, DW TI Response of some head and neck cancers to epidermal growth factor receptor tyrosine kinase inhibitors may be linked to mutation of ERBB2 rather than EGFR SO CLINICAL CANCER RESEARCH LA English DT Article ID SQUAMOUS-CELL CARCINOMA; PHASE-II TRIAL; LUNG-CANCER; GENE AMPLIFICATION; SOMATIC MUTATIONS; GEFITINIB; OVEREXPRESSION; RESPONSIVENESS; SENSITIVITY; EXPRESSION AB Purpose: Small-molecule tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) have shown modest yet reproducible response rates in patients with squamous cell carcinoma of the head and neck (SCCHN). Somatic mutations in EGFR have recently been shown to be predictive of a clinical response in patients with non-small cell lung cancer (NSCLC) treated with these inhibitors. The objective of this study was to determine if such mutations, or recently reported mutations in ERBB2, also underlie EGFR-TKI responsiveness in SCCHN patients. Experimental Design: We sequenced the kinase domain of EGFR and exon 20 of ERBB2 in tumour specimens from eight responsive patients. In addition, mutational analysis was done on tumour specimens from nine gefitinib nonresponders and 65 unselected cases of SCCHN. Results: None of eight TKI-responsive specimens had mutations within the kinase domain of EGFR. EGFR amplification was also not associated with drug responsiveness. However, a single responsive case had a somatic missense mutation within exon 20 of ERBB2. Conclusion: Our data indicate that unlike NSCLC, EGFR kinase mutations are rare in unselected cases os SCCHN within the United States and are not linked to gefitinib or erlotinib responses in SCCHN. Alternative mechanisms, including ERBB2 mutations, may underlie responsiveness in this tumor type. C1 Massachusetts Gen Hosp, Ctr Canc, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Pathol, Cambridge, MA 02139 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, CNY7,149 13th St, Cambridge, MA 02139 USA. EM haber@helix.mgh.harvard.edu FU NCI NIH HHS [N01-CM-17102, P30-CA14599-30] NR 27 TC 92 Z9 95 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 8105 EP 8108 DI 10.1158/1078-0432. PG 4 WC Oncology SC Oncology GA 987HI UT WOS:000233508600019 PM 16299242 ER PT J AU Ross, RW Halabi, S Ou, SS Rajeshkumar, BR Woda, BA Vogelzang, NJ Small, EJ Taplin, ME Kantoff, PW AF Ross, RW Halabi, S Ou, SS Rajeshkumar, BR Woda, BA Vogelzang, NJ Small, EJ Taplin, ME Kantoff, PW TI Predictors of prostate cancer tissue acquisition by an undirected core bone marrow biopsy in metastatic castration-resistant prostate cancer - A Cancer and Leukemia Group B study SO CLINICAL CANCER RESEARCH LA English DT Article ID LUNG-CANCER; PHASE-II; CARCINOMA; MUTATIONS; ASPIRATION; GEFITINIB; MEN AB Purpose: Analyzing metastatic prostate cancer tissue is of considerable importance in evaluating new targeted agents, yet acquiring such tissue presents a challenge due to the predominance of bone metastases. We assessed factors predicting a successful tumor harvest from bone marrow biopsies (BMBx) in castration-resistant metastatic prostate cancer patients. Material and Methods: Data from Cancer and Leukemia Group B study 9663 were reviewed. Bone marrow biopsies were obtained from 184 patients who underwent an office-based, unguided bone marrow biopsy of the posterior iliac crest. Results: Forty-seven of the 184 patients (25.5%) had a positive bone marrow biopsy. When considered in a multivariate logistic regression analysis, lower hemoglobin levels, higher alkaline phosphatase, and higher lactate dehydrogenase levels were associated with a higher likelihood of a positive BMBx. The median survival time was 11 months (95% confidence interval, 8.0-14) among patients with a positive BMBx compared with 23 months (95% confidence interval, 19-27) with a negative BMBx. The median time to progression and time to prostate-specific antigen progression-free survival were also significantly decreased among positive BMBx patients. No patients with a positive BMBx survived beyond 3 years, whereas 11 of the 137 patients with a negative BMBx survived beyond 5 years. Discussion: Using common laboratory values, a specific patient cohort can be defined from whom the yield of a nonguided BMBx would be high enough to justify this approach. For studies that require broader entry criteria, a more directed approach with image guidance is recommended. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Ross, RW (reprint author), Dana Farber Canc Inst, Smith 353,44 Binney St, Boston, MA 02115 USA. EM rwross@partners.org FU NCI NIH HHS [CA31946, U10 CA31946, U01-CA78967, T32 CA009172] NR 24 TC 7 Z9 7 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 8109 EP 8113 DI 10.1158/1078-0432 PG 5 WC Oncology SC Oncology GA 987HI UT WOS:000233508600020 PM 16299243 ER PT J AU Mukohara, T Civiello, G Davis, IJ Taffaro, ML Christensen, J Fisher, DE Johnson, BE Janne, PA AF Mukohara, T Civiello, G Davis, IJ Taffaro, ML Christensen, J Fisher, DE Johnson, BE Janne, PA TI Inhibition of the met receptor in mesothelioma SO CLINICAL CANCER RESEARCH LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; MALIGNANT PLEURAL MESOTHELIOMA; CELL LUNG-CANCER; FACTOR SCATTER FACTOR; PAPILLARY RENAL-CARCINOMAS; DOMAIN BINDING-SITE; C-MET; SOMATIC MUTATIONS; THERAPEUTIC INHIBITION; PROTOONCOGENE PRODUCT AB Background: Expression of the Met receptor and its ligand, hepatocyte growth factor (HGF), has been observed in 74% to 100% and 40% to 85% of malignant pleural mesothelioma (MPM) specimens, respectively. HGF stimulation has been shown to enhance MPM cell proliferation, migration, cell scattering, and invasiveness. Experimental Design: To investigate a potential therapeutic role for the Met receptor in MPM, we examined the effects of PHA-665752, a specific small-molecule inhibitor of the Met receptor tyrosine kinase, in a panel of 10 MPM cell lines. Results: Two of the cell lines, H2461 and JMN-1B, exhibited autocrine HGF production as measured by ELISA (3.9 and 10.5 ng/mL, respectively, versus < 0.05 ng/mL in other cell lines). Evaluation of PHA- 665752 across the 10 MPM cell lines indicated that despite Met expression in all cell lines, only in cell lines that exhibited a Met/HGF autocrine loop, H 2461 and JMN-18, did PHA-665752 inhibit growth with an IC50 of 1 and 2 mu mol/L, respectively. No activating mutations in Met were detected in any of the cell lines, Consistent with observed growth inhibition, PHA-665752 caused cell cycle arrest at G(1)-S boundary accompanied by a dose-dependent decrease in phosphorylation of Met, p70S6K, Akt, and extracellular signal-regulated kinase 1/2. Growth of H2461 cells was also inhibited by neutralizing antibodies to HGF and by RNA interference knockdown of the Met receptor, confirming that growth inhibition observed was through a Met-dependent mechanism. PHA-665752 also reduced MPM in vitro cell migration and invasion, Conclusions: Taken together, these findings suggest that inhibition of the Met receptor may be an effective therapeutic strategy for patients with MPM and provides a mechanism, the presence of a HGF/Met autocrine loop, by which to select patients for PHA-665752 treatment. C1 Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. Pfizer Global Res & Dev, Dept Res Pharmacol, La Jolla Labs, La Jolla, CA USA. RP Janne, PA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lowe Ctr Thorac Oncol, D1234,44 Binney St, Boston, MA 02115 USA. EM pjanne@partners.org FU NCI NIH HHS [1K12CA87723-01] NR 54 TC 52 Z9 53 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 8122 EP 8130 DI 10.1158/1078-043 PG 9 WC Oncology SC Oncology GA 987HI UT WOS:000233508600022 PM 16299245 ER PT J AU Rich, JN Sathornsumetee, S Keir, ST Kieran, MW Laforme, A Kaipainen, A McLendon, RE Graner, MW Rasheed, BKA Wang, L Reardon, DA Ryan, AJ Wheeler, C Dimery, I Bigner, DD Friedman, HS AF Rich, JN Sathornsumetee, S Keir, ST Kieran, MW Laforme, A Kaipainen, A McLendon, RE Graner, MW Rasheed, BKA Wang, L Reardon, DA Ryan, AJ Wheeler, C Dimery, I Bigner, DD Friedman, HS TI ZD6474, a novel tyrosine kinase inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor, inhibits tumor growth of multiple nervous system tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN GLIOBLASTOMA CELLS; HUMAN-BRAIN-TUMORS; IN-VIVO; ACQUIRED-RESISTANCE; ANTITUMOR-ACTIVITY; SIGNALING PATHWAY; MALIGNANT GLIOMA; CANCER-CELLS; LINE TE671; THERAPY AB Purpose: Primary central nervous system (CNS) tumors represent a diverse group of tumor types with heterogeneous molecular mechanisms that underlie their formation and maintenance. CNS tumors depend on angiogenesis and often display increased activity of ErbB-associated pathways. Current nonspecific therapies frequently have poor efficacy in many of these tumor types, so there is a pressing need for the development of novel targeted therapies. Experimental Design: ZD6474 is a novel, orally available low molecular weight inhibitor of the kinase activities associated with vascular endothelial growth factor receptor-2 and epidermal growth factor receptor. We hypothesized that ZD6474 may provide benefit in the treatment of several CNS tumor types. Results: In mice bearing established s.c. tumor xenografts of CNS tumors (malignant glioma and ependymoma) or rhabdomyosarcoma, a limited course of ZD6474 treatment produced significant tumor growth delays and a high rate of partial tumor regression in most models examined. Mice with i.c. malignant glioma xenografts treated with ZD6474 experienced a significant prolongation of survival. Tumors from mice treated with ZD6474 displayed a lower proliferative index and disrupted tumor vascularity. Notably, some of these models are insensitive to low molecular weight kinase inhibitors targeting only vascular endothelial growth factor receptor-2 or epidermal growth factor receptor functions, suggesting that the combined disruption of both epidermal growth factor receptor and vascular endothelial growth factor receptor-2 activities may significantly increase tumor control. Conclusions: In conclusion, ZD6474 shows significant activity against xenograft models of several primary human CNS tumor types. Consideration for clinical development in this disease setting seems warranted. C1 Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Surg Res Lab,Dept Surg, Boston, MA USA. AstraZeneca, Canc Discovery, Macclesfield, Cheshire, England. AstraZeneca, Wilmington, DE USA. RP Rich, JN (reprint author), Duke Univ, Med Ctr, Div Neurol, Box 2900, Durham, NC 27710 USA. EM rich0001@mc.duke.edu OI Kieran, Mark/0000-0003-2184-7692 FU NCI NIH HHS [1 P20 CA096890, CA94231-02, CA11898, P50 CA 10878-01]; NCRR NIH HHS [M01 RR 30]; NINDS NIH HHS [NS20023, NS047409, NS30245-15] NR 50 TC 78 Z9 81 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 8145 EP 8157 DI 10.1158/1078-0432 PG 13 WC Oncology SC Oncology GA 987HI UT WOS:000233508600024 PM 16299247 ER PT J AU Darouiche, RO Thornby, JI Cerra-Stewart, C Donovan, WH Hull, RA AF Darouiche, RO Thornby, JI Cerra-Stewart, C Donovan, WH Hull, RA TI Bacterial interference for prevention of urinary tract infection: A prospective, randomized, placebo-controlled, double-blind pilot trial SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID SPINAL-CORD-INJURY; CATHETER-ASSOCIATED BACTERIURIA; ESCHERICHIA-COLI 83972; TRIMETHOPRIM-SULFAMETHOXAZOLE; MEATAL CARE; PROPHYLAXIS; DISINFECTANT; IRRIGATION; BLADDER; CREAM AB This prospective, randomized, placebo-controlled, doubleblind pilot trial examined the efficacy of bacterial interference in preventing urinary tract infection ( UTI) in 27 patients with spinal cord injury. Patients whose bladders became colonized with Escherichia coli 83972 were half as likely ( Pp) than noncolonized patients to develop UTI during the subsequent year. C1 Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. Inst Rehabil & Res, Houston, TX USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 133 Moursund Ave,Ste A221, Houston, TX 77030 USA. EM rdarouiche@aol.com FU NICHD NIH HHS [HD35856] NR 19 TC 57 Z9 60 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2005 VL 41 IS 10 BP 1531 EP 1534 DI 10.1086/497272 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975NY UT WOS:000232670400022 PM 16231269 ER PT J AU Takahashi, K Ezekowitz, RAB AF Takahashi, K Ezekowitz, RAB TI The role of the mannose-binding lectin in innate immunity SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Annual International Sepsis Forum Colloquium on Identifying Responsive Populations in Sepsis CY JUL 10-12, 2004 CL Cambridge, ENGLAND ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INFLAMMATORY RESPONSE SYNDROME; SEVERE INFECTIONS; SERINE-PROTEASE; ADAPTIVE IMMUNITY; VIRUS-INFECTION; DEFICIENT MICE; GENE-MUTATIONS; ASSOCIATION; SERUM AB The innate immune system, which includes mannose-binding lectin (MBL), recognizes a broad range of molecular patterns on a broad range of infectious agents and is able to distinguish them from self. MBL is a liver-derived serum protein and is secreted into the serum, where it can activate an immune response before the induction of antigen-specific immunity. Circumstantial evidence in human populations suggests that low serum levels of MBL predispose to infection. To analyze the role of MBL in vivo, we created MBL-null mice and challenged these mice with infection under various conditions. Our results suggest that MBL plays an important role as a first-line host defense against certain infectious agents. In addition, it is likely that MBL is a key regulator of inflammation beyond expected roles in the infection. C1 Harvard Univ, Sch Med, Lab Dev Immunol, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Lab Dev Immunol,Sch Med, Dept Pediat, Boston, MA 02114 USA. RP Takahashi, K (reprint author), Harvard Univ, Sch Med, Lab Dev Immunol, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA. EM Ktakahashi1@partners.org NR 53 TC 56 Z9 59 U1 0 U2 4 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 NOV 15 PY 2005 VL 41 SU 7 BP S440 EP S444 DI 10.1086/431987 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975NU UT WOS:000232670000009 PM 16237644 ER PT J AU Nogi, T Levin, M AF Nogi, T Levin, M TI Characterization of innexin gene expression and functional roles of gap-junctional communication in planarian regeneration SO DEVELOPMENTAL BIOLOGY LA English DT Review DE planaria; regeneration; innexins; gap-junctional communication; patterning ID CENTRAL-NERVOUS-SYSTEM; LEFT-RIGHT ASYMMETRY; CHICK LIMB BUD; STEM-CELLS; INTERCELLULAR COMMUNICATION; MEMBRANE CHANNELS; EYE REGENERATION; SELECTIVE DISRUPTION; DROSOPHILA EMBRYO; INSTRUCTIVE ROLE AB Planaria possess remarkable powers of regeneration. After bisection, one blastema regenerates a head, while the other forms a tail. The ability of previously-adjacent cells to adopt radically different fates could be due to long-range signaling allowing determination of position relative to, and the identity of, remaining tissue. However, this process is not understood at the molecular level. Following the hypothesis that gap-junctional communication (GJC) may underlie this signaling, we cloned and characterized the expression of the Innexin gene family during planarian regeneration. Planarian innexins fall into 3 groups according to both sequence and expression. The concordance between expression-based and phylogenetic grouping suggests diversification of 3 ancestral innexin genes into the large family of planarian innexins. Innexin expression was detected throughout the animal, as well as specifically in regeneration blastemas, consistent with a role in long-range signaling relevant to specification of blastema positional identity. Exposure to a GJC-blocking reagent which does not distinguish among gap junctions composed of different Innexin proteins (is not subject to compensation or redundancy) often resulted in bipolar (2-headed) animals. Taken together, the expression data and the respecification of the posterior blastema to an anteriorized fate by GJC loss-of-function suggest that innexin-based GJC mediates instructive signaling during regeneration. (C) 2005 Elsevier Inc. All rights reserved. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org RI Nogi, Taisaku/C-7657-2009; Nogi, Taisaku/F-4675-2017 FU NCI NIH HHS [CO6RR11244] NR 111 TC 92 Z9 93 U1 2 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2005 VL 287 IS 2 BP 314 EP 335 DI 10.1016/j.ydbio.2005.09.002 PG 22 WC Developmental Biology SC Developmental Biology GA 991FN UT WOS:000233797800009 PM 16243308 ER PT J AU Dobens, L Jaeger, A Peterson, JS Raftery, LA AF Dobens, L Jaeger, A Peterson, JS Raftery, LA TI Bunched sets a boundary for Notch signaling to pattern anterior eggshell structures during Drosophila oogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Drosophila oogenesis; Notch signaling; TSC-22/DIP/BUN family ID GROWTH-FACTOR-BETA; FOLLICLE CELL-DIFFERENTIATION; LEUCINE-ZIPPER STRUCTURE; NONMUSCLE MYOSIN-II; WING IMAGINAL DISC; GLAND CANCER-CELLS; STIMULATED CLONE-22; EPITHELIAL MORPHOGENESIS; TRANSCRIPTION FACTOR; LATERAL INHIBITION AB Organized boundaries between different cell fates are critical in patterning and organogenesis. In some tissues, long-range signals position a boundary, and local Notch signaling maintains it. How Notch activity is restricted to boundary regions is not well understood. During Drosophila oogenesis, the long-range signals EGF and Dpp regulate expression of bunched (bun), which encodes a homolog of mammalian transcription factors TSC-22 and GILZ. Here, we show that bun establishes a boundary for Notch signaling in the follicle cell epithelium. Notch signaling is active in anterior follicle cells and is required for concurrent follicle cell reorganizations including centripetal migration and operculum formation. bun is required in posterior columnar follicle cells to repress the centripetal migration fate, including gene expression, cell shape changes and accumulation of cytoskeletal components. bun mutant clones adjacent to the centripetally migrating follicle cells showed ectopic Notch responses. bun is necessary, but not sufficient, to down-regulate Serrate protein levels throughout the follicular epithelium. These data indicate that Notch signaling is necessary, but not sufficient, for centripetal migration and that bun regulates the level of Notch stimulation to position the boundary between centripetally migrating and stationary columnar follicle cells. (C) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Missouri, Sch Biol Sci, Div Biochem & Mol Biol, Kansas City, MO 64110 USA. RP Raftery, LA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. EM laurel.raftery@cbrc2.mgh.harvard.edu RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM060501] NR 100 TC 26 Z9 26 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 2005 VL 287 IS 2 BP 425 EP 437 DI 10.1016/j.ydbio.2005.09.019 PG 13 WC Developmental Biology SC Developmental Biology GA 991FN UT WOS:000233797800017 PM 16223477 ER PT J AU McCampbell, A Truong, D Broom, DC Allchorne, A Gable, K Cutler, RG Mattson, MP Woolf, CJ Frosch, MP Harmon, JM Dunn, TM Brown, RH AF McCampbell, A Truong, D Broom, DC Allchorne, A Gable, K Cutler, RG Mattson, MP Woolf, CJ Frosch, MP Harmon, JM Dunn, TM Brown, RH TI Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEREDITARY SENSORY NEUROPATHY; PERIPHERAL-NERVE INJURY; SPHINGOLIPID SYNTHESIS; CONDUCTION-VELOCITY; NEUROTROPHIC FACTOR; DELTA-SUBUNIT; YEAST LCB1; NEURONS; EXPRESSION; CERAMIDE AB Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause hereditary sensory and autonomic neuropathy (type I) (HSAN1), an adult onset, autosomal dominant neuropathy. HSAN1 patients have reduced SPT activity. Expression of mutant SPTLC1 in yeast and mammalian cell cultures dominantly inhibits SPT activity. We created transgenic mouse lines that ubiquitously overexpress either wild-type (SPTLC1(WT)) or mutant SPTLC1 (SPTLC1(C133W)). We report here that SPTLC1(C133W) mice develop age-dependent weight loss and mild sensory and motor impairments. Aged SPTLC1(C133W) mice lose large myelinated axons in the ventral root of the spinal cord and demonstrate myelin thinning. There is also a loss of large myelinated axons in the dorsal roots, although the unmyelinated fibers are preserved. In the dorsal root ganglia, IB4 staining is diminished, whereas expression of the injury-induced transcription factor ATF3 is increased. These mice represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction. C1 Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Alzheimers Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20184 USA. Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20184 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP McCampbell, A (reprint author), Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. EM amccampbell@partners.org RI Mattson, Mark/F-6038-2012; OI Harmon, Jeffrey/0000-0001-7833-931X FU NINDS NIH HHS [5R01NS047717-02, F32 NS044695-03] NR 58 TC 33 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2005 VL 14 IS 22 BP 3507 EP 3521 DI 10.1093/hmg/ddi380 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 983FL UT WOS:000233216600017 PM 16210380 ER PT J AU Yock, T Schneider, R Friedmann, A Adams, J Fullerton, B Tarbell, N AF Yock, T Schneider, R Friedmann, A Adams, J Fullerton, B Tarbell, N TI Proton radiotherapy for orbital rhabdomyosarcoma: Clinical outcome and a dosimetric comparison with photons SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID MODULATED RADIATION-THERAPY; INDUCED 2ND CANCERS; INTERGROUP RHABDOMYOSARCOMA; MEDULLOBLASTOMA; REDUCTION; CHILDREN; SARCOMA; TUMORS; IMRT; NECK AB Background: Over 85% of pediatric orbital rhabdomyosarcoma (RMS) are cured with combined chemotherapy and radiation. However, the late effects of photon radiation compromise function and cosmetic outcome. Proton radiation can provide excellent tumor dose distributions while sparing normal tissues better than photon irradiation. Methods and Materials: Conformal 3D photon and proton radiotherapy plans were generated for children treated with proton irradiation for orbital RMS at Massachusetts General Hospital. Dose-volume histograms (90%, 50%, 10%) were generated and compared for important orbital and central nervous system structures. Average percentages of total dose prescribed were calculated based on the 3 dose-volume histogram levels for normal orbital structures for both the proton and photon plans. The percent of normal tissue spared by using protons was calculated. Results: Seven children were treated for orbital rhabdomyosarcoma with proton irradiation and standard chemotherapy. The median follow-up is 6.3 years (range, 3.5-9.7 years). Local and distant controls compare favorably to those in other published accounts. There was an advantage in limiting the dose to the brain, pituitary, hypothalamus, temporal lobes, and ipsilateral and contralateral orbital structures. Tumor size and location affect the degree of sparing of normal structures. Conclusions: Fractionated proton radiotherapy is superior to 3D conformal photon radiation in the treatment of orbital RMS. Proton therapy maintains excellent tumor coverage while reducing the radiation dose to adjacent normal structures. Proton radiation therapy minimizes long-term side effects. (c) 2005 Elsevier Inc. C1 Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Yock, T (reprint author), Harvard Univ, Dept Radiat Oncol, Massachusetts Gen Hosp, Sch Med, 100 Blossom St,Cox 341, Boston, MA 02114 USA. EM tyock@partners.org FU NCI NIH HHS [5 PO1 CA 21239-26] NR 21 TC 69 Z9 70 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2005 VL 63 IS 4 BP 1161 EP 1168 DI 10.1016/j.ijrobp.2005.03.052 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 979LQ UT WOS:000232943900025 PM 15950401 ER PT J AU Shih, HA Harisinghani, M Zietman, AL Wolfgang, JA Saksena, M Weissleder, R AF Shih, HA Harisinghani, M Zietman, AL Wolfgang, JA Saksena, M Weissleder, R TI Mapping of nodal disease in locally advanced prostate cancer: Rethinking the clinical target volume for pelvic nodal irradiation based on vascular rather than bony anatomy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 1st Annual Multidisciplinary Prostate Cancer Symposium CY FEB 17-19, 2005 CL Orlando, FL SP Amer Soc Clin Oncol, Amer Soc Therapeut Radiol & Oncol, Amer Soc Urol Oncol, Prostate Canc Fdn DE pelvic nodes; nodal CTV; prostate cancer ID GYNECOLOGIC-ONCOLOGY-GROUP; FIELD RADIATION-THERAPY; PHASE-III TRIAL; NONINVASIVE DETECTION; WHOLE PELVIS; RADIOTHERAPY; CARCINOMA; LYMPHANGIOGRAPHY; LYMPHADENECTOMY; ADENOCARCINOMA AB Purpose: Toxicity from pelvic irradiation could be reduced if fields were limited to likely areas of nodal involvement rather than using the standard "four-field box." We employed a novel magnetic resonance lymphangiographic technique to highlight the likely sites of occult nodal metastasis from prostate cancer. Methods and Materials: Eighteen prostate cancer patients with pathologically confirmed node-positive disease had a total of 69 pathologic nodes identifiable by lymphotropic nanoparticle-enhanced MRI and semiquantitative nodal analysis. Fourteen of these nodes were in the para-aortic region, and 55 were in the pelvis. The position of each of these malignant nodes was mapped to a common template based on its relation to skeletal or vascular anatomy. Results: Relative to skeletal anatomy, nodes covered a diffuse volume from the mid lumbar spine to the superior pubic ramus and along the sacrum and pelvic side walls. In contrast, the nodal metastases mapped much more tightly relative to the large pelvic vessels. A proposed pelvic clinical target volume to encompass the region at greatest risk of containing occult nodal metastases would include a 2.0-cm radial expansion volume around the distal common iliac and proximal external and internal iliac vessels that would encompass 94.5% of the pelvic nodes at risk as defined by our node-positive prostate cancer patient cohort. Conclusions: Nodal metastases from prostate cancer are largely localized along the major pelvic vasculature. Defining nodal radiation treatment portals based on vascular rather than bony anatomy may allow for a significant decrease in normal pelvic tissue irradiation and its associated toxicities. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Shih, HA (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,Cox Lower Level, Boston, MA 02114 USA. EM hshih@partners.org NR 22 TC 66 Z9 66 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2005 VL 63 IS 4 BP 1262 EP 1269 DI 10.1016/j.ijrobp.2005.07.952 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 979LQ UT WOS:000232943900038 PM 16253781 ER PT J AU Qin, XB Dobarro, M Bedford, SJ Ferris, S Miranda, PV Song, WP Bronson, RT Visconti, PE Halperin, JA AF Qin, XB Dobarro, M Bedford, SJ Ferris, S Miranda, PV Song, WP Bronson, RT Visconti, PE Halperin, JA TI Further characterization of reproductive abnormalities in mCd59b knockout mice: A potential new function of mCd59 in male reproduction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COMPLEMENT REGULATORY PROTEINS; OVARIAN FOLLICULAR-FLUID; ACCELERATING FACTOR CD55; TYROSINE PHOSPHORYLATION; TISSUE DISTRIBUTION; TARGETED DELETION; MOUSE SPERMATOZOA; SEMINAL PLASMA; C3 ACTIVATION; COMPONENT C3 AB CD59 is a GPI-linked membrane protein that inhibits formation of the membrane attack complex of complement. We reported recently that mice have two CD59 genes (termed mCd59a and mU59b), and that the targeted deletion of mCd59b (mCd59b(-/-)) results in spontaneous hemolytic anemia and progressive loss of male fertility. Further studies of the reproductive abnormalities in mCd59b(-/-) mice reported in this study revealed the presence of abnormal multinucleated cells and increased apoptotic cells within the walls of the seminiferous tubules, and a decrease in the number, motility, and viability of sperm associated with a significant increase in abnormal sperm morphologies. Both the capacitation-associated tyrosine phosphorylation and the ionophore-induced acrosome reaction as well as luteinizing hormone, follicle-stimulating hormone, and testosterone serum levels were similar in mU59b(-/-) and inU59b(+/+). Surprisingly, the functional deficiency of the complement protein C3 did not rescue the abnormal reproductive phenotype of mCd59b(-/-), although it was efficient in rescuing their hemolytic anemia. These results indicate that the male reproductive abnormalities in mCd59b(-/-) are complement-independent, and that mCd59 may have a novel function in spermatogenesis that is most likely unrelated to its function as an inhibitor of membrane attack complex formation. C1 Harvard Univ, Sch Med, Lab Translat Res, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02115 USA. Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Qin, XB (reprint author), Harvard Univ, Sch Med, Lab Translat Res, 1 Kendall Sq,Bldg 600,3rd Floor, Cambridge, MA 02139 USA. EM xuebin_qin@hms.harvard.edu; jose_halperin@hms.harvard.edu FU NIAID NIH HHS [R01 AI061174]; NICHD NIH HHS [HD44044, HD38082]; NIDDK NIH HHS [R01 DK052855, R01 DK060979] NR 53 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2005 VL 175 IS 10 BP 6294 EP 6302 PG 9 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300008 PM 16272280 ER PT J AU Schelonka, RL Ivanov, II Jung, DH Ippolito, GC Nitschke, L Zhuang, YX Gartland, GL Pelkonen, J Alt, FW Rajewsky, K Schroeder, HW AF Schelonka, RL Ivanov, II Jung, DH Ippolito, GC Nitschke, L Zhuang, YX Gartland, GL Pelkonen, J Alt, FW Rajewsky, K Schroeder, HW TI A single D-H gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN LOCUS; V-H; DIVERSITY; SELECTION; SEQUENCE; REGION; RECOMBINATION; ANTIBODIES; DEXTRAN; MICE AB To test the contribution of individual D gene segments to B cell development and function, we used gene targeting to create mice that contain only DFL16.1 in the D-H locus. We term this D-limited IgH allele Delta D-DFL. Although the absolute number of IgM(+)IgD(-) B cells in the bone marrow was decreased, homozygous Delta D-DFL BALB/c mice contained normal numbers of IgM(+)IgD(+) B cells in bone marrow and spleen and normal numbers of B1a, B1b, and B2 cells in the peritoneal cavity. Bone marrow IgM(+)IgD(+) B cells express a CDR-H3 repertoire similar in length and amino acid composition to the DFL16.1 subset of the wild-type BALB/c repertoire but divergent from sequences that do not contain DFL16.1. This similarity in content is the product of both germline bias and somatic selection, especially in the transition to the mature IgM(+)IgD(+) stage of development. Serum Ig concentrations and the humoral immune response to a T-dependent Ag ([4-hydroxy-3-nitrophenyl]acetyl hapten) were nearly identical to wild-type littermate controls. A greater variance in the immune response to the T-independent Ag (alpha(1 -> 3)-dextran) was observed in Delta D-DFL homozygotes, with half of the mice exhibiting levels below the range exhibited by controls. Although limited to a repertoire specific to DFL16.1, the presence of a single DH gene segment of normal sequence was sufficient for development of normal numbers of mature B cells and for robust humoral immune function. C1 Univ Alabama, Div Dev & Clin Immunol, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Div Dev & Clin Immunol, Dept Genet, Birmingham, AL 35294 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Univ Erlangen Nurnberg, Dept Genet, Erlangen, Germany. Univ Kuopio, Dept Clin Microbiol, FIN-70211 Kuopio, Finland. RP Schroeder, HW (reprint author), Univ Alabama, Div Dev & Clin Immunol, Dept Pediat, WTI 378,1530 3rd Ave S, Birmingham, AL 35294 USA. EM harry.schroeder@ccc.uab.edu FU FIC NIH HHS [F06 TW002130, TW02130]; NIAID NIH HHS [AI48115, AI07051, AI42732, R01 AI020047, R01 AI020047-25, R01 AI048115, T32 AI007051]; NICHD NIH HHS [HD043327] NR 41 TC 25 Z9 25 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2005 VL 175 IS 10 BP 6624 EP 6632 PG 9 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300045 PM 16272317 ER PT J AU Seth, N Kaufmann, D Lahey, T Rosenberg, ES Wucherpfennig, KW AF Seth, N Kaufmann, D Lahey, T Rosenberg, ES Wucherpfennig, KW TI Expansion and contraction of HIV-specific CD4 T cells with short bursts of viremia, but physical loss of the majority of these cells with sustained viral replication SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIRETROVIRAL THERAPY; PCR AMPLIFICATION; CD8-T-CELL MEMORY; CD4-T-CELL HELP; CD8(+); INFECTION; RESPONSES; LYMPHOCYTES; EFFECTOR; ACTIVATION AB Chronic infection with the HIV results in poor HIV-specific CD4 T cell proliferation, but more recent analyses using intracellular cytokine staining demonstrated that IFN-gamma-producing, HIV-specific CD4 T cells can be detected for years in HIV-infected subjects. Because it is not known whether the majority of HIV-specific T cells are lost or become dysfunctional, we examined the kinetics of the T cell response over an extended period of time using a panel of 10 HLA-DR tetramers loaded with HIV p24 peptides. Tetramer(+) CD4 T cells were present at a relatively high frequency during acute infection, but the size of these populations substantially contracted following suppression of viral replication. Short-term cessation of antiretroviral therapy resulted in a burst of viral replication and concomitant expansion of tetramer(+) CD4 T cells, and these populations again contracted following reinitiation of therapy. The kinetics with which these cell populations contracted were characteristic of effector T cells, a conclusion that was supported by their phenotypic (CCR7(-)CD45RA(-)) and functional properties (IFN-gamma(+)). Continued high-level viremia resulted in the physical loss of the majority of tetramer(+) CD4 T cells, and the decline of HIV p24-specific CD4 T cells occurred more rapidly and was more substantial than the reduction of total CD4 T cell numbers. We conclude that the population of HIV p24-specific CD4 T cells is initially responsive to changes in the levels of viral Ags, but that the majority of these cells are lost in a setting of chronic viremia. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03755 USA. Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM Kai_Wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [P01 AI45757, R01 AI040873, R01 AI40873, P01 AI045757]; NIDDK NIH HHS [KO1 DK068383, K01 DK068383] NR 40 TC 26 Z9 26 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 NOV 15 PY 2005 VL 175 IS 10 BP 6948 EP 6958 PG 11 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300083 PM 16272355 ER PT J AU Ackerman, RH Speck, LM McGraw, C Affel, ME AF Ackerman, RH Speck, LM McGraw, C Affel, ME TI Prevalence of moderate stenosis in patients with carotid stroke SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S59 EP S59 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000230 ER PT J AU Grisar, T Chanas, G de Nijs, L Coumans, B Delgado-Escueta, AV Lakaye, B AF Grisar, T Chanas, G de Nijs, L Coumans, B Delgado-Escueta, AV Lakaye, B TI EFHC-I/Myoclonin implicated in juvenile myoclonic epilepsy exibits a DM 10 domain dependent binding to mitotic spindles and the alpha tubulin complex in dividing cells SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Univ Liege, CNCM, B-4000 Liege, Belgium. Univ Calif Los Angeles, Epilepsy Genet Genom Labs, David Geffen Sch Med, Comprehens Epilepsy Programme, Los Angeles, CA 90024 USA. VA GLAHS W Los Angeles, W Los Angeles DVA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S89 EP S89 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000339 ER PT J AU Jansen, A Sancak, O D'Agostino, MD Pandolfo, M Sims, K Thiele, E Andermann, F Kwiatkowski, DJ Halley, DJJ Andermann, E AF Jansen, A Sancak, O D'Agostino, MD Pandolfo, M Sims, K Thiele, E Andermann, F Kwiatkowski, DJ Halley, DJJ Andermann, E TI Codon 905 mutations in the TSC2 gene: Clinical manifestations and functional aspects SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ H3A 2T5, Canada. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. Univ Libre Bruxelles, Dept Neurol, Brussels, Belgium. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. RI Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S154 EP S155 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088001235 ER PT J AU Macklis, JD AF Macklis, JD TI Molecular development and repair of corticospinal motor neuron circuitry SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurosurg, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Nervous Syst Repair,Program Neurosci, Boston, MA USA. Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S24 EP S25 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000098 ER PT J AU Sale, MM Mychaleckyj, JC Hsu, FC Furie, KL Coull, BM Zhong, M Gordon, CJ Gehring, ME Toole, JF Rish, SS AF Sale, MM Mychaleckyj, JC Hsu, FC Furie, KL Coull, BM Zhong, M Gordon, CJ Gehring, ME Toole, JF Rish, SS TI VISPGEN: a resource for genetic studies of recurrent ischemic stroke SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ USA. RI yu, yan/C-2322-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S438 EP S438 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088004077 ER PT J AU Wasterlain, CG Chen, JWY Suchomelova, L Liu, H AF Wasterlain, CG Chen, JWY Suchomelova, L Liu, H TI Status epilepticus SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S7 EP S7 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000028 ER PT J AU Jha, SK Ross, RJ Morrison, AR AF Jha, SK Ross, RJ Morrison, AR TI Sleep-related neurons in the central nucleus of the amygdala of rats and their modulation by the dorsal raphe nucleus SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE amygdala; electrical stimulation; single neuronal activity; sleep-wakefulness ID BASAL FOREBRAIN; UNIT-ACTIVITY; REM-SLEEP; FEAR; PROJECTIONS; SEROTONIN; CAT; CONNECTIONS; STIMULATION; RETROGRADE AB The amygdala (AMY) plays an important role in initiating appropriate neurobehavioral responses to emotionally arousing events. Its major efferents from the central nucleus (Ace) to the basal forebrain, hypothalamus and brainstem permit it to influence sleep mechanisms. To characterize further the neuronal activity of AMY during sleep and wakefulness, we recorded single neuronal activity in Ace across behavioral states in freely moving, normally behaving rats. Of the 49 neurons recorded from Ace, 24 neurons had firing patterns related to sleep -wakefulness (S-W). Of these, 50% (n = 12) had a high firing frequency during wakefulness (W) or both W and REM sleep (REM), 12% (n = 3) were non-REM (NREM)-related, 17% (n = 4) had a high firing rate in REM (REM-ON), and 20% (n = 5) fired at a low rate during REM. Because serotonin introduced into AMY during REM induces short-latency changes of state, we also studied the effects of low frequency (1 Hz) electrical stimulation of the dorsal raphe nucleus (DRN) on Ace neurons. All REM-ON neurons recorded from Ace were inhibited by DRN stimulation, and other cell types were unaffected. Thus, we found that the majority of cells in Ace related to S-W fired slowly during NREM and increased their discharge during W and/or REM, and that the DRN has the potential for modulating the spontaneous activity of REM-ON cells in rats. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Vet Med, Dept Psychiat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Morrison, AR (reprint author), Univ Penn, Sch Vet Med, Dept Psychiat, Philadelphia, PA 19104 USA. EM armsleep@vet.upenn.edu OI Jha, Sushil/0000-0001-8638-898X FU NIMH NIH HHS [MH 42903] NR 49 TC 24 Z9 25 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD NOV 15 PY 2005 VL 86 IS 4 BP 415 EP 426 DI 10.1016/j.physbeh.2005.06.033 PG 12 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 986WG UT WOS:000233479800001 PM 16137725 ER PT J AU Evans, CL Potma, EO Puoris'haag, M Cote, D Lin, CP Xie, XS AF Evans, CL Potma, EO Puoris'haag, M Cote, D Lin, CP Xie, XS TI Chemical imaging of tissue in vivo with video-rate coherent anti-Stokes Raman scattering microscopy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nonlinear microscopy; vibrational imaging; back scattering ID TURBID MEDIA; FLUORESCENCE; CELLS; MICROSPECTROSCOPY; INSTRUMENTATION; EXCITATION; BILAYERS; LIPIDS; CARS AB Imaging living organisms with molecular selectivity typically requires the introduction of specific labels. Many applications in biology and medicine, however, would significantly benefit from a noninvasive imaging technique that circumvents such exogenous probes. In vivo microscopy based on vibrational spectroscopic contrast offers a unique approach for visualizing tissue architecture with molecular specificity. We have developed a sensitive technique for vibrational imaging of tissues by combining coherent anti-Stokes Raman scattering (CARS) with video-rate microscopy. Backscattering of the intense forward-propagating CARS radiation in tissue gives rise to a strong epi-CARS signal that makes in vivo imaging possible. This substantially large signal allows for realtime monitoring of dynamic processes, such as the diffusion of chemical compounds, in tissues. By tuning into the CH2 stretching vibrational band, we demonstrate CARS imaging and spectroscopy of lipid-rich tissue structures in the skin of a live mouse, including sebaceous glands, corneocytes, and adipocytes, with unprecedented contrast at subcellular resolution. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. RP Evans, CL (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, 55 Fruit St, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu; xie@chemistry.harvard.edu RI Cote, Daniel/D-5185-2011 NR 29 TC 574 Z9 582 U1 14 U2 151 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 15 PY 2005 VL 102 IS 46 BP 16807 EP 16812 DI 10.1073/pnas.0508282102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PT UT WOS:000233462900051 PM 16263923 ER PT J AU Katsel, P Davis, KL Haroutunian, V AF Katsel, P Davis, KL Haroutunian, V TI Variations in myelin and oligodendrocyte-related gene expression across multiple brain regions in schizophrenia: A gene ontology study SO SCHIZOPHRENIA RESEARCH LA English DT Review DE schizophrenia; postmortem; gene expression; microarray; oligodendrocyte; myelin; brain regions; hippocampus; cingulate cortex; temporal cortex ID CEREBRAL BLOOD-FLOW; CARDIO-FACIAL SYNDROME; CENTRAL-NERVOUS-SYSTEM; AXON-GLIA INTERACTIONS; RNA-BINDING PROTEINS; PREFRONTAL CORTEX; BIPOLAR DISORDER; MICROARRAY ANALYSIS; MAJOR DEPRESSION; ELDERLY-PATIENTS AB Large-scale gene expression studies in schizophrenia (SZ) have generally focused on the dorsolateral prefrontal cortex. Studies of other brain regions have been less frequent and have rarely been performed in the same subjects. We analyzed postmortem gene expression in multiple cortical regions (Brodmann areas 8, 10, 44, 46, 23/31, 24/32, 20, 21, 22, 36/28, 7 and 17, respectively) as well as in the hippocampus, caudate nucleus, and putamen of 13 SZ and 13 control subjects using Affymetrix GeneChip (R) microarrays. The superior temporal cortex (BA22) and cingulate cortices (BA24/32, 23/3 1) of subjects with SZ demonstrated more profound alterations of gene expression than other brain regions compared to controls [Katsel, P., Davis, K.L., Gorman, J.M., Haroutunian, V, in press. Variations in differential gene expression patterns across multiple brain regions in schizophrenia. Schizophr. Res.]. Functional categorization of genes whose expression was altered revealed multiple gene ontology classes that included oligodendrocyte/myelin-related genes. These myelin-related ontologies were among the top scored categories in temporal and cingulate gyri and in the hippocampus relative to other brain regions. The most altered transcripts in SZ were those encoding for proteins involved in determination of glial differentiation, myelin structure and adhesion proteins participating in axoglial contacts. Hierarchical clustering demonstrated that these myelin-related gene expression abnormalities in SZ were most pronounced in the hippocampus, superior temporal and cingulate cortices. The high representation of abnormally expressed oligodendrocyte/myelin genes in brain regions with the largest numbers of abnormally expressed genes in SZ confirmed their involvement in the disease process and suggested that the integrity of axon-myelin interaction may be impaired in SZ. (c) 2005 Elsevier B.V. All rights reserved. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Haroutunian, V (reprint author), Bronx Vet Adm Med Ctr, Room 4F-33A,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM pavel.katsel@mssm.edu; kenneth.davis@mssm.edu; vahram.haroutunian@mssm.edu FU NCRR NIH HHS [M01-RR-00071]; NIMH NIH HHS [MH064673, MH45212] NR 113 TC 133 Z9 138 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 15 PY 2005 VL 79 IS 2-3 BP 157 EP 173 DI 10.1016/j.schres.2005.06.007 PG 17 WC Psychiatry SC Psychiatry GA 981GC UT WOS:000233074600002 PM 16139990 ER PT J AU Hoerbelt, R Johnston, DR Shoji, T Houser, SL Hasse, RS Ledgerwood, LG Iribarne, A Allan, JS Sayegh, MH Sachs, DH Madsen, JC AF Hoerbelt, R Johnston, DR Shoji, T Houser, SL Hasse, RS Ledgerwood, LG Iribarne, A Allan, JS Sayegh, MH Sachs, DH Madsen, JC TI Combination treatment with donor-specific transfusions and cyclosporine a induces long-term survival of cardiac allografts in miniature swine SO TRANSPLANTATION LA English DT Article DE heart; miniature swine; donor-specific transfusion; cyclosporine A; tolerance; heart transplantation ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANTATION TOLERANCE; BLOOD-TRANSFUSION; HEART ALLOGRAFTS; T-CELLS; CLASS-I; RENAL-TRANSPLANTATION; CYNOMOLGUS MONKEYS; ADULT-RATS; INDUCTION AB Background. To evaluate whether pretransplant donor-specific transfusions (DST) can induce tolerance to cardiac allografts in large animals, heterotopic cardiac transplants were performed across a class I MHC barrier in inbred miniature swine. Methods. Experimental animals received two DSTs, each containing 1.4x10(8) viable peripheral blood mononuclear cells, 14 and 7 days prior to transplantation together with a 12-day course of cyclosporine (CyA) (13 mg/kg IV) starting on postoperative day (POD) 0. Results. Untreated (n = 2) and DST-only (n = 2) treated control animals rejected between POD epsilon and 8. Animals treated with CyA alone (n=3) exhibited graft survival to 53, 52 and 59 days. In contrast, the combination of DST and CyA (n=3) led to stable graft function for > 200 days. Long-term survivors maintained peripheral CML response against donor antigen. Following DSTs, the donor-specific proliferative response of CD8+ recipient T cells was significantly increased (P=0.011), and a significant number of CD8+ T cells underwent apoptosis (10.1% on POD 0;5.2% on POD -14; P=0.04). None of the DST-treated animals developed donor-specific antibodies. Conclusions. These results are the first to demonstrate the ability of DST to induce operational tolerance to cardiac allografts in large animals, and they suggest that peripheral mechanisms of tolerance mediate this effect. C1 Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Renal, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, Transplantat Biol Res Ctr, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [R01 HL54211]; NIAID NIH HHS [P01 AI50157] NR 43 TC 8 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2005 VL 80 IS 9 BP 1275 EP 1282 DI 10.1097/01.tp.0000177638.56260.23 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 990HA UT WOS:000233732600020 PM 16314796 ER PT J AU Mathes, DW Solari, MG Randolph, MA Gazelle, GS Yamada, K Huang, CA Sachs, DH Lee, WPA AF Mathes, DW Solari, MG Randolph, MA Gazelle, GS Yamada, K Huang, CA Sachs, DH Lee, WPA TI Long-term acceptance of renal allografts following prenatal inoculation with adult bone marrow SO TRANSPLANTATION LA English DT Article DE blood transfusion; bone marrow infusion; chimerism and microchimerism; experimental transplantation ID HEMATOPOIETIC STEM-CELLS; IN-UTERO TRANSPLANTATION; MAJOR HISTOCOMPATIBILITY COMPLEX; MHC RECOMBINANT SWINE; VERSUS-HOST DISEASE; MINIATURE SWINE; IMMUNOLOGICAL CHARACTERIZATION; INUTERO TRANSPLANTATION; KIDNEY-TRANSPLANTATION; INDUCE TOLERANCE AB Background. The aim was to investigate if intravascular in utero injection of adult bone marrow into swine fetuses could lead to macrochimerism and tolerance to the donor. Methods. Outbred Yorkshire sows and boars screening negative for MHC allele SLA(c) of MGH miniature swine were bred. A laparotomy was performed on the sows at 50 days gestation to expose the uterus. Bone marrow harvested from SLA(cc) miniature swine was T-cell depleted and injected intravascularly into seventeen fetuses. Flow cytometry was performed to detect donor cells (chimerism) in the peripheral blood after birth. Mixed lymphocyte reactions (MLR) and cell-mediated lympholysis (CML) assays were used to assess the response to donor MHC. Previously frozen skin grafts from the bone marrow donor were placed on the offspring from the first litter. Donor-matched renal transplant from SLA(cc) donors were performed on chimeric swine, with and without a short 12-day course of cyclosporine, and one nonchimeric littermate. Results. Nine inoculated offspring demonstrated donor cell chimerism in the peripheral blood and lymphohemato-poietic tissues. All animals with detectable chimerism within the first three weeks were consistently nonreactive to donor MHC in vitro. Animals challenged with donor skin grafts displayed prolonged graft survival without producing antidonor antibodies. All chimeric animals accepted donor-matched kidney allografts, even one without cyclosporine. The kidney in the nonchimeric littermate rejected by day 21. Conclusions. Transplantation of allogeneic adult bone marrow into immunocompetent fetal recipients resulted in chimerism. In utero inoculation led to operational tolerance to the donor's major histocompatibility antigens and long-term acceptance to organ allografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Lee, WPA (reprint author), Univ Pittsburgh, Sch Med, Div Plast Surg, 690 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM leewpa@upmc.edu OI Mathes, David/0000-0003-4388-1373 FU NCI NIH HHS [1R01 CA79988-01A1]; NHLBI NIH HHS [5R01 HL63430] NR 44 TC 15 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2005 VL 80 IS 9 BP 1300 EP 1308 DI 10.1097/01.tp.0000178933.31987.11 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 990HA UT WOS:000233732600023 PM 16314799 ER PT J AU Solomon, DH Avorn, J Katz, JN Finkelstein, JS Arnold, M Polinski, JM Brookhart, MA AF Solomon, DH Avorn, J Katz, JN Finkelstein, JS Arnold, M Polinski, JM Brookhart, MA TI Compliance with osteoporosis medications SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LONGITUDINAL DATA; DISCONTINUATION; PERSISTENCE; THERAPY; WOMEN AB Background: Long-term compliance with pharmacologic treatments for many asymptomatic conditions may be suboptimal, but little is known about compliance with medications used for osteoporosis. This study was undertaken to assess the level and determinants of compliance with drugs prescribed for osteoporosis. Methods: This retrospective cohort study used pharmacy claims data from US Medicare and filled prescriptions from a state pharmaceutical benefits program. We included persons 65 years or older who initiated use of a medication for osteoporosis (alendronate sodium, calcitonin, hormone therapy, raloxifene hydrochloride, or risedronate) from January 1, 1996, through December 31, 2002. The outcome of interest was suboptimal medication compliance, defined as equal to or less than 66% of days with medication during a 60-day period. Results: One year after initiating treatment for osteoporosis, 45.2% of the 40 002 patients were not continning to fill prescriptions. Five years after initiation, 52.1% of patients were not continuing to fill prescriptions for an osteoporosis medication. Several characteristics independently predicted compliance: female sex, younger age, fewer comorbid conditions, using fewer nonosteoporosis medications, bone mineral density testing before and after initiating a medication, a fracture before and after initiating a medication, and nursing home residence during the 12 months before initiating a medication. However, models adjusted for the significant patient variables explained only 6% of the variation in compliance. Conclusions: Most patients who initiate a medication for osteoporosis do not continue to take it as prescribed. Although several patient characteristics significantly correlated with compliance, adjusted models explained little of the variation. C1 Brigham & Womens Hosp, Div Pharmacoepidemiol, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02120 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Div Pharmacoepidemiol, 1620 Tremont S,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org FU NIAMS NIH HHS [AR-47782, AR-48616]; NIDDK NIH HHS [DK-02759] NR 10 TC 191 Z9 192 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 14 PY 2005 VL 165 IS 20 BP 2414 EP 2419 DI 10.1001/archinte.165.20.2414 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 983SH UT WOS:000233251900014 PM 16287772 ER PT J AU Majumder, PK Sellers, WR AF Majumder, PK Sellers, WR TI Akt-regulated pathways in prostate cancer SO ONCOGENE LA English DT Review DE PTEN; AKT; prostate cancer; phosphoinostide; 3-kinase ID GROWTH-FACTOR-I; TUMOR-SUPPRESSOR GENE; RECEPTOR KINASE INHIBITOR; HUMAN PANCREATIC-CANCER; HIGH GLEASON SCORE; STEM-CELL ANTIGEN; PHOSPHOINOSITIDE 3-KINASE; GERMLINE MUTATIONS; COWDEN-DISEASE; ANTITUMOR-ACTIVITY AB Prostate cancer remains a major cause of cancer-related mortality. Genetic clues to the molecular pathways driving the most aggressive forms of prostate cancer have been limited. Genetic inactivation of PTEN through either gene deletion or point mutation is reasonably common in metastatic prostate cancer and the resulting activation of phosphoinostide 3-kinase, AKT and mTOR provides a major therapeutic opportunity in this disease as mTOR inhibitors, HSP90 inhibitors and PI3K inhibitors begin to enter clinical development. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. RP Sellers, WR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_Sellers@dfci.harvard.edu NR 122 TC 239 Z9 243 U1 3 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 14 PY 2005 VL 24 IS 50 BP 7465 EP 7474 DI 10.1038/sj.onc.1209096 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 982ZW UT WOS:000233201900009 PM 16288293 ER PT J AU Mujat, M Chan, RC Cense, B Park, BH Joo, C Akkin, T Chen, TC de Boer, JF AF Mujat, M Chan, RC Cense, B Park, BH Joo, C Akkin, T Chen, TC de Boer, JF TI Retinal nerve fiber layer thickness map determined from optical coherence tomography images SO OPTICS EXPRESS LA English DT Article ID HIGH-SPEED; SPECTRAL INTERFEROMETRY; DISPERSION COMPENSATION; ULTRAHIGH-RESOLUTION; TEMPORAL RAPHE; ALGORITHM; SNAKES; EYES AB We introduce a method to determine the retinal nerve fiber layer (RNFL) thickness in OCT images based on anisotropic noise suppression and deformable splines. Spectral-Domain Optical Coherence Tomography (SDOCT) data was acquired at 29 kHz A-line rate with a depth resolution of 2.6 m and a depth range of 1.6 mm. Areas of 9.6x6.4 mm(2) and 6.4x6.4 mm(2) were acquired in approximately 6 seconds. The deformable spline algorithm determined the vitreous-RNFL and RNFL-ganglion cell/inner plexiform layer boundary, respectively, based on changes in the reflectivity, resulting in a quantitative estimation of the RNFL thickness. The thickness map was combined with an integrated reflectance map of the retina and a typical OCT movie to facilitate clinical interpretation of the OCT data. Large area maps of RNFL thickness will permit better longitudinal evaluation of RNFL thinning in glaucoma. (c) 2005 Optical Society of America. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Mujat, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 40 Blossom St,BAR 704, Boston, MA 02114 USA. EM mmujat@partners.org; deboer@helix.mgh.harvard.edu RI de Boer, Johannes/B-7590-2012; OI de Boer, Johannes/0000-0003-1253-4950; Joo, Chulmin/0000-0002-1812-2976 NR 29 TC 98 Z9 101 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 NOV 14 PY 2005 VL 13 IS 23 BP 9480 EP 9491 DI 10.1364/OPEX.13.009480 PG 12 WC Optics SC Optics GA 984VY UT WOS:000233334900040 PM 19503151 ER PT J AU Reiber, GE Raugi, GJ AF Reiber, GE Raugi, GJ TI Preventing foot ulcers and amputations in diabetes SO LANCET LA English DT Editorial Material ID CHRONIC CARE MODEL; CHRONIC ILLNESS; MANAGEMENT C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Dept Dermatol, Seattle, WA 98101 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Reiber, GE (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev, Seattle, WA 98101 USA. EM greiber@u.washington.edu NR 15 TC 16 Z9 18 U1 1 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 12 PY 2005 VL 366 IS 9498 BP 1676 EP 1677 DI 10.1016/S0140-6736(05)67674-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 983BP UT WOS:000233206400005 PM 16291047 ER PT J AU Lipsky, BA Armstrong, DG Citron, DM Tice, AD Morgenstern, DE Abramson, MA AF Lipsky, BA Armstrong, DG Citron, DM Tice, AD Morgenstern, DE Abramson, MA TI Ertapenem versus piperacillin/tazobactam for diabetic foot infections (SIDESTEP): prospective, randomised, controlled, double-blinded, multicentre trial SO LANCET LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; SKIN-STRUCTURE INFECTIONS; ANTIBIOTIC-THERAPY; ANTIMICROBIAL THERAPY; COMPLICATED SKIN; MANAGEMENT; ULCERS; PATHOGENS; PREVALENCE; AMPUTATION AB Background Diabetic foot infections are a common and serious problem, yet few randomised trials of adequate quality have compared the efficacy of the various antibiotic regimens available for their treatment. Our aim was to assess the efficacy and safety of ertapenem versus piperacillin/tazobactam for foot infections. Methods We did a randomised, double-blinded, multicentre trial in adults (n=586) with diabetes and a foot infection classified as moderate-to-severe and requiring intravenous antibiotics. We assigned patients intravenous ertapenem (1 g daily; n=295) or piperacillin/tazobactam (3.375 g every 6 h; n=291) given for a minimum of 5 days, after which oral amoxicillin/clavulanic acid (875/125 mg every 12 h) could be given for up to 23 days. Investigators retained the option to administer vancomycin to patients in either group to ensure adequate coverage for potentially antibiotic resistant Enterococcus spp and meticillin-resistant Staphylococcus aureus (MRSA). Our primary outcome was the proportion of patients with a favourable clinical response (cure or improvement) on the day that intravenous antibiotic was discontinued. Analyses were by an evaluable-patient only approach. This study is registered with ClinicalTrials.gov, number NCT00229112. Findings Of the 576 patients treated, 445 were available for assessment at the end of intravenous therapy. Both baseline characteristics and favourable clinical response rates were similar for the 226 who received ertapenem and the 219 who received piperacillin/tazobactam. (94% vs 92%, respectively; between treatment difference 1.9%, 95% CI -2.9 to 6.9). Rates of favourable microbiological responses (eradication rates and clinical outcomes, by pathogen) and adverse events did not differ between groups. Interpretation Clinical and microbiological outcomes for patients treated with ertapenem were equivalent to those for patients treated with piperacillin/tazobactam, suggesting that this once-daily antibiotic should be considered for parenteral. therapy of diabetic foot infections, when deemed appropriate. C1 Univ Washington, Sch Med, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Rosalind Franklin Univ Med & Sci, Scholl Coll Podiatr Med, Chicago, IL USA. Rosalind Franklin Univ Med & Sci, Ctr Lower Extrem Ambulatory Res, Chicago, IL USA. RM Alden Res Lab, Santa Monica, CA USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. Merck & Co Inc, West Point, PA USA. RP Lipsky, BA (reprint author), Univ Washington, Sch Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM Benjamin.Lipsky@med.va.gov OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 53 TC 114 Z9 116 U1 1 U2 9 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 12 PY 2005 VL 366 IS 9498 BP 1695 EP 1703 DI 10.1016/S0140-6736(05)67694-5 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 983BP UT WOS:000233206400024 ER PT J AU Greenman, RL Panasyuk, S Wang, X Lyons, TE Dinh, T Longoria, L Giurini, JM Freeman, J Khaodhiar, L Veves, A AF Greenman, RL Panasyuk, S Wang, X Lyons, TE Dinh, T Longoria, L Giurini, JM Freeman, J Khaodhiar, L Veves, A TI Early changes in the skin microcirculation and muscle metabolism of the diabetic foot SO LANCET LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; NEUROPATHIC FOOT; SKELETAL-MUSCLE; WATER DIURESIS; OXYGENATION; QUANTIFICATION; ULCERATION; RISK; H-1; MRI AB Background Changes in the large vessels and microcirculation of the diabetic foot are important in the development of foot ulceration and subsequent failure to heal existing ulcers. We investigated whether oxygen delivery and muscle metabolism of the lower extremity were factors in diabetic foot disease. Methods We studied 108 patients (21 control individuals who did not have diabetes, 36 patients with diabetes who did not have neuropathy, and 51 patients with both diabetes and neuropathy). We used medical hyperspectral imaging (MHSI) to investigate the haemoglobin saturation (SHSIO2; % of oxyhaemoglobin in total haemoglobin [the sum of oxyhaemoglobin and deoxyhaemoglobin]) in the forearm and foot; we also used P-31-MRI scans to study the cellular metabolism of the foot muscles by measuring the concentrations of inorganic phosphate and phosphocreatine and calculating the ratio of inorganic phosphate to phosphocreatine (Pi/PCr). Findings The forearm SHSIO2 during resting was different in all three groups, with the highest value in controls (mean 42 [SD 17]), followed by the non-neuropathic (32 [8]) and neuropathic (28 [8]) groups (p<0.0001). In the foot at resting, SHSIO2 was higher in the control (38 [22]) and non-neuropathic groups (37 [12]) than in the neuropathic group (30 [12]; p=0.027). The Pi/PCr ratio was higher in the non-neuropathic (0.41 [0.10]) and neuropathic groups (0.58 [0.26]) than in controls (0.20 [0.06]; p<0.0001). Interpretation Our results indicate that tissue SHSIO2 is reduced in the skin of patients with diabetes, and that this impairment is accentuated in the presence of neuropathy in the diabetic foot. Additionally, energy reserves of the foot muscles are reduced in the presence of diabetes, suggesting that microcirculation could be a major reason for this difference. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. HyperMed Inc, Watertown, MA USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 321A,West Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu FU NCRR NIH HHS [RR 01032]; NHLBI NIH HHS [R01 HL0 75678-01]; NIDDK NIH HHS [R21 DK58651, R41 DK69871] NR 29 TC 81 Z9 84 U1 1 U2 10 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 12 PY 2005 VL 366 IS 9498 BP 1711 EP 1717 DI 10.1016/S0140-6736(05)67696-9 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 983BP UT WOS:000233206400026 PM 16291064 ER PT J AU Cavanagh, PR Lipsky, BA Bradbury, AW Botek, G AF Cavanagh, PR Lipsky, BA Bradbury, AW Botek, G TI Treatment for diabetic foot ulcers SO LANCET LA English DT Review ID PERIPHERAL ARTERIAL-DISEASE; LOWER-EXTREMITY AMPUTATION; LOWER-LIMB ISCHEMIA; RESISTANT STAPHYLOCOCCUS-AUREUS; ERYTHROCYTE SEDIMENTATION-RATE; RANDOMIZED-CONTROLLED TRIAL; NEUROPATHIC FOOT; COST-EFFECTIVENESS; PLANTAR ULCERS; THERAPEUTIC FOOTWEAR AB People with diabetes develop foot ulcers because of neuropathy (sensory, motor, and autonomic deficits), ischaemia, or both. The initiating injury may be from acute mechanical or thermal trauma or from repetitively or continuously applied mechanical stress. Patients with clinically significant limb ischaemia should be assessed by a vascular surgeon to determine the need for angioplasty, stenting, or femorodistal bypass. When infection complicates a foot ulcer, the combination can be limb or life-threatening. Infection is defined clinically, but wound cultures reveal the causative pathogens. Tissue specimens are strongly preferred to wound swabs for wound cultures. Antimicrobial therapy should be guided by culture results, and should aim to cure the infection, not to heal the wound. Alleviation of the mechanical load on ulcers (off-loading) should always be a part of treatment. Neuropathic ulcers typically heal in 6 weeks with total contact casting, because it effectively relieves pressure at the ulcer site and enforces patient compliance. The success of other approaches to off-loading similarly depends on the patients' adherence to the effectiveness of pressure relief. Surgery to heal ulcers and prevent recurrence can include tenotomy, tendon lengthening, reconstruction, or removal of bony prominences. However, these procedures may result in secondary ulceration and other complications. Ulcer recurrence rates are high, but appropriate education for patients, the provision of posthealing footwear, and regular foot care can reduce rates of re-ulceration. C1 Cleveland Clin Fdn, Dept Biomed Engn, Diabet Foot Care Program, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Orthopaed Surg, Diabet Foot Care Programme, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Orthopaed Res Ctr, Cleveland, OH 44195 USA. Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA. Univ Washington, Sch Med, VA Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA USA. Univ Birmingham, Dept Vasc Surg, Birmingham, W Midlands, England. Heart England NHS Fdn Trust, Birmingham, W Midlands, England. RP Cavanagh, PR (reprint author), Cleveland Clin Fdn, Dept Biomed Engn, Diabet Foot Care Program, ND20,9500 Euclid Ave, Cleveland, OH 44195 USA. EM cavanap@ccf.org OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 240 TC 169 Z9 178 U1 8 U2 41 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 12 PY 2005 VL 366 IS 9498 BP 1725 EP 1735 DI 10.1016/S0140-6736(05)67699-4 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 983BP UT WOS:000233206400029 PM 16291067 ER PT J AU Barbour, LA Rahman, SM Gurevich, I Leitner, JW Fischer, SJ Roper, MD Knotts, TA Vo, Y McCurdy, CE Yakar, S LeRoith, D Kahn, CR Cantley, LC Friedman, JE Draznin, B AF Barbour, LA Rahman, SM Gurevich, I Leitner, JW Fischer, SJ Roper, MD Knotts, TA Vo, Y McCurdy, CE Yakar, S LeRoith, D Kahn, CR Cantley, LC Friedman, JE Draznin, B TI Increased p85 alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; TRANSGENIC MICE; P85 ALPHA; SUBUNIT; SENSITIVITY; EXPRESSION; INHIBITION; LACKING AB Insulin resistance is a cardinal feature of normal pregnancy and excess growth hormone (GH) states, but its underlying mechanism remains enigmatic. We previously found a significant increase in the p85 regulatory subunit of phosphatidylinositol kinase ( PI3-kinase) and striking decrease in IRS-1-associated PI 3-kinase activity in the skeletal muscle of transgenic animals overexpressing human placental growth hormone. Herein, using transgenic mice bearing deletions in p85 alpha, p85 beta, or insulin-like growth factor-1, we provide novel evidence suggesting that overexpression of p85 alpha is a primary mechanism for skeletal muscle insulin resistance in response to GH. We found that the excess in total p85 was entirely accounted for by an increase in the free p85 alpha-specific isoform. In mice with a liver-specific deletion in insulin-like growth factor-1, excess GH caused insulin resistance and an increase in skeletal muscle p85 alpha, which was completely reversible using a GH-releasing hormone antagonist. To understand the role of p85 alpha in GH-induced insulin resistance, we used mice bearing deletions of the genes coding for p85 alpha or p85 beta, respectively (p85 alpha(+/-) and p85 beta(-/-)). Wild type and p85 beta(-/-) mice developed in vivo insulin resistance and demonstrated overexpression of p85 alpha and reduced insulin-stimulated PI 3-kinase activity in skeletal muscle in response to GH. In contrast, p85 alpha(+/-) mice retained global insulin sensitivity and PI 3-kinase activity associated with reduced p85 alpha expression. These findings demonstrated the importance of increased p85 alpha in mediating skeletal muscle insulin resistance in response to GH and suggested a potential role for reducing p85 alpha as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Vet Affairs Res Serv, Denver, CO 80220 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Childrens Hosp, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Friedman, JE (reprint author), Univ Colorado, Hlth Sci Ctr, Mail Stop 8106,POB 6511, Aurora, CO 80045 USA. EM Jed.Friedman@uchsc.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK062155]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 26 TC 71 Z9 72 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 2005 VL 280 IS 45 BP 37489 EP 37494 DI 10.1074/jbc.M506967200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500025 PM 16166093 ER PT J AU Kang, SH Li, HM Rao, AJ Hogan, PG AF Kang, SH Li, HM Rao, AJ Hogan, PG TI Inhibition of the calcineurin-NFAT interaction by small organic molecules reflects binding at an allosteric site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID QUINOHEMOPROTEIN AMINE DEHYDROGENASE; TYROSINE-PHOSPHATASE 1B; S-TRANSFERASE P1-1; CYCLOSPORINE-A; T-CELLS; TRANSCRIPTION FACTORS; NUCLEAR FACTOR; LYMPHOCYTE-ACTIVATION; SELECTIVE-INHIBITION; SULFUR NUCLEOPHILES AB Transcriptional signaling from the Ca(2+)-calmodulin-activated phosphatase calcineurin to its substrate NFAT ( nuclear factor of activated T cells, also termed NFATc) is critically dependent on a protein-protein docking interaction between calcineurin and the PXIXIT motif in NFAT. Several inhibitors of NFAT-calcineurin association (INCA compounds) prevent binding of NFAT or the peptide ligand PVIVIT to calcineurin. Here we show that the binding site on calcineurin for INCA1, INCA2, and INCA6 is centered on cysteine 266 of calcineurin A alpha and does not coincide with the core PXIXIT-binding site. Although ample evidence indicates that INCA1 and INCA2 react covalently with cysteine 266, covalent derivatization alone is not sufficient for maximal inhibition of the calcineurin-PVIVIT interaction, because the maleimide INCA12 reacts with the same site and produces only very modest inhibition. Thus, inhibition arises through an allosteric change affecting the PXIXIT docking site, which may be assisted by covalent binding but depends on other specific features of the ligand. The spatial arrangement of the binding sites for PVIVIT and INCA makes it probable that the change in conformation involves the beta 11-beta 12 loop of calcineurin. The finding that an allosteric site controls NFAT binding opens new alternatives for inhibition of calcineurin-NFAT signaling. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hogan, PG (reprint author), CBR Inst Biomed Res, 200 Longwood Ave, Boston, MA 02115 USA. EM hogan@cbr.med.harvard.edu FU NIAID NIH HHS [R21 AI059940, R01 AI40127] NR 59 TC 29 Z9 30 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 2005 VL 280 IS 45 BP 37698 EP 37706 DI 10.1074/jbc.M502247200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500047 PM 16148011 ER PT J AU Wang, J Devgan, V Corrado, M Prabhu, NS El-Deiry, WS Riccardi, C Pandolfi, PP Missero, C Dotto, GP AF Wang, J Devgan, V Corrado, M Prabhu, NS El-Deiry, WS Riccardi, C Pandolfi, PP Missero, C Dotto, GP TI Glucocorticoid-induced tumor necrosis factor receptor is a p21(Cip1/WAF1) transcriptional target conferring resistance of keratinocytes to UV light-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; DEATH RECEPTORS; P21(WAF1/CIP1); INDUCTION; GITR; ACTIVATION; LIGAND; GROWTH; TNF; DIFFERENTIATION AB Glucocorticoid-induced tumor necrosis factor receptor ( GITR) is a member of the tumor necrosis factor receptor superfamily, is expressed in T lymphocytes, and exerts an anti-apoptotic function in these cells. We reported that GITR is also highly expressed in the skin, specifically in keratinocytes, and that it is under negative transcriptional control of p21(Cip1/WAF1), independently from the cell cycle. Although GITR expression is higher in p21-deficient keratinocytes and skin, it is down-modulated with differentiation and in response to UVB. The combined analysis of keratinocytes with increased GITR expression versus normal keratinocytes and skin of mice with a disruption of the GITR gene indicates that this protein protects keratinocytes from UVB-induced apoptosis both in vitro and in vivo. C1 Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Telethon Inst Genet & Med, I-80131 Naples, Italy. Univ Penn, Sch Med, Abramson Comprehens Canc Ctr, Philadelphia, PA 19104 USA. Univ Perugia, Sch Med, Pharmacol Sect, Dept Clin & Expt Med, I-06100 Perugia, Italy. Mem Sloan Kettering Canc Ctr, Sloan Kettering Inst, Canc Biol & Genet Program, New York, NY 10021 USA. Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. RP Dotto, GP (reprint author), Univ Lausanne, Dept Biochem, Chemin Boveresses 155, CH-1066 Epalinges, Switzerland. EM gdotto@partners.org RI Riccardi, Carlo/N-4610-2014; OI Riccardi, Carlo/0000-0001-9257-3997; Missero, Caterina/0000-0003-0905-5123 FU NCI NIH HHS [CA16038, CA73796]; NIAMS NIH HHS [AR39190]; Telethon [TGM03P14, TGM06S01] NR 35 TC 21 Z9 21 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 NOV 11 PY 2005 VL 280 IS 45 BP 37725 EP 37731 DI 10.1074/jbc.M507976200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500050 PM 16155000 ER PT J AU Huang, CC Tang, M Zhang, MY Majeed, S Montabana, E Stanfield, RL Dimitrov, DS Korber, B Sodroski, J Wilson, IA Wyatt, R Kwong, PD AF Huang, CC Tang, M Zhang, MY Majeed, S Montabana, E Stanfield, RL Dimitrov, DS Korber, B Sodroski, J Wilson, IA Wyatt, R Kwong, PD TI Structure of a V3-containing HIV-1 gp120 core SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; V3 LOOP; CRYSTAL-STRUCTURE; TYPE-1; RECEPTOR; ANTIBODY; BINDING; NEUTRALIZATION AB The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization. C1 NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. EM richw@mail.nih.gov; pdkwong@nih.gov FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [AI39429, AI24755, AI31783, AI40895]; NIGMS NIH HHS [GM46192] NR 35 TC 516 Z9 533 U1 1 U2 38 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 2005 VL 310 IS 5750 BP 1025 EP 1028 DI 10.1126/science.1118398 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984YN UT WOS:000233343400046 PM 16284180 ER PT J AU Liu, XH Aksan, A Menze, MA Hand, SC Toner, M AF Liu, XH Aksan, A Menze, MA Hand, SC Toner, M TI Trehalose loading through the mitochondrial permeability transition pore enhances desiccation tolerance in rat liver mitochondria SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE trehalose; desiccation; mitochondria; permeabilization; mitochondrial membrane potential; mitochondrial permeability transition pore ID INTRACELLULAR TREHALOSE; MAMMALIAN-CELLS; VITRIFICATION; JC-1; ANHYDROBIOSIS; HETEROGENEITY; STABILITY; MEMBRANES; IMPROVES; SUCROSE AB Trehalose has extensively been used to improve the desiccation tolerance of mammalian cells. To test whether trehalose improves desiccation tolerance of mammalian mitochondria, we introduced trehalose into the matrix of isolated rat liver mitochondria by reversibly permeabilizing the inner membrane using the mitochondrial permeability transition pore (MPTP). Measurement of the trehalose concentration inside mitochondria using high performance liquid chromatography showed that the sugar permeated rapidly into the matrix upon opening the MPTP. The concentration of intra-matrix trehalose reached 0.29 mmol/mg protein (similar to 190 mM) in 5 min. Mitochondria, with and without trehalose loaded into the matrix, were desiccated in a buffer containing 0.25 M trehalose by diffusive drying. After re-hydration, the inner membrane integrity was assessed by measurement of mitochondrial membrane potential with the fluorescent probe JC-1. The results showed that following drying to similar water contents, the mitochondria loaded with trehalose had significantly higher inner membrane integrity than those without trehalose loading. These findings suggest the presence of trehalose in the mitochondrial matrix affords improved desiccation tolerance to the isolated mitochondria. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. RP Toner, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med & Surg Serv, 51 Blossom St, Boston, MA 02114 USA. EM mtoner@sbi.org RI Aksan, Alptekin/A-7187-2008; Aksan, Alptekin/C-1579-2014; OI Aksan, Alptekin/0000-0001-9891-1715; Menze, Michael/0000-0003-1072-5462 FU NIGMS NIH HHS [GM71345] NR 34 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD NOV 10 PY 2005 VL 1717 IS 1 BP 21 EP 26 DI 10.1016/j.bbamem.2005.09.012 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 990AB UT WOS:000233714500003 PM 16242115 ER PT J AU Alencar, H King, R Funovics, M Stout, C Weissleder, R Mahmood, U AF Alencar, H King, R Funovics, M Stout, C Weissleder, R Mahmood, U TI A novel mouse model for segmental orthotopic colon cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colon cancer; mouse model; colonoscopy; magnetic resonance imaging ID MULTIPLE INTESTINAL NEOPLASIA; COLORECTAL-CANCER; CARCINOMA CELLS; MICE; MUTATION; GROWTH; TUMORS; SITE AB Spontaneous colon tumor mouse strains offer numerous advantages in modeling disease. However, the wide temporal window in which lesions form and the stochastic nature of lesion location require larger cohorts for assessment of disease modulation. Reliable, reproducible and inexpensive mouse models of early-stage and invasive cancer would add to existing transgenic models. We show a new method for the creation of orthotopic murine tumors centered in the mucosal and submucosal layers anywhere in the colon, allowing creation of lesions of known age, location and extent. The system overcomes the disadvantages of heterotopic implantation and allows evaluation of lesions distally in the colon as well as proximally, thereby providing an additional method to study the effects of regionality. Invasion, host vascularization and application to disparate cell lines are demonstrated. Noninvasive imaging with magnetic resonance and colonoscopy, allowed in part by the tumor location, show potential applications of this approach. C1 Harvard Univ, Sch Med, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Ctr Mol Imaging Res, Massachusetts Gen Hosp, Bldg 149,13th St,5408, Charlestown, MA 02129 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [R24-CA92782, T32-CA79443]; NIBIB NIH HHS [EB001872] NR 22 TC 22 Z9 25 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 10 PY 2005 VL 117 IS 3 BP 335 EP 339 DI 10.1002/ijc.21185 PG 5 WC Oncology SC Oncology GA 971UW UT WOS:000232411300001 PM 15900588 ER PT J AU Lee, AK D'Amico, AV AF Lee, AK D'Amico, AV TI Utility of prostate-specific antigen kinetics in addition to clinical factors in the selection of patients for salvage local therapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Multidisciplinary Prostate Cancer Symposium CY FEB 17-19, 2005 CL Orlando, FL SP Amer Soc Clin Oncol, Amer Soc Therapeut Radiol & Oncol, Amer Soc Urol Oncol, Prostate Canc Fdn ID RADICAL PROSTATECTOMY; RADIATION-THERAPY; PSA VELOCITY; CANCER; RADIOTHERAPY; PROGRESSION; PREDICTORS; RECURRENCE; RISK; GUIDELINES AB A detectable and rising prostate-specific antigen (PSA) level after radical prostatectomy or a rising PSA above the nadir value after radiation therapy may represent a local failure, distant failure, or both. Determining the site or sites of failure is critical for selecting the appropriate salvage therapy. Nevertheless, although PSA failure precedes clinically evident failure by several years, determining the source of the biochemical failure is often not possible using currently available diagnostic studies. Selecting the optimal therapeutic approach may be guided by the initial clinical factors (eg, T-category, PSA, biopsy Gleason score). If the patient has had a radical prostatectomy, then the pathologic outcomes of the surgery (eg, pathologic T-category and prostatectomy Gleason score, nodal and margin status) may provide further information. Beyond pretreatment clinical and post-treatment pathologic factors, PSA kinetics, and specifically a pretreatment PSA velocity > 2 ng/mL/year, an interval to PSA failure < 3 years and a post-treatment PSA doubling time < 3 months place a man at increased risk for metastases and subsequent prostate cancer-specific mortality, making these men poor candidates for local-only salvage therapy. Therefore, the optimal candidate for local-only salvage therapy is a man whose pretreatment PSA velocity was 2 ng/mL/year or less, interval to PSA failure exceeds 3 years, and post-treatment PSA doubling time is at least 12 months, and who did not have biopsy or prostatectomy Gleason score of 8 to 10 or seminal vesicle or lymph node involvement. C1 Univ Texas, MD Anderson Canc Ctr, Unit 1202, Houston, TX 77030 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lee, AK (reprint author), Univ Texas, MD Anderson Canc Ctr, Unit 1202, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM aklee@mdanderson.org NR 21 TC 43 Z9 44 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 NOV 10 PY 2005 VL 23 IS 32 BP 8192 EP 8197 DI 10.1200/JCO.2005.03.007 PG 6 WC Oncology SC Oncology GA 984NQ UT WOS:000233312000009 PM 16278472 ER PT J AU Michaelson, MD Smith, MR AF Michaelson, MD Smith, MR TI Bisphosphonates for treatment and prevention of bone metastases SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Multidisciplinary Prostate Cancer Symposium CY FEB 17-19, 2005 CL Orlando, FL SP Amer Soc Clin Oncol, Amer Soc Therapeut Radiol & Oncol, Amer Soc Urol Oncol, Prostate Canc Fdn ID PROSTATE-CANCER; ZOLEDRONIC ACID; DOUBLE-BLIND; SKELETAL COMPLICATIONS; AVASCULAR NECROSIS; MULTIPLE-MYELOMA; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; BREAST-CANCER; SOLID TUMORS AB Bone metastases are a major cause of morbidity for men with prostate cancer. Complications of bone metastases include pain, fractures, and spinal cord compression. Although they appear osteoblastic by radiographic imaging, most bone metastases are characterized by excess osteoclast number and activity. In addition, pathologic osteoclast activation is associated with increased risk of skeletal complications. Zoledronic acid, a potent inhibitor of osteoclast activity, differentiation, and survival, decreases the risk of skeletal complications in men with androgen-independent prostate cancer and bone metastases. Other bisphosphonates, including pamidronate and clodronate, seem to be ineffective in this setting. The reduction in risk of skeletal complications with zoledronic acid must be weighed against potential adverse effects. Additional studies are needed to determine the optimal timing, schedule, and duration of treatment in men with bone metastases as well as the potential role of bisphosphonates in other settings including the prevention of bone metastases. C1 Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu OI Michaelson, Dror/0000-0001-9249-6338 NR 23 TC 88 Z9 90 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 NOV 10 PY 2005 VL 23 IS 32 BP 8219 EP 8224 DI 10.1200/JCO.2005.02.9579 PG 6 WC Oncology SC Oncology GA 984NQ UT WOS:000233312000013 PM 16278476 ER PT J AU Smirnakis, SM Schmid, MC Brewer, AA Tolias, AS Schuz, A Augath, M Inhoffen, W Wandell, BA Logothetis, NK AF Smirnakis, SM Schmid, MC Brewer, AA Tolias, AS Schuz, A Augath, M Inhoffen, W Wandell, BA Logothetis, NK TI Neuroscience - Rewiring the adult brain - Reply SO NATURE LA English DT Editorial Material ID PERCEPTUAL FILLING-IN; PRIMARY VISUAL-CORTEX; CORTICAL REORGANIZATION; MACULAR DEGENERATION; MONKEY; SCOTOMA; LESIONS; FMRI C1 Stanford Univ, Program Neurosci, Stanford, CA 94305 USA. Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Boston, MA 02114 USA. Univ Tubingen, Dept Ophthalmol 1, D-72076 Tubingen, Germany. RP Smirnakis, SM (reprint author), Stanford Univ, Program Neurosci, Stanford, CA 94305 USA. EM smsmirnakis@partners.org RI Schmid, Michael/G-1867-2010 OI Schmid, Michael/0000-0003-1424-130X NR 15 TC 3 Z9 3 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 10 PY 2005 VL 438 IS 7065 BP E3 EP E4 DI 10.1038/nature04360 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 982BV UT WOS:000233133500038 ER PT J AU Mellinghoff, IK Wang, MY Vivanco, I Haas-Kogan, DA Zhu, SJ Dia, EQ Lu, KV Yoshimoto, K Huang, JHY Chute, DJ Riggs, BL Horvath, S Liau, LM Cavenee, WK Rao, PN Beroukhim, R Peck, TC Lee, JC Sellers, WR Stokoe, D Prados, M Cloughesy, TF Sawyers, CL Mischel, PS AF Mellinghoff, IK Wang, MY Vivanco, I Haas-Kogan, DA Zhu, SJ Dia, EQ Lu, KV Yoshimoto, K Huang, JHY Chute, DJ Riggs, BL Horvath, S Liau, LM Cavenee, WK Rao, PN Beroukhim, R Peck, TC Lee, JC Sellers, WR Stokoe, D Prados, M Cloughesy, TF Sawyers, CL Mischel, PS TI Molecular determinants of the response of glioblastomas to EGFR kinase inhibitors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; PHASE-II TRIAL; FACTOR-RECEPTOR; HUMAN GLIOMAS; ANAPLASTIC ASTROCYTOMA; PROSTATE-CANCER AB BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, or mutated in glioblastomas, but only 10 to 20 percent of patients have a response to EGFR kinase inhibitors. The mechanism of responsiveness of glioblastomas to these inhibitors is unknown. METHODS: We sequenced kinase domains in the EGFR and human EGFR type 2 (Her2/neu) genes and analyzed the expression of EGFR, EGFR deletion mutant variant III (EGFRvIII), and the tumor-suppressor protein PTEN in recurrent malignant gliomas from patients who had received EGFR kinase inhibitors. We determined the molecular correlates of clinical response, validated them in an independent data set, and identified effects of the molecular abnormalities in vitro. RESULTS: Of 49 patients with recurrent malignant glioma who were treated with EGFR kinase inhibitors, 9 had tumor shrinkage of at least 25 percent. Pretreatment tissue was available for molecular analysis from 26 patients, 7 of whom had had a response and 19 of whom had rapid progression during therapy. No mutations in EGFR or Her2/neu kinase domains were detected in the tumors. Coexpression of EGFRvIII and PTEN was significantly associated with a clinical response (P<0.001; odds ratio, 51; 95 percent confidence interval, 4 to 669). These findings were validated in 33 patients who received similar treatment for glioblastoma at a different institution (P=0.001; odds ratio, 40; 95 percent confidence interval, 3 to 468). In vitro, coexpression of EGFRvIII and PTEN sensitized glioblastoma cells to erlotinib. CONCLUSIONS: Coexpression of EGFRvIII and PTEN by glioblastoma cells is associated with responsiveness to EGFR kinase inhibitors. C1 Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Mol & Med Pharmacol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Human Genet, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Biostat, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurosurg, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Henry E Singleton Brain Tumor Program, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Howard Hughes Med Inst, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Diego, Ludwig Inst Canc Res, San Diego, CA 92103 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Broad Inst, Boston, MA 02115 USA. MIT, Boston, MA USA. RP Mischel, PS (reprint author), Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Ctr Hlth Sci, 10833 Le Conte Ave,Room 13-321, Los Angeles, CA 90095 USA. EM pmischel@mednet.ucla.edu RI Sawyers, Charles/G-5327-2016 FU NCI NIH HHS [T32 CA009172, 5T32CA09056, CA097257, CA105695, CA108633, CA62399, CA95616]; NIGMS NIH HHS [5F31GM067600]; NINDS NIH HHS [NS050151, NS43147] NR 51 TC 923 Z9 961 U1 8 U2 49 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 10 PY 2005 VL 353 IS 19 BP 2012 EP 2024 DI 10.1056/NEJMoa051918 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 981WV UT WOS:000233119600006 PM 16282176 ER PT J AU Sheridan, RL Liu, V Anupindi, S AF Sheridan, RL Liu, V Anupindi, S TI A 10-year-old girl with a bullous skin eruption and acute respiratory failure - Toxic epidermal necrolysis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID STEVENS-JOHNSON-SYNDROME; ERYTHEMA MULTIFORME; BURNED CHILDREN; INTRAVENOUS IMMUNOGLOBULIN; MANIFESTATIONS; MANAGEMENT; MORTALITY; SPECTRUM C1 Shriners Hosp Children, Burn Surg Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Div Burns, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Sheridan, RL (reprint author), Shriners Hosp Children, Burn Surg Serv, Boston, MA 02114 USA. NR 33 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 10 PY 2005 VL 353 IS 19 BP 2057 EP 2066 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 981WV UT WOS:000233119600012 PM 16282181 ER PT J AU Kachroo, A Orlando, LR Grandy, DK Chen, JF Young, AB Schwarzschild, MA AF Kachroo, A Orlando, LR Grandy, DK Chen, JF Young, AB Schwarzschild, MA TI Interactions between metabotropic glutamate 5 and adenosine A(2A) receptors in normal and parkinsonian mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE metabotropic; adenosine; Parkinson's disease; knock-out; locomotion; G-protein-coupled receptor ID A(2A) RECEPTORS; DOPAMINE-D-2 RECEPTORS; MEDIATED MODULATION; LOCOMOTOR-ACTIVITY; MGLU5 RECEPTORS; RAT STRIATUM; ANTAGONIST; MPEP; DISEASE; SENSITIZATION AB Evidence for heteromeric receptor complexes comprising adenosine A(2A) and metabotropic glutamate 5 ( mGlu5) receptors in striatum has raised the possibility of synergistic interactions between striatal A2A and mGlu5 receptors. We investigated the role of striatal A2A receptors in the locomotor stimulant and antiparkinsonian properties of mGlu5 antagonists using complementary pharmacologic and genetic approaches. Locomotion acutely stimulated by the mGlu5 antagonist [2- methyl-6-( phenylethynyl)-pyridine (MPEP)] was absent in mGlu5 knock-out (KO) mice and was potentiated by an A(2A) antagonist KW-6002 [(E)-1,3-diethyl-8-(3,4-dimethoxystyryl)-7methylxanthine], both in normal and in dopamine-depleted (reserpinized) mice. Conversely, the MPEP-induced motor response was markedly attenuated in single and doubleA2A and D2 receptorKOmice. In contrast, motor stimulation by aD1 dopamine agonist was not attenuated in the KO mice. The A(2A) receptor dependence of MPEP- induced motor stimulation was investigated further using a postnatal forebrain- specific conditional ( Cre/ loxP system) KO of the A(2A) receptor. MPEP loses the ability to stimulate locomotion in conditional KO mice, suggesting that this mGlu5 antagonist effect requires the postdevelopmental action of striatal A(2A) receptors. The potentiation of mGlu5 antagonist-induced motor stimulation by an A(2A) antagonist and its dependence on both D-2 and forebrain A(2A) receptors highlight the functional interdependence of these receptors. These data also strengthen a rationale for pursuing a combinational drug strategy for enhancing the antiparkinsonian effects of A(2A) and mGlu5 antagonists. C1 Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02129 USA. Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Schwarzschild, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Room 2900,114 16th St, Boston, MA 02129 USA. EM michaels@helix.mgh.harvard.edu FU PHS HHS [010804, 041083] NR 35 TC 95 Z9 97 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 9 PY 2005 VL 25 IS 45 BP 10414 EP 10419 DI 10.1523/JNEUROSCI.3660-05.2005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 982DB UT WOS:000233137000014 PM 16280580 ER PT J AU Choi, Y Borghesani, PR Chan, JA Segal, RA AF Choi, Y Borghesani, PR Chan, JA Segal, RA TI Migration from a mitogenic niche promotes cell-cycle exit SO JOURNAL OF NEUROSCIENCE LA English DT Article DE proliferation; BDNF; cerebellum; granule cells; Sonic Hedgehog; microenvironment ID CEREBELLAR GRANULE NEURONS; SONIC HEDGEHOG; NEUROTROPHIC FACTOR; MICE LACKING; PRECURSOR PROLIFERATION; MOUSE CEREBELLUM; DIFFERENTIATION; MECHANISMS; RECEPTOR; GROWTH AB During development, neural precursors proliferate in one location and migrate to the residence of their mature function. The transition from a proliferative stage to a migratory stage is a critical juncture; errors in this process may result in tumor formation, mental retardation, or epilepsy. This transition could be the result of a simple sequential process in which precursors exit the cell cycle and then begin to migrate or a dynamically regulated process in which migration away from a mitogenic niche induces precursors to exit the cell cycle. Here, we show, using in vivo and in vitro approaches, that granule cell precursors proliferate when they are exposed to the microenvironment of the external granule cell layer (EGL) and exit the cell cycle as a result of migrating away from this environment. In vivo, granule cell precursors that remain in the EGL because of impaired migration continue to proliferate in the mitogenic niche of the EGL. In vitro, granule cell precursors that are introduced into an organotypic cerebellar slice proliferate preferentially in the EGL. We identify Sonic Hedgehog as a critical component of the EGL mitogenic niche. Together, these data indicate that migration away from a mitogenic niche promotes transition from a proliferative to a nonproliferative, migratory stage. C1 Brigham & Womens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurobiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Segal, RA (reprint author), Brigham & Womens Hosp, Dept Pediat Oncol, Dana Farber Canc Inst, Dana 620,44 Binney St, Boston, MA 02115 USA. EM rosalind_segal@dfci.harvard.edu FU NINDS NIH HHS [NS 37757] NR 38 TC 29 Z9 31 U1 1 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 9 PY 2005 VL 25 IS 45 BP 10437 EP 10445 DI 10.1523/JNEUROSCI.1559-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 982DB UT WOS:000233137000016 PM 16280582 ER PT J AU Wu, WS Heinrichs, S Xu, D Garrison, SP Zambetti, GP Adams, JM Look, AT AF Wu, WS Heinrichs, S Xu, D Garrison, SP Zambetti, GP Adams, JM Look, AT TI Slug antagonizes p53-mediated apoptosis of hematopoietic progenitors by repressing puma SO CELL LA English DT Article ID TRANSCRIPTION FACTORS SNAIL; COLORECTAL-CANCER CELLS; ZINC-FINGER PROTEIN; RADIATION-THERAPY; BREAST-CANCER; BCL-2 FAMILY; C-ELEGANS; P53; EXPRESSION; GENE AB In response to DNA damage, the p53 tumor suppressor can elicit either apoptosis or cell-cycle arrest and repair, but how this critical decision is made in specific cell types remains largely undefined. We investigated the mechanism by which the transcriptional repressor Slug specifically rescues hematopoietic progenitor cells from lethal doses of gamma radiation. We show that Slug is transcriptionally induced by p53 upon irradiation and then protects the damaged cell from apoptosis by directly repressing p53-mediated transcription of puma, a key BH3-only antagonist of the antiapoptotic Bcl-2 proteins. We established the physiologic significance of Slug-mediated repression of puma by demonstrating that mice deficient in both genes survive doses of total-body irradiation that lethally deplete hematopoietic progenitor populations in mice lacking only slug. Thus, Slug functions downstream of p53 in developing blood cells as a critical switch that prevents their apoptosis by antagonizing the trans-activation of puma by p53. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. Walter & Eliza Hall Inst Med Res, Parkville, Vic 3050, Australia. RP Look, AT (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu RI Adams, Jerry/E-1199-2013; Wu, Wen-Shu/I-1258-2014 OI Wu, Wen-Shu/0000-0002-0225-2522 FU NCI NIH HHS [CA-059571, CA103726] NR 40 TC 246 Z9 271 U1 0 U2 11 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 8 PY 2005 VL 123 IS 4 BP 641 EP 653 DI 10.1016/j.cell.2005.09.029 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 987DA UT WOS:000233497400013 PM 16286009 ER PT J AU Irizarry, MC Gurol, ME Raju, S Diaz-Arrastia, R Locascio, JJ Tennis, M Hyman, BT Growdon, JH Greenberg, SM Bottiglieri, T AF Irizarry, MC Gurol, ME Raju, S Diaz-Arrastia, R Locascio, JJ Tennis, M Hyman, BT Growdon, JH Greenberg, SM Bottiglieri, T TI Association of homocysteine with plasma amyloid beta protein in aging and neurodegenerative disease SO NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; PARKINSON-DISEASE; COGNITIVE IMPAIRMENT; CLINICAL-DIAGNOSIS; VASCULAR-DISEASE; OXIDATIVE STRESS; ELDERLY SUBJECTS; L-DOPA AB Background: Elevated plasma total homocysteine (tHcy) is a risk factor for cardiovascular disease and is reported to be an independent risk factor for Alzheimer disease (AD) and cognitive decline. tHcy may potentiate neurotoxic and vasculopathic processes, including amyloid beta protein (A beta) metabolism, implicated in neurodegenerative diseases. Objective: To examine the relationship of plasma total tHcy levels with clinical, demographic, biochemical, and genetic factors in aging, mild cognitive impairment (MCI), AD, cerebral amyloid angiopathy (CAA), and Parkinson disease (PD). Methods: Plasma tHcy, folate, vitamin B-12, creatinine, and A beta levels were assessed in individuals evaluated in the Memory, Stroke, and Movement Disorders Units of Massachusetts General Hospital with diagnoses of AD (n = 145), MCI (n = 47), PD (n = 93), CAA (67), hypertensive intracerebral hemorrhage (hICH) (n = 25), and no dementia (n = 88). Results: The tHcy levels did not differ across AD, MCI, CAA, hICH, and nondemented control subjects but were increased in the PD group (p < 0.01). The elevated levels within the PD group were due to high tHcy in individuals taking levodopa (p < 0.0001). Increasing tHcy was associated with worse cognition in the PD cases, but not the other diagnostic groups. tHcy levels positively correlated with plasma A beta levels even after adjustments for age and creatinine (p < 0.0001). Conclusions: Mean tHcy levels increased with age but did not discriminate diagnostic groups aside from significant elevation in patients with PD taking levodopa. The positive association between tHcy and plasma A beta levels raises the possibility that these circulating factors could interact to affect AD risk and cognition in PD. C1 Massachusetts Gen Hosp, Massachusetts Alzheimer Dis Res Ctr, Boston, MA 02114 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75230 USA. Baylor Inst Metab Dis, Dallas, TX USA. RP Irizarry, MC (reprint author), Massachusetts Gen Hosp E, Alzheimers Dis Res Unit, Ctr Aging Genet, Bldg 114,Room 2010,114 16th St, Charlestown, MA 02129 USA. EM mirizarry@partners.org RI Gurol, Edip/J-2279-2014 OI Gurol, Edip/0000-0002-2169-4457 FU NIA NIH HHS [AG05134, AG17861]; NINDS NIH HHS [1T32NS048005-01] NR 55 TC 77 Z9 82 U1 3 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 8 PY 2005 VL 65 IS 9 BP 1402 EP 1408 DI 10.1212/01.wnl.0000183063.99107.5c PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 981US UT WOS:000233114100013 PM 16275827 ER PT J AU An, JH Vranas, K Lucke, M Inoue, H Hisamoto, N Matsumoto, K Blackwell, TK AF An, JH Vranas, K Lucke, M Inoue, H Hisamoto, N Matsumoto, K Blackwell, TK TI Regulation of the Caenorhabditis elegans oxidative stress defense protein SKN-1 by glycogen synthase kinase-3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE longevity; p38 mitogen-activated protein kinase; stress response; phase II gene ID C-ELEGANS; GENE; NRF2; TRANSCRIPTION; KEAP1; CELL; ACTIVATION; MECHANISM; PATHWAY; ELEMENT AB Oxidative stress plays a central role in many human diseases and in aging. In Caenorhabditis elegans the SKN-1 protein induces phase II detoxification gene transcription, a conserved oxidative stress response, and is required for oxidative stress resistance and longevity. Oxidative stress induces SKN-1 to accumulate in intestinal nuclei, depending on p38 mitogen-activated protein kinase signaling. Here we show that, in the absence of stress, phosphorylation by glycogen synthase kinase-3 (GSK-3) prevents SKN-1 from accumulating in nuclei and functioning constitutively in the intestine. GSK-3 sites are conserved in mammalian SKN-1 orthologs, indicating that this level of regulation may be conserved. If inhibition by GSK-3 is blocked, background levels of p38 signaling are still required for SKN-1 function. WT and constitutively nuclear SKN-1 comparably rescue the skn-1 oxidative stress sensitivity, suggesting that an inducible phase II response may provide optimal stress protection. We conclude that (i) GSK-3 inhibits SKN-1 activity in the intestine, (h) the phase 11 response integrates multiple regulatory signals, and (fit), by inhibiting this response, GSK-3 may influence redox conditions. C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Nagoya Univ, Grad Sch Sci, Div Biol Sci, Chikusa Ku, Nagoya, Aichi 4648602, Japan. RP Blackwell, TK (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu FU NIGMS NIH HHS [GM62891, R01 GM062891] NR 32 TC 100 Z9 107 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2005 VL 102 IS 45 BP 16275 EP 16280 DI 10.1073/pnas.0508105102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700028 PM 16251270 ER PT J AU Albertson, RC Streelman, JT Kocher, TD Yelick, PC AF Albertson, RC Streelman, JT Kocher, TD Yelick, PC TI Integration and evolution of the cichlid mandible: The molecular basis of alternate feeding strategies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE adaptive radiation; bmp4; jaw shape; morphological integration ID DWELLING HAPLOCHROMINES PISCES; LAKE VICTORIA; DEVELOPMENTAL INTEGRATION; PHENOTYPIC PLASTICITY; FUNCTIONAL-MORPHOLOGY; LABRID FISHES; JAW JOINT; ZEBRAFISH; BMP4; PERCIFORMES AB African cichlid fishes have repeatedly evolved highly specialized modes of feeding through adaptations of their oral jaws. Here, we explore the molecular genetic basis of the opening and closing lever mechanisms of the cichlid lower jaw, which have traditionally been used to describe the mechanics of feeding behavior in bony fishes. Quantitative genetic analyses demonstrate that the opening and closing mechanisms are genetically modular and therefore free to evolve independently. Bmp4 (bone morphogenetic protein 4) is one of two loci that segregate with the mechanical advantage of closing and that together account for > 30% of the phenotypic variance in this trait. Species-specific differences in jaw shape are obvious early in cichlid larval development and are correlated with patterns of bmp4 expression in the mandibular primordium. When bmp4 is overexpressed in the obligate suction feeder Danio rerio, mandibular morphology exhibits specific transformations of opening and closing lever ratios. We conclude that patterns of morphological integration of the cichlid jaw reflect a balance among conflicting functional demands. Further, we demonstrate that bmp4 has the potential to alter mandibular morphology in a way that mimics adaptive variation among fish species. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. Univ New Hampshire, Hubbard Ctr Genome Studies, Durham, NH 03824 USA. RP Albertson, RC (reprint author), Forsyth Inst, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. EM calbertson@forsyth.org RI Kocher, Thomas/B-3089-2013 FU NIDCR NIH HHS [R03 DE014446] NR 56 TC 173 Z9 175 U1 5 U2 47 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2005 VL 102 IS 45 BP 16287 EP 16292 DI 10.1073/pnas.0506649102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700030 PM 16251275 ER PT J AU Lee, JG Dahi, S Mahimkar, R Tulloch, NL Alfonso-Jaume, MA Lovett, DH Sarkar, R AF Lee, JG Dahi, S Mahimkar, R Tulloch, NL Alfonso-Jaume, MA Lovett, DH Sarkar, R TI Intronic regulation of matrix metalloproteinase-2 revealed by in vivo transcriptional analysis in ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE angiogenesis; gelatinase; gene expression; skeletal muscle; transcription factor ID SKELETAL-MUSCLE; HINDLIMB ISCHEMIA; MEMBRANE TYPE-1; GENE-EXPRESSION; NUCLEAR FACTOR; C-JUN; CELLS; ANGIOGENESIS; YB-1; FOS AB Matrix metalloproteinase-2 (MMP-2) plays an essential role in angiogenesis and arteriogenesis, two processes critical to restoration of tissue perfusion after ischemia. MMP-2 expression is increased in tissue ischemia, but the responsible mechanisms remain unknown. We studied the transcriptional activation of the MMP-2 gene in a model of hindlimb ischemia by using various MMP-2-lacZ reporter mice and chromatin immunoprecipitation. MMP-2 activity and mRNA were increased after hindlimb ischemia. Mice with targeted deletion of MMP-2 had impaired restoration of perfusion and a high incidence of limb gangrene, indicating that MMP-2 plays a critical role in ischemia-induced revascularization. Ischemia induced the expression and binding of c-Fos, c-Jun, JunB, FosB, and Fra2 to a noncanonical activating protein-1 (AP-1) site present in the MMP-2 promoter and decreased binding of the transcriptional repressor JunD. Ischemia also activated the expression and binding of p53 to an adjacent enhancer site (RE-1) and increased expression and binding of nuclear factor of activated T-cells-c2 to consensus sequences within the first intron. Deletion of either the 5' AP-1/RE-1 region of the promoter or substitution of the first intron abolished ischemia-induced MMP-2 transcription in vivo. Thus, AP-1 transcription factors and intronic activation by nuclear factor of activated T-cells-c2 act in concert to drive ischemia-induced MMP-2 transcription. These findings define a critical role for MMP-2 in ischemia-induced revascularization and identify both previously uncharacterized regulatory elements within the MMP-2 gene and the cognate transcription factors required for MMP-2 activation in vivo after tissue ischemia. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Vasc Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Pacific Vasc Res Lab, San Francisco, CA 94121 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Div Nephrol, San Francisco, CA 94121 USA. RP Sarkar, R (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Div Vasc Surg, San Francisco, CA 94121 USA. EM sarkarr@surgery.ucsf.edu FU NHLBI NIH HHS [P01 HL068738, K08 HL004435, P01 HL 68738] NR 37 TC 36 Z9 36 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2005 VL 102 IS 45 BP 16345 EP 16350 DI 10.1073/pnas.0508085102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700040 PM 16258061 ER PT J AU Wang, PY Koishi, K McGeachie, AB Kimber, M MacLaughlin, DT Donahoe, PK McLennan, IS AF Wang, PY Koishi, K McGeachie, AB Kimber, M MacLaughlin, DT Donahoe, PK McLennan, IS TI Mullerian inhibiting substance acts as a motor neuron survival factor in vitro SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Mullerian Inhibiting Substance type II receptor ID AMYOTROPHIC-LATERAL-SCLEROSIS; ENHANCED PURIFICATION; TRANSDUCTION PATHWAY; NEUROTROPHIC FACTOR; NERVE INJURY; MOTONEURONS; HORMONE; RECEPTOR; EXPRESSION; DEATH AB The survival of motor neurons is controlled by multiple factors that regulate different aspects of their physiology. The identification of these factors is important because of their relationship to motor neuron disease. We investigate here whether Mullerian Inhibiting Substance (MIS) is a motor neuron survival factor. We find that motor neurons from adult mice synthesize MIS and express its receptors, suggesting that mature motor neurons use MIS in an autocrine fashion or as a way to communicate with each other. MIS was observed to support the survival and differentiation of embryonic motor neurons in vitro. During development, male-specific MIS may have a hormone effect because the blood-brain barrier has yet to form, raising the possibility that MIS participates in generating sex-specific differences in motor neurons. C1 Univ Otago, Dept Anat & Struct Biol, Neuromuscular Res Grp, Dunedin, New Zealand. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. RP Univ Otago, Dept Anat & Struct Biol, Neuromuscular Res Grp, POB 913, Dunedin, New Zealand. EM pdonahoe@partners.org OI WANG, PEI-YU/0000-0002-1792-8935 FU NCI NIH HHS [CA 17393, R01 CA017393]; NICHD NIH HHS [HD 32113] NR 36 TC 50 Z9 52 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2005 VL 102 IS 45 BP 16421 EP 16425 DI 10.1073/pnas.0508304102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700053 PM 16260730 ER PT J AU Meeren, HKM van Heijnsbergen, CCRJ de Gelder, B AF Meeren, HKM van Heijnsbergen, CCRJ de Gelder, B TI Rapid perceptual integration of facial expression and emotional body language SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE emotion communication; event-related potentials; visual perception ID TIME-COURSE; SELECTIVE ATTENTION; CAPTURE ATTENTION; FACE RECOGNITION; VISUAL-CORTEX; RESPONSES; AMYGDALA; NEURONS; UPRIGHT; HUMANS AB In our natural world, a face is usually encountered not as an isolated object but as an integrated part of a whole body. The face and the body both normally contribute in conveying the emotional state of the individual. Here we show that observers judging a facial expression are strongly influenced by emotional body language. Photographs of fearful and angry faces and bodies were used to create face-body compound images, with either matched or mismatched emotional expressions. When face and body convey conflicting emotional information, judgment of facial expression is hampered and becomes biased toward the emotion expressed by the body. Electrical brain activity was recorded from the scalp while subjects attended to the face and judged its emotional expression. An enhancement of the occipital P1 component as early as 115 ms after presentation onset points to the existence of a rapid neural mechanism sensitive to the degree of agreement between simultaneously presented facial and bodily emotional expressions, even when the latter are unattended. C1 Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. FC Donders Ctr Cognit Neuroimaging, NL-6500 HB Nijmegen, Netherlands. Harvard Univ, Sch Med, Athinoula A Martinos Ctr Biomed Imaging, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP de Gelder, B (reprint author), Tilburg Univ, Cognit & Affect Neurosci Lab, NL-5000 LE Tilburg, Netherlands. EM degelder@uvt.nl NR 48 TC 244 Z9 250 U1 7 U2 50 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 8 PY 2005 VL 102 IS 45 BP 16518 EP 16523 DI 10.1073/pnas.0507650102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700070 PM 16260734 ER PT J AU Zhang, H Hoffmann, F He, J He, X Kankasa, C Ruprecht, R West, JT Orti, G Wood, C AF Zhang, H Hoffmann, F He, J He, X Kankasa, C Ruprecht, R West, JT Orti, G Wood, C TI Evolution of subtype CHIV-1 Env in a slowly progressing Zambian infant SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; VERTICAL TRANSMISSION; HIV TYPE-1; DISEASE PROGRESSION; PERINATAL TRANSMISSION; CORECEPTOR USAGE; SEQUENCE VARIABILITY; REPLICATION CAPACITY; GENETIC DIVERSITY AB Background: Given the high prevalence of mother to child infection, the development of a better understanding of African subtype C HIV-1 transmission and natural evolution is of significant importance. In this study, we genotypically and phenotypically characterized subtype C viruses isolated over a 67-month follow-up period from an in utero-infected Zambian infant. Changes in genotype and phenotype were correlated to alterations of the host humoral immune response. Results: A comparison of baseline maternal and infant samples indicated that the infant sequences are monophyletic and contain a fraction of the diversity observed in the mother. This finding suggests that selective transmission occurred from mother to child. Peaks in infant HIV-1 Env genetic diversity and divergence were noted at 48 months, but were not correlated with changes in co-receptor usage or syncytia phenotype. Phylogenetic analyses revealed an accumulation of mutations over time, as well as the reappearance of ancestral lineages. In the infant C2-V4 region of Env, neither the median number of putative N-glycosylation sites or median sequence length showed consistent increases over time. The infant possessed neutralizing antibodies at birth, but these decreased in effectiveness or quantity with time. De novo humoral responses were detected in the child after 12 months, and corresponded with an increase in Env diversity. Conclusion: Our study demonstrates a correlation between HIV-1 Env evolution and the humoral immune response. There was an increase in genetic diversification in the infant viral sequences after 12 months, which coincided with increases in neutralizing antibody titers. In addition, episodes of viral growth and successive immune reactions in the first 5 - 6 years were observed in this slow progressor infant with delayed onset of AIDS. Whether this pattern is typical of slow progressing subtype C HIV-1 infected infant needs to be further substantiated. C1 Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. Univ Nebraska, Sch Biol Sci, Lincoln, NE USA. Univ Teaching Hosp, Dept Pediat, Lusaka, Zambia. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Wood, C (reprint author), Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA. EM hongz@unlserve.unl.edu; federicoh@unlserve.unl.edu; jhe1@unl.edu; xhe@unlserve.unl.edu; ckankasa@zamnet.zm; ruth_ruprecht@dfci.harvard.edu; jwest2@unl.edu; gorti@unl.edu; cwood1@unl.edu FU FIC NIH HHS [D43 TW001429, TW01429]; NCI NIH HHS [CA76958]; NCRR NIH HHS [P20 RR015635, RR15635]; NIAID NIH HHS [P01 AI 48240, P01 AI048240, P01 AI34266, R01 AI034266]; NICHD NIH HHS [HD39620, R01 HD039620] NR 66 TC 21 Z9 23 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD NOV 7 PY 2005 VL 2 AR 67 DI 10.1186/1742-4690-2-67 PG 15 WC Virology SC Virology GA 033OC UT WOS:000236857200001 PM 16274482 ER PT J AU Sobell, JL Richard, C Wirshing, DA Heston, LL AF Sobell, JL Richard, C Wirshing, DA Heston, LL TI Failure to confirm association between RGS4 haplotypes and schizophrenia in Caucasians SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE RGS4 gene; schizophrenia; case-control; association; haplotype ID PROTEIN SIGNALING RGS; SUSCEPTIBILITY GENE; MESSENGER-RNA; HUMAN GENOME; REGULATOR; EXPRESSION; RECOMBINATION; POLYMORPHISMS; BLOCKS; BRAIN AB The regulator of G-protein signaling (RGS) and RGS-like proteins are a diverse family of over 30 molecules that function as GTPase activating proteins for G alpha subunits of the Gq and Gi families of heterotrimeric guanine nucleotide-binding proteins (G proteins). By accelerating GTPase activity, RGS proteins drive G proteins into their inactive GDP-bound forms. G-protein coupled dopamine, metabotropie glutamate, and other neurotransmitter receptors can be modulated by RGS4, the predominant form in brain. The recent finding of decreased RGS4 mRNA expression in post-mortem brains from schizophrenic patients, coupled with the map position of RGS4 to a region previously linked to schizophrenia, as well as other biological data, prompted the investigation of the gene as a disease candidate. Multiple family-based and case-control association studies have been conducted, with modest and conflicting support for particular single nucleotide polymorphism (SNP) markers and SNP marker haplotypes. The present case-control analysis of 568 patients and 689 controls, one of the largest single studies to date, failed to confirm support for association of particular RGS4 SNP alleles, or for association of any particular four, three, or two SNP haplotype. (c) 2005 Wiley-Liss, Inc. C1 Univ So Calif, Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. RP Sobell, JL (reprint author), Univ So Calif, Zilkha Neurogenet Inst, 1501 San Pablo St,ZNI 339,MC 2821, Los Angeles, CA 90089 USA. EM sobell@usc.edu NR 23 TC 33 Z9 35 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 23 EP 27 DI 10.1002/ajmg.b.30221 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500006 PM 16082709 ER PT J AU Go, RCP Perry, RT Wiener, H Bassett, SS Blacker, D Devlin, B Sweet, RA AF Go, RCP Perry, RT Wiener, H Bassett, SS Blacker, D Devlin, B Sweet, RA TI Neuregulin-1 polymorphism in late onset Alzheimer's disease families with psychoses SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetics; linkage; SNP; psychotic; haplotype ID AT-RISK HAPLOTYPE; LINKAGE ANALYSIS; GAMMA-SECRETASE; NO ASSOCIATION; SCHIZOPHRENIA; SYMPTOMS; ERBB4; SUSCEPTIBILITY; PHENOTYPE; HEREGULIN AB Probands with late onset Alzheimer's disease (LOAD) exhibit positive symptoms of psychosis, 30-60% of the time. Positive symptoms of psychosis have been shown to appear prior to the onset of dementia to be accompanied by greater cognitive deficits, and to predict a more rapid decline. A study of the distribution of AD with psychosis (ADP) in families from the NIMH Alzheimer's Disease Genetic Initiative sample indicates that the trait is heritable, and linkage studies of multiplex ADP families have found suggestive peaks on 2p, 6q, 8p, and 21q. A genome scan of idiopathic psychosis, schizophrenia, in the Icelandic population identified a risk haplotype within the 5' region of neuregulin-1 (NRG1) on 8p12. Associations with NRG1 SNPs have also been found in other schizophrenia populations from Scotland, Ireland, and China. Here, we report results demonstrating a significant linkage peak for ADP on 8p12 in the NIMH AD dataset, encompassing the NRG1 region. We also demonstrate that there is a significant association with a NRGl SNP (single nucleotide polymorphism), rs392499, with ADP, X-2 = 7.0, P = 0.008. This same SNP is part of a 3-SNP haplotype preferentially transmitted to individuals with this phenotype. Our results suggest that NRG1 plays a role in increasing the genetic risk to positive symptoms of psychosis in a proportion of LOAD families. (c) 2005 Wiley-Liss, Inc. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Johns Hopkins Univ, Baltimore, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. RP Go, RCP (reprint author), Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Ryals Publ Hlth Bldg,Room 230N,1665 Univ Blvd, Birmingham, AL 35294 USA. EM rgo@uab.edu FU NIA NIH HHS [P50 AG005133-210020, P50 AG005133] NR 45 TC 48 Z9 48 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 28 EP 32 DI 10.1002/ajmg.b.30219 PG 5 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500007 PM 16082692 ER PT J AU Tang, YL Anderson, GM Zabetian, CP Kohnke, MD Cubells, JF AF Tang, YL Anderson, GM Zabetian, CP Kohnke, MD Cubells, JF TI Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+1603C -> T) with plasma dopamine beta-hydroxylase activity SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE dopamine beta-hydroxylase; haplotype; enzyme activity; association; polymorphism ID GENOTYPE-CONTROLLED ANALYSIS; FUNCTIONAL POLYMORPHISM; LINKAGE DISEQUILIBRIUM; GENE DBH; LOCUS AB The DBH locus controls plasma dopamine beta-hydroxylase activity (pD beta H). A 5'-upstream single nucleotide polymorphism (SNP) at DBH (-1021C -> T) explains similar to 45% of the variance in pD beta H, and a non-synonymous SNP in exon 11 (+1603C -> T) an additional 2%. However, that regression result underestimates the effect of +1603C -> T because of its low minor allele frequency. We estimated the biological effect of +1603C -> T on pD beta H by comparing subjects of identical -1021C gamma T genotype, in a diagnostically heterogeneous group of subjects of European origin (N = 367). +1603C -> T genotype associated with pD beta H within groups of identical genotype at -1021 C -> T, accounting for 5%-16% of the variance. There was no significant linkage disequilibrium between - 1021C -> T and + 1603C -> T (D - 0.0058, D'= 0.4774, d(2) = 0.0011, P > 0.05), confirming the validity of assessing the two polymorphisms independently. These results suggest that altered homospecific activity of the enzyme can contribute to variation in pD beta H. This conclusion informs how associations between DBH and psychiatric disorders should be approached. (c) 2005 Wiley-Liss, Inc. C1 Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Univ Tubingen Hosp, Univ Hosp Psychiat & Psychotherapy, Tubingen, Germany. RP Cubells, JF (reprint author), Emory Univ, Dept Human Genet, 615 Michael St,Suite 301, Atlanta, GA 30322 USA. EM jcubells@genetics.emory.edu FU NIDA NIH HHS [K02 DA015766, R01 DA12422]; NINDS NIH HHS [K08 NS44138] NR 15 TC 26 Z9 28 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 88 EP 90 DI 10.1002/ajmg.b.30220 PG 3 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500018 PM 16152569 ER PT J AU Faraone, SV Skol, AD Tsuang, DW Young, KA Haverstock, SL Prabhudesai, S Mena, F Menon, AS Leong, L Sautter, F Baldwin, C Bingham, S Weiss, D Collins, J Keith, T vanden Eng, JL Boehnke, M Tsuang, MT Schellenberg, GD AF Faraone, SV Skol, AD Tsuang, DW Young, KA Haverstock, SL Prabhudesai, S Mena, F Menon, AS Leong, L Sautter, F Baldwin, C Bingham, S Weiss, D Collins, J Keith, T vanden Eng, JL Boehnke, M Tsuang, MT Schellenberg, GD TI Genome scan of schizophrenia families in a large veterans affairs cooperative study sample: Evidence for linkage to 18p11.32 and for racial heterogeneity on chromosomes 6 and 14 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genome scan; schizophrenia; race; linkage; genetics; chromosome 18; racial heterogeneity ID CYCLASE-ACTIVATING POLYPEPTIDE; BANTU-SPEAKING FAMILIES; SUSCEPTIBILITY LOCI; BIPOLAR DISORDER; WIDE SCAN; GENETIC-LINKAGE; TYROSINE-HYDROXYLASE; DIAGNOSTIC INTERVIEW; EUROPEAN-AMERICAN; CORTICAL-NEURONS AB Genome-wide linkage analyses of schizophrenia have identified several regions that may harbor schizophrenia susceptibility genes but, given the complex etiology of the disorder, it is unlikely that all susceptibility regions have been detected. We report results from a genome scan of 166 schizophrenia families collected through the Department of Veterans Affairs Cooperative Studies Program. Our definition of affection status included schizophrenia and schizoaffective disorder, depressed type and we defined families as European American (EA) and African American (AA) based on the probands' and parents' races based on data collected by interviewing the probands. We also assessed evidence for racial heterogeneity in the regions most suggestive of linkage. The maximum LOD score across the genome was 2.96 for chromosome 18, at 0.5 cM in the combined race sample. Both racial groups showed LOD scores greater than 1.0 for chromosome 18. The empirical P-value associated with that LOD score is 0.04 assuming a single genome scan for the combined sample with race narrowly defined, and 0.06 for the combined sample allowing for broad and narrow definitions of race. The empirical P-value of observing a LOD score as large as 2.96 in the combined sample, and of at least 1.0 in each racial group, allowing for narrow and broad racial definitions, is 0.04. Evidence for the second and third largest linkage signals come solely from the AA sample on chromosomes 6 (LOD 2.11 at 33.2 cM) and 14 (LOD = 2.13 at 51.0). The linkage evidence differed between the AA and EA samples (chromosome 6 P-value = 0.007 and chromosome 14 P-value = 0.004). (c) 2005 Wiley-Liss, Inc. C1 SUNY Upstate Med Univ, Genet Res Program, Syracuse, NY 13210 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Mental Illness Res Educ & Clin Ctr, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Med Ctr, Waco, TX USA. Vet Affairs Med Ctr, Augusta, GA USA. Vet Affairs Med Ctr, Danville, IL USA. Vet Affairs Med Ctr, Tuskegee, AL USA. Vet Affairs Med Ctr, Cooperat Studies Program, Coordinating Ctr, Perry Point, MD USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Vet Affairs Med Ctr, New Orleans, LA USA. Vet Affairs Med Ctr, Northport, NY USA. Galileo Genom, Montreal, CA USA. Univ Calif San Diego, Inst Behav Genom, Dept Psychiat, San Diego, CA 92103 USA. VA San Diego Hlth Care Syst, San Diego, CA USA. Harvard Univ, Harvard Inst Psychiat Epidemiol & Genet, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Harvard Inst Psychiat Epidemiol & Genet, Dept Psychiat, Boston, MA 02115 USA. Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Genet Res Program, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Faraone, Stephen/0000-0002-9217-3982 NR 90 TC 14 Z9 14 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 91 EP 100 DI 10.1002/ajmg.b.30213 PG 10 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500019 PM 16152571 ER PT J AU Chenine, AL Buckley, KA Li, PL Rasmussen, RA Ong, H Jiang, S Wang, T Augostini, P Secor, WE Ruprecht, RM AF Chenine, AL Buckley, KA Li, PL Rasmussen, RA Ong, H Jiang, S Wang, T Augostini, P Secor, WE Ruprecht, RM TI Schistosoma mansoni infection promotes SHIV clade C replication in rhesus macaques SO AIDS LA English DT Article DE coinfection; rhesus macaques; HIV/SHIV; Schistosoma mansoni; cytokine/chemokine mRNA expression ID POLYMERASE CHAIN-REACTION; BLOOD MONONUCLEAR-CELLS; IMMUNE-RESPONSES; HIV-1 INFECTION; MACACA MULATTA; VIRUS; SUSCEPTIBILITY; INDIVIDUALS; CYTOKINE; HELMINTH AB Objective: To evaluate the hypothesis that parasitic infections that induce T-helper type 2 (Th2) immune responses, such as schistosomiasis, upregulate HIV-1 replication. Design: The effect of concomitant Schistosoma mansoni infection was tested in a primate model of acute and chronic simian-human immunodeficiency virus (SHIV) infection in rhesus macaques using a novel SHIV strain encoding the R5 env gene of a primary HIV clade C isolate from sub-Saharan Africa. Methods: S. mansoni-infected rhesus macaques and controls were exposed to SHIV to assess the effects of schistosomiasis on acute viral infection. Effects on chronic viral infection were evaluated by exposing virus-infected animals to parasites. S. mansoni infection was confirmed by the presence of parasite eggs in stool and eosinophilia. Viral RNA loads,, cytokine and chemokine mRNA expression were measured by real time reverse transcription-PCR. Results: S. mansoni coinfection increased the expression of Th2-associated cytokine responses and SHIV replication during both acute and chronic phases of SHIV infection. Conclusions: These results support the hypothesis that concomitant schistosomiasis upregulates replication of immunodeficiency viruses in coinfected hosts, raising the possibility that parasite-infected individuals may also be more susceptible to acquisition of HIV-1 infection. (c) 2005 Lippincott Williams & Wilkins C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB809, Boston, MA 02115 USA. EM was4@cdc.gov FU NCRR NIH HHS [R01 RR014180]; NIAID NIH HHS [R56 AI 06 2515, P01 AI48240]; NIDCR NIH HHS [R01 DE 016 013] NR 20 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 4 PY 2005 VL 19 IS 16 BP 1793 EP 1797 DI 10.1097/01.aids.0000189857.51935.0b PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 982PO UT WOS:000233174300007 PM 16227786 ER PT J AU Qin, S Pande, AH Nemec, KN He, XM Tatulian, SA AF Qin, S Pande, AH Nemec, KN He, XM Tatulian, SA TI Evidence for the regulatory role of the N-terminal helix of secretory phospholipase A(2) from studies on native and chimeric proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; BETA-SHEET STRUCTURE; INTERFACIAL ACTIVATION; INFRARED-SPECTROSCOPY; STRUCTURAL-CHANGES; MEMBRANE-BINDING; COILED-COILS; ALPHA-HELIX; AGKISTRODON PISCIVORUS; SECONDARY STRUCTURE AB The phospholipase A(2) (PLA(2)) enzymes are activated by binding to phospholipid membranes. Although the N-terminal alpha-helix of group I/II PLA(2)s plays an important role in the productive mode membrane binding of the enzymes, its role in the structural aspects of membrane-induced activation of PLA(2)s is not well understood. In order to elucidate membrane-induced conformational changes in the N-terminal helix and in the rest of the PLA(2), we have created semisynthetic human group IB PLA(2) in which the N-terminal decapeptide is joined with the C-13-labeled fragment, as well as a chimeric protein containing the N-terminal decapeptide from human group IIA PLA(2) joined with a C-13-labeled fragment of group IB PLA(2). Infrared spectral resolution of the unlabeled and C-13-labeled segments suggests that the N-terminal helix of membrane-bound IB PLA(2) has a more rigid structure than the other helices. On the other hand, the overall structure of the chimeric PLA(2) is more rigid than that of the IB PLA(2), but the N-terminal helix is more flexible. A combination of homology modeling and polarized infrared spectroscopy provides the structure of membrane-bound chimeric PLA(2), which demonstrates remarkable similarity but also distinct differences compared with that of IB PLA(2). Correlation is delineated between structural and membrane binding properties of PLA(2)s and their N-terminal helices. Altogether, the data provide evidence that the N-terminal helix of group I/II PLA(2)s acts as a regulatory domain that mediates interfacial activation of these enzymes. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32826 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA 02114 USA. Univ Cent Florida, Dept Chem, Orlando, FL 32816 USA. RP Tatulian, SA (reprint author), Univ Cent Florida, Biomol Sci Ctr, 12722 Res Pkwy, Orlando, FL 32826 USA. EM statulia@mail.ucf.edu FU NHLBI NIH HHS [HL65524] NR 59 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 2005 VL 280 IS 44 BP 36773 EP 36783 DI 10.1074/jbc.M506789200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800031 PM 16103116 ER PT J AU Wei, H Ruthenburg, AJ Bechis, SK Verdine, GL AF Wei, H Ruthenburg, AJ Bechis, SK Verdine, GL TI Nucleotide-dependent domain movement in the ATPase domain of a human type IIA DNA topoisomerase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STRAND-PASSAGE REACTION; STEADY-STATE ANALYSIS; CRYSTAL-STRUCTURE; OPERATED CLAMP; DOUBLE HELIX; GYRASE-B; ALPHA; MECHANISM; TRANSPORT; YEAST AB Type IIA DNA topoisomerases play multiple essential roles in the management of higher-order DNA structure, including modulation of topological state, chromosome segregation, and chromatin condensation. These diverse physiologic functions are all accomplished through a common molecular mechanism, wherein the protein catalyzes transient cleavage of a DNA duplex ( the G-segment) to yield a double-stranded gap through which another duplex ( the T-segment) is passed. The overall process is orchestrated by the opening and closing of molecular "gates" in the topoisomerase structure, which is regulated by ATP binding, hydrolysis, and release of ADP and inorganic phosphate. Here we present two crystal structures of the ATPase domain of human DNA topoisomerase II alpha in different nucleotide-bound states. Comparison of these structures revealed rigid-body movement of the structural modules within the ATPase domain, suggestive of the motions of a molecular gate. C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Program Canc Chem Biol, Boston, MA 02115 USA. RP Verdine, GL (reprint author), Harvard Univ, Dept Chem & Biol Chem, 12 Oxford St,Rm 194, Cambridge, MA 02138 USA. EM Gregory_verdine@harvard.edu RI Ruthenburg, Alexander/C-3941-2008; Ruthenburg, Alexander/F-3992-2015 OI Ruthenburg, Alexander/0000-0003-2709-4564 FU NCRR NIH HHS [RR-15301]; NIGMS NIH HHS [GM044853, R01 GM044853] NR 46 TC 103 Z9 107 U1 2 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 4 PY 2005 VL 280 IS 44 BP 37041 EP 37047 DI 10.1074/jbc.M506520200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800062 PM 16100112 ER PT J AU Podolsky, DK AF Podolsky, DK TI Selective adhesion-molecule therapy and inflammatory bowel disease - A tale of Janus? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; ACTIVE CROHNS-DISEASE; COTTON-TOP TAMARIN; JC VIRUS; MONOCLONAL-ANTIBODY; NATALIZUMAB; INTEGRIN; COLITIS; TISSUES C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 19 TC 26 Z9 27 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 3 PY 2005 VL 353 IS 18 BP 1965 EP 1968 DI 10.1056/NEJMe058212 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 979VJ UT WOS:000232972800015 PM 16267329 ER PT J AU Layfield, D Venegas, JG AF Layfield, D Venegas, JG TI Enhanced parameter estimation from noisy PET data: part I - Methodology SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Functional Pulmonary Imaging CY 2004 CL Univ Penn, Philadelphia, PA SP GlaxoSmithKline, Pfizer, Siemens, Natl Inst Hlth HO Univ Penn DE position emission tomography; parameter estimation; functional imaging ID PULMONARY-FUNCTION; VENTILATION; PERFUSION; KINETICS; IMAGES AB Rationale and Objectives. The reliability of positron emission tomographic (PET) images depends on the number of annihilation events that are detected. Short image durations are required to capture rapid tracer dynamics, and the resultant images are noisy. Consequently, direct parameter estimation from time-activity curves at high resolution often is unreliable. If adjacent voxels are combined into larger regions of interest the reliability of parameter estimation may be improved, but at the expense of decreased spatial resolution. In this report, a method is presented that provides an alternative to degrading image resolution. Materials and Methods. Following the approach of Kimura et al, voxels are grouped not by spatial proximity, but by the similarity of their kinetics. Parameter estimation is performed on these groups, and derived parameters are assigned to all members of the group. Spatial information thus is preserved, but at the expense of parametric discretization. An improvement to the method of Kimura et al is described, in which data are grouped using principal components derived from artificial data. Results. The application of the method is demonstrated by analysis of PET images of human lungs obtained by the nitrogen-13 infusion-washout technique. In a comparison of the accuracy of parameter estimates, the enhanced method is shown to outperform the original method at all noise levels, with the difference increasing as the amount of noise increases. The robustness of this parameter estimation method in the presence of noise is described in part It of this report in this issue of Academic Radiology. Conclusion. A method is described that provides demonstrably robust parameter estimates from noisy PET data, while not compromising image resolution. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Room CLN-237F,55 Fruit St, Boston, MA 02114 USA. EM jvenegas@vqpet.mgh.harvard.edu FU NHLBI NIH HHS [HL068011] NR 10 TC 8 Z9 8 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2005 VL 12 IS 11 BP 1440 EP 1447 DI 10.1016/j.acra.2005.08.012 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981OX UT WOS:000233099000011 PM 16253856 ER PT J AU Marcinkowski, A Layfield, D Tgavalekos, N Venegas, JG AF Marcinkowski, A Layfield, D Tgavalekos, N Venegas, JG TI Enhanced parameter estimation from noisy PET data: part II - Evaluation SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Functional Pulmonary Imaging CY 2004 CL Univ Penn, Philadelphia, PA SP GlaxoSmithKline, Pfizer, Siemens, Natl Inst Hlth HO Univ Penn DE positron emission tomography (PET); parameter estimation; functional imaging ID PULMONARY PERFUSION; VENTILATION AB Rationale and Objectives. Positron emission tomography (PET) is a minimally invasive imaging modality that provides three-dimensional distribution data for a radioactive tracer concentration within the body. Local functional parameters are estimated from these images by fitting tracer kinetic data with mathematical models. However, in some applications, the reliability of parameter estimates may be hindered by the presence of noise. In the accompanying report in this issue of Academic Radiology, a novel method using principal component analysis (PCA) was presented and used for deriving parametric images of lung function from imaged tracer kinetics of intravenously injected nitrogen 13 ((NN)-N-13) in saline solution. The PCA method averages (NN)-N-13 concentrations from groups of voxels (volume elements) selected for their similarity in kinetics, rather than their spatial proximity. The goal of this study is to conduct a Monte Carlo simulation to evaluate the robustness to noise of parameters derived by means of the PCA method. Materials and Methods. This evaluation involved: (1) generating "noise-free" synthetic PET images from experimental PET data, (2) adding noise to these images, (3) applying the PCA method to yield parametric images, and (4) comparing these parametric images with original noise-free images. Results. Local parameters recovered by using the PCA method deviated from noise-free parameters on average by less than 1% for up to 32-fold of expected noise levels. These deviations were much less than those (>10%) recovered by using a direct curve-fitting method. Conclusion. The novel PCA approach provides robust parametric lung functional images while preserving the spatial resolution of the original images. C1 Boston Univ, Dept Biomed Engn, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Boston Univ, Dept Biomed Engn, Room CLN-237F,55 Fruit St, Boston, MA 02114 USA. EM jvenegas@vqpet.mgh.harvard.edu FU NHLBI NIH HHS [HL068011] NR 10 TC 5 Z9 5 U1 0 U2 2 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2005 VL 12 IS 11 BP 1448 EP 1456 DI 10.1016/j.acra.2005.08.011 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981OX UT WOS:000233099000012 PM 16253857 ER PT J AU Nikolaidis, P vanSonnenberg, E Haddad, ZK Chen, YH Zou, KH Tuncali, K Silverman, SG AF Nikolaidis, P vanSonnenberg, E Haddad, ZK Chen, YH Zou, KH Tuncali, K Silverman, SG TI Practice patterns of nonvascular interventional radiology procedures at academic centers in the United States? SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Workshop on Functional Pulmonary Imaging CY 2004 CL Univ Penn, Philadelphia, PA SP GlaxoSmithKline, Pfizer, Siemens, Natl Inst Hlth HO Univ Penn DE interventional radiology; diagnostic procedures; Academic Medical Center; biopsy; drainage ID EXPERIENCE; MANAGEMENT; ABLATION; NEPHROSTOMY; TUMORS AB Rationale and Objectives. To determine and analyze the patterns of practice of nonvascular interventional procedures in academic centers in the United States. Materials and Methods. A survey was administered via e-mail to the chief residents of 112 academic radiology departments in the United States. Recipients of the survey were asked to identify which sections within their respective radiology departments performed each of 43 types of nonvascular interventional procedures. An additional entry for performance of procedures by non-radiologists was provided. A total of 66 (59%) recipients responded. The statistical method used was the analysis of contingency tables. Results. Percutaneous abdominal biopsies are performed mainly by abdominal and body imaging sections (43/66, 65%), followed by vascular/interventional sections (21/66, 32%). Percutaneous abdominal drainages are performed mostly by abdominal, body imaging, and computed tomography sections (40/66, 61%), followed by vascular/interventional sections. Fluoroscopically guided procedures were performed most commonly by vascular/interventional sections, including percutaneous gastrostomy (40/66, 61%), percutaneous nephrostomy (42/66, 64%), and biliary interventions such as percutaneous transhepatic cholangiography (47/66, 71%). Breast and musculoskeletal. procedures are performed by their respective sections most frequently. Non-radiologists perform a significant portion of certain types of procedures: paracenteses, thoracenteses, biliary interventions (particularly stone extractions), enterostomies (particularly percutaneous jejunostomies and cecostomies), and certain biopsies (kidney and prostate). Conclusions. Academic US radiology sections perform nonvascular interventional radiology procedures in a complex and non-uniform manner. The vascular/interventional sections and organ system and modality (especially CT) sections perform the bulk of the procedures included in the survey. Breast imaging sections predominate in procedures in their disciplines. A substantial number and amount of interventional radiology procedures are performed by non-radiologists. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NW Mem Hosp, Dept Radiol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Hosp Special Surg, Dept Radiol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, New York, NY 10021 USA. Nassau Univ Med Ctr, E Meadow, NY 11554 USA. RP Nikolaidis, P (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM p-nikolaidis@northwestern.edu NR 16 TC 2 Z9 2 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2005 VL 12 IS 11 BP 1475 EP 1482 DI 10.1016/j.acra.2005.06.011 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981OX UT WOS:000233099000015 PM 16294438 ER PT J AU Tsukamoto, H AF Tsukamoto, H TI Adipogenic phenotype of hepatic stellate cells SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article; Proceedings Paper CT Satellite Symposium of the International-Society-on-Biomedocal-Research-on-Alcoholism CY SEP 26-28, 2004 CL Bordeaux, FRANCE SP Int Soc Biomed Res Alcoholism DE PPAR gamma; SREBP-1c; LXR alpha; liver fibrosis ID X-RECEPTOR; ACTIVATION; PROMOTER; ALPHA AB Transdifferentiation of hepatic stellate cells (HSC) constitutes a major cellular event in the genesis of alcoholic liver fibrosis and cirrhosis and molecular mechanisms underlying this process is incompletely understood. Our laboratory proposed several years ago that HSC quiescence requires the transcriptional program known to be integral to preadipocyte to adipocyte differentiation. In support of the hypothesis, our research demonstrates the expression of adipogenic transcription factors (C/EBPs, PPAR gamma, SREBP-1c, LXR alpha) and adipocyte-specific genes (adipsin, resistin) are high in quiescent HSC and depleted in activated HSC. Three gain-of-function approaches have been taken to test this notion: the treatment of activated HSC with the adipocyte differentiation cocktail; ectopic expression of PPAR gamma or SREBP-1c. All three treatments coordinately upregulate a panel of putative adipogenic transcrition factors and cause morphologic and biochemical reversal of activated HSC to quiescent cells. These findings establish a new conceptual framework for the treatment of liver fibrosis and propose an intriguing notion concerning the plasticity of HSC. C1 Univ So Calif, Keck Sch Med, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Tsukamoto, H (reprint author), Univ So Calif, Keck Sch Med, Res Ctr Alcohol Liver & Pancreat Dis, 1333 San Pablo St,MMR-412, Los Angeles, CA 90089 USA. EM htsukamo@usc.edu NR 12 TC 34 Z9 35 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2005 VL 29 IS 11 SU S BP 132S EP 133S DI 10.1097/01.alc.0000189279.92602.f0 PG 2 WC Substance Abuse SC Substance Abuse GA 995XA UT WOS:000234136800006 PM 16344597 ER PT J AU Blanco, PG Salem, RO Ollero, M Zaman, MM Cluette-Brown, JE Freedman, SD Laposata, M AF Blanco, PG Salem, RO Ollero, M Zaman, MM Cluette-Brown, JE Freedman, SD Laposata, M TI Ethanol administration to cystic fibrosis knockout mice results in increased fatty acid ethyl ester production SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE CFTR; fatty acids; alcohol; lipids ID TRANSMEMBRANE CONDUCTANCE REGULATOR; PANCREATIC ACINAR-CELLS; ALCOHOLIC LIVER-DISEASE; DELTA-F508 MUTATION; POSTMORTEM MARKERS; EPITHELIAL-CELLS; LIPID CLASSES; GENE; METABOLISM; SYNTHASE AB Background: Fatty acid ethyl esters (FAEE) are nonoxidative ethanol metabolites shown to produce toxic effects in the liver and pancreas in vivo and in vitro. Because alcohol-induced chronic pancreatitis is associated with mutations in the gene responsible for cystic fibrosis (CFTR), we hypothesized that CFTR dysfunction leads to increased levels of these toxic nonoxidative ethanol metabolites following alcohol administration. Methods: Cystic fibrosis (CF) and wild-type (Virr) mice were injected intraperitoneally with 1, 2, or 3 g/kg of 50% ethanol. Mice were sacrificed and the liver and pancreas removed for FAEE analysis. Results: The mean FAEE concentration (pmol/g) detected in the liver of cftr(-/-) mice following injection with 2 g/kg of ethanol was significantly greater than the amount detected in WT (p < 0.005). A similar trend in FAEE concentration was seen in the pancreas, but the difference was not statistically different. In both the liver and pancreas, analysis of individual FAEE species demonstrated a selective increase in ethyl oleate. Conclusion: These data show an association between CFTR dysfunction and qualitative and quantitative changes in FAEE in liver and pancreas upon ethanol exposure. C1 Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Dept Pathol, Div Lab Med, Room 235 Gray Bldg,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org FU NIDDK NIH HHS [DK052765] NR 55 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2005 VL 29 IS 11 BP 2039 EP 2045 DI 10.1097/01.alc.0000187593.86202.e8 PG 7 WC Substance Abuse SC Substance Abuse GA 994EX UT WOS:000234014700017 PM 16340462 ER PT J AU Stein, DJ El-Serag, HB Kuczynski, J Kramer, JR Sampliner, RE AF Stein, DJ El-Serag, HB Kuczynski, J Kramer, JR Sampliner, RE TI The association of body mass index with Barrett's oesophagus SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PROSPECTIVE MULTIVARIATE-ANALYSIS; HIATAL-HERNIA; GASTROESOPHAGEAL-REFLUX; ACID EXPOSURE; GASTRIC CARDIA; RISK-FACTORS; ADENOCARCINOMA; LENGTH; PREVALENCE; OBESITY AB Background: Obesity has been linked to gastro-oesophageal reflux disease symptoms and oesophageal adenocarcinoma; however, there is no published evidence for an association with Barrett's oesophagus. Aim: To investigate the association between obesity and Barrett's oesophagus. Methods: We conducted a retrospective cross-sectional study of patients who underwent upper endoscopy at the Southern Arizona Veteran's Affairs Healthcare System between 1998 and 2004. We examined male patients without malignancy, with available information on weight and height. Based on endoscopic and histological findings, patients were classified as cases with Barrett's oesophagus or non-cases without Barrett's oesophagus. Multivariable logistic regression analysis was conducted to examine the association of body mass index and obesity with Barrett's oesophagus and Barrett's oesophagus length while adjusting for age and race. Results: There were 65 cases with Barrett's oesophagus and 385 non-cases without Barrett's oesophagus. The mean body mass index was significantly higher in cases than in non-cases (29.8 vs. 28.0, P = 0.03). Cases had significantly greater mean weight than controls (206 lb vs. 190, P = 0.005). The proportions of cases with body mass index 25-30 and body mass index >= 30 were greater than those in non-cases (44.6% vs. 37.7%) and (40.0% vs. 33.5%), respectively (P = 0.08). In the multivariable logistic regression model adjusting for race and age, when compared with body mass index < 25, the odds ratio was 2.43 (95% confidence interval: 1.12-5.31) for body mass index 25-30 and 2.46 (1.11-5.44) for body mass index >= 30. When examined as a continuous variable the adjusted odd ratio for each five-point increase in body mass index was 1.35 (95% confidence interval: 1.06-1.71, P = 0.01). The association between weight and Barrett's oesophagus was also statistically significant (adjusted odd ratio for each 10 pound increase = 1.10, 1.03-1.17, P =0.002). Among the 65 cases of Barrett's oesophagus, there was no correlation between the length of Barrett's oesophagus at the time of diagnosis and the body mass index (correlation coefficient = 0.03, P = 0.79). Conclusion: This retrospective cross-sectional study in male veterans shows that overweight is associated with a two-and-half-fold increased risk of Barrett's oesophagus. Larger studies of the underlying mechanism are warranted to better understand how and why obese patients are at greater risk for Barrett's oesophagus. C1 So Arizona VA Healthcare Syst, Tucson, AZ USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ USA. Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 29 TC 65 Z9 67 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD NOV PY 2005 VL 22 IS 10 BP 1005 EP 1010 DI 10.1111/j.1365-2036.2005.02674.x PG 6 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 978RU UT WOS:000232891500014 PM 16268976 ER PT J AU Kavanaugh, M McMillen, RC Pascoe, JM Southward, LH Winickoff, JP Weitzman, M AF Kavanaugh, M McMillen, RC Pascoe, JM Southward, LH Winickoff, JP Weitzman, M TI The co-occurrence of maternal depressive symptoms and smoking in a national survey of mothers SO AMBULATORY PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Societies/Ambulatory-Pediatric-Association CY MAY 03-06, 2003 CL SEATTLE, WA SP Pediat Acad Soc, Amer Pediat Soc, Soc Pediat Res, Ambulatory Pediat Assoc, Tulane Univ Hlth Sci Ctr, Ctr Continuing Educ DE environmental tobacco smoke; maternal depression; Medicaid; smoking ID PARENTAL SMOKING; PRESCHOOL-CHILDREN; YOUNG-CHILDREN; UNITED-STATES; FOLLOW-UP; HEALTH; TOBACCO; PREVALENCE; PREGNANCY; FAMILY AB Context.-Both maternal smoking and depression are common and can adversely impact child health and functioning, yet few studies have explored their co-occurrence among mothers. Objective.-To determine the prevalence and associations of depression and smoking among mothers in the United States. Design.-Random-digit-dial national telephone survey of 1530 households conducted in 2002. Respondents were asked about their sociodemographic characteristics, smoking status, and their children's receipt of Medicaid. A validated 3-item depression screen was administered. Bivariate and multiple regression analyses for maternal smoking and a positive depression screen were performed. Setting.-National sample. Participants.-Seven hundred two mothers with children aged less than 19 years living in their homes. Results.-The response rate was 61%. Among mothers, 24.3% were smokers, 24.4% had a positive depression screen, 8.1% had both, and 40.6% were smokers and/or had a positive depression screen. All rates were greater among mothers whose children receive Medicaid (37.6%, 47.5%, 20.6%, and 64.5%) than those whose children do not receive Medicaid (21.1% 19.0% 4.8%, and 35.3%) (P <.001) for each. In multivariate analyses, maternal smoking was independently associated with a 70% increased risk of depressive symptoms (odds radio, 1.7; 95% confidence interval, 1.1-2.6). Conclusions.-This study highlights both the frequency and the co-occurrence of maternal smoking and maternal depressive symptoms, two negative influences Oil children's health and development, as well as their increased prevalence among mothers whose children receive Medicaid, thereby highlighting the economic disparities associated with both. These findings have significant implications for our nation's children, health care clinicians, and health care payers. C1 Amer Acad Pediat, Ctr Child Hlth Res, Rochester, NY 14620 USA. Univ Rochester, Sch Med & Dent, Rochester, NY USA. Mississippi State Univ, Social Sci Res Ctr, Starkville, MS USA. Tobacco Consortium, Rochester, NY USA. Wright State Univ, Sch Med, Dept Pediat, Dayton, OH USA. Childrens Med Ctr, Dayton, OH USA. MassGen Hosp Children, Div Gen Pediat, Boston, MA USA. MassGen Hosp Children, MGH Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Univ Rochester, Sch Med & Dent, Strong Childrens Res Ctr, Dept Pediat, Rochester, NY USA. RP Weitzman, M (reprint author), Amer Acad Pediat, Ctr Child Hlth Res, 1351 Mt Hope Ave,Suite 130, Rochester, NY 14620 USA. EM michael_weitzman@urmc.rochester.edu RI McMillen, Robert/A-9326-2009 NR 48 TC 12 Z9 12 U1 3 U2 3 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1530-1567 J9 AMBUL PEDIATR JI Ambul. Pediatr. PD NOV-DEC PY 2005 VL 5 IS 6 BP 341 EP 348 DI 10.1367/A04-207R.1 PG 8 WC Pediatrics SC Pediatrics GA 987MM UT WOS:000233522000006 PM 16302835 ER PT J AU Pletcher, MJ Kiefe, CI Sidney, S Carr, JJ Lewis, CE Hulley, SB AF Pletcher, MJ Kiefe, CI Sidney, S Carr, JJ Lewis, CE Hulley, SB TI Cocaine and coronary calcification in young adults: The Coronary Artery Risk Development in Young Adults (CARDIA) study SO AMERICAN HEART JOURNAL LA English DT Article ID MYOCARDIAL-INFARCTION; CALCIUM; DISEASE; ATHEROSCLEROSIS; RECRUITMENT; PREVALENCE; USERS AB Background Cocaine use is associated with myocardial ischemia and infarction, but it is unclear whether this is only because of the acute effects of cocaine on heart rate, blood pressure, and vasomotor tone or whether accelerated atherosclerosis from long-term exposure to cocaine also contributes. Methods We sought to measure the association between cocaine exposure and coronary calcification, a marker for atherosclerosis, among participants in the CARDIA Study who received computed tomography scanning and answered questions about illicit drug use at the year 15 examination in 2000-2001. Results Among 3038 CARDIA participants (age 33-45 years, 55% women and 45% black), past cocaine exposure was reported by 35% and was more common among men, smokers, drinkers, and participants with less education. Powdered cocaine exposure was more common among whites, crack cocaine among blacks. Before adjustment, cocaine exposure was strongly associated with coronary calcification. After adjusting for age, sex, ethnicity, socioeconomic status, family history, and habits, however, these associations disappeared: adjusted odds ratios for coronary calcification were 0.9 (95% CI 0.6-1.3) for 1 to 10, 1.2 (95% CI 0.8-1.7) for 11 to 99, and 1.0 (95% CI 0.6-1.6) for >= 100 lifetime episodes of cocaine use, in comparison with none. Sex, tobacco, and alcohol use appeared to be primarily responsible for the confounding we observed in unadjusted models. Conclusion We found no evidence of a causal relationship between long-term exposure to cocaine and coronary calcification and conclude that acute nonatherogenic mechanisms probably explain most cocaine-associated myocardial infarction. C1 Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Kaiser Permanente, Div Res, Oakland, CA USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. RP Pletcher, MJ (reprint author), 500 Parnassus Ave,MU-420 W, San Francisco, CA 94143 USA. EM mpletcher@epi.ucsf.edu RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095] NR 30 TC 9 Z9 9 U1 2 U2 3 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 NOV PY 2005 VL 150 IS 5 BP 921 EP 926 DI 10.1016/j.ahj.2005.04.016 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986VW UT WOS:000233478800014 PM 16290964 ER PT J AU Rumsfeld, JS Jones, PG Whooley, MA Sullivan, MD Pitt, B Weintraub, WS Spertus, JA AF Rumsfeld, JS Jones, PG Whooley, MA Sullivan, MD Pitt, B Weintraub, WS Spertus, JA TI Depression predicts mortality and hospitalization in patients with myocardial infarction complicated by heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID NATIONAL-REGISTRY; MAJOR DEPRESSION; RANDOMIZED-TRIAL; RATE-VARIABILITY; SYMPTOMS; RISK; DISEASE; SERTRALINE; DISORDERS; SEVERITY AB Background To evaluate whether depressive symptoms are independently predictive of mortality and hospitalization among patients with acute myocardial infarction (AMI) complicated by heart failure. Methods The EPHESUS trial enrolled patients with AMI complicated by heart failure. Patients from Canada, the UK, and the United States completed a Medical Outcomes Study-De press ion questionnaire at baseline in addition to a comprehensive clinical examination. Cox proportional hazards regression was used to determine the relationship between depressive symptoms and outcomes, including 2-year all-cause mortality and cardiovascular death or hospitalization, adjusting for baseline clinical variables. Results Overall, 143 of 634 patients (22.6%) had significant depressive symptoms at baseline (Medical Outcomes Study-Depression score >= 0.06). Depressed patients had higher 2-year mortality (29% vs 18%; P = .004) and cardiovascular death or hospitalization (42% vs 33%; P = .016). After risk adjustment, depressive symptoms remained significantly associated with mortality (hazard ratio 1.75, 95% CI 1.15-2.68, P = .01) and cardiovascular death or hospitalization (hazard ratio 1.41, 95% CI 1.03-1.93, P = .03). Results were consistent across demographic and clinical subgroups. Conclusions Depression is an independent predictor of all-cause mortality and cardiovascular death or hospitalization after AMI complicated by heart failure. Although many factors may mediate outcomes in patients with AMI, studies are warranted to evaluate whether a depression intervention can improve survival and/or reduce hospitalizations. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Cardiol, Denver, CO 80262 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Dept Med, Kansas City, MO 64110 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. Univ Michigan, Sch Med, Div Cardiol, Ann Arbor, MI USA. Emory Univ, Sch Med, Emory Ctr Outcomes Res, Atlanta, GA USA. RP Rumsfeld, JS (reprint author), Denver VA Med Ctr, Cardiol Sect, 1055 Clermont St, Denver, CO 80220 USA. EM john.rumsfeld@med.va.gov NR 32 TC 85 Z9 95 U1 1 U2 5 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 NOV PY 2005 VL 150 IS 5 BP 961 EP 967 DI 10.1016/j.ahj.2005.02.036 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986VW UT WOS:000233478800022 PM 16290972 ER PT J AU Dupuis, J Tardif, JC Rouleau, JL Ricci, J Arnold, M Lonn, E Roux, R Title, LM Amyot, R Bonafede, N Woo, A Cannon, CP AF Dupuis, J Tardif, JC Rouleau, JL Ricci, J Arnold, M Lonn, E Roux, R Title, LM Amyot, R Bonafede, N Woo, A Cannon, CP TI Intensity of lipid lowering with statins and brachial artery vascular endothelium reactivity after acute coronary syndromes (from the BRAVER trial) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID COENZYME-A REDUCTASE; THERAPY; NITROGLYCERIN; CERIVASTATIN; SIMVASTATIN; CHOLESTEROL; INHIBITORS; DISEASE AB The time course and differential effects of statin regimens on endothelial function after acute coronary syndromes (ACSs) are unknown and could contribute to the superiority of a more intense strategy. A subset of subjects who were enrolled in the PROVE IT-TIMI 22 trial (n = 50) underwent evaluation of vascular reactivity by high-resolution brachial ultrasound. Endothelium-dependent flow-mediated dilation (FMD) and endothelium-independent sublingual nitroglycerin-mediated dilation (NMD) were measured at baseline and at 48 hours, 1 month, and 4 months after the initiation of 40 mg of pravastatin (n = 26) or 80 mg of atorvastatin (n = 24). After 4 months, low-density lipoprotein cholesterol was decreased by 32% in the atorvastatin group but was not different from baseline after ACS in the pravastatin group. C-reactive protein decreased similarly in the 2 groups. Brachial artery diameters at rest were similar in the 2 groups and at each time point of the trial. FMD and NMD increased significantly after 4 months by 27% and 24%, respectively (p < 0.05), with no difference between groups. There was no correlation between the change in FMD and the change in lipids or C-reactive protein. In subjects who had received previous statin therapy (n = 15), there was no significant variation in FMD (p = 0.140) and NMD (p = 0.129). In conclusion, initiation of statin therapy soon after ACS is associated with improvements in endothelium-dependent and independent vascular reactivities after 4 months. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Montreal, Res Ctr, Montreal Heart Inst, Montreal, PQ, Canada. Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada. Scarborough Cardiol Res, Scarborough, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. McMaster Univ, Dept Med, Hamilton, ON, Canada. Bur Internistes Drummondville, Drummondville, PQ, Canada. Queen Elizabeth II Hlth Sci Ctr, Halifax, NS, Canada. Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada. Brampton Res Associates, Brampton, ON, Canada. Toronto Gen Hosp, Toronto, ON, Canada. Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Dupuis, J (reprint author), Univ Montreal, Res Ctr, Montreal Heart Inst, Montreal, PQ, Canada. EM jocelyn.dupuis@bellnet.ca RI Dupuis, Jocelyn/B-3898-2009; Dupuis, Jocelyn/C-6613-2013 OI Dupuis, Jocelyn/0000-0002-3193-1014 NR 16 TC 24 Z9 26 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 NOV 1 PY 2005 VL 96 IS 9 BP 1207 EP 1213 DI 10.1016/j.amjcard.2005.06.057 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 984YO UT WOS:000233343500006 PM 16253583 ER PT J AU Shavelle, DM Rasouli, ML Frederick, P Gibson, CM French, WJ AF Shavelle, DM Rasouli, ML Frederick, P Gibson, CM French, WJ CA Natl Registry Myocardial Infarctio TI Outcome in patients transferred for percutaneous coronary intervention (A National Registry of Myocardial Infarction 2/3/4 analysis) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID PRIMARY ANGIOPLASTY; THROMBOLYSIS; THERAPY; DELAY AB Hospital transfer is associated with delays in performance of primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction. Given the limited number of interventional centers in the United States, the transfer of patients is widely practiced. We compared the outcome of patients who were transferred for primary PCI and determined whether prolonged door-to-balloon times were associated with increased mortality. Patients who presented within 12 hours with ST-segment elevation myocardial infarction and underwent transfer for primary PCI were identified from the National Registry of Myocardial Infarction database (NRMI databases 2, 3, and 4, n = 7,133). The short-term outcome of those who received early (>= 2 hours) was compared with that of those who received delayed primary PCI (> 2 hours) using multivariate logistic regression analyses and propensity score methods. The door-to-balloon time for the early PCI group compared with the delayed PCI group was 99 +/- 16 versus 264 +/- 178 minutes, respectively (p < 0.0001). The early PCI group had less recurrent ischemia and angina (5.8% vs 10.1%, p < 0.001), less cardiogenic shock (5.1% vs 8.9%, p < 0.001), and shorter length of hospital stay (4.4 +/- 3.5 vs 5.4 +/- 4.7 days, p < 0.001). In-hospital mortality was lower for the early PCI group than for the delayed PCI group (2.7% vs 6.2%, p < 0.001; entire cohort 5.7%). Comparison of patients matched on propensity score (n = 993) showed that mortality was lower in the early than in the delayed PCI group (2.6% vs 4.6%, p = 0.014, c-statistic 0.67). In conclusion, < 4% of patients who received PCI were treated within the recommended guideline of < 120 minutes by the American College of Cardiology/American Heart Association. Door-to-balloon times < 2 hours in patients who undergo transfer for PCI is associated with a significant decrease in short-term mortality, which suggests that efforts must be made to decrease transfer delays. (c) 2005 Elsevier Inc. All rights reserved. C1 Harbor UCLA Med Ctr, Div Cardiol, Torrance, CA 90509 USA. Ovat Res Grp, Seattle, WA USA. TIMI Study Grp, Boston, MA USA. RP Shavelle, DM (reprint author), Harbor UCLA Med Ctr, Div Cardiol, Torrance, CA 90509 USA. EM dshavelle@hotmail.com OI Frederick, Paul/0000-0002-7936-5488 NR 13 TC 39 Z9 41 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 NOV 1 PY 2005 VL 96 IS 9 BP 1227 EP 1232 DI 10.1016/j.amjcard.2005.06.061 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 984YO UT WOS:000233343500010 PM 16253587 ER PT J AU Tofler, GH Massaro, J Levy, D Mittleman, M Sutherland, P Lipinska, I Muller, JE D'Agostino, RB AF Tofler, GH Massaro, J Levy, D Mittleman, M Sutherland, P Lipinska, I Muller, JE D'Agostino, RB TI Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; LINKED-IMMUNOSORBENT-ASSAY; MYOCARDIAL-INFARCTION; PLASMINOGEN-ACTIVATOR; VONWILLEBRAND-FACTOR; ANGINA-PECTORIS; FACTOR-VIII; CARDIOVASCULAR-DISEASE; SUDDEN-DEATH; RISK FACTOR AB A greater life expectancy has led to an increasing proportion of elderly patients. Increasing age is an important risk factor for cardiovascular disease, but the mechanism of risk is not well understood. Because thrombosis plays a key role in plaque development and the onset of acute coronary syndromes, the age-related increase in cardiovascular risk may be a result of a prothrombotic imbalance. The study aim was to examine the relation between age and thrombotic potential in the Framingham Offspring Cohort. Hemostatic factors previously associated with cardiovascular risk were measured in 3,230 patients (55% women) without evidence of cardiovascular disease who were participating in cycle 5 of the Framingham Offspring Study. The subjects were divided by age into decades. Advancing age was associated with a significant increase in fibrinogen and von Willebrand factor levels and measures of impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigens). For men, the mean fibrinogen levels were 21% higher in those >= 70 years versus those aged < 40 years (326 vs 268 mg/dl, p < 0.001 for linear trend). The mean fibrinogen levels were 15% higher in older than in younger women (330 vs 286 mg/dl, p < 0.001). The significant relations persisted after multivariate adjustment. In conclusion, advancing age is associated with elevated levels of hemostatic factors indicative of a prothrombotic state. Because these factors are also associated with endothelial dysfunction, these findings are consistent with an injurious effect of age on the endothelium. Measures to reduce thrombotic potential may be of particular value in the elderly, because they counter the prothrombotic state that develops with aging. (c) 2005 Elsevier Inc. All rights reserved. C1 Royal N Shore Hosp, Sydney, NSW, Australia. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Math & Stat, Boston, MA USA. RP Tofler, GH (reprint author), Royal N Shore Hosp, Sydney, NSW, Australia. EM gtofler@nsccahs.health.nsw.gov.au OI Massaro, Joseph/0000-0002-2682-4812 FU NHLBI NIH HHS [HC 38038, R01 HL 48157] NR 25 TC 47 Z9 48 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 NOV 1 PY 2005 VL 96 IS 9 BP 1280 EP 1283 DI 10.1016/j.amjcard.2005.06.072 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 984YO UT WOS:000233343500021 PM 16253598 ER PT J AU Wilson, MMG Thomas, DR Rubenstein, LZ Chibnall, JT Anderson, S Baxi, A Diebold, MR Morley, JE AF Wilson, MMG Thomas, DR Rubenstein, LZ Chibnall, JT Anderson, S Baxi, A Diebold, MR Morley, JE TI Appetite assessment: simple appetite questionnaire predicts weight loss in community-dwelling adults and nursing home residents SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE appetite; anorexia; weight loss; elderly; screening tools ID SYMPTOM ASSESSMENT SCALE; ANOREXIA; VALIDATION; MORTALITY; CACHEXIA; WOMEN; RISK; DOCUMENTATION; MALNUTRITION; PREVALENCE AB Background: Anorexia-related weight loss can have devastating consequences on quality-of-life, morbidity, and mortality. Without a simple tool to evaluate appetite, health care providers often use inaccurate surrogates, such as measurement of energy consumption and nutritional risk, to reflect appetite. Objective: We aimed to validate a simple tool for assessing appetite and predicting weight loss. Design: This was a cross-sectional measurement study conducted on long-term care residents and community-dwelling adults. Construct validity of the 8-item Council on Nutrition appetite questionnaire (CNAQ) and its 4-item derivative, the simplified nutritional appetite questionnaire (SNAQ), were examined through correlation with a previously validated research tool: the appetite hunger and sensory perception questionnaire (AHSP). The length and complexity of the AHSP render it inefficient for clinical use. The sensitivity and specificity of the CNAQ and SNAQ to predict significant weight loss were calculated. Results: Cronbach's alpha coefficients for the CNAQ were 0.47 (long-term care group) and 0.72 (community-dwelling group). In the long-term care group, the CNAQ correlated with the AHSP (r = 0.60, P < 0.001) and with the AHSP domains of taste (r = 0.47, P < 0.0001), hunger (r = 0.51, P < 0.0001), and smell (r = 0.53, P < 0.0001). The CNAQ showed sensitivities and specificities for 5% and 10% weight losses of 80.2 and 80.3 and 82.4 and 81.9, respectively. The SNAQ had sensitivities and specificities for 5% and 10% weight losses of 81.3 and 76.4 and 88.2 and 83.5, respectively. Conclusions: The SNAQ and CNAQ are short, simple appetite assessment tools that predict weight loss in community-dwelling adults and long-term care residents. The SNAQ is a 4-item derivative of the CNAQ and thus is clinically more efficient. C1 St Louis Univ, Div Geriatr Med, St Louis, MO 63104 USA. St Louis Univ, Dept Psychiat, St Louis, MO 63104 USA. St Louis Vet Affaris Med Ctr, St Louis, MO USA. VA Greater Los Angeles Healthcare Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Wilson, MMG (reprint author), St Louis Univ, Div Geriatr Med, 1402 S Grand Blvd,Room M238, St Louis, MO 63104 USA. EM wilsonmg@slu.edu RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 NR 39 TC 180 Z9 187 U1 3 U2 15 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2005 VL 82 IS 5 BP 1074 EP 1081 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 982JC UT WOS:000233153000023 PM 16280441 ER PT J AU Kratz, A Bengtsson, HI Casey, JE Keefe, JM Beatrice, GH Grzybek, DY Lewandrowski, KB Van Cott, EM AF Kratz, A Bengtsson, HI Casey, JE Keefe, JM Beatrice, GH Grzybek, DY Lewandrowski, KB Van Cott, EM TI Performance evaluation of the CellaVision DM96 system WBC differentials by automated digital image analysis supported by an artificial neural network SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE image analysis; differentials; hematology analyzers; laboratory automation ID LEUKOCYTES; CELLS AB We evaluated the CellaVision DM96 (CellaVision AB, Lund, Sweden), an automated digital cell morphology and informatics system for peripheral blood smears. Technologists agreed with 82% of the instrument's preclassifications. Correlation coefficients between final results released from. the CellaVision and results obtained by direct microscopy were 0.96 (all neutrophils), 0.94 (lymphocytes), 0.88 (segmented neutrophils), 0.73 (eosinophils), 0.69 (bands), and 0.67 (monocytes). After correction for statistically and clinically insignificant variations, the CellaVision DM96 had 95% sensitivity, and 88% specificity for immature myeloid cells. It was 100% sensitive and 94% specific for blasts, and 100% sensitive and 97% specific for unusual WBCs and nucleated RBCs. Advantages of the Cella Vision DM96 over direct microscopy include the ability to review slides from a remote location, consultation and quality control on a cell-by-cell basis, and potential labor savings. C1 Massachusetts Gen Hosp, Div Lab Med, Clin Hematol Lab, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. CellaVis AB, Lund, Sweden. RP Kratz, A (reprint author), Massachusetts Gen Hosp, Div Lab Med, Clin Hematol Lab, Dept Pathol, 55 Fruit St,GRJ 235, Boston, MA 02114 USA. NR 17 TC 37 Z9 43 U1 0 U2 4 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 NOV PY 2005 VL 124 IS 5 BP 770 EP 781 DI 10.1039/XMB9K0J41LHLATAY PG 12 WC Pathology SC Pathology GA 977XJ UT WOS:000232836500013 PM 16203273 ER PT J AU Kroenke, CH Bennett, GG Fuchs, C Giovannucci, E Kawachi, I Schernhammer, E Holmes, MD Kubzansky, LD AF Kroenke, CH Bennett, GG Fuchs, C Giovannucci, E Kawachi, I Schernhammer, E Holmes, MD Kubzansky, LD TI Depressive symptoms and prospective incidence of colorectal cancer in women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE colorectal neoplasms; depression; women ID NUTRITION EXAMINATION SURVEY; HEALTH SURVEY SF-36; C-REACTIVE PROTEIN; MIDDLE-AGED MEN; FOLLOW-UP; MAJOR DEPRESSION; PHYSICAL-ACTIVITY; BREAST-CANCER; RISK-FACTORS; PERSONALITY-FACTORS AB The authors examined depressive symptoms and prospective incidence of colorectal cancer and distal colorectal adenomas in 81,612 women without prior cancer from the Nurses' Health Study; 400 cases of colorectal cancer and 680 distal colorectal adenomas accrued between 1992 and the year 2000. Depressive symptoms were assessed in 1992 and 1996 with the five-question Mental Health Index (MHI-5), a subscale of the Short-Form 36 health status survey. Scores ranged from 0 to 100, and women with scores between 0 and 52 were defined as having significant depressive symptomatology. The authors also created four categories across the range of Mental Health Index scores: 0-52, 53-75, 76-85, and 86-100 (referent). Cox proportional hazards models were used to analyze the extent of depressive symptoms and colorectal events. Analyses were stratified by body mass index. In multivariate analyses with updated exposure, women with the highest levels of depressive symptoms had an elevated risk of incident colorectal cancer (hazard ratio = 1.43, 95% confidence interval: 0.97, 2.11) compared with women with the lowest levels of symptoms (p(trend) = 0.04). Associations appeared stronger in overweight women. However, depressive symptoms were unrelated to risk of colorectal adenomas. Associations are consistent with a possible role in late promotion of the disease. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Kroenke, CH (reprint author), Channing Labs, 181 Longwood Ave,3rd Floor, Boston, MA 02115 USA. EM candyce.kroenke@channing.harvard.edu FU NCI NIH HHS [CA87969] NR 70 TC 35 Z9 35 U1 2 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2005 VL 162 IS 9 BP 839 EP 848 DI 10.1093/aje/kwi302 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 976PP UT WOS:000232745900006 PM 16207809 ER PT J AU Jensen, DM AF Jensen, DM TI Management of patients with severe hematochezia - With all current evidence available SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID DIVERTICULAR HEMORRHAGE; URGENT COLONOSCOPY; HOSPITAL STAY; DIAGNOSIS; HEMOSTASIS AB A randomized controlled trial (RCT) of routine urgent colonoscopy in severe lower gastrointestinal tract bleeding is reported in this journal from Duke. The only significant differences in results between the standard management (emergency red blood cell (RBC) scanning and angiography with elective colonoscopy) and urgent colonoscopy were in rates of finding a definitive bleeding site-one with a major stigmata of hemorrhage-and in not making a diagnosis. The trial was stopped early for logistics reasons a decade ago. The strengths and limitations of the study are discussed and contrasted with recent reports of other investigators. Similar to management of patients with non-variceal upper gastrointestinal tract (UGI) hemorrhage, triaging patients to level of care by comorbidity scores and stigmata of hemorrhage, successful colonoscopic hemostasis of focal lesions, and individualization of long-term medical, endoscopic, and surgical care are recommended based on promising reports by other investigators. Meanwhile, further RCTs for patients with severe hematochezia are warranted. C1 VA Greater Los Angeles Healthcare Syst, CURE Digest Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. RP Jensen, DM (reprint author), VA Greater Los Angeles Healthcare Syst, CURE Digest Res Ctr, Bldg 115,Rm 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 20 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2005 VL 100 IS 11 BP 2403 EP 2406 DI 10.1111/j.1572-0241.2005.00298.x PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 976ZD UT WOS:000232771300009 PM 16279892 ER PT J AU Jacobson, IM Gonzalez, SA Ahmed, F Lebovics, E Min, AD Bodenheimer, HC Esposito, SP Brown, RS Brau, N Klion, FM Tobias, H Bini, EJ Brodsky, N Cerulli, MA Aytaman, A Gardner, PW Geders, JM Spivack, JE Rahmin, MG Berman, DH Ehrlich, J Russo, MW Chait, M Rovner, D Edlin, BR AF Jacobson, IM Gonzalez, SA Ahmed, F Lebovics, E Min, AD Bodenheimer, HC Esposito, SP Brown, RS Brau, N Klion, FM Tobias, H Bini, EJ Brodsky, N Cerulli, MA Aytaman, A Gardner, PW Geders, JM Spivack, JE Rahmin, MG Berman, DH Ehrlich, J Russo, MW Chait, M Rovner, D Edlin, BR TI A randomized trial of pegylated interferon alpha-2b plus ribavirin in the retreatment of chronic hepatitis C SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID SUSTAINED VIROLOGICAL RESPONSE; WEIGHT-BASED RIBAVIRIN; COMBINATION THERAPY; PEGINTERFERON ALPHA-2A; AFRICAN-AMERICANS; INITIAL TREATMENT; NONRESPONDERS; MULTICENTER; GENOTYPE-1; RESISTANT AB OBJECTIVES: The efficacy of combination therapy with pegylated interferon (PEG IFN) alpha plus ribavirin (RBV) in the retreatment of chronic hepatitis C (CHC) in patients who previously failed combination standard IFN plus RBV or IFN monotherapy has not been well established. METHODS: Three hundred and twenty-one CHC patients including virologic nonresponders to combination IFN plus RBV (n = 219) or IFN monotherapy (n = 47), and relapsers to combination therapy (n = 55) were randomized to receive PEG IFN alpha-2b 1.5 mu g/kg per wk plus RBV 800 mg per day (Regimen A, n = 160) or PEG IFN alpha-2b 1.0 mu g/kg per wk plus RBV 1,000-1,200 mg per day (Regimen B, n = 161) for 48 wks. RESULTS: Sustained virologic response (SVR) occurred in 16% of the overall study population (Regimen A vs B, 18%vs 13%, p= 0.21), in 8% of the combination therapy nonresponders (10%vs 6%, p= 0.35), in 21% of the IFN monotherapy nonresponders (16%vs 27%, p= 0.35), and in 42% of the combination therapy relapsers (50%vs 32%, p= 0.18). In nonresponders to prior combination therapy, HCV ribonucleic acid levels < 100,000 copies/mL at the end of the prior treatment course were associated with an increased SVR compared with levels >= 100,000 copies/mL (21%vs 5%, p= 0.002). In the overall study population, genotype 1 patients had lower SVR rates than others (14%vs 33%, p= 0.01), and African Americans had lower SVR than Caucasians (4%vs 18%, p= 0.01). CONCLUSION: Combination therapy with PEG IFN alpha-2b plus RBV is more effective in patients who relapsed after combination standard IFN plus RBV than in nonresponders to either combination therapy or IFN monotherapy. There was no significant effect of dosing regimen. C1 Cornell Univ, Weill Med Coll, Div Gastroenterol & Hepatol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Ctr Study Hepatitis C, New York, NY 10021 USA. New York Med Coll, Div Gastroenterol & Hepatobiliary Dis, Valhalla, NY 10595 USA. Beth Israel Med Ctr, Div Digest Dis, New York, NY 10003 USA. Hepatobiliary Associates New York, Bayside, NY USA. Columbia Univ, Coll Phys & Surg, Ctr Liver Dis & Transplantat, New York, NY USA. Columbia Univ, Coll Phys & Surg, Div Digest & Liver Dis, New York, NY USA. Bronx Vet Adm Med Ctr, Div Infect Dis, Bronx, NY USA. Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. NYU, Sch Med, Div Gastroenterol, New York, NY USA. New York VA Med Ctr, Div Gastroenterol & Hepatol, New York, NY USA. Palmadessa & Kuan Gastroenterol Associates, Flushing, NY USA. Brooklyn Hosp Ctr, Div Gastroenterol & Hepatol, Brooklyn, NY USA. VA New York Harbor Healthcare Syst, Div Gastroenterol, Brooklyn, NY USA. Gastroenterol Consultants, Stamford, CT USA. New York Methodist Hosp, Div Gastroenterol & Hepatol, Brooklyn, NY USA. Gastroenterol Associates Fairfield Cty, Fairfield, CT USA. Gastrointestinal Associates, Ridgewood, NJ USA. Pk Ave Med & Gastroenterol, New York, NY USA. Gastroenterol Westchester, Bronxville, NY USA. Hartsdale Med Grp, Hartsdale, NY USA. RP Jacobson, IM (reprint author), Cornell Univ, Weill Med Coll, Div Gastroenterol & Hepatol, 450 E 69th St, New York, NY 10021 USA. OI Edlin, Brian/0000-0001-8172-8797 NR 51 TC 90 Z9 97 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD NOV PY 2005 VL 100 IS 11 BP 2453 EP 2462 DI 10.1111/j.1572-0241.2005.00282.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 976ZD UT WOS:000232771300017 PM 16279900 ER PT J AU Donohue, J Hanlon, JT AF Donohue, J Hanlon, JT TI Helping Medicare patients benefit from the new Medicare drug benefit: An overview with practice tips SO AMERICAN JOURNAL OF GERIATRIC CARDIOLOGY LA English DT Review ID BENEFICIARIES; QUALITY AB The new Medicare drug benefit (Part D) will expand drug coverage to the millions of Medicare beneficiaries who currently lack insurance protection against the costs of prescription drugs. This dramatic expansion of benefits could increase medication treatment for many chronic health conditions, but the impact of Part D on the affordability of prescription drugs depends on a series of choices beneficiaries must make including whether to sign up for the voluntary benefit and which of several drug plans to choose. Private prescription drug plans administering the benefit will vary in terms of the cost sharing, premiums, and formulary design. Providers can play an important role in providing patients with the resources necessary to make good choices regarding drug coverage. Medicare will also provide reimbursement for medication therapy management. The transition of Medicare beneficiaries to Part D drug plans provides an important opportunity for providers to review and possibly make changes to their elderly patients' drug regimens to maximize effectiveness while minimizing costs to patients. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med Geriatr, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Hlth Care Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Donohue, J (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, 130 Desoto St, Pittsburgh, PA 15261 USA. EM jdonohue@pitt.edu OI Donohue, Julie/0000-0003-2418-6017 FU NIA NIH HHS [P30 AG024827]; NICHD NIH HHS [1K12HD049109] NR 18 TC 1 Z9 1 U1 0 U2 0 PU LE JACQ LTD PI DARIEN PA 3 PARKLANDS DRIVE, DARIEN, CT 06820 USA SN 1076-7460 J9 AM J GERIATR CARDIOL JI Am. J. Geriatr. Cardiol. PD NOV-DEC PY 2005 VL 14 IS 6 BP 291 EP 297 DI 10.1111/j.1076-7460.2005.04914.x PG 7 WC Cardiac & Cardiovascular Systems; Geriatrics & Gerontology SC Cardiovascular System & Cardiology; Geriatrics & Gerontology GA 010DJ UT WOS:000235166800003 PM 16276125 ER PT J AU Harwood, DG Sultzer, DL Feil, D Monserratt, L Freedman, E Mandelkern, MA AF Harwood, DG Sultzer, DL Feil, D Monserratt, L Freedman, E Mandelkern, MA TI Frontal lobe hypometabolism and impaired insight in Alzheimer disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID NEUROBEHAVIORAL RATING-SCALE; COGNITIVE DEFICITS; BEHAVIORAL DISTURBANCES; PSYCHIATRIC-SYMPTOMS; ANOSOGNOSIA; AWARENESS; DEMENTIA; UNAWARENESS; DEPRESSION; VARIANT AB Objective: The authors examined the relationship between impaired insight regarding cognitive and functional deficits and frontal cortex hypometabolism in 41 patients with Alzheimer disease ( AD). Methods: Regional cerebral glucose metabolism was determined with (18F)fluorodeoxyglucose and positron emission tomography. Level of insight was measured with the clinician-rated Neurobehavioral Rating Scale, and severity of global cognitive impairment was determined with the Mini-Mental State Exam. Results: Inaccurate insight was correlated with glucose metabolic rate in the right lateral frontal cortex ( Brodmann areas 6 and 45, and the lateral aspect of Brodmann areas 8 and 9) after controlling for global cognitive dysfunction. Conclusions: The findings from this study help to further elucidate the neurobiological mechanisms underlying impaired insight in AD, indicating a link between this important clinical phenomenon and dysmetabolism in a focal region of the right prefrontal cortex. C1 Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst & Hosp, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Mental Hlth Serv, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Nucl Med Serv, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys & Radiol Sci, Irvine, CA 92717 USA. RP Sultzer, DL (reprint author), W Los Angeles VA Healthcare Ctr, 11301 Wilshire Blvd,3 S,116AF, Los Angeles, CA 90073 USA. EM dsultzer@ucla.edu FU NIMH NIH HHS [MH56031] NR 52 TC 36 Z9 38 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2005 VL 13 IS 11 BP 934 EP 941 DI 10.1176/appi.ajgp.13.11.934 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 982NQ UT WOS:000233169300003 PM 16286436 ER PT J AU Watson, GS Cholerton, BA Reger, MA Baker, LD Plymate, SR Asthana, S Fishel, MA Kulstad, JJ Green, PS Cook, DG Kahn, SE Keeling, ML Craft, S AF Watson, GS Cholerton, BA Reger, MA Baker, LD Plymate, SR Asthana, S Fishel, MA Kulstad, JJ Green, PS Cook, DG Kahn, SE Keeling, ML Craft, S TI Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone - A preliminary study SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article ID AMYLOID PRECURSOR PROTEIN; INSULIN-RESISTANCE; GAMMA AGONISTS; MEMORY; RISK; PHOSPHORYLATION; MECHANISMS; A-BETA-42; MOLECULES; DEMENTIA AB Objective: Insulin resistance ( impaired insulin action) has been associated with Alzheimer disease ( AD) and memory impairment, independent of AD. Peroxisome proliferator-activated receptor-gamma ( PPAR-gamma) agonists improve insulin sensitivity and regulate in-vitro processing of the amyloid precursor protein (APP). Authors evaluated the effects of the PPAR-gamma agonist rosiglitazone on cognition and plasma levels of the APP derivative beta-amyloid (A beta) in humans. Methods: In a placebo-controlled, double-blind, parallel-group pilot study, 30 subjects with mild AD or amnestic mild cognitive impairment were randomized to a 6-month course of rosiglitazone ( 4 mg daily; N = 20) or placebo ( N = 10). Primary endpoints were cognitive performance and plasma Ab levels. Results: Relative to the placebo group, subjects receiving rosiglitazone exhibited better delayed recall ( at Months 4 and 6) and selective attention ( Month 6). At Month 6, plasma A beta levels were unchanged from baseline for subjects receiving rosiglitazone but declined for subjects receiving placebo, consistent with recent reports that plasma A beta 42 decreases with progression of AD. Conclusions: Findings provide preliminary support that rosiglitazone may offer a novel strategy for the treatment of cognitive decline associated with AD. Future confirmation in a larger study is needed to fully C1 VAPSHCS, GRECC, Seattle, WA 98108 USA. VAPSHCS, Res & Dev Serv, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, GRECC, William S Middleton Mem Vet Hosp, Madison, WI USA. RP Craft, S (reprint author), VAPSHCS, GRECC, S-1482-GRECC,1660 S Columbian Way, Seattle, WA 98108 USA. EM scraft@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 NR 25 TC 338 Z9 363 U1 1 U2 19 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2005 VL 13 IS 11 BP 950 EP 958 DI 10.1176/appi.ajgp.13.11.950 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 982NQ UT WOS:000233169300005 PM 16286438 ER PT J AU Hirschman, KB Joyce, CM AF Hirschman, KB Joyce, CM TI Would caregivers of Alzheimer disease patients involve their relative in a decision to use an AD-slowing medication? SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Gerontological-Society-of-America CY NOV 21-25, 2003 CL San Diego, CA SP Gerontol Soc Amer ID PREFERENCES; TRIAL AB Objectives: The authors examined the factors associated with 1) caregivers' willingness to involve a relative with Alzheimer disease ( AD) in a decision to use an AD-slowing treatment; and 2) how caregivers would resolve a disagreement over this decision with the their relative. Methods: This was a cross-sectional interview study of 102 caregivers of patients with mild-to-severe-stage AD, enrolled in a University Memory Disorders Clinic. Results: Forty- four percent of caregivers (45/102) said that his or her relative would participate in a decision to use an AD-slowing treatment. Logistic regression showed that having less dementia severity, being a female caregiver, and a spousal relationship were all associated with caregivers' involving their relative in this decision. Among the caregivers who said they would involve their relative, the majority said they would resolve disagreements over whether to use the treatment in favor of what the patient wanted, versus what the family wanted for the patient. Male caregivers were less likely to resolve disagreements in favor of the patients' preferences. Conclusion: Although most caregivers of patients in mild-to-moderate stages would include these patients in an AD treatment decision, certain caregiver characteristics, such as gender and relationship, are associated with not involving patients in this decision. Physicians working with dementia patients and their family members should take these characteristics into account when discussing treatment options and work with patient-caregiver dyads to improve the communication of preferences. C1 Univ Penn, Inst Aging, Philadelphia, PA 19104 USA. Univ Penn, Sch Nursing, Div Biobehav & Hlth Sci, Philadelphia, PA 19104 USA. Univ Penn, Dept Sociol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Alzheimers Dis Ctr, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Ctr Hlth Equit Res & Promot, Philadelphia, PA USA. RP Hirschman, KB (reprint author), Univ Penn, Inst Aging, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM hirschk@nursing.upenn.edu FU NIA NIH HHS [K01 AG-00931, P30-AG10124, T32 AG-00255] NR 23 TC 9 Z9 9 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2005 VL 13 IS 11 BP 1014 EP 1021 DI 10.1176/appi.ajgp.13.11.1014 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 982NQ UT WOS:000233169300013 PM 16286446 ER PT J AU Weinreb, NJ Barranger, JA Charrow, J Grabowski, GA Mankin, HJ Mistry, P AF Weinreb, NJ Barranger, JA Charrow, J Grabowski, GA Mankin, HJ Mistry, P TI Guidance on the use of miglustat for treating patients with type 1 Gaucher disease SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Review DE Gaucher disease; miglustat; substrate reduction therapy; enzyme replacement therapy AB Type 1 Gaucher disease (GD) is a progressive lysosomal storage disorder due to an autosomal recessive deficiency of glucocerebrosidase. Clinical manifestations include anemia, thrombocytopenia, hepatosplenomegaly, and bone and pulmonary disease. Intravenous enzyme replacement (ERT) with imiglucerase is the accepted standard for treatment of symptomatic patients. More than 3,500 patients worldwide have received ERT with well-documented beneficial effects on the hematological, visceral, skeletal, and pulmonary manifestations, and with resultant improvement in health-related quality of life. Miglustat, an imino sugar that reversibly inhibits glucosylceramide synthase and reduces intracellular substrate burden, is an oral treatment for patients with type 1 GD that was recently approved in the United States for symptomatic patients with mild to moderate clinical manifestations for whom ERT is not an option. Because responses to miglustat are slower and less robust than those observed with ERT, and because miglustat is associated with significant side effects, clinicians who care for patients with GD should become familiar with the limited indications for miglustat use and the circumstances when it may be prescribed appropriately. This review article and position statement represents the current opinion of American physicians with extensive expertise in GD regarding patient management in the context of the availability of standard imiglucerase treatment and the recent introduction of miglustat. C1 Univ Res Fdn Lysosomal Storage Dis, Hollywood, FL 33021 USA. Univ Res Fdn Lysosmal Storage Dis & NW Oncol Hema, Coral Springs, FL USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL USA. NW Univ, Sch Med, Chicago, IL USA. Childrens Hosp, Res Fdn, Div & Program Human Genet, Cincinnati, OH USA. Massachusetts Gen Hosp, Orthoped Oncol Serv, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Dept Med, New Haven, CT USA. RP Weinreb, NJ (reprint author), Univ Res Fdn Lysosomal Storage Dis, 3730 B 54th Ave, Hollywood, FL 33021 USA. EM boneal@winning.com NR 19 TC 54 Z9 59 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD NOV PY 2005 VL 80 IS 3 BP 223 EP 229 DI 10.1002/ajh.20504 PG 7 WC Hematology SC Hematology GA 981AS UT WOS:000233060000010 PM 16247743 ER PT J AU Gelber, RP Kurth, T Kausz, AT Manson, JAE Buring, JE Levey, AS Gaziano, JM AF Gelber, RP Kurth, T Kausz, AT Manson, JAE Buring, JE Levey, AS Gaziano, JM TI Association between body mass index and CKD in apparently healthy men SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE kidney; obesity; risk factors ID CHRONIC KIDNEY-DISEASE; GLOMERULAR-FILTRATION-RATE; CORONARY HEART-DISEASE; CARDIOVASCULAR-DISEASE; RENAL DYSFUNCTION; SERUM CREATININE; RISK-FACTORS; MYOCARDIAL-INFARCTION; PREDICTION EQUATIONS; METABOLIC SYNDROME AB Background Overweight and obesity are well-established risk factors for cardiovascular disease and decline in kidney function in individuals with existing chronic kidney disease (CKD). Conversely, their association with the development of CKD is less clear. Methods: We evaluated the association between body mass index (BMI) and risk for CKD in a cohort of 11,104 initially healthy men who participated in the Physicians' Health Study and provided a blood sample after 14 years. BMI was calculated from self-reported weight and height. We estimated glomerular filtration rate (GFR) by using the abbreviated equation from the Modification of Diet in Renal Disease Study and defined CKD as GFR less than 60 mL/min/1.73 m(2) (< 1 mL/s/1.73 m(2)). Results: After an average 14-year follow-up, 1,377 participants (12.4%) had a GFR less than 60 mL/min/1.73 m(2) (< 1 mL/s/1.73 m(2)). Higher baseline BMI was associated consistently with increased risk for CKD. Compared with participants in the lowest BMI quintile (< 22.7 kg/m(2)), those in the highest quintile (> 26.6 kg/m(2)) had an odds ratio (OR) of 1.45 (95% confidence interval [CI], 1.19 to 1.76; P trend <0.001) after adjusting for potential confounders. We found similar associations by using different categories of BMI. Compared with men who remained within a +/- 5% range of their baseline BMI, those who reported a BMI increase greater than 10% had a significant increase in risk for CKD (OR, 1.27; 95% Cl, 1.06 to 1.53). Conclusion: In this large cohort of initially healthy men, BMI was associated significantly with increased risk for CKD after 14 years. Strategies to decrease CKD risk might include prevention of overweight and obesity. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02120 USA. Brigham & Womens Hosp, Div Prevent Med, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Div Nephrol, Dept Med, Boston, MA 02111 USA. Boston VA Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. RP Kurth, T (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02120 USA. EM tkurth@rics.bwh.harvard.edu RI Kurth, Tobias/A-9243-2012 OI Kurth, Tobias/0000-0001-7169-2620 FU NCI NIH HHS [CA 34944, CA 40360, R01 CA097193]; NHLBI NIH HHS [HL 26490, HL 34595] NR 46 TC 228 Z9 240 U1 1 U2 5 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 NOV PY 2005 VL 46 IS 5 BP 871 EP 880 DI 10.1053/j.ajkd.2005.08.015 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 993DR UT WOS:000233933400010 PM 16253727 ER PT J AU Watnick, S Wang, PL Demadura, T Ganzini, L AF Watnick, S Wang, PL Demadura, T Ganzini, L TI Validation of 2 depression screening tools in dialysis patients SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE dialysis; depression; screening ID PATIENTS STARTING DIALYSIS; PRIMARY-CARE; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS; MAJOR DEPRESSION; RENAL-DISEASE; MORTALITY; OUTCOMES; IDENTIFICATION; PREDICTOR AB Background Depression is the most common psychiatric disorder in long-term dialysis patients and is a risk factor for morbidity and mortality. An efficient and valid method of diagnosing depression might facilitate recognition and treatment. We sought to validate 2 depression assessment tools, the 21-question Beck Depression Inventory (BDI) and the 9-question Patient Health Questionnaire (PHQ-9), in a dialysis population. Methods: We surveyed patients who had received dialysis for at least 90 days in Portland, OR. We excluded patients with dementia, delirium, or a history of major psychiatric disorders other than depression. The Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, a gold-standard measure for depression, was administered by trained psychologists within 2 weeks of the BDI and PHQ-9. Results: Of 62 enrolled subjects, 16 were diagnosed with a depressive disorder, including 12 patients (19%) with major depression, 3 patients with dysthymia, and I patient with minor depression. Optimal BDI and PHQ-9 cutoff values for depressive disorders combined was 16 or greater and 10 or greater, respectively. Sensitivities were 91% and 92%, specificities were 86% and 92%, positive predictive values were 59% and 71 %, and negative predictive values were both 98%,with kappa valuesof 0.65 and 0.75, respectively. The difference between the 2 receiver operating characteristic curves was not statistically significant (P > 0.9). Conclusion: Our results validate the PHQ-9 and revalidate the BDI against a gold-standard measure for depressive disorders in the dialysis population. Both tools performed equally well. Because depression is prevalent, readily diagnosed, and associated with poor outcomes, screening by means of short and valid measurement tools may lead to better diagnosis and treatment of this modifiable risk factor. This may lead to improved clinical outcomes in dialysis patients. Am J Kidney Dis 46:919-924. (c) 2005 by the National Kidney Foundation, Inc. C1 Oregon Hlth Sci Univ, VA Dialysis Unit, Dept Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97239 USA. Vet Adm Med Ctr, Div Mental Hlth, Portland, OR USA. Vet Adm Med Ctr, Div Hosp & Specialty Med, Portland, OR USA. RP Watnick, S (reprint author), Oregon Hlth Sci Univ, VA Dialysis Unit, Dept Med, Portland, OR 97239 USA. EM watnicks@ohsu.edu NR 24 TC 144 Z9 147 U1 0 U2 7 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 NOV PY 2005 VL 46 IS 5 BP 919 EP 924 DI 10.1053/j.ajkd.2005.08.006 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 993DR UT WOS:000233933400016 PM 16253733 ER PT J AU Luk, AJ Simkin, PA AF Luk, AJ Simkin, PA TI Epidemiology of hyperuricemia and gout SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID SERUM URIC-ACID; NUTRITION EXAMINATION SURVEY; PRACTICE RESEARCH DATABASE; 3RD NATIONAL-HEALTH; CHRONIC HEART-FAILURE; PURINE-RICH FOODS; METABOLIC SYNDROME; CARDIOVASCULAR-DISEASE; ASYMPTOMATIC HYPERURICEMIA; ANTIOXIDANT CAPACITY AB Gout is an increasingly common medical problem. The traditional risk factors of male sex and high red meat or alcohol consumption have been joined by a wave of newer risk factors, such as increased longevity, the metabolic syndrome (hypertension, diabetes, dyslipidemia, truncal obesity, increased cardiovascular disease risk), use of diuretics, low-dose aspirin, or cyclosporine, and end-stage renal disease. Atypical presentations of gout in the elderly can mimic osteoarthritis and rheumatoid arthritis. There is a resurgence of interest in hyperuricemia as an independent and potentially modifiable cardiovascular risk factor. The pharmacologic management of gout in general practice suffers from a number of quality-control issues. This article reviews these and other new epidemiologic data on this ancient disease. C1 Univ Washington, Div Rheumatol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Luk, AJ (reprint author), Univ Washington, Div Rheumatol, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 72 TC 57 Z9 64 U1 0 U2 7 PU AMER MED PUBLISHING, M W C COMPANY PI JAMESBURG PA 241 FORSGATE DR, STE 102, JAMESBURG, NJ 08831 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD NOV PY 2005 VL 11 IS 15 SU S BP S435 EP S442 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 988MD UT WOS:000233604400001 PM 16300457 ER PT J AU Rehman, SU Nietert, PJ Cope, DW Kilpatrick, AO AF Rehman, SU Nietert, PJ Cope, DW Kilpatrick, AO TI What to wear today? Effect of doctor's attire on the trust and confidence of patients SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE physician attire; physician dress; patient trust ID PHYSICIAN ATTIRE; WHITE COAT; ATTITUDES; CLOTHES; STYLE; COMMUNICATION; CONSULTATIONS; DRESS AB PURPOSE: There are very few studies about the impact of physicians' attire on patients' confidence and trust. The objective of this study was to determine whether the way a doctor dresses is an important factor in the degree of trust and confidence among respondents. METHODS: A cross-sectional descriptive study using survey methodology was conducted of patients and visitors in the waiting room of an internal medicine outpatient clinic. Respondents completed a written survey after reviewing pictures of physicians in four different dress styles. Respondents were asked questions related to their preference for physician dress as well as their trust and willingness to discuss sensitive issues. RESULTS: Four hundred respondents with a mean age of 52.4 years were enrolled; 54% were men, 58% were white, 38% were African-American, and 43% had greater than a high school. diploma. On all questions regarding physician dress style preferences, respondents significantly favored the professional attire with white coat (76.3%, P <.0001), followed by surgical scrubs (10.2%), business dress (8.8%), and casual dress (4.7%). Their trust and confidence was significantly associated with their preference for professional dress (P <.0001). Respondents also reported that they were significantly more willing to share their social, sexual, and psychological problems with the physician who is professionally dressed (P <.0001). The importance of physician's appearance was ranked similarly between male and female respondents (P =.54); however, female physicians' dress appeared to be significantly more important to respondents than male physicians' dress (P <.001). CONCLUSION: Respondents overwhelmingly favor physicians in professional attire with a white coat. Wearing professional dress (ie, a white coat with more formal attire) while providing patient care by physicians may favorably influence trust and confidence-building in the medical encounter. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Mt Pleasant, SC 29464 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Univ Calif Los Angeles, San Fernando Valley Program, Los Angeles, CA USA. Olive View UCLA Med Ctr, Sylmar, CA 91342 USA. Med Univ S Carolina, Dept Hlth Adm & Policy, Charleston, SC 29425 USA. RP Rehman, SU (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 214 Hist Dr, Mt Pleasant, SC 29464 USA. EM rehmans@musc.edu OI Nietert, Paul/0000-0002-3933-4986 NR 40 TC 82 Z9 85 U1 2 U2 25 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 NOV PY 2005 VL 118 IS 11 BP 1279 EP 1286 DI 10.1016/j.amjmed.2005.04.026 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 981YD UT WOS:000233123000017 PM 16271913 ER PT J AU Hatton, MP Rubin, PAD Foster, CS AF Hatton, MP Rubin, PAD Foster, CS TI Successful treatment of idiopathic orbital inflammation with mycophenolate mofetil SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID THERAPY AB PURPOSE: To report our experience with the use of mycophenolate mofetil for treatment of idiopathic orbital inflammation (IOI). DESIGN: Noncomparative interventional case series. METHODS: We reviewed the records of five patients with IOI who were treated with mycophenolate mofetil. The indications for use included recurrent inflammation after other therapies (four patients) and to avoid corticosteroid-induced blood sugar elevation in poorly controlled diabetes mellitus (one patient). Treated patients were followed for a median of 8.5 months (range, 4-30 months) after mycophenolate mofetil therapy was begun. Main outcome measures were response to treatment, treatment-related side effects, drug dosage, previous and final treatment regimens, and discontinuation of systemic corticosteroids. RESULTS: Mycophenolate mofetil therapy was discontinued in one patient because of nausea. Each of the remaining four patients experienced complete resolution of orbital inflammation. Of these, only one patient remains on prednisone, but at a significantly reduced dose (1 mg/d). CONCLUSION: Mycophenolate mofetil therapy resulted in the resolution of inflammation in patients with refractory or corticosteroid-dependent IOI and was used successfully for a first episode of IOI in a patient for whom corticosteroids were contraindicated. C1 Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, Cambridge, MA 02142 USA. Massachusetts Eye & Ear Infirm, Dept Oculophast Orbit, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Cosmet Surg, Boston, MA USA. Massachusetts Eye Res & Surg Inst, Boston, MA USA. RP Foster, CS (reprint author), Massachusetts Eye Res & Surg Inst, Ocular Immunol & Uveitis Fdn, 5 Cambridge Ctr,8th Floor, Cambridge, MA 02142 USA. EM fosters@uveitis.org NR 7 TC 16 Z9 16 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 NOV PY 2005 VL 140 IS 5 BP 916 EP 918 DI 10.1016/j.ajo.2005.04.053 PG 3 WC Ophthalmology SC Ophthalmology GA 990PL UT WOS:000233755600022 PM 16310473 ER PT J AU Nagai, H Ota, F Konopacki, R Connor, NP AF Nagai, H Ota, F Konopacki, R Connor, NP TI Discoordination of laryngeal and respiratory movements in aged rats SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID HEAVY-CHAIN ISOFORMS; SWALLOWING DISORDERS; BREATHING PATTERN; INTERNAL BRANCH; MUSCLE-ACTIVITY; NERVE; CAT; VOCALIZATION; RESISTANCE; AFFERENTS AB Voice and swallowing actions require the coordination of multiple motor systems, and this coordination may be impaired with aging. Although recent work has reported impairments in age-related laryngeal kinematics in rats, the temporal relationship of laryngeal excursions to the respiratory cycle is unknown. The goal of this study was to assess laryngeal-respiratory coordination by examining temporal interrelationships between change in laryngeal aperture and chest wall movement during quiet breathing in a rat model. Glottal images were recorded, digitized, and synchronized with respiratory signals, and temporal features were measured. In the young animals, glottal opening began before the onset of inspiration, and glottal and respiratory cycles were phasic and stereotypic. In old animals, however, inspiration often began during the glottal closing phase, and both respiratory signals were asymmetric. Discoordination of laryngeal and respiratory motor actions associated with aging may be caused by a generalized decline in sensorimotor cranial functions and may contribute to age-related swallowing and communication impairment. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg, Madison, WI 53792 USA. Kitasato Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Kanagawa, Japan. Jikei Univ, Sch Med, Dept Otolaryngol Head & Neck Surg, Tokyo, Japan. Univ Wisconsin, Dept Biostat, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. RP Connor, NP (reprint author), Univ Wisconsin, Ctr Clin Sci, Dept Surg, Div Otolaryngol Head & Neck Surg, Madison, WI 53792 USA. EM connor@surgery.wisc.edu NR 43 TC 9 Z9 10 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 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 2005 VL 26 IS 6 BP 377 EP 382 DI 10.1016/j.amjoto.2005.02.015 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 986TQ UT WOS:000233473000003 PM 16275405 ER PT J AU Faulkner, JL Szcykalski, LM Springer, F Barnes, JL AF Faulkner, JL Szcykalski, LM Springer, F Barnes, JL TI Origin of interstitial fibroblasts in an accelerated model of angiotensin II-induced renal fibrosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; 5/6 NEPHRECTOMIZED RATS; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; PROLIFERATIVE GLOMERULONEPHRITIS; PROGRESSIVE GLOMERULOSCLEROSIS; TUBULOINTERSTITIAL FIBROSIS; KIDNEY FIBROSIS; MESANGIAL CELLS; BONE-MARROW AB To determine whether previous renal injury accelerates the progression of glomerulosclerosis and interstitial fibrosis, we examined the effect of treating rats with angiotensin H after Habu venom injury. After initiating disease, we examined the origin of interstitial myofibroblasts by locating a-smooth muscle actin (alpha-SMA)-positive and Na+,K+-ATPase-positive cells relative to interstitial space, tubular epithelial cells, the tubular basement membrane (TBM), and vascular structures. Tubular epithelial-mesenchymal transition was also assessed by examining TBM integrity and by using Texas Red (TR)-dextran in intravital tracking experiments. The staining of alpha-SMA-positive myofibroblasts dramatically increased in peritubular interstitial spaces 48 hours after Habu venom plus angiotensin II, particularly in and around perivascular and periglomerular regions, while tubular epithelial cells were alpha-SMA-negative. Na+,K+-ATPase-positive and TR-dextran-labeled cells were restricted to the tubular epithelium and excluded from the interstitium. By 7 and 14 days, expanded interstitial space contained only alpha-STMA-positive myofibroblasts without TR-dextran endocytic particles. Epithelium of atrophic tubules containing TR-dextran remained confined by surrounding interstitium and myofibroblasts. These studies indicate that early expansion of a-SMA-positive cells in the interstitium and loss of tubular area occur via encroachment of interstitial myofibroblasts from perivascular into atrophic tubular spaces rather than via epithelial-mesenchymal transition and migration of tubular cells through the TBM into the interstitium. C1 Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Med Res Serv, S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Barnes, JL (reprint author), Univ Texas, Hlth Sci Ctr, Div Nephrol, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM barnesj@uthscsa.edu FU NIDDK NIH HHS [P50 DK061597] NR 53 TC 68 Z9 72 U1 0 U2 4 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 NOV PY 2005 VL 167 IS 5 BP 1193 EP 1205 DI 10.1016/S0002-9440(10)61208-4 PG 13 WC Pathology SC Pathology GA 979UK UT WOS:000232970200003 PM 16251405 ER PT J AU Riemenschneider, MJ Mueller, W Betensky, RA Mohapatra, G Louis, DN AF Riemenschneider, MJ Mueller, W Betensky, RA Mohapatra, G Louis, DN TI In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CELL-MIGRATION; EXTRACELLULAR-MATRIX; RAT-BRAIN; TUMORS; FAK; EXPRESSION; INVASION; ALPHA-V-BETA-8; LOCALIZATION; ASTROCYTOMA AB Deregulated integrin signaling is common in cancers, including glioblastoma. integrin binding and growth factor receptor signaling activate focal adhesion kinase (FAK) and subsequently up-regulate extracellular regulated kinases (ERK-1/2), leading to cell-cycle progression and cell migration. Most studies of this pathway have used in vitro systems or tumor lysate-based approaches. We examined these pathways primarily in situ using a panel of 30 glioblastomas and gene expression arrays, immunohistochemistry, and fluorescence in situ hybridization, emphasizing the histological distribution of molecular changes. Within individual tumors, increased expression of FAK, p-FAK, paxillin, ERK-1/2, and p-ERK-1/2 occurred in regions of elevated EGFR and/or PDGFRA expression. Moreover, FAK activation levels correlated with EGFR and PDGFRA expression, and p-FAK and EGFR expression co-localized at the single-cell level. in addition, integrin expression was enriched in EGFR/PDG-FRA-overexpressing areas but was more regionally con-fined than FAK, p-FAK, and paxillin. integrins beta 8 and alpha 5 beta 1 were most commonly expressed, often in a perinecrotic or perivascular pattern. Taken together, our data suggest that growth factor receptor overexpression facilitates alterations in the integrin signaling pathway. Thus, FAK may act in glioblastoma as a downstream target of growth factor signaling, with integrins enhancing the impact of such signaling in the tumor microenvironment. C1 Massachusetts Gen Hosp, Dept Pathol, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp East, Mol Pathol Unit, 149-7151,149 13th St, Charlestown, MA 02129 USA. EM dlouis@partners.org FU NCI NIH HHS [CA57683, R01 CA057683] NR 35 TC 47 Z9 49 U1 0 U2 1 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 NOV PY 2005 VL 167 IS 5 BP 1379 EP 1387 DI 10.1016/S0002-9440(10)61225-4 PG 9 WC Pathology SC Pathology GA 979UK UT WOS:000232970200020 PM 16251422 ER PT J AU Koutkia, P Schurgin, S Berry, J Breu, J Lee, BSH Klibanski, A Grinspoon, S AF Koutkia, P Schurgin, S Berry, J Breu, J Lee, BSH Klibanski, A Grinspoon, S TI Reciprocal changes in endogenous ghrelin and growth hormone during fasting in healthy women SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE nutrition; hunger; neuroendocrine; appetite ID CIRCULATING GHRELIN; DEFICIENT PATIENTS; ANOREXIA-NERVOSA; HUMAN OBESITY; GH SECRETION; WEIGHT-LOSS; PLASMA; HUMANS; STOMACH; IMMUNOREACTIVITY AB Ghrelin stimulates growth hormone (GH) secretion, but it is unknown whether there is a feedback of GH on ghrelin secretion. In this study, we characterized the relatedness of GH and ghrelin in a model of acute caloric deprivation in 10 healthy women ( age 26.7 +/- 1.6 yr) during a 4-day fast in the early follicular phase. GH, ghrelin, and cortisol were assessed every hour over 24 h during an isocaloric diet and after a 4-day complete fast. Sampling during a normal diet at baseline demonstrated that ghrelin decreased 17.9% within 1 h after meals ( P < 0.0001), but there was no meal effect on GH. BMI ( 22.3 +/- 0.4 vs. 21.5 +/- 0.4 kg/m(2), P < 0.0001) and IGF-I ( 312 +/- 28 vs. 124 +/- 22 ng/ ml, P < 0.0001) decreased during fasting. Mean 24-h GH increased (2.6 +/- 0.5 vs. 5.6 +/- 0.5 ng/ ml, P < 0.001), but ghrelin decreased ( 441.3 +/- 59.7 vs. 359.8 +/- 54.2 pg/ml, P = 0.012). The peak ghrelin level decreased from 483.5 to 375.6 pg/ml ( P < 0.0001), and the time of the peak ghrelin changed from 0415 to 1715. In contrast, the diurnal pattern of GH was maintained, with increases in the nadir (1.1 to 3.4 ng/ ml) and peak GH concentrations (4.1 to 7.9 ng/ ml) from the fed to fasted state ( P < 0.0001). The change in morning GH concentrations was inversely related to the change in ghrelin ( r = - 0.79, P = 0.012). During complete short-term caloric deprivation in healthy women, ghrelin decreases, even as GH rises, and these processes appear to be reciprocal, suggesting that GH exhibits feedback inhibition on ghrelin. Our data provide new evidence of the physiological relationship of GH and ghrelin in response to changes in protein-energy metabolism. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neuroendocrine Unit, Boston, MA USA. Massachusetts Gen Hosp, MIT, Gen Clin Res Ctr, Core Lab, Boston, MA USA. Biostat Program, Boston, MA USA. RP Grinspoon, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Program Nutr Metab, 55 Fruit St,LON 207, Boston, MA 02114 USA. EM sgrinspoon@partners.org NR 34 TC 16 Z9 17 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2005 VL 289 IS 5 BP E814 EP E822 DI 10.1152/ajpendo.00093.2005 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 977ML UT WOS:000232807800011 PM 15972272 ER PT J AU Martini, WJZ Chinkes, DL Pusateri, AE Holcomb, JB Yu, YM Zhang, XJ Wolfe, RR AF Martini, WJZ Chinkes, DL Pusateri, AE Holcomb, JB Yu, YM Zhang, XJ Wolfe, RR TI Acute changes in fibrinogen metabolism and coagulation after hemorrhage in pigs SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article ID DISSEMINATED INTRAVASCULAR COAGULATION; TRAUMA PATIENTS; EPIDEMIOLOGY AB Hemorrhagic coagulopathy is involved in the morbidity and mortality of trauma patients. Nonetheless, many aspects of the mechanisms underlying this disorder are poorly understood. We have therefore investigated changes in fibrinogen metabolism and coagulation function after a moderate hemorrhagic shock, using a new stable isotope approach. Twelve pigs were randomly divided into the control ( C) and hemorrhage (H) groups. Hemorrhage was induced by bleeding 35% total blood volume over a 30-min period. A primed constant infusion of [1-C-13] phenylalanine (Phe), d(5)-phenylalanine, and alpha-[1-C-13]ketoisocaproate (KIC) was given to quantify fibrinogen synthesis and breakdown, together with measurements of circulating liver enzyme activities and coagulation function. Mean arterial pressure was decreased by hemorrhage from 89 +/- 4 mmHg in C to 47 +/- 4 mmHg in H ( P < 0.05), followed by a rebound to 68 +/- 5 mmHg afterward. Fibrinogen fractional synthesis rate increased from 2.7 +/- 0.2%/ h in C to 4.2 +/- 0.4%/ h in H by Phe ( P < 0.05) and from 3.1 +/- 0.4%/ h in C to 4.4 +/- 0.5%/ h in H by KIC ( P < 0.05). Fibrinogen fractional breakdown rate increased from 3.6 +/- 1.0%/ h in C to 12.9 +/- 1.8%/ h in H ( P < 0.05). The absolute breakdown rate accelerated from 3.0 +/- 0.4 mg center dot kg(-1) center dot h(-1) in C to 5.4 +/- 0.6 mg center dot kg(-1) center dot h(-1) in H ( P < 0.05), but the absolute synthesis rate remained unchanged. These metabolic changes were accompanied by a reduction in blood clotting time to 92.7 +/- 1.6% of the baseline value by hemorrhage ( P < 0.05). No changes were found in liver enzyme activities. We conclude that the observed changes in coagulation after hemorrhagic shock are mechanistically related to the acute acceleration of fibrinogen degradation. C1 USA, Inst Surg Res, Ft Sam Houston, TX 78234 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Martini, WJZ (reprint author), USA, Inst Surg Res, 3400 Rawley E Chambers Ave, Ft Sam Houston, TX 78234 USA. NR 22 TC 43 Z9 45 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2005 VL 289 IS 5 BP E930 EP E934 DI 10.1152/ajpendo.00137.2005 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 977ML UT WOS:000232807800025 PM 15956050 ER PT J AU Yuan, PQ Yang, H AF Yuan, PQ Yang, H TI Hypothyroidism increases Fos immunoreactivity in cholinergic neurons of brain medullary dorsal vagal complex in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE thyroid hormone; dorsal motor nucleus of the vagus; nucleus tractus solitarii; vagus nerve; area postrema ID THYROTROPIN-RELEASING-HORMONE; CENTRAL-NERVOUS-SYSTEM; CAUDAL RAPHE NUCLEI; THYROID-HORMONE; GENE-EXPRESSION; PARAVENTRICULAR NUCLEUS; RECEPTOR ISOFORM; ACETYLTRANSFERASE GENE; FEEDBACK-REGULATION; SUBSTANCE-P AB Hypo- or hyperthyroidism is associated with autonomic disorders. We studied Fos expression in the medullary dorsal motor nucleus of the vagus (DMV), nucleus tractus solitarii (NTS), and area postrema (AP) in four groups of rats with different thyroid states induced by a combination of drinking water and daily intraperitoneal injection for 1 - 4 wk: 1) tap water and vehicle; 2) 0.1% propylthiouracil (PTU) and vehicle; 3) PTU and thyroxine (T-4; 2 mu g/ 100 g); and 4) tap water and T4 ( 10 mu g/ 100 g). The numbers of Fos immunoreactive (IR) positive neurons in the DMV, NTS, and AP were low in euthyroid rats but significantly higher in the 4-wk duration in hypothyroid rats, which were prevented by simultaneous T4 replacement. Hyperthyroidism had no effect on Fos expression in these areas. There were significant negative correlations between T4 levels and the numbers of Fos-IR-positive neurons in the DMV ( r = - 0.6388, P < 0.008), NTS ( r = - 0.6741, P < 0.003), and AP ( r = - 0.5622, P < 0.004). Double staining showed that Fos immunoreactivity in the DMV of hypothyroid rats was mostly localized in choline acetyltransferase-containing neurons. Thyroid hormone receptors alpha 1 and beta 2 were localized in the observed nuclei. These results indicate that thyroid hormone influences the DMV/NTS/AP neuronal activity, which may contribute to the vagal-related visceral disorders observed in hypothyroidism. C1 Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. RP Yang, H (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, CURE Digest Dis Res Ctr, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM hoyang@ucla.edu FU NIDDK NIH HHS [DK-41301] NR 53 TC 3 Z9 3 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD NOV PY 2005 VL 289 IS 5 BP E892 EP E899 DI 10.1152/ajpendo.00108.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 977ML UT WOS:000232807800020 PM 15985455 ER PT J AU Chao, W Shen, Y Li, L Zhao, HL Meiler, SE Cook, SA Rosenzweig, A AF Chao, W Shen, Y Li, L Zhao, HL Meiler, SE Cook, SA Rosenzweig, A TI Fas-associated death-domain protein inhibits TNF-alpha mediated NF kappa B activation in cardiomyocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE signal transduction; cardiac; inflammation; tumor necrosis factor; nuclear factor-kappa B ID TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE-CELLS; FLOW CONDITIONS; APOPTOSIS; RECEPTOR; HEART; FADD; EXPRESSION; INDUCTION; CASPASE-8 AB Fas-associated death-domain protein ( FADD) is an adaptor molecule that links death receptors to caspase-8 in many cell types including cardiomyocytes (CMs). Although FADD has previously been reported to play an important role in CM apoptosis, the effect of FADD on CM NF-kappa B signaling, which is a proinflammatory pathway, has not been delineated. To investigate the role of FADD in CM NF-kappa B activation, we utilized adenoviral gene transfer of wild-type FADD and a truncation mutant that lacks the death-effector domain (FADD-DED) in rat CMs in vitro. TNF-alpha activated NF-kappa B in CMs as demonstrated by phosphorylation and degradation of inhibitory-kappa B (I kappa B)-alpha-enhanced nuclear p65 and NF-kappa B DNA-binding activity as well as increased mRNA for the NF-kappa B-dependent adhesion molecule VCAM-1 ( 19 +/- 4.1-fold) as measured by quantitative RT-PCR. Gene transfer of FADD inhibited TNF-alpha-induced I kappa B-alpha phosphorylation, decreased p65 nuclear translocation and NF-kappa B DNA-binding activity, and reduced VCAM-1 transcript levels by 53-65%. Interestingly, FADD-DED exhibited a similar but weaker inhibitory effect on NF-kappa B activation. The effects of FADD on NF-kappa B were cell-type specific. FADD expression also inhibited TNF-alpha-mediated NF-kappa B activation in human endothelial cells but not in rat pulmonary artery smooth muscle cells. In contrast, FADD expression actually activated NF-kappa B in human embryonic kidney (HEK)-293 cells. In CMs, FADD inhibited NF-kappa B activation as well as phosphorylation of I kappa B and I kappa B kinase (IKK)-beta in response to cytokine stimulation or expression of the upstream kinases NF-kappa B-inducing kinase and IKK-beta. These data demonstrate that FADD inhibits NF-kappa B activation in CMs, and this inhibition likely occurs at the level of phosphorylation and activation of IKK-beta. C1 Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Med Coll Georgia, Dept Anesthesia, Augusta, GA 30912 USA. RP Rosenzweig, A (reprint author), MGH E,114 16th St,Rm 2600, Charlestown, MA 02139 USA. EM arosenzweig@partners.org RI Cook, Stuart/G-9567-2011 FU NHLBI NIH HHS [HL-04336, HL-59521] NR 37 TC 9 Z9 9 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2005 VL 289 IS 5 BP H2073 EP H2080 DI 10.1152/ajpheart.01216.2005 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 973BI UT WOS:000232497500038 PM 15980038 ER PT J AU Lee, JS Frevert, CW Matute-Bello, G Wurfel, MM Wong, VA Lin, SM Ruzinski, J Mongovin, S Goodman, RB Martin, TR AF Lee, JS Frevert, CW Matute-Bello, G Wurfel, MM Wong, VA Lin, SM Ruzinski, J Mongovin, S Goodman, RB Martin, TR TI TLR-4 pathway mediates the inflammatory response but not bacterial elimination in E-coli pneumonia SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE lipopolysaccharide; toll-like receptor-4; Escherichia coli; bacterial proliferation ID TOLL-LIKE RECEPTOR-4; GRAM-NEGATIVE PNEUMONIA; GENETIC-CONTROL; C57BL/10SCCR MICE; HOST-DEFENSE; MYCOBACTERIUM-TUBERCULOSIS; LEUCOCYTE RESPONSES; INFECTION; LPS; ENDOTOXIN AB We examined the role of Toll-like receptor ( TLR)-4 in modifying the lung inflammatory response and its effects on the bacterial recovery from the lungs following inhaled Escherichia coli in two different strains of TLR-4 mutant mice that are hyporesponsive to LPS. The C57BL/ 10ScN(tlr4(lps-del)) mice containing a deletion mutation in the TLR-4 gene showed lower proinflammatory cytokine levels, lower lung MPO activity, and less parenchymal and peribronchial inflammation compared with the C57BL/10ScSn mice, a related TLR-4 wild-type substrain. However, the C57BL/10ScN(tlr4(lps-del)) mutant showed lower bacterial recovery in the lungs following inhaled E. coli associated with a rapid but transient increase in air space neutrophil counts at 6 h. In comparison, the C3H/HeJ(tlr4(Lps-d)) mutant mice containing a Pro712His substitution in TLR-4 demonstrated lower proinflammatory cytokine levels, lower lung MPO activity, and lower neutrophil accumulation in the air spaces but showed no differences in the bacterial burden of inhaled E. coli at 6 h, when compared with the TLR-4 wild-type C3H/HeSnJ mice. Thus two different TLR-4 mutants showed attenuated inflammatory responses in the lungs, but the reduced inflammatory responses were not consistently associated with either improved or impaired bacterial elimination from the lungs. Our findings indicate that the inflammatory response to inhaled E. coli is TLR-4 dependent, but bacterial elimination depends on other factors in addition to TLR-4. C1 Univ Washington, Dept Med, Div Pulm & Crit Care, Seattle, WA 98108 USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Pittsburgh, Dept Med, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA USA. Chang Gung Mem Hosp, Dept Thorac Med 2, Taipei 10591, Taiwan. RP Martin, TR (reprint author), Univ Washington, Dept Med, Div Pulm & Crit Care, 1600 S Columbian Way,GMR 151-L, Seattle, WA 98108 USA. EM trmartin@u.washington.edu FU NHLBI NIH HHS [HL-072923, HL-70840, HL-70178, HL-73996]; NIGMS NIH HHS [GM-37696] NR 32 TC 36 Z9 39 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2005 VL 289 IS 5 BP L731 EP L738 DI 10.1152/ajplung.00196.2005 PG 8 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 972RB UT WOS:000232469800008 PM 16024722 ER PT J AU Tanaka, T Kojima I Ohse, T Inagi, R Miyata, T Ingelfinger Jr Fujita, T Nangaku, M AF Tanaka, T Kojima, I Ohse, T Inagi, R Miyata, T Ingelfinger, JR Fujita, T Nangaku, M TI Hypoxia-inducible factor modulates tubular cell survival in cisplatin nephrotoxicity SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE apoptosis; mitochondria; caspase ID RENAL-DISEASE; ERYTHROPOIETIN PROTECTS; MITOCHONDRIAL PATHWAYS; GLUCOSE-METABOLISM; HIF-ALPHA; APOPTOSIS; INJURY; FACTOR-1-ALPHA; EXPRESSION; GENE AB Hypoxia-inducible factor (HIF)-1 is a transcription factor mediating cellular response to hypoxia. Although it is expressed in tubular cells of the ischemic kidney, its functional role is not fully clarified in the pathological context. In this study, we investigated a role of HIF in tubular cell apoptosis induced by cisplatin. HIF-1 alpha was expressed in tubular cells in the outer medulla 3 days after cisplatin (6 mg/kg) administration. With the in vivo administration of cobalt to activate HIF, the number of apoptotic renal tubular cells became much smaller in the outer medulla, compared with the vehicle group. We also examined the functional role of HIF-1 in vitro using immortalized rat proximal tubular cells (IRPTC). In hypoxia, IRPTC that express dominant-negative (dn) HIF-1 alpha showed impaired survival in cisplatin injury at variable doses (25-100 mu M, 24 h), which was not obvious in normoxia. The observed difference in cell viability in hypoxia was associated with the increased number of apoptotic cells in dnHIF-1 alpha clones ( Hoechst 33258 staining). Studies on intracellular signaling revealed that the degree of cytochrome c release, dissipation of mitochondrial membrane potentials, and caspase-9 activity were all more prominent in dnHIF-1 alpha clones than in control IRPTC, pointing to the accelerated signaling of mitochondrial pathways. We propose that HIF- 1 mediates cytoprotection against cisplatin injury in hypoxic renal tubular cells, by reducing the number of apoptotic cells through stabilization of mitochondrial membrane integrity and suppression of apoptosis signaling. A possibility was suggested that activation of HIF- 1 could be a new promising therapeutic target for hypoxic renal diseases. C1 Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, Tokyo, Japan. Tokai Univ, Inst Med Sci, Kanagawa 2591100, Japan. Massachusetts Gen Hosp, Div Pediat Nephrol, Boston, MA 02114 USA. RP Nangaku, M (reprint author), Univ Tokyo, Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo, Japan. EM mnangaku-tky@umin.ac.jp RI Miyata, Toshio/A-4872-2010; Nangaku, Masaomi/A-5300-2010 NR 33 TC 58 Z9 61 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2005 VL 289 IS 5 BP F1123 EP F1133 DI 10.1152/ajprenal.00081.2005 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 971LF UT WOS:000232384900022 PM 15956779 ER PT J AU Xu, YZ Osborne, BW Stanton, RC AF Xu, YZ Osborne, BW Stanton, RC TI Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE diabetic nephropathy; pentose phosphate pathway ID ENDOTHELIAL-CELLS; PROTEIN-KINASE; HIGH-GLUCOSE; ENCODING GLUCOSE-6-PHOSPHATE-DEHYDROGENASE; HYDROGEN-PEROXIDE; NITRIC-OXIDE; BLOOD-CELLS; NEPHROPATHY; COMPLICATIONS; ENZYME AB The incidence of diabetic nephropathy has been increasing. Studies have shown that oxidative stress ( due to increased oxidant production and/or decreased antioxidant activity) is a critical underlying mechanism. The principal intracellular reductant is NADPH whose production is mainly dependent on glucose-6-phosphate dehydrogenase (G6PD) activity. Our work in cultured cells previously showed that high glucose caused activation of protein kinase A (PKA) and subsequent phosphorylation and inhibition of G6PD activity and hence decreased NADPH (Zhang Z, Apse K, Pang J, and Stanton RC. J Biol Chem 275: 40042-40047, 2000). The purpose of this study was to determine whether these findings occur in diabetic rats ( induced by streptozotocin) compared with control. G6PD activity and accordingly NADPH levels and glutathione levels were significantly decreased in diabetic kidneys compared with control kidneys. Lipid peroxidation was significantly increased, which correlated with decreased G6PD activity (r = 0.48). G6PD expression was significantly reduced, which correlated with decreased G6PD activity (r = 0.72). PKA activity and serine phosphorylation of G6PD were significantly increased and were closely correlated with decreased G6PD activity (r = 0.51 for PKA activity; r = 0.93 for serine phosphorylation of G6PD). Insulin treatment and/or correction of hyperglycemia ameliorated the changes caused by diabetes. In conclusion, chronic hyperglycemia caused inhibition of G6PD activity via decreased expression and increased phosphorylation of G6PD, which therefore led to increased oxidative stress. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Renal, Boston, MA 02215 USA. RP Stanton, RC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Renal, 1 Joslin Pl, Boston, MA 02215 USA. EM robert.stanton@joslin.harvard.edu FU NIDDK NIH HHS [R01-DK-54380] NR 50 TC 81 Z9 89 U1 0 U2 9 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 NOV PY 2005 VL 289 IS 5 BP F1040 EP F1047 DI 10.1152/ajprenal.00076.2005 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 971LF UT WOS:000232384900012 PM 15956780 ER PT J AU Sassi, RB Stanley, JA Axelson, D Brambilla, P Nicoletti, MA Keshavan, MS Ramos, RT Ryan, N Birmaher, B AF Sassi, RB Stanley, JA Axelson, D Brambilla, P Nicoletti, MA Keshavan, MS Ramos, RT Ryan, N Birmaher, B TI Reduced NAA levels in the dorsolateral prefrontal cortex of young bipolar patients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 47th Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 08-12, 2002 CL Waikoloa, HI SP Amer Coll Neuropsychopharmacol AB Objective: Converging evidence implicates prefrontal circuits in the pathophysiology of bipolar disorder. Proton spectroscopy studies performed in adult bipolar patients assessing prefrontal regions have suggested decreased levels of N-acetylaspartate (NAA), a putative marker of neuronal integrity. In order to examine whether such abnormalities would also be found in younger patients, a H-1 spectroscopy study was conducted that focused on the dorsolateral prefrontal cortex of children and adolescents with bipolar disorder. Method: The authors examined the levels of NAA, creatine plus phosphocreatine, and choline-containing molecules in the left dorsolateral prefrontal cortex of 14 bipolar disorder patients (mean age= 15.5 years, SD=3, eight female) and 18 healthy comparison subjects (mean age= 17.3, SD=3.7, seven female) using short echo time, single-voxel in vivo H-1 spectroscopy. Absolute metabolite levels were determined using the water signal as an internal reference. Results: Bipolar patients presented significantly lower NAA levels and a significant inverse correlation between choline-containing molecules and number of previous affective episodes. No differences were found for other metabolites. Conclusions: These findings suggest that young bipolar patients have decreased NAA levels in the dorsolateral prefrontal cortex, similar to what was previously reported in adult patients. Such changes may reflect an underdevelopment of dendritic arborizations and synaptic connections. These neuronal abnormalities in the dorsolateral prefrontal cortex of bipolar disorder youth are unlikely to represent long-term degenerative processes, at least in the subgroup of patients where the illness had relatively early onset. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Harvard Univ, Sch Med, MGH McLean Psychiat, Dept Psychiat, Boston, MA USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Dept Psychiat, Sao Paulo, Brazil. Univ Pittsburgh, Sch Med, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Udine, Sect Psychiat, Dept Pathol & Expt & Clin Med, Udine, Italy. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Sassi, RB (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI brambilla, paolo/B-4184-2010; Ramos, Renato/G-1566-2013 OI brambilla, paolo/0000-0002-4021-8456; FU NIMH NIH HHS [MH-01736, MH-30915, MH-55123, MH-59929] NR 47 TC 48 Z9 51 U1 0 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2005 VL 162 IS 11 BP 2109 EP 2115 DI 10.1176/appi.ajp.162.11.2109 PG 7 WC Psychiatry SC Psychiatry GA 979XF UT WOS:000232977600017 PM 16263851 ER PT J AU Chang, DS Lee, MH Lee, HY Barack, BM AF Chang, DS Lee, MH Lee, HY Barack, BM TI MDCT of left anterior descending coronary artery to main pulmonary artery fistula SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 VA Greater Los Angeles Healthcare Syst, Div Cardiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Gaffen Sch Med, Los Angeles, CA USA. Olive View UCLA Med Ctr, Dept Radiol, Sylmar, CA 91342 USA. VA Greater Los Angeles Healthcare Syst, Imaging Serv, Los Angeles, CA USA. RP Chang, DS (reprint author), VA Greater Los Angeles Healthcare Syst, Div Cardiol, 11301 Wilshire Blvd,111E, Los Angeles, CA 90073 USA. EM dchang@ucla.edu NR 9 TC 6 Z9 6 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 NOV PY 2005 VL 185 IS 5 BP 1258 EP 1260 DI 10.2214/AJR.04.1415 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 978XI UT WOS:000232905900033 PM 16247146 ER PT J AU Finan, KR Vick, CC Kiefe, CI Neumayer, L Hawn, MT AF Finan, KR Vick, CC Kiefe, CI Neumayer, L Hawn, MT TI Predictors of wound infection in ventral hernia repair SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 29th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAR 11-13, 2005 CL Salt Lake City, UT DE surgical wound infection; hernia; ventral; United States Department of Veterans Affairs; mesh; smoking ID RANDOMIZED CONTROLLED-TRIAL; OF-VETERANS-AFFAIRS; INCISIONAL HERNIA; RISK-FACTORS; MESH REPAIR; SURGICAL CARE; HERNIORRHAPHY; COMPLICATIONS; QUALITY; SUTURE AB Background: Postoperative wound infection is a significant risk factor for recurrence after ventral hernia repair (VHR). The current study examines patient- and procedure-specific variables associated with wound infection. Methods: A cohort of subjects undergoing VHR from 13 regional Veterans Health Administration (VHA) sites was identified. Patient-specific risk variables were obtained from National Surgical Quality Improvement Program (NSQIP) data. Operative variables were obtained from physician-abstracted operative notes. Univariate and multivariable logistic regression analysis was used to model predictors of postoperative wound infection. Results: A total of 1505 VHR cases were used for analysis; wound infection occurred in 5% (n = 74). Best-fit logistic regression models demonstrated that steroid use, smoking, prolonged operative time, and use of absorbable mesh, acting as a surrogate marker for a more complex procedure, were significant independent predictors of wound infection. Conclusion: Permanent mesh placement was not associated with postoperative wound infection. Smoking was the only modifiable risk factor and preoperative smoking cessation may improve. surgical outcomes in VHR. (c) 2005 Excerpta Medica Inc. All rights reserved. C1 Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effect, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Salt Lake VA Hlth Care Syst, Dept Surg, Salt Lake City, UT USA. Univ Utah, Dept Surg, Salt Lake City, UT USA. RP Hawn, MT (reprint author), KB 429,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mhawn@uab.edu NR 35 TC 106 Z9 107 U1 0 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2005 VL 190 IS 5 BP 676 EP 681 DI 10.1016/j.amjsurg.2005.06.041 PG 6 WC Surgery SC Surgery GA 979II UT WOS:000232935200003 PM 16226938 ER PT J AU Fagan, SP Bellows, CF Albo, D Rodriquez-Barradas, M Feanny, M Awad, SS Berger, DH AF Fagan, SP Bellows, CF Albo, D Rodriquez-Barradas, M Feanny, M Awad, SS Berger, DH TI Length of human immunodeficiency virus disease and not immune status is a risk factor for development of anal carcinoma SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 29th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAR 11-13, 2005 CL Salt Lake City, UT DE Bowen's disease; anal carcinoma; HIV; immune status ID SQUAMOUS INTRAEPITHELIAL LESIONS; HUMAN-PAPILLOMAVIRUS INFECTION; HOMOSEXUAL-MEN; CELL CARCINOMA; HIV-INFECTION; POSITIVE MEN; NEOPLASIA; CANCER; INDIVIDUALS; PREVALENCE AB Background: The anal epithelium is subject to dysplastic change in patients with human immunodeficiency virus (HIV). We sought to determine if the duration of HIV disease or the patient's immune status were associated with the development of anal carcinoma. Methods: HIV-positive patients diagnosed with anal neoplasms were reviewed. Statistical analysis was performed via an unpaired Student t test and the Fisher exact test. Results: Fourteen patients were identified, 7 with anal intraepithelial neoplasms (group 1) and 7 with anal carcinoma (group 2). Human papillomavirus was detected in 100% of patients in group 1 and in 67% of patients in group 2. There was no significant difference in the level of immunosuppression as assessed by the CD4 counts (266.9 +/- 48.5 vs. 274.7 +/- 92.0 cell/mu l; P =.94) and viral loads (19,243 18,034 vs. 67,140 +/- 39,570 RNA/mL; P =.29) between groups I and 2, respectively. Group 2 had been HIV positive for a significantly longer period of time (12.6 +/- 2.3 y) compared with group 1 (5.9 +/- 2.0 y P =.05). Conclusions: The most significant factor for the development of invasive anal carcinoma in patients with HIV is duration of disease. As a result of improved long-term survival secondary to new HIV therapy, anal invasive carcinoma will become an increasing problem. (c) 2005 Excerpta Medica Inc. All rights reserved. C1 Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Operat Care Line, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP Fagan, SP (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Michael E DeBakey Dept Surg, Operat Care Line, 2002 Holocombe Blvd,VA 112, Houston, TX 77030 USA. EM sfagan@houston.rr.com NR 23 TC 17 Z9 20 U1 1 U2 3 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2005 VL 190 IS 5 BP 732 EP 735 DI 10.1016/j.amjsurg.2005.07.011 PG 4 WC Surgery SC Surgery GA 979II UT WOS:000232935200014 PM 16226949 ER PT J AU Stewart, L Griffiss, JM Way, LW AF Stewart, L Griffiss, JM Way, LW TI Spectrum of gallstone disease in the veterans population SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 29th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAR 11-13, 2005 CL Salt Lake City, UT DE gallstones; biliary infections; cholangitis; veterans ID NECROSIS-FACTOR-ALPHA; BILE-DUCT STONES; BILIARY-TRACT; PIGMENT GALLSTONES; BACTERIOLOGY; CHOLELITHIASIS; GALLBLADDER; CHOLANGITIS; PATHOGENESIS; ANTIBIOTICS AB Background: Elderly male patients are thought to have a higher incidence of biliary infections. This demographic is common among veterans, so we analyzed the spectrum of gallstone disease in a large veteran population. Methods: A total of 285 patients with gallstone disease were studied. There were 27 women and 258 men, with an average age of 62 years. Gallstones, bile, and blood (as indicated) were cultured. Illness severity was staged as none (no clinical infection), moderate (fever, leukocytosis), or severe (cholangitis, bacteremia, abscess, hypotension, organ failure). Gallstones were grouped by appearance. Three bacterial groups were defined: EK (Escherichia coli or Klebsiella species), N (Enterococcus), or Oth (all other species). Results: Biliary bacteria were present in 145 (51%) patients. Bacterial presence by patient age was 33% for those less than 50 years, 48% for those 50 to 70 years, and 65% for those more than 70 years (P <.02 vs. others). Bacterial presence by stone type was as follows: cholesterol, 11%; mixed, 51%; pigment, 71% (P <.01 vs. others). Illness severity by stone type was as follows for cholesterol: none, 73%; moderate, 27%; severe, 0%; for mixed: none, 62%; moderate, 25%; severe, 13%; for pigment: none, 41%; moderate, 17%; severe, 41% (P <.0001 vs. others). Illness severity by bacterial group was as follows for sterile: none, 77%; moderate, 23%; severe, 0%; for the Oth group: none, 57%; moderate, 22%; severe, 20%; for the N group: none, 32%; moderate, 16%; severe, 52%; for the EK group: none, 18%; moderate, 22%; severe, 60% (P <.0001 vs. sterile/Oth, P =.126 vs. N). Conclusions: Bacterial biliary tree colonization is prevalent in the veterans' population, it increases with age, and is more common with pigment stones. But not all bacterial species cause infectious manifestations. Patients with E coli and/or Klebsiella species commonly showed infectious manifestations, patients with Enterococcus were in an intermediate range, and those with other species had few infectious manifestations. (c) 2005 Excerpta Medica Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Surg Serv, Dept Surg, San Francisco, CA 94121 USA. San Francisco VA Med Ctr, Ctr Immunochem, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. EM lygia.stewart@med.va.gov NR 27 TC 12 Z9 12 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2005 VL 190 IS 5 BP 746 EP 751 DI 10.1016/j.amjsurg.2005.07.014 PG 6 WC Surgery SC Surgery GA 979II UT WOS:000232935200017 PM 16226952 ER PT J AU Deshpande, V Mino-Kenudson, M Brugge, WR Pitman, MB Fernandez-del Castillo, C Warshaw, AL Lauwers, GY AF Deshpande, V Mino-Kenudson, M Brugge, WR Pitman, MB Fernandez-del Castillo, C Warshaw, AL Lauwers, GY TI Endoscopic ultrasound guided fine needle aspiration biopsy of autoimmune pancreatitis - Diagnostic criteria and pitfalls SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE autoimmune pancreatitis; sclerosing pancreatitis; fine-needle aspiration biopsy; endoscopic ultrasound; cytology ID LYMPHOPLASMACYTIC SCLEROSING PANCREATITIS; STEROID-THERAPY; FEATURES; DISEASE; CHOLANGITIS; CARCINOMA; ACCURACY; ENTITY; CANCER AB Autoimmune pancreatitis (AIP) is a benign inflammatory disease of the pancreas that mimics pancreatic malignancy both clinically and radiologically. The fine needle aspiration biopsy (FNAB) features of AIP have not previously been documented. We report our experience with AIP, highlight pitfalls, and perform a comprehensive analysis of the cytomorphologic features of this condition. We identified 16 patients with AIP, initially evaluated by endoscopic ultrasound (EUS)-guided FNAB, 11 of whom subsequently underwent a pancreatoduodenectomy. We compared these to a cohort of EUS-guided aspirates from ductal carcinoma of the pancreas (n = 16) and chronic pancreatitis, not otherwise specified (NOS) (n = 19). On all 51 cases, we semi quantitatively evaluated presence and atypia of ductal cells, presence and cellularity of stromal fragments, and inflammatory cells, type and distribution. Fifty percent (8 of 16) of the AIP cases presented as obstructive jaundice. EUS and CT scan showed mass lesions in 10 and 6 cases, respectively. There were three false-positive cytologic diagnoses, an adenocarcinoma, a solid-pseudopapillary tumor and a mucinous neoplasm. Ductal epithelium was inconspicuous and was seen in 6 cases. The FNAB samples showed background lymphocytes in three AIP cases, a feature absent in the control cohort. Stromal fragments with embedded lymphocytes (greater than 30 per 60X) were seen in 37.5% of AIP cases and only rarely with adenocarcinoma (12.5%) and pancreatitis, NOS (0%). The cellularity of stromal fragments was significantly higher in AIP than in the control group. The presence of stromal fragments of high cellularity with a lymphoid infiltrate in conjunction with clinical and radiology findings could potentially both establish a diagnosis of AIP and exclude carcinoma, thus preventing pancreatic resection. C1 Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Massachusetts Gen Hosp, Gastrointestinal Pathol Serv, Dept Pathol, Warren 831B,55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 31 TC 70 Z9 75 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2005 VL 29 IS 11 BP 1464 EP 1471 DI 10.1097/01.pas.0000173656.49557.48 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 978GB UT WOS:000232860500007 PM 16224213 ER PT J AU Wang, SA Wang, L Hochberg, EP Muzikansky, A Harris, NL Hasserjian, RP AF Wang, SA Wang, L Hochberg, EP Muzikansky, A Harris, NL Hasserjian, RP TI Low histologic grade follicular lymphoma with high proliferation index - Morphologic and clinical features SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE follicular lymphoma; proliferation index; Ki-67; survival; grade ID NON-HODGKINS-LYMPHOMAS; PROGNOSTIC-SIGNIFICANCE; CELL LYMPHOMAS; FLOW-CYTOMETRY; IMAGE-ANALYSIS; KI-67; EXPRESSION; ANTIGEN; ANTIBODY; CLASSIFICATION AB Histologic grading has been used as a guide for clinical management in follicular lymphoma (FL). Proliferation index (PI) of FL generally correlates with tumor grade; however, in cases of discordance, it is not clear whether histologic grade or PI correlates with clinical aggressiveness. To objectively evaluate these cases, we determined PI by Ki-67 immunostaining in 142 cases of FL (48 grade 1, 71 grade 2, and 23 grade 3). A total of 24 cases FL with low histologic grade but high PI (LG-HPI) were identified, a frequency of 18%. On histologic examination, LG-HPI FL often exhibited blastoid features. Patients with LG-HPI FL had inferior disease-specific survival but a higher 5-year disease-free rate than low-grade FL with concordantly low PI (LG-LPI). However, transformation to diffuse large B-cell lymphoma was uncommon in LG-HPI cases (1 of 19; 5%) as compared with LG-LPI cases (27 of 74; 36%). In conclusion, LG-HPI FL appears to be a subgroup of FL with clinical behavior more akin to grade 3 FL. We propose that these LG-HPI FL cases should be classified separately from cases of low histologic grade FL with concordantly low PI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Internal Med,Div Hematol Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Biostat, Boston, MA 02114 USA. RP Hasserjian, RP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, WRN 244,55 Fruit St, Boston, MA 02114 USA. EM rhasserjian@partners.org NR 33 TC 49 Z9 50 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2005 VL 29 IS 11 BP 1490 EP 1496 DI 10.1097/01.pas.0000172191.87176.3b PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 978GB UT WOS:000232860500010 PM 16224216 ER PT J AU Fink, H Bogdanski, R Luppa, P Martyn, JAJ Blobner, M AF Fink, H Bogdanski, R Luppa, P Martyn, JAJ Blobner, M TI Nitric oxide is not a mediator of inflammation-induced resistance to atracurium SO ANESTHESIA AND ANALGESIA LA English DT Article ID SKELETAL-MUSCLE; SYNTHASE; PHARMACODYNAMICS; ENDOTOXEMIA; DYSFUNCTION; VECURONIUM; EXPRESSION; MODELS; ORGAN; RATS AB Resistance to atracurium as a result of increased drug binding to alpha(1)-acid glycoprotein is associated with increased inducible nitric oxide synthase activity and increased nitric oxide levels in plasma. We investigated if the inhibition of inducible nitric oxide synthase and suppression of nitric oxide can reverse the resistance to atracurium. As a model of alpha(1)-acid glycoprotein and nitric oxide increase, 84 male Sprague-Dawley rats received an IV injection of either 60 mg/kg Corynebacterium parvum (CP) or saline (control). The 2 groups (CP/Control) were further divided into subgroups, receiving the selective inducible nitric oxide synthase inhibitor, N-Iminolysine, via drinking water at different concentrations. On day 4 post-CP injection, the pharmacodynamics of atracurium were determined. Plasma concentrations of nitric oxide, atracurium, and alpha(1)-acid glycoprotein were measured and acetylcholine receptor numbers were quantified. In the CP groups, N-Iminolysine suppressed nitric oxide levels in a dose-dependent manner. Resistance to atracurium persisted. alpha(1)-acid glycoprotein serum levels remained increased in all CP groups with no differences in acetylcholine receptor expression. Our results suggest that the mechanism leading to increased expression of alpha(1)-acid glycoprotein and consecutive increased protein binding of atracurium is not mediated by inducible nitric oxide synthase induction and nitric oxide expression. C1 Tech Univ Munich, Klinikum Rechts Isar, Anasthesiol Klin, D-81675 Munich, Germany. Tech Univ Munich, Klinikum Rechts Isar, Inst Klin Chem & Pathobiochem, D-81675 Munich, Germany. Harvard Univ, Sch Med, Dept Anesthesiol & Crit Care, Boston, MA USA. Massachusetts Gen Hosp, Anesthesia Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA USA. RP Fink, H (reprint author), Tech Univ Munich, Klinikum Rechts Isar, Anasthesiol Klin, Ismaninger Str 22, D-81675 Munich, Germany. EM h.fink@lrz.tum.de OI Lewald, Heidrun/0000-0002-5192-425X FU NIGMS NIH HHS [GM 611411-06, GM 55082-08, GM 31569, R01 GM055082] NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2005 VL 101 IS 5 BP 1362 EP 1367 DI 10.1213/01.ANE.0000180832.62367.CC PG 6 WC Anesthesiology SC Anesthesiology GA 977DO UT WOS:000232782800019 PM 16243995 ER PT J AU Khalil, AS Chan, RC Chau, AH Bouma, BE Mofrad, MRK AF Khalil, AS Chan, RC Chau, AH Bouma, BE Mofrad, MRK TI Tissue elasticity estimation with optical coherence elastography: Toward mechanical characterization of In vivo soft tissue SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE optical coherence tomography; soft tissue; elasticity estimation; FEM; regularization ID INTRAVASCULAR ULTRASOUND ELASTOGRAPHY; CORONARY ATHEROSCLEROTIC PLAQUES; TOMOGRAPHY; STRESS; ARTERIES AB High-resolution imaging provides a significant means for accurate material modulus estimation and mechanical characterization. Within the realm of in vivo soft tissue characterization, particularly on small biological length scales such as arterial atherosclerotic plaques, optical coherence tomography (OCT) offers a desirable imaging modality with higher spatial resolution and contrast of tissue as compared with intravascular ultrasound (IVUS). Based on recent advances in OCT imaging and elastography, we present a fully integrated system for tissue elasticity reconstruction, and assess the benefits of OCT on the distribution results of four representative tissue block models. We demonstrate accuracy, with displacement residuals on the order of 10(-6) mm (more than 3 orders of magnitude less than average calculated displacements), and high-resolution estimates, with the ability to resolve inclusions of 0.15 mm diameter. C1 Univ Calif Berkeley, Dept Bioengn, Berkeley, CA 94720 USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Mofrad, MRK (reprint author), Univ Calif Berkeley, Dept Bioengn, 483 Evans Hall 1762, Berkeley, CA 94720 USA. EM mofrad@berkeley.edu FU NHLBI NIH HHS [R01-HL70039] NR 29 TC 50 Z9 72 U1 1 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2005 VL 33 IS 11 BP 1631 EP 1639 DI 10.1007/s10439-005-6766-3 PG 9 WC Engineering, Biomedical SC Engineering GA 992HJ UT WOS:000233874700012 PM 16341928 ER PT J AU Nutting, PA Dickinson, LM Rubenstein, LV Keeley, RD Smith, JL Elliott, CE AF Nutting, PA Dickinson, LM Rubenstein, LV Keeley, RD Smith, JL Elliott, CE TI Improving detection of suicidal ideation among depressed patients in primary care SO ANNALS OF FAMILY MEDICINE LA English DT Article DE suicide; depression; primary care physicians; quality improvement ID RANDOMIZED-TRIAL; QUALITY IMPROVEMENT; GENERAL-PRACTITIONERS; MAJOR DEPRESSION; ECONOMIC BURDEN; MENTAL-ILLNESS; RISK; PHYSICIANS; INTERVENTION; MANAGEMENT AB PURPOSE Primary care clinicians have difficulty detecting suicidal patients. This report evaluates the effect of 2 primary care interventions on the detection and subsequent referral or treatment of patients with depression and recent suicidal ideation. METHODS Adult patients in 12 mixed-payer primary care practices and 9 not-for-profit staff model health maintenance organization (HMO) practices were screened for depression. Matched practices were randomized within plan type to intervention or usual care. The intervention for mixed-payer practices entailed brief training of physicians and office nurses to provide care management. The intervention for HMO practices consisted of guided development of quality improvement teams for depression care. A total of 880 enrolled patients met study criteria for depression, 232 of whom met criteria for recent suicidal ideation. Intervention effects on suicide detection and referral to mental health specialty care were evaluated with mixed-effects multilevel models in intent-to-treat analyses. RESULTS Depressed patients with recent suicidal ideation were detected on 40.7% of index visits in intervention practices, compared with 20.5% in usual care practices (odds ratio = 2.64, 95% confidence interval, 1.45-5.07), with HMO plan type and male sex associated with detection. The interventions had no effect on referral of patients, starting an antidepressant, or suicidal ideation reported at a 6-month follow-up, although power was limited for all 3 analyses. CONCLUSIONS Primary care interventions to improve depression care can improve detection of recent suicidal ideation. Further work is needed to improve physician response to detection, including referral to specialty care and more aggressive treatment, and to observe the effect on outcomes. C1 Ctr Res Strategies, Denver, CO 80203 USA. Univ Colorado, Dept Family Med, Hlth Sci Ctr, Denver, CO USA. RAND Corp, Hlth Program, Santa Monica, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Cent Arkansas Vet Healthcare Syst, QUERI, N Little Rock, AR USA. Colorado Fdn Med Care, Englewood, CO USA. RP Nutting, PA (reprint author), Ctr Res Strategies, 225 E 6th Ave,Suite 1150, Denver, CO 80203 USA. EM Paul.Nutting@CRSLLC.org FU NIMH NIH HHS [R01 MH54444] NR 62 TC 29 Z9 30 U1 3 U2 10 PU ANNALS FAMILY MEDICINE PI LEAWOOD PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672, UNITED STATES SN 1544-1709 J9 ANN FAM MED JI Ann. Fam. Med. PD NOV-DEC PY 2005 VL 3 IS 6 BP 529 EP 536 DI 10.1370/afm.371 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 993VX UT WOS:000233984700010 PM 16338917 ER PT J AU Ay, H Furie, KL Singhal, A Smith, WS Sorensen, AG Koroshetz, WJ AF Ay, H Furie, KL Singhal, A Smith, WS Sorensen, AG Koroshetz, WJ TI An evidence-based causative classification system for acute ischemic stroke SO ANNALS OF NEUROLOGY LA English DT Article ID DIFFUSION-WEIGHTED MRI; ASYMPTOMATIC CAROTID STENOSIS; RANDOMIZED CONTROLLED TRIALS; ACUTE MYOCARDIAL-INFARCTION; MITRAL-VALVE-PROLAPSE; SICK-SINUS SYNDROME; ATRIAL-FIBRILLATION; LACUNAR INFARCTION; CLINICAL-FEATURES; RISK-FACTORS AB Regular, evidence-based assignment of patients to etiologic stroke categories is essential to enable valid comparison among studies. We designed an algorithm (SSS-TOAST) that incorporated recent advances in stroke imaging and epidemiology to identify the most probable TOAST category in the presence of evidence for multiple mechanisms. Based on the weight of evidence, each TOAST subtype was subdivided into 3 subcategories as "evident", "probable", or "possible". Classification into the subcategories was determined via predefined specific clinical and imaging criteria. These criteria included published risks of ischemic stroke from various mechanisms and published reports of the strength of associations between clinical and imaging features and particular stroke mechanisms. Two neurologists independently assessed 50 consecutively admitted patients with acute ischemic stroke through reviews of abstracted data from medical records. The number of patients classified as "undetermined-unclassified" per the original TOAST system decreased from 38-40% to 4% using the SSS-TOAST system. The kappa value for interexaminer reliability was 0.78 and 0.90 for the original TOAST and SSS-TOAST respectively. The SSS-TOAST system successfully classifies patients with acute ischemic stroke into determined etiologic categories without sacrificing reliabilty. The SSS-TOAST is a dynamic algorithm that can accommodate modifications as new epidemiological data accumulate and diagnostic techniques advance. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging,Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Stroke Serv,Dept Neurol, Boston, MA 02115 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Ay, H (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Stroke Serv, Dept Neurol & Radiol, CNY149-2301, Charlestown, MA 02129 USA. EM hay@partners.org FU AHRQ HHS [R01-HS11392-02]; NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04] NR 90 TC 228 Z9 237 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2005 VL 58 IS 5 BP 688 EP 697 DI 10.1002/ana.20617 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 981PC UT WOS:000233099500006 PM 16240340 ER PT J AU Burstein, HJ Lieberman, G Slamon, DJ Winer, EP Klein, P AF Burstein, HJ Lieberman, G Slamon, DJ Winer, EP Klein, P TI Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; central nervous system; brain metastases; HER2; trastuzumab ID BRAIN METASTASES; PREDICTIVE FACTORS; PROGNOSTIC FACTORS; NATURAL-HISTORY; SURVIVAL; INVOLVEMENT; CARCINOMA; PROGRESSION; DISEASE; RISK AB Purpose: The aim of this study was to characterize the prevalence and predictors of central nervous system (CNS) metastasis among women with HER2-overexpressing metastatic breast cancer receiving trastuzumab-based therapy. Methods: The frequency and time course of isolated CNS progression were characterized among women with HER2-positive metastatic breast cancer, receiving chemotherapy with or without trastuzumab as first-line treatment for metastatic disease in two clinical trials. The first trial was a multicenter randomized phase III study of chemotherapy (doxorubicin/cyclophosphamide or paclitaxel) +/- trastuzumab, and the second was a multicenter phase II trial of vinorelbine + trastuzumab. All patients had measurable disease and were free of symptomatic CNS disease at initiation of study treatment. Results: Nearly 10% of patients receiving trastuzumab in combination with chemotherapy developed isolated CNS metastases as first site of tumor progression. Progression in the CNS tended to be a later event than progression at other sites among women receiving trastuzumab-based therapy. Trastuzumab-based treatment did not substantially delay onset of CNS metastases as initial site of progression. Following diagnosis with primary breast cancer, tumors with HER2 gene amplification tend to be associated with greater risk of isolated CNS progression compared with those lacking gene amplification. Conclusions: Patients with HER2-overexpressing metastatic breast cancer are at risk for isolated CNS progression, reflecting improved peripheral tumor control and patient survival through use of trastuzumab-based therapy, and a relative lack of CNS activity with trastuzumab. Clinicians should be aware of this association. Better treatments for CNS recurrences are needed. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. Genentech Inc, Med Affairs, San Francisco, CA 94080 USA. Univ Calif Los Angeles, Sch Med, Div Hematol Oncol, Los Angeles, CA 90024 USA. RP Burstein, HJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM hburstein@partners.org NR 27 TC 83 Z9 87 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2005 VL 16 IS 11 BP 1772 EP 1777 DI 10.1093/annonc/mdi371 PG 6 WC Oncology SC Oncology GA 977QP UT WOS:000232818600008 PM 16150805 ER PT J AU Kumbhani, DJ Healey, NA Biswas, KS Birjiniuk, V Crittenden, MD Treanor, PR Khuri, SF AF Kumbhani, DJ Healey, NA Biswas, KS Birjiniuk, V Crittenden, MD Treanor, PR Khuri, SF TI Adverse 30-day outcomes after cardiac surgery: Predictive role of intraoperative myocardial acidosis SO ANNALS OF THORACIC SURGERY LA English DT Article ID LONG-TERM SURVIVAL; ONLINE MEASUREMENT; RISK-FACTORS; TISSUE PH; COMPLICATIONS; DETERMINANTS; ISCHEMIA; HEART; PCO2; DOG AB Background. Regional myocardial acidosis in patients undergoing cardiac surgery has been shown to be reflective of regional myocardial ischemia. This study elucidates the relationship between intraoperative regional myocardial acidosis and 30-day postoperative outcomes after cardiac surgery. Methods. Intramyocardial tissue pH in the anterior and posterior left ventricular walls was measured in 397 adult patients undergoing valve replacement or coronary revascularization surgery between 1987 and 2001. Dedicated nurses and research assistants prospectively collected preoperative, intraoperative, and outcomes data. Regional myocardial acidosis was defined in terms of pH thresholds identified by recursive partitioning. Adverse 30-day outcome, defined as death or any one of six complications, was the dependent variable in a multivariate logistic regression analysis. A morbidity score was developed on the basis of the sensitivity of each of the six complications in predicting death, and was the dependent variable in a multivariate linear regression analysis. Results. During the period of aortic clamping, a mean intramyocardial tissue pH less than 6.85 was identified to be significant by recursive partitioning, and was encountered in either the anterior or posterior left ventricular wall in 85.4% of patients. After adjusting for preoperative and intraoperative variables, this pH threshold was found to be significantly associated with increased adverse outcomes within 30 days after surgery (p = 0.045). It was also significantly associated with increase in the morbidity score (p = 0.05). Conclusions. Regional myocardial acidosis of a magnitude frequently encountered during aortic clamping is an independent determinant of adverse 30-day outcomes after cardiac surgery. Its reversal by pH-guided myocardial management has the potential of improving postoperative patient outcomes. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Surg Serv, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 32 TC 11 Z9 11 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 NOV PY 2005 VL 80 IS 5 BP 1751 EP 1757 DI 10.1016/j.athoracsur.2005.05.027 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 979UN UT WOS:000232970500029 PM 16242451 ER PT J AU Schwarze, ML Houser, SL Muniappan, A Allan, JS Menard, MT McMorrow, I Maloney, ME Madsen, JC AF Schwarze, ML Houser, SL Muniappan, A Allan, JS Menard, MT McMorrow, I Maloney, ME Madsen, JC TI Effects of mycophenolate mofetil on cardiac allograft survival and cardiac allograft vasculopathy in miniature swine SO ANNALS OF THORACIC SURGERY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; TRANSPLANT ARTERIOSCLEROSIS; IMMUNE-MECHANISMS; T-CELL; HEART; REJECTION; PREVENTS; RECIPIENTS; RS-61443; RAT AB Background. Chronic rejection, as manifested by cardiac allograft vasculopathy, remains the leading cause of late graft failure in heart transplant recipients. Despite recent clinical trials, the efficacy of mycophenolate mofetil in preventing human cardiac allograft vasculopathy remains controversial. We investigated whether mycophenolate mofetil would prevent cardiac allograft vasculopathy and prolong cardiac allograft survival in our well-established miniature swine model of heart transplantation. Methods. Hearts disparate at the major histocompatibility complex class I locus were heterotopically transplanted into miniature swine recipients treated with a 12-day course of mycophenolate mofetil (n = 3) or cyclosporine A (n = 3). Allograft survival, acute rejection, and chronic rejection were monitored in the two groups. Results. Hearts transplanted with 12 days of cyclosporine were rejected between 46 and 61 days, whereas two of the three hearts transplanted with mycophenolate mofetil remained beating beyond 120 days (p = 0.02). At necropsy, there was a 4.9% mean prevalence of cardiac allograft vasculopathy in the mycophenolate mofetil group as compared with 16.6% in the cyclosporine group (p = 0.03). Cardiac allograft rejection and vasculopathy in the cyclosporine-treated group was associated with prominent myocardial interferon-gamma gene expression, a finding absent in two thirds of the mycophenolate mofetil-treated swine. Moreover, the mycophenolate mofetil-treated swine failed to develop IgM or IgG alloantibodies. Conclusions. A short course of mycophenolate mofetil resulted in a longer allograft survival than a similar course of cyclosporine. Moreover, mycophenolate mofetil reduced the prevalence of cardiac allograft vasculopathy as compared with cyclosporine-treated controls. The salutary effect of mycophenolate mofetil may be related to its ability to decrease interferon-gamma expression in the myocardium and prevent the generation of alloantibodies. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiac Surg, Boston, MA 02114 USA. RP Madsen, JC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr,Dept Surg, 55 Fruit St,BUL-01-119, Boston, MA 02114 USA. EM madsen@helix.mgh.harvard.edu FU NHLBI NIH HHS [P01 HL18646, R01 HL67110, R01 HL54211]; NIAID NIH HHS [P01 AI50157] NR 29 TC 8 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 NOV PY 2005 VL 80 IS 5 BP 1787 EP 1793 DI 10.1016/j.athoracsur.2005.04.054 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 979UN UT WOS:000232970500034 PM 16242456 ER PT J AU Mezhir, JJ Schmidt, H Yamini, B Senzer, NN Posner, MC Kufe, DW Weichselbaum, RR AF Mezhir, JJ Schmidt, H Yamini, B Senzer, NN Posner, MC Kufe, DW Weichselbaum, RR TI Chemoinducible gene therapy SO ANTI-CANCER DRUGS LA English DT Review DE adenoviral vector; chemoinducible gene therapy; chemotherapy; DNA-damaging agent; gene therapy; transcriptional targeting; viral gene therapy ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; IONIZING-RADIATION; INTERFERON-GAMMA; PHASE-I; PROMOTER; CANCER; TRANSCRIPTION; CHEMOTHERAPY; VASCULATURE AB Chemoinducible cancer gene therapy is a potential new treatment for solid tumors that may in part enhance the anti-tumor effects of chemotherapy while minimizing toxicity. This approach combines viral vectors expressing cytotoxic transgenes that can be transcriptionally activated by DNA-damaging agents. The development of chemoinducible gene therapy has numerous implications for the treatment of both localized and metastatic disease in patients with solid tumors. C1 Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Univ Chicago Hosp, Dept Radiat Oncol, Chicago, IL 60637 USA. Sammons Canc Ctr, Mary Crowley Med Res Ctr, Dallas, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat & Cellular Oncol, Ctr Adv Med, Room 1329,Mail Code 9006,5758 S Maryland Ave, Chicago, IL 60637 USA. EM rrw@rover.uchicago.edu NR 25 TC 2 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD NOV PY 2005 VL 16 IS 10 BP 1053 EP 1058 DI 10.1097/00001813-200511000-00003 PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 985UJ UT WOS:000233403900003 PM 16222146 ER PT J AU Kirkpatrick, WR Vallor, AC McAtee, RK Ryder, NS Fothergill, AW Rinaldi, MG Patterson, TF AF Kirkpatrick, WR Vallor, AC McAtee, RK Ryder, NS Fothergill, AW Rinaldi, MG Patterson, TF TI Combination therapy with terbinafine and amphotericin B in a rabbit model of experimental invasive aspergillosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EFFICACY AB Antagonistic effects of combination therapy using amphotericin B (AmB) with agents which block ergosterol synthesis are a concern. Terbinafine was evaluated with AmB to assess antagonism or synergy in a rabbit model of invasive aspergillosis. Terbinafine had relatively little activity but did not demonstrate antagonism against AmB in our model. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 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 78284 USA. Novartis Inst Biomed Res Inc, Concord, MA 01742 USA. RP Kirkpatrick, WR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Infect Dis, 7703 Floyd Curl Dr,Mail Code 7881, San Antonio, TX 78229 USA. EM kirkpatrick@uthscsa.edu NR 12 TC 14 Z9 14 U1 1 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 NOV PY 2005 VL 49 IS 11 BP 4751 EP 4753 DI 10.1128/AAC.49.11-4751-4753.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 980LV UT WOS:000233020900043 PM 16251321 ER PT J AU Domingo, MC Huletsky, A Giroux, R Boissinot, K Picard, FJ Lebel, P Ferraro, MJ Bergeron, MG AF Domingo, MC Huletsky, A Giroux, R Boissinot, K Picard, FJ Lebel, P Ferraro, MJ Bergeron, MG TI High prevalence of glycopeptide resistance genes vanB, vanD, and vanG not associated with enterococci in human fecal flora SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HUMAN FECES; ELEMENTS AB The presence of Enterococcus-associated vancomycin resistance genes vanA, vanB, vanD, vanE, and vanG in rectal swabs was investigated in two hospitals using PCR. All vanA genes detected were associated with vancomycin-resistant enterococci (VRE), whereas VRE-associated vanB genes were detected in only one hospital (4.7%). However, in both hospitals, high prevalences of vanB (6.2 and 2.3%), vanD (43.8 and 26.7%), and vanG (10.5 and 6.9%) genes not associated with enterococci were found. C1 Univ Laval, CHUQ, Ctr Rech Infectiol, Quebec City, PQ G1V 4G2, Canada. Univ Laval, Fac Med, Div Microbiol, Laval, PQ, Canada. McGill Univ, Ctr Hlth, Hop Gen Montreal, Dept Microbiol, Montreal, PQ, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Clin Microbiol, Boston, MA USA. RP Bergeron, MG (reprint author), Univ Laval, CHUQ, Ctr Rech Infectiol, Pavillon CHUL,2705 Boul Laurier, Quebec City, PQ G1V 4G2, Canada. EM michel.g.bergeron@crchul.ulaval.ca NR 7 TC 32 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2005 VL 49 IS 11 BP 4784 EP 4786 DI 10.1128/AAC.49.11.4784-4786.2005 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 980LV UT WOS:000233020900053 PM 16251331 ER PT J AU Demidova, TN Hamblin, MR AF Demidova, TN Hamblin, MR TI Photodynamic inactivation of Bacillus spores, mediated by phenothiazinium dyes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID METHYLENE-BLUE; STAPHYLOCOCCUS-AUREUS; BACTERIAL-SPORES; PHOTOBACTERICIDAL ACTIVITY; WOUND INFECTIONS; ESCHERICHIA-COLI; MEGATERIUM SPORE; SUBTILIS SPORES; IN-VIVO; THERAPY AB Spore formation is a sophisticated mechanism by which some bacteria survive conditions of stress and starvation by producing a multilayered protective capsule enclosing their condensed DNA. Spores are highly resistant to damage by heat, radiation, and commonly employed antibacterial agents. Previously, spores have also been shown to be resistant to photodynamic inactivation using dyes and light that easily destroy the corresponding vegetative bacteria. We have discovered that Bacillus spores are susceptible to photoinactivation by phenothiazinium dyes and low doses of red light. Dimethylmethylene blue, methylene blue, new methylene blue, and toluidine blue O are all effective, while alternative photosensitizers such as Rose Bengal, polylysine chlorin(e6) conjugate, a tricationic porphyrin, and a benzoporphyrin derivative, which easily kill vegetative cells, are ineffective. Spores of Bacillus cereus and B. thuringiensis are most susceptible, B. subtilis and B. atrophaeus are also killed, and B. megaterium is resistant. Photoinactivation is most effective when excess dye is washed from the spores, showing that the dye binds to the spores and that excess dye in solution can quench light delivery. The relatively mild conditions needed for spore killing could have applications for treating wounds contaminated by anthrax spores, for which conventional sporicides would have unacceptable tissue toxicity. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Tufts Univ, Sackler Sch Grad Biomed Sci, Grad Program Cell Mol & Dev Biol, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01 AI050875-02] NR 61 TC 64 Z9 69 U1 1 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2005 VL 71 IS 11 BP 6918 EP 6925 DI 10.1128/AEM.71.11.6918-6925.2005 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 983IN UT WOS:000233225000057 PM 16269726 ER PT J AU Echague, AV Astner, S Chen, AA Anderson, RR AF Echague, AV Astner, S Chen, AA Anderson, RR TI Multiple apocrine hidrocystoma of the face treated with a 1450-nm diode laser SO ARCHIVES OF DERMATOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Anderson, RR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Wellman Ctr Photomed, Boston, MA 02114 USA. EM rranderson@partners.org NR 5 TC 10 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2005 VL 141 IS 11 BP 1365 EP 1367 DI 10.1001/archderm.141.11.1365 PG 3 WC Dermatology SC Dermatology GA 982SU UT WOS:000233182700002 PM 16301382 ER PT J AU Zehnder, AF Adams, JC Santi, PA Kristiansen, AG Wacharasindhu, C Mann, S Kalluri, R Gregory, MC Kashtan, CE Merchant, SN AF Zehnder, AF Adams, JC Santi, PA Kristiansen, AG Wacharasindhu, C Mann, S Kalluri, R Gregory, MC Kashtan, CE Merchant, SN TI Distribution of type IV collagen in the cochlea in Alport syndrome SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID BASEMENT-MEMBRANES; INNER-EAR AB Objective: To determine the distribution of alpha 1, alpha 3, and alpha 5 chains of type IV collagen in the cochlea in Alport syndrome. Design: Case-control study. Patients: Two patients with sensorineural hearing loss due to Alport syndrome. Both patients had known mutations in the COL4A5 gene. Main Outcome Measures: Immunostaining was used to study the distribution of type IV collagen (alpha 1, alpha 3, and alpha 5 chains) within the cochlea. Immunostaining was also performed in the cochlear tissues of an unaffected individual used as a control. Results: In the control ear, alpha 1 staining was observed in the basement membrane overlying the basilar membrane, in the basement membrane of cochlear blood vessels and Schwarm cells, and within the spiral limbus. In the control ear, we also observed strong staining for alpha 3 and alpha 5 chains in the basement membrane overlying the basilar membrane and within the spiral ligament. In both cases with Alport syndrome, no immunostaining was observed for alpha 3 or alpha 5 chains within the cochlea, whereas alpha 1 staining was present in locations similar to that seen in the control ear. Conclusions: The results indicate that isotype switching does not occur within the cochlea in Alport syndrome. The results are also consistent with the hypothesis that the sensorineural hearing loss in Alport syndrome may be due to alterations in cochlear micromechanics and/or dysfunction of the spiral ligament. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Univ Basel Hosp, Dept Ear Nose & Throat, CH-4031 Basel, Switzerland. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Ctr Matrix Biol, Dept Med, Boston, MA 02215 USA. Univ Minnesota, Dept Otolaryngol, Minneapolis, MN USA. Univ Minnesota, Dept Neurosci, Minneapolis, MN USA. Univ Minnesota, Div Pediat Nephrol, Dept Pediat, Minneapolis, MN USA. Univ Utah, Dept Med, Med Ctr, Salt Lake City, UT USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM saumil_merchant@meei.harvard.edu RI Kalluri, Raghu/E-2677-2015 OI Kalluri, Raghu/0000-0002-2190-547X NR 23 TC 18 Z9 20 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2005 VL 131 IS 11 BP 1007 EP 1013 DI 10.1001/archotol.131.11.1007 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 983SJ UT WOS:000233252100012 PM 16301374 ER PT J AU Chien, WD Faquin, WC Caruso, PA Rabinov, JD Cunningham, MJ AF Chien, WD Faquin, WC Caruso, PA Rabinov, JD Cunningham, MJ TI Radiology quiz case 4 SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID VASCULAR MALFORMATIONS; CLASSIFICATION; HEMANGIOMAS; ANOMALIES C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Chien, WD (reprint author), Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2005 VL 131 IS 11 BP 1026 EP + DI 10.1001/archotol.131.11.1026 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 983SJ UT WOS:000233252100019 PM 16301381 ER PT J AU LaValley, MP McLaughlin, S Goggins, J Gale, D Nevitt, MC Felson, DT AF LaValley, MP McLaughlin, S Goggins, J Gale, D Nevitt, MC Felson, DT TI The lateral view radiograph for assessment of the tibiofemoral joint space in knee osteoarthritis - Its reliability, sensitivity to change, and longitudinal validity SO ARTHRITIS AND RHEUMATISM LA English DT Article ID DOUBLE-BLIND; AUTOMATED MEASUREMENTS; GLUCOSAMINE SULFATE; CLINICAL-TRIAL; PROGRESSION; PLACEBO; REPRODUCIBILITY; MULTICENTER; ALIGNMENT; EFFICACY AB Objective. To evaluate the reliability, validity, and sensitivity to change of tibiofemoral (TF) narrowing on lateral radiographic views. Methods. In a natural history study of symptomatic knee osteoarthritis (OA), both lateral view and fluoroscopically positioned posteroanterior (PA) semiflexed view radiographs of the knee in 30 degrees of flexion and with weight bearing were obtained at baseline and at 30 months. Test-retest reliability was evaluated using repeat radiographs, with joint space width measured using electronic calipers. All radiographs were scored on a 0-3 scale, and progression of joint space loss was defined as narrowing of the joint space by 1 grade. We evaluated sensitivity to change compared with the PA view. We evaluated validity by examining whether knees with progression showed expected malalignment on full-limb films. Results. Test-retest reliability of the TF joint space using the lateral view had a root mean square error of 0.303 mm, with 92.5% of repeats within I mm. More knees showed progression on the lateral view alone (n = 41) than on the PA view alone (n = 27). Compared with knees without joint space loss, knees with medial compartment loss on the lateral view only were more varus malaligned (P < 0.001), while those with lateral compartment loss were more valgus malaligned (P = 0.008). Conclusion. In the assessment of TF joint space loss, lateral view radiographs are reliable, valid, and more sensitive to change than fluoroscopically positioned PA radiographs. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Healthcare Syst, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Felson, DT (reprint author), Boston Univ, Sch Med, A203,715 Albany St, Boston, MA 02118 USA. EM dfelson@bu.edu OI Felson, David/0000-0002-2668-2447; LaValley, Michael/0000-0002-8488-5170 FU NIAMS NIH HHS [AR 47785] NR 23 TC 33 Z9 33 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2005 VL 52 IS 11 BP 3542 EP 3547 DI 10.1002/art.21374 PG 6 WC Rheumatology SC Rheumatology GA 984EN UT WOS:000233285400027 PM 16255043 ER PT J AU Namjou, B Kelly, JA Kilpatrick, J Kaufman, KM Nath, SK Scofield, RH Harley, JB AF Namjou, B Kelly, JA Kilpatrick, J Kaufman, KM Nath, SK Scofield, RH Harley, JB TI Linkage at 5q14.3-15 in multiplex systemic lupus erythematosus pedigrees stratified by autoimmune thyroid disease SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SUSCEPTIBILITY LOCI; GENOME SCAN; AUTOANTIBODIES; IDENTIFICATION; PEROXIDASE; EPISTASIS; FAMILIES; 1Q AB Objective. To identify genetic effects potentially shared between systemic lupus erythematosus (SLE) and autoimmune thyroiditis (AITD). Methods. Families from the Lupus Multiplex Registry and Repository were studied in which there was at least 1 member who had both SLE and AITD (Graves' disease or Hashimoto thyroiditis). Genome scan genotyping findings in these pedigrees were evaluated for evidence of genetic linkage, by the maximum-likelihood parametric method. Nineteen pedigrees were used in the initial genome scan. Subsequently, an independent sample of 16 pedigrees was used to replicate findings. Results. Studies of the first set of 19 pedigrees yielded a 2-point parametric logarithm of odds (LOD) of 4.97, which was independently confirmed in the replication sample of 16 pedigrees (LOD 2.89). For all 35 pedigrees together, the 2-point LOD was 7.86, under a dominant model used for screening with 90% penetrance and a disease allele frequency of 10%. The multipoint locus homogeneity LOD in the 35 pedigrees was 6.90 (alpha = 1.0) at 5q14.3-15 between D5S1725 and D5S1453, a 12-cM interval, with the peak at D5S1462 at 96.64 cM (nonparametric linkage P = 0.00002). Fine mapping further confirmed the genetic linkage effect and narrowed the region likely to contain the gene to similar to 5 Mb. Conclusion. These results suggest that stratifying SLE pedigrees by the presence of other autoimmune disorders may facilitate the discovery of genes related I to SLE and that 5q14.3-15 harbors a susceptibility gene shared by SLE and AITD. C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. RP Harley, JB (reprint author), Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM john-harley@omrf.ouhsc.edu FU NCRR NIH HHS [RR 015577, RR 020143, RR 14467]; NIAID NIH HHS [AI 54117, AI 053747, AI 24717, AI 31584]; NIAMS NIH HHS [AR 049084, AR 12253, AR 42460, AR 48940]; NIDCR NIH HHS [DE 15223] NR 16 TC 18 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2005 VL 52 IS 11 BP 3646 EP 3650 DI 10.1002/art.21413 PG 5 WC Rheumatology SC Rheumatology GA 984EN UT WOS:000233285400041 PM 16255059 ER PT J AU Papandonatos, GD Santangelo, SL McCaffery, JM Lyons, M Tsuang, MT Niaura, R Buka, S AF Papandonatos, GD Santangelo, SL McCaffery, JM Lyons, M Tsuang, MT Niaura, R Buka, S TI Association of the serotonin transporter gene with nicotine dependence SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 35th Annual Meeting of the Behavior-Genetics-Association CY JUN 29-JUL 02, 2005 CL Hollywood, CA SP Behav Genet Assoc C1 Brown Med Sch, Ctr Stat Sci, Dept Community Hlth, Providence, RI USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Charlestown, MA USA. Brown Univ, Sch Med, Ctr Behav & Prevent Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Miriam Hosp, Providence, RI 02906 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Univ Calif San Diego, Inst Behav Genom, Dept Psychiat, San Diego, CA 92103 USA. Brown Univ, Sch Med, Interdisciplinary Res Ctr, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Butler Hosp, Providence, RI 02906 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. EM gdp@stat.brown.edu RI Lyons, Michael/B-6119-2011; Buka, Stephen/H-7335-2014; Papandonatos, George/J-2328-2014 OI Buka, Stephen/0000-0002-8578-9308; NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2005 VL 35 IS 6 BP 817 EP 817 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 985PZ UT WOS:000233391600100 ER PT J AU Paszty, K Antalffy, G Penheiter, AR Homolya, L Padany, R Ilias, A Filoteo, AG Penniston, JT Enyedi, A AF Paszty, K Antalffy, G Penheiter, AR Homolya, L Padany, R Ilias, A Filoteo, AG Penniston, JT Enyedi, A TI The caspase-3 cleavage product of the plasma membrane Ca2+-ATPase 4b is activated and appropriately targeted SO BIOCHEMICAL JOURNAL LA English DT Article DE activation; apoptosis; calmodulin; caspase-3; localization; plasma membrane Ca2+-ATPase ID ATPASE ISOFORM 4B; CALCIUM-PUMP; CA2+ PUMP; GENE-TRANSFER; APOPTOSIS; PROTEINS; CELLS; MODULATION; DOMAIN; DEATH AB The calmodulin-activated transporter hPMCA4 (human plasma membrane Ca2+-ATPase isoform 4) is a target for cleavage by caspase-3 during apoptosis. We have demonstrated that caspase-3 generates a 120 kDa fragment of this pump which lacks the complete autoinhibitory sequence [Paszty, Verma, Padanyi, Filoteo, Penniston and Enyedi (2002) J. Biol. Chem. 277, 6822-6829]. In the present study we analysed further the characteristics of the fragment of hPMCA4b produced by caspase-3. We did this by overexpressing the caspase-3 cleavage product of hPMCA4b in COS-7 and MDCKII (Madin-Darby canine kidney II) cells. This technique made it possible to clearly define the properties of this fragment, and we showed that it is constitutively active, as it forms a phosphoenzyme intermediate and has high Ca2+ transport activity in the absence of calmodulin. When this fragment of hPMCA4b was stably expressed in MDCKII cell clones, it was targeted without degradation to the basolateral plasma membrane. In summary, our studies emphasize that the caspase-3 cleavage product of hPMCA4b is constitutively active, and that the C-terminus is not required for proper targeting of hPMCA4b to the plasma membrane. Also, for the first time, we have generated cell clones that stably express a constitutively active PMCA. C1 Natl Med Ctr, H-1113 Budapest, Hungary. Hungarian Acad Sci, Membrane Res Grp, H-1051 Budapest, Hungary. Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Hungarian Acad Sci, Inst Enzymol, H-1113 Budapest, Hungary. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Neurosci, Boston, MA 02114 USA. RP Enyedi, A (reprint author), Natl Med Ctr, Dioszegi 64, H-1113 Budapest, Hungary. EM enyedi@biomembrane.hu RI Enyedi, Agnes/N-9742-2013; Homolya, Laszlo/N-1154-2016; OI Enyedi, Agnes/0000-0002-7366-9376; Paszty, Katalin/0000-0003-2457-8555; Ilias, Attila/0000-0003-3196-0795 FU NIGMS NIH HHS [GM28835, R01 GM028835] NR 32 TC 15 Z9 16 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD NOV 1 PY 2005 VL 391 BP 687 EP 692 DI 10.1042/BJ20051012 PN 3 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 983SW UT WOS:000233253400025 PM 16080782 ER PT J AU Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL AF Hahn, T Wall, D Camitta, B Davies, S Dillon, H Gaynon, P Larson, RA Parsons, S Seidenfeld, J Weisdorf, D McCarthy, PL TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in children: An evidence-based review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE acute lymphoblastic leukemia; hematopoietic stem cell transplantation; therapy; pediatric ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; ISOLATED EXTRAMEDULLARY RELAPSE; MATCHED-PAIR ANALYSIS; DOSE CYTOSINE-ARABINOSIDE; HLA-IDENTICAL SIBLINGS; LONG-TERM SURVIVAL; GREFFE-DE-MOELLE; MRC UKALL-X; 2ND REMISSION AB Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia (ALL) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in a table in this review (Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Lymphoblastic Leukemia) and were reached unanimously by a panel of ALL experts. The priority areas of needed future research in pediatric ALL are unrelated marrow or blood donor versus unrelated cord blood donor allogeneic SCT; alternative, nonfamily allogeneic donor versus autollogous SCT; better methods for identifying high-relapse-risk patients; assessments of the effect of current chemotherapy regimens on early relapse; and use of pre-SCT detection of minimal residual disease to predict post-SCT outcomes. (c) 2005 American Society for Blood and Marrow Transplantation C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Texas Transplant Inst, San Antonio, TX USA. Med Coll Wisconsin, Midwest Childrens Ctr, Milwaukee, WI 53226 USA. Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA. Leukemia & Lymphoma Soc, White Plains, NY USA. Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Chicago, Chicago, IL 60637 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02114 USA. Blue Cross & Blue Shield Assoc Technol Evaluat Ct, Chicago, IL USA. Univ Minnesota, Minneapolis, MN USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM theresa.hahn@roswellpark.org OI Larson, Richard/0000-0001-9168-3203 NR 92 TC 44 Z9 45 U1 0 U2 2 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2005 VL 11 IS 11 BP 823 EP 861 DI 10.1016/j.bbmt.2005.08.035 PG 39 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 987LU UT WOS:000233520200002 PM 16275588 ER PT J AU Oral, E Greenbaum, ES Malhi, AS Harris, WH Muratoglu, OK AF Oral, E Greenbaum, ES Malhi, AS Harris, WH Muratoglu, OK TI Characterization of irradiated blends of alpha-tocopherol and UHMWPE SO BIOMATERIALS LA English DT Article DE antioxidant; polyethylene; wear mechanism; lipid; gamma-irradiation; hip replacement prosthesis ID MOLECULAR-WEIGHT POLYETHYLENE; VITAMIN-E; WEAR; COMPONENTS; RESISTANCE; RADIATION AB Adhesive/abrasive wear in ultra-high molecular weight polyethylene (UHMWPE) has been minimized by radiation cross-linking. Irradiation is followed by melting to eliminate residual free radicals and avoid long-term oxidative embrittlement. However, Post-irradiation melting reduces the crystallinity of the polymer and hence its strength and fatigue resistance. We proposed an alternative to post-irradiation melting to be the incorporation of the antioxiclant alpha-tocoplicrol into UHMWPE prior to consolidation. alpha-Tocopherol is known to react with oxygen and oxidized lipids, stabilizing them against further oxidative degradation reactions. We blended GUR 1050 UHMWPE resin powder with alpha-tocopherol at 0.1 and 0.3wt%. and consolidated these blends. Then we gamma-irradiated these blends to 100-kG. We characterized the effect of alpha-tocopherol on the cross-linking efficiency, oxidative stability, wear behavior and mechanical properties of the blends. (1) The cross-link density of virgin. 0.1 and 0.3 wt% alpha-tocopherol blended, 100-kGy irradiated UHMWPEs were 175 +/- 19, 146 +/- 4 and 93 +/- 4mol/m(3), respectively. (II) Maximum oxidation indices For 100-kGy irradiated UHMWPE previously blended with 0, 0.1 and 0.3 wt% alpha-tocopherol that were subjected to accelerated aging at 80 C in air for 5 weeks were 3.32, 0.09. and 0.05, respectively. (III) The pin-on-disc wear rates of 100-kGy irradiated UHMWPE previously blended with 0.1 and 0.3wt% alpha-tocopherol that were subjected to accelerated aging at 80 C in air for 5 weeks were 2.10 +/- 0.17 and 5.01 +/- 0.76mg/million cycles, respectively. (IV) Both accelerated aged, alpha-tocopherol-blended 100-kGy irradiated UHMWPEs showed higher ultimate tensile strength, higher yield strength, and lower elastic modulus when compared to 100-kGy irradiated. virgin UHMWPE. These results showed that alpha-tocopherol-blended 100-kGy irradiated UHMWPEs were not cross-linked to the same extent as the 100-kGy irradiated, virgin UHMWPE. (c) 2005 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Ortopaed Biomech & Biomat Lab, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Ortopaed Biomech & Biomat Lab, Dept Orthopaed Surg, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM orthun@alum.mit.edu FU NIAMS NIH HHS [R01 AR051142-01, R01 AR051142] NR 15 TC 78 Z9 80 U1 4 U2 19 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 NOV PY 2005 VL 26 IS 33 BP 6657 EP 6663 DI 10.1016/j.biomaterials.2005.04.026 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 954XW UT WOS:000231189800027 PM 15993487 ER PT J AU Eniola, AO Krasik, EF Smith, LA Song, G Hammer, DA AF Eniola, AO Krasik, EF Smith, LA Song, G Hammer, DA TI I-domain of lymphocyte function-associated antigen-1 mediates rolling of polystyrene particles on ICAM-1 under flow SO BIOPHYSICAL JOURNAL LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; LEUKOCYTE-ENDOTHELIUM INTERACTIONS; SLOW VISCOUS MOTION; CELL-FREE SYSTEM; P-SELECTIN; FIRM ADHESION; SPHERE PARALLEL; DISTINCT ROLES; DISULFIDE BOND; MOUSE COLON AB In their active state, beta 2-integrins, such as LFA-1, mediate the firm arrest of leukocytes by binding intercellular adhesion molecules (ICAMs) expressed on endothelium. Although the primary function of LFA-1 is assumed to be the ability to mediate firm adhesion, recent work has shown that LFA-1 can contribute to cell tethering and rolling under hydrodynamic flow, a role previously largely attributed to the selectins. The inserted (I) domain of LFA-1 has recently been crystallized in the wildtype (wt) and locked-open conformations and has been shown to, respectively, support rolling and firm adhesion under flow when expressed in alpha(L)beta 2 heterodimers or as isolated domains on cells. Here, we report results from cell-free adhesion assays where wt I-domain-coated polystyrene particles were allowed to interact with ICAM-1-coated surfaces in shear flow. We show that wt I-domain can independently mediate the capture of particles from flow and support their rolling on ICAM-1 surfaces in a manner similar to how carbohydrate-selectin interactions mediate rolling. Adhesion is specific and blocked by appropriate antibodies. We also show that the rolling velocity of I-domain-coated particles depends on the wall shear stress in flow chamber, I-domain site density on microsphere surfaces, and ICAM-1 site density on substrate surfaces. Furthermore, we show that rolling is less sensitive to wall shear stress and ICAM-1 substrate density at high density of I-domain on the microsphere surface. Computer simulations using adhesive dynamics can recreate bead rolling dynamics and show that the mechanochemical properties of ICAM-1-I-domain interactions are similar to those of carbohydrate-selectin interactions. Understanding the biophysics of adhesion mediated by the I-domain of LFA-1 can elucidate the complex roles this integrin plays in leukocyte adhesion in inflammation. C1 Univ Penn, Dept Bioengn, Philadelphia, PA 19104 USA. Univ Penn, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USA. Univ Penn, Inst Med & Engn, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, CBR Biomed Res Inst, Boston, MA 02115 USA. RP Hammer, DA (reprint author), Univ Penn, Dept Bioengn, 120 Hayden Hall,3320 Smith Walk, Philadelphia, PA 19104 USA. EM hammer@seas.upenn.edu RI Eniola-Adefeso, Lola/H-1082-2011; OI Eniola-Adefeso, Omolola/0000-0002-8728-6608 FU NHLBI NIH HHS [HL 18208, P01 HL018208]; NIBIB NIH HHS [EB 00256, R01 EB000256] NR 49 TC 33 Z9 33 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2005 VL 89 IS 5 BP 3577 EP 3588 DI 10.1529/biophysj.104.057729 PG 12 WC Biophysics SC Biophysics GA 979HP UT WOS:000232933300069 PM 16100282 ER PT J AU Richardson, PGG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Xiao, H Esseltine, D Schenkein, D Anderson, KC AF Richardson, PGG Barlogie, B Berenson, J Singhal, S Jagannath, S Irwin, D Rajkumar, SV Hideshima, T Xiao, H Esseltine, D Schenkein, D Anderson, KC CA SUMMIT Investigators TI Clinical factors predictive of outcome with bortezomib in patients with relapsed, refractory multiple myeloma SO BLOOD LA English DT Article ID HIGH-DOSE THERAPY; CHROMOSOME-13 ABNORMALITIES; STAGING SYSTEM; ONCOLOGY-GROUP; SURVIVAL; THALIDOMIDE; PHASE-2; TRIAL AB Bortezomib, a potent and reversible proteasome inhibitor, affects the myeloma cell and its microenviromment, resulting in downregulation of growth and survival signaling pathways and durable responses in patients with relapsed and refractory myeloma. Potential associations between baseline parameters and outcomes with bortezomib were explored in 202 patients who received bortezomib 1.3 mg/m(2) twice weekly for 2 weeks every 3 weeks for up to 8 cycles in a phase 2 trial. Using European Group for Blood and Marrow Transplantation criteria, the response rate (complete or partial response) to bortezomib alone was 27% and was not associated with sex, race, performance status, isotype, chromosome 13 deletion, number or type of previous therapies, or concentration of hemoglobin or beta(2)-microglobulin. By multivariate analysis, factors associated with lower response were being age 65 or older versus younger than 65 (19% vs 32%; P<.05) and plasma-cell infiltration in bone marrow greater than 50% versus 50% or less (20% vs 35%; P<.05). Factors that may be indicative of tumor burden (bone marrow plasma-cell infiltration greater than 50%, hypoalbuminemia, thrombocytopenia) were predictive of overall survival. Chromosome 13 deletion and elevated beta(2)-microglobulin, generally considered poor prognostic factors, were not predictive of poor outcome with bortezomib in this study. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NW Mem Hosp, Chicago, IL 60611 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Mayo Clin, Rochester, MN USA. Millenium Pharmaceut Inc, Cambridge, MA USA. RP Richardson, PGG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833 NR 23 TC 84 Z9 88 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 2977 EP 2981 DI 10.1182/blood-2005-02-0691 PG 5 WC Hematology SC Hematology GA 979BP UT WOS:000232917400017 PM 16020506 ER PT J AU Li, LQ Godfrey, WR Porter, SB Ge, Y June, CH Blazar, BR Boussiotis, VA AF Li, LQ Godfrey, WR Porter, SB Ge, Y June, CH Blazar, BR Boussiotis, VA TI CD4(+)CD25(+) regulatory T-cell lines from human cord blood have functional and molecular properties of T-cell anergy SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; IMMUNOLOGICAL SELF-TOLERANCE; PROTEIN-KINASE-B; SUPPRESSOR FUNCTION; IL-2; ACTIVATION; DEATH; HOMEOSTASIS; P27(KIP1); PHOSPHORYLATION AB CD4(+)CD25(+) regulatory T cells (Tregs) are essential negative regulators of immune responses. Here, we examined the signaling properties of human Tregs, using CD4(+)CD25(+) Treg and CD4(+)CD25(-) control (Tcont) cell lines generated from cord blood. Treg cell lines were markedly hyporesponsive to stimulation with dendritic cells and with anti-CD3/CD28-coated beads. Hyporesponsiveness was reversed by exogenous interleukin-2 (IL-2). T-cell receptor (TCR)-CD3/CD28-mediated activation of Rapt and Akt was retained in Tregs, but activation of Ras, mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated kinase 1/2 (Erk1/2) was impaired. Tregs were blocked from cell cycle progression due to decrease of cyclin E and cyclin A and increase of p27(kip1) (p27(kip) cyclin dependent kinase inhibitor). IL-2 induced sustained increase of cyclin E and cyclin A and prevented up-regulation of p27(kip1). Tregs had high susceptibility to apoptosis that was reversed by IL-2, which correlated with activation of Erk1/2, up-regulation of Bcl-x(L) (B-cell CLL/lymphoma 2-like nuclear gene encoding mitochondrial protein, transcript variant 2), and phosphorylation of Bad (Bcl2 antagonist of cell death) at Ser(112). Thus, Tregs share biochemical characteristics of anergy, including abortive activation of Ras-MEK-Erk, increased activation of Rap1, and increased expression of p27(kip1). In addition, our results indicate that TCR-CD3/CD28-mediated and IL-2 receptor-mediated signals converge at the level of MEK-Erk kinases to regulate Treg survival and expansion and suggest that manipulation of the MEK-Erk axis may represent a novel strategy for Treg expansion for immunotherapy. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Dept Pediat, Minneapolis, MN USA. Univ Penn, Ctr Canc, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Boussiotis, VA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Rm Mayer 547, Boston, MA 02115 USA. EM vassiliki_boussiotis@dfci.harvard.edu FU NCI NIH HHS [CA105216]; NHLBI NIH HHS [HL63452, HL56067]; NIAID NIH HHS [AI 43552, AI 46548, AI34495] NR 30 TC 101 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 NOV 1 PY 2005 VL 106 IS 9 BP 3068 EP 3073 DI 10.1182/blood-2005-04-1531 PG 6 WC Hematology SC Hematology GA 979BP UT WOS:000232917400031 PM 16020508 ER PT J AU Zola, H Swart, B Nicholson, I Aasted, B Bensussan, A Boumsell, L Buckley, C Clark, G Drbal, K Engel, P Hart, D Horejsi, V Isacke, C Macardle, P Malavasi, F Mason, D Olive, D Saalmueller, A Schlossman, SF Schwartz-Albiez, R Simmons, P Tedder, TF Uguccioni, M Warren, H AF Zola, H Swart, B Nicholson, I Aasted, B Bensussan, A Boumsell, L Buckley, C Clark, G Drbal, K Engel, P Hart, D Horejsi, V Isacke, C Macardle, P Malavasi, F Mason, D Olive, D Saalmueller, A Schlossman, SF Schwartz-Albiez, R Simmons, P Tedder, TF Uguccioni, M Warren, H TI CD molecules 2005: human cell differentiation molecules SO BLOOD LA English DT Article ID ANTIGENS AB The immune system works through leukocytes interacting with each other, with other cells, with tissue matrices, with infectious agents, and with other antigens. These interactions are mediated by cell-surface glycoproteins and glycolipids. Antibodies against these leukocyte molecules have provided powerful tools for analysis of their structure, function, and distribution. Antibodies have been used widely in hematology, immunology, and pathology, and in research, diagnosis, and therapy. The associated CD nomenclature is commonly used when referring to leukocyte surface molecules and antibodies against them. It provides an essential classification for diagnostic and therapeutic purposes. The most recent (8th) Workshop and Conference on Human Leukocyte Differentiation Antigens (HLDA), held in Adelaide, Australia, in December 2004, allocated 95 new CD designations and made radical changes to its aims and future operational strategy in order to maintain its relevance to modern human biology and clinical practice. C1 Child Hlth Res Inst, Adelaide, SA 5006, Australia. Royal Vet & Agr Univ, Dept Vet Patobiol, Immunol Lab, Stigbojlen, Denmark. INSERM 448, Fac Med Creteil, Creteil, France. Univ Birmingham, Ctr Immune Regulat, MRC, Dept Rheumatol,Div Immun & Infect, Edgbaston, England. Mater Hosp, Mater Med Res Inst, Brisbane, Qld, Australia. Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic. Univ Barcelona, Dept Immunol, Cellular Biol & Pathol Med Sch, E-08007 Barcelona, Spain. Inst Canc Res, Chester Beatty Labs, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England. Flinders Med Ctr, Dept Immunol, Bedford Pk, SA, Australia. Univ Turin, Sch Med, Immunogenet Lab, Turin, Italy. John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, Oxford OX3 9DU, England. Univ Mediterranee, Lab Immunol Tumeurs, Ctr Lutte Contre Canc, Marseille, France. Fac Med Marseille, F-13385 Marseille, France. Vet Med Univ Wien, Klin Dept Diagnost Verfahren, Klin Immunol, Vienna, Austria. Dana Farber Canc Inst, Boston, MA 02115 USA. German Canc Res Ctr, Tumor Immunol Lab, D-6900 Heidelberg, Germany. Peter MacCallum Canc Inst, Stem Cell Res Labs, Melbourne, Vic, Australia. Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. Inst Res Biomed, Bellinzona, Switzerland. Australian Natl Univ, John Curtin Sch Med Res, Div Immunol & Genet, Canberra, ACT 2601, Australia. RP Zola, H (reprint author), Child Hlth Res Inst, 72 King William Rd, Adelaide, SA 5006, Australia. EM heddy.zola@adelaide.edu.au RI Horejsi, Vaclav/G-3113-2014; Drbal, Karel/G-9329-2011; Bensussan, Armand/E-5434-2017; OI Drbal, Karel/0000-0003-4450-4625; Uguccioni, Mariagrazia/0000-0002-9570-7011; Macardle, Cindy/0000-0001-9880-4258; MALAVASI, Fabio/0000-0002-1844-174X; Saalmuller, Armin/0000-0002-7703-3252 NR 8 TC 53 Z9 60 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3123 EP 3126 DI 10.1182/blood-2005-03-1338 PG 4 WC Hematology SC Hematology GA 979BP UT WOS:000232917400038 PM 16020511 ER PT J AU Stover, EH Chen, J Lee, BH Cools, J McDowell, E Adelsperger, J Cullen, D Coburn, A Moore, SA Okabe, R Fabbro, D Manley, PW Griffin, JD Gilliland, DG AF Stover, EH Chen, J Lee, BH Cools, J McDowell, E Adelsperger, J Cullen, D Coburn, A Moore, SA Okabe, R Fabbro, D Manley, PW Griffin, JD Gilliland, DG TI The small molecule tyrosine kinase inhibitor AMN107 inhibits TEL-PDGFR beta and FIP1L1-PDGFR alpha in vitro and in vivo SO BLOOD LA English DT Article ID IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC EOSINOPHILIC LEUKEMIA; IMATINIB MESYLATE; BCR-ABL; MYELOPROLIFERATIVE DISEASE; CHROMOSOMAL TRANSLOCATION AB AMN107 is a small molecule tyrosine kinase inhibitor developed, in the first instance, as a potent inhibitor of breakpoint cluster region-abelson (BCR-ABL). We tested its effectiveness against fusion tyrosine kinases TEL-platelet-derived growth factor receptor beta (TEL-PDGFR beta) and FlP1-like-1 (FIP1L1)-PDGFR alpha, which cause chronic myelomonocytic leukemia and hypereosinophilic syndrome, respectively. In vitro, AMN107 inhibited proliferation of Ba/F3 cells transformed by both TEL-PDGFR beta and FIP1L1-PDGFR alpha with IC50 (inhibitory concentration 50%) values less than 25 nM and inhibited phosphorylation of the fusion kinases and their downstream signaling targets. The imatinib mesylate-resistant mutant TELPDGF beta T681l was sensitive to AMN107, whereas the analogous mutation in FIP1L1-PDGFR alpha, T6741, was resistant. In an in vivo bone marrow transplantation assay, AMN107 effectively treated myeloproliferative disease induced by TELPDGFR beta and FIP1L1-PDGFR alpha, significantly increasing survival and disease latency and reducing disease severity as assessed by histopathology and flow cytometry. In summary, AMN107 can inhibit myeloid proliferation driven by TEL-PDGFR beta and FIP1L1-PDGFR alpha and may be a useful drug for treatment of patients with myeloproliferative disease who harbor these kinase fusions. C1 Brigham & Womens Hosp, Div Hematol, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Leuven VIB, Dept Human Genet, Louvain, Belgium. Novartis Inst Biomed Res, Basel, Switzerland. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Div Hematol, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu OI Cools, Jan/0000-0001-6626-5843 FU NCI NIH HHS [CA66996]; NIDDK NIH HHS [DK50654]; NIGMS NIH HHS [T32 GM007753, T32GM07753] NR 40 TC 86 Z9 91 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3206 EP 3213 DI 10.1182/blood-2005-05-1932 PG 8 WC Hematology SC Hematology GA 979BP UT WOS:000232917400049 PM 16030188 ER PT J AU Martinussen, M Fischl, B Larsson, HB Skranes, J Kulseng, S Vangberg, TR Vik, T Brubakk, AM Haraldseth, O Dale, AM AF Martinussen, M Fischl, B Larsson, HB Skranes, J Kulseng, S Vangberg, TR Vik, T Brubakk, AM Haraldseth, O Dale, AM TI Cerebral cortex thickness in 15-year-old adolescents with low birth weight measured by an automated MRI-based method SO BRAIN LA English DT Article DE cerebral cortex; very low birth weight; small for gestational age; MRI; IQ ID FOR-GESTATIONAL-AGE; SURFACE-BASED ANALYSIS; CATCH-UP GROWTH; BRAIN-DEVELOPMENT; CORTICAL SURFACE; PRETERM INFANTS; COORDINATE SYSTEM; PREMATURE-INFANT; MOTOR FUNCTION; FETAL SHEEP AB Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight <= 1500 g), 49 term small for gestational age births (SGA, birth weight < 10th percentile at term) and 58 control adolescents. A novel method of cortical surface models yielded measurements of cortical thickness and area for each subject's entire brain and computed cross-subject statistics based on cortical anatomy. The cortical surface models demonstrated regional thinning of the parietal, temporal and occipital lobes in the VLBW group, whereas regional thickening was demonstrated in the frontal and occipital lobes. The areas of change were greatest in those with the shortest gestational age at birth and lowest birth weight. Cortical surface area and cortical volume were lower in the VLBW than in the Control group. Within the VLBW group, there was an association between surface area and estimation of the intelligence quotient IQ (IQ(est)) and between cortical volume and IQ(est). Furthermore, cortical grey matter as a proportion of brain volume was significantly lower in the VLBW, but not in the SGA group compared with Controls. This observed reorganization of the developing brain offers a unique opportunity to investigate any relationship between changes in cortical anatomy and cognitive and social impairments, and the increase in psychiatric disorders that have been found in VLBW children and adolescents. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Boston, MA USA. MIT, Artificial Intelligence Lab, Boston, MA USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Norwegian Univ Sci & Technol, Fac Med, Dept Circulat & Med Imaging, N-7034 Trondheim, Norway. Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth & Gen Practice, N-7034 Trondheim, Norway. Norwegian Univ Sci & Technol, Fac Med, Dept Lab Med Childrens & Womens Hlth, N-7034 Trondheim, Norway. St Olavs Hosp, Dept Med Imaging, Trondheim, Norway. Glostrup Univ Hosp, Funct & Diagnost MR Unit, Glostrup, Denmark. RP Martinussen, M (reprint author), Norwegian Univ Sci & Technol, St Olavs Hosp, Fac Med, Dept Lab Med Childrens & Womens Hlth, N-7006 Trondheim, Norway. EM marit.martinussen@ntnu.no RI Vangberg, Torgil/B-8075-2008; Dale, Anders/A-5180-2010 OI Vangberg, Torgil/0000-0003-4808-5464; FU NCRR NIH HHS [P41-RR14075, R01-RR13609, R01-RR16594]; NICHD NIH HHS [1-HD-1-3127, 1-HD-4-2803]; NINDS NIH HHS [R01-NS39581] NR 43 TC 103 Z9 107 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2005 VL 128 BP 2588 EP 2596 DI 10.1093/brain/awh610 PN 11 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 980UV UT WOS:000233044600011 PM 16123146 ER PT J AU Tefferi, A Lasho, TL Schwager, SM Steensma, DP Mesa, RA Li, CY Wadleigh, M Gilliland, DG AF Tefferi, A Lasho, TL Schwager, SM Steensma, DP Mesa, RA Li, CY Wadleigh, M Gilliland, DG TI The JAK2(V617F) tyrosine kinase mutation in myelofibrosis with myeloid metaplasia: lineage specificity and clinical correlates SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelofibrosis; JAK2; mutation; prognosis; clonality; polycythaemia vera ID CHRONIC MYELOPROLIFERATIVE DISORDERS; POLYCYTHEMIA-VERA; BONE-MARROW; ESSENTIAL THROMBOCYTHEMIA; IDIOPATHIC MYELOFIBROSIS; PROGNOSTIC-FACTORS; JAK2 MUTATION; BCL-X; IDENTIFICATION; ERYTHROPOIETIN AB An association between an activating JAK2 mutation (JAK2(V617F)) and BCR/ABL-negative myeloproliferative disorders was recently reported in multiple simultaneous publications. In the current study, mutation analysis for JAK2(V617F) was performed in peripheral blood mononuclear cells (PBMC) from 157 patients with myelofibrosis with myeloid metaplasia (MMM) including 117 with agnogenic (AMM), 22 with postpolycythaemic (PPMM), and 18 with post-thrombocythaemic (PTMM) myeloid metaplasia. The detection rate for JAK2(V617F) was significantly higher in PPMM (91%; homozygous in 18%) compared with either AMM (45.3%; homozygous in 2.6%) or PTMM (38.9%; homozygous in 11.1%). Concomitant analysis in granulocytes (n = 57) and CD34(+) cells (n = 25) disclosed a higher incidence of homozygous JAK2(V617F) mutation but the overall mutation rate was similar to that obtained from PBMC. JAK2(V617F) was not detected in DNA derived from T cells (n = 19). In AMM, the presence of JAK2(V617F) was associated with an older age at diagnosis and a history of thrombosis or pruritus. Multivariate analysis identified only age and the Dupriez prognostic score as independent prognostic factors; JAK2(V617F) had no prognostic significance. In conclusion, JAK2(V617F) is a myeloid lineage-specific event, its incidence in MMM is significantly higher with an antecedent history of polycythaemia vera (PV), and its presence in AMM does not affect prognosis but is associated with PV-characteristic clinical features. C1 Mayo Clin, Rochester, MN 55905 USA. Mayo Clin Coll Med, Rochester, MN 55905 USA. Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA. RP Tefferi, A (reprint author), Mayo Clin, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu OI Steensma, David/0000-0001-5130-9284 NR 52 TC 160 Z9 172 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2005 VL 131 IS 3 BP 320 EP 328 DI 10.1111/j.1365-2141.2005.05776.x PG 9 WC Hematology SC Hematology GA 975JD UT WOS:000232657100004 PM 16225651 ER PT J AU Dominguez, FJ Jones, JL Zabicki, K Smith, BL Gadd, MA Specht, M Kopans, DB Moore, RH Michaelson, JS Hughes, KS AF Dominguez, FJ Jones, JL Zabicki, K Smith, BL Gadd, MA Specht, M Kopans, DB Moore, RH Michaelson, JS Hughes, KS TI Prevalence of hereditary breast/ovarian carcinoma risk in patients with a personal history of breast or ovarian carcinoma in a mammography population SO CANCER LA English DT Article DE BRCA1 gene; BRCA2 gene; genetic counseling; genetic screening; risk assessment; mass screening; hereditary neoplastic syndromes; breast neoplasm; ovarian neoplasm ID BRCA2 MUTATION CARRIERS; FAMILY-HISTORY; PROPHYLACTIC MASTECTOMY; RANDOMIZED-TRIALS; CANCER-RISK; WOMEN; TAMOXIFEN; EFFICACY; OOPHORECTOMY AB BACKGROUND. identifying BRCA1 and BRCA2 mutation carriers is increasingly important as new management options show promise in decreasing morbidity and mortality in these women. The authors sought to determine the prevalence of family histories suggestive of a hereditary breast carcinoma syndrome in a cohort of patients with a personal history of breast and/or ovarian carcinoma presenting for mammography. METHODS: The authors reviewed the family, histories of all women with a history of breast or ovarian carcinoma presenting for mammography over a 37-week period. Using the Myriad model, the authors evaluated the prevalence of family histories with a >= 10% risk of a BRCA1 or BRCA2 mutation. RESULTS. During the period of the current study, 14,597 women completed a family history questionnaire. Of these women, 1764 had a personal history of breast or ovarian carcinoma, 86.6% had unilateral breast carcinoma, 4.6% had bilateral breast carcinoma, 8.2% had ovarian carcinoma, and 0.5% had both breast and ovarian carcinoma. Overall, 20.6% met the criteria for a ! 10% risk of mutation according to the Myriad model. This incidence was higher among Ashkenazi women (47.3%) and among patients with a personal history of ovarian carcinoma (35.9%). CONCLUSIONS. Application of the Myriad model to women with a personal history of breast and ovarian carcinoma suggested that approximately I in 5 of these women (20.6%) will have family histories suspicious for a genetic mutation. This risk was higher for Ashkenazi women and for those with a personal history of ovarian carcinoma. This prevalence was considerably higher than the rate reported among women with no personal history of cancer, and has significant implications for their management, as well as for the capacity for risk assessment and testing. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Hughes, KS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Surg Oncol, 32 Fruit St,YAW-7-932, Boston, MA 02114 USA. EM kshughes@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 29 TC 13 Z9 14 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 NOV 1 PY 2005 VL 104 IS 9 BP 1849 EP 1853 DI 10.1002/cncr.21393 PG 5 WC Oncology SC Oncology GA 976TE UT WOS:000232755500009 PM 16136597 ER PT J AU Hillner, BE Schrag, D Sargent, DJ Fuchs, CS Goldberg, RM AF Hillner, BE Schrag, D Sargent, DJ Fuchs, CS Goldberg, RM TI Cost-effectiveness projections of oxaliplatin and infusional fluorouracil versus irinotecan and bolus fluorouracil in first-line therapy for metastatic colorectal carcinoma SO CANCER LA English DT Article DE oxaliplatin; irinotecan; colorectal neoplasm; metastatic disease; cost and cost analysis; cost-benefit analysis; decision modeling; survival analysis ID RANDOMIZED-TRIAL; ADJUVANT CHEMOTHERAPY; CANCER; LEUCOVORIN; NICE; GUIDELINES; ONCOLOGY; GUIDANCE; DECISION; HISTORY AB BACKGROUND. The results of a randomized comparison study (N9741) showed that oxaliplatin and infusional fluorouracil (FU) (FOLFOX) was superior to the previous standard of care in the United States, irinotecan and bolus FU (IFL), as first-line therapy for patients with metastatic colon carcinoma. The trade-offs between costs and survival for these two regimens have not been explored. METHODS. A post-hoc, incremental cost-effectiveness (ICE) projection using simulated cohorts of patients starting FOLFOX or IFL was tracked for major clinical events, toxicities, and survival. Recurrence and survival risks were based on clinical trial data. Resource use was projected using observed dose intensity, duration of therapy, delays in therapy, and toxicities Grade > 2 in N9741. The frequency, costs, and consequences of second-line therapy were examined. The time frame was 5 years, and the perspective was that of Medicare as a third-party payer. RESULTS. Initial treatment with FOLFOX versus IFL had an average incremental cost of $29,523, a Survival benefit of 4.4 months, and an ICE of $80,410 per life year (LY), $111,890 per quality-adjusted LY, and $89,080 per progression-free year. By using the 95% confidence interval for the time to progression observed in N9741, the ICE associated with FOLFOX ranged from $121,220 to $59,250 per LY. In the clinical trial, dose delays and skipped doses were frequent. If progression-free patients were treated without delay for the first year or lifetime, then the ICE for FOLFOX increased to $117,910 and $222,200 per LY, respectively. The ICE increased to $84,780 per LY when the model incorporated a revised IFL schedule with lower early toxicity and similar rates of treatment with second-line regimens. CONCLUSIONS. FOLFOX provided substantial benefits that incurred substantial additional costs. The ICE for FOLFOX fell into the upper range of commonly accepted oncology interventions in the context of the United States healthcare system. C1 Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Res Grp, New York, NY 10021 USA. Mayo Clin, Div Biostat, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ N Carolina, Div Hematol & Oncol, Chapel Hill, NC USA. RP Hillner, BE (reprint author), Virginia Commonwealth Univ, Dept Internal Med, 1101 E Marshall St,Room 7013, Richmond, VA 23298 USA. EM hillner@mail2.vcu.edu RI Hillner, Bruce/A-6852-2009; Goldberg , Richard/M-1311-2013; OI Sargent, Daniel/0000-0002-2684-4741 NR 45 TC 23 Z9 23 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 NOV 1 PY 2005 VL 104 IS 9 BP 1871 EP 1884 DI 10.1002/cncr.21411 PG 14 WC Oncology SC Oncology GA 976TE UT WOS:000232755500012 PM 16177989 ER PT J AU Chang, SM Barker, FG AF Chang, SM Barker, FG TI Marital status, treatment, and survival in patients with glioblastoma multiforme - A population-based study SO CANCER LA English DT Article DE glioblastoma multiforme; marital status; radiation therapy; survival ID QUALITY-OF-LIFE; THERAPY ONCOLOGY GROUP-83-02; STAGE BREAST-CANCER; HIGH-GRADE GLIOMA; RESULTS SEER DATA; RADIATION-THERAPY; MALIGNANT GLIOMA; CLINICAL-TRIALS; UNITED-STATES; BRAIN-TUMORS AB BACKGROUND. Social factors influence cancer treatment choices, potentially affecting patient survival. In the current study, the authors studied the interrelations between marital status, treatment received, and survival in patients with glioblastoma multiforme (GM), using population-based data. METHODS. The data source was the Surveillance, Epidemiology, and End Results (SEER) Public Use Database, 1988-2001, 2004 release, all registries. Multivariate logistic, ordinal, and Cox regression analyses adjusted for demographic and clinical variables were used. RESULTS. Of 10,987 patients with GM, 67% were married, 31% were unmarried, and 2% were of unknown marital status. Tumors were slightly larger at the time of diagnosis in unmarried patients (49% of unmarried patients had tumors larger than 45 mm vs. 45% of married patients; P = 0.004, multivariate analysis). Unmarried patients were less likely to undergo surgical resection (vs. biopsy; 75% of unmarried patients vs. 78% of married patients) and were less likely to receive postoperative radiation therapy (RT) (70% of unmarried patients vs. 79% of married patients). Oil multivariate analysis, the odds ratio (OR) for resection (vs. biopsy) in unmarried patients was 0.88 (95% confidence interval [95% CI], 0.790.98; P = 0.02), and the OR for RT in unmarried patients was 0.69 (95% Cl, 0.62-0.77; P < 0.001). Unmarried patients more often refused both surgical resection and RT. Unmarried patients who underwent surgical resection and RT were found to have a shorter survival than similarly treated married patients (hazard ratio for unmarried patients, 1.10; P = 0.003). CONCLUSIONS. Unmarried patients with GM presented with larger tumors, were less likely to undergo both surgical resection and postoperative RT, and had a shorter survival after diagnosis when compared wJith married patients, even after adjustment for treatment and other prognostic factors. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dept Surg, Div Neurosurg, Boston, MA 02115 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 60 TC 48 Z9 48 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2005 VL 104 IS 9 BP 1975 EP 1984 DI 10.1002/cncr.21399 PG 10 WC Oncology SC Oncology GA 976TE UT WOS:000232755500025 PM 16130137 ER PT J AU Hurria, A Gupta, S Zauderer, M Zuckerman, EL Cohen, HJ Muss, H Rodin, M Panageas, KS Holland, JC Saltz, L Kris, MG Noy, A Gomez, J Jakubowski, A Hudis, C Kornblith, AB AF Hurria, A Gupta, S Zauderer, M Zuckerman, EL Cohen, HJ Muss, H Rodin, M Panageas, KS Holland, JC Saltz, L Kris, MG Noy, A Gomez, J Jakubowski, A Hudis, C Kornblith, AB TI Developing a cancer-specific geriatric assessment - A feasibility study SO CANCER LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol DE geriatric assessment; older patient; chemotherapy ID MEMORY-CONCENTRATION TEST; FUNCTIONAL STATUS; COGNITIVE IMPAIRMENT; HOSPITAL ANXIETY; DEPRESSION; QUESTIONNAIRES; RELIABILITY; VALIDATION; MORTALITY; PATIENT AB BACKGROUND. As the U.S. population ages, there is an emerging need to characterize the "functional age" of older patients with cancer to tailor treatment decisions and stratify outcomes based on factors other than chronologic age. The goals of the current study were to develop a brief, but comprehensive, primarily self-administered cancer-specific geriatric assessment measure and to determine its feasibility as measured by 1) the percentage of patients able to complete the measure on their own, 2) the length of time to complete, and 3) patient satisfaction with the measure. METHODS. The geriatric and oncology literature was reviewed to choose validated measures of geriatric assessment across the following domains: functional status, comorbidity, cognition, psychological status, social functioning and support, and nutritional status. Criteria applied to geriatric assessment measurements included reliability, validity, brevity, and ability to self-administer. The measure was administered to patients with breast carcinoma, lung carcinoma, colorectal carcinoma, or lymphoma who were fluent in English and receiving chemotherapy at Memorial Sloan-Kettering Cancer Center (New York, NY) or the University of Chicago (Chicago, IL). RESULTS. The instrument was completed by 43 patients (mean age, 74 yrs; range, 65-87 yrs). The majority had AJCC Stage IV disease (68%). The mean time to completion of the assessment was 27 minutes (range, 8-45 mins). Most patients were able to complete the self-administered portion of the assessment without assistance (78%) and were satisfied with the questionnaire length (90%). There was no association noted between age (P = 0.56) or educational level (P = 0.99) and the ability to complete the assessment without assistance. CONCLUSIONS. In this cohort, this brief but comprehensive geriatric assessment could be completed by the majority of patients without assistance. Prospective trials of its generalizability, reliability, and validity are justified. C1 Mem Sloan Kettering Canc Ctr, Dept Med Psychiat & Behav Sci & Biostat, New York, NY 10021 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Durham Vet Affairs Med Ctr, Ctr Study Aging, Durham, NC USA. Duke Univ, Durham, NC USA. Univ Vermont, Dept Med, Burlington, VT USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hurria, A (reprint author), Mem Sloan Kettering Canc Ctr, Dept Med Psychiat & Behav Sci & Biostat, 1275 York Ave, New York, NY 10021 USA. EM hurriaa@mskcc.org OI Zauderer, Marjorie/0000-0002-6109-5790; Noy, Ariela/0000-0002-3001-4898; Kris, Mark/0000-0002-7317-5341; Saltz, Leonard/0000-0001-8353-4670 NR 30 TC 208 Z9 210 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2005 VL 104 IS 9 BP 1998 EP 2005 DI 10.1002/cncr.21422 PG 8 WC Oncology SC Oncology GA 976TE UT WOS:000232755500028 PM 16206252 ER PT J AU Zhang, H Duan, HO Kirley, SD Zukerberg, LR Wu, CL AF Zhang, H Duan, HO Kirley, SD Zukerberg, LR Wu, CL TI Aberrant splicing of Cables gene, a CDK regulator, in human cancers SO CANCER BIOLOGY & THERAPY LA English DT Article DE cables; aberrant splicing; cdk; emdometrial cancer; colon cancer ID TUMOR SUSCEPTIBILITY GENE; SQUAMOUS-CELL CARCINOMAS; HUMAN BREAST-CANCER; PRE-MESSENGER-RNA; GROWTH-HORMONE GH; MDM2 ONCOGENE; LUNG-CANCER; FHIT GENE; IN-VIVO; TSG101 AB Cables is a novel cell cycle regulatory protein that interacts with cdk2, cdk3, and cdk5. Cables inhibits cdk2 activity by enhancing cdk2 tyrosine 15 phosphorylation by Wee1, which consequently leads to inhibition of cell growth. Loss of Cables expression was found in many human cancers, especially colon and endometrial cancer. However, the role of the Cables gene in cancer development remains unclear. This study was undertaken to analyze transcripts of Cables gene in endometrial and colon cancers. The analysis of RT-PCR products of the Cables gene revealed shortened products in each sample along with the product of the expected size. Sequence analysis indicated that these shortened products represented eight intragenic deletions in Cables mRNA transcripts. Analysis of DNA from the same tumor sample failed to show genomic rearrangements corresponding to the transcripts containing deletions, suggesting that the deletions are the result of RNA splicing. Sequence analysis demonstrated that five of the deletions resulted from alternative splicing ( splicing at the exon/intron boundary consensus sites), whereas the remaining three deletions resulted from aberrant splicing ( splicing at sites not considered to be exon/intron boundary sites). All three aberrant splicing products were only detected in tumor tissues. Ectopic expression of one of the aberrant splicing products, which was detected in both endometrial and colon carcinomas, resulted in increased cell growth rate in human colon carcinoma HT-29 cells, suggesting a role as a dominant negative mutant. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Wu, CL (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM cwu2@partners.org NR 33 TC 9 Z9 9 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 EI 1555-8576 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2005 VL 4 IS 11 BP 1211 EP 1215 DI 10.4161/cbt.4.11.2085 PG 5 WC Oncology SC Oncology GA 022GS UT WOS:000236044100015 PM 16177568 ER PT J AU Flaherty, KT Fuchs, CS Colditz, GA Stampfer, MJ Speizer, FE Willett, WC Curhan, GC AF Flaherty, KT Fuchs, CS Colditz, GA Stampfer, MJ Speizer, FE Willett, WC Curhan, GC TI A prospective study of body mass index, hypertension, and smoking and the risk of renal cell carcinoma (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE hypertension; obesity; renal cell carcinoma; risk factors; smoking ID NEW-SOUTH-WALES; KIDNEY CANCER; ANTIHYPERTENSIVE MEDICATIONS; CIGARETTE-SMOKING; TOBACCO USE; POSTMENOPAUSAL WOMEN; PHYSICAL-ACTIVITY; OBESITY; DIURETICS; MEN AB Objective: We prospectively investigated the independent association of hypertension, thiazide use, body mass index, weight change, and smoking with the risk of renal cell carcinoma among men and women using biennial mailed questionnaires. Methods: The study population included 118,191 women participating in the Nurses' Health Study and 48,953 men participating in the Health Professionals Follow-up Study Results: During 24 years of follow-up for women and 12 years for men, 155 and 110 incident cases of renal cell carcinoma were confirmed, respectively. In multivariate models including age, body mass index (BMI), smoking and hypertension, higher BMI was confirmed as a risk factor for women and smoking as a risk factor for men and women. After adjusting for age, updated BMI and smoking, an updated diagnosis of hypertension was associated with renal cell carcinoma (RCC); the relatve risk (RR) was 1.9 (95% CI 1.4-2.7) for women and 1.8 (95% CI 1.2-2.7) for men. Based on limited data regarding the use of thiazide diuretics, we did not observe a risk associated with their use, independent of the diagnosis of hypertension. Conclusions: Diagnosis of hypertension, higher BMI, and increasing pack-years of smoking appear to independently increase the risk of renal cell carcinoma. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. RP Curhan, GC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM Gary.Curhan@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356, CA55075, CA87969]; NIDDK NIH HHS [DK52866] NR 49 TC 64 Z9 67 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2005 VL 16 IS 9 BP 1099 EP 1106 DI 10.1007/s10552-005-0349-8 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 968CQ UT WOS:000232139900012 PM 16184476 ER PT J AU Chauhan, D Catley, L Li, GL Podar, K Hideshima, T Velankar, M Mitsiades, C Mitsiades, N Yasui, H Letai, A Ovaa, H Berkers, C Nicholson, B Chao, TH Neuteboom, STC Richardson, P Palladino, MA Anderson, KC AF Chauhan, D Catley, L Li, GL Podar, K Hideshima, T Velankar, M Mitsiades, C Mitsiades, N Yasui, H Letai, A Ovaa, H Berkers, C Nicholson, B Chao, TH Neuteboom, STC Richardson, P Palladino, MA Anderson, KC TI A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib SO CANCER CELL LA English DT Article ID NF-KAPPA-B; THERAPEUTIC IMPLICATIONS; ENDOPLASMIC-RETICULUM; MM CELLS; IN-VIVO; ACTIVATION; PS-341; TARGET; CANCER; BAX AB Bortezomib therapy has proven successful for the treatment of relapsed and/or refractory multiple myeloma (MM); however, prolonged treatment is associated with toxicity and development of drug resistance. Here, we show that the novel proteasome inhibitor NPI-0052 induces apoptosis in MM cells resistant to conventional and Bortezomib therapies. NPI-0052 is distinct from Bortezomib in its chemical structure, effects on proteasome activities, mechanisms of action, and toxicity profile against normal cells. Moreover, NPI-0052 is orally bioactive. In animal tumor model studies, NPI-0052 is well tolerated and prolongs survival, with significantly reduced tumor recurrence. Combining NPI-0052 and Bortezomib induces synergistic anti-MM activity. Our study therefore provides the rationale for clinical protocols evaluating NPI-0052, alone and together with Bortezomib, to improve patient outcome in MM. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Nereus Pharmaceut, San Diego, CA 92121 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013; Berkers, Celia/I-3848-2016 FU NCI NIH HHS [P0-1 CA 78373, P50 CA100707, R0-1 CA50947] NR 39 TC 463 Z9 472 U1 10 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2005 VL 8 IS 5 BP 407 EP 419 DI 10.1016/j.ccr.2005.10.013 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 987FA UT WOS:000233502600008 PM 16286248 ER PT J AU Liu, M Yang, SC Sharma, S Luo, J Cui, XY Huang, M Ramirez, RD Shay, JW Minna, JD Dubinett, SM AF Liu, M Yang, SC Sharma, S Luo, J Cui, XY Huang, M Ramirez, RD Shay, JW Minna, JD Dubinett, SM TI TGF-beta 1 and EGF modulate transcriptional and posttranscriptional expression of cyclooxygenase-2 in immortalized human bronchial epithelial cells. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Lung Canc Res Program, Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA USA. RI Shay, Jerry/F-7878-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2717S EP 2718S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200152 ER PT J AU Farwell, WR Sesso, HD Gaziano, JM AF Farwell, WR Sesso, HD Gaziano, JM TI The association between lipids and prostate cancer incidence. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 VA Boston Healthcare Syst, MAVERIC, Boston, MA USA. Brigham & Womens Hosp, Dept Prefent, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2729S EP 2729S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200198 ER PT J AU Koushik, A Tranah, GJ Ma, J Stampfer, M Fuchs, CS Giovannucci, EL Hunter, DJ AF Koushik, A Tranah, GJ Ma, J Stampfer, M Fuchs, CS Giovannucci, EL Hunter, DJ TI p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2729S EP 2729S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200200 ER PT J AU Michaud, DS Batchelor, T Stampfer, M Hunter, D AF Michaud, DS Batchelor, T Stampfer, M Hunter, D TI Meat intake and adult glioma risk: Results from two prospective cohort studies. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Michaud, Dominique/I-5231-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2753S EP 2753S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200297 ER PT J AU Wei, EK Giovannucci, E Liu, JM Fuchs, CS Willett, WC Colditz, GA Ma, J AF Wei, EK Giovannucci, E Liu, JM Fuchs, CS Willett, WC Colditz, GA Ma, J TI A prospective study of birthweight, height and body mass index at age 18 and the risk of colon cancer in women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Peking Univ, Hlth Sci Ctr, Natl Ctr Maternal & Infant Hlth, Beijing, Peoples R China. Peking Univ, Hlth Sci Ctr, Inst Reprod & Child Hlth, Beijing, Peoples R China. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2758S EP 2759S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200318 ER PT J AU Liu, YLE Pu, WP Dackour, R Kang, JX Shi, YE AF Liu, YLE Pu, WP Dackour, R Kang, JX Shi, YE TI Induction of mammary differentiation by alternation of n-6/n-3 fatty acid compositional ratio: Mimicking the pregnancy effect. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2760S EP 2761S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200327 ER PT J AU D'Andrea, AD AF D'Andrea, AD TI The Fanconi Anemia/BRCA pathway in the DNA damage response. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2795S EP 2795S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200408 ER PT J AU Patenaude, AF Peterson, SK AF Patenaude, AF Peterson, SK TI Psychosocial impact and outcomes: Issues in implementation. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2806S EP 2807S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200434 ER PT J AU Dahia, PLM Hao, K Rogus, J Colin, C Pujana, MAG Ross, K Magoffin, D Aronin, N Cascon, A Hayashida, CY Li, C Toledo, SPA Stiles, CD AF Dahia, PLM Hao, K Rogus, J Colin, C Pujana, MAG Ross, K Magoffin, D Aronin, N Cascon, A Hayashida, CY Li, C Toledo, SPA Stiles, CD CA Familial Pheochromocytoma Consort TI Novel pheochromocytoma susceptibility loci identified by integrative genomics SO CANCER RESEARCH LA English DT Article ID GERM-LINE MUTATIONS; LINKAGE ANALYSIS; GENE; CANCER; ARRAY; HYPERCHOLESTEROLEMIA; HETEROZYGOSITY; PARAGANGLIOMA; DISEASE; SDHD AB Pheochromocytomas are catecholamine-secreting tumors that result from mutations of at least six different genes as components of distinct autosomal dominant disorders. However, there remain familial occurrences of pheochromocytoma without a known genetic defect. We describe here a familial pheochromocytoma syndrome consistent with digenic inheritance identified through a combination of global genomics strategies. Multipoint parametric linkage analysis revealed identical LOD scores of 2.97 for chromosome 2cen and 16p13 loci. A two-locus parametric linkage analysis produced maximum LOD score of 5.16 under a double recessive multiplicative model, suggesting that both loci are required to develop the disease. Allele-specific loss of heterozygosity (LOH) was detected only at the chromosome 2 locus in all tumors from this family, consistent with a tumor suppressor gene. Four additional pheochromocytomas with a similar genetic pattern were identified through transcription profiling and helped refine the chromosome 2 locus. High-density LOH mapping with single nucleotide polymorphism-based array identified a total of 18 of 62 pheochromocytomas with LOH within the chromosome 2 region, which further narrowed down the locus to < 2 cM. This finding provides evidence for two novel susceptibility loci for pheochromocytoma and adds a recessive digenic trait to the increasingly broad genetic heterogeneity of these tumors. Similarly, complex traits may also be involved in other familial cancer syndromes. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Div Res, Joslin Diabet Ctr,Dept Biostat, Boston, MA 02115 USA. Interleukin Genet, Waltham, MA USA. Univ Sao Paulo, Sch Med, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Sch Chem, BR-05508 Sao Paulo, Brazil. Hosp Barcelona, Catalan Inst Oncol, Translat Res Lab, Barcelona, Spain. MIT, Broad Inst, Cambridge, MA 02139 USA. Univ Massachusetts, Div Endocrinol, Mem Med Ctr, Worcester, MA 01605 USA. Natl Ctr Oncol Invest, Mol Pathol Program, Madrid, Spain. RP Dahia, PLM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr,Room 5053-R3,MC 7880, San Antonio, TX 78229 USA. EM dahia@uthscsa.edu RI Cascon, Alberto/G-3160-2014; pujana, Miguel Angel/N-3127-2014 OI Cascon, Alberto/0000-0003-2119-891X; pujana, Miguel Angel/0000-0003-3222-4044 FU NHGRI NIH HHS [R01HG02341]; NINDS NIH HHS [NS047572-01A1] NR 32 TC 64 Z9 65 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2005 VL 65 IS 21 BP 9651 EP 9658 DI 10.1158/0008-5472.CAN-05-1427 PG 8 WC Oncology SC Oncology GA 979TF UT WOS:000232967000010 PM 16266984 ER PT J AU Krop, I Parker, MT Bloushtain-Qimron, N Porter, D Gelman, R Sasaki, H Maurer, M Terry, MB Parsons, R Polyak, K AF Krop, I Parker, MT Bloushtain-Qimron, N Porter, D Gelman, R Sasaki, H Maurer, M Terry, MB Parsons, R Polyak, K TI HIN-1, an inhibitor of cell growth, invasion, and AKT activation SO CANCER RESEARCH LA English DT Article ID UTEROGLOBIN-RELATED PROTEIN-1; BREAST-CANCER; PIK3CA GENE; TRANSFORMED PHENOTYPE; SECRETORY PROTEIN; NORMAL-1 HIN-1; FREQUENT EVENT; LUNG-CANCER; EXPRESSION; IDENTIFICATION AB The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1-mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Nagoya City Univ, Sch Med, Dept Surg, Nagoya, Aichi 467, Japan. Columbia Univ, Dept Med, New York, NY 10027 USA. Columbia Univ, Dept Epidemiol, New York, NY 10027 USA. RP Polyak, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,D740C, Boston, MA 02115 USA. EM Kornelia_Polyak@dfci.harvard.edu FU NCI NIH HHS [R01 CA082783-06, 5K12CA87723-03, R01 CA082783, R01 CA974074] NR 41 TC 37 Z9 40 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2005 VL 65 IS 21 BP 9659 EP 9669 DI 10.1158/0008-5472.CAN-05-1663 PG 11 WC Oncology SC Oncology GA 979TF UT WOS:000232967000011 PM 16266985 ER PT J AU Maia, S Haining, WN Ansen, S Xia, ZN Armstrong, SA Seth, NP Ghia, P den Boer, ML Pieters, R Sallan, SE Nadler, LM Cardoso, AA AF Maia, S Haining, WN Ansen, S Xia, ZN Armstrong, SA Seth, NP Ghia, P den Boer, ML Pieters, R Sallan, SE Nadler, LM Cardoso, AA TI Gene express on profiling identifies BAX-delta as a novel tumor antigen in acute lymphoblastic leukemia SO CANCER RESEARCH LA English DT Article ID T-CELL RESPONSES; ADOPTIVE IMMUNOTHERAPY; BONE-MARROW; CANCER REGRESSION; LYMPHOCYTES; PEPTIDES; PROTEIN; CD8(+); VIRUS; EPITOPES AB The identification of new tumor-associated antigens (TAA) is critical for the development of effective immunotherapeutic strategies, particularly in diseases like B-cell acute lymphoblastic leukemia (B-ALL), where few target epitopes are known. To accelerate the identification of novel TAA in B-ALL, we used a combination of expression profiling and reverse immunology. We compared gene expression profiles of primary B-ALL cells with their normal counterparts, B-cell precursors. Genes differentially expressed by WALL cells included many previously identified as TAA in other malignancies. Within this set of overexpressed genes, we focused on those that may be functionally important to the cancer cell. The apoptosis-related molecule, BAX, was highly correlated with the ALL class distinction. Therefore, we evaluated BAX and its isoforms as potential TAA. Peptides from the isoform BAX-delta bound with high affinity to HLA-A*0201 and HLA-DR1. CD8(+) CTLs specific for BAX-delta epitopes or their heteroclitic peptides could be expanded from normal donors. BAX-delta-specific T cells lysed peptide-pulsed targets and BAX-delta-expressing leukemia cells in a MHC-restricted fashion. Moreover, primary B-ALL cells were recognized by BAX-delta-specific CTL, indicating that this antigen is naturally processed and presented by tumor cells. This study suggests that (a) BAX-delta may serve as a widely expressed TAA in B-ALL and (b) gene expression profiling can be a generalizable tool to identify immunologic targets for cancer immunotherapy. C1 Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Pediat Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Dept Canc Immunol & AIDS, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Univ Lisbon, Inst Mol Med, Unit Tumor Biol, Lisbon, Portugal. Erasmus Univ, Med Ctr, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rotterdam, Netherlands. RP Cardoso, AA (reprint author), Harvard Univ, Dept Med Oncol, Sch Med, Dana Farber Canc Inst, Room D-540B,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu RI Maia, Sara/B-2513-2013; Ghia, Paolo/K-7138-2016 OI Maia, Sara/0000-0001-8638-0566; Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [P01-CA68484]; NHLBI NIH HHS [K08HL72750] NR 51 TC 16 Z9 17 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2005 VL 65 IS 21 BP 10050 EP 10058 DI 10.1158/0008-5472.CAN-05-1574 PG 9 WC Oncology SC Oncology GA 979TF UT WOS:000232967000057 PM 16267031 ER PT J AU Kang, JX Liu, J Wang, JD He, CW Li, FP AF Kang, JX Liu, J Wang, JD He, CW Li, FP TI The extract of huanglian, a medicinal herb, induces cell growth arrest and apoptosis by upregulation of interferon-beta and TNF-alpha in human breast cancer cells SO CARCINOGENESIS LA English DT Article ID GENE-EXPRESSION PATTERNS; COPTIDIS-RHIZOMA; BERBERINE; MICROARRAY AB Huanglian (Coptidis rhizoma), a widely used herb in traditional Chinese medicine, has been shown recently to possess anticancer activities. However, the molecular mechanism underlying the anticancer effect of the herb is poorly understood. Specifically, whether huanglian extract affects the expression of cancer-related genes has not been defined. This study used DNA microarray technology to examine the effect of the herbal extract on expression of the common genes involved in carcinogenesis in two human breast cancer cell lines, the ER-positive MCF-7 and ER-negative MDA-MB-231 cells. Treatment of the cancer cells with huanglian extract markedly inhibited their proliferation in a dose- and time-dependent manner. The growth inhibitory effect was much more profound in MCF-7 cell line than that in MDA-MB-231 cells. DNA microarray assay revealed that treatment with huanglian dramatically increased the mRNA expression of interferon-beta (IFN-beta) and tumor necrosis factor-alpha in MCF-7 cells. Quantitative analysis by real-time PCR or western blotting confirmed the upregulation of the two genes (especially IFN-beta) in MCF-7 cells, but not in MDA-MB-231 cells. Addition of neutralizing antibody against IFN-beta to culture medium markedly inhibited the huanglian-induced antiproliferative effect, confirming the involvement of IFN-beta in the huanglian's effect and also suggesting an autocrine pathway for the action of IFN-beta in this setting. Given that IFN-beta is among the most important anticancer cytokines, the upregulation of this gene by huanglian is, at least in part, responsible for its antiproliferative effect. The results of this study implicate huanglian as a promising herb for chemoprevention and chemotherapy of certain cancers. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Room 4433,149 13th St, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu NR 21 TC 57 Z9 61 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2005 VL 26 IS 11 BP 1934 EP 1939 DI 10.1093/carcin/bgi154 PG 6 WC Oncology SC Oncology GA 976PV UT WOS:000232746500012 PM 15958519 ER PT J AU Johnson, J Skaznik-Wikiel, M Lee, HJ Niikura, Y Tilly, JC Tilly, JL AF Johnson, J Skaznik-Wikiel, M Lee, HJ Niikura, Y Tilly, JC Tilly, JL TI Setting the record straight on data supporting postnatal oogenesis in female mammals SO CELL CYCLE LA English DT Article DE germline stem cell; oogenesis; oocyte; ovary; bone marrow; peripheral blood; chemotherapy; ovarian failure; infertility; menopause ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; TOTAL-BODY IRRADIATION; FANCONI-ANEMIA; SUCCESSFUL PREGNANCIES; REDUCED FERTILITY; PERIPHERAL-BLOOD; RHESUS-MONKEY; GERM-CELLS; OVARY AB Of all the 'certainties' in mammalian female reproductive biology, the concept that a non-renewing oocyte reserve is set forth in the ovaries at birth may be the most long-standing and widely held. However, when data from our studies of oocyte apoptosis unintentionally began to contradict this theory in the latter part of 2002, we embarked on an investigation, unbiased by any pre-conceived dogmas, to determine if oocyte production persists in adult female mice. In 2004, we presented our first experimental findings in the journal Nature, which indicated that oogenesis indeed continues in adulthood. Amidst widespread skepticism, we moved forward with our studies and this year published our follow-up experiments in the journal Cell. Results from this latter body of work not only reinforced our earlier conclusions but also identified bone marrow as a surprising source of oocyte-producing germ cells in adults. Although this study has also been met with skepticism, doubts raised in commentaries on our work are largely based on inaccurate or incomplete assessments of our experimental models and results. Here we have attempted to clarify published misperceptions and misinterpretations of our data, and offer additional insights that challenge the idea of fixed endowment of oocytes at birth. C1 Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol,Sch Med, Boston, MA 02114 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Vincent Obstet & Gynecol Serv, Vincent Ctr Reprod Biol,Sch Med, VBK113-GYN,55 Fruit St, Boston, MA 02114 USA. EM jtilly@partners.org NR 57 TC 32 Z9 32 U1 0 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2005 VL 4 IS 11 BP 1471 EP 1477 PG 7 WC Cell Biology SC Cell Biology GA 990OB UT WOS:000233752000004 PM 16222117 ER PT J AU Zago, L Fenske, MJ Aminoff, E Bar, M AF Zago, L Fenske, MJ Aminoff, E Bar, M TI The rise and fall of priming: How visual exposure shapes cortical representations of objects SO CEREBRAL CORTEX LA English DT Article DE behavioral facilitation; fMRI repetition-related response reduction; object representation; occipito-temporal cortex; priming; prior exposure duration; response sharpening and selectivity; visual experience; visual object recognition ID EVENT-RELATED FMRI; INFERIOR PREFRONTAL CORTEX; IMPLICIT MEMORY; TEMPORAL CORTEX; FUNCTIONAL MRI; PERCEPTUAL MEMORY; NEURAL MECHANISMS; EXPLICIT MEMORY; FUSIFORM CORTEX; REPETITION AB How does the amount of time for which we see an object influence the nature and content of its cortical representation? To address this question, we varied the duration of initial exposure to visual objects and then measured functional magnetic resonance imaging (fMRI) signal and behavioral performance during a subsequent repeated presentation of these objects. We report a novel 'rise-and-fall' pattern relating exposure duration and the corresponding magnitude of fMRI cortical signal. Compared with novel objects, repeated objects elicited maximal cortical response reduction when initially presented for 250 ms. Counter-intuitively, initially seeing an object for a longer duration significantly reduced the magnitude of this effect. This 'rise-and-fall' pattern was also evident for the corresponding behavioral priming. To account for these findings, we propose that the earlier interval of an exposure to a visual stimulus results in a fine-tuning of the cortical response, while additional exposure promotes selection of a subset of key features for continued representation. These two independent mechanisms complement each other in shaping object representations with experience. C1 Harvard Univ, Sch Med, Imaging Ctr, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Bar, M (reprint author), Harvard Univ, Sch Med, Imaging Ctr, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM bar@nmr.mgh.harvard.edu RI Zago, Laure/B-7124-2008; GINSPAN, All/B-8714-2008; OI Aminoff, Elissa/0000-0002-6455-8930; Fenske, Mark/0000-0003-4338-7754; Zago, Laure/0000-0001-8235-2154 FU NINDS NIH HHS [R01 NS044319, R01 NS44319] NR 70 TC 51 Z9 55 U1 1 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 EI 1460-2199 J9 CEREB CORTEX JI Cereb. Cortex PD NOV PY 2005 VL 15 IS 11 BP 1655 EP 1665 DI 10.1093/cercor/bhi060 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 974MK UT WOS:000232595700001 PM 15716471 ER PT J AU Lai, PC Singer, MS Crasto, CJ AF Lai, PC Singer, MS Crasto, CJ TI Structural activation pathways from dynamic olfactory receptor-odorant interactions SO CHEMICAL SENSES LA English DT Article DE ligand binding; molecular dynamics; olfactory receptors ID PROTEIN-COUPLED RECEPTORS; FUNCTIONAL EXPRESSION; BOVINE RHODOPSIN; MOLECULAR-BASIS; BINDING-SITE; HUMAN GENOME; GENE FAMILY; MOUSE; IDENTIFICATION; RECOGNITION AB We have simulated an odor ligand's dynamic behavior in the binding region of an olfactory receptor (OR). Our short timescale computational studies (up to 200 ps) have helped identify unprecedented postdocking ligand behavior of ligands. From in vacuo molecular dynamics simulations of interactions between models of rat OR I7 and 10 aldehyde ligands, we have identified a dissociative pathway along which the ligand exits and enters the OR-binding pocket-a transit event. The ligand's transit through the receptor's binding region may mark the beginning of a signal transduction cascade leading to odor recognition. We have graphically traced the rotameric changes in key OR amino acid side chains during the transit. Our results have helped substantiate or refute previously held notions of amino acid contribution to ligand stability in the binding pocket. Our observations of ligand activity when compared to those of experimental (electroolfactogram response) OR-activation studies provide a view to predicting the stability of ligands in the binding pocket as a precursor to OR activation by the ligand. C1 Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. Yale Univ, Sch Med, Yale Ctr Med Informat, New Haven, CT USA. RP Crasto, CJ (reprint author), Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. EM chiquito.crasto@yale.edu FU NIDCD NIH HHS [2 P01 DC 004732-05] NR 48 TC 33 Z9 35 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0379-864X J9 CHEM SENSES JI Chem. Senses PD NOV PY 2005 VL 30 IS 9 BP 781 EP 792 DI 10.1093/chemse/bji070 PG 12 WC Behavioral Sciences; Food Science & Technology; Neurosciences; Physiology SC Behavioral Sciences; Food Science & Technology; Neurosciences & Neurology; Physiology GA 985YR UT WOS:000233415400007 PM 16243965 ER PT J AU Myers, JN O'Neil, KM Walsh, TE Hoffmeister, KJ Venzon, DJ Johnson, BE AF Myers, JN O'Neil, KM Walsh, TE Hoffmeister, KJ Venzon, DJ Johnson, BE TI The pulmonary status of patients with limited-stage small cell lung cancer 15 years after treatment with chemotherapy and chest irradiation SO CHEST LA English DT Article DE lung cancer; oncology; pulmonary function test; radiology; toxicity ID LONG-TERM CHANGES; RADIATION-THERAPY; THORACIC RADIOTHERAPY; HODGKINS-DISEASE; FUNCTION TESTS; FOLLOW-UP; TOXICITY; SURVIVAL; INJURY; PNEUMONITIS AB Study objectives: To describe pulmonary symptoms, signs, pulmonary function, and lung imaging studies in patients with limited-stage small cell lung cancer (SCLC) 2 to 15 years after receiving treatment with chemotherapy and chest radiotherapy. Design: Retrospective review of clinical records and radiographic studies of patients treated in three different prospective combined-modality studies. Setting: Federal hospital. Patients: One hundred fifty-six patients with SCLC who were enrolled between 1974 and 1994. Interventions: Patients with limited-stage SCLC treated on prospective therapeutic studies of combined chemotherapy and radiation therapy were identified. Pulmonary symptoms, physical findings, pulmonary function tests, arterial blood gas measurements, and chest imaging studies were assessed at baseline, and at I to 2 years, at 3 to 5 years, and at > 5 years following the initiation of treatment. Measurements and results: Initial symptoms included cough in 84 (55%), dyspnea in 59 (39%), and sputum production in 26 (17%). Twenty-three patients lived beyond 5 years (15%) without evidence of recurrence. Seven of these 5-year survivors were without pulmonary symptoms. Pulmonary function test results showed no significant changes in percent predicted values for FVC, FEV1, and FEV1/FVC ratio over the time periods reviewed. The percent predicted values for the diffusing capacity of the lung for carbon monoxide decreased from 71% before the start of treatment to 56% (p < 0.032) at I to 2 years. Values improved in most patients beyond 5),Cars after starting treatment. Radiologist interpretations of chest imaging studies were available for 17 of 23 patients surviving > 5),cars. Most patients had minimal to no changes in imaging study findings beyond 5 years. Conclusions: Long-term survivors with limited-stage SCLC who were treated with combined chemotherapy and chest radiotherapy have minimal changes in pulmonary symptoms or function from 5 to 15 years after the start of treatment. A concern for late toxicity from combined-modality therapy should not dissuade clinicians from offering therapy with potentially curative result with minimal to no pulmonary dysfunction. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Natl Naval Med Res Inst, Div Pulm Crit Care, Div Hematol Oncol, Bethesda, MD USA. Montgomery Cty Dept Hlth, Bethesda, MD USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. USN, Med Branch, Bethesda, MD 20084 USA. Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Myers, JN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM JMyers@usuhs.mil RI Venzon, David/B-3078-2008 NR 28 TC 5 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2005 VL 128 IS 5 BP 3261 EP 3268 DI 10.1378/chest.128.5.3261 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 987HG UT WOS:000233508400026 PM 16304271 ER PT J AU Miyoshi, E Fujino, Y Uchiyama, A Mashimo, T Nishimura, A AF Miyoshi, E Fujino, Y Uchiyama, A Mashimo, T Nishimura, A TI Effects of gas leak on triggering function, humidification, and inspiratory oxygen fraction during noninvasive positive airway pressure ventilation SO CHEST LA English DT Article DE gas leak; humidification; inspiratory fraction of oxygen; noninvasive positive pressure ventilation; triggering function ID ACUTE RESPIRATORY-FAILURE; PROSPECTIVE TRIAL; LUNG MODEL; PERFORMANCE; BILEVEL AB Objectives: During noninvasive positive pressure ventilation (NPPV), the gas leak that commonly occurs around the mask can render NPPV ineffective. We evaluated the effects of gas leak on inspiratory trigger function during NPPV With bilevel pressure and ICU ventilators. In addition, We evaluated the effects of gas leak on fraction of inspired oxygen (FIO2) and humidification. Methods: Air leak was created at the airway opening of a model lung by establishing several different-size holes in the circuit. During simulated spontaneous breathing, we evaluated inspiratory trigger performance of two bilevel pressure ventilators (BiPAP Vision and BiPAP S/T-D; Respironics; Murrysville, PA) and two ICU ventilators (Puritan-Bennett 7200ae and Puritan-Bennett 840; Tyco Healthcare; Mansfield, MA). Inspiratory delay time and inspiratory trigger pressure were analyzed. FIO2 at the airway opening and inside the model lung were evaluated during BiPAT S/T-D ventilation at supplemental oxygen flows of 3, 6, 9, 12 and 15 L/min. Measured oxygen concentration was compared to mathematically predicted levels. Finally, using two heated humidifiers, we evaluated the effect of gas leak on humidification. Results: The bilevel pressure ventilators triggered properly at all levels of gas leak, and inspiratory triggering was more effective than with the ICU ventilators. Delivered FIO2 with the BiPAP S/T-D ventilator was affected by gas leak and could be predicted mathematically unless the gas leak was large. With large gas leaks, although relative humidity was maintained, absolute humidity decreased. Conclusion: Gas leak affected triggering of ICU ventilators, FIO2 of the BiPAV S/T-D ventilator, and humidity With both types of humidifiers. C1 Osaka Univ Hosp, Intense Care Unit, Osaka 553, Japan. Univ Tokushima, Grad Sch, Tokushima 770, Japan. RP Miyoshi, E (reprint author), Massachusetts Gen Hosp, Resp Care Serv, 55 Fruit St,Ellison 401, Boston, MA 02114 USA. EM miyoshi@hp-icu.med.osaka-u.ac.jp NR 21 TC 36 Z9 41 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2005 VL 128 IS 5 BP 3691 EP 3698 DI 10.1378/chest.128.5.3691 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 987HG UT WOS:000233508400092 PM 16304335 ER PT J AU Leaf, A Albert, CM Josephson, M Steinhaus, D Kluger, J Kang, JX Cox, B Zhang, H Schoenfeld, D AF Leaf, A Albert, CM Josephson, M Steinhaus, D Kluger, J Kang, JX Cox, B Zhang, H Schoenfeld, D CA Fatty Acid Antiarrhythmia Trial TI Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake SO CIRCULATION LA English DT Article DE fatty acids; cardioversion; arrhythmia; death, sudden; heart arrest ID SUDDEN CARDIAC DEATH; RAT VENTRICULAR MYOCYTES; LONG-CHAIN; CONTROLLED-TRIAL; MYOCARDIAL-INFARCTION; NA+ CHANNELS; FIBRILLATION; SUPPLEMENTATION; CONSUMPTION; DOGS AB Background: The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post-myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients. Methods and Results: Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high ( 35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause ( risk reduction of 28%; P = 0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P = 0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P = 0.034). Conclusions: Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiovasc, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Hartford Hosp, Arrhythmia ICD Clin, Hartford, CT 06115 USA. Massachusetts Gen Hosp, Ctr Biostat, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, E 149 13th St, Charlestown, MA 02129 USA. EM aleaf@partners.org FU NHLBI NIH HHS [HL62154] NR 26 TC 238 Z9 255 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 1 PY 2005 VL 112 IS 18 BP 2762 EP 2768 DI 10.1161/CIRCULATIONAHA.105.549527 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 980BM UT WOS:000232988900004 PM 16267249 ER PT J AU Feltmate, CM Lee, KR Johnson, M Schorge, JO Wong, KK Hao, K Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Feltmate, CM Lee, KR Johnson, M Schorge, JO Wong, KK Hao, K Welch, WR Bell, DA Berkowitz, RS Mok, SC TI Whole-genome allelotyping identified distinct loss-of-heterozygosity patterns in mucinous ovarian and appendiceal carcinomas SO CLINICAL CANCER RESEARCH LA English DT Article ID K-RAS PROTOONCOGENE; GENETIC ALTERATIONS; TUMORS; CANCER; MUTATION; CYSTADENOCARCINOMA; ADENOCARCINOMAS; TUMORIGENESIS; BENIGN; P53 AB Purpose: Mucinous adenocarcinoma of the ovary is one of the common histologic types of ovarian cancer. Its pathogenesis is largely unknown. In addition, the differential diagnosis of metastatic mucinous Carcinomas to the ovaries, particularly those originating from the appendix, remains challenging. The purpose of this study is to identify molecular biomarkers for mucinous ovarian adenocarcinoma and compare them with those of appendiceal origin. Experimental Design: Genome-wide loss-of-heterozygosity (LOH) analysis was done on DNA isolated from 28 microdissected primary mucinous ovarian carcinomas and five appendiceal adenocarcinomas. Markers from high-loss regions were selected for further analysis on a total of 32 ovarian and 14 appendiceal cancers. Results: High levels of LOH rates (> 40%) were detected on chromosome arms 9p, 17p, and 21q in mucinous ovarian carcinoma cases. The frequency of allelic loss was similar between high-grade and low-grade mucinous ovarian carcinoma cases but was significantly higher in ovarian versus appendiceal cases. In addition, LOH rates on five chromosomal loci were statistically different between ovarian and appendiceal carcinomas. Conclusion: A high frequency of LOH can be found in mucinous ovarian adenocarcinomas independent of grade. Despite histologic similarities between mucinous ovarian carcinomas and metastatic appendiceal carcinomas, they have distinct LOH profiles, which may be used for distinguishing the two diseases. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Dana Farber Canc Inst, Gillette Ctr Womens Canc, Boston, MA 02115 USA. Univ Texas, SW Med Sch, Dept Obstet & Gynecol, Div Gynecol Oncol, Dallas, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Feltmate, CM (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol,Div Gynecol Onc, 75 Francis St, Boston, MA 02115 USA. EM cfeltmate@partners.org OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [P50CA165009]; NCRR NIH HHS [RR33CA103595] NR 36 TC 14 Z9 14 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7651 EP 7657 DI 10.1158/1078-0432.CCR-05-1008 PG 7 WC Oncology SC Oncology GA 984VC UT WOS:000233331400011 PM 16278384 ER PT J AU Dalwadi, H Krysan, K Heuze-Vourc'h, N Dohadwala, M Elashoff, D Sharma, S Cacalano, N Lichtenstein, A Dubinett, S AF Dalwadi, H Krysan, K Heuze-Vourc'h, N Dohadwala, M Elashoff, D Sharma, S Cacalano, N Lichtenstein, A Dubinett, S TI Cyclooxygenase-2-dependent activation of signal transducer and activator of transcription 3 by interleukin-6 in non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CARCINOMA CELLS; GENE-REGULATION; UP-REGULATION; CONSTITUTIVE ACTIVATION; TYROSINE KINASES; STAT3 ACTIVATION; MESSENGER-RNA; EXPRESSION; ANGIOGENESIS AB Purpose: Cyclooxygenase-2 (COX-2), phosphorylated signal transducers and activators of transcription 3 (STAT3), and interleukin-6 (IL-6) are elevated in non - small cell lung cancer (NSCLC). These molecules affect numerous cellular pathways, including angiogenesis and apoptosis resistance, and, therefore, may act in concert in NSCLC. Experimental Design: We examined IL-6 and phosphorylated STAT3 in COX-2-overexpressing [COX-2 sense-oriented (COX-2-S)] NSCLC cells and control cells. The effect of IL-6, STAT3, phosphaticlylinositol 3-kinase, and mitogen- activated protein /extracellular signal-regulated kinase kinase on vascular endothelial growth factor (VEGF) production and apoptosis resistance was assessed in COX-2-overexpresing cells. Results: We report that NSCLC cells overexpressing COX-2 (COX-2-S) have increased IL-6 and phosphorylated STAT3 expression compared with control cells. IL-6 induced expression of VEGF in NSCLC cells. Moreover, blocking IL-6, mitogen-activated protein /extracellular signal -regulated kinase kinase, or phosphaticlylinositol 3-kinase decreased VEGF production in COX-2-S cells. The addition of IL-6 to NSCLC cells resulted in increased apoptosis resistance. Furthermore, the inhibition of STAT3 or IL-6 induced apoptosis and reduced survivin expression, a member of the inhibitor of apoptosis protein family in COX-2-S cells. Conclusions: Overall, these findings suggest a novel pathway in which COX-2 activates STAT3 by inducing IL-6 expression. This pathway could contribute to tumor formation by promoting survivin-dependent apoptosis resistance and VEGF production. These findings provide a rationale for the future development of STAT3, IL-6, and/or COX-2-targeted therapies for the treatment of lung cancer. C1 Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Hematol Oncol, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiat Oncol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Dubinett, S (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Lung Canc Res Program, Dept Med, 10833 Le Conte Ave,37-131 CHS, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI HEUZE-VOURC'H, Nathalie/P-8081-2016 FU NCI NIH HHS [CA-16042, P50CA90388]; NHLBI NIH HHS [T32HL072752]; NIAID NIH HHS [AI-28697] NR 56 TC 67 Z9 75 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7674 EP 7682 DI 10.1158/1078-0432.CCR-05-1205 PG 9 WC Oncology SC Oncology GA 984VC UT WOS:000233331400014 PM 16278387 ER PT J AU Linette, GP Zhang, DS Hodi, FS Jonasch, EP Longerich, S Stowell, CP Webb, IJ Daley, H Soiffer, RJ Cheung, AM Eapen, SG Fee, SV Rubin, KM Sober, AJ Haluska, FG AF Linette, GP Zhang, DS Hodi, FS Jonasch, EP Longerich, S Stowell, CP Webb, IJ Daley, H Soiffer, RJ Cheung, AM Eapen, SG Fee, SV Rubin, KM Sober, AJ Haluska, FG TI Immunization using autologous dendritic cells pulsed with the melanoma-associated antigen gp100-derived G280-9V peptide elicits CD8(+) immunity SO CLINICAL CANCER RESEARCH LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; PHASE-I TRIAL; METASTATIC MELANOMA; INDUCTION; VACCINE; RESPONSES; CANCER; CTL; RECOGNITION; REGRESSION AB Purpose: To determine the toxicity, maximal tolerated dose, and clinical and immunologic response to autologous dendritic cells pulsed with melanoma-associated antigen gp100-derived G280-9V peptide. Patients and Methods: Twelve HLA-A*0201(+) patients with advanced melanoma were administered dendritic cells pulsed with G280-9V peptide. Cohorts of three patients were administered 5 x 10(6), 15 x 10(6), and 50 x 10(6) cells i.v. every 3 weeks for six doses according to a dose escalation scheme. Three additional patients were treated at the highest dose. No additional cytokines or therapies were coadministered. The immunogenicity of G280-9V-pulsed dendritic cells was measured by IFN-gamma ELISPOT assay, tetramer assay, and Cr-51 release assay comparing prevaccination to postvaccination blood samples. Response to treatment was assessed by Response Evaluation Criteria in Solid Tumors. Results: CD8(+) immunity to the native G280 was observed in 8 (67%) patients as measured by ELISPOT and in 12 (100%) patients as measured by tetramer assay. Of the 9 patients tested, 9 (100%) had measurable high-avidity CTL activity as defined by lysis of allogeneic melanoma lines, which coexpress HLA-A*0201 and gp100. The median follow-up of the entire cohort is 43.8 months. Two (17%) partial responses were observed and 3 (25%) patients had stable disease. The median survival of the treated population was 37.6 months. At this time, three patients are alive, including one patient who continues to respond without additional treatment. Conclusion: The high rate of immunization as measured by three independent assays and the occurrence of clinical regression support continued investigation of G280-9V peptide as a candidate epitope in melanoma vaccine formulations. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, Sch Med, Div Oncol, St Louis, MO USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, GRJ 1021,55 Fruit St, Boston, MA 02114 USA. EM Haluska.frank@mgh.harvard.edu FU NCI NIH HHS [CA80851, 1 R03 CA83972-01] NR 35 TC 25 Z9 27 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7692 EP 7699 DI 10.1158/1078-0432.CCR-05-1198 PG 8 WC Oncology SC Oncology GA 984VC UT WOS:000233331400016 PM 16278389 ER PT J AU Freedland, SJ Aronson, WJ Trock, B Cohen, P Kane, CJ Amling, CL Presti, JC Terris, MK AF Freedland, SJ Aronson, WJ Trock, B Cohen, P Kane, CJ Amling, CL Presti, JC Terris, MK CA Shared Equal Regional Canc Hosp TI Racial differences in prognostic value of adult height for biochemical progression following radical prostatectomy SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; BONE-MINERAL DENSITY; BODY-MASS INDEX; CANCER RISK; IGF-I; AFRICAN-AMERICAN; EPITHELIAL-CELLS; NATIONAL-HEALTH; UNITED-STATES AB Purpose: Adult height, as a surrogate of childhood and adolescent hormone activity and diet, has been associated with the risk for development and death from prostate cancer in predominantly White populations. However, hormonal activity and diets vary between races. We examined whether height was significantly associated with biochemical progression following radical prostatectomy and whether there was an interaction between height and race. Experimental Design: Multivariate Cox proportional hazards analysis was used to determine if height significantly predicted biochemical progression among 1,503 men (450 Black and 1,053 White) treated with radical prostatectomy between 1988 and 2003. We examined for possible interactions between height and race. Results:Taller men (> 175.3 cm) were significantly younger (P = 0.001), treated in more recent years (P = 0.02), had more clinical stageT(1) disease (P = 0.001), and were less likely to have extraprostatic extension (P = 0.02) than shorter men (<= 175.3 cm). Height was not significantly related to race, preoperative serum prostate-specific antigen concentrations, biopsy or pathologic Gleason sum, positive surgical margins, seminal vesicle invasion, or lymph node metastasis. Height was significantly associated with progression among Black men [relative risk (RR), 1.67; 95% confidence interval (95% CI), 1.00-2.79] but not among White men (RR, 1.03; 95% CI, 0.77-1.38). The interaction between race and height for predicting biochemical progression was statistically significant (P-interaction = 0-05). Conclusions: There was an interaction between height and race in that height predicted progression for Black men but not for White men. The explanation for these findings is unclear, although lower insulin-like growth factor-binding protein-3 concentrations among Black men may be involved. C1 Johns Hopkins Sch Med, Dept Urol, Baltimore, MD 21287 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Urol, Sch Med, San Francisco, CA 94143 USA. San Diego Naval Hosp, Dept Urol, San Diego, CA USA. Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA. Vet Adm Med Ctr, Dept Surg, Augusta, GA 30904 USA. Med Coll Georgia, Urol Sect, Augusta, GA 30912 USA. RP Freedland, SJ (reprint author), Johns Hopkins Sch Med, Dept Urol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM sfreedl1@jhmi.edu OI Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA92131-01A1, R01CA100938]; NIA NIH HHS [R01AG20954]; NICHD NIH HHS [R01HD047013] NR 51 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7735 EP 7742 DI 10.1158/1078-0432.CCR-04-0785 PG 8 WC Oncology SC Oncology GA 984VC UT WOS:000233331400021 PM 16278394 ER PT J AU Cunningham, C Appleman, LJ Kirvan-Visovatti, M Ryan, DP Regan, E Vukelja, S Bonate, PL Ruvuna, F Fram, RJ Jekunen, A Weitman, S Hammond, LA Eder, JP AF Cunningham, C Appleman, LJ Kirvan-Visovatti, M Ryan, DP Regan, E Vukelja, S Bonate, PL Ruvuna, F Fram, RJ Jekunen, A Weitman, S Hammond, LA Eder, JP TI Phase I and pharmacokinetic study of the dolastatin-15 analogue tasidotin (ILX651) administered intravenously on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID MICROTUBULE DYNAMICS; ANTINEOPLASTIC AGENTS; CANCER; TUBULIN; CEMADOTIN; INFUSION; LU103793; DRUGS; INHIBITION; MODULATION AB Purpose: To determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetics of tasidotin (ILX651), a dolastatin-15 analogue, when administered on days 1, 3, and 5 every 3 weeks in patients with advanced solid tumors. Patients and Methods: Thirty-two patients were treated with 92 courses of tasidotin through seven dose levels determined by a modified Fibonacci scheme ranging from 3.9 to 45.7 mg/m(2). Pharmacokinetic samples were collected during the first course. Results: Neutropenia was the principal DLT at the 45.7 mg/m(2)/d dose level. In addition, one patient also experienced grade 3 neutropenia complicated with grade 3 esophageal candidiasis and grade 3 dehydration. Only 1 of 11 patients treated at the MTD, 34.4 mg/m(2), experienced dose-limiting neutropenia. Other common, drug-related toxicities included mild to moderate fatigue, anemia, nausea, anorexia, emesis, alopecia, and diarrhea. The best observed antitumor response consisted of stable disease and was noted in 10 patients (31%); the median duration on study for those patients with stable disease was 99.5 days compared with 37.5 days for those patients with progressive disease. Tasidotin plasma concentrations declined biphasically with an effective half-life of <= 55 minutes, and similar to 11% was excreted unchanged in the urine. Conclusion: The recommended dose for phase II studies and the MTD when tasidotin is administered on days 1, 3, and 5 every 3 weeks is 34.4 mg/m(2). The favorable toxicity profile of tasidotin compared with other antitubulin agents, including other dolastatin analogues, and its novel mechanism of action support further disease-directed evaluation of this agent. C1 Tyler Canc Ctr, Tyler, TX USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Bonate, PL (reprint author), Genzyme Corp, 4545 Horizon Hill Blvd, San Antonio, TX 78229 USA. EM peter.bonate@genzyme.com OI Appleman, Leonard/0000-0003-4951-7388 NR 38 TC 32 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7825 EP 7833 DI 10.1158/1078-0432.CCR-05-0058 PG 9 WC Oncology SC Oncology GA 984VC UT WOS:000233331400032 PM 16278405 ER PT J AU Lassman, AB Rossi, MR Razier, JR Abrey, LE Lieberman, FS Grefe, CN Lamborn, K Pao, W Shih, AH Kuhn, JG Wilson, R Nowak, NJ Cowell, JK DeAngelis, LM Wen, P Gilbert, MR Chang, S Yung, WA Prados, M Holland, EC AF Lassman, AB Rossi, MR Razier, JR Abrey, LE Lieberman, FS Grefe, CN Lamborn, K Pao, W Shih, AH Kuhn, JG Wilson, R Nowak, NJ Cowell, JK DeAngelis, LM Wen, P Gilbert, MR Chang, S Yung, WA Prados, M Holland, EC TI Molecular study of malignant gliomas treated with epidermal growth factor receptor inhibitors: Tissue analysis from North American Brain Tumor Consortium Trials 01-03 and 00-01 SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL LUNG-CANCER; HUMAN GLIOBLASTOMA; TYROSINE KINASE; EGFR MUTATIONS; PHASE-II; GEFITINIB; THERAPY; GENE; IDENTIFICATION; AMPLIFICATION AB Purpose: We investigated the molecular effect of the epidermal growth factor receptor (EGFR) inhibitors erlotinib and gefitinib in vivo on all available tumors from patients treated on North American Brain Tumor Consortium trials 01-03 and 00-01 for recurrent or progressive malignant glioma. Experimental Design: EGFR expression and signaling during treatment with erlotinib or gefitinib were analyzed by Western blot and compared with pre-erlotinib/gefitinib-exposed tissue or unexposed controls. Tumors were also analyzed for EGFR mutations and for other genomic abnormalities by array-based comparative genomic hybridization. Clinical data were used to associate molecular features with tumor sensitivity to erlotinib or gefitinib. Results: Erlotinib and gefitinib did not markedly affect EGFR activity in vivo. No lung signature mutations of EGFR exons 18 to 21 were observed. There was no clear association between erlotinib/gefitinib sensitivity and deletion or amplification events on array-based comparative genomic hybridization analysis, although novel genomic changes were identified. Conclusions: As erlotinib and gefitinib were generally ineffective at markedly inhibiting EGFR phosphorylation in these tumors, other assays may be needed to detect molecular effects. Additionally, the mechanism of erlotinib/gefitinib sensitivity likely differs between brain and lung tumors. Finally, novel genomic changes, including deletions of chromosomes 6, 21, and 22, represent new targets for further research. C1 Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Canc Biol & Genet, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Northwestern Univ, Dept Neurol, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Pittsburgh, Med Ctr Canc Pavill, Pittsburgh, PA USA. Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Washington Univ, Sch Med, Gen Sequencing Ctr, St Louis, MO USA. Dana Farber Canc Inst, Dept Neurol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. RP Lassman, AB (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM lassmana@mskcc.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Cowell, John/0000-0002-2079-5950 FU NCI NIH HHS [5-U01CA62399-09, CA62412, CA62422, CA62426, R01 CA099489, R01 CA100688, R21 CA104504, T32 CA009512, U01 CA894314-1, U01CA62407] NR 39 TC 161 Z9 167 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7841 EP 7850 DI 10.1158/1078-0432.CCR-05-0421 PG 10 WC Oncology SC Oncology GA 984VC UT WOS:000233331400034 PM 16278407 ER PT J AU Fukuhara, H Martuza, RL Rabkin, SD Ito, Y Todo, T AF Fukuhara, H Martuza, RL Rabkin, SD Ito, Y Todo, T TI Oncolytic herpes simplex virus vector G47 Delta in combination with androgen ablation for the treatment of human prostate adenocarcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-I TRIAL; REPLICATION-COMPETENT; ANTITUMOR IMMUNITY; RADIATION-THERAPY; GENE-THERAPY; CANCER HONDA; NUDE-MICE; G207; ADENOVIRUS; MODELS AB Purpose: The use of oncolytic herpes simplex virus type 1 is a promising stategy for cancer treatment. We constructed herpes simplex virus type 1 vector G47 Delta by deleting the alpha 47 gene and the promoter region of US11 from G207. We now report studies demonstrating the potential of G47 Delta as a therapeutic modality for prostate cancer in combination with androgen ablation. Experimental Design:The cytopathic activities of G47 Delta at low multiplicities of infection was tested in human prostate cancer cell lines LNCaP, PC-3, and DU145 in vitro. Two androgen-dependent mouse s.c. tumor models, murine TRAMP and human HONDA, were used to investigate the in vivo efficacy of G47 Delta in combination with androgen ablation. Results: G47 Delta at low multiplicities of infection showed more rapid tumor cell killing than G207 in LNCaP and DU145 in vitro and showed a 22-fold higher virus yield in a single-step growth experiment. In vivo, G47 Delta treatment resulted in reduced tumor growth of established s.c. TRAMP and HONDA tumors and inhibited the growth of recurrent HONDA tumors that once regressed by androgen ablation therapy. In both TRAMP and HONDA tumor xenografts, the combination therapy of G47 Delta with androgen ablation led to significantly enhanced inhibition of the tumor growth and prolonged survival. Conclusions: These results suggest that oncolytic virus therapy with G47 Delta can be usefully combined with androgen ablation therapy for the treatment of prostate cancer. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA USA. Univ Tokyo, Dept Urol, Tokyo, Japan. Univ Tokyo, Dept Neurosurg, Tokyo, Japan. Gunma Univ, Sch Hlth Sci, Gunma, Japan. RP Martuza, RL (reprint author), Brain Tumor Res Ctr, 185 Cambridge St,CPZN-3800,MGH Simches Res Bldg, Boston, MA 02114 USA. EM rmartuza@partners.org RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 FU NCI NIH HHS [R01 CA102139] NR 21 TC 21 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2005 VL 11 IS 21 BP 7886 EP 7890 DI 10.1158/1078-0432.CCR-05-1090 PG 5 WC Oncology SC Oncology GA 984VC UT WOS:000233331400040 PM 16278413 ER PT J AU Podrid, PJ Myerburg, RJ AF Podrid, PJ Myerburg, RJ TI Epidemiology and stratification of risk for sudden cardiac death SO CLINICAL CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Optimal Management of the Patient Post MI With of Without Heart Failure CY JAN 21-22, 2005 CL New York, NY DE sudden cardiac death; ventricular fibrillation; ventricular tachycardia; risk stratification; risk markers ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; CORONARY DEATH; VENTRICULAR-ARRHYTHMIAS; ANTIARRHYTHMIC-DRUGS; CARDIOPULMONARY-RESUSCITATION; CHOLESTEROL LEVELS; UNITED-STATES; HEART-DISEASE AB Sudden cardiac death (SCD) is a major cause of mortality in the United States. Approximately 65% of cases of SCD occur in patients with underlying acute or chronic ischemic heart disease. The incidence of SCD increases 2- to 4-fold in the presence of coronary disease and 6- to 10-fold in the presence of structural heart disease. Ventricular fibrillation (VF) precipitated by ventricular tachycardia (VT) is a common mechanism of cardiac arrest leading to SCD. Triggers for SCD include electrolyte disturbances, heart failure, and transient ischemia. Although a large percentage of patients with out-of-hospital SCD do not survive, successful resuscitation to hospitalization has improved in recent years. One of the challenges for preventing SCD lies in identifying individuals at highest risk for SCD within a lower-risk population. The progression from conventional risk factors of coronary artery dis ease to arrhythmogenesis and SCD can be represented as a cascade of changes associated with levels of increasing risk. At the first level is atherogenesis, followed by changes in atherosclerotic plaque anatomy, which may be mediated by inflammatory processes. Disruption of active plaque formed during a transitional state initiates the thrombotic cascade and acute occlusion, after which acute changes in myocardial electrophysiology become the immediate trigger for arrhythmogenesis and SCD. Each level of the cascade offers different opportunities for risk prediction. Among the classes of risk predictors are clinical markers, such as ECG measures and ejection fraction. Transient risk markers, such as inflammatory markers, are potentially useful for identifying triggers for SCD. In the future, genetic profiling is expected to allow better assessment of individual risks for SCD. C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury VA Div, W Roxbury, MA USA. Univ Miami, Miller Sch Med, Miami, FL 33152 USA. RP Podrid, PJ (reprint author), Boston Univ, Sch Med, VA Boston Healthcare Syst, W Roxbury VA Div, 1400 VFW Pkwy, W Roxbury, MA USA. EM philip.podrid@med.va.gov NR 68 TC 23 Z9 27 U1 0 U2 4 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 2005 VL 28 IS 11 SU S BP I3 EP I11 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 982MF UT WOS:000233161800002 PM 16450807 ER PT J AU Hur, C Gazelle, GS Hsu, EH Halpern, EF Podolsky, DK AF Hur, C Gazelle, GS Hsu, EH Halpern, EF Podolsky, DK TI The effect of prior colonic imaging on endoscopic productivity: Potential impact of computed tomographic colonography SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID VIRTUAL COLONOSCOPY; COLORECTAL NEOPLASIA AB Background & Aims: If computed tomographic colonography (CTC) is used for primary colorectal cancer (CRC) screening with a small polyp size threshold to define a CTC study as positive, a substantial portion of all colonoscopies performed annually will be to follow up positive CTC examinations. Moreover, the majority of positive CTC examinations would be false positives (FP). This case-control study was undertaken to test the hypothesis that colonoscopy examinations resulting from FP CTC studies would take longer to complete than negative screening colonoscopies. Methods: Endoscopic records of a large, urban hospital were reviewed to identify all patients who had either a positive barium enema (BE) study or flexible sigmoidoscopy (FS) and a negative follow-up colonoscopy examination (these patients were used as surrogates for CTC FP cases). For each of the 28 FP patients or cases identified, 2 screening colonoscopies performed by the same endoscopist within the same time period were identified and used as matched controls. A two-way analysis of variance test was performed to assess for differences in time to complete colonoscopies between these 2 groups, controlling for the individual endoscopist. Results: FP colonoscopies took an average of 24.0 minutes to complete, whereas negative screening colonoscopies took 14.9 minutes; FP colonoscopies required 61% more active time to complete. This highly statistically significant difference (P <.0001) persisted with subset analyses that only included BE or FS cases and when fellow or surgeon cases were excluded. Conclusions: FP colonoscopies take longer to perform than negative screening colonoscopies. If CTC is implemented as the primary modality for CRC screening, these FP examinations could comprise a substantial percentage of the colonoscopies performed, potentially leading to a significant decrease in endoscopic productivity. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Hur, C (reprint author), 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM chur@mgh-ita.org OI Hur, Chin/0000-0002-2819-7576 NR 10 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 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2005 VL 3 IS 11 BP 1124 EP 1127 DI 10.1053/S1542-3565(05)00534-3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995ND UT WOS:000234106100015 PM 16271344 ER PT J AU Giampietro, PF Raggio, CL Reynolds, CE Shukla, SK McPherson, E Ghebranious, N Jacobsen, FS Kumar, V Faciszewski, T Pauli, RM Rasmussen, K Burmester, JK Zaleski, C Merchant, S David, D Weber, JL Glurich, I Blank, RD AF Giampietro, PF Raggio, CL Reynolds, CE Shukla, SK McPherson, E Ghebranious, N Jacobsen, FS Kumar, V Faciszewski, T Pauli, RM Rasmussen, K Burmester, JK Zaleski, C Merchant, S David, D Weber, JL Glurich, I Blank, RD TI An analysis of PAX1 in the development of vertebral malformations SO CLINICAL GENETICS LA English DT Article DE CEPH diversity panel; PAX1; polymorphism; vertebral malformation ID SPONDYLOCOSTAL DYSOSTOSIS; CONGENITAL SCOLIOSIS; SPINA-BIFIDA; GENE; MUTATIONS; SEGMENTATION; ANOMALIES; DEFECTS; LIGAND; DLL3 AB Due to the sporadic occurrence of congenital vertebral malformations, traditional linkage approaches to identify genes associated with human vertebral development are not possible. We therefore identified PAX1 as a candidate gene in vertebral malformations and congenital scoliosis due to its mutation in the undulated mouse. We performed DNA sequence analysis of the PAX1 gene in a series of 48 patients with congenital vertebral malformations, collectively spanning the entire vertebral column length. DNA sequence coding variants were identified in the heterozygous state in exon 4 in two male patients with thoracic vertebral malformations. One patient had T9 hypoplasia, T12 hemivertebrae and absent T10 pedicle, incomplete fusion of T7 posterior elements, ventricular septal defect, and polydactyly. This patient had a C (c) under barC (Pro)-> C (T) under barC (Leu) change at amino acid 410. This variant was not observed in 180 chromosomes tested in the National Institute of Environmental Health Sciences (NIEHS) single nucleotide polymorphism (SNP) database and occurred at a frequency of 0.3% in a diversity panel of 1066 human samples. The second patient had a T11 wedge vertebra and a missense mutation at amino acid 413 corresponding to CCA (Pro)-> CTA (Leu). This particular variant has been reported to occur in one of 164 chromosomes in the NIEHS SNP database and was found to occur with a similar frequency of 0.8% in a diversity panel of 1066 human samples. Although each patient's mother was clinically asymptomatic and heterozygous for the respective variant allele, the possibility that these sequence variants have clinical significance is not excluded. C1 Marshfield Clin Fdn Med Res & Educ, Med Genet Serv, Marshfield, WI 54449 USA. Hosp Special Surg, New York, NY 10021 USA. Marshfield Clin & Res Fdn, Clin Res Ctr, Marshfield, WI USA. Marshfield Clin Fdn Med Res & Educ, Mol Diagnost Genotyping Lab, Marshfield, WI USA. Univ Wisconsin, Clin Genet Ctr, Madison, WI USA. Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. Univ Wisconsin, Dept Med, Endocrinol Sect, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Giampietro, PF (reprint author), Marshfield Clin Fdn Med Res & Educ, Med Genet Serv, 1000 N Oak Ave 3C1, Marshfield, WI 54449 USA. EM giampietro.philip@marshfieldclinic.org OI Blank, Robert Daniel/0000-0003-2950-1944 NR 18 TC 25 Z9 32 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2005 VL 68 IS 5 BP 448 EP 453 DI 10.1111/j.1399-0004.2005.00520.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 971NU UT WOS:000232392000011 PM 16207213 ER PT J AU Sax, PE Islam, R Walensky, RP Losina, E Weinstein, MC Goldie, SJ Sadownik, SN Freedberg, KA AF Sax, PE Islam, R Walensky, RP Losina, E Weinstein, MC Goldie, SJ Sadownik, SN Freedberg, KA TI Should resistance testing be performed for treatment-naive HIV-infected patients? A cost-effectiveness analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL-DRUG-RESISTANCE; RANDOMIZED CONTROLLED-TRIAL; SOCIETY-USA PANEL; GENOTYPIC RESISTANCE; PLUS INDINAVIR; THERAPY; TYPE-1; ADULTS; PERSISTENCE AB Background. Data from the United States and Europe show a population prevalence of baseline drug resistance of 8%-10% among human immunodeficiency virus (HIV)-infected patients who are antiretroviral naive. Our objective was to determine the clinical impact and cost-effectiveness of genotype resistance testing for treatment-naive patients with chronic HIV infection. Methods. We utilized a state-transition model of HIV disease to project life expectancy, costs, and cost-effectiveness in a hypothetical cohort of antiretroviral-naive patients with chronic HIV infection. On the basis of a US survey of treatment-naive patients from the Centers for Disease Control and Prevention, we used a baseline prevalence of drug resistance of 8.3%. Results. A strategy of genotype-resistance testing at initial diagnosis of HIV infection increased per-person quality-adjusted life expectancy by 1.0 months, with an incremental cost-effectiveness ratio of $23,900 per quality-adjusted life-year gained, compared with no genotype testing. The cost-effectiveness ratio for resistance testing remained less than $50,000 per quality-adjusted life-year gained, unless the prevalence of resistance was <= 1%, a level lower than those reported in most regions of the United States and Europe. In sensitivity analyses, the cost-effectiveness remained favorable through wide variations in baseline assumptions, including variations in genotype cost, prevalence of resistance overall and to individual drug classes, and sensitivity of resistance testing. Conclusions. Genotype-resistance testing of chronically HIV-infected, antiretroviral-naive patients is likely to improve clinical outcomes and is cost-effective, compared with other HIV care in the United States. Resistance testing at the time of diagnosis should be the standard of care. C1 Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Med, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Risk Anal, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Sax, PE (reprint author), Brigham & Womens Hosp, Div Infect Dis, 15 Francis St,PBBA-4, Boston, MA 02115 USA. EM psax@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [P30-AI42857, K23 AI001794, K23AI01794, K24 AI062476, K24AI062476, K25 AI050436, K25AI50436, P30 AI042851, R01 AI042006, R01-AI42006]; ODCDC CDC HHS [U64/CCU 114927] NR 49 TC 117 Z9 123 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2005 VL 41 IS 9 BP 1316 EP 1323 DI 10.1086/496984 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 971BO UT WOS:000232356300022 PM 16206108 ER PT J AU Hadigan, C AF Hadigan, C TI Insulin resistance among HIV-infected patients: Unraveling the mechanism SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ANTIRETROVIRAL THERAPY; FAT REDISTRIBUTION; THYMIDINE ANALOG; BODY-COMPOSITION; LIPODYSTROPHY; GLUCOSE; ADIPONECTIN; MEN C1 Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. RP Hadigan, C (reprint author), Massachusetts Gen Hosp, Program Nutr Metab, 55 Fruit St LON 207, Boston, MA 02114 USA. EM chadigan@partners.org NR 17 TC 7 Z9 7 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 NOV 1 PY 2005 VL 41 IS 9 BP 1341 EP 1342 DI 10.1086/496990 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 971BO UT WOS:000232356300027 PM 16206113 ER PT J AU Weiner, M Benator, D Peloquin, CA Burman, W Vernon, A Engle, M Khan, A Zhao, Z AF Weiner, M Benator, D Peloquin, CA Burman, W Vernon, A Engle, M Khan, A Zhao, Z CA Tuberculosis Trials Consortium TI Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Scientific Conference on New Trends in Landscape Ecology CY OCT 24-26, 2002 CL Piestany, SLOVAKIA SP Int Assoc Landscape Ecol ID PHARMACOKINETIC INTERACTIONS; RIFAMPICIN; ZIDOVUDINE; NEVIRAPINE; LAMIVUDINE; INDUCTION; THERAPY AB Background. Because of drug-drug interactions mediated by hepatic cytochrome P450, tuberculosis treatment guidelines recommend an increase in rifabutin from 300 mg to 450 or 600 mg when combined with efavirenz-based antiretroviral therapy. To assess this recommendation, rifabutin and efavirenz pharmacokinetic parameters were investigated. Methods. Plasma concentrations of rifabutin were determined as a baseline control in 15 patients with tuberculosis and human immunodeficiency virus (HIV) infection who were treated with rifabutin 300 mg and isoniazid 15 mg/kg ( up to 900 mg) twice weekly. Rifabutin, isoniazid, and efavirenz concentrations were determined after a median of 21 days (interquartile range, 20-34 days) of daily efavirenz-based antiretroviral therapy with twice-weekly rifabutin 600 mg and isoniazid 15 mg/kg. Results. The mean rifabutin area under the concentration-time curve (AUC(0-24)) increased 20% from the baseline value (geometric mean, 5.0 vs. 4.2 mu g*h/mL; ratio of geometric means, 1.2 [90% confidence interval, 1.0-1.4]). Also, the mean efavirenz AUC(0-24) in the 15 patients taking concomitant rifabutin 600 mg twice-weekly was 10% higher than that in 35 historical subjects with HIV infection who were not taking rifabutin. Efavirenz-based antiretroviral therapy was effective; HIV load decreased 2.6 log copies/mL, and the median CD4(+) T cell count increased from 141 to 240 cells/mm(3) after a median of 21 days of efavirenz-based antiretroviral therapy. No statistically significant differences in isoniazid pharmacokinetic parameters were found. Conclusions. The rifabutin dose increase from 300 mg to 600 mg was adequate to compensate for the efavirenz drug interaction in most patients, and no drug interaction with isoniazid was detected. Efavirenz therapy administered at a standard 600-mg dose achieved adequate plasma concentrations in patients receiving intermittent rifabutin and isoniazid therapy, was generally well tolerated, and demonstrated potent antiretroviral activity. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Univ Colorado, Natl Jewish Med & Res Ctr, Sch Pharm, Denver, CO 80202 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Denver Publ Hlth, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA USA. RP Weiner, M (reprint author), VAMC, Div Infect Dis, Rm 111F,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu FU NCRR NIH HHS [M01-RR-01346] NR 26 TC 30 Z9 32 U1 0 U2 5 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 NOV 1 PY 2005 VL 41 IS 9 BP 1343 EP 1349 DI 10.1086/496980 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 971BO UT WOS:000232356300028 PM 16206114 ER PT J AU Jones, DA AF Jones, DA TI Are we abandoning nursing as a discipline? SO CLINICAL NURSE SPECIALIST LA English DT Editorial Material C1 Boston Coll, William F Connell Sch Nursing, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jones, DA (reprint author), Boston Coll, William F Connell Sch Nursing, 140 Commonwealth Ave, Chestnut Hill, MA 02467 USA. EM Dorothy.jones@bc.edu NR 12 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0887-6274 J9 CLIN NURSE SPEC JI Clin. Nurse Spec. PD NOV-DEC PY 2005 VL 19 IS 6 BP 275 EP 277 DI 10.1097/00002800-200511000-00001 PG 3 WC Nursing SC Nursing GA 036OX UT WOS:000237085400001 PM 16294048 ER PT J AU Huddleston, JI Scott, RD Wiinberley, DW AF Huddleston, JI Scott, RD Wiinberley, DW TI Determination of neutral tibial rotational alignment in rotating platform TKA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Meeting of the Knee-Society CY 2005 CL Washington, DC SP Knee Soc ID TOTAL KNEE ARTHROPLASTY; FEMORAL COMPONENT ROTATION; TERM FOLLOW-UP; OSTEOARTHRITIC KNEE; REVISION; MALALIGNMENT; REPLACEMENT; DISLOCATION; POSITION; FAILURE AB Use of a fixed anatomic landmark to set rotation of the tibial component may lead to rotational malalignment. Post wear in stabilized components, backside wear in any conforming modular system, and patellar maltracking may result from tibiofemoral rotational incongruence. We aimed to quantify tibial rotational alignment in 109 primary rotating platform TKAs. After trial components were inserted with the knee properly balanced, we recorded the neutral point of the rotating tibial insert, in extension, relative to the most medial aspect of the tibial tubercle. We hypothesized that all neutral points would lie within 10 degrees of the mean. Divergence of the neutral point was recorded as being internal or external to the medial border of the tibial tubercle to the nearest 50 increment. Our results showed a mean divergence of 5 degrees 5 degrees external to the medial border of the tubercle. Five percent of knees, however, had neutral points >= 10 degrees from the mean. Surgeons who use fixed-bearing modular components with any rotational constraint must be cautious in choosing a fixed anatomic tibial landmark to determine the rotational alignment of the tibial component. Doing so may create tibiofemoral rotational malalignment in full extension that may lead to suboptimal outcomes. C1 Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Fdn Orthped Grp, Houston, TX USA. RP Huddleston, JI (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech & Biomat Lab, Jackson 1124, Boston, MA 02114 USA. EM hutchhuddleston@yahoo.com NR 41 TC 28 Z9 30 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2005 IS 440 BP 101 EP 106 DI 10.1097/01.blo.0000185448.43622.77 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 983KS UT WOS:000233231000019 ER PT J AU Marshall, AD Panuzio, J Taft, CT AF Marshall, AD Panuzio, J Taft, CT TI Intimate partner violence among military veterans and active duty servicemen SO CLINICAL PSYCHOLOGY REVIEW LA English DT Article DE partner abuse; intimate partner violence; military personnel; military veterans ID US-ARMY SOLDIERS; POSTTRAUMATIC-STRESS-DISORDER; SPOUSE ABUSE TREATMENT; PHYSICAL HEALTH CONSEQUENCES; VIETNAM COMBAT VETERANS; DOMESTIC VIOLENCE; TREATMENT PROGRAM; CHILD-ABUSE; MARITAL AGGRESSION; GENDER-DIFFERENCES AB Intimate partner violence (IPV) is a serious public health problem that has received increased attention in the military. We review existing literature regarding prevalence, consequences, correlates, and treatment of IPV perpetration among military veterans and active duty servicemen. Rates of IPV across these military populations range from 13.5% to 58%, with considerably lower rates obtained among samples not selected on the basis of psychopathology. For both military veterans and active duty servicemen, IPV results in significant victim injury and negative child outcomes, and problematic substance use, depression, and antisocial characteristics represent psychiatric correlates of IPV perpetration. For veterans, posttraumatic stress disorder also is an important correlate that largely accounts for the relationship between combat exposure and IPV perpetration. Additional correlates include military service factors, relationship adjustment, childhood trauma, and demographic factors. The only experimentally controlled IPV treatment study indicates that standard treatments are ineffective for active duty servicemen. Further research is needed to advance the development of etiological models of IPV among military populations, to determine whether such models necessarily differ from those developed among civilians, and to rigorously test IPV interventions tailored to the specific characteristics of these individuals. Published by Elsevier Ltd. C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA 02130 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Taft, CT (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 116B-2,150 S Huntington Ave, Boston, MA 02130 USA. EM taft@bu.edu NR 78 TC 107 Z9 107 U1 3 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0272-7358 J9 CLIN PSYCHOL REV JI Clin. Psychol. Rev. PD NOV PY 2005 VL 25 IS 7 BP 862 EP 876 DI 10.1016/j.cpr.2005.05.009 PG 15 WC Psychology, Clinical SC Psychology GA 974CH UT WOS:000232568400002 PM 16006025 ER PT J AU Mackin, RS Horner, MD AF Mackin, RS Horner, MD TI Relationship of the Wender Utah Rating Scale to objective measures of attention SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; DEFICIT/HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; NEUROPSYCHOLOGICAL PERFORMANCE; FRONTAL-LOBE; ADULTS; DYSFUNCTION; SCHIZOPHRENIA; ADHD; BOYS AB The Wender Utah Rating Scale (WURS) is a 25-item self-report questionnaire for the retrospective assessment of childhood attention-deficit hyperactivity disorder (ADHD) symptoms; high scores indicate greater symptoms. The current study used 35 male Veterans Affairs outpatients to determine if WURS scores were associated with objective measures of current attentional functioning, including the Trail Making Test, Gordon Diagnostic System, Wechsler Adult Intelligence Scale-Revised digit span and digit symbol subtests, and Wechsler Memory Scale-Revised mental control subtest. Participants included both adults diagnosed with ADHD (n = 14) and non-ADHD adults (n = 21). After Bonferroni correction, Pearson product moment correlation coefficients revealed that greater symptoms on the WURS were associated with poorer digit symbol performance (r = -0.69, P <.05). To determine which indices best predicted WURS scores, scores on attention tests and demographic variables were entered into a stepwise multiple regression analysis. Digit symbol performance was the only significant predictor of WURS scores (R-2 = 0.59, P <.01). Thus, poor performance on a sensitive, but nonspecific, measure of attention with executive function, response speed, and visuomotor coordination components was related to greater self-report of childhood ADHD symptoms. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Mental Hlth Serv, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. RP Mackin, RS (reprint author), Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. NR 40 TC 15 Z9 15 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2005 VL 46 IS 6 BP 468 EP 471 DI 10.1016/j.comppsych.2005.03.004 PG 4 WC Psychiatry SC Psychiatry GA 987EI UT WOS:000233500800010 PM 16275215 ER PT J AU Meyer, TD Deckersbach, T AF Meyer, TD Deckersbach, T TI No evidence for verbal memory impairment in individuals putatively at risk for bipolar disorder SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID HYPOMANIC PERSONALITY SCALE; NEUROPSYCHOLOGICAL FUNCTION; IMPULSIVE NONCONFORMITY; EUTHYMIC PATIENTS; MAJOR DEPRESSION; EMOTIONAL STROOP; MANIC DEFENSE; RATING-SCALE; TRAITS; PERFORMANCE AB Background: Hypomanic temperament and rigid personality are putative risk factors for affective episodes and even bipolar disorder. Individuals with bipolar disorder exhibit neuropsychological impairments, especially memory difficulties, not only during mood episodes but also when they are euthymic. Such cognitive impairments may also constitute a risk factor for bipolar disorder. The purpose of the present study was to investigate the presence of memory difficulties in individuals with hypomanic and rigid personality traits. Methods: Study participants were 6000 German students recruited from high schools, colleges, and vocational schools in Germany. The students completed the Hypomanic Personality Scale and the Rigidity subscale of the Munich Personality Test. Four groups of students were selected from this sample based on their scores in the Hypomanic Personality Scale and Rigidity subscale: individuals with (1) hypomanic temperament, (2) rigid temperament, or (3) hypomanic-rigid temperament and (4) control participants. These students (n = 153) completed the Rey-Auditory Verbal Learning Test, a well-established measure of verbal learning and memory, as well an IQ test (Leistungsprufsystem). Results: Multiple regression analyses indicated that sex and IQ, but not temperament, predicted learning of the Auditory Verbal Learning Test word list, the number of words recalled at short-delayed recall, and recognition. Limitations: The risk for affective disorders was only defined by psychometric measures, and we did not control for family history of bipolar disorders. Conclusions: Hypomanic temperament and Rigid personality were not associated with verbal learning and memory. Cognitive impairment may be associated with repeated mood episodes rather than constituting a risk factor for bipolar disorder. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Univ Tubingen, Inst Psychol, Dept Clin & Dev Psychol, D-72072 Tubingen, Germany. RP Deckersbach, T (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, 149-2611, Charlestown, MA 02129 USA. EM tdeckersbach@partners.org NR 47 TC 7 Z9 7 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 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2005 VL 46 IS 6 BP 472 EP 476 DI 10.1016/j.comppsych.2005.02.003 PG 5 WC Psychiatry SC Psychiatry GA 987EI UT WOS:000233500800011 PM 16275216 ER PT J AU Barabino, S Raghavan, A Loeffler, J Dana, R AF Barabino, S Raghavan, A Loeffler, J Dana, R TI Radiotherapy-induced ocular surface disease SO CORNEA LA English DT Review DE teletherapy; brachytherapy; fractionation; ocular surface ID EXTERNAL-BEAM IRRADIATION; STEM-CELL DYSFUNCTION; RADIATION-THERAPY; ORBITAL LYMPHOMA; EYE; BRACHYTHERAPY; CARCINOMA; RETINOBLASTOMA; COMPLICATIONS; MELANOMAS AB Today radiation is routinely used as a therapeutic modality for select tumors of the orbit, adnexa, paranasal sinus, and nasopharynx. Despite significant improvements in mechanisms of delivery and protective shielding, acute and chronic complications of radiation can affect different segments of the eye. In this report, we provide an overview of ocular damage secondary to radiotherapy. We identify the characteristic clinical changes and underlying pathophysiologic mechanisms involving the ocular surface and provide a rational approach to their prevention and treatment. C1 Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Univ Genoa, Dept Neurosci Ophthalmol & Genet, I-16126 Genoa, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. RP Dana, R (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, Dept Ophthalmol, 20 Staniford St, Boston, MA 02114 USA. EM dana@vision.eri.harvard.edu NR 44 TC 9 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2005 VL 24 IS 8 BP 909 EP 914 DI 10.1097/01.ico.0000154235.64359.d3 PG 6 WC Ophthalmology SC Ophthalmology GA 984HR UT WOS:000233294200003 PM 16227831 ER PT J AU Nouri, M Durand, ML Dohlman, CH AF Nouri, M Durand, ML Dohlman, CH TI Sudden reversible vitritis after keratoprosthesis - An immune phenomenon? SO CORNEA LA English DT Article DE keratoprosthesis; sterile vitritis ID POSTERIOR CAPSULE OPACIFICATION; ENDOPHTHALMITIS; LENSES AB Purpose: To report our experience with late vitritis associated with keratoprosthesis (KPro). Methods: Between 1990 and 2003, 218 patients underwent an all-polymethylmethacrylate, collar button-shaped KPro surgery. Eight patients developed a total of 12 episodes of sudden, massive vitritis. Five of these patients had an Ahmed shunt implant, 3 had anterior vitrectomy during surgery, and 4 had a soft contact lens in place. Preoperative diagnoses were multiple graft failures, chemical burn, Stevens-Johnson syndrome, or ocular cicatricial pemphigoid. All patients were maintained on prophylactic topical ofloxacin 0.3% or polymyxin-B/trimethoprim, as well as prednisolone acetate 1% (in 2 cases, medroxyprogesterone 1%), at least twice daily. Vancomycin (14 mg/mL) was also given twice daily in 2 patients. Results: Vitritis occurred in 8 patients (12 episodes), 2 to 23 months postoperatively. All patients presented with sudden, very marked decrease in vision, with little or no pain, tenderness, conjunctival redness, or discharge. Eight of the 12 events were subjected to vitreous tap and injection of antibiotics and steroids on the day of presentation. Cultures grew Staphylococcus epidermidis, only in liquid (broth) media, in 3 cases; the other 5 showed no growth. The vitritis episodes resolved after 2 to 9 weeks. Full recovery to pre-episode status of a quiet eye with clear vitreous was seen in all patients. Visual acuity recovered almost completely or completely (mental debilitation in one patient made accurate assessment uncertain). Conclusions: This phenomenon of sudden vitritis after KPro, with few other symptoms and with complete recovery would be uncharacteristic of a bacterial endophthalmitis. It may represent a uveitic immune phenomenon. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP Dohlman, CH (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 18 Z9 20 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 2005 VL 24 IS 8 BP 915 EP 919 DI 10.1097/01.ico.0000159736.60424.ff PG 5 WC Ophthalmology SC Ophthalmology GA 984HR UT WOS:000233294200004 PM 16227832 ER PT J AU Tawakol, A Aziz, K Migrino, R Watkowska, J Zusman, R Alpert, NM Fischman, AJ Gewirtz, H AF Tawakol, A Aziz, K Migrino, R Watkowska, J Zusman, R Alpert, NM Fischman, AJ Gewirtz, H TI Effects of sildenafil on myocardial blood flow in humans with ischemic heart disease SO CORONARY ARTERY DISEASE LA English DT Article DE myocardial blood flow; ischemic heart disease; sildenafil ID CORONARY-ARTERY-DISEASE; ADENOSINE; PERFUSION; EXERCISE; REGIONS AB Background We tested the hypothesis that sildenafil increases myocardial dilator reserve in humans with ischemic heart disease. Methods Positron emission tomography measured myocardial blood flow in 14 patients with ischemic heart disease. Patients were studied twice, in double-blind, placebo-control, cross-over design with sildenafil (or placebo) given similar to 2-3 h before measurements of hemodynamics and myocardial blood flow: at rest, with cold pressor stress and with adenosine. All myocardial segments of each patient with myocardial blood flow < 1.65 ml/min per g with adenosine under placebo conditions were combined into one abnormal zone for that patient. Segments with myocardial blood flow > 1.65 ml/min per g were averaged and combined into a normal zone for that patient. Results At rest, rate pressure product (heart rate x systolic arterial pressure, mmHg/min) was comparable, as was abnormal zone myocardial blood flow (ml/min per g; 0.76 +/- 0.48 placebo versus 0.64 +/- 0.20 sildenafil, both P=NS; mean SD). Both rate pressure product and myocardial blood flow increased (P < 0.01) with cold pressor stress (11 +/- 3 K and 1.14 +/- 0.59 placebo versus 10 +/- 3 K and 1.21 +/- 0.62 sildenafil). However, sildenafil failed to improve the myocardial blood flow response to cold pressor stress in abnormal or normal zones. In contrast, abnormal zone myocardial blood flow reserve with adenosine and sildenafil (2.6 +/- 0.7) exceeded that with adenosine and placebo (2.0 +/- 1.3, P < 0.04, paired sign test). Conclusion Sildenafil improves myocardial blood flow dilator response to adenosine in abnormal zones, possibly by augmenting nitric oxide-mediated increases in cGMP because adenosine response in part is nitric oxide dependent. Failure to improve myocardial blood flow response to cold pressor stress suggests that a-adrenergic constriction may offset enhanced nitric oxide effects. Clinically, the data suggest sildenafil may exert an anti-ischemic effect in patients with coronary artery disease. C1 Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol & Nucl Med, Boston, MA 02115 USA. RP Gewirtz, H (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Yawkey 5E, Boston, MA 02114 USA. EM hgewirtz@partners.org NR 24 TC 14 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0954-6928 J9 CORONARY ARTERY DIS JI Coronary Artery Dis. PD NOV PY 2005 VL 16 IS 7 BP 443 EP 449 DI 10.1097/00019501-200510000-00005 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 979MB UT WOS:000232945000005 PM 16205453 ER PT J AU Lapadat, R DeBiasi, RL Johnson, GL Tyler, KL Shah, I AF Lapadat, R DeBiasi, RL Johnson, GL Tyler, KL Shah, I TI Genes induced by reovirus infection have a distinct modular cis-regulatory architecture SO CURRENT GENOMICS LA English DT Article DE cis-regulation; gene arrays; promoters; sequence modules; transcription factors; Gene Ontology; signaling; reovirus; apoptosis ID NF-KAPPA-B; FACTOR-BINDING SITES; INDUCED APOPTOSIS; COREGULATED GENES; TARGET GENES; IDENTIFICATION; EXPRESSION; ACTIVATION; INTERFERON; DISCOVERY AB The availability of complete genomes and global gene expression profiling has greatly facilitated analysis of complex genetic regulatory systems. We describe the use of a bioinformatics strategy for analyzing the cis-regulatory design of genes diferentially regulated during viral infection of a target cell. The large-scale transcriptional activity of human embryonic kidney (HEK293) cells to reovirus (serotype 3 Abney) infection was measured using the Affymetrix HU95Av2 gene array. Comparing the 2000 base pairs of 5' upstream sequence for the most differentially expressed genes revealed highly preserved sequence regions, which we call "modules". Higher-order patterns of modules, called "supermodules", were significantly over-represented in the 5' upstream regions of transcriptionally responsive genes. These supermodules contain binding sites for multiple transcription factors and tend to define the role of genes in processes associated with reovirus infection. The supermodular design encodes a cis-regulatory logic for transducing upstream signaling for the control of expression of genes involved in similar biological processes. In the case of reovirus infection, these processes recapitulate the integrated response of cells including signal transduction, transcriptional regulation, cell cycle control, and apoptosis. The computational strategies described for analyzing gene expression data to discover cis-regulatory features and associating them with pathological processes represents a novel approach to studying the interaction of a pathogen with its target cells. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Med Microbiol & Immunol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol, Campus Box B-182,4200 E 9th Ave, Denver, CO 80262 USA. EM ken.tyler@uchsc.edu OI Tyler, Kenneth/0000-0003-3294-5888 FU NIA NIH HHS [R01 AG014071]; NIAAA NIH HHS [U01 AA013524]; NIGMS NIH HHS [R01 GM030324, R37 GM030324]; NINDS NIH HHS [R01 NS050138, R01 NS051403] NR 49 TC 1 Z9 1 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD NOV PY 2005 VL 6 IS 7 BP 501 EP 513 DI 10.2174/138920205775067675 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 995LF UT WOS:000234101100002 PM 23335855 ER PT J AU Lentz, MR Taylor, JL Feldman, DA Cheng, LL AF Lentz, MR Taylor, JL Feldman, DA Cheng, LL TI Current clinical applications of in vivo magnetic resonance spectroscopy and spectroscopic imaging SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE magnetic resonance spectroscopy; magnetic resonance spectroscopic imaging; brain; cancer; clinical applications; in vivo ID PROTON MR-SPECTROSCOPY; TEMPORAL-LOBE EPILEPSY; SHORT-ECHO-TIME; AMYOTROPHIC-LATERAL-SCLEROSIS; APPEARING WHITE-MATTER; TRAUMATIC BRAIN-INJURY; REMITTING MULTIPLE-SCLEROSIS; LOCALIZED H-1-NMR SPECTROSCOPY; INVASIVE CERVICAL-CANCER; ABSOLUTE METABOLITE QUANTIFICATION AB Magnetic resonance imaging (MRI) infused Radiology with rejuvenating vigor in the 1980s, owing credit to a couple of magnetic resonance spectroscopy (MRS) experiments performed in 1973. MRI has since been embraced by the radiology and medical communities. If the goal of MRS is to measure many chemicals in a homogeneous magnetic field, then the function of MRI is, in general, to measure one chemical - water - in an artificially created inhomogeneous field. Combining spectroscopy principles with technologies developed over the past two decades for MRI presented the philosophical appeal of non-invasively measuring metabolic molecules in living tissue, and led to the explosive developments in the last decade of in vivo MRS, and more recently MRSI, in the settings of diagnostic radiology. This review is intended to discuss the basic technologies of the current trends in the field of in vivo MRS and MRSI, especially the inherent predilections of individual techniques to the study of certain disease states. Following a historical introduction, individual techniques and their clinical applications, found in publications between January 2000 and October 2004, are reviewed in connection with related ex vivo results, after which the practical aspects of in vivo MRS and MRSI in clinical settings are discussed. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Chicago, Dept Canc Biol, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. RP Cheng, LL (reprint author), Pathol Res CNY-7,149 13th, Charlestown, MA 02139 USA. EM cheng@nmr.mgh.harvard.edu NR 325 TC 6 Z9 6 U1 2 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD NOV PY 2005 VL 1 IS 3 BP 271 EP 301 DI 10.2174/157340505774574781 PG 31 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 988YG UT WOS:000233639500007 ER PT J AU Ray, KK Cannon, CP AF Ray, KK Cannon, CP TI Optimal goals for statin use in patients with coronary artery disease SO CURRENT OPINION IN CARDIOLOGY LA English DT Review DE cholesterol; coronary artery disease; lipid; statin; therapy ID C-REACTIVE PROTEIN; DENSITY-LIPOPROTEIN CHOLESTEROL; PLACEBO-CONTROLLED TRIAL; LIPID-LOWERING THERAPY; APOLIPOPROTEIN-B; POSTMENOPAUSAL WOMEN; HEART-DISEASE; RISK; ATHEROSCLEROSIS; ATORVASTATIN AB Purpose of review Coronary artery disease is the largest cause of premature death in the Western world. Lipid-lowering therapy with statins has revolutionized the management of this condition over the past decade. Recent developments Successive clinical trials have lowered the treatment bar for statin therapy in patients with coronary artery disease. In addition to traditional markers of efficacy such as low-density lipoprotein cholesterol, emerging targets such as C-reactive protein are becoming recognized as important therapeutic goals. Summary This review focuses on the important contributions to the literature during the past year and provides an expert opinion of the therapeutic goals for statin therapy. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. RP Ray, KK (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM kkray@partners.org NR 32 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0268-4705 J9 CURR OPIN CARDIOL JI Curr. Opin. Cardiol. PD NOV PY 2005 VL 20 IS 6 BP 525 EP 529 DI 10.1097/01.hco.0000184529.52832.e6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 984HD UT WOS:000233292600009 PM 16234625 ER PT J AU Lu, H Yamaoka, Y Graham, DY AF Lu, H Yamaoka, Y Graham, DY TI Helicobacter pylori virulence factors: facts and fantasies SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE cag pathogenicity island; duodenal ulcer-promoting; Helicobacter pylori; outer inflammatory protein; VacA; virulence ID CAG PATHOGENICITY ISLAND; ENDONUCLEASE-REPLACING GENE; HUMAN DENDRITIC CELLS; VACUOLATING-CYTOTOXIN; PLASTICITY REGION; DUODENAL-ULCER; GASTRIC-CANCER; MONGOLIAN GERBILS; ANTIGEN-BINDING; PROTEIN AB Purpose of review Virulence factors are related to the ability of a microbe to induce disease. True virulence factors must therefore have a disease association, an in-vivo correlate with disease such as increased mucosal inflammation, or both. Recent findings The cytotoxin-associated gene pathogenicity island; the outer membrane inflammatory protein; the duodenal ulcer-promoting gene, and possibly the blood group antigen-binding adhesion, are the only factors that to date qualify as virulence factors. Numerous recent studies have investigated the interaction of vacuolating cytotoxin A or cytotoxin-associated gene A with cells and cell lines in vitro. It remains unclear, however, whether any of the findings, for example, in-vitro experiments showing that vacuolating cytotoxin A affect the regulation of T or B lymphocytes, have an in-vivo counterpart, or play any role in disease pathogenesis. Summary The criteria for a virulence factor include evidence of an association with a disease or a disease surrogate such as the severity of mucosal inflammation, epidemiologic consistency, and biologic plausibility. Confirmation of the proposed mechanism requires elimination of the effect by gene deletion and restoration by complementation. Cytotoxin-associated gene A has been the subject of elegant biochemistry despite lack of evidence that it is involved in pathogenesis. The current focus of research on Helicobacter pylori relates to exploring the biology of Helicobacter pylori, often using systems that only vaguely relate to the in-vivo conditions or to disease pathogenesis. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Graham, DY (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Rm 3A-320,111D 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dgraham@bcm.tmc.edu NR 61 TC 71 Z9 74 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2005 VL 21 IS 6 BP 653 EP 659 DI 10.1097/01.mog.0000181711.04529.d5 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 976DK UT WOS:000232712800004 PM 16220040 ER PT J AU Sanderson, IR Walker, WA AF Sanderson, IR Walker, WA TI Immunology SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material ID TOLL-LIKE RECEPTOR-4; EXPERIMENTAL COLITIS C1 Massachusetts Gen Hosp, Mucosal Immunol Lab, Harvard Clin Nutr Res Ctr, Hillsborough, MA 02129 USA. Univ London Queen Mary Coll, Barts & London Queen Marys Sch Med & Dent, Res Ctr Gastroenterol, London E1 4NS, England. RP Walker, WA (reprint author), Massachusetts Gen Hosp, Mucosal Immunol Lab, Harvard Clin Nutr Res Ctr, 114 13th St,114-3503, Hillsborough, MA 02129 USA. EM wwalker@partners.org NR 9 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2005 VL 21 IS 6 BP 684 EP 686 DI 10.1097/01.mog.0000183665.41753.84 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 976DK UT WOS:000232712800009 PM 16220045 ER PT J AU Niess, JH Reinecker, HC AF Niess, JH Reinecker, HC TI Lamina propria dendritic cells in the physiology and pathology of the gastrointestinal tract SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE chemokines; dendritic cells; inflammatory bowel disease; microbiota ID INFLAMMATORY-BOWEL-DISEASE; MESENTERIC LYMPH-NODES; REGULATORY T-CELLS; PEYERS PATCH; PERIPHERAL-BLOOD; INTESTINAL-MUCOSA; EPITHELIAL-CELLS; CROHNS-DISEASE; INDUCTION; COLITIS AB Purpose of review The mucosal immune system constantly surveys the intestinal microbiota. The outcome of this interaction is determined by the functional properties of dendritic cells, which play a key role in immune response by facilitating antigen sampling and pathogen recognition, as well as innate host defenses. Recent findings Recent advances have provided insight into the diverse mechanisms involved in the acquisition of intestinal antigens and led to a new appreciation of organ-specific functional subspecification of dendritic cell subsets. Dendritic cells are not a rare cell type in the intestine but populate the entire lamina propria of the gastrointestinal tract as an extensive network. Distinct dendritic cell subsets may be associated with specific immune functions in the lamina propria and Peyer's patches. Newly discovered routes of antigen acquisition, such as the formation of transepithelial dendrites, allow dendritic cells direct access to the intestinal lumen to obtain information about commensal and pathogenic microorganisms. Dendritic cells emerge as key regulators of the intestinal immune system with their ability to direct intestine-specific migration and control of T cells. Summary Dendritic cells play a major role in the complex interactions between the gut microbiota and the innate and adaptive immune system, leading to tolerance and immunity. Recent contributions have yielded important information that may aid in the development of novel therapeutic approaches to the treatment of inflammatory bowl disease and intestinal infections and to new immunization strategies. 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 02115 USA. RP Reinecker, HC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 711,55 Fruit St, Boston, MA 02114 USA. EM hans-christian_reinecker@hms.harvard.edu RI Niess, Jan /E-8361-2017 OI Niess, Jan /0000-0001-6902-5650 NR 40 TC 48 Z9 52 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2005 VL 21 IS 6 BP 687 EP 691 DI 10.1097/01.mog.0000181710.96904.58 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 976DK UT WOS:000232712800010 PM 16220046 ER PT J AU Sackstein, R AF Sackstein, R TI The lymphocyte homing receptors: gatekeepers of the multistep paradigm SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE CD44; cutaneous lymphocyte antigen; hematopoietic cell E-/L selectin ligand; homing receptor; lymphocyte; lymphocyte migration; lymphocyte trafficking; multistep paradigm; P-selectin glycoprotein ligand-1; selectin selectin ligand ID T-CELL EXTRAVASATION; SELECTIN GLYCOPROTEIN LIGAND-1; INTEGRIN-MEDIATED ADHESION; HIGH-ENDOTHELIAL VENULES; CD44 VARIANT ISOFORMS; P-SELECTIN; UP-REGULATION; LEUKOCYTE ADHESION; FIRM ADHESION; TRANSENDOTHELIAL MIGRATION AB Purpose of review Lymphocyte trafficking is regulated by adhesion molecules mediating the initial shear-resistant biding of circulating cells to target endothelium (Step 1). This review focuses on the current and emerging perspectives of the biology of theses 'homing receptors.' Recent findings The conventional multistep paradigm holds that leukocyte migration represents a cascade of events, initiated by tethering and rolling interactions of leukocytes on the endothelial surface (Step 1). These interactions are indispensable, required to dampen velocities sufficiently to allow cells to sense the local chemokines and/or other inflammatory signals resulting in activation of integrin adhesiveness (Step 2), with ensuing firm adherence on the vessel wall (Step 3), followed by endothelial transmigration (Step 4). Mechanistic studies now suggest that some effectors of Step 1 interactions themselves activate integrin adhesiveness and trigger transmigration - in some cases by forming complexes with integrins - thus bypassing the need for chemokine signaling. These findings force a reconsideration of the multistep paradigm, and shift focus not to identifying all relevant effectors to Step 1 interactions using adherence assays performed under shear stress to mimic the dynamic conditions of blood flow. Summary Recent findings suggest that homing receptors are not merely molecular brakes. The cross-talk among the homing receptors and integrins opens a new 'avenue' to lymphocyte migration, suggesting that homing receptors may be sufficient alone, in some cases, to perform the function the name implies. C1 Harvard Univ, Sch Med, Skin Dis Res Ctr, Brigham & Womens Hosp,Dept Dermatol, Boston, MA USA. Harvard Univ, Sch Med, Skin Dis Res Ctr, Brigham & Womens Hosp,Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RP Sackstein, R (reprint author), Harvard Univ, Sch Med, Inst Med, 77 Ave Louis Pasteur,Suite 671, Boston, MA 02115 USA. EM rsackstein@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA84156]; NHLBI NIH HHS [HL 73714, R01 HL60528] NR 70 TC 71 Z9 74 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2005 VL 12 IS 6 BP 444 EP 450 DI 10.1097/01.moh.0000177827.78280.79 PG 7 WC Hematology SC Hematology GA 976DN UT WOS:000232713100002 PM 16217160 ER PT J AU Dunner, DL Wohlreich, MM Mallinckrodt, CH Watkin, JG Fava, M AF Dunner, DL Wohlreich, MM Mallinckrodt, CH Watkin, JG Fava, M TI Clinical consequences of initial duloxetine dosing strategies: Comparison of 30 and 60 mg QD starting doses SO CURRENT THERAPEUTIC RESEARCH-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 17th United States Psychiatric and Mental Health Congress CY NOV 18-21, 2004 CL San Diego, CA DE duloxetine; tolerability; safety; efficacy ID MAJOR DEPRESSIVE DISORDER; CONTROLLED TRIAL; PLACEBO; PAROXETINE AB Background: To reduce the risk for treatment-emergent adverse events and increase patient compliance, clinicians frequently prescribe a suboptimal starting dose of antidepressants, with the goal of increasing the dose once the patient has demonstrated tolerability. Objective: The aim of this study was to examine the tolerability and effectiveness associated with an initial week of duloxetine hydrochloride treatment at 30 mg QD and subsequent dose increase to 60 mg QD, compared with a starting dose of 60 mg QD. Methods: In this open-label study, all patients met the criteria for major depressive disorder (MDD) described in the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Patients were required to wash out from previous antidepressant medications for 21 days, and were then randomized to receive duloxetine 30 or 60 mg QD for 1 week. After 1 week, patients receiving duloxetine 30 mg QD had their dose increased to 60 mg QD. Patients returned for assessments at weeks 2, 4, 6, 8, and 12. During the remainder of the 12-week study period, the duloxetine dose could be titrated based on the degree of response from 60 mg QD (minimum) to 120 mg QD (maximum), with 90 mg QD as an intermediate dose. Tolerability was assessed by means of discontinuation rates, spontaneously reported adverse events, changes in vital signs, and laboratory tests. Effectiveness measures included the 17-item Hamilton Rating Scale for Depression (HAMD(17)) total score, HAMD(17) core and Maier subscales, individual HAMD(17) items, the Hamilton Rating Scale for Anxiety total score, and the Clinical Global Impression of Severity. Results: One hundred thirty-seven patients were enrolled (82 women, 55 men; mean age, 42 years; duloxetine 30 mg QD, 67 patients; duloxetine 60 mu OD, 70 patients). The rate of discontinuation due to adverse events did not differ significantly between patients starting duloxetine at 30 mg QD and 60 mg QD (13.4% vs 18.6%). The most frequently reported adverse events across both treatment groups were nausea, headache, dry mouth, insomnia, and diarrhea. In the first week of treatment, patients receiving duloxetine 30 mg QD had a significantly lower rate of nausea compared with patients receiving 60 mg QD (16.4% vs 32.9%; P = 0.03). Over the 12-week acute-treatment phase, patients starting duloxetine treatment at 30 mg QD had a significantly lower rate of nausea compared with patients initiating treatment at 60 mg QD (P = 0.047). Although between-group differences in the HAMD(17) total score were not statistically significant at any visit, patients starting at 30 mg QD experienced significantly less improvement in HAMD(17) core and Maier subscales at week 1 compared with patients starting at 60 mg QD (core, P = 0.044; Maier, P = 0.047). After 2 weeks of treatment, the magnitude of improvement among patients starting at 30 mg QD did not differ significantly from that observed in patients who started treatment at 60 mg QD, and there were no significant between-group differences in effectiveness at any subsequent visit. Conclusions: Results from this open-label study in patients with MDD suggest that starting duloxetine treatment at 30 mg QD for 1 week, followed by escalation to 60 mg QD, might reduce the risk for treatment-emergent nausea in these patients while producing only a transitory impact on effectiveness compared with a starting dose of 60 mg QD. C1 Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Univ Washington, Ctr Anxiety & Depress, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Wohlreich, MM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. EM mwmd@lilly.com NR 25 TC 21 Z9 22 U1 3 U2 6 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0011-393X J9 CURR THER RES CLIN E JI Curr. Ther. Res.-Clin. Exp. PD NOV-DEC PY 2005 VL 66 IS 6 BP 522 EP 540 DI 10.1016/j.curtheres.2005.12.003 PG 19 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 007FN UT WOS:000234954100005 PM 24678074 ER PT J AU Boag, PR Nakamura, A Blackwell, TK AF Boag, PR Nakamura, A Blackwell, TK TI A conserved RNA-protein complex component involved in physiological germline apoptosis regulation in C-elegans SO DEVELOPMENT LA English DT Article DE germline; oocyte; Caenorhabditis elegans; Drosophila; RNA binding; apoptosis; cytokinesis; P body ID NEMATODE CAENORHABDITIS-ELEGANS; STORED MRNP PARTICLES; DNA-DAMAGE; P-GRANULES; RIBONUCLEOPROTEIN COMPLEX; PROCESSING BODIES; CYTOPLASMIC FOCI; HELICASE P54; CELL-DEATH; DROSOPHILA AB Two conserved features of oogenesis are the accumulation of translationally quiescent mRNA, and a high rate of stage-specific apoptosis. Little is understood about the function of this cell death. In C elegans, apoptosis occurring through a specific 'physiological' pathway normally claims about half of all developing oocytes. The frequency of this germ cell death is dramatically increased by a lack of the RNA helicase CGH-1, orthologs of which are involved in translational control in oocytes and decapping-dependent mRNA degradation in yeast processing (P) bodies. Here, we describe a predicted RNA-binding protein, CAR-1, that associates with CGH-1 and Y-box proteins within a conserved germline RNA-protein (RNP) complex, and in cytoplasmic particles in the gonad and early embryo. The CGH-1/CAR-1 interaction is conserved in Drosophila oocytes. When car-1 expression is depleted by RNA interference (RNAi), physiological apoptosis is increased, brood size is modestly reduced, and early embryonic cytokinesis is abnormal. Surprisingly, if apoptosis is prevented car-1(RNAi) animals are characterized by a progressive oogenesis defect that leads rapidly to gonad failure. Elevated germ cell death similarly compensates for lack of the translational regulator CPB-3 (CPEB), orthologs of which function together with CGH-1 in diverse organisms. We conclude that CAR-1 is of critical importance for oogenesis, that the association between CAR-1 and CGH-1 has been conserved, and that the regulation of physiological germ cell apoptosis is specifically influenced by certain functions of the CGH-1/CAR-1 RNP complex. We propose that this cell death pathway facilitates the formation of functional oocytes, possibly by monitoring specific cytoplasmic events during oogenesis. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. RIKEN, Ctr Dev Biol, Lab Germline Dev, Kobe, Hyogo 6500047, Japan. RP Blackwell, TK (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM keith.blackwell@joslin.harvard.edu NR 71 TC 88 Z9 104 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV PY 2005 VL 132 IS 22 BP 4975 EP 4986 DI 10.1242/dev.02060 PG 12 WC Developmental Biology SC Developmental Biology GA 991RQ UT WOS:000233831800007 PM 16221731 ER PT J AU Kenyon, KL Li, DJ Clouser, C Tran, S Pignoni, F AF Kenyon, KL Li, DJ Clouser, C Tran, S Pignoni, F TI Fly SIK-type homeodomain proteins sine oculis and optix partner with different cofactors during eye development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE Gro; Eya; CG30443; Obp; CG8991; Shp; Taf1; Six3; Six6; Six1 ID DROSOPHILA EYE; GENE-EXPRESSION; TRANSCRIPTIONAL REPRESSION; VISUAL-SYSTEM; FAMILY; GROUCHO; MELANOGASTER; ACTIVATION; ENCODES; ABSENT AB Two members from the Six class of homeobox transcription factors, Sine oculis (SO) and Optix, function during development of the fly visual system. Differences in gain-of-function phenotypes and gene expression suggest that these related factors play distinct roles in the formation of the fly eye. However, the molecular nature of their functional differences remains unclear. In this study, we report the identification of two novel factors that participate in specific partnerships with Sine oculis and Optix during photoreceptor neurons formation and in eye progenitor cells. This work shows that different cofactors likely mediate unique functions of Sine oculis and Optix during the development of the fly eye and that the repeated requirement for SO function at multiple stages of eye development reflects the activity of different SO-cofactor complexes. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pignoni, F (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, MEEI 507-509, Boston, MA 02114 USA. EM francesea_pignoni@meei.harvard.edu FU NEI NIH HHS [R01 EY13167, R01 EY013167] NR 45 TC 34 Z9 34 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2005 VL 234 IS 3 BP 497 EP 504 DI 10.1002/dvdy.20442 PG 8 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 979FF UT WOS:000232927100006 PM 15937930 ER PT J AU Zhang, T Tran, S Clouser, C Pignoni, F AF Zhang, T Tran, S Clouser, C Pignoni, F TI Nicastrin controls aspects of photoreceptor neuron specification and differentiation in the Drosophila eye SO DEVELOPMENTAL DYNAMICS LA English DT Article DE neurogenesis; nuclear migration; neuronal differentiation; gamma-secretase; Notch; presenilin; nuclear position; nct; psn ID MEDIATED TRANSMEMBRANE CLEAVAGE; GAMMA-SECRETASE; CELL-FATE; NUCLEAR ACCESS; NOTCH RECEPTOR; PRESENILIN; EXPRESSION; COMPLEX; GENE; COMMUNICATION AB Nicastrin is a component of the Notch signaling pathway involved in proteolytic release of the Notch receptor intracellular domain. It has been postulated that intracellular Notch is required within the nucleus of fly eye progenitor cells to enhance (proneural enhancement) and then repress (lateral inhibition) transcription of proneural genes. We present here an analysis of Nicastrin function during eye development and find that Nicastrin is essential to early photoreceptor neuron development. Nicastrin mutant tissue displays neuronal loss or hyperplasia; these phenotypes can be rescued by targeted expression of an intracellular form of Notch. Thus, nuclear translocation of Notch and its direct regulation of gene expression appear to be critical to proneural enhancement as well as lateral inhibition. In addition, we show that Nicastrin as well as Notch are required to maintain normal R-cell morphology, because the nuclei of mutant photoreceptor neurons cannot maintain their proper position. Thus, Notch signaling plays a role, not only in cell fate specification, but also in differentiation of photoreceptor neurons. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pignoni, F (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM francesea_pignoni@meei.harvard.edu FU NEI NIH HHS [R01 EY013167, R01 EY13167] NR 40 TC 3 Z9 3 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2005 VL 234 IS 3 BP 590 EP 601 DI 10.1002/dvdy.20543 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 979FF UT WOS:000232927100014 PM 16145661 ER PT J AU Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PW AF Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PW TI Insulin resistance, the metabolic syndrome, and incident cardiovascular events in the Framingham Offspring Study SO DIABETES LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; TREATMENT PANEL-III; CORONARY-HEART-DISEASE; GLUCOSE-TOLERANCE; PLASMA-GLUCOSE; SENSITIVITY; RISK; PREDICTOR; ATHEROSCLEROSIS; CHOLESTEROL AB The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMAIR) and by Gutt et al.'s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age-and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5-2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2-2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartilel: 0.5 [0.3-0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3-0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8-2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P <= 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance. C1 Chester Hosp NHS Trust, Dept Med, Chester CH2 1UL, Cheshire, England. Univ Manchester, Dept Med, Manchester M13 9PL, Lancs, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Rutter, MK (reprint author), Chester Hosp NHS Trust, Dept Med, Liverpool Rd, Chester CH2 1UL, Cheshire, England. EM martin.rutter@coch.nhs.uk OI Rutter, Martin/0000-0001-6380-539X FU NHLBI NIH HHS [N01-HC-25195, R01-HL 073272] NR 34 TC 164 Z9 173 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2005 VL 54 IS 11 BP 3252 EP 3257 DI 10.2337/diabetes.54.11.3252 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100026 PM 16249452 ER PT J AU Canani, LH Capp, C Ng, DPK Choo, SGL Maia, AL Nabinger, GB Santos, K Crispim, D Roisemberg, I Krolewski, AS Gross, JL AF Canani, LH Capp, C Ng, DPK Choo, SGL Maia, AL Nabinger, GB Santos, K Crispim, D Roisemberg, I Krolewski, AS Gross, JL TI The fatty acid-binding protein-2 A54T polymorphism is associated with renal disease in patients with type 2 diabetes SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; NEPHROPATHY; MEN; MICROALBUMINURIA; WOMEN; GENE AB The intestinal fatty-acid binding protein-2 (FABP2) gene codes a protein responsible for the absorption of long-chain fatty acids. To test whether FABP2 is a candidate gene for renal disease in patients with type 2 diabetes, a functional A54T polymorphism was genotyped in 1,042 Brazilians with type 2 diabetes. Patients were classified as having normoalbuminuria (urinary albumin excretion [UAE] < 20 mu g/min; n = 529), microalbuminuria (UAE 20-199 mu g/min; n = 217), or proteinuria (UAE > 199 mu g/min min; n = 160). Patients with end-stage renal disease (ESRD) (n = 136) were also included. The prevalence of the TT genotype was higher in patients with renal involvement compared with those with normoalbuminuria (odds ratio [95% CI] 2.4 [1.1-5.4]) following adjustment for type 2 diabetes duration, BMI, hypertension, A1C, and cholesterol levels. The risk was similar considering different stages of renal involvement. In a second independent patient sample (483 type 2 diabetic Caucasians residing in Massachusetts), a significant association was also observed between the TT genotype and proteinuria or ESRD (2.7 [1.0-7.3]; P = 0.048). This study thus provides evidence that FABP2 confers susceptibility to renal disease in type 2 diabetic patients. C1 Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrine, Serv Endocrinol, BR-90035003 Porto Alegre, RS, Brazil. Univ Fed Rio Grande do Sul, Dept Physiol, BR-90035003 Porto Alegre, RS, Brazil. Natl Univ Singapore, Dept Community Occupat & Family Med, Singapore 117548, Singapore. Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore. Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Univ Fed Rio Grande do Sul, Dept Genet, Porto Alegre, RS, Brazil. RP Gross, JL (reprint author), Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Div Endocrine, Serv Endocrinol, Rua Ramiro Barcelos 2350,Predio 12-4 Andar, BR-90035003 Porto Alegre, RS, Brazil. EM jorgegross@terra.com.br RI Maia, Ana Luiza/F-9201-2012; Canani, Luis/G-9686-2012; Gross, Jorge/G-9138-2012; Crispim, Daisy /C-9144-2013; Santos, Katia/D-2683-2014 OI Maia, Ana Luiza/0000-0002-4186-5532; Canani, Luis/0000-0002-1813-4491; Crispim, Daisy /0000-0001-6822-3014; Santos, Katia/0000-0001-5231-2071 FU NIDDK NIH HHS [DK-058549] NR 23 TC 26 Z9 33 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2005 VL 54 IS 11 BP 3326 EP 3330 DI 10.2337/diabetes.54.11.3326 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100035 PM 16249461 ER PT J AU Mlynarski, WM Placha, GP Wolkow, PP Bochenski, JP Warram, JH Krolewski, AS AF Mlynarski, WM Placha, GP Wolkow, PP Bochenski, JP Warram, JH Krolewski, AS TI Risk of diabetic nephropathy in type 1 diabetes is associated with functional polymorphisms in RANTES receptor gene (CCR5) - A sex-specific effect SO DIABETES LA English DT Article ID HIV-1 DISEASE PROGRESSION; PROMOTER POLYMORPHISM; CHEMOKINE SYSTEM; RENAL-DISEASE; IN-VITRO; EXPRESSION; CELLS; TRANSPLANTATION AB Chemokines and their receptors have been implicated in the development of diabetic nephropathy. To determine whether the risk of diabetic nephropathy is influenced by two functional polymorphisms in the regulated upon activation normal T-cell expressed and secreted (RANTES) receptor gene (CCR5), we recruited patients with type 1 diabetes, including 496 case subjects with overt proteinuria or end-stage renal disease and 298 control subjects with normoalbuminuria. Male carriers of the 59029G allele, which is associated with diminished expression of CCR5 on the surface of immunocompetent cells, had significantly higher risk of developing diabetic nephropathy than noncarriers (OR [95% CI] 1.9 [1.2-3.0]). Similarly, male carriers of the 32-bp deletion, which causes truncation of the protein, had significantly higher risk of diabetic nephropathy than noncarriers (2.3 [1.3-4.2]). Combining both polymorphisms, three haplotypes were distinguished: one nonrisk haplotype carrying the 59029A allele and the 32-bp insertion and two risk haplotypes carrying the 59029A allele with the 32-bp deletion and carrying the 59029G allele with the 32-bp insertion. The distribution of these haplotypes differed significantly (P < 0.00001) in men with and without diabetic nephropathy but was not associated with diabetic nephropathy in women. In conclusion, two functional polymorphisms in CCR5 that decrease expression of the RANTES receptor on immunocompetent cells are associated with increased risk of diabetic nephropathy in type 1 diabetes, but only in men. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Med Univ Lodz, Dept Pediat, PL-90131 Lodz, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM andrzej.krolewski@joslin.harvard.edu FU NIDDK NIH HHS [DK41526] NR 30 TC 30 Z9 32 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2005 VL 54 IS 11 BP 3331 EP 3335 DI 10.2337/diabetes.54.11.3331 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100036 PM 16249462 ER PT J AU He, ZH King, GL AF He, ZH King, GL TI Can protein kinase C beta-selective inhibitor, ruboxistaurin, stop vascular complications in diabetic patients? SO DIABETES CARE LA English DT Editorial Material ID INTENSIVE TREATMENT; INSULIN; NEPHROPATHY; PROGRESSION; AMELIORATION; ACTIVATION; MELLITUS; RATS C1 Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP King, GL (reprint author), Joslin Diabet Ctr, Sect Vasc Cell Biol & Complicat, Room M4504,1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslinharvard.edu NR 20 TC 5 Z9 7 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2005 VL 28 IS 11 BP 2803 EP 2805 DI 10.2337/diacare.28.11.2803 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001PH UT WOS:000234548300035 PM 16249561 ER PT J AU Zrebiec, JF AF Zrebiec, JF TI Internet communities - Do they improve coping with diabetes? SO DIABETES EDUCATOR LA English DT Editorial Material ID SUPPORT-GROUPS AB The purpose of this study was to establish and evaluate a Web-based educational and emotional resource for patients with diabetes and their family members. Activity and characteristics of 331 953 user visits were tracked over 74 months, including a survey of user satisfaction. A 2004 survey showed that users were from 37 different countries, with most from the United States (87%) and Canada (4%). The average length of use was 16:44 minutes. Respondents (n = 791) to the satisfaction survey were 71% female, 46% were insulin users, 84% were aged >30 years, 34% had diabetes >10 years, and 39% visited more than 3 times. A total of 74% of all respondents rated participation in the discussion board as having a positive effect on coping with diabetes, and 71% rated participation as helping them to feel more hopeful. A professionally moderated Internet discussion group appears to be a useful strategy for engaging patients with diabetes and increasing perceived ability to cope with diabetes. C1 Joslin Diabet Ctr, Behav & Mental Hlth Unit, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Zrebiec, JF (reprint author), Joslin Diabet Ctr, Behav & Mental Hlth Unit, 1 Joslin Pl, Boston, MA 02215 USA. EM john.zrebiec@joslin.harvard.edu NR 11 TC 22 Z9 22 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2005 VL 31 IS 6 BP 825 EP + DI 10.1177/0145721705282162 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 987BM UT WOS:000233493400005 PM 16288090 ER PT J AU Powell, MP Glover, SH Probst, JC Laditka, SB AF Powell, MP Glover, SH Probst, JC Laditka, SB TI Barriers associated with the delivery of Medicare-reimbursed diabetes self-management education SO DIABETES EDUCATOR LA English DT Article ID HEALTH-CARE; PROGRAMS AB Purpose The purpose of this study was to explore the barriers that practitioners face in providing diabetes self-management education (DSME) to Medicare beneficiaries, with a special focus on barriers faced by rural providers. Methods Using an e-mail survey, Diabetes Control Program Coordinators (DCPCs) in all US states were asked 3 open-ended questions to understand problems with obtaining American Diabetes Association (ADA) recognition for Medicare reimbursement, differences in obtaining ADA recognition by rural and urban facilities, and facility-level barriers to providing DSME to Medicare patients. Using a mail survey administered to half of ADA-recognized diabetes education centers (DECs), information was collected about perceived barriers to providing DSME in all areas and rural areas. Results Most DCPCs believed it was more difficult for rural providers to obtain ADA recognition than for urban providers; the largest barriers were costs and reporting requirements. The top barriers for rural providers mentioned by DCPCs were the shortage of designated specialists, fewer resources, and high application fees for ADA recognition. Barriers identified by DEC respondents facing rural providers include staffing/institutional support, amount of Medicare reimbursement, lack of hours covered, and transportation. DEC respondents providing care in urban areas only were more likely to perceive barriers to providing diabetes education in rural areas than were rural providers. Conclusions Barriers to DSME are perceived to be higher for rural providers than urban providers. Urban providers perceived that many barriers to DSME are greater for rural providers. The ADA application process is perceived as expensive and laborious. Most respondents perceived Medicare reimbursement for DSME as inadequate. C1 Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Deep S Ctr Effectiveness, Birmingham, AL USA. S Carolina Rural Hlth Res Ctr, Columbia, SC USA. Univ S Carolina, Dept Hlth Serv Management & Policy, Columbia, SC 29208 USA. RP Powell, MP (reprint author), Univ Alabama, Dept Hlth Serv Adm, Webb 501,1530 3rd Ave S, Birmingham, AL 35294 USA. EM mppowell@uab.edu NR 19 TC 11 Z9 12 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2005 VL 31 IS 6 BP 890 EP 899 DI 10.1177/0145721705283039 PG 10 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 987BM UT WOS:000233493400011 PM 16288096 ER PT J AU Goodarzi, MO Bryer-Ash, M AF Goodarzi, MO Bryer-Ash, M TI Metformin revisited: re-evaluation of its properties and role in the pharmacopoeia of modern antidiabetic agents SO DIABETES OBESITY & METABOLISM LA English DT Review DE biguanides; glucose; insulin sensitizer; metformin; oral antidiabetic agents ID DEPENDENT DIABETES-MELLITUS; POLYCYSTIC-OVARY-SYNDROME; ACTIVATED PROTEIN-KINASE; ORAL HYPOGLYCEMIC AGENTS; GLYCEMIC CONTROL; SKELETAL-MUSCLE; INSULIN-RESISTANCE; COMBINATION THERAPY; PLUS METFORMIN; BLOOD-PRESSURE AB Background: The usefulness of metformin as an oral antidiabetic agent is widely accepted. However, several other classes of oral antidiabetic agents have been recently introduced, raising the need to evaluate the role of metformin as initial therapy and in combination with these newer drugs for treatment of type 2 diabetes mellitus (DM). Methods: Synthesis of information was preceded by a comprehensive review of the English language literature using Medline. We also reviewed bibliographies of relevant articles. The studies most pertinent to the mechanism of action, efficacy, toxicity and administration of metformin were selected for citation in this review. Results: Metformin acts by increasing tissue sensitivity to insulin, principally in the liver. Beneficial properties of metformin include weight reduction, favourable effects on the lipid profile and the fibrinolytic pathway, and improvement of ovarian function in some insulin-resistant women. It does not cause hyperinsulinaemia or hypoglycaemia. Metformin is effective as monotherapy and, in combination with both insulin secretagogues and thiazolidinediones (TZDs), may obviate the need for insulin treatment. Several fixed-dose combination pills containing metformin and other agents are available. A protocol for the initiation of therapy with contemporary oral agents for type 2 DM is presented, with emphasis on the continuing central role of metformin. Conclusions: Metformin remains a safe and effective agent for the therapy of patients with type 2 DM. It is useful as monotherapy or in combination regimens with the newer insulin secretagogues, TZDs or insulin. It is still in most circumstances the agent of choice for initial therapy of the typical obese patient with type 2 DM and mild to moderate hyperglycaemia. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Gonda Goldschmied Diabet Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Med Ctr, Med Serv, Los Angeles, CA USA. RP Bryer-Ash, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Div Endocrinol Diabet & Hypertens, Cedars Sinai Med Ctr, 900 Vet Ave,Suite 24-130, Los Angeles, CA 90095 USA. EM mbryerash@mednet.ucla.edu NR 124 TC 69 Z9 69 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD NOV PY 2005 VL 7 IS 6 BP 654 EP 665 DI 10.1111/j.1463-1326.2004.00448.x PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971NH UT WOS:000232390600004 PM 16219009 ER PT J AU Fourlanos, S Dotta, F Greenbaum, CJ Palmer, JP Rolandsson, O Colman, PG Harrison, LC AF Fourlanos, S Dotta, F Greenbaum, CJ Palmer, JP Rolandsson, O Colman, PG Harrison, LC TI Latent autoimmune diabetes in adults (LADA) should be less latent SO DIABETOLOGIA LA English DT Review DE autoimmune diabetes; classification; diagnostic criteria; HLA; latent autoimmune diabetes in adults; LADA; Type 1 diabetes ID GLUTAMIC-ACID DECARBOXYLASE; ISLET-CELL ANTIBODIES; GENETIC-CHARACTERISTICS; POSITIVE PATIENTS; INSULIN GENE; HUMAN THYMUS; TYPE-1; MELLITUS; ONSET; AUTOANTIBODIES AB 'Latent autoimmune diabetes in adults' (LADA) is the term coined to describe adults who have a slowly progressive form of autoimmune or type 1 diabetes that can be treated initially without insulin injections. The diagnosis of LADA is currently based on three clinical criteria: (1) adult age at onset of diabetes; (2) the presence of circulating islet autoantibodies, which distinguishes LADA from type 2 diabetes; and (3) insulin independence at diagnosis, which distinguishes LADA from classic type 1 diabetes. The prevalence of LADA in adults presenting with non-insulin-requiring diabetes is approximately 10%. Recognition of LADA expands the concept and prevalence of autoimmune diabetes, but LADA remains poorly understood at both a clinical and research level. In this perspective, we review the nomenclature, diagnostic criteria, genetics, pathology and therapy of LADA, to arrive at recommendations that might advance knowledge and management of this form of diabetes. C1 Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Autoimmun & Transplantat Div, Parkville, Vic 3050, Australia. Univ Siena, Dept Internal Med, Diabet Unit, I-53100 Siena, Italy. Univ Siena, Dept Endocrine & Metab Sci, I-53100 Siena, Italy. Policlin Le Scotte, I-53100 Siena, Italy. Benaroya Res Inst Virginia Mason, Seattle, WA USA. Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Umea Univ, Umea, Sweden. Royal Melbourne Hosp, Dept Endocrinol & Diabet, Parkville, Vic 3050, Australia. RP Harrison, LC (reprint author), Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Autoimmun & Transplantat Div, 1G Royal Parade, Parkville, Vic 3050, Australia. EM harrison@wehi.edu.au RI Dotta, Francesco/H-3788-2012; OI Dotta, Francesco/0000-0003-4947-7478 NR 58 TC 131 Z9 159 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2005 VL 48 IS 11 BP 2206 EP 2212 DI 10.1007/s00125-005-1960-7 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 983QW UT WOS:000233248200004 PM 16193284 ER PT J AU Patti, ME McMahon, G Mun, EC Bitton, A Holst, JJ Goldsmith, J Hanto, DW Callery, M Arky, R Nose, V Bonner-Weir, S Goldfine, AB AF Patti, ME McMahon, G Mun, EC Bitton, A Holst, JJ Goldsmith, J Hanto, DW Callery, M Arky, R Nose, V Bonner-Weir, S Goldfine, AB TI Severe hypoglycaemia post-gastric bypass requiring partial pancreatectomy: evidence for inappropriate insulin secretion and pancreatic islet hyperplasia SO DIABETOLOGIA LA English DT Article DE gastric bypass; GLP1; glucagon-like peptide 1; hypoglycaemia; incretin; insulin; obesity ID NONINSULINOMA PANCREATOGENOUS HYPOGLYCEMIA; TYPE-2 DIABETES-MELLITUS; HYPERINSULINEMIC HYPOGLYCEMIA; WEIGHT AB Aims/hypothesis: Postprandial hypoglycaemia following gastric bypass for obesity is considered a late manifestation of the dumping syndrome and can usually be managed with dietary modification. We investigated three patients with severe postprandial hypoglycaemia and hyperinsulinaemia unresponsive to diet, octreotide and diazoxide with the aim of elucidating the pathological mechanisms involved. Methods: Glucose, insulin, and C-peptide were measured in the fasting and postprandial state, and insulin secretion was assessed following selective intra-arterial calcium injection. Pancreas histopathology was assessed in all three patients. Results: All three patients had evidence of severe postprandial hyperinsulinaemia and hypoglycaemia. In one patient, reversal of gastric bypass was ineffective in reversing hypoglycaemia. All three patients ultimately required partial pancreatectomy for control of neuroglycopenia; pancreas pathology of all patients revealed diffuse islet hyperplasia and expansion of beta cell mass. Conclusions/interpretation: These findings suggest that gastric bypass-induced weight loss may unmask an underlying beta cell defect or contribute to pathological islet hyperplasia, perhaps via glucagon-like peptide 1-mediated pathways. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Univ Copenhagen, Dept Med Physiol, Copenhagen, Denmark. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Patti, ME (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.elizabeth.patti@joslin.harvard.edu RI McMahon, Graham/D-3740-2009; OI McMahon, Graham/0000-0003-4288-6535; Holst, Jens Juul/0000-0001-6853-3805 FU NCRR NIH HHS [M01-RR01032]; NIDDK NIH HHS [DK02795, DK062948, DK44523] NR 13 TC 181 Z9 182 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2005 VL 48 IS 11 BP 2236 EP 2240 DI 10.1007/s00125-005-1933-x PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 983QW UT WOS:000233248200008 PM 16195867 ER PT J AU Utzschneider, KM Carr, DD Tong, J Wallace, TM Hull, RL Zraika, S Xiao, Q Mistry, JS Retzlaff, BM Knopp, RH Kahn, SE AF Utzschneider, KM Carr, DD Tong, J Wallace, TM Hull, RL Zraika, S Xiao, Q Mistry, JS Retzlaff, BM Knopp, RH Kahn, SE TI Resistin is not associated with insulin sensitivity or the metabolic syndrome in humans SO DIABETOLOGIA LA English DT Article DE adiponectin; insulin resistance; insulin sensitivity; leptin; metabolic syndrome; plasminogen-activator inhibitor 1; resistin ID SERUM RESISTIN; ADIPOSITY; OBESE AB Aims/hypothesis: The aim of this study was to further elucidate the relationship between resistin and insulin sensitivity, body fat distribution and the metabolic syndrome in humans. Methodds: We measured plasma resistin levels in 177 non-diabetic subjects (75 male, 102 female; age 32-75 years). BMI, waist circumference, blood pressure, lipids, glucose, plasminogen-activator inhibitor 1 (PAI-1), adiponectin and leptin levels were also measured. The insulin sensitivity index (S-I) was quantified using Bergman's minimal model. Intra-abdominal fat (IAF) and subcutaneous fat (SQF) areas were quantified by CT scan. Presence of metabolic syndrome criteria was determined using the National Cholesterol Education Program Adult Treatment Panel III guidelines. Results: When subjects were divided into categories based on BMI (< or >= 27.5 kg/m(2)) and S-I (< or >= 7x10(-5) min(-1) [pmol/l](-1)), resistin levels did not differ between the lean, insulin-sensitive (n=53, 5.36 +/- 0.3 ng/ml), lean, insulin-resistant (n=67, 5.70 +/- 0.4 ng/ml) and obese, insulin-resistant groups (n=48, 5.94 +/- 0.4 ng/ml; ANOVA p=0.65). Resistin correlated with age (r=-0.22, p < 0.01), BMI (r=0.16, p=0.03) and SQF (r=0.19, p=0.01) but not with S-I (p=0.31) or IAF (p=0.52). Resistin did not correlate with the number of metabolic syndrome criteria or any of the individual metabolic syndrome criteria. In contrast, adiponectin, PAI-1 and leptin each correlated with IAF, SQF and S-I. Additionally, the number of metabolic syndrome criteria correlated with adiponectin (r=-0.32, p < 0.001), leptin (r=0.31, p < 0.001) and PAI-1 (r=0.26, p=0.001). Conclusions/interpretation: In contrast to other adipokines, resistin is only weakly associated with body fat and is unlikely to be a major mediator of insulin resistance or the metabolic syndrome in humans. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Pugent Sound Hlth Care Syst 151, Dept Med,Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98195 USA. Linco Res, St Charles, MO USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98104 USA. RP Utzschneider, KM (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Vet Affairs Pugent Sound Hlth Care Syst 151, Dept Med,Div Metab Endocrinol & Nutr, 1660 S Columbian Way, Seattle, WA 98108 USA. EM kutzschn@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002; Hull, Rebecca/0000-0001-9690-4087 FU NCRR NIH HHS [RR-16066, RR-37]; NHLBI NIH HHS [HL-07028, HL-30086]; NIDDK NIH HHS [DK-02654, DK-17047, DK-35747, DK-35816] NR 10 TC 102 Z9 111 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2005 VL 48 IS 11 BP 2330 EP 2333 DI 10.1007/s00125-005-1932-y PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 983QW UT WOS:000233248200021 PM 16143861 ER PT J AU Arum, SM Dahia, PLM Schneider, K Braverman, LE AF Arum, SM Dahia, PLM Schneider, K Braverman, LE TI A RET mutation with decreased penetrance in the family of a patient with a "sporadic" pheochromocytoma SO ENDOCRINE LA English DT Article DE pheochromocytoma genetics; MEN2; RET mutation ID MEDULLARY-THYROID CARCINOMA; MULTIPLE ENDOCRINE NEOPLASIA; GERM-LINE MUTATIONS; PROTOONCOGENE MUTATIONS; MALIGNANT PROGRESSION; DIAGNOSIS; SUSCEPTIBILITY; PARAGANGLIOMA; CODON-790/791; CANCER AB We present the case of a 38-yr-old man with a sporadic, multifocal pheochromocytorna and paraganglioma who was discovered to carry a Y791F germline mutation in exon 13 of the RET proto-oncogene. This mutation was found in his 65-yr-old mother and his 86-yr-old maternal grandmother. Neither of them had either biochemical evidence of pheochromocytorna or medullary thyroid carcinoma. The patient had a prophylactic thyroidectomy, which revealed mild C-cell hyperplasia. This case brings to discussion several issues: (1) the benefit of screening patients with apparently sporadic pheochromocytomas for genetic mutations; (2) the management of patients and families with "lower-risk" RET mutations; and (3) the possibility that lower-penetrance RET mutations may contribute to the list of causes of familial pheochromocytomas. C1 Boston Univ, Med Ctr, Dept Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Populat Sci, Boston, MA 02115 USA. RP Braverman, LE (reprint author), 88 E Newton St,Evans 201, Boston, MA 02118 USA. EM lewis.braverman@bmc.org NR 24 TC 7 Z9 7 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD NOV PY 2005 VL 28 IS 2 BP 193 EP 198 DI 10.1385/ENDO:28:2:193 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 999PH UT WOS:000234401400010 PM 16388093 ER PT J AU Linghu, E Matthes, K Mino-Kenudson, M Brugge, WR AF Linghu, E Matthes, K Mino-Kenudson, M Brugge, WR TI Feasibility of endoscopic ultrasound-guided OncoGel (ReGel/paclitaxel) injection into the pancreas in pigs SO ENDOSCOPY LA English DT Article ID BIODEGRADABLE BLOCK-COPOLYMERS; ADENOVIRUS ONYX-015; CLINICAL-TRIAL; CARCINOMA; DELIVERY; THERAPY AB Background and Study Aims: OncoGel (ReGel/paclitaxel) is a formulation of the chemotherapeutic drug paclitaxel which can be injected intratumorally, and which was developed for local treatment of solid tumors. Immediately after injection, and in response to body temperature, an insoluble gel depot of OncoGel is formed inside the tissue. Paclitaxel is released continuously from this depot into the adjacent tissue for up to 6 weeks. The aim of this study was to determine the feasibility of injecting OncoGel into pig pancreas under endoscopic ultrasound (EUS) guidance. Methods: Three pigs were sedated by general anesthesia and OncoGel was injected under EUS guidance into the tail of the pancreas using a 22-gauge needle. The end points of this study were the feasibility of the injections, the presence of gross and/or microscopic evidence of inflammation in the pancreas after injection, and how well the animals tolerated the procedure. Results: EUS-guided fine-needle injection of 2 ml of OncoGel into the tail of the pancreas was performed successfully in all three animals. The injections took an average of 4 minutes and an echo-rich intrapancreatic focus was visible by EUS in the tail of the pancreas after injection. The animals were monitored for 4 days (n = 2)or 5 days (n = 1) after the injection and no fever(average body temperature was 37.8 C), vomiting,or anorexia was observed during this period. After the animals had been killed, a depot of OncoGel was observed in the tail of the pancreas, both grossly and histologically. There was no evidence of extravasation of OncoGel Out of the pancreas, and cross-sectional histological studies demonstrated the depot but no evidence of pancreatitis. There was an abrupt transition from the OncoGel depot to normal pancreatic tissue with no sclerotic or necrotic tissue formation. Conclusions: EUS-guided injection of OncoGel into the pancreas was successful in all the pigs and We found no evidence of pancreatitis. This technique is a potential option for minimally invasive local treatment of unresectable pancreatic cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Gastrointestinal Pathol Serv, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM wbrugge@partners.org NR 10 TC 21 Z9 21 U1 0 U2 7 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD NOV PY 2005 VL 37 IS 11 BP 1140 EP 1142 DI 10.1055/s-870224 PG 3 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 981HB UT WOS:000233077200014 PM 16281147 ER PT J AU Duty, SM Ackerman, RM Calafat, AM Hauser, R AF Duty, SM Ackerman, RM Calafat, AM Hauser, R TI Personal care product use predicts urinary concentrations of some phthalate monoesters SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE environment; personal care products; phthalates; urinary metabolites ID PERCUTANEOUS-ABSORPTION; HUMAN SKIN; IN-VIVO; QUANTITATIVE DETECTION; DIETHYL PHTHALATE; METABOLITES; EXPOSURE; INVITRO; RATS; POPULATION AB Phthalates are multifunctional chemicals used in a variety of applications, including personal care products. The present study explored the relationship between patterns of personal care product use and urinary levels of several phthalate metabolites. Subjects include 406 men who participated in an ongoing semen quality study at the Massachusetts General Hospital Andrology Laboratory between January 2000 and February 2003. A nurse-administered questionnaire was used to determine use of personal care products, including cologne, aftershave, lotions, hair products, and deodorants. Phthalate monoester concentrations were measured in a single spot urine sample by isotope dilution-high-performance liquid chromatography coupled to tandem mass spectrometry. Men who used cologne or aftershave within 48 hr before urine collection had higher median levels of monoethyl phthalate (MEP) (265 and 266 ng/mL, respectively) than those who did not use cologne or aftershave (108 and 133 ng/mL, respectively). For each additional type of product used, MEP increased 33% (95% confidence interval, 14-53%). The use of lotion was associated with lower urinary levels of monobutyl phthalate (MBP) (14.9 ng/mL), monobenzyl phthalate (MBzP) (6.1 ng/mL), and mono(2-ethylhexyl) phthalate (MEHP) (4.4 ng/mL) compared with men who did not use lotion (MBP, 16.8 ng/mL; MBzP, 8.6 ng/mL; MEHP, 7.2 ng/mL). The identification of personal care products as contributors to phthalate body burden is an important step in exposure. C1 Harvard Univ, Occupat Hlth Program, Dept Environm Hlth, Sch Publ Hlth, Boston, MA 02115 USA. Simmons Coll, Sch Hlth Studies, Dept Nursing, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Massachusetts Gen Hosp, Vincent Mem Obstet & Gynecol Serv, Androl Lab, Boston, MA USA. Massachusetts Gen Hosp, In Vitro Fertilizat Unit, Boston, MA USA. RP Hauser, R (reprint author), Harvard Univ, Occupat Hlth Program, Dept Environm Hlth, Sch Publ Hlth, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu FU NIEHS NIH HHS [ES09718, ES00002, P30 ES000002, R01 ES009718, T32 ES007069, T32 ES07069] NR 29 TC 119 Z9 127 U1 2 U2 34 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2005 VL 113 IS 11 BP 1530 EP 1535 DI 10.1289/ehp.8083 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 979BI UT WOS:000232916700034 PM 16263507 ER PT J AU Zhou, W Park, S Liu, G Miller, DP Wang, LI Pothier, L Wain, JC Lynch, TJ Giovannucci, E Christiani, DC AF Zhou, W Park, S Liu, G Miller, DP Wang, LI Pothier, L Wain, JC Lynch, TJ Giovannucci, E Christiani, DC TI Dietary iron, zinc, and calcium and the risk of lung cancer SO EPIDEMIOLOGY LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; IOWA WOMENS HEALTH; PROSTATE-CANCER; COLORECTAL-CANCER; COLON-CANCER; DAIRY-PRODUCTS; SUPPLEMENT USE; VITAMIN-D; ASSOCIATIONS; CELLS AB Background: Iron, zinc, and calcium are all involved in the metabolism of reactive oxygen species and may compete with each other for similar binding sites. Dietary intakes of these micronutrients have been associated with altered risks of colorectal, breast, and prostate cancers. Methods: In this Massachusetts hospital-based case-control study of 923 patients with lung cancer and 1125 healthy controls, we studied the associations between dietary iron, zinc, and calcium intake and the risk of lung cancer. Dietary intake was assessed at the time of recruitment (1992 to 2000) with the use of a 126-item semiquantitative food-frequency questionnaire. We analyzed the data using multiple logistic regression models adjusting for smoking history and other potential risk factors. Results: The adjusted odds ratios of dietary iron, zinc, and calcium from food sources were 1.45 (95% confidence interval = 1.03-2.06), 0.71 (0.50-0.99), and 1.64 (1.17-2.29), respectively, for the highest quintile versus the lowest quintile of each micronutrient. Stronger associations between micronutrients and lung cancer risk were found when iron, zinc, and calcium were included together in the same model. The associations between dietary micronutrients intake and lung cancer risk were stronger among current smokers than among former smokers. When we examined intake from supplements as well as diet, associations were similar to those for diet alone. Conclusions: Dietary iron, zinc, and calcium may play an important role in the development of lung cancer, especially among current smokers. These results need to be confirmed in large prospective studies. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA74386, CA90578]; NIEHS NIH HHS [ES/CA 06409, ES00002] NR 34 TC 29 Z9 29 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2005 VL 16 IS 6 BP 772 EP 779 DI 10.1097/01.ede.0000181311.11585.59 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 976CD UT WOS:000232709500009 PM 16222167 ER PT J AU Zhong, WM Reinherz, EL AF Zhong, WM Reinherz, EL TI CD8 alpha alpha homodimer expression and role in CD8 T cell memory generation during influenza virus A infection in mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE influenza A virus; T cell memory; CD8 coreceptor; thymic leukemia antigen ID CLASS-I MOLECULE; CD8 CORECEPTOR FUNCTION; T-CELLS; LYMPHOCYTES-T; BINDING; REPERTOIRE; ACTIVATION; SURVIVAL; SUBSETS; COMPLEX AB While the precise function of CD8 alpha alpha homodimer expression on peripheral T cells is uncertain, recent evidence indicates that it facilitates survival and differentiation of lymphocytic choriomeningitis virus (LCMV)-specific memory CD8 alpha beta T cell precursors in vivo. Here, we show that the CD8 alpha alpha homodimer is also transiently up-regulated on influenza A virus-specific CD8 alpha beta T cells after infection in vivo, temporally correlating with increased levels of the memory T cell development- and survival-related molecules IL-7R alpha and Bcl-2, respectively. Unlike with LCMV, however, deletion of the CD8 alpha alpha enhancer I does not abrogate CD8 alpha alpha homodimer expression or manifest a significant impact on the generation of virus-specific, functional effector and central memory T cells in influenza A virus infection. These results demonstrate that the role of CD8 alpha alpha in the generation of antiviral CD8 T cell memory is complex, presumably because various viral stimuli differentially regulate CD8 alpha alpha expression. Further studies are needed to define those ligands that induce CD8 alpha alpha on T cells during acute viral infections, and the general relevance of this process to memory T cell formation. C1 Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02115 USA. RP Reinherz, EL (reprint author), Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst,Lab Immunobiol, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM ellis_reinherz@dfci.harvard.edu FU NIAID NIH HHS [AI57330] NR 23 TC 17 Z9 17 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2005 VL 35 IS 11 BP 3103 EP 3110 DI 10.1002/eji.200535162 PG 8 WC Immunology SC Immunology GA 987MQ UT WOS:000233522400004 PM 16231286 ER PT J AU Pottala, KM Kalra, MK Ouellette, K Sahani, D Thrall, JH Saini, S AF Pottala, KM Kalra, MK Ouellette, K Sahani, D Thrall, JH Saini, S TI Multidetector-row CT: economics and workflow SO EUROPEAN RADIOLOGY LA English DT Article; Proceedings Paper CT MDCT Symposium Radiologys Powerhouse CY JUN, 2005 CL Berlin, GERMANY DE CT; standardization of protocols; automation; performance metrics ID COMPUTED-TOMOGRAPHY; MULTISLICE CT; ORDER-ENTRY; HELICAL CT; RADIATION; COST; TECHNOLOGY; MANAGEMENT; RADIOLOGY; TRAUMA AB With rapid evolution of multidetector-row CT (MDCT) technology and applications, several factors such as technology upgrade and turf battles for sharing cost and profitability affect MDCT workflow and economics. MDCT workflow optimization can enhance productivity and reduce unit costs as well as increase profitability, in spite of decrease in reimbursement rates. Strategies for workflow management include standardization, automation, and constant assessment of various steps involved in MDCT operations. In this review article, we describe issues related to MDCT economics and workflow. C1 Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Saini, S (reprint author), Emory Univ, Sch Med, Dept Radiol, 1364 Clifton Rd NE, Atlanta, GA 30322 USA. EM ssaini@emory.edu NR 18 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-7994 J9 EUR RADIOL JI Eur. Radiol. PD NOV PY 2005 VL 15 SU 4 BP D149 EP D152 DI 10.1007/s10406-005-0129-2 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 993SV UT WOS:000233976200031 PM 16479666 ER PT J AU Wang, XR Zhang, HX Sun, BX Dai, HL Hang, JQ Eisen, EA Wegman, DH Olenchock, SA Christiani, DC AF Wang, XR Zhang, HX Sun, BX Dai, HL Hang, JQ Eisen, EA Wegman, DH Olenchock, SA Christiani, DC TI A 20-year follow-up study on chronic respiratory effects of exposure to cotton dust SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE byssinosis; chronic airway disease; cotton dust; endotoxin; lung function; occupational epidemiology ID CHRONIC LUNG-DISEASE; TEXTILE WORKERS; PULMONARY-FUNCTION; EXPERIMENTAL CARDROOM; ENDOTOXIN; SYMPTOMS; EPIDEMIOLOGY; FEV(1) AB In order to evaluate chronic effects of long-term exposure to cotton dust on respiratory health, and the role of dust and endotoxin, longitudinal changes in lung function and respiratory symptoms were observed prospectively from 1981 to 2001 in 447 cotton textile workers, along with 472 silk textile controls. The results from five surveys conducted over the 20-yr period are reported, including standardised questionnaires, pre- and post-shift spirometric measurements, work-area inhalable dust sample collections and airborne Gram-bacterial endotoxin analysis. Cotton workers had more persistent respiratory symptoms and greater annual declines in forced expiratory volume in one second (FEV1) and forced vital capacity as compared with silk workers. After exposure cessation, in the final 5-yr period, the rate of FEV1 decline tended to slow in nonsmoking males, but not in nonsmoking females. Workers who reported byssinotic symptoms more persistently suffered greater declines in FEV1. Chronic loss in lung function was more strongly associated with exposure to endotoxin than to dust. In conclusion, the current study suggests that long-term exposure to cotton dust, in which airborne endotoxin appears to play an important role, results in substantial adverse chronic respiratory effects. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Pulm & Crit Care Unit, Boston, MA USA. Univ Massachusetts, Dept Work Environm, Lowell, MA USA. NIOSH, Morgantown, WV USA. Shanghai Putuo Dist Peoples Hosp, Shanghai, Peoples R China. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohpp.harvard.edu RI Lin, Sihao/A-8412-2012 FU NIEHS NIH HHS [ES00002]; NIOSH CDC HHS [R01OH02421] NR 25 TC 50 Z9 51 U1 0 U2 0 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 2005 VL 26 IS 5 BP 881 EP 886 DI 10.1183/09031936.05.00125604 PG 6 WC Respiratory System SC Respiratory System GA 983IH UT WOS:000233224400020 PM 16264050 ER PT J AU Bu, SZ Yamanaka, M Pei, HP Bielawska, A Bielawski, J Hannun, YA Obeid, L Trojanowska, M AF Bu, SZ Yamanaka, M Pei, HP Bielawska, A Bielawski, J Hannun, YA Obeid, L Trojanowska, M TI Dihydrosphingosine 1-phosphate stimulates MMP1 gene expression via activation of ERK1/2-Ets1 pathway in human fibroblasts SO FASEB JOURNAL LA English DT Article DE sphingosine 1-phosphate; ceramide; NF-kappa B; COX-2 ID NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR-BETA; SPHINGOSINE KINASE; TNF-ALPHA; TRANSCRIPTIONAL REGULATION; PLASMA-MEMBRANE; COLLAGEN GENE; UP-REGULATION; TGF-BETA; CANCER AB Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation of important regulators of inter- and intracellular signaling, sphingosine-1 phosphate (S1P), and dihydrosphingosine 1-phosphate (dhS1P). In this study, we investigated the role of SphK1 in the regulation of expression of matrix metalloproteinase 1 (MMP1) in dermal fibroblasts, a key event in regulation of extra cellular matrix. We show that overexpression of SphK1 up-regulated MMP1 protein, MMP1 mRNA, and MMP1 promoter activity, and this action of SphK1 required activation of the ERK1/2-Ets1 and NF-kB pathways. Furthermore, experiments using SphK1 specific siRNA demonstrated that SphK1 is required for the TNF-alpha stimulation of MMP1. Additional data revealed a specific role of dhS1P, and not S1P, as a mediator of SphK1-dependent activation of ERK1/2 and up-regulation of MMP1. The stimulatory effect of dhS1P was sensitive to pertussis toxin, suggesting a possible involvement of a G-protein-coupled receptor. In contrast, S1P, but not dhS1P, stimulated the induction of COX-2, which demonstrated selective actions of these two closely related bioactive lipids. In conclusion, this study describes a novel mode of SphK1 signaling through generation of dhS1P with a key role in mediating transcriptional responses to TNF-alpha. This is the first report of selective function of dhS1P as compared with the better studied S1P. C1 Med Univ S Carolina, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC USA. RP Med Univ S Carolina, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912,POB 250637, Charleston, SC 29425 USA. EM trojanme@musc.edu NR 28 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD NOV PY 2005 VL 19 IS 13 BP 184 EP + DI 10.1096/fj.05-4646.fje PG 20 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 994TC UT WOS:000234053100017 ER PT J AU Kim, A Oberley, LW Oberley, TD AF Kim, A Oberley, LW Oberley, TD TI Induction of apoptosis by adenovirus-mediated manganese superoxide dismutase overexpression in SV-40-transformed human fibroblasts SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 11th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 17-21, 2004 CL St Thomas, VI SP Soc Free Rad Biol & Med DE MnSOD; apoptosis; mitochondria; hydrogen peroxide; superoxide anion; peroxiredoxin; mitochondrial redox; ROS; free radicals ID INCREASES OXIDATIVE STRESS; PROSTATE CARCINOMA-CELLS; REACTIVE OXYGEN; PERMEABILITY TRANSITION; ROS GENERATION; UP-REGULATION; MITOCHONDRIAL; DEATH; TRANSCRIPTION; MECHANISMS AB Although mitochondrial reactive oxygen species (ROS) have been implicated both as an initiator and as an effector of apoptosis, the exact role of mitochondrial ROS has been difficult to establish due to the lack of an appropriate experimental system where ROS could be specifically generated from mitochondria and subsequent effects on cells analyzed. In this study, a manganese superoxide dismutase (MnSOD) activity-mediated apoptosis model was established and characterized. It was shown that despite early increases in the steady-state levels of ROS upon MnSOD overexpression, cellular oxidative damage was decreased significantly at later time points. Alterations in levels of peroxiredoxin (Prxnl) protein preceded the onset of apoptosis after MnSOD overexpression. A time course study demonstrated that increases in MnSOD activity prior to the onset of apoptosis correlated with alterations in the levels of nitration of tyrosine residue(s) of MnSOD protein. A direct correlation between MnSOD activity and the degree of apoptosis was demonstrated using a mutant MnSOD with decreased activity. The current study supports a causative role of mitochondrial ROS leading to the onset of apoptosis. The MnSOD activity-mediated apoptosis model described here could be further utilized to study mitochondrial apoptotic pathways. (c) 2005 Elsevier Inc. All rights reserved. C1 Stanford Univ, Dept Neurol & Neurol Sci, Palo Alto, CA 94304 USA. Univ Iowa, Dept Radiat Oncol, Free Radical & Radiat Biol Program, Iowa City, IA USA. Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Pathol & Lab Med Serv, Madison, WI 53705 USA. RP Oberley, TD (reprint author), Vet Mem Hosp, Room A35,2500 Overlook Terrace, Madison, WI 53705 USA. EM toberley@wisc.edu FU NCI NIH HHS [CA66081] NR 40 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD NOV 1 PY 2005 VL 39 IS 9 BP 1128 EP 1141 DI 10.1016/j.freeradbiomed.2005.06.007 PG 14 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 978JZ UT WOS:000232870700002 PM 16214029 ER PT J AU Sweetser, DA Peniket, AJ Haaland, C Blomberg, AA Zhang, YT Zaidi, ST Dayyani, F Zhao, Z Heerema, NA Boultwood, J Dewald, GW Paietta, E Slovak, ML Willman, CL Wainscoat, JS Bernstein, ID Daly, SB AF Sweetser, DA Peniket, AJ Haaland, C Blomberg, AA Zhang, YT Zaidi, ST Dayyani, F Zhao, Z Heerema, NA Boultwood, J Dewald, GW Paietta, E Slovak, ML Willman, CL Wainscoat, JS Bernstein, ID Daly, SB TI Delineation of the minimal commonly deleted segment and identification of candidate tumor-suppressor genes in del(9q) acute myeloid leukemia SO GENES CHROMOSOMES & CANCER LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; FACTOR-KAPPA-B; PML/RAR-ALPHA; P53 GENE; DEFINITIVE HEMATOPOIESIS; TRANSCRIPTION FACTOR; TRANSGENIC MICE; MOUSE MODEL; EXPRESSION; MUTATIONS AB Deletion of the long arm of chromosome 9, del(9q), is a recurring chromosomal aberration in acute myeloid leukemia (AML) that is frequently associated with t(8;21). The critical gene products affected by del(9q) are unknown but likely cooperate with the AML/ETO fusion gene created by t(8;21) in leukemogenesis. In 43 AML samples with del(9q), we used high-density microsatellite markers to define the commonly deleted region (CDR) to less than 2.4 Mb. We found no homozygous loss at any locus tested. The CDR contains 7 known genes, FRMD3, UBQLN1, GKAP42, KIF27, HNRPK, SLC28A3, and NTRK2, and 4 novel genes, RASEF C9orf103, C9orf64, and C9orf76. In addition, TLE1 and TLE4 are adjacent to the CDR. We per-formed a comprehensive mutational analysis of the coding regions of all these genes. No sequence variations absent in normal controls were seen in more than a single del(9q) AML sample. Expression of 7 of the 10 genes examined was significantly down-regulated in del(19q)AML as compared with the CD34-purified progenitors from normal individuals, a pattern distinct from that seen in AML samples with a normal karyotype. The results of our studies are consistent with a model of tumor suppression mediated by haploinsufficiency of critical genes in del(9q) AML. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Childrens Oncol Grp, Arcadia, CA USA. Univ Oxford, Leukaemia Res Fund Mol Haematol Unit, Oxford, England. UK Med Res Council, London, England. Fred Hutchinson Canc Res Ctr, Dept Pediat Oncol, Seattle, WA 98104 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Mayo Clin, Cytogenet Lab, Rochester, MN USA. Eastern Cooperat Oncol Grp, Boston, MA USA. New York Med Coll, Immunol Lab, Lady Mercy Canc Ctr, Bronx, NY USA. City Hope Natl Med Ctr, Dept Cytogenet, Duarte, CA 91010 USA. SW Oncol Grp, San Antonio, TX USA. Univ New Mexico, Sch Med, Dept Pathol & Cell Biol, Albuquerque, NM USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. RP Sweetser, DA (reprint author), Massachusetts Gen Hosp, Dept Pediat, 55 Fruit St,Jackson 904, Boston, MA 02114 USA. EM dsweetser@partners.org; andy.peniket@orh.nhs.uk OI Boultwood, Jacqueline/0000-0002-4330-2928 FU NCI NIH HHS [CA 32102, CA 13539, CA 98543, CA 30206, CA 60437] NR 54 TC 27 Z9 31 U1 2 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2005 VL 44 IS 3 BP 279 EP 291 DI 10.1002/gcc.20236 PG 13 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 969QA UT WOS:000232248300007 PM 16015647 ER PT J AU Laud, PR Multani, AS Bailey, SM Wu, L Ma, J Kingsley, C Lebel, M Pathak, S DePinho, RA Chang, S AF Laud, PR Multani, AS Bailey, SM Wu, L Ma, J Kingsley, C Lebel, M Pathak, S DePinho, RA Chang, S TI Elevated telomere-telomere recombination in WRN-deficient, telomere dystunctional cells promotes escape from senescence and engagement of the ALT pathway SO GENES & DEVELOPMENT LA English DT Article DE Werner; alternative lengthening of telomeres; cancer; escape from senescence; telomeres ID WERNER-SYNDROME PROTEIN; HOMOLOGOUS RECOMBINATION; IN-VITRO; LACKING TELOMERASE; RECQ HELICASES; SYNDROME GENES; MUTANT P53; HIGH-RATES; DNA; MAINTENANCE AB Werner Syndrome (WS) is characterized by premature aging, genomic instability, and cancer. The combined impact of WRN helicase deficiency and limiting telomere reserves is central to disease pathogenesis. Here, we report that cells doubly deficient for telomerase and WRN helicase show chromosomal aberrations and elevated recombination rates between telomeres of sister chromatids. Somatic reconstitution of WRN function, but not a WRN helicase-deficient mutant, abolished telomere sister chromatid exchange (T-SCE), indicating that WRN normally represses T-SCEs. Elevated T-SCE was associated with greater immortalization potential and resultant tumors maintained telomeres via the alternative lengthening of telomere (ALT) pathway. We propose that the increased incidence of chromosomal instability and cancer in WS relates in part to aberrant recombinations between sister chromatids at telomeres, which facilitates the activation of ALT and engenders cancer-relevant chromosomal aberrations and tumor formation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Univ Laval, Hop Hotel Dieu, Ctr Rech Cancerol, Quebec City, PQ G1R 2J6, Canada. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Chang, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. EM ron_depinho@dfci.harvard.edu; schang@mdanderson.org FU NCI NIH HHS [U01CA84313, R01 CA084628, R01CA84628, U01 CA084313] NR 53 TC 120 Z9 127 U1 0 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2005 VL 19 IS 21 BP 2560 EP 2570 DI 10.1101/gad.1321305 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 981AP UT WOS:000233059700007 PM 16264192 ER PT J AU Wilk, JB Manning, AK Dupuis, J Cupples, LA Larson, MG Newton-Cheh, C Demissie, S DeStefano, AL Hwang, SJ Liu, C Yang, Q Lunetta, KL AF Wilk, JB Manning, AK Dupuis, J Cupples, LA Larson, MG Newton-Cheh, C Demissie, S DeStefano, AL Hwang, SJ Liu, C Yang, Q Lunetta, KL TI No evidence of major population substructure in the Framingham Heart Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 Boston Univ, Sch Med & Publ Hlth, NHLBI, Framingham Heart Study, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Yang, Qiong/G-5438-2014 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 177 BP 286 EP 286 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200184 ER PT J AU Davison, EM Harrison, MM Walhout, AJM Vidal, M Horvitz, HR AF Davison, EM Harrison, MM Walhout, AJM Vidal, M Horvitz, HR TI lin-8, which antagonizes Caenorhabditis elegans Ras-mediated vulval induction, encodes a novel nuclear protein that interacts with the LIN-35 Rb protein SO GENETICS LA English DT Article ID C-ELEGANS; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE; NEGATIVE REGULATOR; RB/E2F PATHWAY; CELL-LINEAGE; THAP DOMAIN; GENES; COMPLEX; EXPRESSION AB Ras-mediated vulval development in C. elegans is inhibited by the functionally redundant sets of class A, B, and C synthetic Multivulva (synMuv) genes. Three of the class B synMuv genes encode an Rb/DP/E2F complex that, by analogy with its mammalian and Drosophila counterparts, has been proposed to silence genes required for vulval specification through chromatin modification and remodeling. Two class A synMuv genes, lin-15A and lin-56, encode novel nuclear proteins that appear to function as a complex. We show that a third class A synMuv gene, lin-8, is the defining member of a novel C. elegans gene family. The LIN-8 protein is nuclear and can interact physically with the product of the class B synMuv gene lin-35, the C. elegans homolog of mammalian Rb. LIN-8 likely acts with the synMuvA proteins LIN-15A and LIN-56 in the nucleus, possibly in a protein complex with the synMuv B protein LIN-35 Rb. Other LIN-8 family members may function in similar complexes in different cells or at different stages. The nuclear localization of LIN-15A, LIN-56, and LIN-8, as well as our observation of a direct physical interaction between class A and class B synMuv proteins, supports the hypothesis that the class A synMuv genes control vulval induction through the transcriptional regulation of gene expression. C1 MIT, Howard Hughes Med Inst, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP MIT, Howard Hughes Med Inst, Dept Biol, Room 68-425,77 Massachusetts Ave, Cambridge, MA 02139 USA. EM horvitz@mit.edu OI Walhout, Marian/0000-0001-5587-3608 FU NIGMS NIH HHS [R01 GM024663, R37 GM024663, GM24663] NR 61 TC 8 Z9 13 U1 0 U2 0 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD NOV PY 2005 VL 171 IS 3 BP 1017 EP 1031 DI 10.1534/genetics.104.034173 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 993PK UT WOS:000233967200013 PM 16020796 ER PT J AU Schaffner, SF Foo, C Gabriel, S Reich, D Daly, MJ Altshuler, D AF Schaffner, SF Foo, C Gabriel, S Reich, D Daly, MJ Altshuler, D TI Calibrating a coalescent simulation of human genome sequence variation SO GENOME RESEARCH LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; SINGLE-NUCLEOTIDE POLYMORPHISMS; CLASS-II REGION; LINKAGE DISEQUILIBRIUM; HAPLOTYPE BLOCKS; RECOMBINATION HOTSPOTS; MEIOTIC RECOMBINATION; GENETIC-VARIATION; SELECTION; PATTERNS AB Population genetic models play an important role in human genetic research, connecting empirical observations about sequence variation with hypotheses about underlying historical and biological causes. More specifically, models are used to compare empirical measures of sequence variation, linkage disequilibrium (LD), and selection to expectations under a "null" distribution. In the absence of detailed information about human demographic history, and about variation in mutation and recombination rates, simulations have of necessity used arbitrary models, usually simple ones. With the advent of large empirical data sets, it is now possible to calibrate Population genetic models with genome-wide data, permitting for the first time the generation of data that are consistent with empirical data across a wide range of characteristics. We present here the first such calibrated model and show that, while still arbitrary, it successfully generates simulated data (for three populations) that closely resemble empirical data in allele frequency, linkage disequilibrium, and population differentiation. No assertion is made about the accuracy of the proposed historical and recombination model, but its ability to generate realistic data meets a long-standing need among geneticists. We anticipate that this model, for which software is Publicly available, and others like it will have numerous applications in empirical studies of human genetics. C1 Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Schaffner, SF (reprint author), Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. EM sfs@broad.mit.edu RI Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011 OI Altshuler, David/0000-0002-7250-4107; NR 30 TC 387 Z9 394 U1 1 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD NOV PY 2005 VL 15 IS 11 BP 1576 EP 1583 DI 10.1101/gr.3709305 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 978QZ UT WOS:000232889400013 PM 16251467 ER PT J AU Mitoma, JY Gauguet, JM Petryniak, B Kawashima, H Schaerli, P Lowe, JB von Andrian, UH Fukuda, M AF Mitoma, JY Gauguet, JM Petryniak, B Kawashima, H Schaerli, P Lowe, JB von Andrian, UH Fukuda, M TI Lymphocyte trafficking in mice deficient in MECA-79 antigen: Analysis of core 1 extension enzyme (beta 1,3-N-acetylglucosaminyltransferase-3) knockout mice SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Burnham Inst, Glycobiol Program, Canc Res Ctr, La Jolla, CA 92037 USA. Univ Michigan, Sch Med, Howard Hughes Med Inst, Dept Pathol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 50 BP 1199 EP 1199 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300063 ER PT J AU Denny, CA Kasperzyk, JL Gorham, KN Kiebish, MA Mukherjee, P Bronson, RT Seyfried, TN AF Denny, CA Kasperzyk, JL Gorham, KN Kiebish, MA Mukherjee, P Bronson, RT Seyfried, TN TI Caloric restriction extends longevity without altering brain glycolipids in Sandhoff disease mice SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Denny, Christine Ann/I-5235-2015 OI Denny, Christine Ann/0000-0002-6926-2020 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 150 BP 1223 EP 1223 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300163 ER PT J AU Silvescu, CI Newburg, DS Reinhold, VN AF Silvescu, CI Newburg, DS Reinhold, VN TI Lactadherin: O-linked and N-linked glycan analysis SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Univ New Hampshire, Dept Biochem & Mol Biol, Durham, NH 03824 USA. Massachusetts Gen Hosp, Div Pediat Gastroenterol & Nutr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 178 BP 1230 EP 1231 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300191 ER PT J AU Burdick, MM Chu, JT Knoblauch, CA Sackstein, R AF Burdick, MM Chu, JT Knoblauch, CA Sackstein, R TI Comparative analysis of sialomucin and glycolipid E-selectin ligand activities: Effects of HCELL knockdown SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Skin Dis Res Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 249 BP 1249 EP 1249 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300262 ER PT J AU Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES D'Amico, D Miller, JW AF Kalayoglu, MV Bula, D Arroyo, J Gragoudas, ES D'Amico, D Miller, JW TI Identification of Chlamydia pneumoniae within human choroidal neovascular membranes secondary to age-related macular degeneration SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 04-09, 2003 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol DE infection; inflammation; age-related macular degeneration ID ENDOTHELIAL GROWTH-FACTOR; PIGMENT EPITHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; MESSENGER-RNA; FACTOR VEGF; RISK-FACTOR; EXPRESSION; INFECTION; ANGIOGENESIS AB Age-related macular degeneration (AMD) is a leading cause of blindness in the United States, and increasing evidence suggests that it is an inflammatory disease. The prokaryotic obligate intracellular pathogen Chlamydia pneumoniae is emerging as a novel risk factor in cardiovascular disease, and recent sero-epidemiological data suggest that C pneumoniae infection is also associated with AMD. In this study, we examined choroidal neovascular membrane (CNV) tissue from patients with neovascular AMD for the presence of C. pneumoniae and determined whether the pathogen can dysregulate the function of key cell types in ways that can cause neovascular AMD. Nine CNV removed from patients with neovascular AMD were examined for the presence of C. pneumoniae by immunohistochemistry (IHC) and polymerase chain reaction (PCR); in addition, we performed PCR on nine non-AMD eyes, and IHC on five non-AMD CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD. CNV, seven non-AMD eyes, and one internal limiting membrane specimen. Finally, human monocyte-derived macrophages and retinal pigment epithelial (RPE) cells were exposed to C. pneumoniae and assayed in vitro for the production of pro-angiogenic immunomodulators (VEGF, IL-8, and MCP-1). C pneumoniae was detected in four of nine AMD CNV by IHC and two of nine AMD CNV by PCR, induced VEGF production by human macrophages, and increased production of IL-8 and MCP-1 by RPE cells. In contrast, none of the 22 non-AMD specimens showed evidence for C. pneumoniae. These data indicate that a pathogen capable of inducing chronic inflammation and pro-angiogenic cytokines can be detected in some AMD CNV, and suggest that infection may contribute to the pathogenesis of AMD. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Angiogenesis Lab, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, 8th Floor,243 Charles St, Boston, MA 02114 USA. EM Joan_Miller@meei.harvard.edu NR 43 TC 47 Z9 52 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD NOV PY 2005 VL 243 IS 11 BP 1080 EP 1090 DI 10.1007/s00417-005-1169-y PG 11 WC Ophthalmology SC Ophthalmology GA 994SR UT WOS:000234052000002 PM 15909160 ER PT J AU Lee, CW Matulonis, UA Castells, MC AF Lee, CW Matulonis, UA Castells, MC TI Rapid inpatient/outpatient desensitization for chemotherapy hypersensitivity: Standard protocol effective in 57 patients for 255 courses SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT ASCO Congress 2005 CY JAN 27-29, 2005 CL Orlando, FL SP ASCO GI DE chemotherapy desensitization; carboplatin hypersensitivity; paclitaxel hypersensitivity ID EPITHELIAL OVARIAN-CANCER; CARBOPLATIN-HYPERSENSITIVITY; TAXOL; PACLITAXEL; EXPERIENCE; CISPLATIN; ANAPHYLAXIS; RETREATMENT; CARCINOMA; ALLERGY AB Objectives. Hypersensitivity reactions (HR) to chemotherapy often prompt permanent discontinuation and deprive the patient of the most active regimen. We investigated the safety and effectiveness of a rapid desensitization protocol used in inpatient and outpatient settings for patients with HR to various chemotherapy and related agents. Methods. A 3-solution, 12-step protocol delivered doubling drug doses by step, infusing the target dose over 5.8 h for inpatient and 3.8 h for outpatient administration. Results. 57 consecutive patients who had moderate to severe HR to chemotherapy were evaluated for desensitization. All 57 patients successfully completed 255 courses of desensitization (127 to carboplatin, 114 to paclitaxel, and 14 to four other agents) where 16 patients received 5 1 courses in the outpatient setting (34 to carboplatin and 17 to paclitaxel). 225 courses (88.2%) were completed without any HR. 18 patients had breakthrough symptoms (BS) over 30 courses (11.8%) that were less severe than their initial HR. After management of breakthrough symptoms, these patients finished all 30 courses and tolerated subsequent desensitizations on a modified protocol. 21 of 26 patients (81%) with HR to carboplatin had positive skin tests to carboplatin. Cancer response to chemotherapy administered by desensitization was within the expected range after 1-3 years of follow-up. Conclusion. The rapid desensitization protocol was safe and effective in both the inpatient and outpatient settings and allowed appropriate patients with moderate to severe HR to continue chemotherapy. This study warrants the incorporation of the protocol into standard clinical practice. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Castells, MC (reprint author), 850 Boylston St,Suite 540, Chestnut Hill, MA 02467 USA. EM mcastells@partners.org NR 29 TC 67 Z9 69 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2005 VL 99 IS 2 BP 393 EP 399 DI 10.1016/j.ygyno.2005.06.028 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 981YO UT WOS:000233124100024 PM 16054201 ER PT J AU Koido, S Nikrui, N Ohana, M Xia, JC Tanaka, Y Liu, CL Durfee, JK Lerner, A Gong, JL AF Koido, S Nikrui, N Ohana, M Xia, JC Tanaka, Y Liu, CL Durfee, JK Lerner, A Gong, JL TI Assessment of fusion cells from patient-derived ovarian carcinoma cells and dendritic cells as a vaccine for clinical use SO GYNECOLOGIC ONCOLOGY LA English DT Review DE DC/OVCA fusion cells; T cell activation; MHC class I-restricted cytotoxicity; preparation of fusion cells for clinical use ID TUMOR-ASSOCIATED ANTIGEN; ANTITUMOR IMMUNITY; ADOPTIVE TRANSFER; AUTOLOGOUS TUMOR; T-LYMPHOCYTES; IN-VITRO; CANCER; EXPRESSION; INDUCTION; STIMULATION AB Purpose. To evaluate a protocol that allowed the successful generation of DC and OVCA cells, fusion of these two cell types and assessment of stimulatory ability of the fusion cells for clinical use. Patients and methods. Ovarian cancer (OVCA) cells and dendritic cells (DC) were isolated or generated from 22 patients with OVCA and Subsequently fused with PEG. The stimulatory ability of fusion cells including T cell proliferation and induction of cytotocic T lymphocytes (CTL) was assessed. In addition, the impact of radiation, freezing and thawing of the fusion cells was evaluated. Results. OVCA cells derived from 22 patients were successfully fused with autologous DC. The created heterokaryons expressed tumor-associated antigens, such as MUCI and CA-125, and DC-derived MHC class II and costimulatory molecules. The fusion cells were functional in stimulating the proliferation of autologous T cells. In addition, CD4 and CD8 T cells derived from patients with ovarian cancer were stimulated by fusion cells and produced IFN-gamma as demonstrated with intracellular staining. Significantly, T cells primed by fusion cells produced MHC class I-dependent lysis of autologous ovarian tumor cells. One cycle of fusion-cell stimulation call maintain the CTL activity up to 25 days. Conclusions. The fusion of human OVCA cells and DC created immunogenic cells capable of stimulating CD4 and CD8 T cells. The effects of the processes required for preparing a vaccine for clinical use, including freezing and thawing and irradiation, do not interfere with the immunogenic properties of the fusion cells. (c) 2005 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Gong, JL (reprint author), Boston Univ, Sch Med, Dept Med, 650 Albany St,X309, Boston, MA 02118 USA. EM jgong@bu.edu FU NCI NIH HHS [R01 CA87057] NR 27 TC 29 Z9 37 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2005 VL 99 IS 2 BP 462 EP 471 DI 10.1016/j.ygyno.2005.07.019 PG 10 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 981YO UT WOS:000233124100035 PM 16137749 ER PT J AU Goff, DC AF Goff, DC TI Pharmacologic implications of neurobiological models of schizophrenia SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE genetics; models; neurobiology; pharmacology; schizophrenia ID GRAY-MATTER VOLUME; NEUROTROPHIC FACTOR; TARDIVE-DYSKINESIA; 1ST-EPISODE SCHIZOPHRENIA; VITAMIN-E; CONVENTIONAL NEUROLEPTICS; DEPOLARIZATION BLOCK; PROGRESSIVE DECREASE; CORTICAL DEVELOPMENT; ANTIPSYCHOTIC-DRUGS AB The dopamine model of schizophrenia has been supplanted by several additional models in order to account for genetic findings, risk factors, course of illness, and the diversity of symptom domains. The increasing number and complexity of potential models for this heterogeneous disorder offer new targets for pharmacologic treatment that differ in their appropriate time points for intervention and in their potential effects on the course of illness. This article reviews relevant neurodevelopmental, biochemical, and neurodegenerative models with respect to potential pharmacologic opportunities. C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Schizophrenia Program, Boston, MA 02114 USA. RP Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM goff@psych.mgh.harvard.edu FU NIMH NIH HHS [K24 MH 02025] NR 80 TC 4 Z9 5 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1067-3229 EI 1465-7309 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2005 VL 13 IS 6 BP 352 EP 359 DI 10.1080/10673220500433262 PG 8 WC Psychiatry SC Psychiatry GA 012PP UT WOS:000235351700003 PM 16373329 ER PT J AU Goldman, DP Shang, BP Hattacharya, J Garber, AM Hurd, M Joyce, GF Lakdawalla, DN Panis, C Shekelle, PG AF Goldman, DP Shang, BP Hattacharya, J Garber, AM Hurd, M Joyce, GF Lakdawalla, DN Panis, C Shekelle, PG TI Consequences of health trends and medical innovation for the future elderly SO HEALTH AFFAIRS LA English DT Article ID UNITED-STATES; CHRONIC DISABILITY; PREVALENCE AB Recent innovations in biomedicine seem poised to revolutionize medical practice. At the same time, disease and disability are increasing among younger populations. This paper considers how these confluent trends will affect the elderly's health status and health care spending over the next thirty years. Because healthier people live longer, cumulative Medicare spending varies little with a beneficiary's disease and disability status upon entering Medicare. On the other hand, ten of the most promising medical technologies are forecast to increase spending greatly. It is unlikely that a "silver bullet" will emerge to both improve health and dramatically reduce medical spending. C1 RAND Corp, Ctr Study Aging, Santa Monica, CA 90406 USA. Stanford Univ, Stanford, CA 94305 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Deloitte & Touche LLP, Los Angeles, CA USA. RAND Corp, Evidence Based Practice Ctr, Santa Monica, CA USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. RP Goldman, DP (reprint author), RAND Corp, Ctr Study Aging, Santa Monica, CA 90406 USA. EM dgoldman@rand.org RI Garber, Alan/F-1476-2010; Lakdawalla, Darius/B-4409-2011 FU NIA NIH HHS [P30AG024968] NR 12 TC 3 Z9 3 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP W5R5 EP W5R17 PG 13 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500053 PM 16186147 ER PT J AU Shekelle, PG Ortiz, E Newberry, SJ Rich, MW Rhodes, SL Brook, RH Goldman, DP AF Shekelle, PG Ortiz, E Newberry, SJ Rich, MW Rhodes, SL Brook, RH Goldman, DP TI Identifying potential health care innovations for the future elderly SO HEALTH AFFAIRS LA English DT Article ID ALZHEIMERS-DISEASE; ATRIAL-FIBRILLATION; RHYTHM CONTROL; VACCINE; THERAPY; CANCER; HUMANS AB We used a method that combined literature review and expert judgment to assess potential medical innovations for older adults. We evaluated innovations in four domains: cardiovascular disease, cancer, the biology of aging, and neurologic disease. The innovations can be categorized by common themes: improved disease prevention, better detection of subclinical or early clinical disease, and treatments for established disease. We report the likelihood, potential impact, and potential cost implications for thirty-four innovations, and we revisit this forecast five years later. Many of the innovations have the potential to greatly affect the costs and outcomes of health care. C1 RAND Corp, Evidence Based Practice Ctr, Santa Monica, CA 90406 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. George Washington Univ, Sch Med, Washington, DC 20052 USA. RAND Res Commun Grp, Santa Monica, CA USA. Univ Washington, Sch Med, St Louis, MO USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Shekelle, PG (reprint author), RAND Corp, Evidence Based Practice Ctr, Santa Monica, CA 90406 USA. EM shekelle@rand.org NR 29 TC 1 Z9 1 U1 0 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP W5R67 EP W5R76 DI 10.1377/hlthaff.W5.R67 PG 10 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500058 PM 16186152 ER PT J AU McGuire, J Bikson, K Blue-Howells, J AF McGuire, J Bikson, K Blue-Howells, J TI How many social workers are needed in primary care? A patient-based needs assessment example SO HEALTH & SOCIAL WORK LA English DT Article DE primary care; social needs; social work staffmg ID SYSTEM AB This study measured levels of self-reported social need in a sample of 684 veterans seen in four primary care clinics of a large Veterans Affairs health care system, using the Social Needs Checklist, and calculated levels of social work staffing to meet these needs. Data were obtained on the presence and severity of 15 areas of social needs, housing status, patient requests for social work services, and current access to other providers for social services. Data were also obtained from primary care social workers who estimated the average time needed to provide basic social work services. Nearly two-thirds of the sample had problems related to finances and personal stress. Three in four patients reported multiple needs. One-third requested social work services. Social work staffing needed for highest acuity patients was estimated to be 61 percent higher than actual staffing available. The study presents a method of estimating staffing levels based on social needs reported by patients. C1 W Los Angeles VA Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Publ Policy, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP McGuire, J (reprint author), W Los Angeles VA Healthcare Ctr, 10H-5,Bldg 500,Room 6651,11030 Wilshire Blvd, Los Angeles, CA 90073 USA. EM James.McGuire@med.va.gov NR 20 TC 7 Z9 7 U1 1 U2 5 PU NATL ASSOC SOCIAL WORKERS PI WASHINGTON PA 750 FIRST ST, NE, STE 700, WASHINGTON, DC 20002-4241 USA SN 0360-7283 J9 HEALTH SOC WORK JI Health Soc. Work PD NOV PY 2005 VL 30 IS 4 BP 305 EP 313 PG 9 WC Social Work SC Social Work GA 984RX UT WOS:000233323100005 PM 16323722 ER PT J AU Noseworthy, PA Malchano, ZJ Ahmed, J Holmvang, G Ruskin, JN Reddy, VY AF Noseworthy, PA Malchano, ZJ Ahmed, J Holmvang, G Ruskin, JN Reddy, VY TI The impact of respiration on left atrial and pulmonary venous anatomy: Implications for image-guided intervention SO HEART RHYTHM LA English DT Article DE electrophysiology; registration; magnetic resonance imaging; electroanatomical mapping; left atrium; pulmonary veins; respiration; atrial fibrillation; ablation ID CATHETER ABLATION; VEIN MORPHOLOGY; FIBRILLATION; TOMOGRAPHY AB BACKGROUND Image-guided intervention using pre-acquired CT/MR 3-dimensional images is an emerging strategy for atrial fibrillation (AF) ablation but may be limited by its use of static images to depict dynamic physiology. The effect of biologic factors such as respiration on the left atrial-pulmonary venous (LA-PV) anatomy is not well understood but is likely to have important implications. Conventional CT/MR imaging is performed during an inspiratory breath-hold, while electroanatomical mapping (EAM) during "quiet" breathing approximates an expiratory breath-hold. This study examined the effects of respiration on LA-PV anatomy and the error introduced by respiration on the integration of EAM with 3D MR imaging. METHODS Pre-procedural MRI angiography was performed at both end-expiration (EXP) and end -inspiration (INSP) in 20 patients undergoing AF catheter ablation. 3D INSP and EXP surface reconstructions of the LA-PVs were compared. In selected pts, EAM data acquired during the ablation procedure (n=7) were integrated with the 3D MRI datasets. RESULTS Qualitative assessment of the INSP and EXP 3D images revealed splaying of the PVs and reduction in PV caliber of the right-sided PVs during held inspiration. After aligning these two datasets, the average surface-to-surface distance calculated by region ranged from 1.99mm (right middle PV) to 3.79mm (left superior PV). Registration of the EAM to the MRI models was better for the EXP dataset (2.30 +/- 0.73mm) than the INSP dataset (3.03 +/- 0.57mm; p=0.004). CONCLUSION There are significant changes in LA-PV anatomy with respiration. MR images acquired during standard held inspiration may introduce unnecessary errors in registration during image-guided intervention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI Unit,Radiol Dept, Boston, MA 02114 USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org NR 13 TC 73 Z9 73 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2005 VL 2 IS 11 BP 1173 EP 1178 DI 10.1016/j.hrthm.2005.08.008 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981QK UT WOS:000233102900002 PM 16253905 ER PT J AU Reddy, VY Neuzil, P Ruskin, JN AF Reddy, VY Neuzil, P Ruskin, JN TI Intracardiac echocardiographic imaging of the left atrial appendage SO HEART RHYTHM LA English DT Editorial Material C1 Harvard Univ, Cardiac Arrhythima Serv, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Na Homolce Hosp, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Cardiac Arrhythima Serv, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM vreddy@partners.org NR 1 TC 17 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 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2005 VL 2 IS 11 BP 1272 EP 1273 DI 10.1016/j.hrthm.2005.06.027 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 981QK UT WOS:000233102900020 PM 16253923 ER PT J AU Heist, EK Ruskin, JN AF Heist, EK Ruskin, JN TI Drug-induced proarrhythmia and use of QTc-prolonging agents: Clues for clinicians SO HEART RHYTHM LA English DT Article; Proceedings Paper CT 25th Annual Scientific Session of the NASPE-Heart-Rhythm-Society CY MAY 19-22, 2004 CL San Francisco, CA SP N Amer Soc Pacing & Electrophysiol Heart Rhythm Soc DE arrhythmia; clinical practice; drug; QT intervals; QTc interval; Torsades de pointes ID TORSADE-DE-POINTES; VENTRICULAR-ARRHYTHMIAS; MACROLIDE ANTIBIOTICS; CELLULAR MECHANISMS; RISK; PROLONGATION; TERFENADINE; MODEL; AMIODARONE; INTERVAL AB Use of drugs with the potential for prolongation of the QTc interval and proarrhythmia is a growing challenge facing clinicians. Many pharmaceutical agents have been denied approval for human use, approved with restrictions and warnings regarding proarrhythmia, or withdrawn from the market based upon arrhythmic risk. Despite known risk factors for QTc prolongation and drug-induced arrhythmia, precise prediction of the risk of torsades de pointes (TdP) in an individual patient remains difficult. The mechanism of drug-induced TdP typically involves use of an agent that blocks the I (Kr) cardiac potassium current, often in combination with risk-aniplifying factors such as high drug levels, reduced drug metabolism, polypharmacy, and patient-specific factors such as gender, age. and genetic polymorphism. For the clinician, an integrated approach involving appreciation of the risk factors for proarrhythmia combined with computer-based risk assessment is the best method for reducing the risk of drug-induced proarrhythmia in clinical practice. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 32 Fruit St,GRB-122, Boston, MA 02114 USA. EM jruskin@partners.org NR 37 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2005 VL 2 SU 2 BP S1 EP S8 DI 10.1016/j.hrthm.2005.07.017 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 982GG UT WOS:000233145500001 PM 16253926 ER PT J AU Johnson, T AF Johnson, T TI The quest for quality SO HOSPITALS & HEALTH NETWORKS LA English DT Editorial Material C1 New York Presbyterian Hosp, New York, NY USA. Amer Hosp Assoc, Chicago, IL 60606 USA. N Mississippi Med Ctr, Tupelo, MS 38801 USA. Massachusetts Gen Hosp, Ctr Performance Excellence, Boston, MA 02114 USA. El Camino Hosp, Mountain View, CA 94040 USA. Lehigh Valley Hosp, Allentown, PA 18105 USA. RP Johnson, T (reprint author), Amer Hosp Assoc, Chicago, IL 60606 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HEALTH FORUM INC PI CHICAGO PA ONE NORTH FRANKLIN ST, CHICAGO, IL 60606 USA SN 1068-8838 J9 HOSP HEALTH NETWORK JI Hosp. Health Netw. PD NOV PY 2005 VL 79 IS 11 BP 67 EP 77 PG 11 WC Health Policy & Services SC Health Care Sciences & Services GA 990TN UT WOS:000233766200020 ER PT J AU Ellinor, PT Yoerger, DM Ruskin, JN MacRae, CA AF Ellinor, PT Yoerger, DM Ruskin, JN MacRae, CA TI Familial aggregation in lone atrial fibrillation SO HUMAN GENETICS LA English DT Article DE heart; genetics; arrhythmia ID RECURRENCE-RISK RATIO; NATURAL-HISTORY; FOLLOW-UP; DISEASE; STROKE; LOCUS; KCNQ1 AB Atrial fibrillation (AF) is the most common clinical arrhythmia and a major risk factor for stroke. To investigate the role of genetic factors in a typical clinical population, we determined the extent of familial aggregation in patients with lone AF. To estimate the relative risk to family members, the prevalence of AF for each class of relative was compared to the prevalence in the comparable age and sex group from the general population. Family members had an increased relative risk of AF compared to the general population (risk ratio; 95% confidence intervals): sons (8.1; 2.0-32), daughters (9.5; 1.3-67), brothers (70; 47-102), sisters (34; 14-80), mothers (4.0; 2.5-6.5) and fathers (2.0; 1.2-3.6). Relatives of probands with lone AF are at a substantially increased risk of developing this arrhythmia suggesting a Mendelian genetic contribution to the etiology of this common trait. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 149 13th St,4th Floor, Charlestown, MA 02129 USA. EM macrae@cvrc.mgh.harvard.edu FU NHLBI NIH HHS [HL-71632, HL-075431, R01 HL075431] NR 30 TC 136 Z9 137 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2005 VL 118 IS 2 BP 179 EP 184 DI 10.1007/s00439-005-0034-8 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 993YN UT WOS:000233996300004 PM 16133178 ER PT J AU McCombie, DB Reisner, AT Asada, HH AF McCombie, DB Reisner, AT Asada, HH TI Laguerre-model blind system identification: Cardiovascular dynamics estimated from multiple peripheral circulatory signals SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE arterial blood pressure; biomedical signal processing; blind system identification; cardiac output; multiple sensor fusion; physiologic monitoring ID GENERALIZED ORTHONORMAL BASIS; CARDIAC-OUTPUT; ALGORITHM; PRESSURE AB This paper presents a method for comparing multiple circulatory waveforms measured at different locations to improve cardiovascular parameter estimation from these signals. The method identifies the distinct vascular dynamics that shape each waveform signal, and estimates the common cardiac How input shared by them. This signal-processing algorithm uses the Laguerre function series expansion for modeling the hemodynamics of each arterial branch, and identifies unknown parameters in these models from peripheral waveforms using multichannel blind system identification. An effective technique for determining the Laguerre base pole is developed, so that the Laguerre expansion captures and quickly converges to the intrinsic arterial dynamics observed in the two circulatory signals, Furthermore, a novel deconvolution method is developed in order to stably invert the identified dynamic models for estimating the cardiac output (CO) waveform from peripheral pressure waveforms. The method is applied to experimental swine data. A mean error of less than 5% with the measured peripheral pressure waveforms has been achieved using the models and excellent agreement between the estimated CO waveforms and the gold standard measurements have been obtained. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP McCombie, DB (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM mccombie@mit.edu; areisner@partners.org; asada@mit.edu FU NIBIB NIH HHS [1 R21 EB002258-01] NR 17 TC 22 Z9 22 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 2005 VL 52 IS 11 BP 1889 EP 1901 DI 10.1109/TBME.2005.856260 PG 13 WC Engineering, Biomedical SC Engineering GA 978UG UT WOS:000232897900011 PM 16285393 ER PT J AU Verma, A Artiushin, S Matsunaga, J Haake, DA Timoney, JF AF Verma, A Artiushin, S Matsunaga, J Haake, DA Timoney, JF TI LruA and LruB, novel lipoproteins of pathogenic Leptospira interrogans associated with equine recurrent uveitis SO INFECTION AND IMMUNITY LA English DT Article ID INDUCED IMMUNE DEVIATION; OUTER-MEMBRANE PROTEIN; AQUEOUS-HUMOR; MOLECULAR CHARACTERIZATION; MAMMALIAN INFECTION; ANTERIOR-CHAMBER; SHARES EPITOPES; SIGNAL PEPTIDES; HORSES; CORNEA AB Recurrent uveitis as a sequela to Leptospira infection is the most common infectious cause of blindness and impaired vision of horses worldwide. Leptospiral proteins expressed during prolonged survival in the eyes of horses with lesions of chronic uveitis were identified by screening a phage library of Leptospira interrogans DNA fragments with eye fluids from uveitic horses. Inserts of reactive phages encoded several known leptospiral proteins and two novel putative lipoproteins, LruA and LruB. LruA was intrinsically labeled during incubation of L. interrogans in medium containing [C-14] palmitic acid, confirming that it is a lipoprotein. lruA and lruB were detected by Southern blotting in infectious Leptospira interrogans but not in nonpathogenic Leptospira biflexa. Fractionation data from cultured Leptospira indicate that LruA and LruB are localized in the inner membrane. Uveitic eye fluids contained significantly higher levels of immunoglobulin A (IgA) and IgG specific for each protein than did companion sera, indicating strong local antibody responses. Moreover, LruA- and LruB-specific antisera reacted with equine ocular components, suggesting an immunopathogenic role in leptospiral uveitis. C1 Univ Kentucky, MH Gluck Equine Res Ctr 325, Dept Vet Sci, Lexington, KY 40546 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Timoney, JF (reprint author), Univ Kentucky, MH Gluck Equine Res Ctr 325, Dept Vet Sci, Lexington, KY 40546 USA. EM jtimoney@uky.edu FU NIAID NIH HHS [AI-34431, R01 AI034431, R01 AI034431-08, R21 AI034431, R29 AI034431] NR 47 TC 42 Z9 47 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7259 EP 7266 DI 10.1128/IAI.73.11.7259-7266.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800021 PM 16239521 ER PT J AU Harris, JB Khan, AI LaRocque, RC Dorer, DJ Chowdhury, F Faruque, ASG Sack, DA Ryan, ET Qadri, F Calderwood, SB AF Harris, JB Khan, AI LaRocque, RC Dorer, DJ Chowdhury, F Faruque, ASG Sack, DA Ryan, ET Qadri, F Calderwood, SB TI Blood group, immunity, and risk of infection with Vibrio cholerae in an area of endemicity SO INFECTION AND IMMUNITY LA English DT Article ID ENTEROTOXIGENIC ESCHERICHIA-COLI; GROUP-O; SUSCEPTIBILITY; BANGLADESH; DETERMINANTS; PROTECTION; ANTIBODIES; RECEPTORS; EPIDEMIC; EFFICACY AB Individuals with blood group O are more susceptible than other individuals to severe cholera, although the mechanism underlying this association is unknown. To assess the respective roles of both intrinsic host factors and adaptive immune responses that might influence susceptibility to infection with Vibrio cholerae, we prospectively followed a cohort of household contacts of patients with cholera in Bangladesh. In this study, we made the novel observation that persons with blood group O were less likely than those with other blood groups to become infected with V. cholerae O1 (odds ratio [OR], 0.67; 95% confidence interval [CI], 0.53 to 0.85; P = 0.008). Consistent with prior studies, however, household contacts with blood group O were more likely to develop severe illness if infected with V. cholerae O1 (OR, 2.3; 95% CI, 0.98 to 5.59; P = 0.05). While blood group O protected significantly against infection with V. cholerae O1, there was no evidence of protection against V. cholerae O139. A multivariate analysis demonstrated that the association between blood group O and protection from infection with V. cholerae O1 was independent of age, gender, and baseline anti-cholera toxin and vibriocidal antibody titers. Based on this epidemiologic evidence, we propose a hypothesis for understanding the association between blood group O and the risk of infection with V. cholerae O1 and O139 as well as the risk of developing severe symptoms once infected. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. ICDDR, B, Ctr Hlth & Populat Res, Dhaka, Bangladesh. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Harris, JB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM jbharris@partners.org FU FIC NIH HHS [D43 TW005572, D43 TW05572, K01 TW007144, K01 TW07144]; NIAID NIH HHS [R01 AI040725, AI40725, T32 AI007061, U01 AI058935, U01 AI58935]; NICHD NIH HHS [K12 HD000850, K12-HD00850] NR 29 TC 72 Z9 77 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7422 EP 7427 DI 10.1128/IAI.73.11.7422-7427.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800042 PM 16239542 ER PT J AU Kudo, T Lu, H Wu, JY Graham, DY Casola, A Yamaoka, Y AF Kudo, T Lu, H Wu, JY Graham, DY Casola, A Yamaoka, Y TI Regulation of RANTES promoter activation in gastric epithelial cells infected with Helicobacter pylori SO INFECTION AND IMMUNITY LA English DT Article ID CYTOKINE MESSENGER-RNA; NF-KAPPA-B; TRANSCRIPTION FACTORS; INTERLEUKIN-8 PRODUCTION; PATHOGENICITY ISLAND; MAP KINASES; C-JUN; EXPRESSION; MUCOSA; GENE AB RANTES, a CC chemokine, plays an important role in the inflammatory response associated with Helicobacter pylori infection. However, the mechanism by which H. pylori induces RANTES expression in the gastric mucosa is unknown. We cocultured gastric epithelial cells with wild-type H. pylori, isogenic oipA mutants, cag pathogenicity island (PAI) mutants, or double knockout mutants. Reverse transcriptase PCR showed that RANTES mRNA was induced by H. pylori and that the expression was both OipA and cag PAI dependent. Luciferase reporter gene assays and electrophoretic mobility shift assays showed that maximal H. pylori-induced RANTES gene transcription required the presence of the interferon-stimulated responsive element (ISRE), the cyclic AMP-responsive element (CRE), nuclear factor-interleukin 6 (NF-IL-6), and two NF-kappa B sites. OipA- and cag PAI-dependent pathways included NF-kappa B -> NF-kappa B/NF-IL-6/ISRE pathways, and cag PAI-dependent pathways additionally included Jun N-terminal kinase -> CRE/NF-kappa B pathways. The OipA-dependent pathways additionally included p38 -> CRE/ISRE pathways. We confirmed the in vitro effects in vivo by examining RANTES mRNA levels in biopsy specimens from human gastric antral mucosa. RANTES mRNA levels in the antral mucosa were significantly higher for patients infected with cag PAI/OipA-positive H. pylori than for those infected with cag PAI/OipA-negative H. pylori or uninfected patients. The mucosal inflammatory response to H. pylori infection involves different signaling pathways for activation of the RANTES promoter, with both OipA and the cag PAI being required for full activation of the RANTES promoter. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. RP Yamaoka, Y (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Med, 2002 Holcombe Blvd,111D Rm 3A-320, Houston, TX 77030 USA. EM yyamaoka@bcm.tmc.edu FU NIAID NIH HHS [K08 AI01763]; NIDDK NIH HHS [DK56338, P30 DK056338, R01 DK062813, R01 DK062813-03, R01 DK62813] NR 39 TC 38 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 2005 VL 73 IS 11 BP 7602 EP 7612 DI 10.1128/IAi.73.11.7602-7612.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800064 PM 16239564 ER PT J AU Isaacs, KL Lewis, JD Sandborn, WJ Sands, BE Targan, SR AF Isaacs, KL Lewis, JD Sandborn, WJ Sands, BE Targan, SR TI State of the art: IBD therapy and clinical trials in IBD SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL DE Crohn's disease; inflammatory bowel disease; pathogenesis; ulcerative colitis ID ACTIVE CROHNS-DISEASE; INFLAMMATORY-BOWEL-DISEASE; DEPENDENT ULCERATIVE-COLITIS; PLACEBO-CONTROLLED TRIAL; TERM FOLLOW-UP; DOUBLE-BLIND; MAINTENANCE TREATMENT; NATURAL-HISTORY; ORAL BUDESONIDE; MULTICENTER TRIAL AB Inflammatory bowel diseases (IBD) encompass Crohn's disease and ulcerative colitis, which are diseases characterized by chronic intestinal inflammation. IBD is believed to result from predisposing genetic and environmental factors (specific antigens and pathogen-associated molecular patterns) acting on the inummoregulatory system and causing inflammation of the gastrointestinal mucosa. IBD may be the result of an imbalance of effector (proinflammatory) and regulatory T-cell responses. Three scenarios indicative of the outcome of this balance exist in animal models: balanced effector and regulatory T cells resulting in a normal controlled inflammation; overactive effector T cells resulting in inflammation and disease; and an absence of regulatory T cells resulting in uncontrolled inflammation and severe, aggressive disease. The number of products under study for the treatment of IBD has increased from 3 products and I target in 1993 to more than 30 products and more than 10 targets in 2005. The number of products under development and continued investigations into the pathogenesis of IBD emphasize the need to expand clinical research efforts in IBD. C1 Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Mayo Clin, Coll Med, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. RP Isaacs, KL (reprint author), Crohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 82 TC 57 Z9 59 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S3 EP S12 DI 10.1097/01.MIB.0000184852.84558.b2 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000002 PM 16254481 ER PT J AU Sandler, RS Lewis, JD Robuck, PR Sands, BE AF Sandler, RS Lewis, JD Robuck, PR Sands, BE TI Funding and grantsmanship SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL DE Crohn's & Colitis Foundation of America; National Institutes of Health; research funding; research grant ID CLINICAL-RESEARCH AB Medical research funding in the United States has 4 predominant sources: the federal government; the pharmaceutical industry; institutions; and private foundations. In each case, the grant application process is the first step in obtaining funding. Successful grant applications are logical, organized, and easy to read. The research question should be both specific and significant. Comprehensive and detailed study methods addressing the study population, timeline, and data collection and management increase the likelihood of obtaining funding. Funding for inflammatory bowel disease preclinical and clinical research is available from the National Institutes of Health and Crohn's & Colitis Foundation of America. C1 Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIDDK, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sandler, RS (reprint author), Cohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S34 EP S37 DI 10.1097/01.MIB.0000184847.54063.fe PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000007 ER PT J AU Sands, BE Abreu, MT Ferry, GD Griffiths, AM Hanauer, SB Isaacs, KL Lewis, JD Sandborn, WJ Steinhart, AH AF Sands, BE Abreu, MT Ferry, GD Griffiths, AM Hanauer, SB Isaacs, KL Lewis, JD Sandborn, WJ Steinhart, AH TI Design issues and outcomes in IBD clinical trials SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL DE biomarker; disease activity index; inflammatory bowel disease; patient subtype ID CROHNS-DISEASE ACTIVITY; INFLAMMATORY-BOWEL-DISEASE; ACTIVE ULCERATIVE-COLITIS; C-REACTIVE PROTEIN; QUALITY-OF-LIFE; ACTIVITY INDEX; 5-AMINOSALICYLIC ACID; PROSPECTIVE MULTICENTER; VALIDATION; SEVERITY AB Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the difrerentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting. Validated, easy-to-use disease activity indices allow interpretation of results across trials. The use of biomarkers as surrogate clinical endpoints provides reproducibility, ease of statistical handling as a continuous variable, and consistent measurement of response to treatment. Despite these potential advantages, biomarkers of disease activity lack specificity and will need to be validated against clinically meaningful outcomes. Careful subject selection, standardization of disease activity indices, and precise outcome measurement are the keys to continued improvement of the inflammatory bowel disease research process. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY USA. Baylor Coll Med, Houston, TX 77030 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Toronto, Toronto, ON, Canada. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Mayo Clin & Mayo Fdn, Coll Med, Rochester, MN USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. RP Sands, BE (reprint author), Crohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 30 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S22 EP S28 DI 10.1097/01.MIB.0000184849.38816.39 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000005 PM 16254479 ER PT J AU Sands, BE Isaacs, KL AF Sands, BE Isaacs, KL TI IBD clinical trials courses principles and practice - A comprehensive overview for health care professionals interested in clinical investigation - Introduction SO INFLAMMATORY BOWEL DISEASES LA English DT Editorial Material C1 Massachusetts Gen Hosp, CCFA Clin Res Alliance, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. Univ N Carolina, Multidisciplinary IBD Ctr, Chapel Hill, NC USA. RP Sands, BE (reprint author), Massachusetts Gen Hosp, CCFA Clin Res Alliance, Boston, MA 02114 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S1 EP S2 DI 10.1097/01.MIB.0000184853.92181.d4 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000001 ER PT J AU Monticelli, S Lee, DU Nardone, J Bolton, DL Rao, A AF Monticelli, S Lee, DU Nardone, J Bolton, DL Rao, A TI Chromatin-based regulation of cytokine transcription in T(h)2 cells and mast cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE differentiation; gene expression; lymphocytes ID LOCUS-CONTROL REGION; HYPERSENSITIVE SITES; COORDINATE REGULATOR; GENE-CLUSTER; MURINE IL-13; TH2 CELLS; T-CELLS; IN-VIVO; C-MAF; DIFFERENTIATION AB T(h)2 cells and mast cells are major sources of IL4, IL5 and IL13, cytokines that mediate immunity against parasites and are also central players in the pathophysiology of asthma, allergy and atopic disease. We asked whether T(h)2 cells and mast cells, which belong to the lymphoid and myeloid lineages, respectively, use different cis-acting regulatory regions to transcribe the cytokine genes. Comparison of DNase I hypersensitivity patterns at the RAD50/IL4/IL13 locus revealed that most hypersensitive sites (HSs) are common to T(h)2 and mast cells, but two regions [conserved non-coding sequence (CNS) 1 and mast cell HSs] show cell type-specific differences. CNS-1, one of the most highly conserved CNS regions in the RAD50/IL13/IL4 locus, displays two strong DNase I HSs in T(h)2 cells but is not DNase I hypersensitive in mast cells, explaining a previous finding that deletion of CNS-1 impairs cytokine expression in T(h)2 cells but not in mast cells. Conversely, two constitutive HSs (mast cell HSs) in the first intron of the IL13 gene are present in mast cells but not in T(h)2 cells; these sites develop early during mast cell differentiation and may have a role in maintaining accessibility of the IL13 locus to high-level transcription in stimulated cells. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA 02115 USA. Univ Milan, Dept Biol & Genet Med Sci, I-20133 Milan, Italy. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM arao@cbr.med.harvard.edu FU NIAID NIH HHS [AI44432] NR 50 TC 20 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2005 VL 17 IS 11 BP 1513 EP 1524 DI 10.1093/intimm/dxh329 PG 12 WC Immunology SC Immunology GA 976QZ UT WOS:000232749600015 PM 16199489 ER PT J AU Franko, DL Dorer, DJ Keel, PK Jackson, S Manzo, MP Herzog, DB AF Franko, DL Dorer, DJ Keel, PK Jackson, S Manzo, MP Herzog, DB TI How do eating disorders and alcohol use disorder influence each other? SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating disorders; alcohol abuse; alcohol use disorder ID RESEARCH DIAGNOSTIC-CRITERIA; BULIMIA-NERVOSA; ANOREXIA-NERVOSA; DSM-III; PSYCHIATRIC COMORBIDITY; SUBSTANCE USE; PREDICTORS; MORTALITY; RELIABILITY; RECOVERY AB Objective: Although eating disorders and alcohol use disorder (AUD) are known to co-occur, the influence of one on the other has not been studied. Method: In a prospective study, women diagnosed with either anorexia nervosa (AN; n = 136) or bulimia nervosa (BN; n = 110) were interviewed and assessed for Research Diagnostic Criteria (RDC) AUD every 6-12 months over 8.6 years. Results: Over one fourth of the sample (n = 66 [27%]) reported a lifetime history of AUD. Ten percent of the study subjects (n = 24) developed AUD over the course of the study. AUD did not influence recovery from either eating disorder. Poor psychosocial functioning and history of substance use predicted prospective onset of an episode of AUD for both diagnostic groups. Unique predictors for AUD for women with AN were depression, overconcern with body image, and vomiting. Recovery from AUD was predicted by group therapy and hospitalization (women with AN) and individual therapy and exercise (women with BN). Conclusion: The influence of eating disorders on AUD appears to be greater than the reverse. A substantial number of patients who initially present with an eating disorder develop alcohol problems over the course of time, suggesting that the risk is an ongoing one that should be monitored by clinicians. (c) 2005 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Harvard Eating Disorders Ctr, Boston, MA 02114 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Franko, DL (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Harvard Eating Disorders Ctr, 2 Fruit St,AW 6900, Boston, MA 02114 USA. EM d.franko@neu.edu FU NIAAA NIH HHS [R03 AA 13614-0198]; NIMH NIH HHS [R01 MH38333-10] NR 32 TC 40 Z9 43 U1 5 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2005 VL 38 IS 3 BP 200 EP 207 DI 10.1002/eat.20178 PG 8 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 983CR UT WOS:000233209200002 PM 16216020 ER PT J AU Bast, RC Badgwell, D Lu, Z Marquez, R Rosen, D Liu, J Baggerly, KA Atkinson, EN Skates, S Lokshin, A Menon, U Jacobs, I Lu, K AF Bast, RC Badgwell, D Lu, Z Marquez, R Rosen, D Liu, J Baggerly, KA Atkinson, EN Skates, S Lokshin, A Menon, U Jacobs, I Lu, K TI New tumor markers: CA125 and beyond SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE ovarian cancer; tumor markers; CA125; early detection ID EPITHELIAL OVARIAN-CANCER; COLONY-STIMULATING FACTOR; TRANSVAGINAL ULTRASONOGRAPHY; MONOCLONAL-ANTIBODY; TAXOL RESISTANCE; CA 125; SERUM; CARCINOMA; DIAGNOSIS; CA-125 AB A variety of biomarkers have been developed to monitor growth of ovarian cancer and to detect disease at an early interval. CA125 (MUC16) has provided a useful serum tumor marker for monitoring response to chemotherapy, detecting disease recurrence, distinguishing malignant from benign pelvic masses, and potentially improving clinical trial design. A rapid fall in CA125 during chemotherapy predicts a favorable prognosis and could be used to redistribute patients on multiarmed randomized clinical trials. Several studies now document that CA125 can serve as a surrogate marker for response in phase 11 trials. Serial measurement of CA125 might also provide a useful marker for monitoring stabilization of disease with cytostatic targeted therapeutic agents. The greatest potential for serum markers may be in detecting ovarian cancer at an early stage. A rising CA125 can be used to trigger transvaginal sonography (TVS) in a small fraction of patients. An algorithm has been developed that calculates risk of ovarian cancer based on serial CA125 values and refers patients at highest risk for TVS. Use of the algorithm is currently being evaluated in a trial with 200,000 women in the UK that will test critically the ability of a two-stage screening strategy to improve survival in ovarian cancer. Whatever the outcome, as 20% of ovarian cancers have little or no expression of CA125, additional serum markers will be required to detect all patients in an initial phase of screening. More than 30 serum markers have been evaluated alone and in combination with CA125 by different investigators. Some of the most promising include: HE4, mesothelin, M-CSF, osteopontin, kallikrein(s), and soluble EGF receptor. Two proteomic approaches have been used: one examines the pattern of peaks on mass spectroscopy and the other uses proteomic analysis to identify a limited number of critical markers that can be assayed by more conventional methods. Both approaches are promising and require further development. Several groups are placing markers on multiplex platforms to permit simultaneous assay of multiple markers with very small volumes of serum. Mathematical techniques are being developed to analyze combinations of marker levels to improve sensitivity and specificity. In the future, serum markers should improve the sensitivity of detecting recurrent disease as well as facilitate earlier detection of ovarian cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Translat Res, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Pittsburgh Canc Inst, Pittsburgh, PA 15213 USA. UCL, Inst Womens Hlth, London, England. RP Bast, RC (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Translat Res, 1515 Holcombe Blvd,Unit 355, Houston, TX 77030 USA. EM rbast@mdanderson.org RI Menon, Usha/C-4716-2008; Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013; Lu, Zhen/E-5221-2015 OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624; FU NCI NIH HHS [CA83639] NR 50 TC 276 Z9 282 U1 2 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 2005 VL 15 SU 3 BP 274 EP 281 DI 10.1111/j.1525-1438.2005.00441.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 991HQ UT WOS:000233803600015 PM 16343244 ER PT J AU Penson, RT Campos, SM Seiden, MV Krasner, C Fuller, AF Goodman, A Roche, M Willman, A Muzikansky, A Matulonis, UA AF Penson, RT Campos, SM Seiden, MV Krasner, C Fuller, AF Goodman, A Roche, M Willman, A Muzikansky, A Matulonis, UA TI A phase II study of fixed dose rate gemcitabine in patients with relapsed mullerian tumors SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE chemotherapy; clinical trials; ovarian cancer ID ADVANCED OVARIAN-CANCER; CELLULAR PHARMACOLOGY; CHEMOTHERAPY; PLATINUM; PLASMA; AGENT AB Gemcitabine ( 2',2'- difluorodeoxycytidine) is a novel purine analog with clinical activity against ovarian cancer. Accumulation of gemcitabine triphosphate ( dFdCTP) increases in a linear fashion with prolonged infusions of gemcitabine, and there is a strong relationship between intracellular accumulation of dFdCTP and DNA damage. Women with ovarian, fallopian tube, or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. Patients could not have received more than four prior lines of chemotherapy and had to have measurable or evaluable disease. Gemcitabine 800 mg/ m(2) administered by intravenous infusion at 10 mg/ m(2)/ min ( fixed dose rate [ FDR]) on days 1 and 8 of a 21- day schedule. Twenty- eight patients with a median age 60 ( range, 40 - 77) years were treated. Although 43% were Eastern Cooperative Oncology Group 0, 50% had liver metastases. Eighty- eight cycles of therapy were delivered ( median 2 [ range, 1 - 6]). Five of the first ten patients treated at 800 mg/ m 2 could not receive day 8 FDR- gemcitabine because of neutropenia, and the starting dose was reduced to 700 mg/ m(2). Even at this dose there was cumulative hematologic toxicity resulting in dose reductions. Vomiting, mucositis, diarrhea, allergy, rash, fever, and alopecia were mild. In 28 patients, there was only one partial response ( 4%, 95% CI 0 - 18%) and median time to progression was 1.7 ( interquartile range, 1.2 - 3.9) months. FDR- gemcitabine 700 mg/ m(2) administered by intravenous infusion at an FDR of 10 mg/ m(2)/ min had minimal activity against heavily pretreated recurrent tumors of mullerian origin. The optimal dose and schedule of gemcitabine is yet to be defined in this population. C1 Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Div Gynecol Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Ctr Biostat, Boston, MA 02114 USA. RP Penson, RT (reprint author), Massachusetts Gen Hosp, Dept Med, Div Hematol & Oncol, Yawkey 9066,55 Fruit St, Boston, MA 02114 USA. EM rpenson@partners.org NR 20 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 2005 VL 15 IS 6 BP 1035 EP 1041 DI 10.1111/j.1525-1438.2005.00482.x PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 984FZ UT WOS:000233289200005 PM 16343179 ER PT J AU Hurwitz, MD Kaplan, ID Hansen, JL Prokopios-Davos, S Topulos, GP Wishnow, K Manola, J Bornstein, BA Hynynen, K AF Hurwitz, MD Kaplan, ID Hansen, JL Prokopios-Davos, S Topulos, GP Wishnow, K Manola, J Bornstein, BA Hynynen, K TI Hyperthermia combined with radiation in treatment of locally advanced prostate cancer is associated with a favourable toxicity profile SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; toxicity; thermometry; prostate cancer ID THERAPY ONCOLOGY GROUP; RADIOTHERAPY; TRIAL; CARCINOMA; GOSERELIN AB Purpose: Hyperthermia is used to treat several pelvic tumours. An important step in establishing a broader role for hyperthermia in treatment of prostate cancer is verification of an acceptable toxicity profile. In this report, short- and long-term toxicity profiles of a completed phase II trial of transrectal ultrasound hyperthermia combined with radiation in treatment of locally advanced prostate cancer are presented. Methods and materials: Thirty-seven patients enrolled on a phase II study of external beam radiation +/- androgen suppression with two transrectal ultrasound hyperthermia treatments were assessed for short- and long-term toxicity. Prostatic and anterior rectal wall temperatures were monitored. Rectal wall temperatures were limited to 40 degrees C (19 patients), 41 degrees C (three patients) and 42 degrees C (15 patients). Univariate logistic regression was used to estimate the log hazard of developing NCI CTC Grade 2 toxicity based on temperature parameters. Hazard ratios, 95% confidence intervals, p-values for statistical significance of each parameter and proportion of variability explained for each of the parameters were calculated. Results: Median follow-up was 42 months. Both short- and long-term GI toxicity were limited to grade 2 or less. Acute grade 2 proctitis was greater for patients with allowable rectal wall temperature of >40 degrees C. Eleven of 18 patients in this group had acute grade 2 proctitis vs three of 19 patients with rectal wall temperatures limited to 40 degrees C (p = 0.004). Long-term grade 2 GI and GU toxicity occurred in 5% and 19% of patients. No late grade 3 or greater toxicity occurred. Late GI and GU toxicity were not associated with the allowable rectal wall temperature. Conclusion: Transrectal ultrasound hyperthermia combined with radiation for treatment of advanced clinically localized prostate cancer is safe and well tolerated. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Urol, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Hurwitz, MD (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM mhurwitz@lroc.harvard.edu FU NCI NIH HHS [P-01 CA 31303] NR 14 TC 15 Z9 16 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD NOV PY 2005 VL 21 IS 7 BP 649 EP 656 DI 10.1080/02656730500331967 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 981VE UT WOS:000233115300005 PM 16278168 ER PT J AU Friedrich, C Holtkamp, N Cinatl, J Sakuma, S Mautner, VF Wellman, S Michaelis, M Henze, G Kurtz, A Driever, PH AF Friedrich, C Holtkamp, N Cinatl, J Sakuma, S Mautner, VF Wellman, S Michaelis, M Henze, G Kurtz, A Driever, PH TI Overexpression of Midkine in malignant peripheral nerve sheath tumor cells inhibits apoptosis and increases angiogenic potency SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE MPNST; NF1; midkine; apoptosis; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; NEUROFIBROMATOSIS TYPE-1; SCHWANN-CELLS; EXPRESSION; PLEIOTROPHIN; NEUROBLASTOMAS; TRANSFORMATION; TUMORIGENESIS; DELETIONS; MITOGEN AB Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue tumors arising sporadically although more frequently in patients with Neurofibromatosis type 1. Prognosis remains dismal as chemo- and radiotherapy have not been shown to be successful. The heparin-binding growth factor, Midkine (MK), is implicated in the tumorigenesis of benign and plexiform neurofibromas, and thereof arising MPNSTs. MK is mitogenic, anti-apoptotic, angiogenic and can promote tumorigenicity in several cell types. Thus, we investigated the role of MK in malignant biology and tumorigenicity in MPNSTs by stable transfection into MPNST cell lines. Overexpression of MK in the MPNST cell line, S462, increased cell viability and protected cells from apoptosis under serum deprivation, but did not induce proliferation. In addition, MK-transfected S462 cells were partially protected from vincristine-induced cell death. Conditioned medium of MK-transfected S462 cells was a potent mitogen for human umbilical venous endothelial cells. Furthermore, MK overexpression in S462 cells was accompanied by higher levels of VEGF mRNA. Yet, stable overexpression of MK in S462 as well as in ST88-14 cells was not sufficient to promote xenograft tumor growth in nude mice. However, increasing survival and enhanced angiogenic potency of MK-transfected S462 cells highlight the importance of developing specific inhibitors for MK as part of new therapeutic concepts against MPNSTs. C1 Charite Univ Med Berlin, Dept Pediat Oncol Hematol, D-13353 Berlin, Germany. Charite Univ Med Berlin, Inst Neuropathol, D-13353 Berlin, Germany. Univ Frankfurt, Inst Med Virol, D-60596 Frankfurt, Germany. Cell Signals Inc, Tsurumi Ku, Yokohama, Kanagawa 2300046, Japan. Univ Klinikum Hamburg Eppendorf, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurosurg Lab, Charlestown, MA 02129 USA. RP Driever, PH (reprint author), Charite Univ Med Berlin, Dept Pediat Oncol Hematol, Campus Virchow Hosp,Augustenburger Pl 1, D-13353 Berlin, Germany. EM pablo.hernaiz@charite.de RI Wellmann, Sven/A-2771-2017 NR 37 TC 17 Z9 22 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD NOV PY 2005 VL 27 IS 5 BP 1433 EP 1440 PG 8 WC Oncology SC Oncology GA 974FT UT WOS:000232577400030 PM 16211240 ER PT J AU Gentile, MA Chuang, SK Dodson, TB AF Gentile, MA Chuang, SK Dodson, TB TI Survival estimates and risk factors for failure with 6 x 5.7-mm implants SO INTERNATIONAL JOURNAL OF ORAL & MAXILLOFACIAL IMPLANTS LA English DT Article DE dental implants; implant survival; oral surgery; risk factors; short implants ID OF-THE-LITERATURE; SUPPORTED OVERDENTURES; DENTAL IMPLANTS; ITI IMPLANTS; BONE-GRAFTS; SUCCESS; MAXILLA AB Purpose: Short dental implants facilitate prosthetic restoration in the setting of limited alveolar bone height. The study objectives were to (1) estimate the 1-year survival of Bicon 6 x 5.7-mm implants, (2) compare the 1-year survival of 6 x 5.7-mm implants with that of non-6 x 5.7-mm implants, and (3) identify risk factors associated with implant failure. Materials and Methods: A retrospective cohort study design was used. The sample was composed of patients who had received at least one 6 x 5.7-mm implant. Predictor variables were categorized as demographic, health status, anatomic, implant-specific, prosthetic, perioperative, and reconstructive. The outcome variable was implant failure, defined as explantation. Appropriate descriptive, bivariate, and multivariate survival statistics were computed. Results: The sample was composed of 35 patients in whom 172 implants had been placed (45 of which were 6 x 5.7-mm). The 1-year survival rates for 6 x 5.7-mm and non-6 x 5.7-mm implants were 92.2% and 95.2%, respectively (P =.76). After adjusting for covariates in a multivariate model, implant size was not associated with failure (P =.95). Discussion: The comparable survival estimates for 6 x 5.7-mm implants and non-6 x 5.7-mm implants in this study suggested that 6 x 5.7-mm implants can become osseointegrated and bear a functional load after placement. Conclusions: The survival of 6 x 5.7-mm implants was comparable to that of non-6 x 5.7-mm implants. C1 Univ N Carolina, Sch Dent, Dept Oral & Maxillofacial Surg, Chapel Hill, NC USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP POB 67376,Chestnut Hill Stn, Chestnut Hill, MA 02467 USA. EM schuang@hsph.harvard.edu FU NIDCR NIH HHS [K24 DE00448] NR 42 TC 42 Z9 48 U1 1 U2 1 PU QUINTESSENCE PUBLISHING CO INC PI HANOVER PARK PA 4350 CHANDLER DRIVE, HANOVER PARK, IL 60133 USA SN 0882-2786 EI 1942-4434 J9 INT J ORAL MAX IMPL JI Int. J. Oral Maxillofac. Implants PD NOV-DEC PY 2005 VL 20 IS 6 BP 930 EP 937 PG 8 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 996HK UT WOS:000234164800013 PM 16392351 ER PT J AU Shih, HA Betensky, RA Dorfman, MV Louis, DN Loeffler, JS Batchelor, TT AF Shih, HA Betensky, RA Dorfman, MV Louis, DN Loeffler, JS Batchelor, TT TI Genetic analyses for predictors of radiation response in glioblastoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE glioblastoma; genetics; predictors; radiotherapy response ID GROWTH-FACTOR RECEPTOR; RECURSIVE PARTITIONING ANALYSIS; PROGNOSTIC-SIGNIFICANCE; MALIGNANT GLIOMA; GRADE ASTROCYTOMAS; P53 MUTATIONS; MULTIFORME; SURVIVAL; EXPRESSION; EGFR AB Purpose: Radiotherapy (RT) for patients with glioblastoma improves survival and is recommended for nearly all patients with this diagnosis. However, the response to RT is variable in this patient population. Prior studies have suggested that underlying genetic alterations in the tumor may account for some of this treatment-related heterogeneity. It has been previously reported that epidermal growth factor receptor (EGFR) gene amplification and TP53 mutation correlate with the response to RT in patients with glioblastoma. Methods and Materials: We sought to identify molecular markers that could predict the response to RT, progression-free survival after RT, and overall survival among 75 glioblastoma patients treated with RT at a single institution. Genetic analyses assessed EGFR amplification, TP53 mutations, CDKN2A/p16 deletion, and losses of chromosomes 1p, 10q, and 19q. Results: Unlike previous reports, no association of EGFR amplification with response to RT, progression-free survival, or overall survival was found. Moreover, no association was found between these endpoints and the other genetic alterations assayed (TP53 mutation, CDKN2A/p16 deletion, loss of heterozygosity 1p, loss of heterozygosity 10q, and loss of heterozygosity 19q). However, in accordance with recent observations that the prognostic effects of genetic alterations in glioblastoma may depend on patient age, we observed age-dependent prognostic effects of TP53 and CDKN2A/p16 alterations in our patient population. For patients 2:57 years old, those harboring TP53 mutations had a decreased overall survival compared with patients without TP53 mutations. Similarly, deletion of CDKN2A/p16 in patients >= 57 years was associated with decreased progression-free survival after RT and a trend toward a shorter time to progression after RT compared with similar patients without the deletion. Conclusion: These data contrast with previous studies regarding the significant prognostic effect of EGFR with respect to RT response. Although our observations regarding the age-dependent prognostic effects of TP53 and CDKN2A/p16 are consistent with a prior report regarding these alterations, the present results should be considered preliminary, given the small sample size. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Stephen E & Catherine Pappas Ctr Neurooncol, Dept Neurol, Yawkey 9E,55 Fruit St,Cox 3, Boston, MA 02114 USA. EM tbatchelor@partners.org FU NCI NIH HHS [CA57683] NR 34 TC 16 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2005 VL 63 IS 3 BP 704 EP 710 DI 10.1016/j.ijrob.2005.03.059 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 971UZ UT WOS:000232411600007 PM 15978739 ER PT J AU Kupelian, P Thames, H Levy, L Horwitz, E Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A Kuban, D AF Kupelian, P Thames, H Levy, L Horwitz, E Martinez, A Michalski, J Pisansky, T Sandler, H Shipley, W Zelefsky, M Zietman, A Kuban, D TI Year of treatment as independent predictor of relapse-free survival in patients with localized prostate cancer treated with definitive radiotherapy in the PSA era SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE localized prostate cancer; radiotherapy; biochemical relapse-free survival; year of therapy; stage migration ID RADICAL PROSTATECTOMY; STAGE MIGRATION AB Purpose: To study the use of the year of therapy as an independent predictor of outcomes, serving as a proxy for time-related changes in therapy and tumor factors in the treatment of prostate cancer. Accounting for these changes would facilitate the retrospective comparison of outcomes for patients treated in different periods. Methods and Materials: Nine institutions combined data on 4,537 patients with Stages T1 and T2 adenocarcinoma of the prostate who had a pretherapy prostate-specific antigen (PSA) level and biopsy Gleason score, and who had received >= 60 Gy external beam radiotherapy without neoadjuvant androgen deprivation or planned adjuvant androgen deprivation. All patients were treated between 1986 and 1995. Two groups were defined: those treated before 1993 (Yr <= 92) vs. 1993 and after (Yr >= 93). Patients treated before 1993 had their follow-up truncated to make the follow-up time similar to that for patients treated in 1993 and after. Therefore, the median follow-up time was 6.0 years for both groups (Yr <= 92 and Yr >= 93). Two separate biochemical failure endpoints were used. Definition A consisted of the American Society for Therapeutic Radiology Oncology endpoint (three PSA rises backdated, local failure, distant failure, or hormonal therapy). Definition B consisted of PSA level greater than the current nadir plus two, local failure, distant failure, or hormonal therapy administered. Multivariate analyses for factors affecting PSA disease-free survival (PSA-DFS) rates using both endpoints were performed for all cases using the following variables: T stage (T1b, T1c, T2a vs. T2b, T2c), pretreatment PSA (continuous variable), biopsy Gleason score (continuous variable), radiation dose (continuous variable), and year of treatment (continuous variable). The year variable (defined as the current year minus 1960) ranged from 26 to 35. To evaluate the effect of radiation dose, the multivariate analyses were repeated with the 3,897 cases who had received < 72 Gy using the same variables except for radiation dose. Results: For all 4,537 patients, the 5- and 8-year PSA-DFS estimate using definition A (ASTRO consensus definition) was 60% and 55%, respectively. The 8-year PSA-DFS estimate for Yr < 93 vs. Yr 2:93 was 52% vs. 57%, respectively (p < 0.001). In the subgroup of patients receiving < 72 Gy, the 8-year PSA-DFS estimate for Yr < 93 vs. Yr >= 93 was 52% and 55%, respectively (p = 0.004). The differences in PSA-DFS rates in the different subgroups were similar when definition B was used. The multivariate analyses for all 4,537 cases with either PSA-DFS definition revealed T stage (p < 0.001), pretherapy PSA level (p < 0.001), Gleason score (p < 0.001), radiation dose (p < 0.001), and year of treatment (p < 0.001) to be independent predictors of outcomes. The multivariate analyses restricted to the 3,897 cases receiving < 72 Gy still revealed year of treatment to be an independent predictor of outcomes (p < 0.001), in addition to T stage (p < 0.001), pretherapy PSA level (p < 0.001), and Gleason score (p < 0.001). Conclusions: Independent of tumor stage, radiation dose, failure definition, and follow-up parameters, the year in which RT was performed was an independent predictor of outcomes. These findings indicate a more favorable presentation of localized prostate cancer in current years that is not necessarily reflected in the patients' PSA levels or Gleason scores. This phenomenon is probably related to a combination of factors, such as screening, increased patient awareness leading to earlier biopsies and earlier diagnosis, more aggressive pretherapy staging, and unrecognized improvements in therapy, but perhaps also to changing tumor biology. Outcomes predictions should be based on contemporaneous series. Alternatively, the year of therapy could be incorporated as a variable in outcomes analyses of localized prostate cancer patients treated in different periods within the PSA era. (c) 2005 Elsevier Inc. C1 MD Anderson Canc Ctr, Dept Radiat Oncol, Orlando, FL 32806 USA. Cleveland Clin Fdn, Dept Radiat Oncol, Cleveland, OH 44195 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Oncol & Biostat, Houston, TX 77030 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. William Beaumont Hosp, Dept Radiat Oncol, Detroit, MI USA. Washington Univ, Sch Med, Dept Radiat Oncol, Mallinckrodt Inst Radiol, St Louis, MO USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. RP Kupelian, P (reprint author), MD Anderson Canc Ctr, Dept Radiat Oncol, 1400 S Orange Ave, Orlando, FL 32806 USA. EM kupelian@orhs.org NR 11 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2005 VL 63 IS 3 BP 795 EP 799 DI 10.1016/j.ijrobp.2005.03.029 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 971UZ UT WOS:000232411600020 PM 15925452 ER PT J AU Kepka, L DeLaney, TF Suit, HD Goldberg, SI AF Kepka, L DeLaney, TF Suit, HD Goldberg, SI TI Results of radiation therapy for unresected soft-tissue sarcomas SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the European-Society-for-Therapeutic-Radiology-and-Oncology (ESTRO 23) CY OCT 24-28, 2004 CL Amsterdam, NETHERLANDS SP European Soc Therapeut Radiol & Oncol DE soft-tissue sarcoma; definitive radiotherapy; radiotherapy complications ID POSTOPERATIVE RADIOTHERAPY; PROGNOSTIC FACTORS; EXTREMITIES; IRRADIATION; MANAGEMENT; SURVIVAL; SURGERY; TIME AB Purpose: Definitive radiotherapy is uncommonly used in the management of soft-tissue sarcoma (STS). The purpose of the study was to evaluate the results of radiotherapy for unresected STSs treated in a single institution. Methods and Materials: Between 1970 and 2001, 112 patients with STSs underwent radiotherapy for gross disease. Locations of the tumor were 43% in the extremities, 26% retroperitoneal, 24% in the head and neck, and 7% in the truncal wall. Histologic grades were 11% G1 and 89% G2 to G3. Median size of tumor at radiotherapy was 8 cm (range, 1-30 cm). Median radiation dose was 64 Gy (range, 25-87.5 Gy). Twenty percent of patients received chemotherapy. Local control (LC), disease-free survival (DFS), and overall survival (OS) rates were evaluated in univariate (log-rank) and then multivariate (Cox model) analysis to determine prognostic factors for STS. Results: Median follow-up for patients is 139 months (range, 30-365 months). The 5-year actuarial LC, DFS, and OS were 45%, 24%, and 35%, respectively. Tumor size at radiotherapy and radiation dose influenced LC, DFS, and OS in univariate analysis. LC at 5 years was 51%, 45%, and 9% for tumors less than 5 cm, 5 to10 cm, and greater than 10 cm, respectively. Patients who received doses of less than 63 Gy had 5-year LC, DFS, and OS rates of 22%, 10%, and 14%, respectively, compared with 5-year LC, DFS, and OS rates of 60%, 36%, and 52%, respectively, for patients who received doses of 63 Gy or more. AJCC stage was related to the OS and DFS without statistically significant influence on LC. Use of chemotherapy, histologic grade, age, and location did not influence results. In multivariate analysis, LC was related to total dose (p = 0.02), T size at radiotherapy (p = 0.003), and AJCC stage (p = 0.04); DFS was related to total dose (p = 0.007), T size at radiotherapy (p = 0.01), and AJCC stage (p < 0.0001); and OS was related to AJCC stage (p = 0.0001) and total dose (p = 0.002), but not to T size, at radiotherapy. Major radiotherapy complications were noted in 14% of patients; 27% of patients who received doses of 68 Gy or more had these complications compared with 8% of patients treated with doses of less than 68 Gy. Conclusions: Definitive radiotherapy for STS should be considered in clinical situations where no acceptable surgical option is available. Higher radiation doses yield superior tumor control and survival. A rise in complications occurs in patients who receive doses of 68 Gy or more, which provides a therapeutic window for benefit in these patients. (c) 2005 Elsevier Inc. C1 M Curie Sklodowska Mem Canc Ctr, Dept Radiat Oncol, PL-02781 Warsaw, Poland. Inst Oncol, Dept Radiat Oncol, PL-02781 Warsaw, Poland. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. RP Kepka, L (reprint author), M Curie Sklodowska Mem Canc Ctr, Dept Radiat Oncol, Roentgena 5, PL-02781 Warsaw, Poland. EM lucynak@coi.waw.pl NR 25 TC 57 Z9 65 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2005 VL 63 IS 3 BP 852 EP 859 DI 10.1016/j.ijrobp.2005.03.004 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 971UZ UT WOS:000232411600027 PM 16199316 ER PT J AU Zhou, P Ng, AK Silver, B Li, SG Hua, L Mauch, PM AF Zhou, P Ng, AK Silver, B Li, SG Hua, L Mauch, PM TI Radiation therapy for orbital lymphoma SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE orbital lymphoma; radiation; MALT; follicular; local control ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; MARGINAL ZONE; OCULAR ADNEXA; RADIOTHERAPY; TISSUE; CLASSIFICATION; TUMORS AB Purpose: To describe radiation techniques and evaluate outcomes for orbital lymphoma. Methods and Materials: Forty-six patients (and 62 eyes) with orbital lymphoma treated with radiotherapy between 1987 and 2003 were included. The majority had mucosa-associated lymphoid tissue (48%) or follicular (30%) lymphoma. Seventeen patients had prior lymphoma at other sites, and 29 had primary orbital lymphoma. Median follow-up was 46 months. Results: The median dose was 30.6 Gy; one-third received < 30 Gy. Electrons were used in 9 eyes with disease confined to the conjunctiva or eyelid, and photons in 53 eyes with involvement of intraorbital tissues to cover entire orbit. Local control rate was 98% for all patients and 100% for those with indolent lymphoma. Three of the 26 patients with localized primary lymphoma failed distantly, resulting in a 5-year freedom-from-distant-relapse rate of 89%. The 5-year disease-specific and overall survival rates were 95% and 88%, respectively. Late toxicity was mainly cataract formation in patients who received radiation without lens block. Conclusions: A dose of 30 Gy is sufficient for indolent orbital lymphoma. Distant relapse rate in patients with localized orbital lymphoma was lower than that reported for low-grade lymphoma presenting in other sites. Orbital radiotherapy can be used for salvage of recurrent indolent lymphoma. (c) 2005 Elsevier Inc. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. RP Zhou, P (reprint author), BROF, 375 Longwood Ave, Boston, MA 02215 USA. EM pzhou@partners.org NR 24 TC 31 Z9 33 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2005 VL 63 IS 3 BP 866 EP 871 DI 10.1016/j.ijrobp.2005.03.005 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 971UZ UT WOS:000232411600029 PM 15925453 ER PT J AU Paganetti, H AF Paganetti, H TI Changes in tumor cell response due to prolonged dose delivery times in fractionated radiation therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 16-20, 2005 CL Denver, CO SP Amer Soc Therapeut Radiol & Oncol DE dose rate; cell survival; prolonged dose delivery ID DAMAGE; RADIOSENSITIVITY; RADIOTHERAPY; RECOVERY; REPAIR; LETHAL; LINES; IMRT AB Purpose: Dynamic radiation therapy, such as intensity-modulated radiation therapy, delivers more complex treatment fields than conventional techniques. The increased complexity causes longer dose delivery times for each fraction. The cellular damage after a full treatment may depend on the dose rate, because sublethal radiation damage can be repaired more efficiently during prolonged dose delivery. The goal of this study was to investigate the significance of this effect in fractionated radiation therapy. Methods and Materials: The lethal/potentially lethal model was used to calculate lesion induction rates for repairable and nonrepairable lesions. Dose rate effects were analyzed for 9 different cell lines (8 human tumor xenografts and a C3H10T1/2 cell line). The effects of single-fraction as well as fractionated irradiation for different dose rates were studied. Results: Significant differences can be seen for dose rates lower than about 0.1 Gy/min for all cell lines considered. For 60 Gy delivered in 30 fractions, the equivalent dose is reduced by between 1.3% and 12% comparing 2 Gy delivery over 30 min per fraction with 2 Gy delivery over 1 min per fraction. The effect is higher for higher doses per fraction. Furthermore, the results show that dose rate effects do not show a simple correlation with the alpha/beta ratio for ratios between 3 Gy and 31 Gy. Conclusions: If the total dose delivery time for a treatment fraction in radiation therapy increases to about 20 min, a correction for dose rate effects may have to be considered in treatment planning. Adjustments in effective dose may be necessary when comparing intensity-modulated radiation therapy with conventional treatment plans. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Paganetti, H (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM hpaganetti@partners.org NR 12 TC 40 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 2005 VL 63 IS 3 BP 892 EP 900 DI 10.1016/j.ijrobp.2005.07.953 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 971UZ UT WOS:000232411600033 PM 16199319 ER PT J AU Wright, JL Lin, DW Dewan, P Montgomery, RB AF Wright, JL Lin, DW Dewan, P Montgomery, RB TI Tumor lysis syndrome in a patient with metastatic, androgen independent prostate cancer SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE hormone refractory; prostate cancer; tumor lysis syndrome ID DOCETAXEL; MITOXANTRONE; PREDNISONE AB Tumor lysis syndrome (TLS) is an uncommon, but well described, clinical entity that typically occurs following chemotherapy in patients with rapidly growing hematological malignancies. It is rarely described in patients with solid tumors. We report a case of TLS in a patient with metastatic adenocarcinoma of the prostate after treatment with paclitaxel chemotherapy. C1 Univ Washington, Med Ctr, Dept Med, Div Oncol, Seattle, WA 98195 USA. Univ Washington, Dept Urol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care, Seattle, WA USA. RP Montgomery, RB (reprint author), Univ Washington, Med Ctr, Dept Med, Div Oncol, Hlth Sci Bldg,1959 NE Pacific,SP 1301,Box 358280, Seattle, WA 98195 USA. EM rbmontgo@u.washington.edu NR 7 TC 10 Z9 11 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0919-8172 J9 INT J UROL JI Int. J. Urol. PD NOV PY 2005 VL 12 IS 11 BP 1012 EP 1013 DI 10.1111/j.1442-2042.2005.01196.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 985WG UT WOS:000233408800017 PM 16351664 ER PT J AU Frederickson, CJ Cuajungco, MP Frederickson, CJ AF Frederickson, CJ Cuajungco, MP Frederickson, CJ TI Is zinc the link between compromises of brain perfusion (excitotoxicity) and Alzheimer's disease? SO JOURNAL OF ALZHEIMERS DISEASE LA English DT Article ID AMYLOID PRECURSOR PROTEIN; CEREBRAL CORTICAL-NEURONS; OXIDE SYNTHASE INHIBITORS; CLOSED-HEAD INJURY; NITRIC-OXIDE; TRANSGENIC MICE; APOLIPOPROTEIN-E; EXTRACELLULAR ACCUMULATION; MITOCHONDRIAL DYSFUNCTION; CEREBROSPINAL-FLUID AB Prior brain injury is a major risk factor in the development of Alzheimer's disease. This is true for traumatic brain injury, stroke or ischemic brain injury, and (more speculatively) for brain injury resulting from the hypo-perfusion-reperfusion in cardiac arrest or cardiac bypass surgery and even hypo- or hypertension. Here we propose that the release of excess, toxic, "floods" of free zinc into the brain that occurs during and after all excitotoxic brain injury is a key factor that sets the stage for the later development of Alzheimer's disease. Rapid and aggressive administration of zinc buffering compounds to patients suffering brain injury may therefore not only ameliorate the acute injury but might also reduce the risk of subsequent development of Alzheimer's disease. C1 NeuroBioTex Inc, Galveston, TX 77550 USA. Univ Texas, Sch Med, Galveston, TX 77550 USA. Harvard Univ, Sch Med, Dept Otol & Laryngologist, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. RP Frederickson, CJ (reprint author), NeuroBioTex Inc, Galveston, TX 77550 USA. EM cathy@neurobiotex.com RI Cuajungco, Math/B-2647-2008 OI Cuajungco, Math/0000-0003-0749-9564 FU NINDS NIH HHS [NS40215, NS41682, NS42882] NR 99 TC 17 Z9 17 U1 0 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1387-2877 J9 J ALZHEIMERS DIS JI J. Alzheimers Dis. PD NOV PY 2005 VL 8 IS 2 BP 155 EP 160 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 021XE UT WOS:000236018400008 PM 16308484 ER PT J AU Abadie, JM Allison, KH Black, DA Garbin, J Saxon, AJ Bankson, DD AF Abadie, JM Allison, KH Black, DA Garbin, J Saxon, AJ Bankson, DD TI Can an immunoassay become a standard technique in detecting oxycodone and its metabolites? SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID DRUG-ABUSE DEATHS; OPIATE IMMUNOASSAYS; URINE; INVOLVEMENT C1 Univ Washington, Med Ctr, Dept Lab Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Pathol & Lab Med, Seattle, WA 98195 USA. RP Abadie, JM (reprint author), Univ Washington, Med Ctr, Dept Lab Med, 1959 NW Pacific St,NW 120,Box 357110, Seattle, WA 98195 USA. EM judeabadie@medscape.com NR 13 TC 8 Z9 8 U1 2 U2 4 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 2005 VL 29 IS 8 BP 825 EP 829 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 986KP UT WOS:000233448800011 PM 16374942 ER PT J AU Jordan, AS Wellman, A Edwards, JK Schory, K Dover, L MacDonald, M Patel, SR Fogel, RB Malhotra, A White, DP AF Jordan, AS Wellman, A Edwards, JK Schory, K Dover, L MacDonald, M Patel, SR Fogel, RB Malhotra, A White, DP TI Respiratory control stability and upper airway collapsibility in men and women with obstructive sleep apnea SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE pharyngeal critical closing pressure; loop gain; gender ID HYPERCAPNIC VENTILATORY RESPONSE; GENDER-DIFFERENCES; HEALTHY-MEN; NREM SLEEP; RESISTANCE; OBESITY; AGE; AROUSAL; ADULTS; SIZE AB Obstructive sleep apnea (OSA) is two to three times more common in men as in women. The mechanisms leading to this difference are currently unclear but could include gender differences in respiratory stability [loop gain (LG)] or upper airway collapsibility [pharyngeal critical closing pressure (Pcrit)]. The aim of this study was to compare LG and Pcrit between men and women with OSA to determine whether the factors contributing to apnea are similar between genders. The first group of 11 men and 11 women were matched for OSA severity (mean +/- SE apnea-hypopnea index = 43.8 +/- 6.1 and 44.1 +/- 6.6 events/h). The second group of 12 men and 12 women were matched for body mass index (BMI; 31.6 +/- 1.9 and 31.3 +/- 1.8 kg/m(2), respectively). All measurements were made during stable supine non-rapid eye movement sleep. LG was determined using a proportional assist ventilator. Pcrit was measured by progressively dropping the continuous positive airway pressure level for three to five breaths until airway collapse. Apnea-hypopnea index-matched women had a higher BMI than men (38.0 +/- 2.4 vs. 30.0 +/- 1.9 kg/m(2); P = 0.03), but LG and Pcrit were similar between men and women (LG: 0.37 +/- 0.02 and 0.37 +/- 0.02, respectively, P = 0.92; Pcrit: 0.35 +/- 0.62 and -0.18 +/- 0.87, respectively, P = 0.63). In the BMI-matched subgroup, women had less severe OSA during non-rapid eye movement sleep (30.9 +/- 7.4 vs. 52.5 +/- 8.1 events/h; P = 0.04) and lower Pcrit (-2.01 +/- 0.62 vs. 1.16 +/- 0.83 cmH(2)O; P = 0.005). However, LG was not significantly different between genders (0.38 +/- 0.02 vs. 0.33 +/- 0.03; P = 0.14). These results suggest that women may be protected from developing OSA by having a less collapsible upper airway for any given degree of obesity. C1 Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Jordan, AS (reprint author), Brigham & Womens Hosp, Sleep Disorders Res Program, BIDMC, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM ajordan@rics.bwh.harvard.edu OI Jordan, Amy/0000-0001-8561-9766; Patel, Sanjay/0000-0002-9142-5172 FU NCRR NIH HHS [M01 RR001032, M01 RR-02635, M01 RR002635, RR-01032]; NHLBI NIH HHS [F32 HL-072560-01, F32 HL072560, P50 HL-60292, P50 HL060292, R01 HL-48531, R01 HL048531, R01 HL073146, R01 HL073146-02]; NIA NIH HHS [K23 AG024837, K23 AG024837-02] NR 49 TC 71 Z9 75 U1 0 U2 5 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 NOV PY 2005 VL 99 IS 5 BP 2020 EP 2027 DI 10.1152/japplphysiol.00410.2004 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 974QZ UT WOS:000232607800051 PM 15994243 ER PT J AU Gilliam, LK Brooks-Worrell, BA Palmer, JP Greenbaum, CJ Pihoker, C AF Gilliam, LK Brooks-Worrell, BA Palmer, JP Greenbaum, CJ Pihoker, C TI Autoimmunity and clinical course in children with type 1, type 2, and type 1.5 diabetes SO JOURNAL OF AUTOIMMUNITY LA English DT Article; Proceedings Paper CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc DE autoantibody; human leukocyte antigen; type 1 diabetes; type 2 diabetes; type 1.5 diabetes ID GLUTAMIC-ACID DECARBOXYLASE; AUTOANTIBODIES; RELATIVES; GAD65; YOUTH AB Aims: Both type 1 (T1D) and type 2 diabetes (T2D) are increasing in incidence in children; often an admixture of T1D and T2D features are present at diagnosis. We examined the relationship between diabetes autoantibodies (DAA), human leukocyte antigen (HLA), and clinical course in subjects grouped by clinical diabetes type. Methods: Subjects 8-18 years old with T1D, T2D, and mixed clinical features (T1.5D), were studied at diagnosis. DAA were measured in all subjects; a subset of subjects underwent HLA genotyping. Clinical course was followed in 84% of subjects for 47.9 + 8.7 months. Results: Eighty-nine percent of T1.5D subjects were positive for at least one DAA; 88% of HLA-typed subjects had risk HLA genotypes. Two subjects initially treated with oral agents were subsequently treated with insulin (50%); one had risk HLA, and the other was DAA positive. Thirty-three percent of T2D subjects were DAA positive and 93% were treated with oral agents at diagnosis. Three subjects were subsequently treated with insulin (21%); of these, two were DAA positive, and one had risk HLA. No subject who remained on diet therapy or oral agents had a combination of DAA-positivity and risk HLA genotype. Conclusions: Children clinically classified with T1.5D or T2D have a high frequency of autoimmune markers and T1D-associated HLA alleles which appears to indicate a more aggressive diabetes disease process, as has been shown for DAA-positive adults with phenotypic T2D. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Benaroya Res Inst, Seattle, WA 98101 USA. Univ Washington, Childrens Hosp, Dept Pediat, Div Pediat Endocrinol, Seattle, WA 98105 USA. Univ Washington, Reg Med Ctr, Seattle, WA 98105 USA. RP Gilliam, LK (reprint author), Univ Washington, Dept Med, 1959 NE Pacific St,Box 357710, Seattle, WA 98195 USA. EM lgilliam@u.washington.edu; bbrooks@u.washington.edu; jpp@u.washington.edu; cjgreen@benaroyaresearch.org; cpihok@chmc.org FU NCRR NIH HHS [M01-RR00037]; NIDDK NIH HHS [DK17047] NR 18 TC 37 Z9 39 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2005 VL 25 IS 3 BP 244 EP 250 DI 10.1016/j.jaut.2005.09.013 PG 7 WC Immunology SC Immunology GA 992NQ UT WOS:000233891200011 PM 16243484 ER PT J AU Colombo, G Padera, R Langer, R Kohane, DS AF Colombo, G Padera, R Langer, R Kohane, DS TI Prolonged duration local anesthesia with lipid-protein-sugar particles containing bupivacaine and dexamethasone SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A LA English DT Article DE prolonged duration local anesthesia; microparticle; biocompatibility; controlled release; inflammation ID SCIATIC-NERVE BLOCKADE; IN-VIVO; LIPOSOMAL BUPIVACAINE; MICROSPHERES; BIOCOMPATIBILITY; TETRODOTOXIN; RELEASE; MODEL; RAT AB Glucocorticoids prolong block duration from polymeric microspheres containing bupivacame, but not from unencapsulated drug. Here we investigate this effect applies to particles with much more rapid drug release and improved long-term biocompatibility. Male Sprague-Dawley rats were given sciatic nerve blocks with 75 mg of 3% or 60% (w/w) dipalmitoylphosphatidylcholine (DPPC) spray-dried lipid-protein-sugar particles (LPSPs) containing 10% (w/w) bupivacame and 0%, 0.05%, or 0.1% (w/w) dexamethasone. Sensory nerve block from bupivacaine-containing 3% and 60% (w/w) DPPC particles without dexamethasone yielded blocks lasting 301 +/- 56 and 321 +/- 127 min, respectively. Addition of 0.05% (w/w) dexamethasone increased block durations to 610 +/- 182 and 538 +/- 222 min, respectively; increasing dexamethasone loading to 0.1% did not further increase duration. One day after injection, dexamethasone-containing particles resulted in lower inflammation scores and capsule thickness than dexamethasone-free particles, but the difference was gone by day 4. Excipient composition had prominent effects at all time points. For all groups, inflammation was largely resolved by 2 weeks after injection. Dexamethasone approximately doubled the duration of nerve block from bupivacaine-loaded LPSPs, while maintaining excellent biocompatibility. Such formulations could be useful in clinical applications when nerve blockade is needed for 24 hours or less. (c) 2005 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Kohane, DS (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Ellison 317, Boston, MA 02114 USA. EM dkohane@partners.org RI Colombo, Gaia/G-6837-2012 OI Colombo, Gaia/0000-0001-9033-2305 FU NIGMS NIH HHS [GM00684, GM26698] NR 18 TC 30 Z9 30 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1549-3296 J9 J BIOMED MATER RES A JI J. Biomed. Mater. Res. Part A PD NOV 1 PY 2005 VL 75A IS 2 BP 458 EP 464 DI 10.1002/jbm.a.30443 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 974GE UT WOS:000232578500024 PM 16088895 ER PT J AU Alt, C Framme, C Schnell, S Lee, H Brinkmann, R Lin, CP AF Alt, C Framme, C Schnell, S Lee, H Brinkmann, R Lin, CP TI Selective targeting of the retinal pigment epithelium using an acousto-optic laser scanner SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article; Proceedings Paper CT 12th Conference on Ophthalmic Technologies CY JAN 19-20, 2002 CL SAN JOSE, CA SP SPIE DE retinal pigment epithelium; selective laser treatment; laser scanning; central serous retinopathy; age-related macular degeneration; diabetic macular edema ID TIME REGIMEN; THRESHOLD; DAMAGE; PHOTOCOAGULATION; RPE; EXPOSURE; LESIONS; INJURY AB Selective targeting of the retinal pigment epithelium (RPE) is a new strategy for treating certain retinal disorders while preserving adjacent photoreceptors. The treatment currently relies on a complex laser system to produce the required microsecond pulse structure. In our new approach, we scan the focus of a continuous-wave (cw) laser beam with acousto-optic deflectors to produce microsecond-long exposures at each RPE cell. Experiments were performed in vitro with a bench-top scanner on samples of young bovine RPE and in vivo on Dutch belted rabbits with a slit-lamp adapted scanner. Effective dose 50% (ED50) for RPE damage was determined in vitro by fluorescence cell viability assay and in vivo by fluorescein angiography. Damage to individual RPE cells was achieved with laser power on the order of 100 mW. Using separated scan lines, we demonstrate selectivity in the form of alternating lines of dead and surviving cells that resemble the scan pattern. Selectivity is also shown by the absence of retinal thermal coagulation in vivo. Selective RPE damage is feasible by rapidly scanning a cw laser beam. The scanning device is an attractive alternative to conventional laser coagulation and pulsed laser targeting of the RPE. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Tufts Univ, Dept Biomed Engn, Medford, MA USA. Med Laser Ctr Lubeck, Lubeck, Germany. Univ Eye Hosp Regensburg, Regensburg, Germany. Univ Appl Sci Hamburg, Hamburg, Germany. RP Alt, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR822,55 Fruit St, Boston, MA 02114 USA. EM alt@helix.mgh.harvard.edu; lin@helix.mgh.harvard.edu RI Brinkmann, Ralf/E-6701-2012 FU NEI NIH HHS [EY 12970] NR 24 TC 11 Z9 11 U1 1 U2 3 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2005 VL 10 IS 6 AR 064014 DI 10.1117/1.2136314 PG 11 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 005XJ UT WOS:000234859400016 PM 16409079 ER PT J AU Ntziachristos, V Turner, G Dunham, J Windsor, S Soubret, A Ripoll, J Shih, HA AF Ntziachristos, V Turner, G Dunham, J Windsor, S Soubret, A Ripoll, J Shih, HA TI Planar fluorescence imaging using normalized data SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE transillumination; light scattering; optical imaging; molecular imaging; diffusion ID OPTICAL MAMMOGRAPHY; RECONSTRUCTION; TOMOGRAPHY; ANIMALS; TUMORS; LIGHT AB Fluorescence imaging of tissues has gained significant attention in recent years due to the emergence of appropriate reporter technologies that enable noninvasive sensing of molecular function in vivo. Two major approaches have been used so far for fluorescence molecular imaging, i.e., epi-illumination (reflectance) imaging and fluorescence molecular tomography. Transillumination is an alternative approach that has been employed for imaging tissues in the past and could be similarly beneficial for fluorescence molecular imaging. We investigate data normalization schemes in reflectance and transillumination mode and experimentally demonstrate that normalized transillumination offers significant advantages over planar reflectance imaging and over nonnormalized methods. Our observations, based on phantoms and on postmortem and in vivo mouse measurements display image quality improvement, superior depth sensitivity, and improved imaging accuracy over the nonnormalized methods examined. Normalized planar imaging retains implementation simplicity and could be used to improve on standard fluorescence reflectance imaging and as a simplified alternative to the more integrated and accurate tomographic methods. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Ctr Mol Imaging Res, Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Ntziachristos, V (reprint author), Massachusetts Gen Hosp, Dept Radiol, 149 13th St Rm 5404, Charlestown, MA 02129 USA. EM vasilis@helix.mgh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [N01-CO-17016-32] NR 21 TC 48 Z9 49 U1 0 U2 6 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2005 VL 10 IS 6 AR 064007 DI 10.1117/1.2136148 PG 8 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 005XJ UT WOS:000234859400009 PM 16409072 ER PT J AU Popescu, G Ikeda, T Best, CA Badizadegan, K Dasari, RR Feld, MS AF Popescu, G Ikeda, T Best, CA Badizadegan, K Dasari, RR Feld, MS TI Erythrocyte structure and dynamics quantified by Hilbert phase microscopy SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE microscopy; cells; phase retrieval; medical imaging ID RED-BLOOD-CELLS AB We present a new quantitative method for investigating red blood cell morphology and dynamics. The instrument integrates quantitative phase microscopy with an inverted microscope, which makes it particularly suitable for the noninvasive assessment of live erythrocytes. In particular, we demonstrate the ability of this approach to quantify noninvasively cell volume and dynamic morphology. The subnanometer path-length sensitivity at the millisecond time scales is exemplified by measuring the hemoglobin flow out of the cell during hemolysis. (C) 2005 Society of Photo-Optical Instrumentation Engineers. C1 MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Hamamatsu Photon KK, Shizuoka 4348601, Japan. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Popescu, G (reprint author), MIT, George R Harrison Spect Lab, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM gpopescu@mit.edu FU NCRR NIH HHS [P41 RR 02594] NR 15 TC 106 Z9 110 U1 2 U2 7 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2005 VL 10 IS 6 AR 060503 DI 10.1117/1.2149847 PG 3 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 005XJ UT WOS:000234859400003 PM 16409066 ER PT J AU Bhattacharyya, T Yeon, H Harris, MB AF Bhattacharyya, T Yeon, H Harris, MB TI The medical-legal aspects of informed consent in orthopaedic surgery SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background: Orthopaedic surgeons routinely obtain informed consent prior to surgery. Legally adequate informed consent requires a thorough discussion of treatment options and risks and proper documentation; however, there is little data to guide orthopaedic surgeons regarding effective methods of obtaining informed consent. Methods: We performed a closed claims analysis on malpractice claims involving an allegation of inadequate informed consent brought during a twenty-four-year period with two malpractice insurers. Relevant malpractice claims were reviewed, and data were abstracted. We then performed statistical analyses to identify factors that positively correlated with a successful defense. Results: We identified twenty-eight lawsuits that included a claim of inadequate informed consent. All of the cases involved elective orthopaedic surgical procedures; there were no emergent cases. Three cases involved a disputed surgical site; all three cases involved foot and ankle surgery and resulted in an indemnity payment. Documentation of appropriate informed consent in the office notes of the surgeon was associated with a decreased indemnity risk (p < 0.005). Obtaining the informed consent on the hospital ward or in the preoperative holding area was associated with an increased indemnity risk (p < 0.004). When informed consent was obtained in the office by the operating surgeon, the risk of malpractice payment was significantly decreased (p < 0.004). Conclusions: Surgeons may be able to decrease the risk of a malpractice claim by obtaining informed consent in their offices, rather than in the preoperative holding area, and by documenting the informed consent discussion within their dictated office or operative notes. C1 Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, Boston, MA 02114 USA. Med Profess Mutual Insurance Co ProMutual, Boston, MA USA. Risk Management Fdn, Boston, MA USA. RP Bhattacharyya, T (reprint author), Massachusetts Gen Hosp, Partners Orthopaed Trauma Serv, 35 Fruit,Yawkey 3600, Boston, MA 02114 USA. EM tbhattacharyya@partners.org NR 12 TC 35 Z9 37 U1 2 U2 4 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 NOV PY 2005 VL 87A IS 11 BP 2395 EP 2400 DI 10.2106/JBJS.D.02877 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 979ZU UT WOS:000232984500004 PM 16264113 ER PT J AU Novobrantseva, TI Majeau, GR Amatucci, A Kogan, S Brenner, I Casola, S Shlomchik, MJ Koteliansky, V Hochman, PS Ibraghimov, A AF Novobrantseva, TI Majeau, GR Amatucci, A Kogan, S Brenner, I Casola, S Shlomchik, MJ Koteliansky, V Hochman, PS Ibraghimov, A TI Attenuated liver fibrosis in the absence of B cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article AB Analysis of mononuclear cells in the adult mouse liver revealed. that B cells represent as much as half of the intrahepatic lymphocyte population. Intrahepatic B cells (IHB cells) are phenotypically similar to splenic B2 cells but express lower levels of CD23 and CD21 and higher levels of CD5. IHB cells proliferate as well as splenic B cells in response to anti-IgM and LPS stimulation in vitro. VDJ gene rearrangements in IHB cells contain insertions of N,P region nucleotides characteristic of B cells maturing in the adult bone marrow rather than in the fetal liver. To evaluate whether B cells can have an impact on liver pathology, we compared CCl4-induced fibrosis development in B cell-deficient and wild-type mice. CCl4 caused similar acute liver injury in mutant and wild-type mice. However, following 6 weeks Of CCl4 treatment, histochemical analyses showed markedly reduced collagen deposition in B cell-deficient as compared with wild-type mice. By analyzing mice that have normal numbers of B cells but lack either T cells or immunoglobulin in the serum, we established that B cells have an impact on fibrosis in an antibody- and T cell-independent manner. C1 Biogen Idec, Dept Immunol, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA USA. Yale Univ, Sch Med, Dept Lab Med, New Haven, CT USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT USA. RP Novobrantseva, TI (reprint author), Biogen Idec, Dept Immunol, 14 Cambridge Ctr, Cambridge, MA 02142 USA. EM brantseva@biogenidec.com NR 58 TC 124 Z9 128 U1 1 U2 4 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 NOV PY 2005 VL 115 IS 11 BP 3072 EP 3082 DI 10.1172/JCI24798 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100017 PM 16276416 ER PT J AU Beignon, AS McKenna, K Skoberne, M Manches, O DaSilva, I Kavanagh, DG Larsson, M Gorelick, RJ Lifson, JD Bhardwaj, N AF Beignon, AS McKenna, K Skoberne, M Manches, O DaSilva, I Kavanagh, DG Larsson, M Gorelick, RJ Lifson, JD Bhardwaj, N TI Endocytosis of HIV-1 activates plasmacytoid dendritic cells via toll-like receptor-viral RNA interactions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-PRODUCING CELLS; HERPES-SIMPLEX-VIRUS; HEPATITIS-C VIRUS; IFN-ALPHA; INFECTED INDIVIDUALS; ADAPTIVE IMMUNITY; CPG-DNA; T-CELLS; CHEMOKINE RECEPTORS AB HIV-1 directly activates human plasmacytoid DCs (pDCs) by upregulating the expression of costimulatory and MHC molecules and maturation markers, increasing T cell stimulatory activity, and inducing the production of type I interferons and TNF-alpha. A consequence of this activation is the bystander maturation of myeloid DCs and overall enhancement of antigen-presenting function. However, little is known about the mechanism(s) of pDC activation by HIV-1. Here we demonstrate by in vitro studies that IFN-alpha production by pDC in response to HIV-1 requires at least 2 interactions between the cell and virus. Initially, envelope-CD4 interactions mediate endocytosis of HIV-1, as demonstrated through the use of inhibitors of binding, fusion, endocytosis, and endosomal acidification. Subsequently, endosomally delivered viral nucleic acids, particularly RNA, stimulate pDCs through TLRs, as activation is reproduced with purified genomic RNA but not viral RNA packaging-deficient HIV-1 and blocked with different inhibitory TLR ligands. Finally, by using genetic complementation, we show that TLR7 is the likely primary target. Viral RNA rather than DNA in early retrotranscripts appears to be the active factor in HIV-1 that induces IFN-alpha secretion by pDCs. Since the decline in pDCs in chronic HIV-1 infection is associated with high viral loads and opportunistic infections, exploiting this natural adjuvant activity of HIV-1 RNA might be useful in the development of vaccines for the prevention of AIDS. C1 NYU, Sch Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21701 USA. RP Bhardwaj, N (reprint author), NYU, Sch Med, 550 1St Ave,MSB 507, New York, NY 10016 USA. EM bhardn02@popmail.med.nyu.edu OI BEIGNON, Anne-Sophie/0000-0003-0863-983X FU NCI NIH HHS [P01 CA084512, CA84512, N01-CO-124000]; NIAID NIH HHS [AI44628, AI55274, F32 AI058457, R01 AI044628, R21 AI055274, R37 AI044628]; Wellcome Trust NR 83 TC 394 Z9 416 U1 4 U2 16 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 NOV PY 2005 VL 115 IS 11 BP 3265 EP 3275 DI 10.1172/JCI26032 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100036 PM 16224540 ER PT J AU Corby, PM Lyons-Weiler, J Bretz, WA Hart, TC Aas, JA Boumenna, T Goss, J Corby, AL Junior, HM Weyant, RJ Paster, BJ AF Corby, PM Lyons-Weiler, J Bretz, WA Hart, TC Aas, JA Boumenna, T Goss, J Corby, AL Junior, HM Weyant, RJ Paster, BJ TI Microbial risk indicators of early childhood caries SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MOLECULAR ANALYSIS; DECAY AB The aim of this study was to use molecular identification methods, such as 16S RNA gene sequence and reverse-capture checkerboard hybridization, for identification of the bacteria associated with dental caries and with dental health in a subset of 204 twins aged 1.5 to 7 years old. A total of 448 plaque samples (118 collected from caries-free subjects and 330 from caries-active subjects) were used for analysis. We compared the bacteria found in biofilms of children exhibiting severe dental caries, with different degrees of lesion severity, with those found in biofilms of caries-free children. A panel of 82 bacterial species was selected, and a PCR-based reverse-capture checkerboard method was used for detection. A simple univariate test was used to determine the overabundance and underabundance of bacterial species in the diseased and in the healthy groups. Features identified with this univariate test were used to construct a probabilistic disease prediction model. Furthermore, a method for the analysis of global patterns of gene expression was performed to permit simultaneous analysis of the abundance of significant species by allowing cross-bacterial comparisons of abundance profiles between caries-active and caries-free subjects. Our results suggested that global patterns of microbial abundance in this population are very distinctive. The top bacterial species found to be over-abundant in the caries-active group were Actinomyces sp. strain B 19SC, Streptococcus mutans, and Lactobacillus spp., which exhibited an inverse relationship to beneficial bacterial species, such as Streptococcus parasanguinis, Abiotrophia defectiva, Streptococcus mitis, Streptococcus oralis, and Streptococcus sanguinis. C1 Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Pittsburgh, Hillman Canc Ctr, Pittsburgh, PA USA. Natl Inst Dent & Craniofacial Res, Div Intramural Clin Res, NIH, Bethesda, MD USA. Forsyth Inst, Boston, MA USA. Univ Oslo, Inst Oral Biol, Oslo, Norway. Twins Inst Genet Res, Montes Claros, Brazil. UNIMONTES, Montes Claros, Brazil. RP Corby, PM (reprint author), Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, 3501 Terrace St,Room 386, Pittsburgh, PA 15261 USA. EM pcorby@pitt.edu RI Aas, Jorn /A-3805-2008 FU NIDCR NIH HHS [R01 DE015351, DE15351, DE14528, K12 DE014528] NR 13 TC 93 Z9 106 U1 3 U2 16 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 NOV PY 2005 VL 43 IS 11 BP 5753 EP 5759 DI 10.1128/JCM.43.11.5753-5759.2005 PG 7 WC Microbiology SC Microbiology GA 984NS UT WOS:000233312200051 PM 16272513 ER PT J AU Rebbeck, TR Friebel, T Wagner, T Lynch, HT Garber, JE Daly, MB Isaacs, C Olopade, OI Neuhausen, SL van 't Veer, L Eeles, R Evans, DG Tomlinson, G Matloff, E Narod, SA Eisen, A Domchek, S Armstrong, K Weber, BL AF Rebbeck, TR Friebel, T Wagner, T Lynch, HT Garber, JE Daly, MB Isaacs, C Olopade, OI Neuhausen, SL van 't Veer, L Eeles, R Evans, DG Tomlinson, G Matloff, E Narod, SA Eisen, A Domchek, S Armstrong, K Weber, BL TI Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; HYSTERECTOMY; CARCINOMA; TAMOXIFEN; LIFE; BIAS AB Purpose Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HIRT. Methods We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HIRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years. Results Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96). Conclusion Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers. C1 Univ Penn, Sch Med, Abramson Canc Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Res Inst, Philadelphia, PA 19104 USA. Sunnybrook Reg Canc Ctr, Womens Coll Hosp, Toronto, ON, Canada. Med Univ Vienna, Vienna, Austria. Creighton Univ, Omaha, NE 68178 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. Univ Chicago, Chicago, IL 60637 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Royal Marsden Hosp, Sutton, Surrey, England. St Marys Hosp, Manchester M13 0JH, Lancs, England. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75235 USA. Yale Univ, New Haven, CT USA. RP Rebbeck, TR (reprint author), Univ Penn, Sch Med, Abramson Canc Ctr, Ctr Clin Epidemiol & Biostat, 904 Blockley Hall, Philadelphia, PA 19104 USA. EM trebbeck@cceb.med.upenn.edu OI Eeles, Rosalind/0000-0002-3698-6241; Evans, Gareth/0000-0002-8482-5784 FU NCI NIH HHS [CA74415, N01-CN-6700, R01-CA83855] NR 28 TC 181 Z9 185 U1 2 U2 18 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 NOV 1 PY 2005 VL 23 IS 31 BP 7804 EP 7810 DI 10.1200/JCO.2004.00.8151 PG 7 WC Oncology SC Oncology GA 981DE UT WOS:000233066700010 PM 16219936 ER PT J AU Smith, MR Lee, WC Brandman, J Wang, Q Botteman, M Pashos, CL AF Smith, MR Lee, WC Brandman, J Wang, Q Botteman, M Pashos, CL TI Gonadotropin-releasing hormone agonists and fracture risk: A claims-based cohort study of men with nonmetastatic prostate cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID ANDROGEN-DEPRIVATION THERAPY; BONE-MINERAL DENSITY; RANDOMIZED CONTROLLED-TRIAL; CARCINOMA; OSTEOPOROSIS; ORCHIECTOMY; PAMIDRONATE; SUPPRESSION; DIAGNOSIS; BLOCKADE AB Purpose Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density, a surrogate for fracture risk, in men with prostate cancer. We conducted a claims-based cohort study to characterize the relationship between GnRH agonists and risk for clinical fractures in men with nonmetastatic prostate cancer. Patients and Methods Using medical claims data from a 5% national random sample of Medicare beneficiaries, we identified a study group of men with nonmetastatic prostate cancer who initiated GnRH agonist treatment from 1992 to 1994 (n = 3,887). A comparison group of men with nonmetastatic prostate cancer who did not receive GnRH agonist treatment during the study period (n = 7,774) was matched for age, race, geographic location, and comorbidity. Clinical fractures were identified using inpatient, outpatient, and physician claims during 7 years of follow-up. Results In men with nonmetastatic prostate cancer, GnRH agonists significantly increased fracture risk. The rate of any clinical fracture was 7.88 per 100 person-years at risk in men receiving a GnRH agonist compared with 6.51 per 100 person-years in matched controls (relative risk, 1.21; 95% CI, 1.14 to 1.29; P <.001). Rates of vertebral fractures (relative risk, 1.45; 95% CI, 1.19 to 1.75; P < .001) and hip/femur fractures (relative risk, 1.30; 95% CI, 1.10 to 1.53; P =.002) were also significantly higher in men who received a GnRH agonist. GnRH agonist treatment independently predicted fracture risk in multivariate analyses. Longer duration of treatment conferred greater fracture risk. Conclusion GnRH agonists significantly increase risk for any clinical fracture, hip fractures, and vertebral fractures in men with prostate cancer. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Abt Associates Clin Trials, Bethesda, MD USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, 100 Blossom St,Cox 640, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 29 TC 190 Z9 194 U1 0 U2 4 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 NOV 1 PY 2005 VL 23 IS 31 BP 7897 EP 7903 DI 10.1200/JCO.2004.00.6908 PG 7 WC Oncology SC Oncology GA 981DE UT WOS:000233066700022 PM 16258089 ER PT J AU Menon, U Skates, SJ Lewis, S Rosenthal, AN Rufford, B Sibley, K MacDonald, N Dawnay, A Jeyarajah, A Bast, RC Oram, D Jacobs, IJ AF Menon, U Skates, SJ Lewis, S Rosenthal, AN Rufford, B Sibley, K MacDonald, N Dawnay, A Jeyarajah, A Bast, RC Oram, D Jacobs, IJ TI Prospective study using the risk of ovarian cancer algorithm to screen for ovarian cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the European-Society-of-Gynecological-Oncology CY MAY, 2003 CL Brussels, BELGIUM SP European Soc Gynecol Oncol ID POSTMENOPAUSAL WOMEN; TRIAL; PROSTATE; LUNG; ULTRASONOGRAPHY; MANAGEMENT; ULTRASOUND; ELEVATION; CA125 AB Purpose To evaluate prevalence screening in the first prospective trial of a new ovarian cancer screening (OCS) strategy (risk of ovarian cancer or ROC algorithm) on the basis of age and CA125 profile. Patients and Methods Postmenopausal women, >= 50 years were randomly assigned to a control group or screen group. Screening involved serum CA125, interpreted using the ROC algorithm. Participants with normal results returned to annual screening; those with intermediate results had repeat CA125 testing; and those with elevated values underwent transvaginal ultrasound (TVS). Women with abnormal or persistently equivocal TVS were referred for a gynecologic opinion. Results Thirteen thousand five hundred eighty-two women were recruited. Of 6,682 women randomly assigned to screening, 6,532 women underwent the first screen. After the initial CA125, 5,213 women were classified as normal risk, 91 women elevated, and 1,228 women intermediate. On repeat CA125 testing of the latter, a further 53 women were classified as elevated risk. All 144 women with elevated risk had TVS. Sixteen women underwent surgery. Eleven women had benign pathology; one woman had ovarian recurrence of breast cancer; one woman had borderline; and three women had primary invasive epithelial ovarian cancer (EOC). The specificity and positive predictive value (PPV) for primary invasive EOC were 99.8% (95% CI, 99.7 to 99.9) and 19% (95% CI, 4.1 to 45.6), respectively Conclusion An OCS strategy using the ROC algorithm is feasible and can achieve high specificity and PPV in postmenopausal women. It is being used in the United Kingdom Collaborative Trial of Ovarian Cancer Screening and in the United States in both the Cancer Genetics Network and the Gynecology Oncology Group trials of high-risk women. C1 UCL, Inst Womens Hlth, EGA Hosp, London WC1E 6DH, England. UCL, Inst Womens Hlth, Dept Gynecol Oncol, London WC1E 6DH, England. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. UCL Hosp, Barts & London NHS Trust, US Dept Gynecol Oncol, Barts & London NHS Trust,London Dept Clin Biochem, London, England. MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. RP Jacobs, IJ (reprint author), UCL, Inst Womens Hlth, EGA Hosp, Huntley St, London WC1E 6DH, England. EM i.jacobs@ucl.ac.uk RI Menon, Usha/C-4716-2008; Bast, Robert/E-6585-2011; Jacobs, Ian/F-1743-2013; OI Bast, Robert/0000-0003-4621-8462; Jacobs, Ian/0000-0002-8112-4624; Rosenthal, Adam/0000-0001-6924-0721 NR 19 TC 110 Z9 119 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2005 VL 23 IS 31 BP 7919 EP 7926 DI 10.1200/JCO.2005.01.6642 PG 8 WC Oncology SC Oncology GA 981DE UT WOS:000233066700025 PM 16258091 ER PT J AU Bell, DW Lynch, TJ Haserlat, SM Harris, PL Okimoto, RA Brannigan, BW Sgroi, DC Muir, B Riemenschneider, MJ Iacona, RB Krebs, AD Johnson, DH Giaccone, G Herbst, RS Manegold, C Fukuoka, M Kris, MG Baselga, J Ochs, JS Haber, DA AF Bell, DW Lynch, TJ Haserlat, SM Harris, PL Okimoto, RA Brannigan, BW Sgroi, DC Muir, B Riemenschneider, MJ Iacona, RB Krebs, AD Johnson, DH Giaccone, G Herbst, RS Manegold, C Fukuoka, M Kris, MG Baselga, J Ochs, JS Haber, DA TI Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: Molecular analysis of the IDEAL/INTACT gefitinib trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PHASE-III TRIAL; TYROSINE KINASE DOMAIN; EGFR MUTATIONS; ACQUIRED-RESISTANCE; ERLOTINIB; INHIBITOR; CHEMOTHERAPY; SENSITIVITY; COMBINATION; EFFICACY AB Purpose Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase 11 (IDEAL) and phase III (INTACT) trials of gefitinib. Patients and Methods We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC. Results EGFR mutations correlated with previously identified clinical features of gefitinib response, including adenocarcinoma histology, absence of smoking history, female sex, and Asian ethnicity. No such association was seen in patients whose tumors had EGFR amplification, suggesting that these molecular markers identify different biologic subsets of I In the IDEAL trials, responses to gefitinib were seen in six of 13 tumors (46%) with an EGFR mutation, two of seven tumors (29%) with amplification, and five of 56 tumors (9%) with neither mutation nor amplification (P =.001 for either EGFR mutation or amplification v neither abnormality). Analysis of the INTACT trials did not show a statistically significant difference in response to gefitinib plus chemotherapy according to EGFR genotype. Conclusion EGFR mutations and, to a lesser extent, amplification appear to identify distinct subsets of NSCLC with an increased response to gefitinib. The combination of gefitinib with chemotherapy does not improve survival in patients with these molecular markers. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Pathol, Charlestown, MA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Free Univ Amsterdam Hosp, Amsterdam, Netherlands. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Heidelberg, Med Ctr, D-6800 Mannheim, Germany. Kinki Univ, Sch Med, Osaka 589, Japan. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Barcelona, Vall Hebron Hosp, Barcelona, Spain. AstraZeneca, Wilmington, DE USA. RP Haber, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, CNY7 149,13th St, Charlestown, MA 02129 USA. EM haber@helix.mgh.harvard.edu RI Johnson, David/A-7437-2009; Giaccone, Giuseppe/E-8297-2017; OI Giaccone, Giuseppe/0000-0002-5023-7562; Kris, Mark/0000-0002-7317-5341 FU PHS HHS [P01 95281] NR 39 TC 457 Z9 474 U1 4 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 NOV 1 PY 2005 VL 23 IS 31 BP 8081 EP 8092 DI 10.1200/JCO.2005.02.7078 PG 12 WC Oncology SC Oncology GA 981DE UT WOS:000233066700045 PM 16204011 ER PT J AU Ricuarte, O Gutierrez, O Cardona, H Kim, JG Graham, DY El-Zimaity, HMT AF Ricuarte, O Gutierrez, O Cardona, H Kim, JG Graham, DY El-Zimaity, HMT TI Atrophic gastritis in young children and adolescents SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; INTESTINAL METAPLASIA; SYDNEY SYSTEM; CANCER; CLASSIFICATION; INFLAMMATION; LOUISIANA; BIOPSY; MUCOSA; CARCINOGENESIS AB Background: Helicobacter pylori associated gastric cancer arises via a multistage process, with atrophic gastritis being the precursor lesion. Helicobacter pylori is typically acquired in childhood, yet little is known of the prevalence of atrophic gastritis in childhood. Aim: To study atrophic gastritis among children from countries with high gastric cancer incidence. Methods: Sections from topographically mapped gastric biopsy specimens from children undergoing clinically indicated endoscopy in Korea and Colombia were evaluated using visual analogue scales. Atrophy was defined as loss of normal glandular components, including replacement with fibrosis, intestinal metaplasia (IM), and/or pseudopyloric metaplasia of the corpus (identified by the presence of pepsinogen I in mucosa that was topographically corpus but phenotypically antrum). Results: One hundred and seventy three children, 58 from Korea (median age, 14 years) and 115 from Colombia (median age, 13 years), were studied. Helicobacter pylori was present in 85% of Colombian children versus 17% of Korean children (p < 0.01). Atrophic mucosa near the antrum-corpus border was present in 16% of children, primarily as pseudopyloric metaplasia (31%, IM; 63%, pseudopyloric metaplasia; 6%, both). The median age of children with corpus atrophy was 15 (range, 7-17) years. Conclusion: Gastric atrophy occurs in H pylori infected children living in countries with high gastric cancer incidence. Identification and characterisation of the natural history of H pylori gastritis requires targeted biopsies to include the lesser and greater curve of the corpus, starting just proximal to the anatomical antrum-corpus junction, in addition to biopsies targeting the antrum and cardia. C1 Univ Nacl Colombia, Dept Gastroenterol, Bogota, Colombia. Korea Univ, Coll Med, Guro Hosp, Seoul 136701, South Korea. Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Dept Pathol, Houston, TX 77030 USA. RP El-Zimaity, HMT (reprint author), Michael E DeBakey VA Med Ctr, Gastrointestinal Mucosa Pathol Lab, 111-D,Room 3A-320,2002 Holcombe Blvd, Houston, TX 77030 USA. EM hzimaity@bcm.tmc.edu FU NIDDK NIH HHS [P30 DK056338] NR 42 TC 38 Z9 44 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 EI 1472-4146 J9 J CLIN PATHOL JI J. Clin. Pathol. PD NOV PY 2005 VL 58 IS 11 BP 1189 EP 1193 DI 10.1136/jcp.2005.026310 PG 5 WC Pathology SC Pathology GA 978RF UT WOS:000232890000014 PM 16254110 ER PT J AU Pollack, MH Roy-Byrne, PP Van Ameringen, M Snyder, H Brown, C Ondrasik, J Rickels, K AF Pollack, MH Roy-Byrne, PP Van Ameringen, M Snyder, H Brown, C Ondrasik, J Rickels, K TI The selective GABA Reuptake inhibitor tiagabine for the treatment of generalized anxiety disorder: Results of a placebo-controlled study SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 24th Congress of the Collegium-Internationale-Neuro-Psychopharmacologicum CY JUN 20-24, 2004 CL Paris, FRANCE SP Collegium Int Neuro Psychopharmacol ID NATIONAL-COMORBIDITY-SURVEY; DOUBLE-BLIND; LONG-TERM; CLINICAL-COURSE; POOLED ANALYSIS; DSM-IV; PAROXETINE; TRIAL; OUTPATIENTS; ABECARNIL AB Objective: To evaluate the efficacy and tolerability of tiagabine, a selective gamma-aminobutyric acid (GABA) reuptake inhibitor, in adults with generalized anxiety disorder (GAD). Method: This 8-week, randomized, doubleblind, multicenter, placebo-controlled study enrolled patients with GAD (DSM-IV). Tiagabine was initiated at 4 mg/day and then flexibly dosed twice a day to a maximum dose of 16 mg/day. Study drug was tapered after week 8 in decrements of 2 mg every other day. Efficacy assessments included the Hamilton Rating Scale for Anxiety (HAM-A) and Sheehan Disability Scale. Adverse events, sexual functioning, and change in depressive symptoms were monitored. Data were collected from May 2003 to January 2004. Results: A total of 266 patients (tiagabine, N = 134; placebo, N = 132) were included in safety analyses; 260 patients (tiagabine N = 130; placebo N = 130) were included in efficacy analyses. Tiagabine reduced symptoms of GAD according to the observed case and mixed models repeated-measures (MMRM) analyses but not the primary last-observation-carried-forward (LOCF) analysis. At final visit, the reduction from baseline in mean HAM-A total score was 11.8 for tiagabine, compared with 10.2 for placebo (LOCF analysis, p =.27). In a post hoc MMRM analysis, a significant difference in the mean reduction in HAM-A total score over the efficacy evaluation period was found, favoring tiagabine over placebo (p <.01). Tiagabine had an early onset of effect, as shown by significant reduction from baseline in mean HAM-A total score compared with placebo at week I (observed cases, p <.05). Tiagabine was generally well tolerated and not associated with changes in sexual functioning or depressive status. Symptoms of a discontinuation syndrome during taper were not observed. Conclusion: The primary LOCF analysis was negative; however, results from the observed case and MMRM analyses suggest that tiagabine may be a useful treatment option for adult patients diagnosed with GAD. These findings warrant further evaluation in randomized clinical studies. C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Anxiety Disorders Program, Boston, MA 02114 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. McMaster Univ, Med Ctr, Anxiety Disorders Clin, Hamilton, ON, Canada. Cepalon Inc, Frazer, PA USA. Univ Penn, Dept Mood & Anxiety Disorders, Philadelphia, PA 19104 USA. RP Pollack, MH (reprint author), Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Anxiety Disorders Program, Simches Res Bldg,185 Cambridge St,Suite 2200,2nd, Boston, MA 02114 USA. EM mpollack@partners.org NR 33 TC 56 Z9 56 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2005 VL 66 IS 11 BP 1401 EP 1408 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 988VI UT WOS:000233628800009 PM 16420077 ER PT J AU Burg, G Kempf, W Cozzio, A Feit, J Willemze, R Jaffe, ES Dummer, R Berti, E Cerroni, L Chimenti, S Diaz-Perez, JL Grange, F Harris, NL Kazakov, DV Kerl, H Kurrer, M Knobler, R Meijer, CJLM Pimpinelli, N Ralfkiaer, E Russell-Jones, R Sander, C Santucci, M Sterry, W Swerdlow, SH Vermeer, MH Wechsler, J Whittaker, S AF Burg, G Kempf, W Cozzio, A Feit, J Willemze, R Jaffe, ES Dummer, R Berti, E Cerroni, L Chimenti, S Diaz-Perez, JL Grange, F Harris, NL Kazakov, DV Kerl, H Kurrer, M Knobler, R Meijer, CJLM Pimpinelli, N Ralfkiaer, E Russell-Jones, R Sander, C Santucci, M Sterry, W Swerdlow, SH Vermeer, MH Wechsler, J Whittaker, S TI WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Review ID T-CELL LYMPHOMA; GRANULOMATOUS-SLACK-SKIN; WORINGER-KOLOPP-DISEASE; OF-THE-LITERATURE; FOLLICULAR MYCOSIS-FUNGOIDES; BCL-2 PROTEIN EXPRESSION; HEAVY-CHAIN GENE; SEZARY-SYNDROME; INTRAVASCULAR LYMPHOMATOSIS; PAGETOID RETICULOSIS AB The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. Aim: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. Methods: Extensive review of the literature cited in Medline and own data of the authors. Results: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. Conclusion: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Histol Diagnost, Kemp & Pfaltz, Zurich, Switzerland. Univ Hosp Brno, Dept Pathol, Brno, Czech Republic. Leiden Univ, Med Ctr, Netherlands Lab Pathol, Dept Dermatol, Leiden, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Dermatol, Milan, Italy. Graz Univ, Dept Dermatol, Graz, Austria. Univ Rome, Dept Dermatol, Rome, Italy. Cruces Hosp, Dept Dermatol, Bilbao, Spain. Univ Reims, Dept Dermatol, Reims, France. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Charles Univ, Med Fac Hosp, Sikls Dept Pathol, Plzen, Czech Republic. Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. Univ Vienna, Dept Dermatol, Vienna, Austria. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. Univ Florence, Dept Dermatol Sci, Florence, Italy. Univ Copenhagen, Dept Pathol, Copenhagen, Denmark. St Thomas Hosp, St Johns Inst Dermatol, Skin Tumour Unit, London, England. Allgemeines Krankenhaus St Georg, Dept Dermatol, Hamburg, Germany. Univ Florence, Dept Human Pathol & Oncol, Florence, Italy. Humboldt Univ, Charite, Dept Dermatol, Berlin, Germany. Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. RP Burg, G (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM g.burg@usz.ch RI Berti, Emilio/F-5256-2012 NR 212 TC 165 Z9 176 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2005 VL 32 IS 10 BP 647 EP 674 DI 10.1111/j.0303-6987.2005.00495.x PG 28 WC Dermatology; Pathology SC Dermatology; Pathology GA 984OQ UT WOS:000233314600001 PM 16293178 ER PT J AU Bartlett, JD AF Bartlett, JD TI Making the cut in dental enamel - The discovery of enamelysin (MMP-20) SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material DE cloning; enamel; matrix metalloproteinase ID AMELOGENESIS IMPERFECTA; IDENTIFICATION; MATURATION; TOOTH; PIG C1 Harvard Univ, Sch Med & Dent, Dept Dev Biol, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Harvard Univ, Sch Med & Dent, Dept Dev Biol, 140 Fenway, Boston, MA 02115 USA. EM JBartlett@forsyth.org FU NIDCR NIH HHS [R01 DE014084] NR 12 TC 0 Z9 0 U1 0 U2 0 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2005 VL 84 IS 11 BP 986 EP 988 PG 3 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 977KA UT WOS:000232801100003 PM 16246927 ER PT J AU Nagurney, JT Brown, DFM Chae, C Chang, YC Chung, WG Cranmer, H Dan, L Fisher, J Grossman, S Tedrow, U Lewandrowski, K Jang, IK AF Nagurney, JT Brown, DFM Chae, C Chang, YC Chung, WG Cranmer, H Dan, L Fisher, J Grossman, S Tedrow, U Lewandrowski, K Jang, IK TI The sensitivity of cardiac markers stratified by symptom duration SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 12-13, 2003 CL Boston, MA SP Amer Coll Emergency Physicians DE acute coronary syndrome; acute myocardial infarction; cardiac markers; troponin; time interval ID ACUTE MYOCARDIAL-INFARCTION; CHEST PAIN PATIENTS; CREATINE KINASE-MB; TROPONIN-T ASSAY; EMERGENCY-DEPARTMENT; RISK STRATIFICATION; NATIONAL ACADEMY; EARLY DIAGNOSIS; MYOGLOBIN; EXCLUSION AB We compared the sensitivity of three commonly used cardiac markers between two subpopulations, those who came to the Emergency Department (ED) late (6-24 h) after their symptoms began, and those who arrived earlier (<6 h), in a prospective comparative trial. Among all adult patients who presented to our ED with symptoms suggestive of acute myocardial infarction (MI), we drew serum for myoglobin, CK-MB, and troponin I upon arrival (time 0) and 2 h later. Outcomes, including acute MI, were determined. Sensitivities for all three markers between the subpopulations who arrived fewer than 6 h from symptom onset were compared to those who arrived later (6-24 h). We enrolled 346 eligible subjects, 36% of whom described cardiac symptoms as beginning 6 or more hours earlier; 14% suffered acute MIs. For time 0, the sensitivity of all three markers for acute MI was significantly higher among those subjects with symptoms of 6 or more hours' duration as compared to those with less. For troponin I, the increase in sensitivity between these two subpopulations approached 300%. At the time of the 2-h sample, the differences in sensitivities were much less and were not statistically significant. We conclude that cardiac marker values obtained at time 0 among Emergency Department patients who arrive 6 or more hours after cardiac symptom onset provide significantly higher sensitivities as compared to those obtained in patients who arrive earlier. For troponin I, the increase in sensitivity approaches threefold. (c) 2005 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Affiliated Emergency Med Residency, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Hosp, Boston, MA USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,Clin Bldg 115, Boston, MA 02114 USA. NR 37 TC 5 Z9 5 U1 0 U2 2 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 NOV PY 2005 VL 29 IS 4 BP 409 EP 415 DI 10.1016/j.jemermed.2005.05.011 PG 7 WC Emergency Medicine SC Emergency Medicine GA 979QI UT WOS:000232959500007 PM 16243197 ER PT J AU Macias, WL Kabrhel, C Nadel, ES Brown, DFM AF Macias, WL Kabrhel, C Nadel, ES Brown, DFM TI Pleuritic chest pain and exertional dyspnea SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID HELICAL COMPUTED-TOMOGRAPHY; CONSTRICTIVE PERICARDITIS; RESTRICTIVE CARDIOMYOPATHY; PULMONARY-EMBOLISM; DIAGNOSIS; ECHOCARDIOGRAPHY C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Bulfinch 105,15 Fruit St, Boston, MA 02114 USA. OI Kabrhel, Christopher/0000-0002-8699-7176 NR 14 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 NOV PY 2005 VL 29 IS 4 BP 467 EP 473 DI 10.1016/j.jemermed.2005.07.002 PG 7 WC Emergency Medicine SC Emergency Medicine GA 979QI UT WOS:000232959500019 PM 16243209 ER PT J AU Lee, JH Volinic, JL Banz, C Yao, KM Thomas, MK AF Lee, JH Volinic, JL Banz, C Yao, KM Thomas, MK TI Interactions with p300 enhance transcriptional activation by the PDZ-domain coactivator Bridge-1 SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID INSULIN GENE-TRANSCRIPTION; BINDING-PROTEIN; DIABETES-MELLITUS; DISEASE; RECRUITMENT; PROTEASOME; MUTATIONS; PANCREAS; PDX-1; DEGRADATION AB Transcriptional coactivators are essential mediators of signal amplification in the regulation of gene expression in response to hormones and extracellular signals. We previously identified Bridge-1 (PSMD9) as a PDZ-domain coregulator that augments insulin gene transcription via interactions with the basic helix-loop-helix transcription factors E12 and E47, and that increases transcriptional activation by the homeodomain transcription factor PDX-1. In these studies, we find that transcriptional activation by Bridge-1 can be regulated via interactions with the histone acetyltransferase and nuclear receptor coactivator p300. In transfection assays, transcriptional activation by Bridge-1 is increased by the inhibition of endogenous histone deacetylase activity with trichostatin A, indicating that the transcriptional activation function of Bridge-1. can be regulated by histone modifications. The exogenous expression of p300 enhances the transcriptional activation by Bridge-1 in a dose-dependent mariner. In contrast, the sequestration of p300 by the overexpression of the adenoviral protein E1A, but not by an E1A mutant protein that is unable to interact with p300, suppresses the transcriptional activation by Bridge-1. We demonstrate that p300 and Bridge-1 proteins interact in immunoprecipitation and glutathione-S-transferase (GST) pull-down assays. Bridge-1 interacts directly with multiple regions within p300 that encompass C/H1 or C/H2 cysteine- and histidine-rich protein interaction domains and the histone acetyltransferase domain. Deletion or point mutagenesis of the Bridge-1 PDZ domain substantially reduces transcriptional activation by Bridge-1 and interrupts interactions with p300. We propose that p300 interactions with Bridge-1 can augment the transcriptional activation of regulatory target genes by Bridge-1. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Hong Kong, Fac Med, Dept Biochem, Hong Kong, Peoples R China. RP Thomas, MK (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, Wellman 340,50 Blossom St, Boston, MA 02114 USA. EM mthomas1@partners.org RI Yao, Kwok Ming/C-4457-2009 FU NIDDK NIH HHS [DK59419, DK02476] NR 34 TC 13 Z9 14 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD NOV PY 2005 VL 187 IS 2 BP 283 EP 292 DI 10.1677/joe.1.06305 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 989IU UT WOS:000233666900011 PM 16293776 ER PT J AU Khachemoune, A Guldbakke, KK AF Khachemoune, A Guldbakke, KK TI A young girl with scaly skin plaques SO JOURNAL OF FAMILY PRACTICE LA English DT Editorial Material ID PSORIASIS; TRIAL C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, Boston, MA 02114 USA. RP Khachemoune, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed,Dept Dermatol, BAR 314,40 Blossom St, Boston, MA 02114 USA. EM amorkh@pol.net NR 9 TC 0 Z9 0 U1 0 U2 0 PU DOWDEN PUBLISHING CORP PI MONTVALE PA 110 SUMMIT AVE, MONTVALE, NJ 07645-1712 USA SN 0094-3509 J9 J FAM PRACTICE JI J. Fam. Pract. PD NOV PY 2005 VL 54 IS 11 BP 947 EP 951 PG 5 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 985DV UT WOS:000233357300008 PM 16266599 ER PT J AU Aspinall, SL DeSanzo, BE Trilli, LE Good, CB AF Aspinall, SL DeSanzo, BE Trilli, LE Good, CB TI Bleeding risk index in an anticoagulation clinic - Assessment by indication and implications for care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE bleeding risk; warfarin; anticoagulation clinic ID NONRHEUMATIC ATRIAL-FIBRILLATION; GASTROINTESTINAL HEMORRHAGE; WARFARIN; THERAPY; EPIDEMIOLOGY; PREDICTION; MANAGEMENT AB BACKGROUND: The Outpatient Bleeding Risk Index (BRI) prospectively classified patients who were at high, intermediate, or low risk for warfarin-related major bleeding. However, there are only 2 published validation studies of the index and neither included veterans. OBJECTIVE: To determine the accuracy of the BRI in patients attending a Veterans Affairs (VA) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation. DESIGN: Retrospective cohort study. PATIENTS AND MEASURMENTS: Using the BRI, all patients managed by the Anticoagulation Clinic between January 1, 2001 and December 31, 2002 were classified as high, intermediate, or low risk for major bleeding. Bleeds were identified via quality-assurance reports. Poisson regression was used to determine whether there was an association between the index and the development of bleeding. RESULTS: The rate of major bleeding was 10.6%, 2.5%, and 0.8% per patient-year of warfarin in the high-, intermediate-, and low-risk groups, respectively. Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group (incidence rate ratio (IRR) 14; 95% confidence interval (CI), 1.9 to 104.7). The rate of major bleeding was significantly different between the high- and intermediate-risk categories (P <.001). Among those with atrial fibrillation, patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined (IRR=6; 95% CI, 2.4 to 15.3). CONCLUSIONS: The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic, including those with atrial fibrillation. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot 151C CU, Pittsburgh, PA 15240 USA. Butler Vet Affairs Med Ctr, Dept Pharm, Butler, PA USA. VA Pittsburgh Healthcare Syst, Dept Pharm, Pittsburgh, PA USA. RP Aspinall, SL (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot 151C CU, Univ Dr C, Pittsburgh, PA 15240 USA. EM sherrie.aspinall@med.va.gov NR 17 TC 31 Z9 32 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2005 VL 20 IS 11 BP 1008 EP 1013 DI 10.1111/j.1525-1497.2005.0229.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 978SH UT WOS:000232892800006 PM 16307625 ER PT J AU Green, AR Ngo-Metzger, Q Legedza, ATR Massagli, MP Phillips, RS Iezzoni, LI AF Green, AR Ngo-Metzger, Q Legedza, ATR Massagli, MP Phillips, RS Iezzoni, LI TI Interpreter services, language concordance, and health care quality - Experiences of Asian Americans with limited English proficiency SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE Asian Americans; immigrant health; interpreters; language barriers; communication ID MEDICAL INTERPRETATION; NATIONAL-SURVEY; SATISFACTION; EMERGENCY; IMPACT; PERFORMANCE; OUTPATIENTS; ENCOUNTERS; BARRIERS; RATINGS AB BACKGROUNG: Patients with limited English proficiency (LEP) have more difficulty communicating with health care providers and are less satisfied with their care than others. Both interpreter- and language-concordant clinicians may help overcome these problems but few studies have compared these approaches. OBJECTIVE: To compare self-reported communication and visit ratings for LEP Asian immigrants whose visits involve either a clinic interpreter or a clinician speaking their native language. DESIGN: Cross-sectional survey-response rate 74%. PATIENTS: Two thousand seven hundred and fifteen LEP Chinese and Vietnamese immigrant adults who received care at 11 community-based health centers across the U.S. MEASUREMENTS: Five self-reported communication measures and overall rating of care. RESULTS: Patients who used interpreters were more likely than language-concordant patients to report having questions about their care (30.1% vs 20.9%, P <.001) or about mental health (25.3% vs 18.2%, P=.005) they wanted to ask but did not. They did not differ significantly in their response to 3 other communication measures or their likelihood of rating the health care received as "excellent" or "very good" (51.7% vs 50.9%, P=.8). Patients who rated their interpreters highly ("excellent" or "very good") were more likely to rate the health care they received highly (adjusted odds ratio 4.8, 95% confidence interval, 2.3 to 10.1). CONCLUSIONS: Assessments of communication and health care quality for outpatient visits are similar for LEP Asian immigrants who use interpreters and those whose clinicians speak their language. However, interpreter use may compromise certain aspects of communication. The perceived quality of the interpreter is strongly associated with patients' assessments of quality of care overall. C1 Harvard Univ, Inst Hlth Policy, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Irvine, Coll Med, Div Gen Med & Primary Care, Irvine, CA 92717 USA. Univ Calif Irvine, Coll Med, Ctr Hlth Policy Res, Irvine, CA 92717 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Green, AR (reprint author), Harvard Univ, Inst Hlth Policy, Sch Med, Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM argreen@partners.org FU AHRQ HHS [R01 HS010316, RQ R01-HS10316]; NCCIH NIH HHS [K24 AT000589, K24 AT00589-03]; PHS HHS [T32 HP11001-15] NR 41 TC 98 Z9 98 U1 3 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2005 VL 20 IS 11 BP 1050 EP 1056 DI 10.1111/j.1525-1497.2005.0223.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 978SH UT WOS:000232892800014 PM 16307633 ER PT J AU Harness, N Blazar, PE AF Harness, N Blazar, PE TI Causative microorganisms in surgically treated pediatric hand infections SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE hand; infection; pediatric; microorganism ID CHILDREN AB Purpose: The causative organisms in many pediatric musculoskeletal infections are distinct from their adult counterparts. We investigated the organisms found in surgically treated hand infections in the pediatric population. Methods: We reviewed the hospital charts and computer records of all patients who had surgical intervention for infections of the forearm, wrist, and hand from 1996 through 2002 at The Children's Hospital of Boston. Results: Thirty-eight surgical procedures were performed on 31 children for 32 different upper-extremity infections. One patient was treated for 2 separate infections. In the 32 primary procedures 7 cultures grew mixed aerobic/anaerobic organisms, 19 grew aerobic organisms only, 6 grow no organisms, and 2 patients had no cultures. One culture from a secondary surgery was positive for Candida parapsilosis. Staphylococcus aureus was isolated in 15 of the primary cases and was the primary organism in 12. Five of 7 mixed infections were associated with paronychia; 2 of the paronychial infections were complicated by flexor tenosynovitis. Chronic nail biting caused 2 infections and 1 was associated with thumb sucking. Conclusions: In the adult population S aureus is the primary organism cultured in 50% to 80% of cases and anaerobic or mixed infection may occur in upward of 29% of patients. In this series S aureus was the primary organism in only 37%. Group A Streptococcus pyogenes was present in 20% of cases. The percentage of children with a mixed aerobic/anaerobic infection was similar to that found in adults; however, the presumed route of introduction was digital sucking/biting. Based on the number of anaerobic/mixed infections without predisposing factors we recommend a broad-spectrum antibiotic regimen including anaerobic coverage as the initial antibiotic in the setting of pediatric hand infections. C1 Brigham & Womens Hosp, Dept Orthopaed Surg, Hand Surg Serv, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harvard Combined Orthopaed Surg Residency, Boston, MA 02114 USA. RP Blazar, PE (reprint author), Brigham & Womens Hosp, Dept Orthopaed Surg, Hand Surg Serv, 25 Francis St, Boston, MA 02115 USA. EM pblazar@partners.org NR 6 TC 7 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 2005 VL 30A IS 6 BP 1294 EP 1297 DI 10.1016/j.jhsa.2005.06.018 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 998QX UT WOS:000234335300028 PM 16344191 ER PT J AU Lepore, JJ Dec, GW Zapol, WM Bloch, KD Semigran, MJ AF Lepore, JJ Dec, GW Zapol, WM Bloch, KD Semigran, MJ TI Combined administration of intravenous dipyridamole and inhaled nitric oxide to assess reversibility of pulmonary arterial hypertension in potential cardiac transplant recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID HEART-TRANSPLANTATION; VASCULAR-RESISTANCE; LUNG TRANSPLANTATION; FAILURE; CANDIDATES; RISK; NITROPRUSSIDE; PROSTACYCLIN; MORTALITY; PRESSURE AB Background: irreversible, severe pulmonary hypertension (PH) can produce right heart failure and early mortality after cardiac transplantation. We hypothesized that dipyridamole, an inhibitor of Type 5 phosphodiesterase, would augment the ability of inhaled nitric oxide (NO) to identify reversibility of PH. Methods: In 9 patients with congestive heart failure (CHF) and severe PH who were breathing 100% oxygen during right heart catheterization, we administered inhaled NO (80 ppm) alone and in combination with intravenous dipyridamole (0.2-mg/kg bolus, with an infusion of 0.0375 mg/kg/min). Results: Compared with, breathing oxygen alone, NO inhalation decreased pulmonary artery pressure and pulmonary vascular resistance (PVR) (by 10 +/- 4% and 26 +/- 12% [mean +/- SEM], respectively; both P < 0.05). The combination of NO and dipyridamole reduced PVR (43 +/- 7%;P < 0.05) to a greater extent than did administration of No alone, and increased the duration of pulmonary vasodilation produced by NO inhalation. Combined administration of inhaled NO and intravenous dipyridamole increased cardiac index (by 23 +/- 10%) and reduced SVR (by 19 +/- 6%, both p < 0.05) without changing systemic arterial pressure. NO inhalation reduced PVR to <200 dyne (.)s/cm(5) in 3 of 7 patients who had a PVR of >200 dyne (.)s/cm(5) when breathing oxygen alone, whereas the combination of NO and dipyridamole decreased PVR to <200 dyne (.)s/cm(5) in 2 additional patients. Conclusions: Intravenous dipyridamole augments and prolongs the pulmonary vasodilator effects of inhaled NO in CHF patients with severe PH and, when administered in combination with NO inhalation, can identify PH reversibility in potential cardiac transplant recipients in whom a pulmonary vasodilator response to inhalation of NO alone is not observed. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Heart Failure & Cardiac Transplantat Unit, Bigelow 800,Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org NR 34 TC 7 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2005 VL 24 IS 11 BP 1950 EP 1956 DI 10.1016/j.healun.2005.04.007 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 985XP UT WOS:000233412300035 PM 16297803 ER PT J AU Peura, JL Zile, MR Feldman, DS Vanbakel, AB McClure, C Uber, W Haynes, H Pereira, NL AF Peura, JL Zile, MR Feldman, DS Vanbakel, AB McClure, C Uber, W Haynes, H Pereira, NL TI Effects of conversion from cyclosporine to tacrolimus on left ventricular structure in cardiac allograft recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article ID TRANSPLANTATION; HYPERTENSION; HYPERTROPHY; EXPRESSION AB Twelve heart transplant recipients selected for conversion from cyclosporine to tacrolimus because of adverse effects of cyclosporine therapy underwent echocardiography at baseline and 6 months after conversion. Left ventricular mass decreased by 24% and left ventricular geometry returned toward normal at 6 months after conversion, without significant changes in blood pressure. C1 Med Univ S Carolina, Div Cardiol, Dept Internal Med, Gazes Cardiac Res Inst, Charleston, SC 29425 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Charleston, SC USA. RP Pereira, NL (reprint author), Med Univ S Carolina, Div Cardiol, Dept Internal Med, Gazes Cardiac Res Inst, 135 Rutledge Ave,Suite 1201,POB 250592, Charleston, SC 29425 USA. EM pereiran@musc.edu NR 9 TC 11 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD NOV PY 2005 VL 24 IS 11 BP 1969 EP 1972 DI 10.1016/j.healun.2005.02.011 PG 4 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 985XP UT WOS:000233412300038 PM 16297806 ER PT J AU Akins, CW Bitondo, JM Hilgenberg, AD Vlahakes, GJ Madsen, JC MacGillivray, TE AF Akins, CW Bitondo, JM Hilgenberg, AD Vlahakes, GJ Madsen, JC MacGillivray, TE TI Early and late results of the surgical correction of cardiac prosthetic paravalvular leaks SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT 3rd Biennial Meeting of Society-for-Heart-Valve-Diseases CY JUN 17-20, 2005 CL Vancouver, CANADA SP Soc Heart Valve Dis ID MITRAL-VALVE-REPLACEMENT; PERIPROSTHETIC LEAKAGE; REOPERATION; MORTALITY; SURGERY; CLOSURE; RISK AB Background and aim of the study: Although the incidence of paravalular leaks, the most common cause of non-structural dysfunction after valve replacement, is well defined, the results of their surgical correction are not. Given the growing enthusiasm for interventional catheter-based correction of paravalvular leaks, a current surgical baseline against which to compare these results is important. Methods: All patients who had surgical correction of an aortic or mitral paravalvular leak unrelated to acute bacterial endocarditis between 1986 and 2001 were identified from a computerized registry. Hospital records were reviewed, and follow up data obtained. Results: A total of 136 consecutive patients (73 males, 63 females; mean age 64 years) underwent surgical correction of a paravalvular leak. Of the valves, 44 (32%) were aortic and 92 (68%) mitral. More than one previous cardiac operation had been performed in 68 patients (50%). In 107 patients (79%; 32 aortic (73%), 75 mitral (82%)), the leak was the primary indication for reoperation, while for 29 patients (21%; 12 aortic (27%), 17 mitral (18%)) the correction was secondary to another cardiac procedure. In 65 patients (48%; 12 aortic (27%), 53 (58%) mitral)) the leak was repaired primarily, while in 71 patients (52%; 32 aortic (73%), 39 (42%) mitral)) the prosthesis was replaced. Operative mortality was 6.6% (n = 9). There were no significant multivariable predictors of hospital death. Perioperative stroke occurred in seven cases (5.1%), and hospital stay was > 14 days in 40 patients (29%). The 10-year Kaplan-Meier survival was 30 (CI 20-39)%. Ten-year actual versus actuarial freedom from repeat paravalvular leak was 84 (CI 68-92)% versus 63 (CI 49-76)%. Conclusion: Surgical correction of cardiac paravalvular leaks can be performed with acceptable mortality and morbidity. Patients with surgically corrected paravalvular leaks have a limited life expectancy, but reasonable freedom from recurrent paravalvular leak. C1 Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, Boston, MA 02114 USA. RP Akins, CW (reprint author), Massachusetts Gen Hosp, Dept Surg, Cardiac Surg Unit, White 503,55 Fruit St, Boston, MA 02114 USA. EM cakins@partners.org NR 14 TC 51 Z9 52 U1 0 U2 0 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD NOV PY 2005 VL 14 IS 6 BP 792 EP 799 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 987CY UT WOS:000233497200018 PM 16359061 ER PT J AU Yeung, E Chung, RT AF Yeung, E Chung, RT TI Rethinking hepatitis C viral kinetics: Insights into host-virus interactions in 'difficult-to-treat' groups and implications for novel treatment approaches SO JOURNAL OF HEPATOLOGY LA English DT Editorial Material ID ALPHA-2A PLUS RIBAVIRIN; LIVER-TRANSPLANTATION; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; PEGINTERFERON; RESPONSES; DECLINE C1 Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org NR 30 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD NOV PY 2005 VL 43 IS 5 BP 748 EP 750 DI 10.1016/j.jhep.2005.08.001 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 980GW UT WOS:000233003600001 PM 16171895 ER PT J AU Reddy, J Waldner, H Zhang, XM Illes, Z Wucherpfennig, KW Sobel, RA Kuchroo, VK AF Reddy, J Waldner, H Zhang, XM Illes, Z Wucherpfennig, KW Sobel, RA Kuchroo, VK TI Cutting edge: CD4(+)CD25(+) regulatory T cells contribute to gender differences in susceptibility to experimental autoimmune encephalomyelitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN PROTEOLIPID PROTEIN; SELF-TOLERANCE; RECEPTOR-ALPHA; SJL MICE; DISEASE; LYMPHOCYTES; RESISTANCE; RESPONSES; THERAPY; DRIVES AB Female B10.S mice are-highly resistant to proteolipid protein (PLP) 139-151-induced experimental autoimmune encephalomyelitis (EAE) and depletion of PLP 139-151-reactive CD4(+)CD25(+) regulatory T (Treg) cells can slightly increase their EAE susceptibility. Although male B10.S mice are moderately susceptible to EAE, we report that depletion of Treg cells in male B10.S mice before immunization with PLP 139-151 renders them highly susceptible to severe EAE with more CNS neutrophil infiltrates than nondepleted controls. Increased susceptibility is associated with an enhanced PLP 139-151-specific T cell response and greater production of IFN-gamma, IL-6, and IL-17. Male CD4(+) CD25(-) effector cells depleted of Treg cells proliferate to a greater degree than those from females in response to either anti-CD3 or PLP 139-151. These data suggest that because of their capacity to regulate potent autoaggressive effector cells, Treg cells partly contribute to the resistance to autoimmunity in the male mice. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. RP Kuchroo, VK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM vkuchroo@rics.bwh.harvard.edu RI Reddy, Jay/K-7200-2014 OI Reddy, Jay/0000-0003-4082-9254 FU NIAID NIH HHS [R01 AI44880]; NINDS NIH HHS [P01 NS38037, NS 046414, R01 NS44914, R01 NS30843]; PHS HHS [P01 A145757] NR 24 TC 72 Z9 73 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 5591 EP 5595 PG 5 WC Immunology SC Immunology GA 977EW UT WOS:000232786300006 PM 16237044 ER PT J AU De, AK Miller-Graziano, CL Calvano, SE Laudanski, K Lowry, SF Moldawer, LL Remick, DG Rajicic, N Schoenfeld, D Tompkins, RG AF De, AK Miller-Graziano, CL Calvano, SE Laudanski, K Lowry, SF Moldawer, LL Remick, DG Rajicic, N Schoenfeld, D Tompkins, RG TI Selective activation of peripheral blood T cell subsets by endotoxin infusion in healthy human subjects corresponds to differential chemokine activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AUTOIMMUNE-DISEASE; EXPRESSION; MEMORY; LYMPHOCYTES; RECEPTOR; INFECTION; EFFECTOR; INNATE; ROLES; MICE AB Although activation of human innate immunity after endotoxin administration is well established, in vivo endotoxin effects on human T cell responses are not well understood. Most naive human T cells do not express receptors for LPS, but can respond to endotoxin-induced mediators such as chemokines. In this study, we characterized the in vivo response of peripheral human T cell subsets to endotoxin infusion by assessing alterations in isolated T cells expressing different phenotypes, intracellular cytokines, and systemic chemokines concentration, which may influence these indirect T cell responses. Endotoxin administration to healthy subjects produced T cell activation as confirmed by a 20% increase in intracellular IL-2, as well as increased CD28 and IL-2R alpha-chain (CD25) expression. Endotoxin induced indirect activation of T cells was highly selective among the T cell subpopulations. Increased IL-2 production (36.0 +/- 3.7 to 53.2 +/- 4.1) vs decreased IFN-gamma production (33.8 +/- 4.2 to 19.1 +/- 3.2) indicated selective Th1 activation. Th2 produced IL-13 was minimally increased. Differentially altered chemokine receptor expression also indicated selective T cell subset activation and migration. CXCR3(+) and CCR5(+) expressing Th1 cells were decreased (CXCR3 44.6 +/- 3.2 to 33.3 +/- 4.6 and CCR5 24.8 +/- 2.3 to 12 +/- 1.4), whereas plasma levels of their chemokine ligands IFN-gamma-inducible protein 10 and MIP-1 alpha were increased (61.4 +/- 13.9 to 1103.7 +/- 274.5 and 22.8 +/- 6.2 to 55.7 +/- 9.5, respectively). In contrast, CCR4(+) and CCR3 (Th2) proportions increased or remained unchanged whereas their ligands, eotaxin and the thymus and activation-regulated chemokine TARC, were unchanged. The data indicate selective activation among Th1 subpopulations, as well as differential Th1/Th2 activation, which is consistent with a selective induction of Th1 and Th2 chemokine ligands. C1 Univ Rochester, Med Ctr, Dept Surg, Rochester, NY 14627 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, Piscataway, NJ 08854 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Univ Michigan, Dept Med Sci, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, MGH Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Burn Hosp, Boston, MA 02114 USA. RP Miller-Graziano, CL (reprint author), Univ Rochester, Med Ctr, Dept Surg, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Carol_Miller_Graziano@urmc.rochester.edu OI Laudanski, Krzysztof /0000-0002-7373-0851 FU NIGMS NIH HHS [U54 GM-62119-04, U54 GM062119] NR 30 TC 20 Z9 20 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 6155 EP 6162 PG 8 WC Immunology SC Immunology GA 977EW UT WOS:000232786300074 PM 16237112 ER PT J AU Bae, J Yu-Tzu, T Neri, P Carrasco, R Sukhdeo, K Prabhala, R Anderson, KC Munshi, NC AF Bae, J Yu-Tzu, T Neri, P Carrasco, R Sukhdeo, K Prabhala, R Anderson, KC Munshi, NC TI Identification of novel myeloma-specific peptides able to generate specific and effective cytotoxic T lymphocytes: Potential therapeutic application in multiple myeloma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 610 EP 611 DI 10.1097/01.cji.0000190940.79761.47 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800016 ER PT J AU Woodberry, T Suscovich, TJ Henry, LM Davis, JK Frahm, N Walker, BD Scadden, DT Wang, F Brander, C AF Woodberry, T Suscovich, TJ Henry, LM Davis, JK Frahm, N Walker, BD Scadden, DT Wang, F Brander, C TI Differential targeting and shifts in the immunodominance of Epstein-Barr virus-specific CD8 and CD4 T cell responses during acute and persistent infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR ANTIGEN EBNA1; LYMPHOCYTE RESPONSES; PERIPHERAL-BLOOD; CYCLE PROTEINS; EBV; EPITOPE; LATENT; IDENTIFICATION AB The evolution of Epstein-Barr virus (EBV) - specific T cell responses that occurs during the acute and persistent stages of infection remains poorly characterized despite its importance for developing immune interventions for EBV-associated disorders. This study assessed T cell responses to 113 EBV-derived epitopes in 40 subjects with acute or persistent EBV infection. Although no significant differences were seen in the breadth of CD8 and CD4 T cell responses, their magnitude differed significantly over time; acutely infected subjects generated especially strong responses to lytic viral antigens. The cross-sectional shift in immunodominance was also confirmed in subjects followed longitudinally from acute to persistent infection. In addition, human leukocyte antigen - matched siblings with discordant histories of symptomatic EBV infection showed no significant differences in their response patterns, suggesting that symptomatic EBV infection does not lead to unique persistent-stage responses. These data provide an assessment of immunodominance patterns and guidance for developing immunotherapeutic interventions for EBV-associated disorders. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Brander, C (reprint author), Partners AIDS Res Ctr, 5th Fl MGH E 5214,149 13th St, Charlestown, MA 02129 USA. EM cbrander@partners.org FU NIDCR NIH HHS [P01 DE01438-01] NR 52 TC 45 Z9 48 U1 0 U2 2 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 NOV 1 PY 2005 VL 192 IS 9 BP 1513 EP 1524 DI 10.1086/491741 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 970TR UT WOS:000232333000003 PM 16206065 ER PT J AU Ramduth, D Chetty, P Mngquandaniso, NC Nene, N Harlow, JD Honeyborne, I Ntumba, N Gappoo, S Henry, C Jeena, P Addo, MM Altfeld, M Brander, C Day, C Coovadia, H Kiepiela, P Goulder, P Walker, B AF Ramduth, D Chetty, P Mngquandaniso, NC Nene, N Harlow, JD Honeyborne, I Ntumba, N Gappoo, S Henry, C Jeena, P Addo, MM Altfeld, M Brander, C Day, C Coovadia, H Kiepiela, P Goulder, P Walker, B TI Differential immunogenicity of HIV-1 clade C proteins in eliciting CD8(+) and CD4(+) cell responses SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Oppprtunistic Infections CY FEB, 2004 CL San Francisco, CA ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC-T-LYMPHOCYTE; CHRONIC VIRAL-INFECTION; AIDS VACCINE DESIGN; CD8-T-CELL MEMORY; CD4-T-CELL HELP; TYPE-1; ESCAPE; LOAD; INDIVIDUALS AB Background. The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8(+) and CD4(+) cell responses has not been defined. Methods. HIV- 1 - specific T cell responses were evaluated in 65 chronically HIV- 1 - infected untreated subjects by interferon-gamma flow cytometry with peptides spanning the clade C consensus sequence. Results. The magnitude of HIV- 1 - specific CD8(+) T cell responses correlated significantly with CD4(+) cell responses, but the percentage of CD8(+) T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4(+) cells ( median, 0.24%). Although CD8(+) T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4(+) cell responses. There was no consistent relationship between virus-specific CD8(+) or CD4(+) cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8(+) T cell target was significantly lower than that in subjects in whom non-Gag proteins were the main target (P =.007). Conclusions. Gag-specific responses dominate the CD4(+) T cell response to HIV, whereas CD8(+) T cell responses are broadly distributed, which indicates differential immunogenicity of these cells against HIV-1. The preferential targeting of Gag by CD8(+) T cells is associated with enhanced control of viral load. C1 Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Oxford, Oxford, England. RP Ramduth, D (reprint author), Univ KwaZulu Natal, Nelson R Mandela Sch Med, Doris Duke Med Res Inst, HIV Pathogenesis Programme, Durban, South Africa. EM ramduthd1@ukzn.ac.za RI Day, Cheryl/J-9844-2012 FU NCRR NIH HHS [P51 RR001676-43]; NIAID NIH HHS [N01 AI 15442, R01 AI46995-01A1, R01-AI-46366, R01-AI-49120, R01-AI-52056]; Wellcome Trust NR 36 TC 45 Z9 48 U1 2 U2 5 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 NOV 1 PY 2005 VL 192 IS 9 BP 1588 EP 1596 DI 10.1086/496894 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 970TR UT WOS:000232333000011 PM 16206073 ER PT J AU Ikawa, K Nishioka, T Yu, ZQ Sugawara, Y Kawagoe, J Takizawa, T Primo, V Nikolic, B Kuroishi, T Sasano, T Shimauchi, H Takada, H Endo, Y Sugawara, S AF Ikawa, K Nishioka, T Yu, ZQ Sugawara, Y Kawagoe, J Takizawa, T Primo, V Nikolic, B Kuroishi, T Sasano, T Shimauchi, H Takada, H Endo, Y Sugawara, S TI Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE PMN; serine proteases; G protein-coupled receptor; cytokine; inflammation ID ORAL EPITHELIAL-CELLS; INDUCED LIVER-INJURY; KAPPA-B ACTIVATION; TNF-ALPHA; MACROPHAGE DEPLETION; NAFAMSTAT MESILATE; T-CELLS; INTERLEUKIN-18; EXPRESSION; NAFAMOSTAT AB Activated neutrophils produce serine proteases, which activate cells through proteaseactivated receptor 2 (PAR2). As proteinase 3 (PR3) induces the secretion of interleukin (IL)-18 from epithelial cells in combination with lipopolysaccharide (LPS) in vitro, we examined whether nentrophils, serine proteases, and PAR2 are involved in the induction of serum IL-18 and IL-18-dependent liver injury in mice treated with heat-killed Propionibacterium acnes and LPS. LPS-induced serum IL-18 levels in P. acnes- mice were reduced significantly by anti-Gr-1 injection (depletion of neutrophils and macrophages) but not by a macrophage "suicide" technique, using liposomes encapsulating clodronate. The IL-18 induction was decreased significantly by coadministration of a serine protease inhibitor [Nafamostat mesilate (FUT-175)] with LPS. Serum levels of tumor necrosis factor alpha and liver enzymes induced by P. acnes and LPS were abolished by anti-Gr-1 treatment, and concomitantly, liver injury (necrotic change and granuloma formation) and Gr-1(+) cell infiltration into the liver were prevented by the treatment. A deficiency of PAR2 in mice significantly impaired IL-18 induction by treatment with P. acnes and LPS, and only slight pathological changes in hepatic tissues occurred in the PAR2-deficient mice treated with P. acnes and LPS. Furthermore, coadministration of exogenous murine PR3 or a synthetic PAR2 agonist (ASKH95) with LPS in the anti-Gr-1-treated mice restored the serum IL-18 levels to those in control mice treated with P. acnes and LPS. These results indicate that nentrophil recruitment and PAR2 activation by neutrophil serine proteases are critically involved in the induction of IL-18 and IL-18-dependent liver injury in vivo. C1 Tohoku Univ, Grad Sch Dent, Dept Oral Biol, Div Oral Immunol,Aoba Ku, Sendai, Miyagi 9808575, Japan. Tohoku Univ, Grad Sch Dent, Div Periodontol & Endodontol, Sendai, Miyagi, Japan. Tohoku Univ, Grad Sch Dent, Div Oral Microbiol, Dept Biol, Sendai, Miyagi, Japan. Tohoku Univ, Grad Sch Dent, Dept Oral Med & Surg, Div Oral Biol, Sendai, Miyagi, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Renal Unit, Boston, MA USA. RP Sugawara, S (reprint author), Tohoku Univ, Grad Sch Dent, Dept Oral Biol, Div Oral Immunol,Aoba Ku, 4-1 Seiryo Machi, Sendai, Miyagi 9808575, Japan. EM sugawars@mail.tains.tohoku.ac.jp RI Yu, Zhiqian/M-5041-2016 OI Yu, Zhiqian/0000-0002-4827-5922 NR 48 TC 20 Z9 20 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2005 VL 78 IS 5 BP 1118 EP 1126 DI 10.1189/jlb.0305151 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 981NL UT WOS:000233095200010 PM 16260585 ER PT J AU Bertram, L Parkinson, M McQueen, MB Mullin, K Hsiao, M Menon, R Moscarillo, TJ Blacker, D Tanzi, RE AF Bertram, L Parkinson, M McQueen, MB Mullin, K Hsiao, M Menon, R Moscarillo, TJ Blacker, D Tanzi, RE TI Further evidence for LBP-1c/CP2/LSF association in Alzheimer's disease families SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID BUTYRYLCHOLINESTERASE-K VARIANT; PEDIGREE DISEQUILIBRIUM TEST; GENETIC ASSOCIATION; CHROMOSOME 12; APOLIPOPROTEIN E4; GENOME SCREEN; PROTEIN GENE; POLYMORPHISM; LINKAGE; METAANALYSIS AB Objectives: Several studies suggested chromosome 12 harbours an Alzheimer's disease (AD) risk factor gene. Significant association of a single nucleotide polymorphism (SNP) in the 3' UTR of transcription factor CP2 (LBP-1c/CP2/LSF or TFCP2) at 12q13 was reported in three independent case-control studies, but no family based analyses have been performed to date. Methods: Genotypes for three SNPs were generated in two independent AD family samples. A meta-analysis on all published case-control studies was also performed. Results: The A allele of the 39 UTR SNP was associated with increased risk for AD in one sample (odds ratio (OR) 2.1, 95% confidence interval (95% CI) 1.1 to 4.3), but not in the other, possibly due to low power. Haplotype analyses showed that this allele is part of a putative risk-haplotype overtransmitted to affected individuals in one sample and in both samples combined. Meta-analysis of the previously associated 39 UTR SNP showed a trend towards a protective effect of the A allele in AD (OR 0.73, 95% CI 0.5 to 1.1). Conclusions: This is the first study to examine LBP-1c/CP2/LSF in AD families, and the fifth to independently show significant association. While our results support a role of this gene in AD pathogenesis, the direction of the effect remains uncertain, possibly indicating linkage disequilibrium with another variant nearby. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,Gerontol Res Unit, Charlestown, MA USA. RP Tanzi, RE (reprint author), MGH E MIND, Genet & Aging Res Unit, 114 16th St, Charlestown, MA 02129 USA. EM tanzi@helix.mgh.harvard.edu RI Bertram, Lars/K-3889-2015 OI Bertram, Lars/0000-0002-0108-124X FU NICHD NIH HHS [R01 HD060726]; NIMH NIH HHS [T32 MH17119] NR 37 TC 9 Z9 10 U1 1 U2 1 PU B M J PUBLISHING 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 NOV PY 2005 VL 42 IS 11 BP 857 EP 862 DI 10.1136/jmg.2004.024596 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 980XB UT WOS:000233050400008 PM 16272261 ER PT J AU Rorabaugh, BR Gaivin, RJ Papay, RS Shi, T Simpson, PC Perez, DM AF Rorabaugh, BR Gaivin, RJ Papay, RS Shi, T Simpson, PC Perez, DM TI Both alpha(1A)- and alpha(1B)-adrenergic receptors crosstalk to downregulate beta(1)-ARs in mouse heart: coupling to differential PTX-sensitive pathways SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE adrenergic receptor; inotropy; transgenic; cardiac function ID RAT CARDIAC MYOCYTES; FAILING HUMAN-HEART; PROTEIN-KINASE; INOTROPIC RESPONSE; SIGNALING PATHWAYS; TRANSGENIC MICE; KNOCKOUT MOUSE; SUBTYPES; OVEREXPRESSION; HYPERTROPHY AB Adrenergic receptors (ARs) play an important role in the regulation of cardiac function. Cardiac inotropy is primarily regulated by (beta(1)-ARs. However, alpha(1)-ARs may play an important role in inotropy during heart failure. Previous work has suggested that the alpha(1B)-AR modulates beta(1)-AR function in the heart. The potential role of the alpha(1A)-AR has not been previously studied. We used transgenic mice that express constitutively active mutant (CAM) forms of the alpha(1A)-AR or alpha(1B)-AR regulated by their endogenous promoters. Expression of the CAM a,A-AR or CAM alpha(1B)-AR had no effect on basal cardiac function (developed pressure, +dP/dT, -dP/dT, heart rate, flow rate). However, both alpha(1)-AR subtypes significantly decreased isoproterenol-stimulated +dP/dT. Pertussis toxin had no effect on +dP/dT in CAM a, A-AR hearts but restored +dP/dT to non-transgenic values in CAM alpha(1B)-AR hearts. Radioligand binding indicated a selective decrease in the density of beta(1)-ARs in both CAM mice. However, G-proteins, cAMP, or the percentage of high and low affinity states were unchanged in either transgenic compared with control. These data demonstrate that CAM alpha(1A)- and alpha(1B)-ARs both downregulate beta(1)-AR-mediated inotropy in the mouse heart. However, alpha(1)-AR subtypes are coupled to different beta-AR mediated signaling pathways with the alpha(1B)-AR being pertussis toxin sensitive. (c) 2005 Elsevier Ltd. All rights reserved. C1 Cleveland Clin Fdn, Dept Mol Cardiol, Lerner Res Inst, Cleveland, OH 44195 USA. Univ Calif San Francisco, Div Cardiol, San Francisco VA Med Ctr, CVRI, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. RP Perez, DM (reprint author), Cleveland Clin Fdn, Dept Mol Cardiol, Lerner Res Inst, NB5,9500 Euclid Ave, Cleveland, OH 44195 USA. EM perezd@ccf.org FU NHLBI NIH HHS [R01 HL031113, T32 HL07914, R01 HL61438, R01 HL31113] NR 35 TC 16 Z9 17 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2005 VL 39 IS 5 BP 777 EP 784 DI 10.1016/j.yjmcc.2005.07.015 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 982HS UT WOS:000233149300006 PM 16171811 ER PT J AU Ogino, S Wilson, RB Gold, B Flodman, P AF Ogino, S Wilson, RB Gold, B Flodman, P TI Bayesian risk assessment in genetic testing for autosomal dominant disorders with age-dependent penetrance, including hereditary cancer syndromes. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Natl Canc Inst Frederick, Frederick, MD USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 654 EP 655 PG 2 WC Pathology SC Pathology GA 978LA UT WOS:000232873500043 ER PT J AU Ouahchi, K Xin, W Sims, K AF Ouahchi, K Xin, W Sims, K TI Identification of frizzled-4 (FZD4) mutation in a Norrie patient. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. MGH, Neurogenet DNA Diagnost Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 658 EP 658 PG 1 WC Pathology SC Pathology GA 978LA UT WOS:000232873500058 ER PT J AU Longtine, J Lee, S Parvu, V Brown, M Rainen, L AF Longtine, J Lee, S Parvu, V Brown, M Rainen, L TI Comparison of PAXgene (TM) blood RNA system with standard EDTA/TRIzol RNA extraction for BCR-ABL mRNA testing in a cohort of patients accrued through an Internet based clinical protocol. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. BD Pre AnalytiX, Franklin Lakes, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 664 EP 664 PG 1 WC Pathology SC Pathology GA 978LA UT WOS:000232873500081 ER PT J AU Ogino, S Meyerhardt, J Cantor, M Brahmandam, M Ryan, D Namgyal, C Kawasaki, T Kinsella, K Enzinger, P Clark, J Kulke, M Loda, M Fuchs, C AF Ogino, S Meyerhardt, J Cantor, M Brahmandam, M Ryan, D Namgyal, C Kawasaki, T Kinsella, K Enzinger, P Clark, J Kulke, M Loda, M Fuchs, C TI Molecular predictors of response to combination chemotherapy with gefitinib (zd1839, EGFR tyrosine kinase inhibitor) for advanced colorectal cancer. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. DFCI, Boston, MA USA. MGH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 682 EP 682 PG 1 WC Pathology SC Pathology GA 978LA UT WOS:000232873500156 ER PT J AU Amicarelli, G Shehi, E Makrigiorgos, MG Adlerstein, D AF Amicarelli, G Shehi, E Makrigiorgos, MG Adlerstein, D TI Detection and genotyping of Kras codon 12 mutations by a new restriction endonuclease-based amplification reaction. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 DiaSorin Biomol Sci, Biomol Sci, Milan, Italy. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 685 EP 685 PG 1 WC Pathology SC Pathology GA 978LA UT WOS:000232873500166 ER PT J AU Ogino, S Kawasaki, T Cantor, M Namgyal, C Brahmandam, M Kirkner, G Laird, PW Loda, M Fuchs, C AF Ogino, S Kawasaki, T Cantor, M Namgyal, C Brahmandam, M Kirkner, G Laird, PW Loda, M Fuchs, C TI Validation of quantitative real-time PCR for methylation of MGMT, MLH1 and CDKN2A (p16) promoters in paraffin-embedded tissue. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. DFCI, Boston, MA 02115 USA. Univ So Calif, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 692 EP 692 PG 1 WC Pathology SC Pathology GA 978LA UT WOS:000232873500195 ER PT J AU Gurrera, RJ Nestor, PG O'Donnell, BF Rosenberg, V McCarley, RW AF Gurrera, RJ Nestor, PG O'Donnell, BF Rosenberg, V McCarley, RW TI Personality differences in schizophrenia are related to performance on neuropsychological tasks SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE schizophrenia; personality; personality traits; cognitive neuroscience; personality disorders ID FINE MOTOR-PERFORMANCE; PREMORBID PERSONALITY; TRAITS; DEFICITS; DYSFUNCTION; PSYCHOPATHOLOGY; ASSOCIATION; NEUROTICISM; COMMUNITY; DISORDER AB Altered cognition and personality appear to emerge in tandem and adversely affect outcome in schizophrenia, yet little research has been done to determine whether these are related or independent domains. In this study, the relationship between the Big Five personality traits-neuroticism, extraversion, openness, agreeableness, conscientiousness-and cognitive and motor performance in outpatients with chronic, clinically stable schizophrenia (N = 30) and age-matched healthy comparison subjects (N = 45) was examined. Subjects completed tests of attention, executive and motor functions, and the NEO-Five Factor Personality Inventory. Patients scored significantly higher on neuroticism and lower on extraversion and agreeableness, but after variance due to neuropsychological performance was statistically removed from NEO scale scores, personality dimensions and profiles no longer differed between groups. Neuropsychological performance and demographic variables, but not diagnosis, uniquely accounted for statistically significant amounts of personality variance, and neuropsychological task performance was correlated with personality dimensions in both patients and comparison subjects. These cross-sectional data provide preliminary evidence that personality dysfunction in schizophrenia may be mediated by disease-related changes in cognitive operations, or the neural processes underlying them. Longitudinal studies utilizing more comprehensive measures of neurocognitive performance are needed to define further the relationship between neuropsychological function and personality in schizophrenia. C1 VA Boston Healthcare Syst, Brockton, MA 02301 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Indiana Univ, Dept Psychol, Bloomington, IN USA. RP Gurrera, RJ (reprint author), VA Boston Healthcare Syst, 116A,940 Belmont St, Brockton, MA 02301 USA. RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH-40779] NR 41 TC 16 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2005 VL 193 IS 11 BP 714 EP 721 DI 10.1097/01.nmd.0000185938.30783.6b PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 982DS UT WOS:000233138700002 PM 16260924 ER PT J AU Farabaugh, A Ongur, D Fava, M Hamill, SK Burns, AM Alpert, J AF Farabaugh, A Ongur, D Fava, M Hamill, SK Burns, AM Alpert, J TI Personality disorders and the trimensional personality questionnaire factors in major depressive disorder SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article DE personality disorders; TPQ; temperament; depression ID PANIC DISORDER; TEMPERAMENT; DIMENSIONS; CHARACTER; FEATURES AB We assessed the potential relationship between personality disorder (PD) clusters, as assessed by the SCID-II, and temperamental traits assessed by the Tridimensional Personality Questionnaire (TPQ) among a well-characterized, unmedicated cohort of outpatients with major depressive disorder (MDD). The TPQ and SCID-II were administered to 263 depressed outpatients (mean age = 39.9 +/- 10.5 years; women 139, 53%; initial 17-item Hamilton Rating Scale for Depression 19.6 +/- 3.4) who currently met criteria for MDD and who were enrolled in an 8-week treatment trial. The multiple linear regression method was used to evaluate the relationship between TPQ factors and personality disorder clusters, controlling for age, gender, and initial 17-item Hamilton Rating Scale for Depression score as necessary. Among outpatients with M[DD, meeting criteria for a Cluster A PD diagnosis was related to high harm avoidance (HA) scores, as well as low reward dependence and novelty seeking (NS) scores. Additionally, high HA scores were associated with meeting criteria for a Cluster C PD diagnosis, while high NS scores were associated with meeting criteria for a Cluster B PD diagnosis. Certain temperament traits, especially HA and NS, appear to be associated with specific patterns of personality clusters among depressed patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Depress Clin & Res Program, Boston, MA 02114 USA. RP Farabaugh, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Psychiat, Depress Clin & Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. OI Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [R01-MH-48-483-05] NR 16 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD NOV PY 2005 VL 193 IS 11 BP 747 EP 750 DI 10.1097/01.nmd.0000185873.36662.76 PG 4 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 982DS UT WOS:000233138700009 PM 16260931 ER PT J AU Aghi, M Kiehl, TR Brisman, JL AF Aghi, M Kiehl, TR Brisman, JL TI Breast adenocarcinoma metastatic to epidural cervical spine meningioma: case report and review of the literature SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE breast cancer; E-cadherin; spinal epidural tumor; spinal meningioma; spinal metastases ID CELL-ADHESION MOLECULE; HUMAN BRAIN-TUMORS; INTRACRANIAL MENINGIOMA; CANCER-CELLS; E-CADHERIN; CARCINOMA; ASSOCIATION; EXPRESSION; LUNG; PROGNOSIS AB While several cases of cancer metastatic to cranial meningiomas have been reported, metastasis to spinal meningioma has been reported only once, and a mechanism for such metastases has not been investigated. We report a case of breast carcinoma metastatic to an epidural cervical meningioma, summarize the literature on metastases to central nervous system meningiomas, and suggest a possible mechanism. Our patient, a 55-year-old woman, presented with difficulty walking, back pain, and quadriparesis. Magnetic resonance imaging revealed an enhancing C3-4 epidural lesion and an L4 compression fracture. Because of concern that the fracture and epidural lesion might represent metastases, we performed a metastatic work-up, which revealed a right breast mass. The patient underwent C3-C4 laminectomies and an epidural lesion was encountered. Intraoperative frozen section revealed mixed meningioma and breast adenocarcinoma. A gross total resection was achieved and the patient subsequently received spinal irradiation and hormonal therapy. Whereas a literature review revealed numerous reports of metastases to cranial meningiomas, this represents only the second reported case of such pathology in the spine. Mechanisms of this unusual process likely include meningiomas' vascularity, meningiomas' slow growth providing nutrient availability, and perhaps, as suggested by our analysis, E-cadherin expression by both meningiomas and breast cancer. Metastasis to meningioma must be considered in an epidural spinal lesion in all patients with a known malignancy, with surgical aggressiveness tailored to the intraoperative pathologic diagnosis. C1 Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Roosevelt Med Ctr, Ctr Endovasc Surg, New York, NY USA. RP Aghi, M (reprint author), Massachusetts Gen Hosp, Dept Neurosurg, White Bldg,Room 502,55 Fruit St, Boston, MA 02114 USA. EM maghi@partners.org NR 57 TC 24 Z9 24 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2005 VL 75 IS 2 BP 149 EP 155 DI 10.1007/s11060-005-1408-4 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 983MP UT WOS:000233236800007 PM 16132512 ER PT J AU Saura, J Angulo, E Ejarque, A Casado, V Tusell, JM Moratalla, R Chen, JF Schwarzschild, MA Lluis, C Franco, R Serratosa, J AF Saura, J Angulo, E Ejarque, A Casado, V Tusell, JM Moratalla, R Chen, JF Schwarzschild, MA Lluis, C Franco, R Serratosa, J TI Adenosine A(2A) receptor stimulation potentiates nitric oxide release by activated microglia SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adenosine; astrocyte; glial activation; lipopolysaccharide; microglia; nitric oxide ID A(2A) RECEPTORS; RAT MICROGLIA; SYNTHASE EXPRESSION; ALZHEIMERS-DISEASE; CEREBRAL-ISCHEMIA; PARKINSON-DISEASE; QUINOLINIC ACID; CAFFEINE INTAKE; CELLS; ASTROCYTES AB The absence of adenosine A(2A) receptors, or its pharmacological inhibition, has neuroprotective effects. Experimental data suggest that glial A(2A) receptors participate in neurodegeneration induced by A(2A) receptor stimulation. In this study we have investigated the effects of A(2A) receptor stimulation on control and activated glial cells. Mouse cortical mixed glial cultures (75% astrocytes, 25% microglia) were treated with the A(2A) receptor agonist CGS21680 alone or in combination with lipopolysaccharide (LPS). CGS21680 potentiated lipopolysaccharide-induced NO release and NO synthase-II expression in a time- and concentration-dependent manner. CGS21680 potentiation of lipopolysaccharide-induced NO release was suppressed by the A(2A) receptor antagonist ZM-241385 and did not occur on mixed glial cultures from A(2A) receptor-deficient mice. In mixed glial cultures treated with LPS + CGS21680, the NO synthase-II inhibitor 1400W abolished NO production, and NO synthase-II immunoreactivity was observed only in microglia. Binding experiments demonstrated the presence of A(2A) receptors on microglial but not on astroglial cultures. However, the presence of astrocytes was necessary for CGS21680 potentiating effect. In light of the reported neurotoxicity of microglial NO synthase-II and the neuroprotection of A(2A) receptor inhibition, these data suggest that attenuation of microglial NO production could contribute to the neuroprotection afforded by A(2A) receptor antagonists. C1 CSIC, IDIBAPS, IIBB, Dept Pharmacol & Toxicol, Barcelona 08036, Spain. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain. IDIBAPS, Mol Biol Unit, Barcelona, Spain. CSIC, IDIBAPS, IIBB, Dept Neurochem, Barcelona, Spain. CSIC, Inst Cajal, E-28002 Madrid, Spain. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Saura, J (reprint author), CSIC, IDIBAPS, IIBB, Dept Pharmacol & Toxicol, Rossello 161,Planta 6, Barcelona 08036, Spain. EM jsafat@iibb.csic.es RI Saura, Josep/I-4428-2012; Franco, Rafael/C-3694-2015; Moratalla, Rosario/H-9280-2015; Casado, Vicent/K-1660-2014; OI Franco, Rafael/0000-0003-2549-4919; Moratalla, Rosario/0000-0002-7623-8010; Casado, Vicent/0000-0002-1764-3825; Saura, Josep/0000-0002-5601-4466 FU NIEHS NIH HHS [ES10804] NR 58 TC 78 Z9 83 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2005 VL 95 IS 4 BP 919 EP 929 DI 10.1111/j.1471-4159.2005.03395.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 978CO UT WOS:000232850000002 PM 16092928 ER PT J AU Benn, SC Ay, I Bastia, E Chian, RJ Celia, SA Pepinsky, RB Fishman, PS Brown, RH Francis, JW AF Benn, SC Ay, I Bastia, E Chian, RJ Celia, SA Pepinsky, RB Fishman, PS Brown, RH Francis, JW TI Tetanus toxin fragment C fusion facilitates protein delivery to CNS neurons from cerebrospinal fluid in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebrospinal fluid; fusion protein; motor neurons; protein delivery; superoxide dismutase; tetanus toxin fragment C ID AMYOTROPHIC-LATERAL-SCLEROSIS; RETROGRADE AXONAL-TRANSPORT; PLACEBO-CONTROLLED TRIAL; CENTRAL-NERVOUS-SYSTEM; SUPEROXIDE-DISMUTASE; NEUROTROPHIC FACTOR; GENE-THERAPY; TARGETED DELIVERY; IMMUNE-RESPONSES; RAT-BRAIN AB To improve protein delivery to the CNS following intracerebroventricular administration, we compared the distribution of a human Cu/Zn superoxide dismutase:tetanus toxin fragment C fusion protein (SOD1:TTC) in mouse brain and spinal cord with that of tetanus toxin fragment C (TTC) or human SOD1 (hSOD1) alone, following continuous infusion into the lateral ventricle. Mice infused with TTC or SOD1:TTC showed intense anti-TTC or anti-hSOD1 labeling, respectively, throughout the CNS. In contrast, animals treated with hSOD1 revealed moderate staining in periventricular tissues. In spinal cord sections from animals infused with SOD1:TTC, the fusion protein was found in neuron nuclear antigen-positive (NeuN(+)) neurons and not glial fibrillary acidic protein-positive (GFAP(+)) astrocytes. The percentage of NeuN(+) ventral horn cells that were co-labeled with hSOD1 antibody was greater in mice treated with SOD1:TTC (cervical cord = 73 +/- 8.5%; lumbar cord = 62 +/- 7.7%) than in mice treated with hSOD1 alone (cervical cord = 15 +/- 3.9%; lumbar cord = 27 +/- 4.7%). Enzyme-linked immunosorbent assay for hSOD1 further demonstrated that SOD1:TTC-infused mice had higher levels of immunoreactive hSOD1 in CNS tissue extracts than hSOD1-infused mice. Following 24 h of drug washout, tissue extracts from SOD1:TTC-treated mice still contained substantial amounts of hSOD1, while extracts from hSOD1-treated mice lacked detectable hSOD1. Immunoprecipitation of SOD1:TTC from these extracts using anti-TTC antibody revealed that the recovered fusion protein was structurally intact and enzymatically active. These results indicate that TTC may serve as a useful prototype for development as a non-viral vehicle for improving delivery of therapeutic proteins to the CNS. C1 Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Mol Neurobiol Lab, Charlestown, MA USA. BiogenIdec Inc, Cambridge, MA USA. Baltimore Vet Affairs Med Ctr, Res Serv, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. RP Francis, JW (reprint author), Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Dept Neurol, Bldg 114,16th St,Room 3003, Charlestown, MA 02129 USA. EM jwfrancis@partners.org NR 39 TC 19 Z9 20 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2005 VL 95 IS 4 BP 1118 EP 1131 DI 10.1111/j.1471-4159.2005.03459.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 978CO UT WOS:000232850000019 PM 16271047 ER PT J AU Dong, SM Nutt, CL Betensky, RA Stemmer-Rachamimov, AO Denko, NC Ligon, KL Rowitch, DH Louis, DN AF Dong, SM Nutt, CL Betensky, RA Stemmer-Rachamimov, AO Denko, NC Ligon, KL Rowitch, DH Louis, DN TI Histology-based expression profiling yields novel prognostic markers in human glioblastoma SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE glioma; glioblastoma; hypoxia; necrosis; prognosis ID CANCER PROGRESSION; TUMOR-CELLS; HYPOXIA; GROWTH; IDENTIFICATION; SURVIVAL; NECROSIS; GENES; CLASSIFICATION; POPULATION AB Although the prognosis for patients with glioblastoma is poor, survival is variable, with some patients surviving longer than others. For this reason, there has been longstanding interest in the identification of prognostic markers for glioblastoma. We hypothesized that specific histologic features known to correlate with malignancy most likely express molecules that are directly related to the aggressive behavior of these tumors. We further hypothesized that such molecules could be used as biomarkers to predict behavior in a manner that might add prognostic power to sole histologic observation of the feature. We reasoned that perinecrotic tumor cell palisading, which denotes the most aggressive forms of malignant gliomas, would be a striking histologic feature on which to test this hypothesis. We therefore used laser capture microdissection and oligonucleotide arrays to detect molecules differentially expressed in perinecrotic palisades. A set of RNAs (including POFUT2, PTDSR, PLOD2, ATF5, and HK2) that were differentially expressed in 3 initially studied, microdissected glioblastomas also provided prognostic information in an independent set of 28 glioblastomas that did not all have perinecrotic palisades. On validation in a second, larger independent series, this approach could be applied to other human glioma types to derive tissue biomarkers that could offer ancillary prognostic and predictive information alongside standard histopathologic examination. C1 Massachusetts Gen Hosp, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Stanford Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Stanford, CA 94305 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Louis, DN (reprint author), Massachusetts Gen Hosp, Mol Pathol Unit, CNY7,149 13th St, Charlestown, MA 02129 USA. EM dlouis@partners.org RI Nutt, Catherine/K-8794-2012; denko, nicholas/F-8444-2010 FU NCI NIH HHS [CA57683, CA95616, P01 CA095616, R01 CA057683] NR 45 TC 47 Z9 48 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD NOV PY 2005 VL 64 IS 11 BP 948 EP 955 DI 10.1097/01.jnen.0000186940.14779.90 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 983RN UT WOS:000233249900003 PM 16254489 ER PT J AU Amin-Hanjani, S Butler, WE Ogilvy, CS Carter, BS Barker, FG AF Amin-Hanjani, S Butler, WE Ogilvy, CS Carter, BS Barker, FG TI Extracranial-intracranial bypass in the treatment of occlusive cerebrovascular disease and intracranial aneurysms in the United States between 1992 and 2001: a population-based study SO JOURNAL OF NEUROSURGERY LA English DT Review DE extracranial-intracranial bypass; cerebrovascular disease; aneurysm; surgical outcome ID INTERNAL CAROTID-ARTERY; EC-IC BYPASS; CEREBRAL REVASCULARIZATION; SUBARACHNOID HEMORRHAGE; HOSPITAL VOLUME; SURGEON VOLUME; PROVIDER CASELOAD; MORTALITY-RATES; BRAIN-TUMORS; VERTEBROBASILAR INSUFFICIENCY AB Object. The authors assessed the results of extracranial-intracranial (EC-IC) bypass surgery in the treatment of occlusive cerebrovascular disease and intracranial aneurysms in the US between 1992 and 2001 by using population-based methods. Methods. This is a retrospective cohort study based on data from the Nationwide Inpatient Sample (Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality, Rockville, MD). Five hundred fifty-eight operations were per-formed at 158 hospitals by H 5 identified surgeons. The indications for surgery were cerebral ischemia in 74% of the operations (2.4% mortality rate), unruptured aneurysms in 19% of the operations (7.7% mortality rate), and ruptured aneurysms in 7% of the operations (21% mortality rate). Overall, 4.6% of the patients died and 4.7% of the patients were discharged to long-term facilities, 16.4% to short-term facilities, and 74.2% to their homes. The annual number of admissions in the US increased from 190 per year (1992-1996) to 360 per year (1997-2001), whereas the mortality rates increased from 2.8% (1992-1996) to 5.7% (1997-2001). The median annual number of procedures was three per hospital (range one-27 operations) or two per surgeon (range one-21 operations). For 29% of patients, their bypass procedure was the only one recorded at their particular hospital during that year; for these institutions the mean annual caseload was 0.4 admissions per year. For 42% of patients, their particular surgeon performed no other bypass procedure during that year. Older patient age (p < 0.001) and African-American race (p = 0.005) were risk factors for adverse outcome. In a multivariate analysis in which adjustments were made for age, sex, race, diagnosis, admission type, geographic region, medical comorbidity, and year of surgery, high-volume hospitals less frequently had an adverse discharge disposition (odds ratio 0.54, p = 0.03). Conclusions. Most EC-IC bypasses performed in the US during the last decade were performed for occlusive cerebrovascular disease. Community mortality rates for aneurysm treatment including bypass procedures currently exceed published values from specialized centers and, during the period under study, the mortality rates increased with time for all diagnostic subgroups. This technically demanding procedure has become a very low-volume operation at most US centers. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg Neurosurg, Boston, MA 02115 USA. Univ Illinois, Dept Neurosurg, Chicago, IL USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Fruit St, Boston, MA 02114 USA. EM barker@helix.mgh.harvard.edu NR 103 TC 50 Z9 52 U1 0 U2 4 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2005 VL 103 IS 5 BP 794 EP 804 DI 10.3171/jns.2005.103.5.0794 PG 11 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 979GN UT WOS:000232930500008 PM 16304982 ER PT J AU Hayashi, Y Shumsky, JS Connors, T Otsuka, T Fischer, I Tessler, A Murray, M AF Hayashi, Y Shumsky, JS Connors, T Otsuka, T Fischer, I Tessler, A Murray, M TI Immunosuppression with either cyclosporine A or FK506 supports survival of transplanted fibroblasts and promotes growth of host axons into the transplant after spinal cord injury SO JOURNAL OF NEUROTRAUMA LA English DT Article DE allograft survival; axonal growth; cyclosporine A; FK506; immunophilin ligands; spinal cord injury; transplantation ID TRAUMATIC BRAIN-INJURY; BDNF-PRODUCING FIBROBLASTS; IMMUNOPHILIN LIGAND FK506; RAT SCIATIC-NERVE; ADULT RATS; FUNCTIONAL RECOVERY; LIPID-PEROXIDATION; IMMUNE SUPPRESSION; SCHWANN-CELLS; IN-VIVO AB Fibroblasts that have been genetically modified to secrete neurotrophins can stimulate axonal regeneration, rescue injured neurons, and improve function when grafted into a spinal cord injury site. These grafts are usually allografts that require immunosuppression to prevent rejection. In this study, we compared the effects of two immunophilin-ligands (cyclosporine A [CsA] and FK506) that are used clinically to prevent transplant rejection on protection of grafted fibroblasts. As there are risks associated with prolonged immunosuppression, we compared the effects of 2 or 8 weeks of administration of these drugs, in combination with our standard methylprednisolone protocol, in animals that survived for 8 weeks, to determine whether a shorter course of immunosuppression would be effective. Outcome measures included fibroblast survival, infiltration of activated macrophages and microglia into the graft, final lesion size, and growth of host axons into the graft. The graft consisted of a Vitrogen matrix into which fibroblasts were suspended; the graft was placed into a C3/C4 lateral funiculus lesion. The fibroblasts were isolated from a transgenic strain of Fischer rats that produce the marker alkaline phosphatase (Fb/AP). This enabled us to track the grafted fibroblasts and to evaluate the extent of their survival. The grafted matrix filled the lesion cavity. The density of fibroblasts within the matrix differed according to treatment. Fibroblast survival was most robust in animals that received 8 weeks of immunophilin-ligand treatment. FK506 supported greater Fb/AP survival than CsA. ED-1 immunostaining for activated microglia and macrophages showed an inverse correlation between AP immunoreactivity and the density of immune cells within the graft. Thus, prolonged administration of either FK506 or CsA was necessary for maximal fibroblast survival and for limiting the macrophage invasion of the graft. None of the FK506 or CsA protocols modified the size of the lesion, indicating that these immunophilin-ligands had little effect on secondary enlargement of the lesion and therefore little neuroprotective effect. Because immunophilin-ligands have been shown to be neurotrophic, we used RT-97 immunostaining for neurofilaments and calcitonin gene related protein (CGRP) staining for dorsal root axons to visualize axons that grew into the graft. Some axons grew into the matrix even in the absence of immunophilin-ligand treatment, suggesting that the Vitrogen matrix itself is permissive, but all of the immunophilin-ligand protocols were much more effective in eliciting axonal growth. Growth of axons into the transplants was equally increased by drug treatment for 2 or 8 weeks. Thus, both treatments improved fibroblast survival, diminished immune cell invasion, and promoted axonal growth, and a 2-week course of treatment with either immunophilin-ligand was as effective as 8 weeks in stimulating axonal growth. C1 Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. Nagoya City Univ, Sch Med, Dept Orthoped Surg, Nagoya, Aichi 467, Japan. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Murray, M (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, 299 Queen Lane, Philadelphia, PA 19129 USA. EM mm72@drexel.edu RI Fischer, Itzhak/D-1080-2012 OI Fischer, Itzhak/0000-0003-3187-8740 FU NINDS NIH HHS [NS24707] NR 55 TC 28 Z9 34 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD NOV PY 2005 VL 22 IS 11 BP 1267 EP 1281 DI 10.1089/neu.2005.22.1267 PG 15 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 989OI UT WOS:000233683000001 PM 16305315 ER PT J AU Olender, L AF Olender, L TI Hospitalists - A chief nursing officer's perspective SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID HEALTH SYSTEM; MEDICINE; SERVICE; CARE; OUTCOMES; FACULTY AB The hospitalist "specialty" is sweeping the inpatient setting with numbers of physicians choosing this specialty expected to exceed 20,000 by 2010. Yet, little is known about the involvement of nursing in the design, implementation, and evaluation of a hospitalist initiative. The author suggests the chief nursing officer's pivotal role in proactively encouraging the design and implementation of a hospitalist-nurse manager patient-centered care delivery model. The chief nursing officer can create an environment to foster research designed to identify outcomes from this partnership of hospitalist and clinical (nurse) manager. C1 Bronx Vet Adm Med Ctr, Bronx, NY 10468 USA. RP Olender, L (reprint author), Bronx Vet Adm Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Lynda.olender@med.va.gov NR 23 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2005 VL 35 IS 11 BP 497 EP 501 DI 10.1097/00005110-200511000-00006 PG 5 WC Nursing SC Nursing GA 986SD UT WOS:000233469100006 PM 16282827 ER PT J AU Lombardo, ER Tan, G Jensen, MP Anderson, KO AF Lombardo, ER Tan, G Jensen, MP Anderson, KO TI Anger management style and associations with self-efficacy and pain in male veterans SO JOURNAL OF PAIN LA English DT Article DE chronic pain; anger; self-efficacy; veterans ID NEGATIVE AFFECT; EXPERIENCE; SCALE; ADJUSTMENT; EXPRESSION; ARTHRITIS; PEOPLE; MOOD AB Despite the high prevalence of anger and maladaptive anger management among persons with chronic pain, the association between pain and anger has received little empirical attention. The purpose of the current study was to investigate the relationship between pain and anger management style and test for the hypothesized role of self-efficacy as a moderator of this association. Five hundred sixty-four veterans with chronic pain were administered measures of pain, self-efficacy, and anger management. As expected, the results demonstrated a significant positive relationship between pain intensity and maladaptive anger management and a significant negative association between self-efficacy and maladaptive anger. Furthermore, pain intensity and the interaction of self-efficacy and pain intensity were significant predictors of maladaptive anger management. Surprisingly, patients reporting high self-efficacy and high pain intensity demonstrated more maladaptive anger management than individuals reporting high self-efficacy and low pain intensity. Patients reporting low self-efficacy demonstrated high levels of maladaptive anger management, regardless of pain intensity level. Perspective: Maladaptive anger management is associated with pain intensity and self-efficacy beliefs. Additional research is needed to explore the interaction of pain and self-efficacy and its impact on anger management. (c) 2005 by the American Pain Society. C1 Dallas Mind Body Med, Dallas, TX 75205 USA. Baylor Coll Med, Chron Pain Ctr, VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Texas, MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. RP Lombardo, ER (reprint author), Dallas Mind Body Med, 4514 Travis St,Suite 218, Dallas, TX 75205 USA. EM dr.Lombardo@mind-body-wellness.com NR 25 TC 18 Z9 19 U1 3 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1526-5900 J9 J PAIN JI J. Pain PD NOV PY 2005 VL 6 IS 11 BP 765 EP 770 DI 10.1016/j.jpain.2005.07.003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 987DF UT WOS:000233497900007 PM 16275601 ER PT J AU Tsao, JCI Dobalian, A Myers, CD Zeltzer, LK AF Tsao, JCI Dobalian, A Myers, CD Zeltzer, LK TI Pain and use of complementary and alternative medicine in a national sample of persons living with HIV SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE complementary medicine; alternative medicine; human immunodeficiency virus; pain ID HUMAN-IMMUNODEFICIENCY-VIRUS; AMBULATORY AIDS PATIENTS; LOW-PREVALENCE DISEASES; QUALITY-OF-LIFE; UNITED-STATES; INFECTED PATIENTS; SERVICES UTILIZATION; THERAPY USE; PROBABILITY SAMPLES; HEALTH SURVEY AB The current study investigated the relationship of pain to use of complementary and alternative medicine (CAM) in a U.S. nationally representative sample of 2466 persons with human immunodeficiency virus (HIV), using data from the HIV Cost and Services Utilization Study. Pain was conceptualized as a need characteristic within the context of predisposing, enabling, and need (PEN) characteristics following Andersen's Behavioral Model of Health Services Use. Multivariate analyses were used to examine the association of baseline PEN characteristics with CAM use by follow-up (approximately 6 months later), including use of five specific CAM domains. Change in pain from baseline to follow-up was also examined in relation to CAM use. Baseline pain was a strong predictor of CAM use, and increased pain over time was associated with use of unlicensed or underground drugs with potential for harm. These results highlight the importance of medical efforts to control pain in persons living with HIV. C1 Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Pediat Pain Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Anesthesiol, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst HSR&D, Ctr Excellence Study Healthcare Provider Behav, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Dept Interdisciplinary Oncol, Coll Med, Tampa, FL USA. RP Tsao, JCI (reprint author), Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Pediat Pain Program, 10940 Wilshire Blvd,Suite 1450, Los Angeles, CA 90024 USA. OI Zeltzer, Lonnie/0000-0001-9306-9450 FU AHRQ HHS [U01HS08578, U01 HS008578]; NIDA NIH HHS [DA017026, R03 DA017026] NR 48 TC 28 Z9 29 U1 7 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD NOV PY 2005 VL 30 IS 5 BP 418 EP 432 DI 10.1016/j.jpainsymman.2005.05.012 PG 15 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 996LR UT WOS:000234175900005 PM 16310616 ER PT J AU Kieran, MW Turner, CD Rubin, JB Chi, SX Zimmerman, MA Chordas, C Klement, G Laforme, A Gordon, A Thomas, A Neuberg, D Browder, T Folkman, J AF Kieran, MW Turner, CD Rubin, JB Chi, SX Zimmerman, MA Chordas, C Klement, G Laforme, A Gordon, A Thomas, A Neuberg, D Browder, T Folkman, J TI A feasibility trial of antiangiogenic (Metronomic) chemotherapy in pediatric patients with recurrent or progressive cancer SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE angiogenesis; antiangiogenesis; clinical trial; metronontic; pediatric; therapy ID LOW-DOSE CYCLOPHOSPHAMIDE; ENDOTHELIAL GROWTH-FACTOR; CELL LUNG-CANCER; ORAL ETOPOSIDE; PHASE-II; TUMOR ANGIOGENESIS; IN-VIVO; THERAPY; THALIDOMIDE; THROMBOSPONDIN-1 AB Standard chemotherapeutic drugs, when modified by the frequency and dose of administration, can target angiogenesis. This approach is referred to as antiangiogenic chemotherapy, low-dose chemotherapy, or metronomic chemotherapy. This study evaluated the feasibility of 6 months of metronomic chemotherapy, its toxicity and tolerability, surrogate markets of activity, and preliminary evidence of activity in children with recurrent or progressive cancer. Twenty consecutive children were enrolled and received continuous oral thalidomide and celecoxib with alternating oral etoposide and cyclophosphamide every 21 days for a planned duration of 6 months using antiangiogenic doses of all four drugs. Surrogate markers including bFGF, VEGF, endostatin, and thrombospondin were also evaluated. Therapy was well tolerated in this heavily pretreated population. Toxicities (predominantly reversible bone marrow suppression) responded to dose modifications. Sixty percent of the patients received less than the prescribed 6 months of therapy due to toxicity (one case of deep vein thrombosis), personal choice (1 patient), or disease progression (10 patients). Forty percent of the patients completed the 6 months of therapy, resulting in prolonged or persistent disease-free status. One quarter of all patients continue to be progression free more than 123 weeks from starting therapy. Sixteen percent of patients showed a radiographic partial response. Only elevated thrombospondin-1 levels appeared to correlate with prolonged response. This oral antiangiogenic chemotherapy regimen was well tolerated in this heavily pretreated pediatric population, which showed prolonged or persistent disease-free status, supporting the continued study of antiangiogenic/metronomic chemotherapy in human clinical trials. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Washington Univ, Sch Med, St Louis Childrens Hosp, St Louis, MO USA. RP Kieran, MW (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Room SW331, Boston, MA 02115 USA. EM mark_kieran@dfci.harvard.edu OI Kieran, Mark/0000-0003-2184-7692 NR 40 TC 122 Z9 133 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV PY 2005 VL 27 IS 11 BP 573 EP 581 DI 10.1097/01.mph.0000183863.10792.d4 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 986SQ UT WOS:000233470400002 PM 16282886 ER PT J AU Walton, DS Katsavounidou, G AF Walton, DS Katsavounidou, G TI Newborn primary congenital glaucoma: 2005 update SO JOURNAL OF PEDIATRIC OPHTHALMOLOGY & STRABISMUS LA English DT Article ID SURGERY AB Background: Newborn primary congenital glaucoma is an unusual and important subtype of primary congenital glaucoma. Affected patients typically manifest specific signs that facilitate its recognition at birth and become important in the assessment and determination of appropriate treatment for this severe expression of primary congenital glaucoma. Patients and Methods: The medical records of 35 patients with newborn primary congenital glaucoma were reviewed to determine its clinical manifestations and response to therapy. The published literature related to newborn primary congenital glaucoma was reviewed and referenced. Results: Newborn primary congenital glaucoma is recognized at birth because of the associated corneal opacification. Ocular examination reveals anterior segment abnormalities of the cornea, iris, and filtration angle as well as related elevated intraocular pressure. Genetic analysis of a subset of patients with newborn primary congenital glaucoma confirmed its relationship with the less severe infantile form of primary congenital glaucoma, which is characterized by favorable results after goniosurgery. In contrast, goniosurgery was found to have unfavorable results and be less successful compared with trabeculectomy and glaucoma drainage tube shunts as initial therapy for newborn primary congenital glaucoma. Conclusions: Newborn primary congenital glaucoma is an important subtype of primary congenital glaucoma. It can be differentiated from the more frequent and familiar infantile type by history and careful anterior segment examinations to enable and support appropriate choices for its successful surgical treatment. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. MIT, Cambridge, MA 02139 USA. RP Walton, DS (reprint author), 2 Longfellow Pl,Suite 201, Boston, MA 02114 USA. NR 24 TC 20 Z9 21 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0191-3913 J9 J PEDIAT OPHTH STRAB JI J. Pediatr. Ophthalmol. Strabismus. PD NOV-DEC PY 2005 VL 42 IS 6 BP 333 EP 341 PG 9 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 006ZW UT WOS:000234937600004 PM 16382557 ER PT J AU Emery, MJ Krous, HF Nadeau-Manning, JM Marck, BT Matsumoto, AM AF Emery, MJ Krous, HF Nadeau-Manning, JM Marck, BT Matsumoto, AM TI Serum testosterone and estradiol in sudden infant death SO JOURNAL OF PEDIATRICS LA English DT Article ID OBSTRUCTIVE SLEEP-APNEA; CENTRAL NERVOUS-SYSTEM; SEXUAL-DIFFERENTIATION; HYPOGONADAL MEN; ARCUATE NUCLEUS; ANDROGENS; PATTERNS; STEROIDS; MORTALITY; PREMATURE AB Objective To test the hypothesis that among infants who die unexpectedly, testosterone and/or estradiol levels are elevated in those diagnosed with SIDS versus those with known causes of death (controls). Study design Postmortem blood was collected and coded from infant autopsies, and serum was prepared and frozen until assayed for total testosterone and estradiol by fluoroimniunoassay. Subject information was then collected from the medical examiner's report. Results Testosterone, but not estradiol, was significantly higher in 127 SIDS cases versus 42 controls for both males (4.8 +/- 0.4 vs 2.2 +/- 0.4 nmol, respectively; P <.005) and females (2.4 +/- 0.2 vs 1.6 +/- 0.2 nmol, respectively; P < 0.03). Conclusions Higher testosterone levels in infant victims of unexpected, unexplained death may indicate a role for testosterone or related steroids in SIDS. Further research is needed to understand the potential utility of testosterone as an indicator of SIDS risk. C1 Univ Miami, Sch Med, Dept Physiol & Biophys, Miami, FL USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Childrens Hosp, Dept Pathol, San Diego, CA USA. Childrens Hosp, Dept Pediat, San Diego, CA USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. GRECC, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Emery, MJ (reprint author), Univ Washington, Dept Neurol, Sch Med, Box 356465, Seattle, WA 98195 USA. EM mjemery@u.washington.edu NR 34 TC 4 Z9 4 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2005 VL 147 IS 5 BP 586 EP 591 DI 10.1016/j.jpeds.2005.05.011 PG 6 WC Pediatrics SC Pediatrics GA 987EA UT WOS:000233500000009 PM 16291346 ER PT J AU Taubman, MA Valverde, P Han, XZ Kawai, T AF Taubman, MA Valverde, P Han, XZ Kawai, T TI Immune response: The key to bone resorption in periodontal disease SO JOURNAL OF PERIODONTOLOGY LA English DT Article; Proceedings Paper CT Symposium on Host-Pathogen Relationships in Health and Disease CY SEP 10-12, 2004 CL Buffalo, NY DE B lymphocytes; osteoprotegerin; periodontal disease; T lymphocytes ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T-HELPER CELLS; ADOPTIVE TRANSFER; RECEPTOR ACTIVATOR; SELECTIVE BLOCKADE; ORAL INFECTION; B-CELLS; LIGAND; EXPRESSION; RATS AB Periodontal disease infection with oral biofilm microorganisms initiates host immune response and signs of periodontitis, including bone resorption. This review delineates some mechanisms underlying the host immune response in periodontal infection and alveolar bone resorption. Activated T lymphocytes have been historically implicated in experimental periodontal bone resorption. An experimental rat adoptive transfer/ gingival challenge periodontal disease model has been demonstrated to require antigen-specific T lymphocytes and gingival instillation of antigen and LPS for bone resorption. Interference with costimulatory interactions between T cells and antigen-presenting cells abrogated bone resorption, further emphasizing the significance of immune response in periodontal disease. Receptor activator of nuclear factor kappa B ligand (RANKL), a critical osteoclast differentiation factor, is expressed on T lymphocytes in human periodontal disease as determined by immunohistochemical and confocal microscopic analyses. Interference with RANKL by systemic administration of osteoprotegerin (OPG), the decoy receptor for (and inhibitor of) RANKL, resulted in abrogation of periodontal bone resorption in the rat model. This finding indicated that T cell-mediated bone resorption is RANKL-dependent. In additional experiments, treatment of T cell-transferred rats with kaliotoxin (a scorpion venom potassium channel inhibitor) resulted in decreases in T-cell RANKL expression, diminished induction of RANKL-dependent osteoclastogenesis, and abrogation of bone resorption, implicating an important role of immune response/RANKL expression in osteoclastogenesis/bone resorption. In other experiments, adoptive transfer of antigen-specific, RANKL-expressing B cells, and infection with the antigen-bearing Actinobaccillus actinomycetemcomitans gave rise to periodontal bone resorption, indicating that B cells also have the capacity to mediate bone resorption, probably via RANKL expression. In humans, prominent T lymphocytes have been identified in periodontal disease, and diseased tissues showed elevate RANKL mRNA expression, as well as decreased OPG mRNA expression. Mononuclear cells from periodontal lesions involving T cells and B cells of patients induced osteoclastogenesis in vitro. In summary, a biofilm interface initiates immune cell infiltration, stimulating osteoclastogenesis/bone resorption in periodontal disease. This resorption can be ameliorated by inhibition of RANKL activity or by diminishing immune cell stimulation. These two procedures, if localized, have the potential to lead to the prevention or therapeutic management of periodontal disease and therefore require further study. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Tufts Univ, Sch Dent Med, Div Oral Biol, Boston, MA 02111 USA. RP Taubman, MA (reprint author), Forsyth Inst, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. EM mtaubman@forsyth.org RI Valverde, Paloma/A-9897-2008 FU NIDCR NIH HHS [DE014551, DE03420, R01 DE003420] NR 37 TC 200 Z9 210 U1 1 U2 12 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD NOV PY 2005 VL 76 IS 11 SU S BP 2033 EP 2041 DI 10.1902/jop.2005.76.11-S.2033 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 986HD UT WOS:000233439800003 PM 16277573 ER PT J AU Dietrich, T Garcia, RI AF Dietrich, T Garcia, RI TI Associations between periodontal disease and systemic disease: Evaluating the strength of the evidence SO JOURNAL OF PERIODONTOLOGY LA English DT Article; Proceedings Paper CT Symposium on Host-Pathogen Relationships in Health and Disease CY SEP 10-12, 2004 CL Buffalo, NY DE cerebrovascular disease; coronary heart disease; epidemiologic studies; periodontal disease; randomized controlled trials; stroke. ID CORONARY-HEART-DISEASE; SELF-REPORTED SMOKING; CARDIOVASCULAR-DISEASE; CIGARETTE-SMOKING; ISCHEMIC-STROKE; ORAL-HEALTH; CEREBROVASCULAR DISEASES; EPIDEMIOLOGIC RESEARCH; RELATIVE RISK; CAUSAL AB Much work has been published on the association between periodontal disease and systemic disease, including original reports, narrative reviews, systematic reviews, and meta-analyses. Based on the existent work, one can assign an evidence level and grade, using standard evidence-based criteria, to the data available in the four major categories of medical outcomes studied: cardiovascular/cerebrovascular, pregnancy, pulmonary, and diabetes. We discuss methodologic and conceptual problems in the study of oral-systemic associations, focusing as an example on the association between periodontal disease and cardiovascular/cerebrovascular disease. We argue that the hierarchical ranking of studies by levels of evidence may be misleading. In particular, while randomized controlled trials (RCTs) are needed to determine the efficacy of periodontal treatment to reduce the risk of cardiovascular events, they may be of limited value in determining the etiologic role of periodontal disease on coronary heart disease and stroke. We discuss limitations of RCTs as well as the limitations of currently available data from epidemiologic studies, including study design and confounding and misclassification errors. We conclude that well-designed observational studies into the associations between periodontal disease and systemic disease need to remain an integral component of future research efforts in order to fully understand such associations. C1 Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02118 USA. Boston Univ, Goldman Sch Dent Med, Dept Periodontol & Oral Biol, Boston, MA 02118 USA. VA Boston Healthcare Syst, VA Normat Aging Study, Boston, MA USA. RP Garcia, RI (reprint author), Boston Univ, Goldman Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, 715 Albany St,560 3rd Fl, Boston, MA 02118 USA. EM rig@bu.edu OI Dietrich, Thomas/0000-0002-2557-7645 FU NIDCR NIH HHS [K24 DE00419] NR 65 TC 42 Z9 42 U1 0 U2 4 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD NOV PY 2005 VL 76 IS 11 SU S BP 2175 EP 2184 DI 10.1902/jop.2005.76.11-S.2175 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 986HD UT WOS:000233439800021 PM 16277591 ER PT J AU Solt, K Stevens, RJ Davies, PA Raines, DE AF Solt, K Stevens, RJ Davies, PA Raines, DE TI General anesthetic-induced channel gating enhancement of 5-hydroxytryptamine type 3 receptors depends on receptor subunit composition SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTOR; NUCLEUS-TRACTUS-SOLITARIUS; GATED ION-CHANNEL; GABA(A) RECEPTOR; 5-HT3 RECEPTORS; VOLATILE ANESTHETICS; INHIBITION; MODULATION; ACTIVATION; EXPRESSION AB 5-Hydroxytryptamine (serotonin) (5-HT) type 3 (5-HT3) receptors are members of an anesthetic-sensitive superfamily of Cys-loop ligand-gated ion channels that can be formed as homomeric 5-HT3A or heteromeric 5-HT3AB receptors. When the efficacious agonist 5-HT is used, the inhaled anesthetics halothane and chloroform ( at clinically relevant concentrations) significantly reduce the agonist EC50 for 5-HT3A receptors but not for 5-HT3AB receptors. In the present study, we used dopamine (DA), a highly inefficacious agonist for 5-HT3 receptors, to determine whether the difference in sensitivity between 5-HT3A and 5-HT3AB receptors to the potentiating effects of halothane and chloroform is due to differential modulation of agonist affinity, channel gating, or both. Using the two-electrode voltage-clamp technique with 5-HT3A and 5-HT3AB receptors expressed in Xenopus oocytes, we found that chloroform and halothane enhanced currents evoked by receptor-saturating concentrations of DA for both receptor subtypes in a concentration-dependent manner but that the magnitude of enhancement was substantially greater for 5-HT3A receptors than for 5-HT3AB receptors. Isoflurane induced only a small enhancement of currents evoked by receptor-saturating concentrations of DA for 5-HT3A receptors and no enhancement for 5-HT3AB receptors. For both receptor subtypes, none of the three test anesthetics significantly altered the agonist EC50 for DA, implying that these anesthetics do not affect agonist binding affinity. Our results show that chloroform, halothane, and ( to a much lesser degree) isoflurane enhance channel gating for 5-HT3A receptors and that the incorporation of 5-HT3B subunits to produce heteromeric 5-HT3AB receptors markedly attenuates the ability of these anesthetics to enhance channel gating. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Univ Calif San Diego, Program Neurosci, San Diego, CA USA. RP Solt, K (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Edwards 505, Boston, MA 02114 USA. EM ksolt@partners.org OI Davies, Paul/0000-0002-3973-3143; Solt, Ken/0000-0001-5328-2062 FU NIGMS NIH HHS [GM61927, T32-GM07592] NR 24 TC 25 Z9 28 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 771 EP 776 DI 10.1124/jpet.104.090621 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300034 PM 16081679 ER PT J AU Palmer-Toy, DE Krastins, B Sarracino, DA Nadol, JB Merchant, SN AF Palmer-Toy, DE Krastins, B Sarracino, DA Nadol, JB Merchant, SN TI Efficient method for the proteomic analysis of fixed and embedded tissues SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; mass spectrometry; tissue; formaldehyde; paraffin; fixative; histochemistry; temporal bone ID SECTIONS; PROTEINS; DATABASE; DFNA9 AB Formalin-fixed and paraffin-embedded (FFPE) tissues present a particular challenge for proteomic analysis. Yet, most of the archived tissues in hospitals and tissue banks worldwide are only available in this form. We have developed conditions for removal of the embedding medium and protein digestion, such that informative tryptic peptides are released from fixed proteins which are suitable for analysis by liquid chromatography-mass spectrometry (LC-MS). We demonstrate that the peptide identifications made by this approach compare favorably to those made from matched fresh frozen tissue. Moreover, we demonstrate that a high level of sequence coverage can be observed for proteins of interest. C1 Massachusetts Gen Hosp, Harvard Partners Ctr Genet & Genom, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Med, Renal Unit, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Otol & Neurotol Unit, Boston, MA 02114 USA. RP Palmer-Toy, DE (reprint author), SCPMG, Reg Reference Labs, 11668 Sherman Way, N Hollywood, CA 91605 USA. EM dept@alum.mit.edu NR 8 TC 88 Z9 90 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV-DEC PY 2005 VL 4 IS 6 BP 2404 EP 2411 DI 10.1021/pr050208p PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 994CH UT WOS:000234007200061 PM 16335994 ER PT J AU Biederman, J Faraone, SV Wozniak, J Mick, E Kwon, A Cayton, GA Clark, SV AF Biederman, J Faraone, SV Wozniak, J Mick, E Kwon, A Cayton, GA Clark, SV TI Clinical correlates of bipolar disorder in a large, referred sample of children and adolescents SO JOURNAL OF PSYCHIATRIC RESEARCH LA English DT Article DE bipolar disorder; mania; ADHD; comorbidity; adolescents; children ID DEFICIT HYPERACTIVITY DISORDER; MANIC-DEPRESSIVE ILLNESS; ONSET MANIA; THERAPEUTIC CONSIDERATIONS; PREPUBERTAL CHILDREN; VARIANT SYNDROME; CHILDHOOD; COMORBIDITY; DIAGNOSIS; ADHD AB Objective: To compare the prevalence, clinical correlates, and comorbidity among children and adolescents with bipolar disorder (BPD) assessed in the early 1990s (first cohort) with those evaluated over the last 7 years (second cohort). Methods: Subjects were consecutively referred children (N = 108) and adolescents (N = 197) with a DSM-III-R BPD diagnosis, referred to a child psychiatry service and evaluated with identical structured assessment methods. Results: Mania was identified in 16% of referred youth in both age groups and cohorts; in both age groups and cohorts, the clinical picture was predominantly irritable and mixed, and the course was chronic. Youth with BPD in both age groups and cohorts frequently had comorbidity with ADHD, psychosis and anxiety disorders. They also had high rates of psychiatric hospitalization and evidence of severely impaired psychosocial functioning. Conclusions: The consistency of clinical features of bipolar disorder seen across age groups (children vs. adolescents) and cohorts (early and late cohorts) over the past decade supports the hypothesis that BPD in the young is a severe condition afflicting a sizeable minority of referred youth. These findings replicate and extend our previous characterization of an early onset mania, which may represent a developmental subtype of BPD. (c) 2004 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Johnson & Johnson Ctr Study Pediat Psychopathol, Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Stanley Ctr Treatment Pediat Bipolar Disorder, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pretcher Ctr Genet Pediat Bipolar Disorder, Boston, MA 02114 USA. SUNY Syracuse, Syracuse, NY 13210 USA. RP Biederman, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Pediat Psychopharmacol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 NR 45 TC 86 Z9 88 U1 3 U2 10 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 NOV PY 2005 VL 39 IS 6 BP 611 EP 622 DI 10.1016/j.jpsychires.2004.08.003 PG 12 WC Psychiatry SC Psychiatry GA 971UB UT WOS:000232409200008 PM 16009376 ER PT J AU Baethge, C Blumentritt, H Berghofer, A Bschor, T Glenn, T Adli, M Schlattmann, P Bauer, M Finke, R AF Baethge, C Blumentritt, H Berghofer, A Bschor, T Glenn, T Adli, M Schlattmann, P Bauer, M Finke, R TI Long-term lithium treatment and thyroid antibodies: a controlled study SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article ID BIPOLAR DISORDER; CLINICAL HYPOTHYROIDISM; AUTOIMMUNE-THYROIDITIS; ANTITHYROID ANTIBODIES; THERAPY; PREVALENCE; DISEASE; RISK AB Objective: Because the role of thyroid autoimmunity in the development of lithium-induced thyroid dysfunction remains controversial, we compared the prevalence of thyroid autoantibodies in patients with affective disorders receiving long-term lithium maintenance therapy with that of age- and sex- matched controls. Methods: We conducted a cross-sectional study with 100 adult patients with major affective disorders diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, revised (DSM-III-R), who were undergoing lithium therapy for 6 months or more at a specialized lithium university clinic and 100 age- and sex- matched controls with no history of an axis I psychiatric disorder. Serum autoantibodies against thyroid peroxidase (TPOAb), thyroglobulin (TgAb) and TSH receptors (TRAb) were measured. Results: TPOAb were found in 7 patients and 11 controls, and TgAb were found in 8 patients and 15 controls. TRAb were not found in either group. Conclusions: In this sample of patients with affective disorders, long- term lithium treatment did not increase the prevalence of thyroid autoimmunity. C1 Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, D-10117 Berlin, Germany. Harvard Univ, Sch Med, Dept Psychiat,Massachusetts Gen Hosp, Bipolar & Psychot Disorders Program,McLean Div, Belmont, MA 02178 USA. Univ Cologne, Dept Psychiat, Cologne, Germany. Paul Ehrlich Inst, Dept Hematol, D-6070 Langen, Germany. Charite Univ Med Berlin, Inst Social Med Epidemiol & Hlth Econ, Berlin, Germany. Tech Univ Dresden, Dept Psychiat, Carl Gustav Carus Hosp, D-8027 Dresden, Germany. Free Univ Berlin, Charite, Inst Med Informat Epidemiol & Biometry, D-1000 Berlin, Germany. Benjamin Franklin Univ Hosp, Berlin, Germany. IGSLI, ChronoRecord Assoc Inc, Fullerton, CA USA. RP Bauer, M (reprint author), Charite Univ Med Berlin, Dept Psychiat & Psychotherapy, Campus Charite Mitte,Schumannstr 20-21, D-10117 Berlin, Germany. EM michael.bauer@charite.de RI Schlattmann, Peter/B-5289-2008 NR 28 TC 17 Z9 18 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD NOV PY 2005 VL 30 IS 6 BP 423 EP 427 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979KX UT WOS:000232942000005 PM 16327876 ER PT J AU Shaw, SE Morris, DM Uswatte, G Mckay, S Meythaller, JM Taub, E AF Shaw, SE Morris, DM Uswatte, G Mckay, S Meythaller, JM Taub, E TI Constraint-induced movement therapy for recovery of upper-limb function following traumatic brain injury SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE behavioral therapy; constraint-induced movement therapy; functional abilities; massed practice; motor function; motor impairment; neurological injury; physical rehabilitation; training; traumatic brain injury ID MOTOR FUNCTION-TEST; LEARNED NONUSE; CHRONIC STROKE; CORTICAL REORGANIZATION; FORCED USE; REHABILITATION; PLASTICITY; INTENSITY; DEFICITS; OUTCOMES AB A volunteer sample of 22 participants with chronic traumatic brain injury (TBI) (onset > 1 year) and relative hemiplegia that revealed moderate disability in the more-affected upper limb (UL) participated. Constraint-induced (CI) movement therapy (CI therapy) was employed for a 2-week period; treatments included massed practice, shaping of the more-affected UL, behavioral contracts, and other behavioral techniques for affecting transfer to a real-world setting. We used the Wolf Motor Function Test, the Fugl-Meyer Motor Performance Assessment, and the Motor Activity Log to measure outcomes. All outcome measures improved significantly as a result of the intervention. More-adherent participants had more improvement compared with less-adherent participants. These preliminary results suggest that Cl therapy may be effective for improving UL motor function following chronic TBI. C1 Univ Alabama, Dept Phys Therapy, Birmingham, AL 35294 USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Alabama, Dept Phys Med & Rehabil, Birmingham, AL 35294 USA. Birmingham VA Med Ctr, Dept Vet Affairs, Res Serv, Birmingham, AL USA. RP Shaw, SE (reprint author), Univ Alabama, Dept Phys Therapy, RMSB 360,1530 3rd Ave S, Birmingham, AL 35294 USA. EM sshaw@uab.edu RI Uswatte, Gitendra/C-4913-2009 FU PHS HHS [R49/CCR 403541-12] NR 45 TC 36 Z9 40 U1 0 U2 7 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 NOV-DEC PY 2005 VL 42 IS 6 BP 769 EP 778 DI 10.1682/JRRD.2005.06.0094 PG 10 WC Rehabilitation SC Rehabilitation GA 047MQ UT WOS:000237883800007 PM 16680614 ER PT J AU Berge, JS Czerniecki, JM Klute, GK AF Berge, JS Czerniecki, JM Klute, GK TI Efficacy of shock-absorbing versus rigid pylons for impact reduction in transtibial amputees based on laboratory, field, and outcome metrics SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE amputation.. artificial limbs; biomechanics; gait impact force; gait mechanics; prosthetics; rehabilitation; residual-limb pain; rigid pylon; shock-absorbing pylon ID GROUND REACTION FORCES; LEG STIFFNESS; LOWER-LIMB; GAIT; WALKING; PROSTHESIS; PARAMETERS; AMPUTATION; SURFACES; FATIGUE AB Prosthetic manufacturers have marketed shock-absorbing pylons (SAPs) for attenuation of injurious loads from foot-ground contact. In this study, we compared a commonly prescribed SAP with a conventional rigid pylon, using a within-subject design (n = 15 unilateral transtibial amputees), to assess effect on gait mechanics, measure transmitted accelerations in situ, and determine functional outcomes using step counts and questionnaires. No differences were found across pylons for self-selected walking speed, prosthetic-side step length, prosthetic-side loading rate and decelerative peak of the vertical ground reaction force, peak pylon acceleration, step count per week, or questionnaire results that examined pylon performance and subjects' pain and fatigue levels. The only statistically significant finding was for the prosthetic-side knee angle at initial contact, where subjects displayed an average of 2.6 degrees more flexion with the rigid pylon than the SAP while walking at a controlled speed (p = 0.004); this result indicates that transtibial amputees are able to modulate the effective stiffness of their residual limb in response to changes in prosthetic component stiffness. The results from the laboratory, field, and subjective outcome measurements suggest that the SAP in this study is as effective as a rigid pylon for unilateral transtibial amputees. C1 VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, Seattle, WA 98108 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Mech Engn, Seattle, WA 98195 USA. Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. RP Klute, GK (reprint author), VA Puget Sound Hlth Care Syst, Dept Vet Affairs, Rehabil Res & Dev Ctr Excellence Limb Loss Preven, 1660 S Columbian Way,MS 151, Seattle, WA 98108 USA. EM gklute@u.washington.edu NR 30 TC 13 Z9 15 U1 2 U2 10 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 NOV-DEC PY 2005 VL 42 IS 6 BP 795 EP 807 DI 10.1682/JRRD.2005.02.0034 PG 13 WC Rehabilitation SC Rehabilitation GA 047MQ UT WOS:000237883800010 PM 16680617 ER PT J AU Fitzgerald, SG Collins, DM Cooper, RA Tolerico, M Kelleher, A Hunt, P Martin, S Impink, B Cooper, R AF Fitzgerald, SG Collins, DM Cooper, RA Tolerico, M Kelleher, A Hunt, P Martin, S Impink, B Cooper, R TI Issues in maintenance and repairs of wheelchairs: A pilot study SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Article DE community participation; maintenance; manual wheelchair; outcomes; power wheelchair; satisfaction; wheelchair; wheelchair age; wheelchair repairs; wheelchair use ID MANUAL WHEELCHAIRS; ANSI/RESNA STANDARDS; POWERED WHEELCHAIRS; OUTDOOR MOBILITY; UNITED-STATES; USERS; ACCIDENTS; SATISFACTION; TECHNOLOGY; RESIDENTS AB In this pilot study, we assessed wheelchair durability and its effect on user satisfaction. Specifically, we examined the characteristics of the participants' wheelchairs, the types of maintenance and repairs completed, and whether the participants' satisfaction was affected by problems with their wheelchairs. A convenience sample of 130 participants who used wheelchairs as their primary means of mobility was recruited. Participants completed a questionnaire about their wheelchairs, the maintenance and repair history.. and their satisfaction levels. Results showed that 26% of the participants had completed a wheelchair repair in the past 6 months, 16% had completed general maintenance, and 27% had completed tire repairs. Neither hours of wheelchair use nor wheelchair age affected repair or maintenance frequency. Participants were generally satisfied with their wheelchairs. Better understanding, of wheelchair maintenance and repair issues will guide improvements in wheelchair design and enhance the community participation of individuals who use wheelchairs. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Vet Affairs, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Engn, Dept Bioengn, Pittsburgh, PA 15260 USA. RP Fitzgerald, SG (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs, Ctr Excellence Wheelchairs & Related Technol, Dept Vet Affairs, 7180 Highland Dr,Bldg 4,2nd Floor E,151R-1, Pittsburgh, PA 15213 USA. EM sgf9@pitt.edu NR 37 TC 12 Z9 12 U1 0 U2 1 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 NOV-DEC PY 2005 VL 42 IS 6 BP 853 EP 862 DI 10.1682/JRRD.2004.10.0130 PG 10 WC Rehabilitation SC Rehabilitation GA 047MQ UT WOS:000237883800015 PM 16680622 ER PT J AU Olatunji, BO Sawchuk, CN AF Olatunji, BO Sawchuk, CN TI Disgust: Characteristic features, social manifestations, and clinical implications SO JOURNAL OF SOCIAL AND CLINICAL PSYCHOLOGY LA English DT Review ID OBSESSIVE-COMPULSIVE DISORDER; COMMON INDIGENOUS ANIMALS; DISEASE-AVOIDANCE MODEL; NERVOUS-SYSTEM ACTIVITY; BLOOD-INJECTION-INJURY; SPIDER PHOBIA; EATING-DISORDERS; INDIVIDUAL-DIFFERENCES; BULIMIA-NERVOSA; FACIAL EMG AB Emotions have been a long-standing cornerstone of research in social and clinical psychology. Although the systematic examination of emotional processes has yielded a rather comprehensive theoretical and scientific literature, dramatically less empirical attention has been devoted to disgust. In the present article, the nature, experience, and other associated features of disgust are outlined. We also review the domains of disgust and highlight how these domains have expanded over time. The function of disgust in various social constructions, such as cigarette smoking, vegetarianism, and homophobia, is highlighted. Disgust is also becoming increasingly recognized as an influential emotion in the onset, maintenance, and treatment of various phobic states, Obsessive-Compulsive Disorder and eating disorders. In comparison to the other emotions, disgust offers great promise for future social and clinical research efforts, and prospective studies designed to improve our understanding of disgust are outlined. C1 Univ Massachusetts, Amherst, MA 01003 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Olatunji, BO (reprint author), Massachusetts Gen Hosp, Dept Psychiat, WAC 812,15 Parkman St, Boston, MA 02114 USA. EM bolatunji@partners.org NR 104 TC 99 Z9 101 U1 4 U2 24 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0736-7236 J9 J SOC CLIN PSYCHOL JI J. Soc. Clin. Psychol. PD NOV PY 2005 VL 24 IS 7 BP 932 EP 962 DI 10.1521/jscp.2005.24.7.932 PG 31 WC Psychology, Clinical; Psychology, Social SC Psychology GA 993ZB UT WOS:000233997800002 ER PT J AU Feldman, SR Kimball, AB Krueger, GG Woolley, JM Lalla, D Jahreis, A AF Feldman, SR Kimball, AB Krueger, GG Woolley, JM Lalla, D Jahreis, A TI Etanercept improves the health-related quality of life of patients with psoriasis: Results of a phase III randomized clinical trial SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Investigative-Dermatology CY APR 24, 2004 CL Providence, RI SP Soc Investigative Dermatol ID ATOPIC-DERMATITIS; DERMATOLOGY; DISEASE; DLQI AB In this randomized, double-blind, phase III trial, patients with psoriasis received etanercept for 24 weeks or placebo for 12 weeks followed by etanercept for 12 weeks. At week 12, improvement in Dermatology Life Quality Index was 47% to 61% with etanercept compared with 11% with placebo (P <.0001). Etanercept rapidly and substantially improved patients' health-related quality of life. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Dermatol, Winston Salem, NC 27157 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Utah Hlth Sci Ctr, Salt Lake City, UT USA. Amgen Inc, Thousand Oaks, CA USA. RP Feldman, SR (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Dermatol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM sfeldman@wfubmc.edu OI Feldman, Steven/0000-0002-0090-6289 NR 13 TC 49 Z9 52 U1 0 U2 2 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 NOV PY 2005 VL 53 IS 5 BP 887 EP 889 DI 10.1016/j.jaad.2005.06.053 PG 3 WC Dermatology SC Dermatology GA 978UH UT WOS:000232898000028 PM 16243150 ER PT J AU Singh, JP Hall, WJ McNitt, S Wang, HY Daubert, JP Zareba, W Ruskin, JN Moss, AJ AF Singh, JP Hall, WJ McNitt, S Wang, HY Daubert, JP Zareba, W Ruskin, JN Moss, AJ CA MADIT-II Investigators TI Factors influencing appropriate firing of the implanted defibrillator for ventricular tachycardia/fibrillation SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CARDIAC-RESYNCHRONIZATION THERAPY; CONGESTIVE-HEART-FAILURE; CARDIOVERTER-DEFIBRILLATORS; DILATED CARDIOMYOPATHY; QRS DURATION; RISK STRATIFICATION; PRIMARY PREVENTION; DEATH; ARRHYTHMIAS; TRIAL AB OBJECTIVES The purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population. BACKGROUND There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction. METHODS We used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function. RESULTS We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) > 25, body mass index (BMI) >= 30 kg/mz, and New York Heart Association functional class > 11 were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p < 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p < 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02). CONCLUSIONS These results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Univ Rochester, Cardiol Unit, Dept Med, Med Ctr, Rochester, NY 14642 USA. RP Singh, JP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 27 TC 104 Z9 105 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 1 PY 2005 VL 46 IS 9 BP 1712 EP 1720 DI 10.1016/j.jacc.2005.05.088 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 978XH UT WOS:000232905800016 PM 16256874 ER PT J AU Avansino, JR Chen, DC Hoagland, VD Woolman, JD Haigh, WG Stelzner, M AF Avansino, JR Chen, DC Hoagland, VD Woolman, JD Haigh, WG Stelzner, M TI Treatment of bile acid malabsorption using ileal stem cell transplantation SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID MUCOSAL NUTRIENT TRANSPORT; RESECTION AB BACKGROUND: We hypothesized that ileal stem cell clusters transplanted into a segment of jejunum can be used to treat bile acid malabsorption. STUDY DESIGN: In adult Lewis rats, a 15-cm segment of jejunum was isolated with its blood circulation left intact and partially stripped of enterocytes using luminal high-velocity perfusions with 3 mmol/L ethylenediamine tetra-acetic acid solutions. Continuity was restored by anastomosing the proximal and distal gut. Ileal stem cell clusters were harvested from neonatal Lewis rats and transplanted into the stripped segments to generate a "neoileum." After 4 weeks, recipients underwent resection of the native ileum, and the isolated neoileum was anastomosed in its place. After an additional 4 weeks, a 48-hour stool collection was performed. The engrafted segment was harvested for taurocholate uptake studies, ileal bile acid transporter (IBAT) protein by immunohistomorphometry, and IBAT mRNA quantitation by reverse transcription polymerease chain reaction. Data were analyzed by ANOVA/t-test. Rats undergoing ileectomy, jejunectomy, or sham operations served as controls. RESULTS: Total bile acid loss in the stool was markedly lower in rats with a neoileum compared with rats with an ileectomy (p < 0.001). Total taurocholate uptake was notably increased in the neoileum compared with the jejunum (p < 0.001). IBAT protein signal intensity was considerably higher in the neoileum compared with jejunum (p < 0.001). IBAT mRNA amounts in the neoileal group were comparable with those in normal rat ileum and were considerably higher (p = 0.003) than in the jejunum. CONCLUSIONS: Ileal stem cell clusters were used to establish a new zone of bile acid uptake and IBAT expression in a jejunal segment. This neoileum eliminated loss of bile acids in the stool after ileectomy. This is the first time that transplantation of intestinal stem cell clusters has been shown to correct a clinical malabsorption syndrome. C1 Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Seattle, WA 98105 USA. Univ Washington, Dept Gastroenterol, VA Puget Sound Hlth Care Syst, Seattle, WA 98105 USA. Univ Calif Los Angeles, Dept Surg, VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA 90024 USA. RP Avansino, JR (reprint author), Univ Washington, Dept Surg, VA Puget Sound Hlth Care Syst, Box 356410, Seattle, WA 98105 USA. NR 20 TC 18 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD NOV PY 2005 VL 201 IS 5 BP 710 EP 720 DI 10.1016/j.jamcollsurg.2005.06.270 PG 11 WC Surgery SC Surgery GA 980OF UT WOS:000233027100009 PM 16256913 ER PT J AU Kielar, ML John, R Bennett, M Richardson, JA Shelton, JM Chen, LY Jeyarajah, DR Zhou, XJ Zhou, H Chiquett, B Nagami, GT Lu, CY AF Kielar, ML John, R Bennett, M Richardson, JA Shelton, JM Chen, LY Jeyarajah, DR Zhou, XJ Zhou, H Chiquett, B Nagami, GT Lu, CY TI Maladaptive role of IL-6 in ischemic acute renal failure SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REPERFUSION INJURY; ISCHEMIA/REPERFUSION INJURY; INTERLEUKIN-6-DEFICIENT MICE; MACROPHAGE INFILTRATION; INFLAMMATORY RESPONSE; ADHESION MOLECULES; HEMORRHAGIC-SHOCK; IMMUNE-RESPONSES; CELLS; NEUTROPHIL AB The role of IL-6 was investigated in murine ischemic acute renal failure. The renal pedicles were clamped for 17 min, and the mice were studied at various times after reperfusion. We found that serum IL-6 increased after murine ischemic renal injury. This increase was associated with increased IL-6 mRNA in the ischemic kidney but not in the contralateral kidney or the liver. Maximal IL-6 production occurred at 4 to 8 h and decreased to baseline by 24 h. Reperfusion of the kidney was required for IL-6 production. In situ hybridization and immunohistochemistry showed that macro phages infiltrated areas adjacent to the vascular bundles in the outer medulla within hours of reperfusion and showed that these macrophages produced IL-6 mRNA. For understanding how macrophages were stimulated to produce IL-6, an in vitro model in which S3 proximal tubular cells were injured by reactive oxygen species was set up. These injured cells released molecules that activated macrophages to produce IL-6 in vitro. IL-6 that was produced in response to renal ischemia was maladaptive because transgenic knockout of IL-6 ameliorated renal injury as measured by serum creatinine and histology. IL-6 transgenic knockout mice were lethally irradiated, and their bone marrow was reconstituted with wild-type IL-6 cells. Such bone marrow transfers abolished the protective effects of transgenic IL-6 knockout. It is concluded that macrophages infiltrate the area of the vascular bundles of the outer medulla, these macrophages produce IL-6, and this IL-6 exacerbates ischemic murine acute renal failure. C1 Univ Texas, SW Med Sch, Dept Internal Med Nephrol, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Dept Mol Biol, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Dept Internal Med Cardiol, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Dept Surg, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Grad Program Immunol, Dallas, TX 75390 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Med Res Serv, Serv Nephrol, Los Angeles, CA USA. RP Lu, CY (reprint author), Univ Texas, SW Med Sch, Dept Internal Med Nephrol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM christopher.lu@utsouthwestern.edu NR 50 TC 131 Z9 139 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2005 VL 16 IS 11 BP 3315 EP 3325 DI 10.1681/asn.2003090757 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 978BS UT WOS:000232847800021 PM 16192425 ER PT J AU Ishii, O Shin, M Sueda, T Vacanti, JP AF Ishii, O Shin, M Sueda, T Vacanti, JP TI In vitro tissue engineering of a cardiac graft using a degradable scaffold with an extracellular matrix-like topography SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID CARDIOMYOCYTES; MUSCLE; CELLS; TRANSPLANTATION; DIFFERENTIATE; MANIPULATION; MYOCARDIUM; REPAIR; MODEL AB Objective: Cardiac tissue engineering has been proposed as a treatment to repair impaired hearts. Bioengineered cardiac grafts are created by combining autologous cell transplantation with a degradable scaffold as a temporary extracellular matrix. Here we present a system for engineered myocardium combining cultured cardio myocytes and a novel biodegradable scaffold with a unique extracellular matrix-like topography. Methods: Cardiomyocytes were harvested from neonatal rats and cultured in vitro on biodegradable electrospun nanotibrous poly (epsilon-caprol actone) meshes. Between-dimensional cardiac grafts. On days 5 and 7, the meshes were overlaid to construct 3 day 14 of in vitro culture, the engineered cardiac grafts were analyzed by means of histology, immunohistochemistry, and scanning electron microscopy. Results: The cultured cardiomyocytes attached well to the meshes, and strong beating was observed throughout the experimental period. The average fiber diameter of the scaffold is about 250 nm, well below the size of an individual cardiomyocyte. Hence the number of cell-cell contacts is maximized. Constructs with up to 5 layers could be formed without any incidence of core ischemia. The individual layers adhered intimately. Morphologic and electrical communication between the layers was established, as verified by means of histology and immunohistochemistry. Synchronized beating was also observed. Conclusions: This report demonstrates the formation of thick cardiac grafts in vitro and the versatility of biodegradable electrospun meshes for cardiac tissue engineering. It is envisioned that cardiac grafts with clinically relevant dimensions can be created by using this approach and combining it with new technologies to induce vascularization. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hiroshima Univ, Sch Med, Dept Surg 1, Hiroshima, Japan. RP Shin, M (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. EM michael.shin@gmail.com NR 25 TC 59 Z9 62 U1 2 U2 9 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 NOV PY 2005 VL 130 IS 5 BP 1358 EP 1363 DI 10.1016/j.jtcvs.2005.05.048 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 981XA UT WOS:000233120100017 PM 16256789 ER PT J AU Wright, CD Wain, JC Wong, DR Donahue, DM Gaissert, HA Grillo, HC Mathisen, DJ AF Wright, CD Wain, JC Wong, DR Donahue, DM Gaissert, HA Grillo, HC Mathisen, DJ TI Predictors of recurrence in thymic tumors: Importance of invasion, World Health Organization histology, and size SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 85th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 10-13, 2005 CL San Francisco, CA SP Amer Assoc Thorac Surg ID MULTIMODALITY TREATMENT; ADJUVANT RADIATION; SURGICAL-TREATMENT; THYMOMA; CLASSIFICATION; SURVIVAL; THERAPY AB Objective: This study sought to define predictors of recurrence after resection of thymic tumors. Methods: A single-institution retrospective study was performed of 179 patients who underwent resection of a thymic tumor from 1972 through 2003. Results: Resection was complete in 90% (161/179) of patients. After a median follow-up of 115 months, the recurrence rate was 11% (20/179), the tumor-related death rate was 7.8% (14/179), and the overall death rate was 36.3% (65/179). Tumor recurrence correlated with advanced stage and histology (P < .0001). The difference in recurrence between Masaoka stage I (0) and II(1.7% [1/59]) was insignificant. Recurrence rates correlated with World Health Organization tumor type: A and AB, 0%; B1 and B2, 8% (4/51); B3, 27% (14/51); and C, 50% (2/4; P < .0001). Tumor size separation into quintiles demonstrated a step-up of recurrence at 8 cm (< 8 cm, 1.8% [2/113]; >= 8 cm, 28% [18/64]; P <.003). Multivariate Cox modeling demonstrated that Masaoka stage (odds ratio, 5.70; P <.001), World Health Organization histology (odds ratio, 5.77; P =.003), and size (odds ratio, 1.16; P = .001) were independent predictors of recurrence. Conclusion: The Masaoka staging system could be collapsed to 3 degrees of invasion by combining stages I and II. The World Health Organization histologic type can be simplified for clinical. use into A (A, AB), early B (B 1, 132), advanced B (133), and C tumors. Size of 8 cm or larger is an independent risk factor, even when patients with Masaoka stage III tumors are considered alone, and might identify candidates for preoperative therapy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Thorac Surg, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gen Thorac Surg, Blake 1570, Boston, MA 02114 USA. EM wright.Cameron@mgh.harvard.edu NR 18 TC 110 Z9 120 U1 0 U2 1 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 NOV PY 2005 VL 130 IS 5 BP 1413 EP 1421 DI 10.1016/j.jtcvs.2005.07.026 PG 9 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 981XA UT WOS:000233120100025 PM 16256797 ER PT J AU Brown, CVR Neville, AL Rhee, P Salim, A Velmahos, GC Demetriades, D AF Brown, CVR Neville, AL Rhee, P Salim, A Velmahos, GC Demetriades, D TI The impact of obesity on the outcomes of 1,153 critically injured blunt trauma patients SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 35th Annnual Meeting of the Western-Trauma-Association CY FEB 27-MAR 05, 2005 CL Jackson Hole, WY SP Western Trauma Assoc ID MORTALITY AB Background: Several small series have had mixed conclusions regarding the impact of obesity on outcomes of trauma patients. The purpose of the present study was to evaluate a large cohort of critically injured patients to better understand the influence of obesity on the outcomes of patients after severe blunt trauma. Methods: Retrospective review using the trauma registry and intensive care unit (ICU) database of all blunt trauma patients admitted to the ICU at our urban, Level I trauma center over a 5-year period (1998-2003). Obese patients (body mass index [BMI] >= 30 kg/m(2)) were compared with non-obese patients (BMI <30 kg/m(2)). Results: There were 1,153 blunt trauma patients admitted to the ICU during the study period, including 283 (25%) obese (mean BMI=35 +/- 6 kg.m(2)) and 870 (75%) non-obese (mean BMI=25 +/- 3 kg/m(2)) patients. There was no difference between groups regarding age, sex, Injury Severity Score, or admission vitals. Obese patients had fewer head injuries (42 versus 55%; p=0.0001) but more chest (45 versus 38%; p=0.05) and lower extremity (53 versus 38%; p<0.0001) injuries. There was no difference in the need for laparotomy, thoracotomy, or craniotomy. Obese patients suffered more complications (42 versus 32%; p=0.002). Although there was only a trend toward higher mortality in obese patients (22 versus 17%; p=0.10), stepwise logistic regression revealed obesity as an independent risk factor for mortality (odds ratio, 1.6; 95% confidence interval, 1.0-2.3;p=0.03). Among survivors, obese patients required longer stays in the hospital (24 +/- 21 versus 19 +/- 17 days; p=0.01), the ICU (13 +/- 14 versus 10 +/- 10 days; p=0.005), and 2 more days of mechanical ventilation (8 +/- 13 versus 6 +/- 9 days; p=0.07). C Conclusion: Obese patients incur different injuries after severe blunt trauma than their non-obese counterparts. Despite sustaining fewer head injuries, obese patients suffer more complications, require longer stays in the hospital, more days of mechanical ventilation, and obesity is independently associated with mortality. C1 Univ So Calif, Dept Surg, Div Trauma & Crit Care, Los Angeles, CA USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Crit Care, Boston, MA USA. RP Brown, CVR (reprint author), LAC USC Med Ctr, 1200 N State St,Room 6341, Los Angeles, CA 90033 USA. EM carlosbr@use.edu NR 8 TC 143 Z9 143 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2005 VL 59 IS 5 BP 1048 EP 1051 DI 10.1097/01.ta.0000189047.65630.c5 PG 4 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 001DO UT WOS:000234514000003 PM 16385276 ER PT J AU Weng, J Brown, CVR Rhee, P Salim, A Chan, L Demetriades, D Velmahos, GC AF Weng, J Brown, CVR Rhee, P Salim, A Chan, L Demetriades, D Velmahos, GC TI White blood cell and platelet counts can be used to differentiate between infection and the normal response after splenectomy for trauma: Prospective validation SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 35th Annnual Meeting of the Western-Trauma-Association CY FEB 27-MAR 05, 2005 CL Jackson Hole, WY SP Western Trauma Assoc DE spleen; splenectomy; leukocytosis; infection; sepsis ID CDC DEFINITIONS AB Background: Transient elevations of the serum white blood cell count (WBC) and platelet count (PC) are normal physiologic responses after splenectomy. The clinician is often challenged to identify an infection in a postsplenectomy patient with an elevated WBC. A previous retrospective study found that a WBC greater than 15 x 10(3)/mu L and a PC/WBC ratio < 20 on postoperative day 5, in addition to an Injury Severity Score > 16, were highly associated with infection and should not be considered as part of the physiologic response to splenectomy. The current study intends to prospectively validate the WBC and PC/WBC ratio on postoperative day 5 as markers of infection after splenectomy for trauma. Methods: Consecutive trauma patients admitted to an urban, Level I trauma center who underwent splenectomy from June 2002 to December 2004 were collected prospectively. In addition to admission demographics, variables collected included daily WBC, PC, and PC/WBC ratio during the first 10 postoperative days. Outcome was the presence of infection. Patients with infection (infected group) were compared with those without infection (noninfected group). Injury Severity Score > 16, postoperative day 5 WBC > 15 x 10(3)/mu L, and PC/WBC ratio < 20 were investigated as risk factors for postsplenectomy infection. Results: There were 96 trauma patients who underwent splenectomy during the study period, and 44 (46%) developed a postoperative infection. Infectious complications included pneumonia (n = 30 [31%]), followed by septicemia (n = 20 [21%]), urinary tract infection (n = 12 [13), abdominal abscess (n = 9 [9%]), and wound infection (n = 4 [4%]). Postoperative day 5 was the first day that infected patients had a higher WBC (16 +/- 6 x 10(3)/mu L vs. 14 +/- 4 X 10(3)/mu L, p = 0.03) and a lower PC/BC ratio (15 +/- 9 vs. 24 12, p = 0.002) than noninfected patients. The presence of two or more risk factors for infection was associated with a 79% rate of infection, and no patient developed an infection if all three risk factors were absent. Conclusion: On postoperative day 5 after splenectomy for trauma, a WBC greater than 15 x 10(3)/mu L and a PC/WBC ratio less than 20 are reliable markers of infection. C1 Univ So Calif, Dept Surg, Div Trauma & Crit Care, Los Angeles, CA USA. Univ So Calif, Los Angeles Cty Med Ctr, Los Angeles, CA 90033 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Div Trauma Emergency Surg & Crit Care, Boston, MA USA. RP Brown, CVR (reprint author), LAC & USC Med Ctr, 1200 N State St,Room 6341, Los Angeles, CA 90033 USA. EM carlosbr@use.edu NR 8 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2005 VL 59 IS 5 BP 1076 EP 1080 DI 10.1097/01.ta.0000189001.00670.d2 PG 5 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 001DO UT WOS:000234514000010 PM 16385282 ER PT J AU Velmahos, GC AF Velmahos, GC TI Pelvic angiography for recurrent traumatic pelvic arterial hemorrhage - Editorial comment SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2005 VL 59 IS 5 BP 1173 EP 1174 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 001DO UT WOS:000234514000029 ER PT J AU Lin, T Koustova, E Chen, HZ Rhee, PM Kirkpatrick, J Alam, HB AF Lin, T Koustova, E Chen, HZ Rhee, PM Kirkpatrick, J Alam, HB TI Energy substrate-supplemented resuscitation affects brain monocarboxylate transporter levels and gliosis in a rat model of hemorrhagic shock SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article; Proceedings Paper CT 63rd Annual Meeting of the American-Association-for-the-Surgery-of-Trauma CY SEP 29-OCT 02, 2004 CL Maui, HI SP Amer Assoc Surg Trauma DE hemorrhagic shock; monocarboxylates; astrocytes; microglia; GFAP; MCT1; GLUT1 ID PULMONARY APOPTOSIS; MOUSE-BRAIN; LACTATE; EXPRESSION; GLUCOSE; KETONE; ASTROCYTES; ACTIVATION; NUTRIENT; PYRUVATE AB Background. Monocarboxylate (MC)-supplemented resuscitation has been shown to attenuate cellular injury after hemorrhagic shock. However, little is known about its effect on the central nervous system. The brain can use MCs such as lactate, pyruvate, and beta-hydroxybutyrate as energy substrates. The transit of MCs into the central nervous system is facilitated by the monocarboxylate transporters (MCTs), and their blockage can exacerbate neuronal damage. We examined the expression of MCT1 and markers specific for activation of astroglia and microglia in the brains of rats subjected to hemorrhagic shock and resuscitation. The hypothesis was that resuscitation with MC-based fluids would be accompanied by MCTI up-regulation and glial response. Methods. Rats (n = 30) were subjected to volume-controlled hemorrhage. Test groups included: sham, no resuscitation, resuscitation with normal saline, resuscitation with racemic lactated Ringer's solution, resuscitation with pyruvate Ringer's solution, and resuscitation with beta-hydroxybutyrate-containing ketone Ringer's solution. Plasma levels of MC were measured serially. The brains were investigated using GFAP, CD11b, CD43, MCT1, and GLUT1 immunohistochemistry. Results: Rats resuscitated with MC- containing fluids had increased levels of MCTI in brain endothelial cells and neuropil compared with sham rats. Enhanced staining was localized to the choroid plexus, astrocytic end feet, and white matter structures. None of the resuscitation treatment induced astrocytic hyperplasia, and pyruvate Ringer's solution and ketone Ringer's solution resuscitation led to hypertrophy of astrocytes. Conclusion:. In hemorrhagic shock, resuscitation with MC-based fluids increased brain MCTI level and led to activation of astrocytes. Enhanced MC trafficking could be an essential route for energy supply to neurons under adverse circulatory conditions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Washington Hosp Ctr, Dept Surg, Washington, DC 20010 USA. RP Alam, HB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM hbalam@partners.org NR 26 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2005 VL 59 IS 5 BP 1191 EP 1202 DI 10.1097/01.ta.0000188646.86995.9d PG 12 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 001DO UT WOS:000234514000035 PM 16385299 ER PT J AU Fitzsimons, MG Peralta, R Hurford, W AF Fitzsimons, MG Peralta, R Hurford, W TI Cricoid fracture after physical assault SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article ID LARYNGEAL TRAUMA; INJURY; MANAGEMENT; PROTOCOL C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Fitzsimons, MG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM mfitzsimons@partners.org RI Hurford, William/G-6386-2013 OI Hurford, William/0000-0003-1201-0313 NR 11 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 2005 VL 59 IS 5 BP 1237 EP 1238 DI 10.1097/01.ta.0000197557.16613.a4 PG 2 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 001DO UT WOS:000234514000046 PM 16385308 ER PT J AU Oh, WK AF Oh, WK TI Phase II trial of tesmilifene plus mitoxantrone and prednisone for hormone refractory prostate cancer: High subjective and objective response in patients with symptomatic metastases - Editorial comment SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2005 VL 174 IS 5 BP 1813 EP 1813 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 974VO UT WOS:000232619700027 ER PT J AU Bailey, A Martin, ML Girman, C McNaughton-Collins, M Barry, MJ AF Bailey, A Martin, ML Girman, C McNaughton-Collins, M Barry, MJ TI Development of a multiregional United States Spanish version of the International Prostate Symptom Score and the Benign Prostatic Hyperplasia Impact Index SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic hyperplasia; outcome assessment (health care); questionnaires; translations ID CULTURAL-ADAPTATION; PRO MEASURES; TRANSLATION; VALIDATION; IPSS AB Purpose: The International Prostate Symptom Score (I-PSS) and Benign Prostatic Hyperplasia Impact Index (1311) have gained widespread use in clinical practice and clinical trials. Although Spanish translations of the I-PSS are available, to our knowledge none was developed for the Spanish speaking population in the United States using a methodology to ensure appropriateness for the diverse United States Spanish speaking population. An existing translation intended for another Spanish speaking country, such as Mexico, or a translation developed without input from each language group may not be understood by those who immigrated from other Latin American regions. Hence, the development of a Spanish translation for the United States should involve input from translators from each region of Latin America. Materials and Methods: We reviewed and modified an existing United States Spanish translation of I-PSS using a multiregional reconciliation panel comprised of representatives from each of the major Spanish language groups in the United States. For BII full translation methodology was used to develop a translation for the United States, including 2 forward translations using translators from more than 1 region, a multiregional reconciliation panel meeting, a back translation evaluation, cognitive debriefing interviews with representatives from each language group, developer review, a final evaluation for consistency and proofreading. Results: The revised I-PSS better reflects common Spanish wording in the United States, while the BII translation was confirmed to be comprehended by Spanish speakers in the United States originating from multiple regions of Latin America.. Conclusions: United States Spanish translations of patient reported outcome measures should consider the diversity of the growing Spanish speaking population in the United States to ensure comprehension across the broad population originating from the multiple regions of Latin America. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Hlth Res Associates Inc, Seattle, WA USA. Merck Res Labs Inc, West Point, PA USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM mbarry@partners.org NR 17 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2005 VL 174 IS 5 BP 1896 EP 1901 DI 10.1097/01.ju.0000177072.59090.f7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 974VO UT WOS:000232619700048 PM 16217332 ER PT J AU Wah, TM Koenig, P Irving, HC Gervais, DA Mueller, PR AF Wah, TM Koenig, P Irving, HC Gervais, DA Mueller, PR TI Radiofrequency ablation of a central renal tumor: Protection of the collecting system with a retrograde cold dextrose pyeloperfusion technique SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CELL CARCINOMA; CLINICAL-EXPERIENCE; SALINE PERFUSION; HYPOTHERMIA; MASSES AB Renal radiofrequency (RF) ablation therapy is a safe and effective therapy for small renal cell carcinoma. Although the risk of complications is low, the potential for ureteral or calyceal injury does increase in the case of a centrally located lesion. A retrograde cold dextrose pyeloperfusion technique was designed to protect the collecting system in a patient who underwent percutaneous RF ablation of a central tumor of the left kidney. C1 St James Univ Hosp, Dept Radiol, Leeds LS9 7TF, W Yorkshire, England. St James Univ Hosp, Dept Urol, Leeds LS9 7TF, W Yorkshire, England. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Wah, TM (reprint author), St James Univ Hosp, Dept Radiol, Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM tze.wah@leedsth.nhs.uk NR 19 TC 24 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2005 VL 16 IS 11 BP 1551 EP 1555 DI 10.1097/01.RVI.0000175322.05225.0A PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 989MM UT WOS:000233678000022 PM 16319166 ER PT J AU Black, JH LaMuraglia, GM Kwolek, CJ Brewster, DC Watkins, MT Cambria, RP AF Black, JH LaMuraglia, GM Kwolek, CJ Brewster, DC Watkins, MT Cambria, RP TI Contemporary results of angioplasty-based infrainguinal percutaneous interventions SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 19-21, 2003 CL Newport, RI SP New England Soc Vasc Surg ID LOWER-LIMB ISCHEMIA; LOWER-EXTREMITY REVASCULARIZATION; TRANS-LUMINAL ANGIOPLASTY; STAGE RENAL-DISEASE; 1-YEAR FOLLOW-UP; TRANSLUMINAL ANGIOPLASTY; SUBINTIMAL ANGIOPLASTY; THREATENING ISCHEMIA; BALLOON ANGIOPLASTY; REPORTING STANDARDS AB Introduction: Although lower-extremity bypass grafting has been the gold standard for infrainguinal revascularization, endovascular therapies have been increasingly applied to avoid operative morbidities. This study addresses the initial results of an implementation of infrainguinal percutaneous transluminal angioplasty (PTA) performed by vascular surgeons to treat lower-extremity ischemia. Methods: From January 2002 to July 2003, 95 consecutive patients presenting with the spectrum of lower-extremity ischemic manifestations, in whom infrainguinal PTA was the initial choice of treatment, were assessed for treatment efficacy by clinical and noninvasive evaluation. Study end points of angiographic, hemodynamic, and clinical successes (Society of Vascular Surgery reporting standards) were recorded, and variables associated with ischemic category improvement were analyzed by univariate and multivariate analysis. During the same study interval, 87 patients underwent bypass grafting (not further considered). Results: PTA was used to treat 100 limbs in 95 consecutive patients: 63 limbs (63%) had femoropopliteal PTA, 17 limbs (17%) had tibioperoneal PTA, and 20 limbs (20%) had multilevel PTA. Tissue-threatening ischemia was present in 47% of patients, and 53% were treated for claudication. Complications (no mortality) included one myocardial infarction (1%) and two access site hematomas (2%). Angiographic and hemodynamic success (a.10 increase in ankle-brachial index) was obtained in 97% and 90% of the treated limbs, respectively. With a mean follow-up of 14 months, clinical success was obtained in 85% of the treated limbs, and limb salvage for critical ischemia was achieved in 75% (30/40 limbs). Of the PTA failures, five patients (5%) underwent bypass grafting, and five patients (5%) underwent major amputation because of no further reconstructive options or extensive necrosis. Insulin-dependent diabetes mellitus (risk ratio [RR], 3.1; 95% confidence interval [CI], 1.1 to 8.7, P =.02), poor runoff into the foot (RP, 3.7; 95% CI, 1.6 to 8.6, P =.001), and renal insufficiency (serum creatinine >1.5 mg/dL) (RR, 3.7; 95% CI, 1.8 to 7.6, P =.001) were predictive of PTA failure. Conclusion: Infrainguinal percutaneous transluminal angioplasty for lower-extremity ischemia is feasible, safe and provides acceptable hemodynamic and clinical results. PTA will become the initial treatment for most patients requiring lower-extremity revascularization. C1 Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Cambria, RP (reprint author), WACC 458,15 Parkman St, Boston, MA 02114 USA. EM rcambria@partners.org NR 39 TC 50 Z9 53 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2005 VL 42 IS 5 BP 932 EP 939 DI 10.1016/j.jvs.2005.06.024 PG 8 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 981LL UT WOS:000233090000024 PM 16275450 ER PT J AU Allen, TM Altfeld, M Geer, SC Kalife, ET Moore, C O'Sullivan, KM DeSouza, I Feeney, ME Eldridge, RL Maier, EL Kaufmann, DE Lahaie, MP Reyor, L Tanzi, G Johnston, MN Brander, C Draenert, R Rockstroh, JK Jessen, H Rosenberg, ES Mallal, SA Walker, BD AF Allen, TM Altfeld, M Geer, SC Kalife, ET Moore, C O'Sullivan, KM DeSouza, I Feeney, ME Eldridge, RL Maier, EL Kaufmann, DE Lahaie, MP Reyor, L Tanzi, G Johnston, MN Brander, C Draenert, R Rockstroh, JK Jessen, H Rosenberg, ES Mallal, SA Walker, BD TI Selective escape from CD8(+) T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution SO JOURNAL OF VIROLOGY LA English DT Article ID LONG-TERM NONPROGRESSORS; VIRAL ESCAPE; LYMPHOCYTE ESCAPE; IN-VIVO; NEUTRALIZING ANTIBODIES; REVERSE-TRANSCRIPTASE; INFECTION; REPLICATION; VARIANTS; EPITOPE AB The sequence diversity of human immunodeficiency virus type 1 (HIV-1) represents a major obstacle to the development of an effective vaccine, yet the forces impacting the evolution of this pathogen remain unclear. To address this issue we assessed the relationship between genome-wide viral evolution and adaptive CD8(+) T-cell responses in four clade B virus-infected patients studied longitudinally for as long as 5 years after acute infection. Of the 98 amino acid mutations identified in nonenvelope antigens, 53% were associated with detectable CD8(+) T-cell responses, indicative of positive selective immune pressures. An additional 18% of amino acid mutations represented substitutions toward common clade B consensus sequence residues, nine of which were strongly associated with HLA class I alleles not expressed by the subjects and thus indicative of reversions of transmitted CD8 escape mutations. Thus, nearly two-thirds of all mutations were attributable to CD8(+) T-cell selective pressures. A closer examination of CD8 escape mutations in additional persons with chronic disease indicated that not only did immune pressures frequently result in selection of identical amino acid substitutions in mutating epitopes, but mutating residues also correlated with highly polymorphic sites in both clade B and C viruses. These data indicate a dominant role for cellular immune selective pressures in driving both individual and global HIV-1 evolution. The stereotypic nature of acquired mutations provides support for biochemical constraints limiting HIV-1 evolution and for the impact of CD8 escape mutations on viral fitness. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Infect Dis, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Aids, Boston, MA 02115 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA 6000, Australia. Jessen Praxis, Berlin, Germany. Univ Bonn, Dept Internal Med, D-5300 Bonn, Germany. RP Walker, BD (reprint author), MGH East,CNY 5212,149 13th St, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [N01-AI-15442] NR 57 TC 221 Z9 228 U1 0 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13239 EP 13249 DI 10.1128/JVI.79.21.13239-13249.2005 PG 11 WC Virology SC Virology GA 975MJ UT WOS:000232666300005 PM 16227247 ER PT J AU Chang, HS Dittmer, DP Chul, SY Hong, YK Jung, JU AF Chang, HS Dittmer, DP Chul, SY Hong, YK Jung, JU TI Role of notch signal transduction in Kaposi's sarcoma-associated herpesvirus gene expression SO JOURNAL OF VIROLOGY LA English DT Article ID EPSTEIN-BARR-VIRUS; COMPLEX CLASS-I; LYTIC SWITCH PROTEIN; DNA-BINDING PROTEIN; DE-NOVO INFECTION; RBP-J-KAPPA; ENDOTHELIAL-CELLS; TRANSCRIPTIONAL ACTIVATION; NUCLEAR ANTIGEN; DOWN-REGULATION AB Kaposi's sarcoma-associated herpesvirus (KSHV) RTA transcription factor is recruited to its responsive elements through interaction with a Notch-mediated transcription factor, RBP-J kappa, indicating that RTA mimics cellular Notch signal transduction to activate viral lytic gene expression. To test whether cellular Notch signal transduction and RTA are functionally exchangeable for viral gene expression, human Notch intracellular (hNIC) domain that constitutively activates RBP-J kappa transcription factor activity was expressed in KSHV-infected primary effusion lymphoma BCBL1 cells (TRExBCBL1-hNIC) in a tetracycline-inducible manner. Gene expression profiling showed that like RTA, hNIC robustly induced expression of a number of viral genes, including viral interleukin 6 (vIL-6), K3, and K5. Unlike RTA, however, hNIC was not capable of evoking the full repertoire of lytic viral gene expression and thereby lytic replication. To further understand the role of Notch signal transduction in KSHV gene expression, vIL-6 growth factor and K5 immune modulator genes were selected for detailed analysis. Despite the presence of multiple RBP-J kappa binding sites, hNIC targeted the specific RBP-J kappa binding sites of vIL-6 and K5 promoter regions to regulate their gene expression. These results indicate that cellular Notch signal transduction not only is partially exchangeable with RTA in regard to activation of viral lytic gene expression but also provides a novel expression profile of KSHV growth and immune deregulatory genes that is likely different from that of RTA-independent standard latency program as well as RTA-dependent lytic reproduction program. C1 Harvard Univ, Sch Med, Div Tumor Virol, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Jung, JU (reprint author), Harvard Univ, Sch Med, Div Tumor Virol, New England Reg Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM jae_jung@hms.harvard.edu FU NCI NIH HHS [R01 CA115284, CA115284, CA86841, R01 CA091819, CA91819, R01 CA109232, CA109232]; NCRR NIH HHS [P51 RR000168, K26 RR000168, RR00168] NR 66 TC 44 Z9 50 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14371 EP 14382 DI 10.1128/JVI.79.22.14371-14382.2005 PG 12 WC Virology SC Virology GA 980ER UT WOS:000232997500053 PM 16254371 ER PT J AU Mische, CC Javanbakht, H Song, BW Diaz-Griffero, F Stremnlau, M Strack, B Si, ZH Sodroski, J AF Mische, CC Javanbakht, H Song, BW Diaz-Griffero, F Stremnlau, M Strack, B Si, ZH Sodroski, J TI Retroviral restriction factor TRIM5 alpha is a trimer SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SPECIES-SPECIFIC TROPISM; AMINO-TERMINAL DOMAIN; MONKEY CELLS; COILED COILS; SIMIAN CELLS; POSTENTRY RESTRICTION; CRYSTAL-STRUCTURE; HOST RESTRICTION; OLD-WORLD AB The retrovirus restriction factor TRIM5 alpha targets the viral capsid soon after entry. Here we show that the TRIM5 alpha protein oligomerizes into trimers. The TRIM5 alpha coiled-coil and B30.2(SPRY) domains make important contributions to the formation and/or stability of the trimers. A functionally defective TRIM5a mutant with the RING and B-box 2 domains deleted can form heterotrimers with wild-type TRIM5 alpha, accounting for the observed dominant-negative activity of the mutant protein. Trimerization potentially allows TRIM5 alpha to interact with threefold pseudosymmetrical structures on retroviral capsids. C1 Harvard Univ, Dept Canc Immunol & AIDS, Div Aids, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Dept Canc Immunol & AIDS, Div Aids, Dana Farber Canc Inst,Sch Med, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu FU NHLBI NIH HHS [HL54785, P50 HL054785]; NIAID NIH HHS [AI28691, R01 AI063987, P30 AI028691, AI063987] NR 41 TC 109 Z9 116 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14446 EP 14450 DI 10.1128/JVI.79.22.14446-14450.2005 PG 5 WC Virology SC Virology GA 980ER UT WOS:000232997500062 PM 16254380 ER PT J AU Yamada, K AF Yamada, K TI Life-supporting pig-to-baboon renal transplantation using GalT knockout donors: Benefit of cotransplanting a vascularized donor thymic graft SO KIDNEY INTERNATIONAL LA English DT Meeting Abstract CT Meeting on Stem Cell and Regeneration of the Kidney CY JAN 20-22, 2005 CL Karuizawa, JAPAN SP Int Soc Nephrol C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. EM Kaz.yamada@tbrc.mgh.harvard.edu NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2005 VL 68 IS 5 BP 1971 EP 1971 DI 10.1111/j.1523-1755.2005.00630_19.x PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 971MQ UT WOS:000232388800030 ER PT J AU Jacobsen, E Lomo, L Briccetti, F Longtine, J Freedman, A AF Jacobsen, E Lomo, L Briccetti, F Longtine, J Freedman, A TI Follicular lymphoma with bilateral testicular and epididymal involvement: Case report and review of the literature SO LEUKEMIA & LYMPHOMA LA English DT Review DE follicular lymphoma; testicular lymphoma ID LARGE-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMA; MALIGNANT-LYMPHOMA; TESTIS; CHILDHOOD; CHILDREN AB Testicular involvement with indolent lymphoma is extremely rare, particularly in the absence of transformation to an aggressive histology. We report a case of a 64-year-old man who presented with cervical lymphadenopathy. Staging CT scans revealed extensive lymphadenopathy as well as bilateral testicular and epididymal masses. Histologic examination of lymph node, bone marrow, and testicular/epididymal biopsies revealed involvement with grade I follicular lymphoma. The patient was started on chemotherapy with cyclophosphamide, vincristine, prednisone, and rituximab in addition to intrathecal methotrexate and testicular radiation. He is now 6 months into therapy and responding well. A review of the literature demonstrated this to be the first confirmed case of testicular and epididymal involvement with grade I follicular lymphoma. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. New Hampshire Oncol Hematol, Concord, NH USA. RP Freedman, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM Arnold_Freedman@dfci.harvard.edu NR 22 TC 0 Z9 1 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD NOV PY 2005 VL 46 IS 11 BP 1663 EP 1666 DI 10.1080/10428190500178548 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 975RA UT WOS:000232678400018 PM 16236619 ER PT J AU Onitilo, AA Kio, EA Singh, AK Lazarchick, J AF Onitilo, AA Kio, EA Singh, AK Lazarchick, J TI Cytogenetic remission with imatinib therapy in hypereosinophilic syndrome with trisomy 8 and resolution of severe cardiac dysfunction SO LEUKEMIA & LYMPHOMA LA English DT Article DE cytogenetics; hypereosinophilic syndrome; imatinib; tyrosine kinase; FIP1-like-1-platelet-derived growth factor alpha (FIP1L1-PDGFRA); remission ID CHRONIC EOSINOPHILIC LEUKEMIA; FACTOR RECEPTOR-BETA; TYROSINE KINASE; MESYLATE; FUSION; INVOLVEMENT AB We report a 50-year-old patient with idiopathic hypereosinophilic syndrome with trisomy 8 who experienced a complete and durable hematological and cytogenetic remission with low-dose imatinib therapy. He also had a significant reversal of cardiac dysfunction with a reduction in cardiac hypertrophy, resolution of pericardial effusion and mitral and tricuspid regurgitation. He remained in remission 3 years after therapy. C1 Marshfield Clin Fdn Med Res & Educ, Wausau Ctr, Dept Hematol Oncol, Marshfield, WI 54449 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Med Univ S Carolina, Div Hematol Oncol, Charleston, SC 29425 USA. Ralph H Jphnson Vet Adm Med Ctr, Dept Lab Med & Pathol, Charleston, SC USA. RP Onitilo, AA (reprint author), Marshfield Clin Fdn Med Res & Educ, Wausau Ctr, Dept Hematol Oncol, 2727 Plaza Dr, Marshfield, WI 54449 USA. EM onitilo.adedayo@marshfieldclinic.org NR 21 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD NOV PY 2005 VL 46 IS 11 BP 1667 EP 1670 DI 10.1080/10428190500220514 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 975RA UT WOS:000232678400019 PM 16236620 ER PT J AU Julapalli, VR Kramer, JR El-Serag, HB AF Julapalli, VR Kramer, JR El-Serag, HB TI Evaluation for liver transplantation: Adherence to AASLD referral guidelines in a large Veterans Affairs Center SO LIVER TRANSPLANTATION LA English DT Article ID ALCOHOLIC CIRRHOSIS; RENAL-TRANSPLANTATION; RACIAL-DIFFERENCES; ACCESS; DISEASE; RECIDIVISM; ALLOCATION; DISPARITY; SURVIVAL; COHORT AB Access of patients to liver transplantation involves three levels: referral for evaluation for transplantation, placement on a waiting list for transplantation, and receipt of a liver transplant. No study has formally evaluated access to liver transplantation at the referral level. Therefore, we sought to estimate the magnitude and determinants of consideration of liver transplantation in patients at a single, large Veterans Affairs medical center. Patients with liver disease were identified between October 2002 and September 2003, and their entire medical records were examined for encounters involving potential indications for liver transplantation according to American Association for the Study of Liver Diseases (AASLD) guidelines, mention of liver transplantation, and potential contraindications. Liver transplantation was mentioned in only 59 (20%) of 300 encounters, constituting 41 (21%) of 199 patients satisfying AASLD guidelines for referral. The significant negative independent determinants of mention of liver transplantation were older age (adjusted odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13-0.77, P = 0.01), alcoholic liver disease (adjusted OR: 0.10; 95% CI: 0.02-0.57, P = 0.01), and black race (OR: 0.15; 95% CI: 0.02-0.96, P = 0.045). Most patients had potential contraindications that were inferred (but not documented) as reasons for not being evaluated for transplantation; however, a small but significant proportion (7%) had no recorded evidence of contraindications. In conclusion, we found a low rate of mention of liver transplantation in patients who satisfied AASLD guidelines for referral, particularly among patients with alcoholic liver disease and blacks. Deficiencies at the referral level may lead to disparities at further levels of access to liver transplantation. C1 Houston Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu NR 31 TC 41 Z9 41 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1527-6465 J9 LIVER TRANSPLANT JI Liver Transplant. PD NOV PY 2005 VL 11 IS 11 BP 1370 EP 1378 DI 10.1002/lt.20434 PG 9 WC Gastroenterology & Hepatology; Surgery; Transplantation SC Gastroenterology & Hepatology; Surgery; Transplantation GA 978KA UT WOS:000232870800012 PM 16184521 ER PT J AU Wang, FN Huang, TY Lin, FH Chuang, TC Chen, NK Chung, HW Chen, CY Kwong, KK AF Wang, FN Huang, TY Lin, FH Chuang, TC Chen, NK Chung, HW Chen, CY Kwong, KK TI PROPELLER EPI: An MRI technique suitable for diffusion tensor Imaging at high field strength with reduced geometric distortions SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article; Proceedings Paper CT 12th Annual Meeting of the ISMRM CY 2004 CL Kyoto, JAPAN SP ISMRM DE PROPELLER imaging; EPI; geometric distortions; specific absorption rate; diffusion tensor imaging ID MAGNETIC-RESONANCE; WHITE-MATTER; MULTIPLE-SCLEROSIS; BRAIN; ARTIFACTS; NAVIGATOR; MOTION AB A technique suitable for diffusion tensor imaging (DTI) at high field strengths is presented in this work. The method is based on a periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) k-space trajectory using EPI as the signal readout module, and hence is dubbed PROPELLER EPI. The implementation of PROPELLER EPI included a series of correction schemes to reduce possible errors associated with the intrinsically higher sensitivity of EPI to off-resonance effects. Experimental results on a 3.0 Tesla MR system showed that the PROPELLER EPI images exhibit substantially reduced geometric distortions compared with single-shot EPI, at a much lower RF specific absorption rate (SAR) than the original version of the PROPELLER fast spin-echo (FSE) technique. For DTI, the self-navigated phase-correction capability of the PROPELLER EPI sequence was shown to be effective for in vivo imaging. A higher signal-to-noise ratio (SNR) compared to single-shot EPI at an identical total scan time was achieved, which is advantageous for routine DTI applications in clinical practice. C1 Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. Natl Taiwan Univ, Dept Elect Engn, Taipei 10764, Taiwan. Tri Serv Gen Hosp, Dept Radiol, Taipei, Taiwan. Massachusetts Gen Hosp, MIT, MGH, HMS,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Huang, TY (reprint author), Natl Taiwan Univ Sci & Technol, Dept Elect Engn, Taipei, Taiwan. EM tyhuang@mail.ntust.edu.tw RI Teng-Yi, Huang/C-7433-2011; Lin, Fa-Hsuan/G-6988-2012; Chen, Nan-kuei/E-7791-2016; OI Lin, Fa-Hsuan/0000-0002-9539-1731; Chen, Nan-kuei/0000-0001-6564-4219; Chung, Hsiao-Wen/0000-0001-7127-1244 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NIBIB NIH HHS [R03 EB003902, R03-REB003902A]; NICHD NIH HHS [R01 HD040712, R01-HD040712]; NINDS NIH HHS [R01 NS037462, R01-NS037462] NR 25 TC 57 Z9 59 U1 0 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD NOV PY 2005 VL 54 IS 5 BP 1232 EP 1240 DI 10.1002/mrm.20677 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981PE UT WOS:000233099700023 PM 16206142 ER PT J AU Ohliger, MA Greenman, RL Giaquinto, R McKenzie, CA Wiggins, G Sodickson, DK AF Ohliger, MA Greenman, RL Giaquinto, R McKenzie, CA Wiggins, G Sodickson, DK TI Concentric coil arrays for parallel MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE concentric; coil array; parallel MRI; SNR; cardiac MRI ID SENSE AB A new type of coil array is proposed that consists of concentrically placed coil elements, each of which is characterized by symmetrically arranged lobes that have alternating current directions. Symmetries in the coil elements' conductor paths allow for the minimization of mutual inductance and noise correlations. In addition, the concentric arrangement of the coil elements provides spatial encoding capabilities in multiple directions, which is valuable when arrays are used with parallel MRI. Simulations are presented that describe the signal-to-noise ratio (SNR) properties of individual concentric array elements, and a four-element prototype concentric array is constructed. This prototype array is compared experimentally with three alternative four-element array designs. The overall SNR of the concentric array is comparable to the SNR of the competing arrays. Reconstruction of twofold undersampled data using the concentric array yields an average g-factor of less than 1.3 in all directions parallel to the plane of the array. There is some degradation in performance when threefold undersampled data are reconstructed, but the array still shows substantial directional invariance compared to alternative designs. Both fully-sampled and undersampled cardiac images acquired using the concentric array are shown. These results suggest that concentric structures can be useful tools for designing specialized coil arrays for parallel MRI. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Mit Div Hlth Sci & Technol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Cardiovasc, Boston, MA 02215 USA. Gen Elect Corp, Global Res Ctr, Niskayuna, NY USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. RP Ohliger, MA (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, Rm AN 235,330 Brookline Ave, Boston, MA 02215 USA. EM mohliger@mit.edu RI McKenzie, Charles/I-6014-2012; OI McKenzie, Charles/0000-0002-9614-1582; Sodickson, Daniel/0000-0002-2436-4664 FU NHLBI NIH HHS [R29 HL60802]; NIBIB NIH HHS [R01 EB00447] NR 17 TC 10 Z9 10 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD NOV PY 2005 VL 54 IS 5 BP 1248 EP 1260 DI 10.1002/mrm.20647 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981PE UT WOS:000233099700025 PM 16206147 ER PT J AU Parchman, ML Noel, PH Lee, S AF Parchman, ML Noel, PH Lee, S TI Primary care attributes, health care system hassles, and chronic illness SO MEDICAL CARE LA English DT Article ID PATIENT SATISFACTION; GENERAL-PRACTICE; VETERANS-HEALTH; COMORBIDITY; PREVALENCE; SERVICES; DISEASES; QUALITY; NUMBER AB Background: Patients with a chronic illness are likely to report difficulties in their encounters with the health care system. Although most patients with a chronic illness are managed by primary care clinicians, little is known about how the attributes of primary care might be related to health care system hassles. Objective: We sought to examine the relationship between attributes of primary care and health care system hassles among veterans with one or more chronic illnesses. Research Design: This was a cross-sectional mailed survey. Subjects: We included veterans with one or more chronic illnesses who were cared for in the South Texas Veteran's health care system. Measures: The Components of Primary Care Instrument was used to measure 4 attributes of primary care: accumulated knowledge of the patient by the clinician, coordination of care, communication, and preference for first contact with their primary care clinician. A 16-item health care systems hassles scale was constructed and demonstrated good face validity and reliability with a Cronbach's alpha of 0.94. Results: Of the 720 surveys administered by mail, 422 (59%) were returned. Patients with multiple chronic illnesses reported a higher level of hassles than patients with a single chronic illness. After controlling for patient characteristics, primary care communication and coordination of care were inversely associated with patient hassles score: as communication and coordination improved, the reported level of hassles decreased. Conclusions: Effective delivery of primary care to patients with one or more chronic illnesses may be important in decreasing the level of hassles they experience as they interact with the health care delivery system. C1 VERDICT Hlth Serv Res Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Family & Community Med, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78285 USA. RP Parchman, ML (reprint author), Audie Murphy VA Hosp VERDICT, 11C6,7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Parchman, Michael/0000-0001-7129-2889 FU AHRQ HHS [K08 HS013008-02] NR 32 TC 29 Z9 29 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2005 VL 43 IS 11 BP 1123 EP 1129 DI 10.1097/01.mlr.0000182530.52979.29 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 983YO UT WOS:000233268500009 PM 16224306 ER PT J AU Kuhlthau, K Ferris, TG Davis, RB Perrin, JM Iezzoni, LI AF Kuhlthau, K Ferris, TG Davis, RB Perrin, JM Iezzoni, LI TI Pharmacy- and diagnosis-based risk adjustment for children with Medicaid SO MEDICAL CARE LA English DT Article; Proceedings Paper CT Meeting of the Ambulatory-Pediatric-Association CY MAY 06, 2002 CL Baltimore, MD SP Ambulatory Pediat Assoc DE Medicaid; child; expenditures; risk adjustment; diagnosis; pharmacy ID FOSTER-CARE; MENTAL-HEALTH; SERVICES; MODEL AB Background: Risk adjustment is useful for adjusting health care payments based on patients' health status. Objective: This work seeks to examine how well pharmacy- and diagnosis-based risk adjusters predict child health expenditures in Medicaid populations. Research Design: We used 1994-1995 Medicaid claims files for all children ages 0-18 years who were not covered by managed care in 3 states: Georgia, New Jersey, and Wisconsin. We examined separately 6 risk adjustment methods, 2 pharmacy-based and 4 diagnosis-based. We compared predictive accuracy of the methods for the whole sample and stratified by state and Medicaid enrollment category. Findings: Models with risk adjustment (either diagnosis- or pharmacy-based) had better predictive accuracy than demographic models. The pharmacy and diagnosis-based models had similar predictive accuracy. Risk adjuster performance differed by Medicaid enrollment category and state. Risk-adjusted models generally underpredict expenditures in populations with worse health status (eg, those in the Supplemental Security Income program [SSI]). The pharmacy-based models performed well for children in SSI relative to children in foster care. Conclusions: Both pharmacy- and diagnosis-based risk adjustment improved the prediction of health expenditures compared models without risk adjustment. No single risk adjuster performed best in all situations, suggesting that optimal choices of risk adjusters may differ by purpose and context. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy,Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Inst Hlth Policy,Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Gen Med & Primary Care,Charles A Dan, Boston, MA 02114 USA. Harvard Thorndike Lab, Boston, MA 02114 USA. RP Kuhlthau, K (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy,Dept Pediat, 50 Staniford St,Suite 901, Boston, MA 02114 USA. EM kkuhlthau@partners.org FU AHRQ HHS [3R01HS1012] NR 26 TC 7 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2005 VL 43 IS 11 BP 1155 EP 1159 DI 10.1097/01.mlr.0000182551.87591.73 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 983YO UT WOS:000233268500013 PM 16224310 ER PT J AU Engelsman, M Rosenthal, SJ Michaud, SL Adams, JA Schneider, RJ Bradley, SG Flanz, JB Kooy, HM AF Engelsman, M Rosenthal, SJ Michaud, SL Adams, JA Schneider, RJ Bradley, SG Flanz, JB Kooy, HM TI Intra- and interfractional patient motion for a variety of immobilization devices SO MEDICAL PHYSICS LA English DT Article ID REPOSITIONING ACCURACY; RADIATION-THERAPY; RADIOTHERAPY; SYSTEM; FRAME; HEAD; VERIFICATION AB The magnitude of inter- and intrafractional patient motion has been assessed for a broad set of immobilization devices. Data was analyzed for the three ordinal directions-left-right (x), sup-inf (y), and ant-post (z)-and the combined spatial displacement. We have defined "rigid" and "non-rigid" immobilization devices depending on whether they could be rigidly and reproducibly connected to the treatment couch or not. The mean spatial displacement for intrafractional motion for rigid devices is 1.3 mm compared to 1.9 mm. for nonrigid devices. The modified Gill-Thomas-Cosman frame performed best at controlling intrafractional patient motion, with a 95% probability of observing a three-dimensional (3D) vector length of motion (V-95) of less than 1.8 mm, but could not be evaluated for interfractional motion. All other rigid and nonrigid immobilization devices had a V95 of more than 3 turn for intrafractional patient motion. Interfractional patient motion was only evaluated for the rigid devices. The mean total interfractional displacement was at least 3.0 turn for these devices while V95 was at least 6.0 mm. (c) 2005 American Association of Physicists in Medicine. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Massachusetts Gen Hosp, NE Proton Therapy Ctr, 55 Fruit St, Boston, MA 02114 USA. EM hkooy@partners.org OI Schneider, Robert/0000-0001-5807-5564 FU NCI NIH HHS [5 PO1 CA21239-24] NR 11 TC 31 Z9 32 U1 0 U2 1 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 NOV PY 2005 VL 32 IS 11 BP 3468 EP 3474 DI 10.1118/1.2089507 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 985NW UT WOS:000233385800030 PM 16372417 ER PT J AU Seldin, EB AF Seldin, EB TI Anomalies in health care attributable to the separation of medicine and dentistry SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Editorial Material ID AMERICAN-HEART-ASSOCIATION; INFECTIVE ENDOCARDITIS; BACTERIAL-ENDOCARDITIS; RECOMMENDATIONS; PREVENTION; JAWS C1 Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Seldin, EB (reprint author), Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. NR 13 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2005 VL 12 IS 6 BP 658 EP 660 DI 10.1097/01.gme.0000184218.78706.2b PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 986MM UT WOS:000233453700003 PM 16278606 ER PT J AU Kingsberg, S Shifren, P Wekselman, K Rodenberg, C Derogatis, L AF Kingsberg, S Shifren, P Wekselman, K Rodenberg, C Derogatis, L TI Testosterone transdermal system (TTS) provides a clinically relevant benefit in surgically menopausal women (SM) with hypoactive sexual desire disorder (HSDD) SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 16th Annual Meeting of the North-American-Menopause-Society CY SEP 28-OCT 01, 2005 CL San Diego, CA SP N Amer Menopause Soc C1 Procter & Gamble Co, Mason, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Ctr Sexual Hlth & Med, Lutherville Timonium, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2005 VL 12 IS 6 BP 801 EP 801 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 986MM UT WOS:000233453700115 ER PT J AU Song, MK Rosenthal, MJ Song, AM Yang, H Ao, Y Yamaguchi, DT AF Song, MK Rosenthal, MJ Song, AM Yang, H Ao, Y Yamaguchi, DT TI Raw vegetable food containing high cyclo (his-pro) improved insulin sensitivity and body weight control SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID DEPENDENT DIABETES-MELLITUS; IMPROVED GLUCOSE-TOLERANCE; ARACHIDONIC-ACID; DEGRADING ENZYME; PPAR-GAMMA; ZINC SUPPLEMENTATION; GLYCEMIC CONTROL; RATS; TRANSPORT; OBESITY AB Cyclo (his-pro), controlled-energy diet, soy protein hydrolysate (SPH), and raw vegetable food (RVF) are known to improve insulin sensitivity and body weight (BW) control. Enhancement of high cyclo (his-pro) content in SPH (HCS) was performed by refluxing SPH with 1 N KH2CO3 dissolved in 70% ethanol for 2 weeks at room temperature. Using this material, we examined the effects of HCS plus RVF on glucose metabolism and BW control in genetically diabetic Goto-Kakizaki (G-K) and insulin-resistant aged overweight Sprague-Dawley (S-D) rats. Thirty 7-week-old G-K rats and 18 16- to 18-month-old S-D rats were divided into 3 groups and treated with normal chow (NC), RVF diet, or HCS diet for 8 weeks. Raw vegetable food diet was made of 1:3 RVF and 2:3 NC; HCS diet was made of 1:27 portion HCS, 8:27 RVF, and 2:3 NC. Oral glucose tolerance significantly improved in both RVF (P <.01) and HCS-treated (P <.001) G-K rats and worsened in NC-fed rats compared with the baseline values. Similarly, oral glucose tolerance also improved in aged overweight S-D rats when treated with RVF (P <.05) and with HCS (P <.01), compared with the baseline values. Although HCS diet treatment very significantly lowered fed plasma insulin levels compared with NC diet treatment in G-K rats (P <.01), RVF diet treatment alone did not decrease plasma insulin levels. In contrast, there was no change of insulin levels in overweight aged S-D rats after either RVF or HCS diet treatment. Postfeeding glucose levels in G-K rats fed RVF or HCS significantly fell, compared with the rats fed NC (P <.05). Interestingly, fasting blood glucose levels in RVF- or HCS-fed rats were very significantly lower than in NC-fed rats (P <.001). There was no change of blood glucose levels in S-D rats due to treatments with different diet. In G-K rats, food intake did not decrease during the first 3 weeks but fell very significantly from the fifth to eighth weeks with RVF (P <.01) and HCS (P <.001) treatments in G-K rats. However, food intake reduction in aged S-D rats was shown only for the HCS-treated rat group (P <.05). Water intake slightly decreased in G-K rats with either RVF or HCS treatment (P <.05) but very significantly decreased in S-D rats with HCS treatment (P <.01). Body weight gain in young G-K rats and BW in aged S-D rats significantly decreased only when rats were treated with HCS diet (P <.05). These data suggest that regular consumption of HCS diet helps to control blood glucose metabolism in diabetic G-K rats and BW control in aged obese S-D rats. (c) 2005 Elsevier Inc. All rights reserved. C1 VA Greater Los Angles Healthcare Syst, Res Serv, Los Angeles, CA 91326 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Educ Clin Ctr, Los Angeles, CA 90073 USA. Kaiser Permanente Med Ctr, Dept Surg, Panorama, CA 91402 USA. RP Song, MK (reprint author), VA Greater Los Angles Healthcare Syst, Res Serv, Los Angeles, CA 91326 USA. EM moon.song2@med.va.gov FU NIDDK NIH HHS [1 R43 DK 56546-01] NR 65 TC 17 Z9 17 U1 1 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2005 VL 54 IS 11 BP 1480 EP 1489 DI 10.1016/j.metabol.2005.05.014 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984HP UT WOS:000233294000011 PM 16253637 ER PT J AU Tyrrell, JA Mahadevan, V Tong, RT Brown, EB Jain, RK Roysam, B AF Tyrrell, JA Mahadevan, V Tong, RT Brown, EB Jain, RK Roysam, B TI A 2-D/3-D model-based method to quantify the complexity of microvasculature imaged by in vivo multiphoton microscopy SO MICROVASCULAR RESEARCH LA English DT Article DE complexity analysis; angiogenesis; tumor vasculature; vasculature tracing; vasculature segmentation; automated morphometry; multiphoton microscopy ID VASCULAR-PERMEABILITY FACTOR; HUMAN ADENOCARCINOMA LS174T; FIBROBLAST-GROWTH-FACTOR; 3-DIMENSIONAL ANALYSIS; MICROVESSEL DENSITY; RETINAL-VESSELS; SCID MICE; ANGIOGENESIS; TORTUOSITY; QUANTITATION AB This paper presents model-based information-theoretic methods to quantify the complexity of tumor microvasculature, taking into account shape, textural, and structural irregularities. The proposed techniques are completely automated, and are applicable to optical slices (3-D) or projection images (2-D). Improvements upon the prior literature include: (i) measuring local (vessel segment) as well as global (entire image) vascular complexity without requiring explicit segmentation or tracing; (ii) focusing on the vessel boundaries in the complexity estimate; and (iii) added robustness to image artifacts common to tumor microvasculature images. Vessels are modeled using a family of super-Gaussian functions that are based on the superquadric modeling primitive common in computer vision. The superquadric generalizes a simple ellipsoid by including shape parameters that allow it to approximate a cylinder with elliptical cross-sections (generalized cylinder). The super-Gaussian is obtained by composing a superquadric with an exponential function giving a form that is similar to a standard Gaussian function but with the ability to produce level sets that approximate generalized cylinders. Importantly, the super-Gaussian is continuous and differentiable so it can be fit to image data using robust non-linear regression. This fitting enables quantification of the intrinsic complexity of vessel data vis-a-vis the super-Gaussian model within a minimum message length (MML) framework. The resulting measures are expressed in units of information (bits). Synthetic and real-data examples are provided to illustrate the proposed measures. (c) 2005 Elsevier Inc. All rights reserved. C1 Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Roysam, B (reprint author), Rensselaer Polytech Inst, Dept Elect Comp & Syst Engn, Troy, NY 12180 USA. EM roysam@ecse.rpi.edu RI Tyrrell, James/A-6359-2010 NR 49 TC 19 Z9 21 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 0026-2862 J9 MICROVASC RES JI Microvasc. Res. PD NOV PY 2005 VL 70 IS 3 BP 165 EP 178 DI 10.1016/j.mvr.2005.08.005 PG 14 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 987MS UT WOS:000233522600006 PM 16239015 ER PT J AU Yano, EM Asch, SM Phillips, B Anaya, H Bowman, C Chang, S Bozzette, S AF Yano, EM Asch, SM Phillips, B Anaya, H Bowman, C Chang, S Bozzette, S TI Organization and management of care for military veterans with human immunodeficiency virus/acquired immunodeficiency syndrome in Department of Veterans Affairs Medical Centers SO MILITARY MEDICINE LA English DT Article ID HIV-INFECTED VETERANS; UNITED-STATES; RURAL-AREAS; ANTIRETROVIRAL THERAPY; SERVICE DELIVERY; AMBULATORY CARE; CHRONIC ILLNESS; AIDS; HIV/AIDS; PHYSICIANS AB Objective: As the largest provider of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome health care services, the Department of Veterans Affairs (VA) has launched a national quality improvement program. As a first step, an assessment of how care for veterans with HIV/acquired immunodeficiency syndrome was organized was conducted. Methods: Structured surveys were administered to senior HIV clinicians in 118 VA facilities, about local approaches to structuring, staffing, and delivering HIV health services. Results: HIV care was chiefly delivered in special VA-based HIV clinics. HIV-related services were widely available on site, with non-VA referrals being more commonly needed to meet long-term care needs. Urban VA facilities had greater HIV caseloads, were more likely to have separate HIV clinics, and had greater access to HIV expertise, whereas rural practices focused on primary care-based models and tended to rely on off-site VA HIV experts. Conclusions: Understanding the organization and management of VA-based HIV services will help design systematic quality improvement efforts and meet the treatment needs of HIV-infected veterans. C1 Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Vet Affairs Greater Los Angeles Hlth Serv Res, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90095 USA. Vet Affairs San Diego Healthcare Syst, Vet Affairs Qual Enhancement Res Inst HIV, La Jolla, CA 92161 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. RAND Hlth, Santa Monica, CA 90407 USA. Vet Affairs Palo Alto Healthcare Syst, Vet Affairs Ctr Qual Management Publ Hlth, Palo Alto, CA 94304 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Yano, EM (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, Ctr Study Healthcare Provider Behav, Vet Affairs Greater Los Angeles Hlth Serv Res, Sepulveda, CA 91343 USA. NR 64 TC 12 Z9 13 U1 1 U2 1 PU ASSN MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD NOV PY 2005 VL 170 IS 11 BP 952 EP 959 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 019JS UT WOS:000235832000009 PM 16450823 ER PT J AU Kim, M Murphy, K Liu, F Parker, SE Dowling, ML Baff, W Kao, GD AF Kim, M Murphy, K Liu, F Parker, SE Dowling, ML Baff, W Kao, GD TI Caspase-mediated specific cleavage of BubR1 is a determinant of mitotic progression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; CHECKPOINT PROTEIN BUBR1; HUMAN CANCER-CELLS; HELA-CELLS; CENP-E; KINETOCHORE LOCALIZATION; INDUCED APOPTOSIS; HL-60 CELLS; PACLITAXEL; PHOSPHORYLATION AB The fidelity of chromosomal duplication is monitored by cell cycle checkpoints operational during mitosis. One such cell cycle delay is invoked by microtubule-targeting agents such as nocodazole or paclitaxel (Taxol) and is mediated by mitotic checkpoint proteins that include BubR1. Relatively little is known about the regulation of expression and stability of BubR1 (or other checkpoint proteins) and how these factors dictate the durability of the cell cycle delay. We report here that treatment of HeLa cells with spindle-disrupting agents resulted in caspase activation and precipitated the cleavage of BubR1. This mechanism ultimately leads to reduced levels of full-length protein, which are accompanied by abrogation of the mitotic block; the checkpoint abrogation is substantially accelerated by inhibition of de novo protein synthesis. In contrast, inhibition of caspase activity blocked BubR1 degradation and prolonged mitosis. To confirm a direct link between caspase activity and BubR1 protein expression, we identified by site-directed mutagenesis the specific caspase cleavage sites cleaved after exposure to paclitaxel. Surprisingly, BubR1 has two sites of cleavage: primarily at Asp607/Asp610 and secondarily at Asp576/Asp579. BubR1 mutated at both locations (BubR1 Delta 579 Delta 610) was resistant to paclitaxel-induced degradation. Expression of BubR1 Delta 579 Delta 610 augmented the mitotic delay induced by spindle disruption in transfected cells as well as in clones engineered to inducibly express the mutant protein upon exposure to doxycycline and ultimately led to increased aneuploidy. Underscoring the importance of these caspase cleavage sites, both tetrapeptide motifs are identified in the amino acid sequences of human, mouse, chicken, and Xenopus BubR1. These results are potentially the first to link the control of the stability of a key mitotic checkpoint protein to caspase activation, a regulatory pathway that may be involved in killing defective cells and that has been evolutionarily conserved. C1 Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Dept Radiat Oncol, Philadelphia, PA 19104 USA. RP Kao, GD (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, John Morgan Bldg 180 H,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM Kao@xrt.upenn.edu FU NCI NIH HHS [CA 107956-01, T32 CA009677, R01 CA107956, 5T32 CA 009677] NR 48 TC 42 Z9 44 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9232 EP 9248 DI 10.1128/MCB.25.21.9232-9248.2005 PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600007 PM 16227576 ER PT J AU Luo, J McMullen, JR Sobkiw, CL Zhang, L Dorfman, AL Sherwood, MC Logsdon, MN Horner, JW DePinho, RA Izumo, S Cantley, LC AF Luo, J McMullen, JR Sobkiw, CL Zhang, L Dorfman, AL Sherwood, MC Logsdon, MN Horner, JW DePinho, RA Izumo, S Cantley, LC TI Class I-A phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ATRIAL-NATRIURETIC-PEPTIDE; INCREASED INSULIN SENSITIVITY; FOXO TRANSCRIPTION FACTORS; GUANYLYL CYCLASE-A; MICE LACKING; EMBRYONIC LETHALITY; SIGNALING PATHWAYS; PRESSURE-OVERLOAD; CATALYTIC SUBUNIT; P85-ALPHA SUBUNIT AB Class I-A phosphoinositide 3-kinases (PI3Ks) are activated by growth factor receptors, and they regulate, among other processes, cell growth and organ size. Studies using transgenic mice overexpressing constitutively active and dominant negative forms of the p110 alpha catalytic subunit of class I-A PI3K have implicated the role of this enzyme in regulating heart size and physiological cardiac hypertrophy. To further understand the role of class I-A PI3K in controlling heart growth and to circumvent potential complications from the overexpression of dominant negative and constitutively active proteins, we generated mice with muscle-specific deletion of the p85 alpha regulatory subunit and germ line deletion of the p85 beta regulatory subunit of class I-A PI3K. Here we show that mice with cardiac deletion of both p85 subunits exhibit attenuated Akt signaling in the heart, reduced heart size, and altered cardiac gene expression. Furthermore, exercise-induced cardiac hypertrophy is also attenuated in the p85 knockout hearts. Despite such defects in postnatal developmental growth and physiological hypertrophy, the p85 knockout hearts exhibit normal contractility and myocardial histology. Our results therefore provide strong genetic evidence that class I-A PI3Ks are critical regulators for the developmental growth and physiological hypertrophy of the heart. C1 Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Div Signal Transduct, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02115 USA. Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cantley, LC (reprint author), Beth Israel Deaconess Med Ctr, Div Signal Transduct, 77 Ave Louis Pasteur,10th Floor, Boston, MA 02115 USA. EM lewis_cantley@hms.harvard.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NCI NIH HHS [CA 089021, P01 CA089021]; NHLBI NIH HHS [R01 HL 65742, R01 HL065742]; NIGMS NIH HHS [GM 41890, R01 GM041890, R37 GM041890] NR 56 TC 124 Z9 129 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9491 EP 9502 DI 10.1128/MCB.25.21.9491-9502.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600030 PM 16227599 ER PT J AU Kim, YB Peroni, OD Aschenbach, WG Minokoshi, Y Kotani, K Zisman, A Kahn, CR Goodyear, LJ Kahn, BB AF Kim, YB Peroni, OD Aschenbach, WG Minokoshi, Y Kotani, K Zisman, A Kahn, CR Goodyear, LJ Kahn, BB TI Muscle-specific deletion of the Glut4 glucose transporter alters multiple regulatory steps in glycogen metabolism SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AMINO-ACID-SEQUENCE; RAT SKELETAL-MUSCLE; INSULIN-RESISTANCE; PROTEIN PHOSPHATASE-1; TARGETING SUBUNIT; TRANSGENIC MICE; SYNTHASE ACTIVATION; GENE-EXPRESSION; KNOCKOUT MICE; KINASE-B AB Mice with muscle-specific knockout of the Glut4 glucose transporter (muscle-G4KO) are insulin resistant and mildly diabetic. Here we show that despite markedly reduced glucose transport in muscle, muscle glycogen content in the fasted state is increased. We sought to determine the mechanism(s). Basal glycogen synthase activity is increased by 34% and glycogen phosphorylase activity is decreased by 17% (P < 0.05) in muscle of muscle-G4KO mice. Contraction -induced glycogen breakdown is normal. The increased glycogen synthase activity occurs in spite of decreased signaling through the insulin receptor substrate 1 (IRS-1)-phosphoinositide (PI) 3-kinase-Akt pathway and increased glycogen synthase kinase 3 beta (GSK3 beta) activity in the basal state. Hexokinase 11 is increased, leading to an approximately twofold increase in glucose-6-phosphate levels. In addition, the levels of two scaffolding proteins that are glycogen-targeting subunits of protein phosphatase 1 (PP1), the muscle-specific regulatory subunit (RGL) and the protein targeting to glycogen (PTG), are strikingly increased by 3.2- to 4.2-fold in muscle of muscle-G4KO mice compared to wild-type mice. The catalytic activity of PP1, which dephosphorylates and activates glycogen synthase, is also increased. This dominates over the GSK3 effects, since glycogen synthase phosphorylation on the GSK3-regulated site is decreased. Thus, the markedly reduced glucose transport in muscle results in increased glycogen synthase activity due to increased hexokinase 11, glucose-6-phosphate, and RGL and PTG levels and enhanced PP1 activity. This, combined with decreased glycogen phosphorylase activity, results in increased glycogen content in muscle in the fasted state when glucose transport is reduced. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Kahn, BB (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, 99 Brookline Ave, Boston, MA 02215 USA. EM bkahn@bidmc.harvard.edu FU NIDDK NIH HHS [DK 33201, DK 068626, DK 57521, P30 DK057521, DK 43051, R01 DK043051, R01 DK033201, R01 DK068626, R37 DK043051] NR 65 TC 28 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9713 EP 9723 DI 10.1128/MCB.25.21.9713-9723.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600048 PM 16227617 ER PT J AU Gillette, WK Esposito, D Frank, PH Zhou, M Yu, LR Jozwik, C Zhang, XY McGowan, B Jacobowitz, DM Pollard, HB Hao, T Hill, DE Vidal, M Conrads, TP Veenstra, TD Hartley, JL AF Gillette, WK Esposito, D Frank, PH Zhou, M Yu, LR Jozwik, C Zhang, XY McGowan, B Jacobowitz, DM Pollard, HB Hao, T Hill, DE Vidal, M Conrads, TP Veenstra, TD Hartley, JL TI Pooled ORF expression technology (POET) - Using proteomics to screen pools of open reading frames for protein expression SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID IMMOBILIZED PH GRADIENTS; ORFEOME VERSION 1.1; FUNCTIONAL GENOMICS; C-ELEGANS; ELECTROPHORESIS; CLONING; STATE; TAGS; DNA AB We have developed a pooled ORF expression technology, POET, that uses recombinational cloning and proteomic methods (two-dimensional gel electrophoresis and mass spectrometry) to identify ORFs that when expressed are likely to yield high levels of soluble, purified protein. Because the method works on pools of ORFs, the procedures needed to subclone, express, purify, and assay protein expression for hundreds of clones are greatly simplified. Small scale expression and purification of 12 positive clones identified by POET from a pool of 688 Caenorhabditis elegans ORFs expressed in Escherichia coli yielded on average 6 times as much protein as 12 negative clones. Larger scale expression and purification of six of the positive clones yielded 47-374 mg of purified protein/liter. Using POET, pools of ORFs can be constructed, and the pools of the resulting proteins can be analyzed and manipulated to rapidly acquire information about the attributes of hundreds of proteins simultaneously. C1 NCI, Prot Express Lab, NIH, SAIC Frederick Inc,Res Technol Program, Frederick, MD 21702 USA. NCI, Lab Proteom & Anal Technol, NIH, SAIC Frederick Inc,Res Technol Program, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Hartley, JL (reprint author), NCI, Prot Express Lab, NIH, SAIC Frederick Inc,Res Technol Program, POB B, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov RI Hill, David/B-6617-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 21 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2005 VL 4 IS 11 BP 1647 EP 1652 DI 10.1074/mcp.M500128-MCP200 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 981ZF UT WOS:000233125800001 PM 16113400 ER PT J AU Sans, MQ Chen, JW Weissleder, R Bogdanov, AA AF Sans, MQ Chen, JW Weissleder, R Bogdanov, AA TI Myeloperoxidase activity imaging using Ga-67 labeled substrate SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE myeloperoxidase; desferrioxamine; gallium; SPECT-CT ID PEROXIDASE; OXIDATION; MECHANISM; DISEASE; LESIONS; AGENTS AB Purpose: The aim of the study is to assess the feasibility of imaging specific activity of myeloperoxidase (MPO), a leukocyte enzyme with important roles in inflammation and atherosclerosis, by single photon emission computed tomography (SPECT) using a novel Ga-67-labeled radiotracer obtained by conjugating desferrioxamine (DF) and hydroxyindolyl acetic acid in vivo. Materials and Methods: A reducing substrate of MPO (I) was synthesized by reacting commercially available DF with 2-(5-hydroxy-1H-indol-3-yl) acetic acid in the presence of a coupling agent [dicyclohexyl carbodiimide (DCC)]. The chelating unit was labeled with Ga-67, and its interaction with MPO was characterized using MALDI-TOF and UV-vis. Mice with Matrigel implants containing human MPO were used to model diseased tissues rich in MPO. Three hours after the injection of Ga-67-I, SPECT/computed tomography (CT) imaging was performed on a high-resolution Gamma Medica X-SPECT system. Biodistribution studies were performed six hours after the injection of the radiotracer. Results: The feasibility of compound I oligomerization in the presence of MPO and MPO-mediated cross-linking with proteins was initially confirmed in vitro. In vivo, a 2.7-fold increase in target-to-muscle ratio could be measured in MPO-containing Matrigel implants in mice. Biodistribution experiments demonstrated a 60% increase of radioactivity in MPO-containing vs. control (contralateral) Matrigel implants. Conclusion: Ga-67-I can be used to image MPO activity in a model system. The accumulation mechanism is based on a differential pharmacokinetics because of the size increase resulting from Ga-67-I interaction with the target enzyme. C1 Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Hillsborough 02129, North Ireland. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@umassmed.edu NR 24 TC 8 Z9 8 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD NOV-DEC PY 2005 VL 7 IS 6 BP 403 EP 410 DI 10.1007/s11307-005-0020-5 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 996CE UT WOS:000234151200004 ER PT J AU Chen, ZY Tseng, CC AF Chen, ZY Tseng, CC TI 15-Deoxy-Delta(12,14) prostaglandin J(2) up-regulates Kruppel-like factor 4 expression independently of peroxisome proliferator-activated receptor gamma by activating the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signal transduction pathway in HT-29 colon cancer cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID PPAR-GAMMA; GENE-EXPRESSION; PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH ARREST; CYCLE ARREST; DIFFERENTIATION; P21(WAF1/CIP1); APOPTOSIS; LIGAND; LINE AB 15-Deoxy-Delta(12,14) prostaglandin J(2) (15d-PGJ(2)) is a natural ligand for the peroxisome proliferator-activated receptor gamma (PPAR gamma) that exhibits antiproliferative activity in colon cancer cells, but its mechanism of action is still poorly understood. In this study, we showed that Kruppel-like factor 4 (KLF4) is one of the downstream effectors of 15d-PGJ(2). Treatment of HT-29 cells with 15d-PGJ(2) resulted in up-regulation of both KLF4 mRNA and protein expression, and these increases were also observed in other colon cancer cell lines. Down-regulation of KLF4 expression by small interfering RNA ( siRNA) targeting KLF4 reduced 15d-PGJ(2)-mediated G(1) phase arrest, suggesting that KLF4-mediated function of 15d-PGJ(2). The effect of 15d-PGJ(2) on KLF4 expression seems not to involve its nuclear receptor PPAR gamma, in that our data show that: 1) KLF4 gene promoter does not contain putative PPRE sequence, 2) 15d-PGJ(2) rapidly activates extracellular signal-regulated kinase (ERK) and induces KLF4 mRNA expression, 3) KLF4 is induced by 15d-PGJ(2) but not by rosiglitazone, a synthetic PPAR gamma ligand, and 4) 15d-PGJ(2) is unable to stimulate PPAR-dependent promoter activity in the absence of cotransfected PPAR gamma. Moreover, 15d-PGJ(2)- mediated KLF4 mRNA expression was blocked by 2'-amino-3'- methoxyflavone (PD98059) or 1,4-diamino-2,3- dicyano-1,4-bis(methylthio) butadiene (U0126), two ERK kinase MAP inhibitors, whereas the phosphoinositol-3 kinase inhibitors wortmannin and 2-(4-morpholinyl)-8-phenyl-4H- 1-benzopyran-4-one (LY294002) had no such effect. Furthermore, KLF4 induction by 15d-PGJ(2) occurred only in signal transducer and activator of transcription 1 (STAT1)-expressing, not in STAT1-knockout cells. Together, these results suggest that 15d-PGJ(2)-induced growth inhibition of colon cancer cells is mediated, at least in part, through up-regulation of KLF4 expression. This induction is unlikely to be mediated through the PPAR gamma receptor but may involve the mitogen-activated protein kinase kinase/ERK pathway and is STAT1-dependent. C1 Boston Univ, Sch Med, Gastroenterol Sect, Boston, MA 02118 USA. VA Boston Healthcare Syst, Gastroenterol Sect, Boston, MA USA. RP Chen, ZY (reprint author), Boston Univ, Sch Med, Gastroenterol Sect, EBRC X-513,650 Albany St, Boston, MA 02118 USA. EM zhiyi.chen@bmc.org NR 40 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2005 VL 68 IS 5 BP 1203 EP 1213 DI 10.1124/mol.105.014944 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 977VZ UT WOS:000232832900003 PM 16077033 ER PT J AU Fleming, A Cook, KF Nelson, ND Lai, EC AF Fleming, A Cook, KF Nelson, ND Lai, EC TI Proxy reports in Parkinson's disease: Caregiver and patient self-reports of quality of life and physical activity SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; health-related quality of life; proxy evaluation; PDQ-39 ID HEALTH; AGREEMENT; RELIABILITY; RESPONSES; INDEX; OLDER AB We evaluated patient-proxy agreement in a population of veterans with Parkinson's disease and compared levels of agreement by patient subgroups. Patient and caregiver pairs completed questionnaires composed of standard measures and additional demographic and activity questions. Participants completed the Center for Epidenniologic Studies Depression Scale (CES-D), the PD Questionnaire 39 (PDQ-39), and three questions regarding physical activity. Caregivers completed proxy forms of the PDQ-39 and the physical activity questionnaire. The proxy forms asked caregivers to choose the answers that best described their "friend's/patient's situation." The results of our comparison of patient and proxy reports of quality of life were consistent with findings in other diseases. On average, proxies rated patient disability higher and quality of life lower than did patients. However, our comparison of patient and proxy reports of frequency of exercise diverged from previously published work. Less agreement was observed between patient and proxy reports of physical activity, even though this is a more objective variable than are the domains measured by the PDQ-39. Proxy reports may diverge appreciably from patient self-reports. These differences should be considered in research design and clinical decision making. Alternative approaches to the measurement of patient relevant outcomes could supplement traditional, retrospective self-reports. (c) 2005 Movement Disorder Society. C1 Michael E DeBakey Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Houston, TX USA. Univ Washington, Dept Rehabil Med, Seattle, WA USA. Baylor Coll Med, Dept Neurol, Houston, TX USA. METRIC, Houston, TX USA. RP Cook, KF (reprint author), Houston VAMC, 127-PD 801 Cortland St, Houston, TX 77007 USA. EM karonc2@u.washington.edu NR 20 TC 22 Z9 22 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 2005 VL 20 IS 11 BP 1462 EP 1468 DI 10.1002/mds.20592 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 984TI UT WOS:000233326800010 PM 16028212 ER PT J AU Weissleder, R Kelly, K Sun, EY Shtatland, T Josephson, L AF Weissleder, R Kelly, K Sun, EY Shtatland, T Josephson, L TI Cell-specific targeting of nanoparticles by multivalent attachment of small molecules SO NATURE BIOTECHNOLOGY LA English DT Article ID QUANTUM DOTS; IN-VIVO; FLUORESCENT; PROBES; EXPRESSION; AGENTS AB Nanomaterials with precise biological functions have considerable potential for use in biomedical applications. Here we investigate whether multivalent attachment of small molecules can increase specific binding affinity and reveal new biological properties of such nanomaterials. We describe the parallel synthesis of a library comprising 146 nanoparticles decorated with different synthetic small molecules. Using fluorescent magnetic nanoparticles, we rapidly screened the library against different cell lines and discovered a series of nanoparticles with high specificity for endothelial cells, activated human macrophages or pancreatic cancer cells. Hits from the last-mentioned screen were shown to target pancreatic cancer in vivo. The method and described materials could facilitate development of functional nanomaterials for applications such as differentiating cell lines, detecting distinct cellular states and targeting specific cell types. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Weissleder, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5403, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu NR 29 TC 584 Z9 593 U1 14 U2 164 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2005 VL 23 IS 11 BP 1418 EP 1423 DI 10.1038/nbt1159 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 984FN UT WOS:000233288000038 PM 16244656 ER PT J AU Shaywitz, DA AF Shaywitz, DA TI Entrepreneurs: the missing link in the training of medical scientists SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Stem Cell Inst, Boston, MA 02114 USA. RP Shaywitz, DA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Stem Cell Inst, 55 Fruit St, Boston, MA 02114 USA. EM dshaywitz@mcb.harvard.edu NR 0 TC 2 Z9 2 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2005 VL 23 IS 11 BP 1447 EP 1448 DI 10.1038/nbt1105-1447 PG 2 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 984FN UT WOS:000233288000042 PM 16273076 ER PT J AU Larsen, PR AF Larsen, PR TI Not just another journal SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Larsen, PR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2005 VL 1 IS 1 BP 1 EP 1 DI 10.1038/ncpendmet0021 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 009AA UT WOS:000235082300001 ER PT J AU Loeffler, JS Nachtigall, LB AF Loeffler, JS Nachtigall, LB TI Is fractionated stereotactic radiotherapy effective in pituitary adenomas? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE adenoma; fractionated; pituitary; stereotactic; toxicity C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Neuroendocrine Clin Ctr, Boston, MA 02114 USA. RP Loeffler, JS (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St, Boston, MA 02114 USA. EM jloeffler@partners.org NR 2 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD NOV PY 2005 VL 2 IS 11 BP 548 EP 549 DI 10.1038/ncponc0327 PG 2 WC Oncology SC Oncology GA 982LW UT WOS:000233160900005 PM 16270093 ER PT J AU Wade, CM Daly, MJ AF Wade, CM Daly, MJ TI Genetic variation in laboratory mice SO NATURE GENETICS LA English DT Article ID MOUSE GENOME; SEQUENCE VARIATION; INBRED STRAINS; HYBRID ZONE; WORMY MICE; HOUSE MICE; CHROMOSOME; EVOLUTION; TRAITS; POLYMORPHISMS AB Characterizing the patterns of genetic variation in an organism provides fundamental insight into the evolutionary history of the organism and defines the scope and nature of studies that must be designed to correlate genotype to phenotype. Given the pre-eminent role of the inbred mouse in biomedical research, considerable effort has been undertaken in recent years to describe more fully the nature and amount of genetic variation among the numerous strains of mice that are in widest use. Here, we discuss recent studies that have contributed to an emerging understanding of the unique variation patterns found in inbred strains of mice and how they have arisen through a combination of natural evolution and human-directed breeding. These preliminary results have ramifications for genetic research into complex biomedical traits and are the basis for the development of future variation resources. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Ctr Human Genet Res, Boston, MA 02114 USA. Broad Inst Harvard & MIT, Cambridge, MA 02141 USA. RP Daly, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Simches Res Ctr,Ctr Human Genet Res, CPZN-6818,185 Cambridge St, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu OI Wade, Claire/0000-0003-3413-4771 NR 36 TC 97 Z9 99 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2005 VL 37 IS 11 BP 1175 EP 1180 DI 10.1038/ng1666 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 980VB UT WOS:000233045200013 PM 16254563 ER PT J AU de Bakker, PIW Yelensky, R Pe'er, I Gabriel, SB Daly, MJ Altshuler, D AF de Bakker, PIW Yelensky, R Pe'er, I Gabriel, SB Daly, MJ Altshuler, D TI Efficiency and power in genetic association studies SO NATURE GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; LINKAGE-DISEQUILIBRIUM; TAGGING SNPS; GENOTYPE DATA; UNRELATED INDIVIDUALS; HAPLOTYPE DIVERSITY; TAG SNPS; SELECTION; TESTS AB We investigated selection and analysis of tag SNPs for genome-wide association studies by specifically examining the relationship between investment in genotyping and statistical power. Do pairwise or multimarker methods maximize efficiency and power? To what extent is power compromised when tags are selected from an incomplete resource such as HapMap? We addressed these questions using genotype data from the HapMap ENCODE project, association studies simulated under a realistic disease model, and empirical correction for multiple hypothesis testing. We demonstrate a haplotype-based tagging method that uniformly outperforms single-marker tests and methods for prioritization that markedly increase tagging efficiency. Examining all observed haplotypes for association, rather than just those that are proxies for known SNPs, increases power to detect rare causal alleles, at the cost of reduced power to detect common causal alleles. Power is robust to the completeness of the reference panel from which tags are selected. These findings have implications for prioritizing tag SNPs and interpreting association studies. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN-6818, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu; altshuler@molbio.mgh.harvard.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009 OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858 NR 36 TC 1290 Z9 1311 U1 3 U2 60 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2005 VL 37 IS 11 BP 1217 EP 1223 DI 10.1038/ng1669 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 980VB UT WOS:000233045200021 PM 16244653 ER PT J AU Uchimura, K Gauguet, JM Singer, MS Tsay, D Kannagi, R Muramatsu, T von Andrian, UH Rosen, SD AF Uchimura, K Gauguet, JM Singer, MS Tsay, D Kannagi, R Muramatsu, T von Andrian, UH Rosen, SD TI A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules SO NATURE IMMUNOLOGY LA English DT Article ID SIALYL-LEWIS-X; CORE-2 BRANCHING BETA-1,6-N-ACETYLGLUCOSAMINYLTRANSFERASE; PERIPHERAL LYMPH-NODES; P-SELECTIN; CARBOHYDRATE SULFOTRANSFERASES; CHROMOSOMAL LOCALIZATION; MOLECULAR-CLONING; T-LYMPHOCYTES; CAPPING GROUP; O-GLYCANS AB The interaction of L-selectin on lymphocytes with sulfated ligands on high endothelial venules leads to rolling and is critical for recruitment of lymphocytes into peripheral lymph nodes. Peripheral node addressin represents a class of L-selectin ligands recognized by the function-blocking monoclonal antibody MECA-79. Its epitope overlaps with sialyl 6-sulfo Lewis X, an L-selectin recognition determinant. Here, mice lacking two N-acetylglucosamine-6-O-sulfotransferases (GlcNAc6ST-1 and GlcNAc6ST-2) demonstrated elimination of both peripheral node addressin and sialyl 6-sulfo Lewis X in high endothelial venules, considerably reduced lymphocyte homing to peripheral lymph nodes and reduced sticking of lymphocytes along high endothelial venules. Our results establish an essential function for the sulfotransferases in L-selectin ligand synthesis and may have relevance for therapy of inflammatory diseases. C1 Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anat, Program Immunol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Aichi Canc Ctr, Res Inst, Program Mol Pathol, Nagoya, Aichi 4648681, Japan. Nagoya Univ, Grad Sch Med, Dept Biochem, Nagoya, Aichi 464, Japan. RP Rosen, SD (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, Dept Anat, Program Immunol, Box 0130, San Francisco, CA 94143 USA. EM sdr@itsa.ucsf.edu RI von Andrian, Ulrich/A-5775-2008 FU NHLBI NIH HHS [HL54936, HL56949, P01 HL056949]; NIAID NIH HHS [AI061663]; NIGMS NIH HHS [R37-GM23547, R01-GM57411] NR 56 TC 104 Z9 107 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2005 VL 6 IS 11 BP 1105 EP 1113 DI 10.1038/ni1258 PG 9 WC Immunology SC Immunology GA 977WD UT WOS:000232833300011 PM 16227986 ER PT J AU Sykes, M Spitzer, TR AF Sykes, M Spitzer, TR TI Protecting the host naturally SO NATURE MEDICINE LA English DT Editorial Material ID KILLER T-CELLS; ANTIGEN-PRESENTING CELLS; LYMPHOID IRRADIATION; DISEASE; PREVENTS; TRANSPLANTATION C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplant Unit, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. EM megan.sykes@tbrc.mgh.harvard.edu NR 11 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2005 VL 11 IS 11 BP 1164 EP 1165 DI 10.1038/nm1105-1164 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 981VF UT WOS:000233115400026 PM 16270073 ER PT J AU Jiang, DH Liang, JR Fan, J Yu, S Chen, SP Luo, Y Prestwich, GD Mascarenhas, MM Garg, HG Quinn, DA Homer, RJ Goldstein, DR Bucala, R Lee, PJ Medzhitov, R Noble, PW AF Jiang, DH Liang, JR Fan, J Yu, S Chen, SP Luo, Y Prestwich, GD Mascarenhas, MM Garg, HG Quinn, DA Homer, RJ Goldstein, DR Bucala, R Lee, PJ Medzhitov, R Noble, PW TI Regulation of lung injury and repair by Toll-like receptors and hyaluronan SO NATURE MEDICINE LA English DT Article ID NF-KAPPA-B; BLEOMYCIN-INDUCED PNEUMONOPATHY; MURINE MACROPHAGES; PULMONARY-FIBROSIS; CASPASE INHIBITOR; EPITHELIAL-CELLS; IMMUNE-RESPONSE; FAS LIGAND; EXPRESSION; MICE AB Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor ( TLR) 4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner. Myd88(-/-) and Tlr4(-/-)Tlr2(-/-) mice showed impaired transepithelial migration of inflammatory cells but decreased survival and enhanced epithelial cell apoptosis after lung injury. Lung epithelial cell-specific overexpression of high-molecular-mass hyaluronan was protective against acute lung injury. Furthermore, epithelial cell-surface hyaluronan was protective against apoptosis, in part, through TLR-dependent basal activation of NF-kappa B. Hyaluronan-TLR2 and hyaluronan-TLR4 interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity and promote recovery from acute lung injury. C1 Yale Univ, Sch Med, Dept Med, Pulm & Crit Care Med Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Univ Utah, Dept Med Chem, Salt Lake City, UT 84132 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Yale Univ, Sch Med, Cardiol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Rheumatol Sect, New Haven, CT 06520 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA. RP Noble, PW (reprint author), Yale Univ, Sch Med, Dept Med, Pulm & Crit Care Med Sect, 333 Cedar St, New Haven, CT 06520 USA. EM paul.noble@yale.edu RI Jiang, Dianhua/B-1421-2009 OI Jiang, Dianhua/0000-0002-4508-3829 FU NHLBI NIH HHS [HL57486]; NIAID NIH HHS [AI52487] NR 40 TC 742 Z9 772 U1 8 U2 71 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2005 VL 11 IS 11 BP 1173 EP 1179 DI 10.1038/nm1315 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 981VF UT WOS:000233115400029 PM 16244651 ER PT J AU Dackis, C O'Brien, C AF Dackis, C O'Brien, C TI Neurobiology of addiction: treatment and public policy ramifications SO NATURE NEUROSCIENCE LA English DT Editorial Material ID OPIOID RECEPTOR GENE; DOPAMINE-D-2 RECEPTORS; COCAINE DEPENDENCE; ALCOHOL DEPENDENCE; BETA-ENDORPHIN; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR; CENTRAL SWEDEN; D2 RECEPTORS AB In the United States, efforts to treat addiction are hampered by prejudice and a public view that treats it as a disorder of self-control, not a disease. We highlight select advances in addiction research that, if disseminated to the public, could reverse these misconceptions and facilitate changes in policy to improve treatment access and care delivery for this highly prevalent disease. C1 Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Treatment Res Ctr, Philadelphia, PA USA. RP Dackis, C (reprint author), Univ Penn, Dept Psychiat, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM dackis@mail.med.upenn.edu NR 50 TC 107 Z9 109 U1 4 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1431 EP 1436 DI 10.1038/nn1105-1431 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600010 PM 16251982 ER PT J AU Cheng, LP Samad, OA Xu, Y Mizuguchi, R Luo, P Shirasawa, S Goulding, M Ma, QF AF Cheng, LP Samad, OA Xu, Y Mizuguchi, R Luo, P Shirasawa, S Goulding, M Ma, QF TI Lbx1 and Tlx3 are opposing switches in determining GABAergic versus glutamatergic transmitter phenotypes SO NATURE NEUROSCIENCE LA English DT Article ID DORSAL SPINAL-CORD; GENE-EXPRESSION; PAIN MECHANISMS; HOMEOBOX GENES; NEURONS; SPECIFICATION; INTERNEURONS; CIRCUITS; GABA; RECEPTORS AB Most neurons in vertebrates make a developmental choice between two principal neurotransmitter phenotypes (glutamatergic versus GABAergic). Here we show that the homeobox gene Lbx1 determines a GABAergic cell fate in the dorsal spinal cord at early embryonic stages. In Lbx1(-/-) mice, the presumptive GABAergic neurons are transformed into glutamatergic cells. Furthermore, overexpression of Lbx1 in the chick spinal cord is sufficient to induce GABAergic differentiation. Paradoxically, Lbx1 is also expressed in glutamatergic neurons. We previously reported that the homeobox genes Tlx1 and Tlx3 determine glutamatergic cell fate. Here we show that impaired glutamatergic differentiation, observed in Tlx3(-/-) mice, is restored in Tlx3(-/-) Lbx1(-/-) mice. These genetic studies suggest that Lbx1 expression defines a basal GABAergic differentiation state, and Tlx3 acts to antagonize Lbx1 to promote glutamatergic differentiation. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Salk Inst Biol Studies, Mol Neurobiol Lab, La Jolla, CA 92037 USA. Int Med Ctr Japan, Dept Pathol, Shinjuku Ku, Tokyo 1628655, Japan. RP Ma, QF (reprint author), Dana Farber Canc Inst, 1 Jimmy Fund Way, Boston, MA 02115 USA. EM Qiufu_ma@dfci.harvard.edu RI samad, omar/K-1921-2012 NR 37 TC 106 Z9 110 U1 2 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1510 EP 1515 DI 10.1038/nn1569 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600025 PM 16234809 ER PT J AU Barabasi, AL AF Barabasi, AL TI Taming complexity SO NATURE PHYSICS LA English DT Editorial Material ID SMALL-WORLD NETWORKS; COMMUNITY STRUCTURE; METABOLIC NETWORKS; INTERNET C1 Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. RP Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. EM alb@nd.edu NR 22 TC 46 Z9 50 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 EI 1745-2481 J9 NAT PHYS JI Nat. Phys. PD NOV PY 2005 VL 1 IS 2 BP 68 EP 70 DI 10.1038/nphys162 PG 3 WC Physics, Multidisciplinary SC Physics GA 006HJ UT WOS:000234888300002 ER PT J AU Alencar, H Mahmood, U Kawano, Y Hirata, T Weissleder, R AF Alencar, H Mahmood, U Kawano, Y Hirata, T Weissleder, R TI Novel multiwavelength microscopic scanner for mouse imaging SO NEOPLASIA LA English DT Article DE confocal microscopy; reconstruction; imaging; near-infrared; fluorescence ID IN-VIVO; FLUORESCENT PROTEINS; TUMORS; MICROCIRCULATION; ANGIOGENESIS; CELLS; LIVER; COLON; LENS AB Real-time in vivo imaging of molecular targets at (sub)cellular resolution is essential in better understanding complex biology. Confocal microscopy and multiphoton microscopy have been used in the past to achieve this goal, but their true capabilities have often been limited by bulky optics and difficult experimental set-ups requiring exteriorized organs. We describe here the development and validation of a unique near-infrared laser scanning microscope system that uses novel optics with a millimeter footprint. Optimized for use in the far red and near-infrared ranges, the system allows an imaging depth that extends up to 500 mu m from a 1.3-mm-diameter stick objective, which is up to 2 cm in length. We show exceptionally high spatial, temporal, and multiwavelength resolutions of the system and show that it can be applied to virtually any internal organ through a keyhole surgical access. We demonstrate that, when combined with novel far red imaging probes, it is possible to image the cellular details of many organs and disease processes. The new optics, coupled with the use of near-infrared probes, should prove immensely valuable for in vivo cancer imaging. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Olympus Corp, BioBusiness Dev Dept, Bioscence Div, Tokyo 1928512, Japan. RP Weissleder, R (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,5408, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu OI Kawano, Yoshihiro/0000-0001-6442-8733 FU NCI NIH HHS [P50 CA086355, P50CA86355, R24 CA092782, R24CA92782] NR 19 TC 54 Z9 54 U1 0 U2 7 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD NOV PY 2005 VL 7 IS 11 BP 977 EP 983 DI 10.1593/neo.05376 PG 7 WC Oncology SC Oncology GA 994HC UT WOS:000234020800002 PM 16331883 ER PT J AU Cantuti-Castelvetria, I Lin, MT Zheng, KN Keller-McGandy, CE Betensky, RA Johns, DR Beal, MF Standaert, DG Simon, DK AF Cantuti-Castelvetria, I Lin, MT Zheng, KN Keller-McGandy, CE Betensky, RA Johns, DR Beal, MF Standaert, DG Simon, DK TI Somatic mitochondrial DNA mutations in single neurons and glia SO NEUROBIOLOGY OF AGING LA English DT Article DE mitochondria; somatic; mutation; laser capture microdissection; allele-specific PCR; single cell; Parkinson's disease; aging; acquired; oxidative stress; dopaminergic ID MTDNA CONTROL REGION; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; POINT MUTATIONS; HUMAN TISSUES; HUMAN BRAIN; HUMAN-CELLS; OXIDATIVE STRESS; AGE; ACCUMULATION AB Somatic mitochondrial DNA (mtDNA) point mutations reach high levels in the brain. However, the cell types that accumulate mutations and the patterns of mutations within individual cells are not known. We have quantified somatic mtDNA mutations in 28 single neurons and in 18 single glia from post-mortem human substantia nigra of six control subjects. Both neurons and glia contain mtDNA with somatic mutations. Single neurons harbor a geometric mean (95% Cl) of 200.3 (152.9-262.4) somatic rntDNA point mutations per million base pairs, compared to 133.8 (97.5-184.9) for single glia (p = 0.0251). If mutations detected multiple times in the same cell are counted only once, the mean mutation level per million base pairs remains elevated in single neurons (146.9; 124.0-174.2) compared to single glia (100.5; 81.5-126.5; p = 0.009). Multiple distinct somatic point mutations are present in different cells from the same subject. Most of these mutations are individually present at low levels (less than 10-20% of mtDNA molecules), but with high aggregate mutation levels, particularly in neurons. These mutations may contribute to changes in brain function during normal aging and neurodegenerative disorders. (c) 2004 Elsevier Inc. All rights reserved. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Dept Neurol & Neurosci, New York, NY 10021 USA. RP Simon, DK (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Room 847,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM dsimon1@bidmc.harvard.edu OI Standaert, David/0000-0003-2921-8348 FU NIA NIH HHS [AG20729]; NIMH NIH HHS [R24-MH068855]; NINDS NIH HHS [K02 NS044482] NR 56 TC 44 Z9 44 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2005 VL 26 IS 10 BP 1343 EP 1355 DI 10.1016/j.neurobiolaging.2004.11.008 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 981DX UT WOS:000233068700002 PM 16243605 ER PT J AU Liang, ZQ Wang, XX Wang, YM Chuang, DM DiFiglia, M Chase, TN Qin, ZH AF Liang, ZQ Wang, XX Wang, YM Chuang, DM DiFiglia, M Chase, TN Qin, ZH TI Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; excitotoxicity; striatum; apoptosis; neurodegeneration; cholinergic interneurons ID D-ASPARTATE RECEPTORS; KAPPA-B ACTIVATION; HUNTINGTONS-DISEASE GENE; INDUCED CELL-DEATH; QUINOLINIC ACID; RAT STRIATUM; MEDIATED EXCITOTOXICITY; TRANSGENIC MICE; MESSENGER-RNA; CASPASE-3-LIKE PROTEASE AB The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT(+)) and parvalbumin positive (PARV(+)) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT(+) and PARV(+) survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28(+)) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i. (c) 2005 Elsevier Inc. All rights reserved. C1 Soochow Univ, Sch Med, Dept Pharmacol, Suzhou 215007, Peoples R China. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Qin, ZH (reprint author), Soochow Univ, Sch Med, Dept Pharmacol, 48 Ren Min Rd, Suzhou 215007, Peoples R China. EM qinzh555@peoplepc.com NR 84 TC 18 Z9 18 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2005 VL 20 IS 2 BP 562 EP 573 DI 10.1016/j.nbd.2005.04.011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 981OA UT WOS:000233096700039 PM 15922606 ER PT J AU Dhond, RP Witzel, T Dale, AM Halgren, E AF Dhond, RP Witzel, T Dale, AM Halgren, E TI Spatiotemporal brain maps of delayed word repetition and recognition SO NEUROIMAGE LA English DT Article DE MEG; episodic; retrieval; memory; words; priming ID EVENT-RELATED POTENTIALS; HUMAN HIPPOCAMPAL-FORMATION; ANTERIOR PREFRONTAL CORTEX; DEPTH-RECORDED POTENTIALS; LETTER-STRING PERCEPTION; TEMPORAL-LOBE ATROPHY; RETRIEVAL SUCCESS; CORTICAL ACTIVITY; MEMORY RETRIEVAL; EPISODIC MEMORY AB Whole-head magnetoencephalography (MEG) was used to spatiotemporally map the brain response underlying episodic retrieval of words studied a single time following a long delay (similar to 40 min). Recognition following a long delay occurs as a strong, sustained, differential response, within bilateral, ventral, and lateral prefrontal cortex, anterior temporal and medial parietal regions from similar to 500 ms onward, as well as ventral occipitotemporal regions from similar to 700 ms onward. In comparison with previous tasks using multiple repetitions at short delays, these effects were centered within the same areas (anteroventral temporal and ventral prefrontal) but were shifted to longer latencies (similar to 500 ms vs. similar to 200 ms), were less left-lateralized, and appear more in anterolateral prefrontal regions and less in lateral temporal cortex. Furthermore, comparison of correctly classified words with misclassified, novel and repeated words, suggests that these frontotemporal-parietocingulate responses are sensitive to actual as well as perceived repetition. The results also suggest that lateral prefrontal regions may participate more in controlled effortful retrieval, while left ventral frontal and anterior temporal responses may support sustained lexicosemantic processing. Additionally, left ventromedial temporal sites may be relatively more involved in episodic retrieval, while lateral temporal sites may participate more in automatic priming. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. INSERM, E9926, F-13258 Marseille, France. RP Dhond, RP (reprint author), Massachusetts Gen Hosp, MIT, Athinoula A Martinos Ctr Biomed Imaging, Room 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM polly@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Witzel, Thomas/P-1402-2014 FU NCRR NIH HHS [P41 RR014075, P41RR14075]; NINDS NIH HHS [R01NS18741, R01 NS018741, R01 NS044623, R01NS44623] NR 99 TC 15 Z9 16 U1 3 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2005 VL 28 IS 2 BP 293 EP 304 DI 10.1016/j.neuroimage.2005.06.027 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 977QB UT WOS:000232817200001 PM 16084111 ER PT J AU Badjatia, N Rosand, J AF Badjatia, N Rosand, J TI Intracerebral hemorrhage SO NEUROLOGIST LA English DT Review DE intracerebral hemorrhage; intracranial pressure; intraventricular hemorrhage ID CEREBRAL AMYLOID ANGIOPATHY; TISSUE-PLASMINOGEN ACTIVATOR; CENTRAL-NERVOUS-SYSTEM; PROSPECTIVE RANDOMIZED TRIAL; COMMUNITY STROKE PROJECT; ACUTE ISCHEMIC-STROKE; LOW SERUM-CHOLESTEROL; INTRACRANIAL HEMORRHAGE; RISK-FACTORS; BLOOD-FLOW AB Introduction: Intracerebral hemorrhage (ICH) occurs from the rupture of small vessels into the brain parenchyma and accounts for approximately 10% of all strokes in the United States, and carries with it a significantly high morbidity and mortality. Summary: This article reviews the course and management of ICH. The most common chronic vascular diseases that lead to ICH are chronic hypertension and cerebral amyloid angiopathy. Additional factors that predispose to ICH include vascular malformations, chronic alcohol use, hypocholesterolemia, and use of anticoagulant medications. The understanding of mechanisms leading to ICH has advanced significantly, but questions regarding site predilection and timing of spontaneous hemorrhage still remain. Management in the acute setting is first focused on reducing hematoma expansion. Although no specific therapy has yet been proven effective, promising agents, particularly recombinant Factor VIIa, are on the horizon. Subsequent care is focused on controlling hemostasis, hemodynamics, and intracranial pressure in efforts to minimize secondary brain injury. Conclusion: The morbidity and mortality associated with ICH remain high despite recent advances in our understanding of the clinical course of ICH. Novel preventive and acute treatment therapies are needed and may be on the horizon. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Neurocrit Care & Acute Stroke Serv, Boston, MA USA. RP Badjatia, N (reprint author), Neurol Inst, Div Stroke & Crit Care, 710 W 168th St,Box 29, New York, NY 10032 USA. EM nbadjatia@neuro.columbia.edu NR 161 TC 46 Z9 47 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1074-7931 J9 NEUROLOGIST JI Neurologist PD NOV PY 2005 VL 11 IS 6 BP 311 EP 324 DI 10.1097/01.nrl.0000178757.68551.26 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 985XT UT WOS:000233412700001 PM 16286875 ER PT J AU Verfaellie, M Page, K Orlando, F Schacter, DL AF Verfaellie, M Page, K Orlando, F Schacter, DL TI Impaired implicit memory for gist information in amnesia SO NEUROPSYCHOLOGY LA English DT Article DE amnesia; false memory; gist memory; implicit memory ID ILLUSORY RECOGNITION MEMORY; FUZZY-TRACE THEORY; FALSE RECOGNITION; COGNITIVE NEUROSCIENCE; KORSAKOFF PATIENTS; LEXICAL DECISION; VERBAL RESPONSES; STEM COMPLETION; RECALL; TRUE AB In 2 experiments using a converging associates paradigm, the authors evaluated implicit memory for gist information in amnesic patients. In Experiment 1, participants saw multiple sets of associates, each converging on a nonpresented theme word, and were then tested using an implicit word stem completion test and an explicit cued recall test. Amnesic patients showed intact implicit and impaired explicit memory for studied words, but memory for nonpresented lures was impaired, regardless of retrieval instructions. To evaluate whether impaired implicit memory for lures was due to accelerated forgetting of gist information, short study lists were used in Experiment 2, each consisting of a single set of associates. Amnesics' implicit memory for lures was again impaired. These results point to an inability to encode robust gist representations as the cause of impaired gist memory in amnesia. C1 Boston VA Healthcare Syst, Memory Disorders Res Ctr, Boston, MA 02130 USA. Boston Univ, Sch Med, Memory Disorders Res Ctr, Boston, MA 02215 USA. Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Verfaellie, M (reprint author), Boston VA Healthcare Syst, Memory Disorders Res Ctr, 151A,150 S Huntington Ave, Boston, MA 02130 USA. EM verf@bu.edu OI Schacter, Daniel/0000-0002-2460-6061; Verfaellie, Mieke/0000-0001-5535-4584 FU NIA NIH HHS [AG08441]; NIMH NIH HHS [MH 57681]; NINDS NIH HHS [NS 26985] NR 51 TC 13 Z9 13 U1 5 U2 14 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2005 VL 19 IS 6 BP 760 EP 769 DI 10.1037/0894-4105.19.6.760 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 993TJ UT WOS:000233977700005 PM 16351351 ER PT J AU Hoh, BL Nogueira, RG Ledezma, CJ Pryor, JC Ogilvy, CS AF Hoh, BL Nogueira, RG Ledezma, CJ Pryor, JC Ogilvy, CS TI Safety of heparinization for cerebral aneurysm coiling soon after external ventriculostomy drain placement SO NEUROSURGERY LA English DT Article DE aneurysm; coiling; complications; heparin; hydrocephalus; subarachnoid hemorrhage; ventriculostomy ID COMBINED NEUROVASCULAR TEAM; GUGLIELMI DETACHABLE COILS; SUBARACHNOID HEMORRHAGE; INTRACRANIAL ANEURYSMS; ENDOVASCULAR TREATMENT; EMBOLIZATION AB OBJECTIVE: Our practice has been to heparinize patients for cerebral aneurysm coiling even after recent external ventriculostomy drain (EVD) placement. The current medical literature cites a 12.5% symptomatic hemorrhage rate with heparinization after recent EVD placement. We reviewed our experience to determine our level of safety with this practice. METHODS: A search of our prospectively collected computerized aneurysm database revealed that from February 1998 to February 2004, 356 aneurysms were coiled, of which 119 patients had had recent EVD placement before coiling. During the same time period, 251 subarachnoid hemorrhage patients underwent EVD placement without coiling or heparinization. We reviewed the head computed tomographic scan reports and medical records to determine the incidence of EVD-related hemorrhage in heparinized patients compared with nonheparinized patients. RESULTS: There was only 1 patient in the heparinized group who had a symptomatic EVD-related hemorrhage attributable to heparinization (0.8%) and 11 patients with asymptomatic EVD-related hemorrhage (9.2%). Among the nonheparinized patients, there were 3 patients who had symptomatic EVD-related hemorrhages (1.2%) and 22 patients with asymptomatic EVD-related hemorrhages (8.8%) (P = not significant for both symptomatic and asymptomatic EVD-related hemorrhages). The time interval between EVD placement and heparinization in the heparinized patient with symptomatic EVD-related hemorrhage was 0.5 day; the mean time interval in the heparinized patients with asymptomatic EVD-related hemorrhage was 0.8 day; and in the heparinized patients with no hemorrhage, it was 0.8 day. The peak activated prothrombin time of the heparinized patient with symptomatic EVD-related hemorrhage was >150 seconds, the mean peak activated prothrombin time of the heparinized patients with asymptomatic EVD-related hemorrhage was 73.1 seconds, and that of the heparinized patients with no hemorrhage was 90.3 seconds. CONCLUSION: Heparinization for cerebral aneurysm coiling can be safely performed even after EVD placement within 24 hours, particularly if the activated prothrombin time is kept strictly controlled. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA USA. RP Ogilvy, CS (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, VBK 710,55 Fruit St, Boston, MA 02114 USA. EM cogilvy@partners.org NR 14 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD NOV PY 2005 VL 57 IS 5 BP 845 EP 848 DI 10.1227/01.NEU.0000180814.95032.07 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 982PF UT WOS:000233173400008 PM 16284554 ER PT J AU Loening, NM Chamberlin, AM Zepeda, AG Gonzalez, RG Cheng, LL AF Loening, NM Chamberlin, AM Zepeda, AG Gonzalez, RG Cheng, LL TI Quantification of phosphocholine and glycerophosphocholine with P-31 edited H-1 NMR spectroscopy SO NMR IN BIOMEDICINE LA English DT Article DE P-31 edited H-1 NMR; INEPT; choline compounds; human brain tumor extracts ID MAGNETIC-RESONANCE-SPECTROSCOPY; PROTON MR SPECTROSCOPY; IN-VITRO; PHOSPHOLIPID-METABOLISM; BREAST-CANCER; BRAIN-TUMORS; H-1 MRS; EX-VIVO; CHOLINE; TISSUE AB Choline and the related compounds phosphocholine (PC) and glycerophosphocholine (GPC) are considered to be important metabolites in oncology. Past studies have demonstrated correlations linking the relative ratios and concentrations of these metabolites with the development and progression of cancer. Currently, in vivo and tissue ex vivo magnetic resonance spectroscopy methods have mostly centered on measuring the total concentration of these metabolites and have difficulty in differentiating between them. Here, a new scheme that uses P-31 edited H-1 spectroscopy to quantify the concentrations of choline, PC and GPC in biological samples is reported and its applicability is demonstrated using samples of human brain tumor extracts. This method is particularly well-suited for analytical situations where the PC and GPC resonances are not sufficiently resolved and/or are obscured by other metabolites. Consequently, this scheme has the potential to be used for the analysis of choline compounds in ex vivo tissue samples. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Lewis & Clark Coll, Dept Chem, Portland, OR 97219 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Loening, NM (reprint author), Lewis & Clark Coll, Dept Chem, 0615 SW Palatine Hill Rd, Portland, OR 97219 USA. EM loening@lclark.edu FU NCI NIH HHS [CA77727, CA095624, CA83159]; NIBIB NIH HHS [EB002026]; NINDS NIH HHS [F32 NS42425-01] NR 40 TC 25 Z9 26 U1 0 U2 11 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 NOV PY 2005 VL 18 IS 7 BP 413 EP 420 DI 10.1002/nbm.973 PG 8 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 984NI UT WOS:000233311200001 PM 16075415 ER PT J AU Sisterson, JM Brooks, FD Buffler, A Allie, MS Jones, DTL Chadwick, MB AF Sisterson, JM Brooks, FD Buffler, A Allie, MS Jones, DTL Chadwick, MB TI Cross-section measurements for neutron-induced reactions in copper at neutron energies of 70.7 and 110.8 MeV SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article DE spallation reactions; quasi-monoenergetic neutron beams; cross-section measurements ID COSMOGENIC NUCLIDES; RADIONUCLIDES; SPECTRA; PROTONS; CU AB Cross-sections for neutron-induced reactions on copper producing relatively short-lived radionuclides were measured at incident neutron energies of 70.7 and 110.8 MeV. These measurements were made using quasi-monoenergetic neutrons obtained from the Be + p reaction. Corrections were made for the contribution of the low energy tail in the incident neutron spectrum of these measurements. The measured cross-sections were compared with some of the few reported cross-section measurements for neutron-induced reactions at high energies, theoretical cross-sections calculated using MC-ALICE and with the cross-sections for the corresponding proton-induced reactions. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, NE Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Cape Town, Dept Phys, ZA-7700 Rondebosch, South Africa. iThemba LABS, ZA-7129 Somerset W, South Africa. Los Alamos Natl Lab, Adv Simulat & Comp, Los Alamos, NM 87544 USA. RP Sisterson, JM (reprint author), Massachusetts Gen Hosp, NE Proton Therapy Ctr, 30 Fruit St, Boston, MA 02114 USA. EM jsisterson@partners.org NR 20 TC 18 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD NOV PY 2005 VL 240 IS 3 BP 617 EP 624 DI 10.1016/j.nimb.2005.06.005 PG 8 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 984ZH UT WOS:000233345400003 ER PT J AU Obrzut, SL Koren, AO Mandelkern, MA Brody, AL Hoh, CK London, ED AF Obrzut, SL Koren, AO Mandelkern, MA Brody, AL Hoh, CK London, ED TI Whole-body radiation dosimetry of 2-[F-18]fluoro-A-85380 in human PET imaging studies SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE 2-[F-18]FA; dosimetry; PET; nicotinic acetylcholine receptor; whole-body distribution ID NICOTINIC ACETYLCHOLINE-RECEPTORS; IN-VIVO; HUMAN BRAIN; POSITRON-EMISSION; ALZHEIMER BRAINS; BINDING-SITES; H-3 NICOTINE; TRACER; BIODISTRIBUTION; QUANTIFICATION AB 2-[F-18]Fluoro-A-85380 (2- [F-18]fluoro-3-(2(S)-azetidinylmethoxy)pyridine, 2-[18F]FA) is a recently developed PET radioligand for noninvasive imaging of nicotinic acetylcholine receptors. Previous radiation absorbed dose estimates for 2-[F-18]FA were limited to evaluation of activity in only several critical organs. Here, we performed 2-[F-18]FA radiation dosimetry studies on two healthy human volunteers to obtain data for all important body organs. Intravenous injection of 2.9 MBq/kg of 2-[F-18]FA was followed by dynamic PET imaging. Regions of interest were placed over images of each organ to generate time-activity curves, from which we computed residence times. Radiation absorbed doses were calculated from the residence times using the MIRDOSE 3.0 program (version 3.0, ORISE, Oak Ridge, TN). The urinary bladder wall receives the highest radiation absorbed dose (0.153 mGy/MBq, 0.566 rad/mCi, for a 2.4-h voiding interval), followed by the liver (0.0496 mGy/MBq, 0.184 rad/mCi) and the kidneys (0.0470 mGy/MBq, 0.174 rad/mCi). The mean effective dose equivalent is estimated to be 0.0278 mSv/MBq (0.103 rem/mCi), indicating that radiation dosimetry associated with 2-[F-18]FA is within acceptable limits. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif San Diego, Div Nucl Med, Dept Radiol, La Jolla, CA 92093 USA. VA Greater Los Angeles Healthcare Syst, Positron Emiss Tomog Ctr, Los Angeles, CA 90073 USA. Univ Calif Irvine, Dept Phys, Irvine, CA 92697 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. RP London, ED (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu NR 32 TC 14 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD NOV PY 2005 VL 32 IS 8 BP 869 EP 874 DI 10.1016/j.nucmedbio.2005.06.005 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 983RM UT WOS:000233249800010 PM 16253812 ER PT J AU Norman, LD Donelan, K Buerhaus, PI Willis, G Williams, M Ulrich, B Dittus, R AF Norman, LD Donelan, K Buerhaus, PI Willis, G Williams, M Ulrich, B Dittus, R TI The older nurse in the workplace: Does age matter? SO NURSING ECONOMICS LA English DT Article ID SATISFACTION; WORKFORCE; CAREER AB Of the additional 185,000 nurses that joined the workforce in 2002 and 2003, 70% were age 50 and over. Part five of this series focuses on older RNs and characteristics of this growing cohort that impact the current and future nursing workforce such as employment patterns, attitudes, health, and perceptions of the nursing shortage relative to their younger counterparts. While 46% of older nurses surveyed provide direct patient care, only 38% of older nurses work in acute care settings. Older nurses are more satisfied with their current jobs and with nursing as a career than younger nurses; still, a third intend to leave their current position within 3 years with the likely intention to retire or change professions. Given that older nurses are the fastest growing cohort of the workforce, the findings of this research deserve careful consideration by policymakers, health care leaders, and managers. Efforts to retain older nurses with, for example, incentives to delay retirement may mitigate the shortages that are now likely to surface in non-acute care settings given the concentration of older nurses in these areas. C1 Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Nurseweek Publ Inc, Houston, TX USA. RP Norman, LD (reprint author), Vanderbilt Univ, Sch Nursing, Nashville, TN 37240 USA. NR 29 TC 23 Z9 23 U1 0 U2 3 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD NOV-DEC PY 2005 VL 23 IS 6 BP 282 EP 289 PG 8 WC Nursing SC Nursing GA 046HO UT WOS:000237802400002 PM 16459900 ER PT J AU Rempusheski, VF O'Hara, CT AF Rempusheski, VF O'Hara, CT TI Psychometric properties of the Grandparent Perceptions of Family Scale (GPFS) (vol 54, pg 363, 2005) SO NURSING RESEARCH LA English DT Correction DE family; grandparents; psychometric testing ID RAISING GRANDCHILDREN; GRANDMOTHERS; PROFILE; EXPERIENCES; CAREGIVER; SUPPORT; HISTORY; ADULTS AB Background. For the majority of grandparents, rarely are their perceptions of family assessed, acknowledged, or viewed in the context of potential effect on individual and family health. Objective: To develop and test an instrument to measure grandparent perceptions of family. Method. An inductively derived semantic differential instrument comprising 112 items, 8 stimuli, and 27 adjective pairs within 2 domains and framed by the Becoming a Grandparent theoretical model was content validated by an expert panel, revised, and evaluated on a convenience sample of 306 community-dwelling grandparents, aged 41-92 years (M = 64, SD = 9.8), 72% female, 93% U.S. born, 62% college educated, 55% economically comfortable, and 71% living with a spouse or partner. Assessment procedures included internal consistency reliability, item and scale correlation coefficients, and principal components factor analysis with varimax rotation to evaluate construct validity, structure, and magnitude of the scale. Results: The final scale consists of 25 items using 3 stimuli (grandparent's view of grandchild, mother of grandchild, father of grandchild) measuring a single domain (overall view of family). The Grandparent Perceptions of Family Scale (GPFS) includes 5 factors for a total explained variance of 60%. Coefficient a for the total scale is .90. Discussion: The GPFS should be helpful to clinicians and researchers in their assessment of grandparents within multigenerational families and in planning appropriate interventions to address the roles and relationships of grandparents within families. Further GPFS evaluation is suggested with grandparents of diverse racial or ethnic identification; social economic position; education; and family definition, roles, composition, and structure. C1 Univ Kansas, Sch Nursing, Kansas City, KS 66160 USA. SUNY Upstate Med Univ, Joslin Diabet Ctr, Syracuse, NY USA. RP Rempusheski, VF (reprint author), Univ Kansas, Sch Nursing, Mail Stop 4043,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM vrempusheski@kumc.edu NR 50 TC 2 Z9 2 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD NOV-DEC PY 2005 VL 54 IS 6 BP 419 EP 427 DI 10.1097/00006199-200511000-00009 PG 9 WC Nursing SC Nursing GA 990JT UT WOS:000233739800008 PM 16372397 ER PT J AU Allen, RH Tuomala, RE AF Allen, RH Tuomala, RE TI Herpes simplex virus hepatitis causing acute liver dysfunction and thrombocytopenia in pregnancy SO OBSTETRICS AND GYNECOLOGY LA English DT Article AB BACKGROUND: Herpes simplex virus (HSV) hepatitis in pregnant women is a rare condition. We report a case confirmed by liver biopsy and successfully treated with empiric intravenous acyclovir. CASE: A 25-year-old primigravida at 34 weeks of gestation presented with fever, thrombocytopenia, and markedly elevated liver enzymes. The patient was treated empirically and was delivered by cesarean. After delivery failed to correct her condition, a liver biopsy revealed HSV hepatitis. The fetus was unaffected and the patient recovered with an extended course of acyclovir. CONCLUSION: Pregnant women are susceptible to disseminated HSV causing hepatitis. A high index of suspicion is necessary to diagnose HSV hepatitis and begin appropriate treatment with acyclovir. Herpes simplex virus hepatitis should be included in the differential diagnosis for liver failure during pregnancy. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Maternal Fetal Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Allen, RH (reprint author), Brigham & Womens Hosp, Dept Obstet & Gynecol, 75 Francis St, Boston, MA 02115 USA. EM rallen@partners.org NR 6 TC 11 Z9 13 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2005 VL 106 IS 5 BP 1187 EP 1189 DI 10.1097/01.AOG.0000160481.11517.a0 PN 2 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 980LB UT WOS:000233018900019 PM 16260566 ER PT J AU Ryan, DP Clark, JW AF Ryan, DP Clark, JW TI Management of anal cancer in the HIV-positive population - The Kauh/Koshy/Gunthel et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID COMBINED-MODALITY THERAPY; EPIDERMOID CARCINOMA; RANDOMIZED TRIAL; RADIOTHERAPY; CHEMOTHERAPY; MITOMYCIN C1 Massachusetts Gen Hosp, Ctr Canc, Clin Programs, Boston, MA 02114 USA. RP Ryan, DP (reprint author), Massachusetts Gen Hosp, Ctr Canc, Clin Programs, Boston, MA 02114 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2005 VL 19 IS 12 BP 1638 EP + PG 3 WC Oncology SC Oncology GA 052ET UT WOS:000238215000019 ER PT J AU Sequist, LV Lynch, TJ AF Sequist, LV Lynch, TJ TI The Buter/Giaccone article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID CELL LUNG-CANCER; RECEPTOR TYROSINE KINASE; PHASE-III TRIAL; NEVER-SMOKERS; GEFITINIB; MUTATIONS; ERLOTINIB; GENE; INHIBITOR; SENSITIVITY C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. RP Sequist, LV (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02115 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2005 VL 19 IS 13 SI SI BP 1711 EP + PG 3 WC Oncology SC Oncology GA 052EU UT WOS:000238215100013 ER PT J AU Hayes, C Ponte, PR Coakley, A Stanghellini, E Gross, A Perryman, S Hanley, D Hickey, N Somerville, J AF Hayes, C Ponte, PR Coakley, A Stanghellini, E Gross, A Perryman, S Hanley, D Hickey, N Somerville, J TI Retaining oncology nurses: Strategies for today's nurse leaders SO ONCOLOGY NURSING FORUM LA English DT Editorial Material C1 Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Hayes, C (reprint author), Brigham & Womens Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. EM carolyn_hayes@dfci.harvard.edu NR 11 TC 6 Z9 6 U1 0 U2 0 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2005 VL 32 IS 6 BP 1087 EP 1090 DI 10.1188/05.ONF1087-1090 PG 4 WC Oncology; Nursing SC Oncology; Nursing GA 988EQ UT WOS:000233574800002 ER PT J AU Rubin, PAD Hatton, MP Bilyk, JR AF Rubin, PAD Hatton, MP Bilyk, JR TI Orbital perforating branch of the infraorbital artery: An important landmark in orbital surgery SO OPHTHALMIC PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery CY OCT 23, 2004 CL New Orleans, LA SP Amer Soc Ophthalm Plast & Reconstruct Surg AB The orbital branch of the infraorbital artery is an important surgical landmark but is frequently omitted from texts that discuss orbital anatomy and surgical technique. This report reviews the anatomy of this artery to familiarize the reader with its existence and location to reduce the risk of intraoperative hemorrhage from this vessel. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Wills Eye Hosp & Res Inst, Philadelphia, PA USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM Eye_plastics@meei.harvard.edu NR 3 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0740-9303 J9 OPHTHAL PLAST RECONS JI Ophthalmic Plast. Reconstr. Surg. PD NOV PY 2005 VL 21 IS 6 BP 447 EP 449 DI 10.1097/01.iop.0000181347.60734.25 PG 3 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 988EC UT WOS:000233573400010 PM 16304524 ER PT J AU Scrivani, SJ Mathews, ES Maciewicz, RJ AF Scrivani, SJ Mathews, ES Maciewicz, RJ TI Trigeminal neuralgia SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTOLOGY LA English DT Review ID CLUSTER-TIC SYNDROME; GAMMA-KNIFE RADIOSURGERY; ATYPICAL FACIAL-PAIN; SPINAL NERVE ROOTS; OF-THE-LITERATURE; HEMIFACIAL SPASM; MULTIPLE-SCLEROSIS; MICROVASCULAR DECOMPRESSION; NEUROPATHIC PAIN; NEUROVASCULAR COMPRESSION AB Trigeminal Neuralgia (TN) is a well recognized syndrome characterized by lancinating attacks of severe facial pain. The diagnosis of TN is based on a history of characteristic pain attacks that are consistent with specific widely accepted criteria for the diagnosis. TN pain attacks may result from physiologic changes induced by a chronic partial injury to the brainstem trigeminal nerve root from a variety of causes. An early and accurate diagnosis of TN is important, because therapeutic interventions can reduce or eliminate pain attacks in the large majority of TN patients. C1 Tufts Univ, New England Med Ctr, Craniofacial Pain Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. PBS Med Consulting, Boston, MA USA. RP Scrivani, SJ (reprint author), Tufts Univ, New England Med Ctr, Craniofacial Pain Ctr, 1 Kneeland St, Boston, MA 02111 USA. EM steven.scrivani@tufts.edu NR 164 TC 23 Z9 26 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD NOV PY 2005 VL 100 IS 5 BP 527 EP 538 DI 10.1016/j.tripleo.2005.06.004 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 980PD UT WOS:000233029600002 PM 16243236 ER PT J AU Dougherty, CM Thompson, EA Lewis, FM AF Dougherty, CM Thompson, EA Lewis, FM TI Long-term outcomes of a telephone intervention after an ICD SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE sudden cardiac arrest; ICD; clinical trial; telephone intervention; psychological; health care costs; nursing ID INTERNAL CARDIOVERTER-DEFIBRILLATOR; SUDDEN CARDIAC-ARREST; QUALITY-OF-LIFE; NURSING INTERVENTION; IMPACT; IMPLANTATION; DEPRESSION; VALIDATION; SYMPTOMS; ANXIETY AB Background: The purpose of this study was to determine the long-term benefits of participating in a structured, 8-week educational telephone intervention delivered by expert cardiovascular nurses post-ICD. The intervention was aimed to (1) increase physical functioning, (2) increase psychological adjustment, (3) improve self-efficacy in managing the challenges of ICD recovery, and (4) lower levels of health care utilization over usual care in the first 12 months post-ICD, This article reports on the 6- and 12-month outcomes of the nursing intervention trial. Methods and Results: A two-group (N = 168) randomized control group design was used to evaluate intervention efficacy with persons receiving an ICD for the secondary prevention of sudden cardiac arrest. Measures were obtained at baseline, 6 and 12 months post hospitalization. Outcomes included (1) physical functioning (Patient Concerns Assessment [PCA], Short Form Health Survey [SF-12], ICD shocks), (2) psychological adjustment (State-Trait Anxiety Inventory [STAI], Centers for Epidemiologic Studies-Depression [CES-D], fear of dying), (3) self-efficacy (Sudden Cardiac Arrest-Self-Efficacy [SCA-SE], Sudden Cardiac Arrest-Behavior [SCA-B], Sudden Cardiac Arrest-Knowledge [SCA-K]), and(4)health care utilization (emergency room [ER] visits, outpatient visits, hospitalizations). Using repeated measures ANOVA, the 6- and 12-month benefits of the intervention over usual care were in reductions in physical concerns (P = 0.006), anxiety (P = 0.04), and fear of dying (P = 0.01), with enhanced self-confidence (P = 0.04) and knowledge (P = 0.001) to manage ICD recovery There were no statistically significant differences between the groups on total outpatient visits, hospitalizations, or ER visits over 12 months. Conclusion: A structured 8-week post-hospital telephone nursing intervention after an ICD had sustained 12-month improvements on patient concerns, anxiety, fear of dying, self-efficacy, and knowledge. Results may not apply to individuals with congestive heart failure who receive an ICD for primary prevention of sudden cardiac arrest. C1 Univ Washington, Sch Nursing, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Dougherty, CM (reprint author), Univ Washington, Sch Nursing, Box 357266,Room T608D, Seattle, WA 98195 USA. EM cindyd@u.washington.edu FU NINR NIH HHS [R01NR04766] NR 32 TC 39 Z9 38 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 2005 VL 28 IS 11 BP 1157 EP 1167 DI 10.1111/j.1540-8159.2005.09500.x PG 11 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 990MM UT WOS:000233747500002 PM 16359281 ER PT J AU Jung, BF Herrmann, D Griggs, J Oaklander, AL Dworkin, RH AF Jung, BF Herrmann, D Griggs, J Oaklander, AL Dworkin, RH TI Neuropathic pain associated with non-surgical treatment of breast cancer SO PAIN LA English DT Review DE neuropathic pain; breast cancer; radiation plexopathy; chemotherapy neuropathy ID INDUCED PERIPHERAL NEUROPATHY; RADIATION-THERAPY; NEUROLOGIC COMPLICATIONS; COMBINATION CHEMOTHERAPY; BRACHIAL PLEXOPATHY; DOCETAXEL TAXOTERE; PACLITAXEL; RADIOTHERAPY; CISPLATIN; TOXICITY C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Med Hematol Oncol, Rochester, NY 14642 USA. Univ Rochester, Sch Med & Dent, Dept Community & Prevent Med, Rochester, NY 14642 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nerve Injury Unit,Dept Anesthesiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, 601 Elmwood Ave,Box 604, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.edu FU NINDS NIH HHS [NS 42866] NR 41 TC 32 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2005 VL 118 IS 1-2 BP 10 EP 14 DI 10.1016/j.pain.2005.09.014 PG 5 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 984DD UT WOS:000233281800005 PM 16213086 ER PT J AU Lu, Q Zeltzer, LK Tsao, JCI Kim, SC Turk, N Naliboff, BD AF Lu, Q Zeltzer, LK Tsao, JCI Kim, SC Turk, N Naliboff, BD TI Heart rate mediation of sex differences in pain tolerance in children SO PAIN LA English DT Article DE sex differences; laboratory pain; pain tolerance; heart rate; puberty; children and adolescents ID ADOLESCENTS SELF-ASSESSMENT; HEMODYNAMIC-RESPONSES; LABORATORY PAIN; MATURATION; STIMULI; GENDER; GIRLS; SENSITIVITY; DEPRESSION; VALIDITY AB Despite evidence supporting the existence of important sex-related differences in pain, the mechanisms underpinning such differences are not well understood. The aim of this study is to examine the relationship between sex and pubertal differences in autonomic arousal and pain tolerance to laboratory pain stimuli in healthy children. We tested the following specific hypotheses: (1) females would have greater autonomic arousal and less pain tolerance than males, and (2) this sex difference in pain tolerance would be mediated by autonomic arousal. Participants were 244 healthy children (50.8% female, mean age 12.73 +/- 2.98 years, range 8-18 years). Separate 4-trial blocks of cutaneous pressure and thermal pain stimuli were presented in counterbalanced order. Heart rate (HR) was recorded during 2-3 min periods preceding each block and a 1-min period between trials. Results indicated lower tolerance in females for cutaneous pressure, but not thermal pain, compared to males. In addition, pre-trial HR was greater for females than males. Mediation analyses Suggested that sex differences in pressure pain tolerance were accounted for by sex differences in pre-trial HR. There were also significant effects for puberty, but these did not vary by sex. Overall, early pubertal children had greater pre-trial HR and less pain tolerance than those in late puberty for both cutaneous pressure and thermal pain across sex. These results suggest that autonomic arousal may be a mediator of sex-related differences in pain responses in children. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, UCLA Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Vet Adm Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Pediat Pain Program, Los Angeles, CA 90073 USA. RP Naliboff, BD (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, UCLA Ctr Neurovisceral Sci & Womens Hlth, Bldg 115,Rm 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM naliboff@ucla.edu OI Zeltzer, Lonnie/0000-0001-9306-9450 FU NCCIH NIH HHS [R24 AT002681]; NCRR NIH HHS [MO1-RR-00865]; NIDCR NIH HHS [R01 DE12754-01A1]; NINR NIH HHS [R01 NR007768] NR 39 TC 21 Z9 22 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2005 VL 118 IS 1-2 BP 185 EP 193 DI 10.1016/j.pain.2005.08.008 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 984DD UT WOS:000233281800024 PM 16213093 ER PT J AU Gallagher, RM AF Gallagher, RM TI Pulsed radiofrequency treatment: Biological mechanisms and clinical evidence SO PAIN MEDICINE LA English DT Editorial Material C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. NR 5 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2005 VL 6 IS 6 BP 401 EP 402 DI 10.1111/j.1526-4637.2005.00077.x PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 989DX UT WOS:000233654200001 PM 16336476 ER PT J AU Mossey, JM Kerr, NDS Welz-Bosna, M Gallagher, RM AF Mossey, JM Kerr, NDS Welz-Bosna, M Gallagher, RM TI Preliminary evaluation of the Health Background Questionnaire for Pain and Clinical Encounter Form for Pain SO PAIN MEDICINE LA English DT Article DE Health Background Questionnaire; Medical Outcome Study Short Form-3; Clinical Encounter Form ID BACK-PAIN; INSTRUMENT; MANAGEMENT; MEDICINE; OUTCOMES; QUALITY; SF-36; ANGER; CARE AB Objectives. The principal aims of this study were to evaluate the extent to which patients completed, understood, and were satisfied with the Health Background Questionnaire for Pain (HBQ-P), a health and pain history questionnaire that includes a modification of the Medical Outcome Study Short Form-36, the Treatment Outcomes in Pain Survey, and to examine the degree to which the questionnaire produced reliable and valid responses. A secondary aim was to determine the length of time for a physician to complete the Clinician Evaluation Form for Pain (CEF-P), a brief questionnaire designed to obtain key elements resulting from clinical assessment and management decisions. Methods. This cross-sectional study utilized data from consecutive new patients seen from January to December 2001 in Drexel University College of Medicine's Pain Medicine and Comprehensive Rehabilitation Center at Graduate Hospital in Philadelphia, PA. The HBQ-P and an accompanying brief satisfaction inventory were completed at home by the patient prior to the individual's initial office visit. The CEF-P was completed by the physician after seeing the patient. Results. Ten of 11 comparisons of patient responses to similar questions on the HBQ-P showed significant consistency. Of eight comparisons between the CEF-P and HBQ-P, two pain duration comparisons showed moderate agreement and one depression comparison showed significant association. Patients consistently had difficulty in answering six single questions and two question sets. Overall patient satisfaction was high. The mean time for the physician to complete the CEF-P was 90 seconds. Conclusions. Analyses indicate patient responses to similar HBQ-P questions have sufficient reliability to support the use of the Health Background Questionnaire for clinically related data collection and for outcome evaluation of treatments for chronic and recurring pain. The consistently missed questions on the HBQ-P should be revised. C1 Philadelphia VA Med Ctr, Pain Management Serv, Philadelphia, PA 19014 USA. Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Univ Penn, Ctr Pain Med Res & Policy, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Gallagher, RM (reprint author), Philadelphia VA Med Ctr, Pain Management Serv, Univ & Woodland Ave, Philadelphia, PA 19014 USA. EM rgallagh@mail.med.upenn.edu NR 26 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2005 VL 6 IS 6 BP 443 EP 451 DI 10.1111/j.1526-4637.2005.00075.x PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 989DX UT WOS:000233654200006 PM 16336481 ER PT J AU Rich, BA Casarett, D Battin, MP AF Rich, BA Casarett, D Battin, MP TI Ethics forum SO PAIN MEDICINE LA English DT Editorial Material C1 Univ Calif Davis, Sacramento, CA 95817 USA. Univ Penn, Div Geriatr Med, Philadelphia VAMC, Ctr Hlth Equity Res & Promot, Philadelphia, PA 19104 USA. Univ Utah, Dept Philosophy, Salt Lake City, UT USA. Univ Utah, Div Med Eth, Salt Lake City, UT USA. RP Rich, BA (reprint author), Univ Calif Davis, Sacramento, CA 95817 USA. NR 11 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1526-2375 J9 PAIN MED JI Pain Med. PD NOV-DEC PY 2005 VL 6 IS 6 BP 459 EP 463 DI 10.1111/j.1526-4637.2005.00074.x PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 989DX UT WOS:000233654200008 PM 16336483 ER PT J AU Longnecker, DS Adsay, NV Fernandez-del Castillo, C Hruban, RH Kasugai, T Klimstra, DS Kloppel, G Luttges, J Memoli, VA Tosteson, TD Yanagisawa, A Wilentz, R Zamboni, G AF Longnecker, DS Adsay, NV Fernandez-del Castillo, C Hruban, RH Kasugai, T Klimstra, DS Kloppel, G Luttges, J Memoli, VA Tosteson, TD Yanagisawa, A Wilentz, R Zamboni, G TI Histopathological diagnosis of pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms: Interobserver agreement SO PANCREAS LA English DT Article DE intraductal papillary-mucinous neoplasm; pancreatic carcinoma; PanIN ID DUCTAL ADENOCARCINOMA; CYSTIC TUMORS; CLASSIFICATION; EXPRESSION; MALIGNANCY; EPITHELIUM; FEATURES; PATTERN AB Objectives: The goal of this study was to evaluate the consistency of distinction between pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary-mucinous neoplasms (IPMN) and the hypothesis that guidelines for their distinction might be inadequate. Methods: A group of 93 pancreas specimens from surgical resections or autopsies that contained lesions consistent with histopathological diagnoses of PanIN-1A, PanIN-1B, PanIN-2, or IPMN ( adenoma or borderline) was collected. The classification of these neoplasms by 6 pathologists, 2 from Europe, 2 from Japan, and 2 from the United States, was compared. The pathologists initially used guidelines current in their practice and then reviewed 47 of the 93 specimens a second time using new consensus definitions and guidelines for PanIN and IPMN that were developed in 2003. Results: The initial comparison showed frequent disagreement regarding both category and grade of the lesions. Agreement was greater for category than grade. In the second review, agreement among the 6 reviewers improved, remaining higher for category, although disagreements persisted for both category and grade. Conclusions: We conclude that the new definitions of PanIN and IPMN improve the consistency in classifying these lesions, but additional work is needed to further improve the reproducibility of their classification. C1 Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Johns Hopkins Med Inst, Sol Goldman Ctr Pancreat Canc Res, Dept Pathol & Oncol, Baltimore, MD 21205 USA. Osaka Kouseinenkin Hosp, Dept Pathol, Osaka, Japan. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Univ Kiel, Dept Pathol, D-2300 Kiel, Germany. Dartmouth Hitchcock Med Ctr, Dept Community & Family Med, Lebanon, NH 03756 USA. Kyoto Prefectural Univ Med, Dept Pathol, Kyoto 602, Japan. Skin & Canc Associates, Pathol Lab, Hallandale, FL USA. Univ Verona, Dept Pathol, I-37100 Verona, Italy. RP Longnecker, DS (reprint author), Dartmouth Hitchcock Med Ctr, Dept Pathol, Lebanon, NH 03756 USA. EM daniel.s.longnecker@dartmouth.edu RI Giuseppe, Zamboni/A-5991-2016 OI Giuseppe, Zamboni/0000-0001-7428-4673 FU NCI NIH HHS [CA023108, P30 CA023108, P50 CA62924] NR 34 TC 53 Z9 56 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2005 VL 31 IS 4 BP 344 EP 349 DI 10.1097/01.mpa.0000186245.35716.18 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 980KM UT WOS:000233017400006 PM 16258368 ER PT J AU Jonker, SS Faber, JJ Anderson, DF Thomburg, KL Rodgers, RK Hou, EF Giraud, GD AF Jonker, SS Faber, JJ Anderson, DF Thomburg, KL Rodgers, RK Hou, EF Giraud, GD TI Prenatal hypertension induced by plasma infusion programs cardiac growth and maturation in fetal sheep SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med Cardiol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Heart Res Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1018 EP 1018 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000066 ER PT J AU Jimenez-Chillaron, JC Faucette, RR Reamer, C Barry, K Ruest, S Otis, J Patti, ME AF Jimenez-Chillaron, JC Faucette, RR Reamer, C Barry, K Ruest, S Otis, J Patti, ME TI Intergenerational effects of fetal programming: Potential role of imprinted genes for the inheritance of low birth weight and obesity SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1038 EP 1039 PG 2 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000137 ER PT J AU Jonker, SS Karamlou, T Faber, JJ Anderson, DF Giraud, GD Thornburg, KL AF Jonker, SS Karamlou, T Faber, JJ Anderson, DF Giraud, GD Thornburg, KL TI NCX and SERCA genes are not regulated by hemodynamic stress in the fetal sheep heart SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Oregon Hlth Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Med Cardiol, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1082 EP 1082 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000303 ER PT J AU Bagby, SP Roullet, JB Xue, H Saunders, K AF Bagby, SP Roullet, JB Xue, H Saunders, K TI Endothelium-independent mesenteric vascular hyperreactivity to pressors in hypertensive prepubertal microswine offspring exposed to maternal protein restriction SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Oregon Hlth Sci Univ, Dept Med, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Vasc Surg, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Comparat Med, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR 97239 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1107 EP 1107 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000393 ER PT J AU Iuga, AO Reddy, VB Lerner, EA AF Iuga, AO Reddy, VB Lerner, EA TI Identification of novel hexapeptide agonists at the Xenopus laevis melanophore melanocortin receptor SO PEPTIDES LA English DT Article DE MSH; melanocortin; G-protein coupled receptor; melanophore; peptide; screening ID PROTEIN-COUPLED RECEPTORS; ALPHA-MELANOTROPIN; FRAMESHIFT MUTATION; ACTH RECEPTOR; LIGANDS; ANALOGS; DESIGN; PEPTIDES; HORMONE; POTENT AB We used a combinatorial chemical approach to identify novel agonists for the endogenous melanocortin receptor expressed in Xenopus laevis melanophores. A random one-bead one-compound hexapeptide library was screened to detect new molecules able to induce pigment dispersion in melanophores. Our approach led to the discovery of seven related novel peptides able to stimulate pigment dispersion with EC50 in the range of 0.1-10 mu M. Their action was inhibited by the amphibian melanocortin receptor antagonist dWRL. These novel peptides share no significant sequence homology with known melanocortins. This study may aid in the understanding of the chemical interaction between the melanocortin receptors and their ligands. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Lerner, EA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. EM ethan.lerner@cbrc2.mgh.harvard.edu FU NIAMS NIH HHS [R0-AR 42005, R0-AR 44510] NR 27 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2005 VL 26 IS 11 BP 2124 EP 2128 DI 10.1016/j.peptides.2005.03.001 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 985JI UT WOS:000233373100012 PM 16269347 ER PT J AU Naleid, AM Grace, MK Cummings, DE Levine, AS AF Naleid, AM Grace, MK Cummings, DE Levine, AS TI Ghrelin induces feeding in the mesolimbic reward pathway between the ventral tegmental area and the nucleus accumbens SO PEPTIDES LA English DT Article DE ghrelin; reward; opioid; food intake; microinjection; rat ID OPIOID ANTAGONIST NALTREXONE; GROWTH-HORMONE SECRETAGOGUE; NEUROPEPTIDE-Y; ENERGY-BALANCE; FOOD-INTAKE; PARAVENTRICULAR NUCLEUS; ARCUATE NUCLEUS; SOLITARY TRACT; MESSENGER-RNA; RAT AB Ghrelin, a powerful orexigenic peptide released from the gut, stimulates feeding when injected centrally and has thus far been implicated in regulation of metabolic, rather than hedonic, feeding behavior. Although ghrelin's effects are partially mediated at the hypothalamic arcuate nucleus, via activation of neurons that co-express neuropeptide Y and agouti-related protein (NPY/Agrp neurons), the ghrelin receptor is expressed also in other brain sites. One of these is the ventral tegmental area (VTA), a primary node of the mesolimbic reward pathway, which sends dopaminergic projections to the nucleus accumbens (Acb), among other sites. We injected saline or three doses of ghrelin (0, 0.003, 0.03, or 0.3 nmol) into the VTA or Acb of rats. We found a robust feeding response with VTA injection of ghrelin, and a more moderate response with Acb injection. Because opioids modulate feeding in the VTA and Acb, we hypothesized that ghrelin's effects in one site were dependent on opioid signaling in the opposite site. The general opioid antagonist, naltrexone (NTX), injected into the Acb did not affect feeding elicited by ghrelin, injection into the VTA, and NTX in the VTA did not affect feeding elicited by ghrelin injected into the Acb. These results suggest interaction of a metabolic factor with the reward system in feeding behavior, indicating that hedonic responses can be modulated by homeostatic factors. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Minnesota, Grad Program Neurosci, Minneapolis, MN 55415 USA. Vet Adm Med Ctr, Minnesota Obes Ctr, Minneapolis, MN 55417 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. Univ Minnesota, Dept Food Sci & Nutr, St Paul, MN 55108 USA. Univ Minnesota, Minnesota Craniofacial Res Training Program, Minneapolis, MN 55455 USA. RP Levine, AS (reprint author), Univ Minnesota, Grad Program Neurosci, Minneapolis, MN 55415 USA. EM aslevine@umn.edu FU NIDA NIH HHS [DA-03999]; NIDCR NIH HHS [T32-DE07288]; NIDDK NIH HHS [P 30 DK-50456, P01 DK68384] NR 33 TC 212 Z9 216 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD NOV PY 2005 VL 26 IS 11 BP 2274 EP 2279 DI 10.1016/j.peptides.2005.04.025 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 985JI UT WOS:000233373100032 PM 16137788 ER PT J AU Ryu, H Rosas, HD Hersch, SM Ferrante, RJ AF Ryu, H Rosas, HD Hersch, SM Ferrante, RJ TI The therapeutic role of creatine in Huntington's disease SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE Huntington's disease; therapy; bioenergetics; creatine; mitochondrial dysfunction; triplet repeat disorders ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MOUSE MODELS; GUANIDINOACETATE METHYLTRANSFERASE DEFICIENCY; MONOHYDRATE INCREASES STRENGTH; TOXIN 3-NITROPROPIONIC ACID; HEREDITARY OPTIC NEUROPATHY; NEURODEGENERATIVE DISEASES; SKELETAL-MUSCLE; IN-VIVO; DIETARY-SUPPLEMENT AB Huntington's disease (HD) is an autosomal dominant and fatal neurological disorder characterized by a clinical triad of progressive choreiform movements, psychiatric symptoms, and cognitive decline. HD is caused by an expanded trinucleotide CAG repeat in the gene coding for the protein huntingtin. No proven treatment to prevent the onset or to delay the progression of HD currently exists. While a direct causative pathway from the gene mutation to the selective neostriatal neurodegeneration remains unclear, it has been hypothesized that interactions of the mutant huntingtin protein or its fragments may result in a number of interrelated pathogenic mechanisms triggering a cascade of molecular events that lead to the untimely neuronal death observed in HD. One putative pathological mechanism reported to play a prominent role in the pathogenesis of HD is mitochondrial dysfunction and the subsequent reduction of cellular energy. Indeed, if mitochondrial impairment and reduced energy stores play roles in the neuronal loss in HD, then a therapeutic strategy that buffers intracellular energy levels may ameliorate the neurodegenerative process. Sustained ATP levels may have both direct and indirect importance in ameliorating the severity of many of the pathogenic mechanisms associated with HD. Creatine, a guanidino compound produced endogenously and acquired exogenously through diet, is a critical component in maintaining much needed cellular energy. As such, creatine is one of a number of ergogens that may provide a relatively safe and immediately available therapeutic strategy to HD patients that may be the cornerstone of a combined treatment necessary to delay the relentless progression of HD. (c) 2005 Elsevier Inc. All rights reserved. C1 Bedford VA Med Ctr, Expt Neuropathol Unit, Bedford, MA USA. Bedford VA Med Ctr, Translat Therapeut Lab, Geriatr Res Educ Clin Ctr, Bedford, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. RP Ferrante, RJ (reprint author), Edith Nourse Rogers Mem Vet Adm Med Ctr, Expt Neuropathol Unit, Translat Therapeut Lab, GRECC Unit, Bldg 18, Bedford, MA 01730 USA. EM rjferr@bu.edu FU NCCIH NIH HHS [AT00613]; NINDS NIH HHS [NS045242, NS045806] NR 187 TC 45 Z9 47 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD NOV PY 2005 VL 108 IS 2 BP 193 EP 207 DI 10.1016/j.pharmthera.2005.04.008 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 984OO UT WOS:000233314400004 PM 16055197 ER PT J AU O'Neill, JL Flanagan, PS Zaleon, CR Copeland, LA AF O'Neill, JL Flanagan, PS Zaleon, CR Copeland, LA TI Safety of outpatient dalteparin therapy in veterans with mechanical heart valves SO PHARMACOTHERAPY LA English DT Article DE dalteparin; low-molecular-weight heparin; LMWH; mechanical heart valve; periprocedural anticoagulation; international normalized ratio; INR AB Study Objectives. To determine the rate of bleeding and thromboembolic events within 1 month of outpatient dalteparin therapy in veterans with mechanical heart valves, to evaluate potential risk factors associated with these events, and to examine the prescribing patterns of dalteparin in this patient population. Design. Single-center retrospective electronic chart review. Setting. Large, academically affiliated Veterans Affairs hospital. Subjects. Thirty-eight men with mechanical heart valves who received outpatient prescriptions for dalteparin from October 1, 1998-june 30, 2003. Measurements and Main Results. Charts were reviewed for thromboembolic and bleeding events. Demographic, clinical, and drug utilization variables were assessed. The associations of adverse events with potential risk factors, indication for dalteparin therapy, and prescribing clinic were analyzed. Sixty-four dalteparin regimens were evaluated. No thromboembolic events were reported in any case within 1 month after receiving dalteparin for thromboembolic prophylaxis during warfarin interruption for periprocedural anticoagulation or for anticoagulation during an unintentional subtherapeutic international normalized ratio. Bleeding events occurred in 15 (23%) of the 64 regimens. Most bleeding events resolved spontaneously and without intervention. No potential risk factors for bleeding were identified. Conclusion. Dalteparin appeared to be a safe, effective means of short-term thromboembolic prophylaxis in this population of ambulatory male veterans with mechanical heart valves. Large, randomized, controlled, prospective trials are warranted. C1 Vet Affairs Ann Arbor Healtchare Syst, Dept Pharm, Ann Arbor, MI 48105 USA. Vet Affairs Ann Arbor Healtchare Syst, Dept Ambulatory Care, Ann Arbor, MI 48105 USA. S Texas Vet Healthcare Syst, Audie L Murphy Div, San Antonio, TX USA. RP O'Neill, JL (reprint author), Vet Affairs Ann Arbor Healtchare Syst, Dept Pharm, 2215 Fuller Rd 119,, Ann Arbor, MI 48105 USA. EM Jessica.Oneill@med.va.gov OI Copeland, Laurel/0000-0002-9478-0209 NR 16 TC 2 Z9 2 U1 0 U2 0 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD NOV PY 2005 VL 25 IS 11 BP 1560 EP 1565 DI 10.1592/phco.2005.25.11.1560 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 981AM UT WOS:000233059400006 PM 16232019 ER PT J AU Purtilo, RB AF Purtilo, RB TI Beyond disclosure: Seeking forgiveness SO PHYSICAL THERAPY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Inst Hlth Profess, Eth Initiat, Boston, MA 02114 USA. RP Purtilo, RB (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Eth Initiat, Boston, MA 02114 USA. EM rpurtilo@mghihp.edu NR 2 TC 3 Z9 4 U1 0 U2 1 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD NOV PY 2005 VL 85 IS 11 BP 1124 EP 1126 PG 3 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 981BR UT WOS:000233062600002 PM 16253042 ER PT J AU Flowers, RS Nassif, JM Rubin, PAD Hayakawa, T Lehr, SK AF Flowers, RS Nassif, JM Rubin, PAD Hayakawa, T Lehr, SK TI A key to canthopexy: The tarsal strap. A fresh cadaveric study SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LATERAL CANTHAL TENDON; LOWER EYELID LAXITY; CANTHOPLASTY; BLEPHAROPLASTY; ANATOMY; EVOLUTION AB Background: This article describes a poorly understood yet clinically significant eyelid structure the authors have labeled the tarsal strap. The tarsal strap anchors the tarsus to the periosteum of the inferolateral orbit. Releasing this tethering band is the cornerstone of achieving lasting, superior surgical results during lateral canthopexy and periorbital restoration in aesthetic and reconstructive surgery. Methods: An 87-year-old, male, fresh cadaveric head of Caucasian origin was studied. The dissection was repeated on 15 cadaver heads, including both male and female cadavers, from various ethnic backgrounds, to confirm the anatomy of the tarsal strap described in this article. Results: The tarsal strap was identified in all 16 cadaver dissections and appeared in a consistently similar location. Conclusions: Until now, the tarsal strap has been a poorly understood entity, despite being an anatomically and clinically significant eyelid structure. Knowledge of its significance is essential to restoring the lateral canthus and returning periorbital structures to their youthful state. It should be routinely sought out and properly released. C1 St Lukes Cataract & Laser Inst, Plast Surg Ctr Pacific, Tarpon Springs, FL 34689 USA. Massachusetts Eye & Ear Infirm, Boston, MA USA. Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. Cornell Coll, Mt Vernon, IA 52314 USA. RP Nassif, JM (reprint author), St Lukes Cataract & Laser Inst, Plast Surg Ctr Pacific, 43309 US Hwy 19 N, Tarpon Springs, FL 34689 USA. EM jmnassif@gmail.com NR 36 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 2005 VL 116 IS 6 BP 1752 EP 1758 DI 10.1097/01.prs.0000185998.53701.17 PG 7 WC Surgery SC Surgery GA 981WY UT WOS:000233119900026 PM 16267442 ER PT J AU Sabeti, PC Walsh, E Schaffner, SF Varilly, P Fry, B Hutcheson, HB Cullen, M Mikkelsen, TS Roy, J Patterson, N Cooper, R Reich, D Altshuler, D O'Brien, S Lander, ES AF Sabeti, PC Walsh, E Schaffner, SF Varilly, P Fry, B Hutcheson, HB Cullen, M Mikkelsen, TS Roy, J Patterson, N Cooper, R Reich, D Altshuler, D O'Brien, S Lander, ES TI The case for selection at CCR5-Delta 32 SO PLOS BIOLOGY LA English DT Article ID HUMAN GENOME; NATURAL-SELECTION; HAPLOTYPE RECONSTRUCTION; POSITIVE SELECTION; MAP; ALLELE; GENE; RESISTANCE; SIGNATURES; ORIGIN AB The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta 32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta 32 arose within the past 1,000 y and rose to its present high frequency (5% - 14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta 32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta 32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen at CCR5-Delta 32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome. C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Loyola Univ, Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Sabeti, PC (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pardis@broad.mit.edu RI Mikkelsen, Tarjei/A-1306-2007; Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Varilly, Patrick/C-8118-2013 OI Mikkelsen, Tarjei/0000-0002-8133-3135; Altshuler, David/0000-0002-7250-4107; Varilly, Patrick/0000-0003-4619-8174 NR 32 TC 118 Z9 123 U1 7 U2 37 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2005 VL 3 IS 11 BP 1963 EP 1969 AR e378 DI 10.1371/journal.pbio.0030378 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 988OA UT WOS:000233609300015 PM 16248677 ER PT J AU LaFramboise, T Weir, BA Zhao, XJ Beroukhim, R Li, C Harrington, D Sellers, WR Meyerson, M AF LaFramboise, T Weir, BA Zhao, XJ Beroukhim, R Li, C Harrington, D Sellers, WR Meyerson, M TI Allele-specific amplification in cancer revealed by SNP array analysis SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID NUCLEOTIDE POLYMORPHISM ARRAYS; COPY-NUMBER; OLIGONUCLEOTIDE ARRAYS; LUNG-CANCER; NONRANDOM DUPLICATION; HUMAN GENOME; EXPRESSION; MICROARRAYS; CARCINOMAS; HETEROZYGOSITY AB Amplification, deletion, and loss of heterozygosity of genomic DNA are hallmarks of cancer. In recent years a variety of studies have emerged measuring total chromosomal copy number at increasingly high resolution. Similarly, loss-of-heterozygosity events have been finely mapped using high-throughput genotyping technologies. We have developed a probe-level allele-specific quantitation procedure that extracts both copy number and allelotype information from single nucleotide polymorphisim (SNP) array data to arrive at allele-specific copy number across the genome. Our approach applies an expectation-maximization algorithm to a model derived from a novel classification of SNP array probes. This method is the first to our knowledge that is able to (a) determine the generalized genotype of aberrant samples at each SNP site (e.g., CCCCT at an amplified site), and (b) infer the copy number of each parental chromosome across the genome. With this method, we are able to determine not just where amplifications and deletions occur, but also the haplotype of the region being amplified or deleted. The merit of our model and general approach is demonstrated by very precise genotyping of normal samples, and our allele-specific copy number inferences are validated using PCR experiments. Applying our method to a collection of lung cancer samples, we are able to conclude that amplification is essentially monoallelic, as would be expected under the mechanisms currently believed responsible for gene amplification. This suggests that a specific parental chromosome may be targeted for amplification, whether because of germ line or somatic variation. An R software package containing the methods described in this paper is freely available at http://genome.dfci.harvard.edu/-tlaframb/PLASQ. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Meyerson, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM matthew_meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 FU NCI NIH HHS [R01 CA109038, R01CA109038, T32 CA009172]; NIAID NIH HHS [2R01 AI052817, R01 AI052817] NR 39 TC 79 Z9 86 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD NOV PY 2005 VL 1 IS 6 BP 507 EP 517 AR e65 DI 10.1371/journal.pcbi.0010065 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 003WS UT WOS:000234713300009 PM 16322765 ER PT J AU Greulich, H Chen, TH Feng, W Janne, PA Alvarez, JV Zappaterra, M Bulmer, SE Frank, DA Hahn, WC Sellers, WR Meyerson, M AF Greulich, H Chen, TH Feng, W Janne, PA Alvarez, JV Zappaterra, M Bulmer, SE Frank, DA Hahn, WC Sellers, WR Meyerson, M TI Oncogenic transformation by inhibitor-sensitive and -resistant EGFR mutants SO PLOS MEDICINE LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; CELL LUNG-CANCER; FACTOR-RECEPTOR GENE; TYROSINE PHOSPHORYLATION; KINASE DOMAIN; GEFITINIB TREATMENT; MUTATIONS; ERBB; RESPONSIVENESS; ACTIVATION AB Background Somatic mutations in the kinase domain of the epidermal growth factor receptor tyrosine kinase gene EGFR are common in lung adenocarcinoma. The presence of mutations correlates with tumor sensitivity to the EGFR inhibitors erlotinib and gefitinib, but the transforming potential of specific mutations and their relationship to drug sensitivity have not been described. Methods and Findings Here, we demonstrate that EGFR active site mutants are oncogenic. Mutant EGFR can transform both fibroblasts and lung epithelial cells in the absence of exogenous epidermal growth factor, as evidenced by anchorage-independent growth, focus formation, and tumor formation in immunocompromised mice. Transformation is associated with constitutive autophosphorylation of EGFR, Shc phosphorylation, and STAT pathway activation. Whereas transformation by most EGFR mutants confers on cells sensitivity to erlotinib and gefitinib, transformation by an exon 20 insertion makes cells resistant to these inhibitors but more sensitive to the irreversible inhibitor CL-387,785. Conclusion Oncogenic transformation of cells by different EGFR mutants causes differential sensitivity to gefitinib and erlotinib. Treatment of lung cancers harboring EGFR exon 20 insertions may therefore require the development of alternative kinase inhibition strategies. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Greulich, H (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM heidig@broad.mit.edu; William_Sellers@dfci.harvard.edu; Matthew_Meyerson@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 35 TC 387 Z9 400 U1 2 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD NOV PY 2005 VL 2 IS 11 BP 1167 EP 1176 AR e313 DI 10.1371/journal.pmed.0020313 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 998FC UT WOS:000234303000032 PM 16187797 ER PT J AU Cooppan, R AF Cooppan, R. TI Commentary: Metabolic syndrome and its evolving link to diabetes SO POSTGRADUATE MEDICINE LA English DT Article C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cooppan, R (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM chan.cooppan@joslin.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 0 PU VENDOME GROUP LLC PI NEW YORK PA 149 FIFTH AVE, 10TH FLOOR, NEW YORK, NY 10010 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD NOV PY 2005 VL 118 IS 5 BP 7 EP + PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA V44DQ UT WOS:000202983800001 PM 16329526 ER PT J AU Wang, XC Inoue, S Gu, JG Miyoshi, E Noda, K Li, WZ Mizuno-Horikawa, Y Nakano, M Asahi, M Takahashi, M Uozumi, N Ihara, S Lee, SH Ikeda, Y Yamaguchi, Y Aze, Y Tomiyama, Y Fujii, J Suzuki, K Kondo, A Shapiro, SD Lopez-Otin, C Kuwaki, T Okabe, M Honke, K Taniguchi, N AF Wang, XC Inoue, S Gu, JG Miyoshi, E Noda, K Li, WZ Mizuno-Horikawa, Y Nakano, M Asahi, M Takahashi, M Uozumi, N Ihara, S Lee, SH Ikeda, Y Yamaguchi, Y Aze, Y Tomiyama, Y Fujii, J Suzuki, K Kondo, A Shapiro, SD Lopez-Otin, C Kuwaki, T Okabe, M Honke, K Taniguchi, N TI Dysregulation of TGF-beta 1 receptor activation leads to abnormal lung development and emphysema-like phenotype in core fucose-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fucosylation; glycobiology; matrix metalloproteinase ID TGF-BETA; PULMONARY-EMPHYSEMA; N-ACETYLGLUCOSAMINE; TARGETED MUTATION; MARFAN-SYNDROME; CELL-LINES; EXPRESSION; GENE; FUCOSYLATION; TRANSFERASE AB The core fucosylation (alpha 1,6-fucosylation) of glycoproteins is widely distributed in mammalian tissues, and is altered under pathological conditions. To investigate physiological functions of the core fucose, we generated alpha 1,6-fucosyltransferase (Fut8)-null mice and found that disruption of Fut8 induces severe growth retardation and death during postnatal development. Histopathological analysis revealed that Fut8(-1-) mice showed emphysema-like changes in the lung, verified by a physiological compliance analysis. Biochemical studies indicated that lungs from Fut8-1- mice exhibit a marked overexpression of matrix metalloproteinases (MMPs), such as MMP-12 and MMP-13, highly associated with lung-destructive phenotypes, and a down-regulation of extracellular matrix (ECM) proteins such as elastin, as well as retarded alveolar epithelia cell differentiation. These changes should be consistent with a deficiency in TGF-beta 1 signaling, a pleiotropic factor that controls ECM homeostasis by down-regulating MMP expression and inducing ECM protein components. In fact, Fut8-1- mice have a marked dysregulation of TGF-beta 1 receptor activation and signaling, as assessed by TGF-beta 1 binding assays and Smad2 phosphorylation analysis. We also show that these TGF-beta 1 receptor defects found in Fut8-1- cells can be rescued by reintroducing Fut8 into Fut8(-/-)cells. Furthermore, exogenous TGF-beta 1 potentially rescued emphysema-like phenotype and concomitantly reduced MMP expression in Fut8-1- lung. We propose that the lack of core fucosylation of TGF-beta 1 receptors is crucial for a developmental and progressive/ destructive emphysema, suggesting that perturbation of this function could underlie certain cases of human emphysema. C1 Osaka Univ, Grad Sch Med, Dept Biochem, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Glycotherapeut, Suita, Osaka 5650871, Japan. Saga Univ, Sch Med, Dept Cell Biol, Saga 8098501, Japan. Hyogo Med Univ, Dept Biochem, Nishinomiya, Hyogo 6638501, Japan. Ono Pharmaceut Co, Fukui Safety Inst, Fukui 9138538, Japan. Yamagata Univ, Sch Med, Dept Biochem, Yamagata 9908585, Japan. Brigham & Womens Hosp, Dept Med, Pulm & Crit Care Med Sect, Boston, MA 02115 USA. Univ Oviedo, Inst Oncol, Dept Bioquim & Biol Mol, E-33006 Oviedo, Spain. Chiba Univ, Grad Sch Med, Dept Mol & Integrat Physiol, Chiba 2608670, Japan. Osaka Univ, Genome Informat Res Ctr, Dept Expt Genome Res, Suita, Osaka 5650871, Japan. Kochi Univ, Sch Med, Dept Mol Genet, Kochi 7838505, Japan. RP Taniguchi, N (reprint author), Osaka Univ, Grad Sch Med, Dept Biochem, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. EM proftani@biochem.med.osaka-u.ac.jp RI Lee, Seung Ho/B-2961-2008; Okabe, Masaru/B-6917-2015; Lopez-Otin, Carlos/C-6657-2013 OI Okabe, Masaru/0000-0002-0803-9044; Lopez-Otin, Carlos/0000-0001-6964-1904 NR 38 TC 202 Z9 209 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2005 VL 102 IS 44 BP 15791 EP 15796 DI 10.1073/pnas.0507375102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 981LU UT WOS:000233090900016 PM 16236725 ER PT J AU Lee, LF Xu, BH Michie, SA Beilhack, GF Warganich, T Turley, S McDevitt, HO AF Lee, LF Xu, BH Michie, SA Beilhack, GF Warganich, T Turley, S McDevitt, HO TI The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse: Analysis of dendritic cell maturation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immune tolerance; autoreactive T cells; pancreatic lymph nodes ID NECROSIS-FACTOR-ALPHA; T-CELL; AUTOIMMUNE-DISEASE; LYMPH-NODES; IN-VIVO; MICE; MELLITUS; IDENTIFICATION; DEATH AB TNF-alpha has been linked to the development of type 1 diabetes (T1D). We previously reported that neonatal treatment of nonobese diabetic (NOD) mice with TNF-alpha accelerated the onset of T1D, whereas TNF-alpha blockade in the same time period resulted in a complete absence of diabetes. The mechanisms by which TNF-alpha modulates development of T1D in NOD mice remain unclear. Here we tested the effects of TNF-alpha on the maturation of dendritic cells (DCs) in the NOD mouse. We found that neonatal treatment with TNF-alpha caused an increase in expression of maturation markers on CD11c(+)CD11b(+) DC subpopulations, whereas treatment with anti-TNF-alpha resulted in a decrease in expression of maturation markers in the CD11c(+)CD11b(+) subset. Moreover, neonatal treatment with TNF-alpha resulted in skewed development of a CD8 alpha(+)CD11b(-)CD11c(+) DC subset such that TNF-alpha decreases the CD8 alpha(+)CD11c(+) DC subset, increases the CD11c(+)CD11b(+) subset, and causes an increase in the expression of CD40 and CD54 on mature DCs capable of inducing immunity. Anti-TNF-alpha-treated mice had an increase in the CD8 alpha(+)CD11c(+) DCs. Notably, adoptively transferred naive CD4(+) T cells from BDC2.5 T cell receptor transgenic mice proliferated in the pancreatic lymph nodes in TNF-alpha-treated NOD mice but not in anti-TNF-alpha-treated mice. Finally, we show that anti-TNF-alpha-treated mice showed immunological tolerance to islet cell proteins. We conclude that TNF-alpha plays an important role in the initiation of T1D in the NOD mouse by regulating the maturation of DCs and, thus, the activation of islet-specific pancreatic lymph node T cells. C1 Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Bone Marrow Transplant, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP McDevitt, HO (reprint author), Stanford Univ, Sch Med, Dept Microbiol & Immunol, Fairchild D345, Stanford, CA 94305 USA. EM hughmcd@stanford.edu FU NIDDK NIH HHS [R01 DK051705, K01DK064656, K01 DK064656, R01DK51705] NR 21 TC 52 Z9 56 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 1 PY 2005 VL 102 IS 44 BP 15995 EP 16000 DI 10.1073/pnas.0508122102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 981LU UT WOS:000233090900051 PM 16247001 ER PT J AU Ruzek, JI Friedman, MJ Murray, S AF Ruzek, JI Friedman, MJ Murray, S TI Toward a knowledge management system for posttraumatic stress disorder treatment in. veterans healthcare SO PSYCHIATRIC ANNALS LA English DT Article ID EXPOSURE THERAPY; PRACTICE GUIDELINES; CLINICAL-PRACTICE; PTSD; IMPROVEMENT; DISSEMINATION; STRATEGIES; PATTERNS; PROGRAMS; CENTERS C1 US Dept Vet Affairs, Natl Ctr PTSD, VA Palo Alto Hlth Care Syst, Educ Div, Menlo Pk, CA 94025 USA. Vet Adm Med Ctr, Natl Ctr Post Traumat Stress Disorder, White River Jct, VT USA. Dartmouth Coll Sch Med, Hanover, NH USA. Upstate New York Vet Adm Healthcare Syst, Network 2, Behav Hlth Care Line, Albany, NY USA. RP Ruzek, JI (reprint author), US Dept Vet Affairs, Natl Ctr PTSD, VA Palo Alto Hlth Care Syst, Educ Div, 795 Willow Rd, Menlo Pk, CA 94025 USA. EM josef.ruzek@med.va.gov NR 46 TC 4 Z9 4 U1 1 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2005 VL 35 IS 11 BP 911 EP 920 PG 10 WC Psychiatry SC Psychiatry GA 984MI UT WOS:000233308600011 ER PT J AU Hashimoto, K Iyo, M Freedman, R Stevens, KE AF Hashimoto, K Iyo, M Freedman, R Stevens, KE TI Tropisetr in DBA/2 on improves deficient inhibitory auditory processing mice: role of alpha 7 nicotinic acetylcholine receptors SO PSYCHOPHARMACOLOGY LA English DT Article DE nicotinic receptors; schizophrenia; antipsychotic; sensory gating ID HIPPOCAMPAL INTERNEURONS; SENSORY INHIBITION; EVOKED-POTENTIALS; SCHIZOPHRENIA; RAT; MOUSE; MODULATION; P50; CLOZAPINE; AGONISTS AB Rationale: Deficient inhibitory processing of the P50 auditory evoked potential is a pathophysiological feature of schizophrenia. Several lines of evidence suggest that alpha 7 nicotinic receptors play a critical role in this phenomenon. Similar to schizophrenic patients, DBA/2 mice spontaneously exhibit a deficit in inhibitory processing of the P20-N40 auditory evoked potential, which is thought to be a rodent analog of the human P50 auditory evoked potential. Objective: The present study was undertaken to examine whether tropisetron, a partial agonist at alpha 7 nicotinic receptors and an antagonist at 5-hydroxytryptamine-3 receptors, improves this deficit in DBA/2 mice. Results: Administration of tropisetron (1 mg/kg i.p.) significantly improved the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. Coadministration of methyllycaconitine (MLA; 3 mg/kg i.p.), a partially selective antagonist at alpha 7 nicotinic receptors, significantly blocked the normalizing effect of tropisetron. Furthermore, MLA alone did not alter the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice. Conclusions: The data suggest that tropisetron improves the deficient inhibitory processing of the P20-N40 auditory evoked potential in DBA/2 mice by effects on alpha 7 and perhaps alpha 4 beta 2 nicotinic receptors. Tropisetron may be useful for the treatment of deficient inhibitory processing in schizophrenia. C1 Chiba Univ, Div Clin Neurosci, Ctr Forens Mental Hlth, Chiba 2608670, Japan. Chiba Univ, Grad Sch Med, Dept Psychiat, Chiba 2608670, Japan. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. RP Hashimoto, K (reprint author), Chiba Univ, Div Clin Neurosci, Ctr Forens Mental Hlth, 1-8-1 Inohana, Chiba 2608670, Japan. EM hashimoto@faculty.chiba-u.jp NR 52 TC 47 Z9 48 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 183 IS 1 BP 13 EP 19 DI 10.1007/s00213-005-0142-0 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 988BK UT WOS:000233566200002 PM 16136299 ER PT J AU Streeter, CC Hennen, J Ke, Y Jensen, JE Sarid-Segal, F Nassar, LE Knapp, C Meyer, AA Kwak, T Renshaw, PF Ciraulo, DA AF Streeter, CC Hennen, J Ke, Y Jensen, JE Sarid-Segal, F Nassar, LE Knapp, C Meyer, AA Kwak, T Renshaw, PF Ciraulo, DA TI Prefrontal GABA levels in cocaine-dependent subjects increase with pramipexole and venlafaxine treatment SO PSYCHOPHARMACOLOGY LA English DT Article DE MRS; GABA; cocaine; prefrontal; treatment; spectroscopy; pramipexole; venlafaxine; addiction severity index; antidepressant ID GAMMA-AMINOBUTYRIC-ACID; MAGNETIC-RESONANCE-SPECTROSCOPY; VENTRAL TEGMENTAL AREA; ENDOGENOUS OPIOID SYSTEMS; HUMAN BRAIN; DEPRESSED-PATIENTS; IN-VIVO; INDUCED REINSTATEMENT; CONTAINING NEURONS; NUCLEUS-ACCUMBENS AB Rationale: There is evidence that prefrontal lobe GABA levels are low in cocaine-dependent (CD) individuals, and treatment with GABA agonists decreases cocaine self-administration. Objectives: The aim of the study is to measure changes in GABA levels in CD subjects at baseline and after 8 weeks of treatment with pramipexole, venlafaxine, or placebo. Methods: CD subjects enrolled in a treatment trial for cocaine dependence were recruited for this proton (H-1) magnetic resonance spectroscopy (MRS) study. GABA levels in the prefrontal lobe were measured before and after treatment. Results: Mean percentage changes in GABA levels were as follows: pramipexole +17.0 +/- 28.0%, venlafaxine +13.0 +/- 11.0%, and placebo -2.1 +/- 19.5%. Pramipexole-treated subjects had significantly increased brain GABA levels compared to placebo (p=0.031). Venlafaxine treatment was nonsignificantly associated with increased GABA levels compared to placebo (p=0.16). The overall statistical model for the effect of drug treatment vs placebo on brain GABA levels, including adjustment for baseline levels, was highly significant (p=0.002). Despite significant changes in GABA levels, there were no significant differences in the number of urine samples positive for cocaine metabolites. Conclusions: This study demonstrates that H-1 MRS can measure changes in GABA levels following pharmacologic treatment. The increase in GABA levels, although significant, is modest compared to other MRS studies of depression or epilepsy, associated with clinical improvements. The failure to see larger increases in GABA levels and an associated reduction in cocaine consumption may reflect the relatively low doses of medication used. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. Boston VA Healthcare Syst, Boston, MA USA. McLean Hosp, Belmont, MA 02178 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Streeter, CC (reprint author), Boston Univ, Sch Med, Div Psychiat, 85 E Newton St,M912E, Boston, MA 02118 USA. EM streeter@bu.edu OI Knapp, Clifford/0000-0003-4482-7678; Ciraulo, Domenic/0000-0001-7706-8765 FU NIAAA NIH HHS [K23AA13149]; NIDA NIH HHS [DA50038, DA09448, DA15116] NR 67 TC 22 Z9 23 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 182 IS 4 BP 516 EP 526 DI 10.1007/s00213-005-0121-5 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986NW UT WOS:000233458000008 PM 16075286 ER PT J AU Sahani, DV Kadavigere, R Saokar, A Fernandez-del Castillo, C Brugge, WR Hahn, PF AF Sahani, DV Kadavigere, R Saokar, A Fernandez-del Castillo, C Brugge, WR Hahn, PF TI Cystic pancreatic lesions: A simple imaging-based classification system for guiding management SO RADIOGRAPHICS LA English DT Article ID PAPILLARY-MUCINOUS TUMORS; SEROUS CYSTADENOMA; HELICAL CT; NEOPLASMS; DIAGNOSIS; EUS; CYSTADENOCARCINOMA; FEATURES AB Cystic lesions of the pancreas are increasingly being recognized due to the widespread use of cross-sectional imaging. The initial evaluation of a pancreatic cyst should be directed toward exclusion of a pseudocyst. Patients with pseudocysts generally have a history of acute or chronic pancreatitis, whereas those with cystic tumors most often lack such a history. Several types of cystic lesions are encountered in the pancreas. Because of morphologic overlap at imaging, accurate characterization of these lesions can be difficult. Computed tomography and magnetic resonance imaging are excellent modalities for both initial detection and characterization of cystic pancreatic lesions. An imaging classification system for these lesions has been proposed that is based on the morphologic features of the lesion. This system can be helpful in characterizing lesions, narrowing the differential diagnosis, and making decisions regarding the treatment of affected patients. Endoscopic ultrasonography - guided aspiration and biopsy is useful in cases that are indeterminate at cross-sectional imaging or that require observation. C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, Boston, MA 02114 USA. RP Sahani, DV (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal Imaging, 55 Fruit St,White 270, Boston, MA 02114 USA. EM dsahani@partners.org NR 46 TC 157 Z9 169 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2005 VL 25 IS 6 BP 1471 EP 1484 DI 10.1148/rg.256045161 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 034SV UT WOS:000236951800004 PM 16284129 ER PT J AU Singh, AK Gervais, DA Hahn, PF Sagar, P Mueller, PR Novelline, RA AF Singh, AK Gervais, DA Hahn, PF Sagar, P Mueller, PR Novelline, RA TI Acute epiploic appendagitis and its mimics SO RADIOGRAPHICS LA English DT Article ID CT FINDINGS; OMENTAL INFARCTION; SCLEROSING MESENTERITIS; DIAGNOSIS; US; MANIFESTATIONS; PANNICULITIS; APPEARANCE; EMERGENCY; TORSION AB Acute epiploic appendagitis most commonly manifests with acute lower quadrant pain. Its clinical features are similar to those of acute diverticulitis or, less commonly, acute appendicitis. The conditions that may mimic acute epiploic appendagitis at computed tomography ( CT) include acute omental infarction, mesenteric panniculitis, fat-containing tumor, and primary and secondary acute inflammatory processes in the large bowel ( eg, diverticulitis and appendicitis). Whereas the location of acute epiploic appendagitis is most commonly adjacent to the sigmoid colon, acute omental infarction is typically located in the right lower quadrant and often is mistaken for acute appendicitis. It is important to correctly diagnose acute epiploic appendagitis and acute omental infarction on CT images because these conditions may be mistaken for acute abdomen, and the mistake may lead to unnecessary surgery. The CT features of acute epiploic appendagitis include an oval lesion 1.5 - 3.5 cm in diameter, with attenuation similar to that of fat and with surrounding inflammatory changes, that abuts the anterior sigmoid colon wall. The CT features of acute omental infarction include a well-circumscribed triangular or oval heterogeneous fatty mass with a whorled pattern of concentric linear fat stranding between the anterior abdominal wall and the transverse or ascending colon. As CT increasingly is used for the evaluation of acute abdomen, radiologists are likely to see acute epiploic appendagitis and its mimics more often. Recognition of these conditions on CT images will allow appropriate management of acute abdominal pain and may help to prevent unnecessary surgery. C1 Univ Massachusetts, Med Ctr, Dept Radiol, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Univ Massachusetts, Med Ctr, Dept Radiol, Worcester, MA 01605 USA. EM pallaviajay@hotmail.com NR 30 TC 79 Z9 90 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2005 VL 25 IS 6 BP 1521 EP 1534 DI 10.1148/rg.256055030 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 034SV UT WOS:000236951800007 PM 16284132 ER PT J AU Singh, AK Saokar, A Hahn, PF Harisinghani, MG AF Singh, AK Saokar, A Hahn, PF Harisinghani, MG TI Imaging of penile neoplasms SO RADIOGRAPHICS LA English DT Article ID SQUAMOUS-CELL CARCINOMA; LYMPH-NODES; ILIOINGUINAL LYMPHADENECTOMY; METASTASIS SECONDARY; GROIN DISSECTION; TUMOR STAGE; CANCER; SURVIVAL; EXTENT; SURVEILLANCE AB The assessment of penile cancer on the basis of clinical findings alone can often result in inaccurate staging and suboptimal treatment. Imaging of primary penile cancer and metastatic lymphadenopathy can help optimize planning of both primary tumor resection and treatment for lymph node metastases. Magnetic resonance ( MR) imaging is the most accurate imaging modality in the assessment of primary penile cancers, which usually manifest as solitary, ill-defined infiltrating tumors that are hypointense on both T1- and T2-weighted MR images. T2-weighted MR imaging allows delineation of the tumor margin and of any extension into the penile shaft. On gadolinium-enhanced T1-weighted images, the tumors enhance to a greater extent than do the corpora cavernosa. In addition, the recently introduced technique known as lymphotrophic nanoparticle - enhanced MR imaging can help identify metastatic lymph node disease. However, further studies will be needed to determine the role of this imaging technique in clinical practice. Computed tomography does not clearly depict the local extension of primary penile cancer; however, it is useful in assessing metastases and postoperative complications. C1 Massachusetts Gen Hosp, Div Emergency Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Singh, AK (reprint author), Massachusetts Gen Hosp, Div Emergency Radiol, White 270,55 Fruit St, Boston, MA 02114 USA. EM Pallaviajay@hotmail.com NR 43 TC 12 Z9 12 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 2005 VL 25 IS 6 BP 1629 EP 1638 DI 10.1148/rg.256055069 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 034SV UT WOS:000236951800014 PM 16284139 ER PT J AU Krishnasetty, V Fischman, AJ Halpern, EL Aquino, SL AF Krishnasetty, V Fischman, AJ Halpern, EL Aquino, SL TI Comparison of alignment of computer-registered data sets: Combined PET/CT versus independent PET and CT of the thorax SO RADIOLOGY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; IMAGE REGISTRATION; LUNG-CANCER; ONCOLOGY; BRAIN AB PURPOSE: To retrospectively determine whether alignment of registered positron emission tomographic (PET) and computed tomographic (CT) data sets obtained independently varies significantly from alignment of data sets acquired from a combined PET/CT scanner. MATERIALS AND METHODS: The study was approved by the institution's Human Research Committee with a waiver of informed consent and complied with HIPAA. Whole-body combined PET/CT data sets and separate routinely positioned thoracic CT data sets were obtained from 12 patients (six men, six women; mean age, 48.6 years; range, 24-62 years). Separate PET and thoracic CT data sets matched for patient positioning and respiration were, acquired on the same day for nine patients (four men, five women; mean age, 171 years; range, 51-90 years). Computer nonlinear registration was performed on PET and CT data sets from combined PET/CT (fusion group 1), PET data sets from combined PET/CT with unmatched thoracic CT (fusion group 2), and data sets from separate PET and CT matched for patient positioning and respiration (fusion group 3). Quality of alignment was assessed by two radiologists in consensus blinded to the source of registered data in each fusion group at the following anatomic locations: diaphragm, aortic arch, heart, thoracic spine, and lung apices. Results were compared by using the Wilcoxon paired signed rank and unpaired rank sum tests. RESULTS: Quality of alignment did not significantly differ between fusion group I and fusion group 3. Fusion group I provided significantly better alignment in two of five anatomic locations (P =.008 for diaphragm and P =.031 for heart) than fusion group 2. Fusion group 3 provided significantly better alignment in two of five anatomic locations (P = .037 for diaphragm and P = .009 for heart) than fusion group 2. CONCLUSION: Thoracic anatomic alignment does not significantly differ between registered PET and CT data sets acquired on a combined PET/CT scanner or from separate PET and CT scanners obtained on the same day when carefully matched for anatomic positioning and respiration. (c) RSNA, 2005. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 202, Boston, MA 02114 USA. EM saquino@partners.org NR 19 TC 21 Z9 21 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 NOV PY 2005 VL 237 IS 2 BP 635 EP 639 DI 10.1148/radiol.2372041719 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 976OP UT WOS:000232743300036 PM 16244272 ER PT J AU Oei, T vanSonnenberg, E Shankar, S Morrison, PR Tuncali, K Silverman, SG AF Oei, T vanSonnenberg, E Shankar, S Morrison, PR Tuncali, K Silverman, SG TI Radiofrequency ablation of liver tumors: A new cause of benign portal venous gas SO RADIOLOGY LA English DT Article ID BLUNT ABDOMINAL-TRAUMA; CLINICAL-SIGNIFICANCE; VEIN GAS; HEPATIC METASTASES; PNEUMATOSIS; CT; INTESTINALIS; ADULTS AB PURPOSE: To retrospectively describe and categorize the presence of portal venous gas (PVG) from radiofrequency (RF) ablation of hepatic tumors. MATERIALS AND METHODS: The study was HIPAA compliant, and informed consent was waived. Thirty-four consecutive computed tomography (CT)-guided percutaneous RF ablations of liver tumors in 26 patients (13 men, 13 women; mean age, 69 years) with five hepatocellular carcinomas and 21 metastatic liver tumors (13 colon, five other, and three unknown primary tumors) were performed with an institutional review board-approved protocol. Two treatment modalities were used: RF ablation alone (13 procedures) and combined RF ablation and ethanol injection (21 procedures). Presence of PVG was quantified with three parameters: maximum length Of a portal venous branch with gas, number of Couinaud segments in which PVG was seen, and total number of portal venous branch points with gas. Then an overall PVG score from 0 to 5 was determined. Also, when tumoral gas was seen on CT scans, the largest cross-sectional area of gas was measured. The two ablation methods were compared for quantities of PVG and tumoral gas. The role of N2O anesthetic in PVG and tumoral gas formation during ablation also was studied. Statistical analyses were performed with Wilcoxon rank sum and Student t tests. RESULTS: In 25 procedures (74%), gas was found in portal vein branches; in 30 procedures (88%), gas was also found in tumoral and peritumoral tissues. There was no significant difference in frequency of PVG between the ablation methods. Combined therapy yielded significantly greater lengths of PVG (P <.002) and more portal venous branch points (P <.001) than did RF ablation alone. Mean PVG score was 2.4 +/- 0.4 (standard error of the mean) for combined therapy and 0.9 +/- 0.2 for RF ablation alone (P <.004). N2O anesthetic was associated with greater amounts of tumoral gas (P <.008) and PVG (P <.03). Tumoral gas, peritumoral gas, and PVG dissipated within 20 minutes after ablation in all patients. No morbidity or mortality was associated with PVG. CONCLUSION: RF ablation is a common yet benign cause of transient PVG, tumoral gas, and peritumoral gas. Combined RF and ethanol ablation was associated with more PVG than was RF ablation alone. (c) RSNA, 2005. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. RP vanSonnenberg, E (reprint author), St Josephs Hosp, Dept Radiol, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM Eric.vanSonnenberg@CHW.edu NR 29 TC 9 Z9 9 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2005 VL 237 IS 2 BP 709 EP 717 DI 10.1148/radiol.2372041295 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 976OP UT WOS:000232743300047 PM 16244279 ER PT J AU O'Connor, KJ Delmonico, FL AF O'Connor, KJ Delmonico, FL TI Increasing the supply of kidneys for transplantation SO SEMINARS IN DIALYSIS LA English DT Article ID UNITED-STATES; DONORS; DONATION AB Kidney transplantation confers a survival advantage for patients with end-stage renal disease (ESRD) when compared to dialysis and improves the quality of life in a cost-effective manner. Currently there are more than 60,000 patients on the U.S. waiting list for kidney transplantation. In 2004, 16,879 kidney transplants, including 880 simultaneous kidney and pancreas transplants, were performed in this country. Recent strategies for increasing the supply of kidneys hold promise, such as systematic programs designed to improve consent rates for deceased donor organ procurement. Efforts to increase donation after cardiac death (DCD) have been highly successful and now account for more than 5% of all deceased organ donors. Transplantation of kidneys from DCD donors yields 1-year graft and patient survival rates equivalent to kidneys from brain-dead donors. Expanded criteria donor (ECD) kidneys from donors >= 60 years of age (or donors age 50-59 years with certain comorbidities) confer a survival benefit for end-stage renal disease (ESRD) patients compared to remaining on dialysis on the waiting list. The number of live donor kidney transplants, both from biologically related and unrelated donors, is increasing. Paired live donor kidney transplants provide yet another transplantation opportunity for ESRD patients with willing but incompatible (by ABO or direct antibody) living donors. C1 New England Organ Bank Inc, Newton, MA 02492 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP O'Connor, KJ (reprint author), New England Organ Bank Inc, 1 Gateway Ctr, Newton, MA 02492 USA. EM kocon@neob.org NR 13 TC 17 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0894-0959 J9 SEMIN DIALYSIS JI Semin. Dial. PD NOV-DEC PY 2005 VL 18 IS 6 BP 460 EP 462 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 987KC UT WOS:000233515800004 PM 16398706 ER PT J AU Jovin, TG Gupta, R Uchino, K Jungreis, CA Wechsler, LR Hammer, MD Tayal, A Horowitz, MB AF Jovin, TG Gupta, R Uchino, K Jungreis, CA Wechsler, LR Hammer, MD Tayal, A Horowitz, MB TI Emergent stenting of extracranial internal carotid artery occlusion in acute stroke has a high revascularization rate SO STROKE LA English DT Article DE angioplasty; endovascular therapy; stents; carotid arteries ID INTRAARTERIAL THROMBOLYSIS; HYPERPERFUSION SYNDROME; COMPUTED-TOMOGRAPHY; ISCHEMIC-STROKE; RECANALIZATION; ENDARTERECTOMY; PENUMBRA AB Background and Purpose - Acute ischemic stroke attributable to extracranial internal carotid artery ( ICA) occlusion is frequently associated with severe disability or death. In selected cases, revascularization with carotid artery stenting has been reported, but the safety, recanalization rate, and clinical outcomes in consecutive case series are not known. Methods - We retrospectively reviewed all of the cases of ICA occlusions that underwent cerebral angiography with the intent to revascularize over a 38-month period. Two groups were identified: (1) patients who presented with an acute clinical presentation within 6 hours of symptom onset (n = 15); and (2) patients who presented subacutely with neurologic fluctuations because of the ICA occlusion (n = 10). Results - Twenty-five patients with a mean age of 62 +/- 11 years and median National Institutes of Health Stroke Scale ( NIHSS) of 14 were identified. Twenty-three of the 25 patients (92%) were successfully revascularized with carotid artery stenting. Patients in group 1 were younger and more likely to have a tandem occlusion and higher baseline NIHSS when compared with group 2. Patients in group 2 were more likely to show early clinical improvement defined as a reduction of their NIHSS by >= 4 points and a modified Rankin Score of <= 2 at 30-day follow-up. Two clinically insignificant adverse events were noted: 1 asymptomatic hemorrhage and 1 nonflow-limiting dissection. Conclusions - Endovascular treatment of acute ICA occlusion appears to have a high-recanalization rate and be relatively safe in our cohort of patients with acute ICA occlusion. Future prospective studies are necessary to determine which patients are most likely to benefit from this form of therapy. C1 Univ Pittsburgh, Med Ctr, Stroke Inst, Pittsburgh, PA 15213 USA. Dept Neurol, Pittsburgh, PA USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. Dept Radiol, Pittsburgh, PA USA. Dept Neurosurg, Pittsburgh, PA USA. RP Uchino, K (reprint author), Univ Pittsburgh, Med Ctr, Stroke Inst, PUH C-400,200 Lothrop St, Pittsburgh, PA 15213 USA. EM uchinok@upmc.edu OI Uchino, Ken/0000-0001-9468-4172 NR 18 TC 113 Z9 116 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2005 VL 36 IS 11 BP 2426 EP 2430 DI 10.1161/01.STR.0000185924.22918.51 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977VS UT WOS:000232832200032 PM 16224082 ER PT J AU Smith, EE Abdullah, AR Petkovska, I Rosenthal, E Koroshetz, WJ Schwamm, LH AF Smith, EE Abdullah, AR Petkovska, I Rosenthal, E Koroshetz, WJ Schwamm, LH TI Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke SO STROKE LA English DT Article DE angiography; computed tomography; outcome; stroke, acute; tissue plasminogen activator ID CEREBRAL-ISCHEMIA; DETERIORATION; ELIGIBILITY; THERAPY; TRIAL AB Background and Purpose: Some patients with mild or improving ischemic stroke symptoms do not receive intravenous tissue plasminogen activator (tPA) because they look "too good to treat" (TGT); however, some have poor outcomes. Methods: We retrospectively analyzed data from a prospective single-center study between 2002 and 2004. TGT patients were those arriving within 3 hours of symptom onset and not treated with intravenous tPA solely because of mild or improving symptoms. Results: Of 128 patients presenting within 3 hours, 41 (34%) were not given tPA because of mild or improving stroke. Of the TGT patients, 11 of 41 (27%) died or were not discharged home because of neurological worsening (n = 6) or persistent "mild" neurological deficit (n = 5). No single variable at presentation was associated with death or lack of home discharge. There were 10 of 41 TGT patients (24%) who had >= 4-point improvement in National Institutes of Health Stroke Scale score before tPA decision; these patients were more likely to have subsequent neurological worsening (relative risk, 4.1, 95% CI, 1.1 to 15.4; P = 0.05). Conclusion: A substantial minority of patients deemed too good for intravenous tPA were unable to be discharged home. A re-evaluation of the stroke severity criteria for tPA eligibility may be indicated. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Calif Los Angeles, Dept Radiol Sci, Los Angeles, CA 90024 USA. Beth Israel Deaconess Med Ctr, Dept Internal Med, Boston, MA 02215 USA. RP Smith, EE (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 802,55 Fruit St, Boston, MA 02114 USA. EM eesmith@partners.org OI Schwamm, Lee/0000-0003-0592-9145; Smith, Eric/0000-0003-3956-1668; Rosenthal, Eric/0000-0003-3900-356X FU NINDS NIH HHS [K23 NS046327]; ODCDC CDC HHS [U50/CCU120238-01-1] NR 9 TC 140 Z9 140 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2005 VL 36 IS 11 BP 2497 EP 2499 DI 10.1161/01.STR.0000185798.78817.f3 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 977VS UT WOS:000232832200048 PM 16210552 ER PT J AU Warshaw, AL Flum, DR Sarr, MG Pellegrini, CA AF Warshaw, AL Flum, DR Sarr, MG Pellegrini, CA TI Special section: Connecting quality to compensation - Introduction: The rise of translational outcomes research SO SURGERY LA English DT Editorial Material C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. Mayo Clin & Mayo Grad Sch Med, Dept Surg, Rochester, MN USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, 55 Fruit St,WHT506, Boston, MA 02114 USA. EM awarshaw@partners.org NR 0 TC 3 Z9 3 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 NOV PY 2005 VL 138 IS 5 BP 813 EP 814 DI 10.1016/j.surg.2005.09.003 PG 2 WC Surgery SC Surgery GA 989DL UT WOS:000233653000001 ER PT J AU Khuri, SF AF Khuri, SF TI The NSQIP: A new frontier in surgery SO SURGERY LA English DT Article ID QUALITY IMPROVEMENT PROGRAM; AFFAIRS SURGICAL RISK; POSTOPERATIVE COMPLICATIONS; CARE; ADJUSTMENT; COSTS C1 Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. EM shukri.khuri@med.va.gov NR 11 TC 289 Z9 292 U1 2 U2 4 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 NOV PY 2005 VL 138 IS 5 BP 837 EP 843 DI 10.1016/j.surg.2005.08.016 PG 7 WC Surgery SC Surgery GA 989DL UT WOS:000233653000006 PM 16291383 ER PT J AU Sewell, WF Mroz, EA Evans, JE AF Sewell, WF Mroz, EA Evans, JE TI Extracts of retina and brain that excite afferent fibers innervating hair cells contain a compound related to hydroxyphenylglycine-N-carbamoyl SO SYNAPSE LA English DT Article DE hearing; cochlea; neurotransmitter; endogenous; hydroxyphenylglycine-N-carbamoyl; glutamate ID GLUTAMATE RECEPTORS; VESTIBULAR SYSTEM; LATERAL-LINE; SYNAPSE; ACID; PURIFICATION; INHIBITION; ORGAN AB To identify new neurotransmitter and modulator candidates that might be important in transmission from sensory hair cells to afferent nerves, we examined extracts of neural tissue for compounds that excite afferent fibers innervating hair cells. Here, we describe the extraction and purification from retina and brain of a potent, unstable, excitatory compound with pharmacological activity similar to glutamate on afferent fibers innervating hair cells. This compound, however, was clearly distinguished from glutamate, other common amino acids, and known endogenous glutamate-receptor agonists. After derivatization and analysis by gas chromatography-mass spectrometry, the major compound found in highly purified neuroactive chromatographic fractions had the same gas chromatographic elution time and mass spectrum as the compound formed by derivatization Of L-p-hydroxyphenylglycine-N-carbamoyl. Hydroxyphenylglycine-N-carbamoyl, however, did not copurify with the neuroactive compound and was not neuroactive. We thus hypothesize that the detected compound was produced from a precursor, structurally related to L-p-hydroxyphenylglycine-N-carbamoyl, that was a major component of the neuroactive chromatographic fractions. Because several compounds related to hydroxyphenylglycine are known to act on glutamate receptors, such a compound is an interesting candidate to be an endogenous glutamate-receptor ligand in the mammalian nervous system. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Proteom & Mass Spect Facil, Worcester, MA 01605 USA. RP Sewell, WF (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. EM wfs@epi.meei.harvard.edu FU NIDCD NIH HHS [R01 DC000767, R01 DC000767-12, R01 DC000767-11, R01 DC000767-13, R01 DC000767-10, R01 DC000767-14, R01 DC000767-09] NR 31 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD NOV PY 2005 VL 58 IS 2 BP 129 EP 140 DI 10.1002/syn.20192 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 963EL UT WOS:000231786100007 PM 16088953 ER PT J AU Gao, X Bashirova, A Iversen, AN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M AF Gao, X Bashirova, A Iversen, AN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M TI AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 SAIC FREdrick Inc, Basic Res Program, Frederick, MD 60611 USA. Consolidated Safety Serv Inc, Fairfax, VA 60611 USA. Univ Oxford, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, 20892, England. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL USA. Northwestern Univ, Fineberg Sch Med, Chicago, IL USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 223 BP 424 EP 424 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700225 ER PT J AU Agrawal, YP Freedman, M Szczepiorkowski, ZM AF Agrawal, YP Freedman, M Szczepiorkowski, ZM TI Long-term transfusion of polymerized bovine hemoglobin in a Jehovah's Witness following chemotherapy for myeloid leukemia: a case report SO TRANSFUSION LA English DT Article ID CROSS-LINKED HEMOGLOBINS; SUBSTITUTES; ANEMIA AB A 52-year-old female Jehovah's Witness presented with relapsed secondary acute myeloid leukemia. Because of chemotherapy-induced anemia, she was infused with the bovine hemoglobin (Hb)-based oxygen carrier HBOC-201 (Biopure) as the sole means of transfusion support. HBOC-201 has only been used for management of acute hemorrhage, and its utility in providing longer term transfusion support is unknown. Over a period of 18 days, a total dose of 1230 g of HBOC-201 was delivered. Although the patient succumbed to the disease after 18 days of treatment, this case documents our experience with the highest dose and duration of HBOC-201 ever used. Although possible renal toxicity could not be definitively excluded, the homogeneous extraction of oxygen by the brain in the presence of and perhaps from HBOC-201 was demonstrated. C1 Dartmouth Hitchcock Med Ctr, Dept Pathol, Blood Bank & Transfus Serv, Lebanon, NH 03756 USA. Univ Iowa Hosp & Clin, Iowa City, IA 52242 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Szczepiorkowski, ZM (reprint author), Dartmouth Hitchcock Med Ctr, Dept Pathol, Blood Bank & Transfus Serv, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM szczepiorkowski@hitchcock.org RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 NR 8 TC 11 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2005 VL 45 IS 11 BP 1735 EP 1738 DI 10.1111/j.1537-2995.2005.00599.x PG 4 WC Hematology SC Hematology GA 977AL UT WOS:000232774700009 PM 16271098 ER PT J AU Stowell, CP AF Stowell, CP TI What happened to blood substitutes? SO TRANSFUSION CLINIQUE ET BIOLOGIQUE LA English DT Article DE blood substitutes; transfusion; hemoglobin based oxygen carriers; oxygen delivery ID CROSS-LINKED HEMOGLOBIN; HUMAN POLYMERIZED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; TRAUMATIC HEMORRHAGIC-SHOCK; TARGETED O-2 DELIVERY; OXYGEN-TRANSPORT; NITRIC-OXIDE; POLYETHYLENE-GLYCOL; BOVINE HEMOGLOBIN; PLASMA VISCOSITY AB Concerns about the safety and adequacy of the blood supply have fostered twenty years of research into the so-called "blood substitutes" among them the oxygen carriers based on modified hemoglobin. Although none of these materials has yet been licensed for use in North America or Europe, the results of research and clinical trials have increased our understanding of oxygen delivery and its regulation. In particular, the examination of the basis for the vasoactivity observed with some of the hemoglobin based oxygen carriers has led to the insight that several colligative properties of hemoglobin solutions, such as their diffusion coefficient for oxygen, viscosity and colloid oncotic pressure. are important determinants of efficacy. (c) 2005 Elsevier SAS. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. RP Stowell, CP (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Blood Transfus Serv, 55 Fruit St, Boston, MA 02114 USA. EM cstowell@partners.org NR 68 TC 13 Z9 15 U1 0 U2 2 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1246-7820 J9 TRANSFUS CLIN BIOL JI Transfu. Clin. Biol. PD NOV PY 2005 VL 12 IS 5 BP 374 EP 379 DI 10.1016/j.tracli.2005.10.002 PG 6 WC Hematology; Immunology SC Hematology; Immunology GA 998KB UT WOS:000234316300006 PM 16326128 ER PT J AU Chemaly, ER Yoneyama, R Frangioni, JV Hajjar, RJ AF Chemaly, ER Yoneyama, R Frangioni, JV Hajjar, RJ TI Tracking stem cells in the cardiovascular system SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID IN-VIVO TRACKING; MYOCARDIAL-INFARCTION; PROGENITOR CELLS; CONTRAST AGENTS; TRANSPLANTATION; MIGRATION; SERIAL; FERUMOXIDES; ULTRASOUND; EXPRESSION AB Stem cells are a promising approach to cardiovascular therapeutics. Animal experiments have assessed the fate of injected stem cells through ex vivo methods on sacrificed animals. Approaches are needed for in vivo tracking of stem cells. Various imaging techniques and contrast agents for stem cell tracking will be reviewed. C1 Massachusetts Gen Hosp, Cardiol Lab Integrat Physiol & Imaging, Cardiovasc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Hajjar, RJ (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, 149 13th St,Room 4215, Charlestown, MA 02129 USA. EM rhajjar@partners.org NR 40 TC 23 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD NOV PY 2005 VL 15 IS 8 BP 297 EP 302 AR PII S1050-1738(05)00180-5 DI 10.1016/j.tcm.2005.09.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 990TC UT WOS:000233765100005 PM 16297767 ER PT J AU McDougal, WS AF McDougal, WS TI Advances in the treatment of carcinoma of the penis SO UROLOGY LA English DT Article ID FOLLOW-UP; LYMPHADENECTOMY; CANCER AB The aim of this article is to define the therapeutic advances in the treatment of penile cancer over the past 2 decades. A literature search was conducted for articles in which a major change in therapy was documented as beneficial. Case records were then reviewed in patients who underwent such procedures. Major advances have involved less disfiguring treatment of the primary lesion in selected cases and the recognition of improved survival by altering the timing of groin dissection for those at risk for metastatic disease. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. RP McDougal, WS (reprint author), Massachusetts Gen Hosp, Dept Urol, 55 Fruit St, Boston, MA 02114 USA. EM wmcdougal@partners.org NR 11 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2005 VL 66 IS 5A SU S BP 114 EP 117 DI 10.1016/j.urology.2005.06.007 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 991OZ UT WOS:000233824600019 PM 16194717 ER PT J AU Beard, C Chen, MH Cote, K Loffredo, M Renshaw, A Hurwitz, M D'Amico, AV AF Beard, C Chen, MH Cote, K Loffredo, M Renshaw, A Hurwitz, M D'Amico, AV TI Pretreatment predictors of posttreatment PSA doubling times for patients undergoing three-dimensional conformal radiotherapy for clinically localized prostate cancer SO UROLOGY LA English DT Article ID RADIATION-THERAPY; RADICAL PROSTATECTOMY; END-POINT; ANTIGEN; MORTALITY; SURVIVAL AB Objectives. To determine whether pretreatment risk groups also predict for posttreatment prostate-specific antigen (PSA) doubling times (PSADTs). Pretreatment risk groups predict for posttreatment biochemical failure (BF) after conformal radiotherapy in patients with prostate cancer and posttreatment PSADTs can predict for prostate cancer-related deaths. Methods. The study cohort consisted of 416 patients with clinically localized prostate cancer treated with conformal radiotherapy between 1989 and 2001. The patients were divided into low, intermediate, and high-risk groups. BF was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Patients with BF were grouped according to their PSADT (3 months or less, longer than 3 months to less than 6 months, 6 months to less than 12 months, and 12 months or longer). A Mantle-Haenszel chi-square metric tested for an association between the pretreatment risk group and the PSADT. Logistic regression multivariate analysis was performed to evaluate whether the pretreatment risk group predicted the PSADT. Results. Of the 416 patients, 96 (23%), 194 (47%), and 126 (30%) were categorized as low, intermediate, and high risk, respectively. A total of 92 patients (22%) experienced BF Of these 92 patients, the PSADT was 3 months or less in 6 (7%), longer than 3 months to less than 6 months in 13 (14%), 6 months to less than 12 months in 35 (36%), and 12 months or longer in 38 (41%). The pretreatment risk group correlated significantly with the PSADT (P = 0.026). Logistic regression analysis revealed that intermediate and high-risk disease was significantly associated with shorter PSADTs (P = 0.039). Conclusions. A significant association between the pretreatment risk group and posttreatment PSADT was demonstrated. Use of this selection criterion at diagnosis for more aggressive treatment appears warranted. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Connecticut, Dept Biostat, Storrs, CT USA. RP Beard, C (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, Dana Farber Canc Inst, 75 Francis St,ASB1,L2, Boston, MA 02115 USA. EM cbeard@lroc.harvard.edu NR 16 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 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2005 VL 66 IS 5 BP 1020 EP 1023 DI 10.1016/j.urology.2005.05.039 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 993DY UT WOS:000233934100022 PM 16286116 ER PT J AU Harisinghani, MG Saksena, M Ross, RW Tabatabaei, S Dahl, D McDougal, S Weissleder, R AF Harisinghani, MG Saksena, M Ross, RW Tabatabaei, S Dahl, D McDougal, S Weissleder, R TI A pilot study of lymphotrophic nanoparticle-enhanced magnetic resonance imaging technique in early stage testicular cancer: A new method for noninvasive lymph node evaluation SO UROLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; CONTRAST AGENT; METASTASES AB Objectives. To evaluate whether lymphotrophic nanoparticle-enhanced magnetic resonance imaging (LNMRI) can be used as a method for detecting metastatic disease within retroperitoneal nodes in patients with testicular cancer. Methods. Stage I testicular cancer patients were prospectively enrolled and underwent a pelvic MRI both before and 24 hours after intravenous ferumoxtran-10 administration. Nodal sampling was performed by computed tomography-guided biopsy or laproscopic surgery and reviewed by a pathologist without knowledge of the LNMRI results. Results. In 18 patients, 42 nodes were sampled, of which 25 were benign and 17 were malignant. The sensitivity of LNMRI for malignant lymph node involvement was 88.2%, specificity was 92%, and the accuracy was 90.4%. On the other hand, the sensitivity of size criteria for detecting malignant nodes was 70.5%, the specificity was 68%, and the accuracy was 69%. Conclusions. Lymphotrophic nanoparticle-enhanced MRI is safe and accurate for detecting nodal metastases in patients with testicular cancer. Lymphotrophic nanoparticle-enhanced MRI yields higher sensitivity and specificity when compared with unenhanced MRI or conventional CT scanning. Although our results are encouraging, the precise role of this too[ in early stage testicular cancer remains to be determined. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Urol, Boston, MA USA. RP Harisinghani, MG (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Bldg 149,13th St,Room 5406, Charlestown, MA 02129 USA. EM mharisinghani@partners.org NR 12 TC 54 Z9 55 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2005 VL 66 IS 5 BP 1066 EP 1071 DI 10.1016/j.urology.2005.05.049 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 993DY UT WOS:000233934100031 PM 16286125 ER PT J AU Jeong, J Becker, ER Mauldin, PD Weintraub, WS AF Jeong, J Becker, ER Mauldin, PD Weintraub, WS TI A comparison of self-selectivity corrections in economic evaluations and outcomes research SO VALUE IN HEALTH LA English DT Article DE angioplasty; bypass surgery; multipart model; sample selection model; self-selectivity ID SAMPLE-SELECTION; CORONARY ANGIOPLASTY; LEAST-SQUARES; 2-PART MODELS; VARIABLES; SURGERY; CHOICE AB Objective: Two alternative selectivity correction methods have been widely applied in the health economics literature: the sample selection model (SSM) and the multipart model (MPM). The difference between these two approaches results from their initial assumptions about the distribution of error terms. Because the distributional assumptions cannot be theoretically verified, the usefulness of the methods can only be evaluated by real world comparison. This article reviews and empirically tests the two alternative selectivity correction methods to give a reality-based evaluation. Methods: Using a randomized sample of patients as the "gold standard," the SSM and MPM are applied to a nonrandomized sample of patients with an identical set of dependent and independent variables. By comparing the actual estimates of the two methods, we evaluate the robustness of the two approaches. Results: The results show that neither method is empirically robust in replicating the results of the randomized trial. There is no consistent pattern in the coefficients from either selectivity-correction method for replicating the coefficients in the randomized sample. Conclusions: Researchers should be cautious in applying these correction methods, and any conclusions based on these approaches may need to be qualified. C1 Yonsei Univ, Dept Econ, Seoul 120749, South Korea. Emory Univ, Sch Publ Hlth, Atlanta, GA USA. Med Univ S Carolina, Coll Pharm, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Emory Univ, Sch Med, Atlanta, GA USA. RP Jeong, J (reprint author), Yonsei Univ, Dept Econ, Seoul 120749, South Korea. EM jinook@yonsei.ac.kr NR 19 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 IS 6 BP 656 EP 666 DI 10.1111/j.1524-4733.2005.00054.x PG 11 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 980MD UT WOS:000233021700006 PM 16283866 ER PT J AU Oh, WK Proctor, K Nakabayashi, M Evan, C Tormey, LK Breierova, L Smith, M Neary, M Duh, MS AF Oh, WK Proctor, K Nakabayashi, M Evan, C Tormey, LK Breierova, L Smith, M Neary, M Duh, MS TI A comparison of logistic regression and Cox proportional hazards models for identification of risk factors for renal impairment in hormone refractory prostate cancer (HRPC) patients with bone metastases (BM) treated with zoledronic acid (ZA) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 IS 6 BP A16 EP A17 DI 10.1016/S1098-3015(10)67190-2 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 980MD UT WOS:000233021700055 ER PT J AU Weeks, JC Romanus, D Herndon, JE Schrag, D Mayer, RJ Kemeny, N AF Weeks, JC Romanus, D Herndon, JE Schrag, D Mayer, RJ Kemeny, N TI Cost-effectiveness of hepatic artery infusion for metastatic colorectal cancer (CALGB 9481) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CALGB Stat Ctr, Durham, NC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 IS 6 BP A37 EP A37 DI 10.1016/S1098-3015(10)67251-8 PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 980MD UT WOS:000233021700116 ER PT J AU Abetz, L Coombs, JH Keininger, DL Earle, CC Wade, C Bury-Maynard, D Copley-Merriman, K Hsu, MA AF Abetz, L Coombs, JH Keininger, DL Earle, CC Wade, C Bury-Maynard, D Copley-Merriman, K Hsu, MA TI Development of the cancer therapy satisfaction questionnaire: Item generation and content validity testing SO VALUE IN HEALTH LA English DT Article DE cancer; chemotherapy; patient outcome assessment; questionnaire design; satisfaction ID RANDOMIZED CONTROLLED-TRIAL; CELL LUNG-CANCER; STAGE BREAST-CANCER; QUALITY-OF-LIFE; CROSSOVER TRIAL; CHEMOTHERAPY; PREFERENCES; MODEL AB Objectives: This study was undertaken to develop a new questionnaire, the Cancer Therapy Satisfaction Questionnaire (CTSQ), to focus on the issues oncology patients consider when evaluating chemotherapy in terms of expectations and satisfaction. Methods: Items of the CTSQ were generated through the review of responses from interviews with oncology patients, physicians, and nurses. Analysis of the data was stratified by disease stage, disease type, and country to explore potential differences between these groups. Two rounds of face and content validity testing were then conducted. Results: Patients explained their hopes for efficacy and factors related to treatment satisfaction. Content validity testing in 30 patients, followed by additional testing in 10 patients on oral therapy, suggested that patients felt the questionnaire was clear, comprehensive, relevant, and easy to complete. Minor revisions were implemented to improve clarity, resulting in deletion of 12 items, modification of 17 items and the rewording of "chemotherapy" to "cancer therapy" to ensure patients on oral therapy were able to respond. The CTSQ contains 21 items and assesses seven domains: Expectations of cancer therapy, Feelings about side effects, Oral cancer therapy adherence, Convenience, Satisfaction with cancer therapy, Stopping cancer therapy, and Reasons for nonadherence. Conclusions: The CTSQ was designed for adults with a wide range of cancer types and stages, receiving a variety of cancer treatment formulations. A validation study is currently underway to examine the psychometric properties, further refine the questionnaire and develop scoring methods for the CTSQ. C1 Mapi Values, Macclesfield SK10 5JB, Cheshire, England. Pfizer Inc, Ann Arbor, MI USA. Mapi Values, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Inc, New London, CT USA. RP Abetz, L (reprint author), Mapi Values, Adelphi Mill,Grimshaw Lane, Macclesfield SK10 5JB, Cheshire, England. EM Linda.abetz@mapivalues.com NR 24 TC 22 Z9 22 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 SU 1 BP S41 EP S53 DI 10.1111/j.1524-4733.2005.00073.x PG 13 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 987QG UT WOS:000233531800006 PM 16336488 ER PT J AU Velmahos, GC Constantinou, C Gkiokas, G AF Velmahos, GC Constantinou, C Gkiokas, G TI Does nephrectomy for trauma increase the risk of renal failure? SO WORLD JOURNAL OF SURGERY LA English DT Article ID GUNSHOT WOUNDS; UNILATERAL NEPHRECTOMY; MANAGEMENT; INJURY; RECONSTRUCTION; BLUNT; KIDNEY AB Renal failure is a feared complication following operations for severe trauma. Injuries to the kidney may be managed by nephrectomy or nephrorrhaphy. Nephrectomy may increase the risk of renal failure in already at-risk trauma patients. Nephrectomy for trauma should be avoided to the extent possible because it is associated with renal failure. From a prospectively collected trauma database, 59 patients with nephrectomy were matched at 1:1 ratio with 59 patients with nephrorrhaphy. Matching criteria were age (5 years), Injury Severity Score (3), abdominal Abbreviated Injury Score (1), and mechanism of injury (blunt or penetrating). The rates of renal function compromise (defined as a serum creatinine level >2 mg/dl for more than 2 days) and renal replacement therapy (continuous or intermittent) were compared in the two groups. The two groups were well-matched and similar with regard to injury severity and organs injured. Between nephrectomy and nephrorrhaphy patients, there were no differences in renal function compromise (10% vs. 14%, p = 0.57), renal replacement therapy (5% vs. 0%, p = 0.12), length of hospital stay (19 26 vs. 20 21, p = 0.8), and mortality (15% vs. 12%, p = 0.59). Salvaging the injured kidney does not seem to offer an obvious clinical benefit regarding postoperative renal function. Given the increased operative complexity of nephrorrhaphy in comparison to nephrectomy and the frequent need to abbreviate the operation in patients with severe trauma, nephrectomy should not be avoided when appropriate. C1 Dept Surg, Div Trauma & Crit Care, Los Angeles, CA 90033 USA. Univ So Calif, Med Ctr, Los Angeles, CA 90033 USA. RP Velmahos, GC (reprint author), Massachusetts Gen Hosp, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 20 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2313 J9 WORLD J SURG JI World J.Surg. PD NOV PY 2005 VL 29 IS 11 BP 1472 EP 1475 DI 10.1007/s00268-005-7874-1 PG 4 WC Surgery SC Surgery GA 979YJ UT WOS:000232980800017 PM 16136286 ER PT J AU Armstrong, DG Lipsky, B Joseph, W Lavery, L AF Armstrong, DG Lipsky, B Joseph, W Lavery, L TI A guide to new classifications for diabetic foot infections SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Editorial Material C1 Rosalind Franklin Univ Med, William M Scholl Coll Padiat Med, Chicago, IL USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Antiobiot Res Clin, Seattle, WA USA. Coatesville Vet Affairs Med Ctr, Coatesville, PA USA. Texas A&M Univ, Dept Surg, Hlth Sci Ctr, Coll Med, College Stn, TX 77843 USA. RP Armstrong, DG (reprint author), Rosalind Franklin Univ Med, William M Scholl Coll Padiat Med, Chicago, IL USA. RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD NOV PY 2005 SU S BP 6 EP 9 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 993SF UT WOS:000233974500002 ER PT J AU Armstrong, DG Lavery, L Lipsky, BA Joseph, WS AF Armstrong, DG Lavery, L Lipsky, BA Joseph, WS TI Current concepts in culturing and treating infected wounds SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Editorial Material C1 Rosalind Franklin Univ Med, William M Scholl Coll Padiat Med, Chicago, IL USA. Coatesville Vet Affairs Med Ctr, Coatesville, PA USA. Texas A&M Univ, Dept Surg, Hlth Sci Ctr, Coll Med, College Stn, TX 77843 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Antiobiot Res Clin, Seattle, WA USA. RP Armstrong, DG (reprint author), Rosalind Franklin Univ Med, William M Scholl Coll Padiat Med, Chicago, IL USA. RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD NOV PY 2005 SU S BP 10 EP 12 PG 3 WC Dermatology; Surgery SC Dermatology; Surgery GA 993SF UT WOS:000233974500003 ER PT J AU Armstrong, DG Lavery, L Lipsky, BA Joseph, WS AF Armstrong, DG Lavery, L Lipsky, BA Joseph, WS TI Key considerations in appropriate antibiotic selection SO WOUNDS-A COMPENDIUM OF CLINICAL RESEARCH AND PRACTICE LA English DT Editorial Material C1 Rosalind Franklin Univ Med, William M Scholl Coll Podiat Med, Chicago, IL USA. Coatesville Vet Affairs Med Ctr, Coatesville, PA USA. Texas A&M Univ, Dept Surg, Hlth Sci Ctr, Coll Med, College Stn, TX 77843 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. VA puget Sound Hlth Care Syst, Gen Internal Med Clin, Seattle, WA USA. VA puget Sound Hlth Care Syst, Antiobiot Res Clin, Seattle, WA USA. RP Armstrong, DG (reprint author), Rosalind Franklin Univ Med, William M Scholl Coll Podiat Med, Chicago, IL USA. RI Lipsky, Benjamin/B-4645-2013; OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 0 TC 0 Z9 0 U1 0 U2 0 PU H M P COMMUNICATIONS PI MALVERN PA 83 GENERAL WARREN BLVD, STE 100, MALVERN, PA 19355 USA SN 1044-7946 J9 WOUNDS JI Wounds-Compend. Clin. Res. Pract. PD NOV PY 2005 SU S BP 13 EP 16 PG 4 WC Dermatology; Surgery SC Dermatology; Surgery GA 993SF UT WOS:000233974500004 ER PT J AU Low, AF O'Donnell, CJ Kathiresan, S Everett, B Chae, CU Shaw, SY Ellinor, PT MacRae, CA AF Low, AF O'Donnell, CJ Kathiresan, S Everett, B Chae, CU Shaw, SY Ellinor, PT MacRae, CA TI Aging syndrome genes and premature coronary artery disease SO BMC MEDICAL GENETICS LA English DT Article ID HUTCHINSON-GILFORD PROGERIA; LAMIN-A; HEART-DISEASE; RISK-FACTORS; ASSOCIATION; KLOTHO; SUSCEPTIBILITY; MUTATIONS; DESIGNS; LOCUS AB Background: Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods: We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan(R) probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results: Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion: Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM mdclowa@nus.edu.sg; codonnell@partners.org; skathiresan@partners.org; beverett@partners.org; cchae@partners.org; sshaw@partners.org; pellinor@partners.org; cmacrae@partners.org FU NHLBI NIH HHS [HL-71632, K23 HL071632]; NIA NIH HHS [R21 AG037925] NR 28 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD OCT 31 PY 2005 VL 6 AR 38 DI 10.1186/1471-2350-6-38 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 987XK UT WOS:000233550800001 PM 16262891 ER PT J AU Yu, LY Quinn, DA Garg, HG Hales, CA AF Yu, LY Quinn, DA Garg, HG Hales, CA TI Cyclin-dependent kinase inhibitor p27(Kip1), but not p21(WAF1/cip1), is required for inhibition of hypoxia-induced pulmonary hypertension and remodeling by heparin in mice SO CIRCULATION RESEARCH LA English DT Article DE p27(Kip1); p21(WAF1/cip1); heparin; pulmonary hypertension; hypoxia; mouse ID SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE; GROWTH-FACTOR; C-MYC; PROLIFERATION; EXPRESSION; HYPERPLASIA; P27; FIBROBLASTS; SENESCENCE AB Heparin has growth inhibitory effects on pulmonary artery smooth muscle cell (PASMC) in vitro and in vivo. However, the mechanism has not been fully defined. In this study, we investigated the role of cyclin-dependent kinase inhibitors, p21(WAF1/cip1) (p21) and p27(Kip1) (p27), in the inhibitory effect of heparin on PASMC proliferation in vitro and on hypoxia-induced pulmonary hypertension in vivo using p21 and p27-null mice. In vitro, loss of the p27 gene negated the inhibitory effect of heparin on PASMC proliferation, but p21 was not critical for this inhibition. In vivo, heparin significantly inhibited the development of hypoxia-induced pulmonary hypertension and remodeling, as evidenced by decreased right ventricular systolic pressure, ratio of right ventricular weight to left ventricle plus septum weight, and percent wall thickness of pulmonary artery, in p21(+/+), p21(-/-), p27(+/+), and p27(+/-), but not in p27(-/-) mice. We also observed that hypoxia decreased p27 expression significantly in mouse lung, which was restored by heparin. Heparin inhibited Ki67 proliferative index in terminal bronchial vessel walls in p27(+/+) and p27(+/-), but not in p27(-/-) mice exposed to hypoxia. Therefore, we conclude that the cyclin-dependent kinase inhibitor p27, but not p21, is required for the inhibition of hypoxic pulmonary vascular remodeling by heparin. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, Boston, MA 02114 USA. RP Hales, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit,Dept Med, 55 Fruit St,Bulfinch 148, Boston, MA 02114 USA. EM chales@partners.org FU NHLBI NIH HHS [HL03920, R01 HL039150, HL39150] NR 44 TC 48 Z9 49 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 28 PY 2005 VL 97 IS 9 BP 937 EP 945 DI 10.1161/01.RES.0000188211.83193.1a PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 978OX UT WOS:000232884000013 PM 16195480 ER PT J AU Huang, LQ Cao, J Wang, H Vo, LA Brand, JG AF Huang, LQ Cao, J Wang, H Vo, LA Brand, JG TI Identification and functional characterization of a voltage-gated chloride channel and its novel splice variant in taste bud cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-CELLS; SWEET TASTE; ALPHA-GUSTDUCIN; MESSENGER-RNA; BITTER TASTE; SOUR TASTE; CYCLIC-NUCLEOTIDES; SYNAPTIC VESICLES; MEMBRANE CURRENTS; ACTION-POTENTIALS AB Taste bud cells are epithelial cells with neuronal properties. Voltage-dependent ion channels have been physiologically described in these cells. Here, we report the molecular identification and functional characterization of a voltage-gated chloride channel (ClC-4) and its novel splice variant (ClC-4A) from taste bud cells. ClC-4A skipped an exon near its 5'-end, incurring the loss of 60 amino acids at the N terminus. In situ hybridization and immunohistochemistry localized these two channels' transcripts and proteins to a subset of taste bud cells. Electrophysiological recordings of the heterologously expressed channels in Xenopus oocytes showed that ClC-4 and ClC-4A have opposite sensitivity to pH and unique ion selectivity. The chloride channel blockers niflumic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid had a slight or no inhibitory effect on the conductance of ClC-4, but both blockers inhibited ClC-4A, suggesting that ClC-4A is a candidate channel for an acid-induced 5-nitro-2-( 3-phenylpropylamino) benzoic acid-sensitive current. Furthermore, these two channels may play a role in bitter-, sweet-, and umami-mediated taste transmission by regulating transmitter uptake into synaptic vesicles. C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Univ Penn, Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Biochem, Philadelphia, PA 19104 USA. RP Huang, LQ (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM lhuang@monell.org FU NIDCD NIH HHS [DC05154, R03 DC005154-04, R03 DC005154] NR 82 TC 14 Z9 16 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 2005 VL 280 IS 43 BP 36150 EP 36157 DI 10.1074/jbc.M507706200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976IM UT WOS:000232726900046 PM 16129671 ER PT J AU Kegel, KB Sapp, E Yoder, J Cuiffo, B Sobin, L Kim, YJ Qin, ZH Hayden, MR Aronin, N Scott, DL Isenberg, F Goldmann, WH DiFiglia, M AF Kegel, KB Sapp, E Yoder, J Cuiffo, B Sobin, L Kim, YJ Qin, ZH Hayden, MR Aronin, N Scott, DL Isenberg, F Goldmann, WH DiFiglia, M TI Huntingtin associates with acidic phospholipids at the plasma membrane SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUTANT HUNTINGTIN; HOMOLOGY DOMAINS; BINDING-PROTEIN; HEAT REPEATS; SWISS-MODEL; WILD-TYPE; CLATHRIN; HIP1; ENDOCYTOSIS; EXPRESSION AB We have identified a domain in the N terminus of huntingtin that binds to membranes. A three-dimensional homology model of the structure of the binding domain predicts helical HEAT repeats, which emanate a positive electrostatic potential, consistent with a charge-based mechanism for membrane association. An amphipathic helix capable of inserting into pure lipid bilayers may serve to anchor huntingtin to the membrane. In cells, N-terminal huntingtin fragments targeted to regions of plasma membrane enriched in phosphatidylinositol 4,5-bisphosphate, receptor bound-transferrin, and endogenous huntingtin. N-terminal huntingtin fragments with an expanded polyglutamine tract aberrantly localized to intracellular regions instead of plasma membrane. Our data support a new model in which huntingtin directly binds membranes through electrostatic interactions with acidic phospholipids. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Univ British Columbia, Vancouver, BC V5Z 4H4, Canada. Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA 01655 USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02129 USA. Tech Univ Munich E22, Dept Biophys, D-85747 Garching, Germany. Univ Erlangen Nurnberg, Zent Inst Biomed Tech, D-91052 Erlangen, Germany. RP Kegel, KB (reprint author), MA Gen Hosp E, Dept Neurol, 114 CNY 16th St,Rm 2125, Charlestown, MA 02129 USA. EM kegel@helix.mgh.harvard.edu RI Hayden, Michael/D-8581-2011; Goldmann, Wolfgang/H-5572-2013; Kim, Yun Joong/E-7117-2015 OI Hayden, Michael/0000-0001-5159-1419; Kim, Yun Joong/0000-0002-2956-1552 FU NINDS NIH HHS [NS16367, NS35711, NS38194] NR 39 TC 86 Z9 87 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 28 PY 2005 VL 280 IS 43 BP 36464 EP 36473 DI 10.1074/jbc.M503672200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976IM UT WOS:000232726900080 PM 16085648 ER PT J AU Zhang, Q Carter, EA Ma, BY White, M Fischman, AJ Tompkins, RG AF Zhang, Q Carter, EA Ma, BY White, M Fischman, AJ Tompkins, RG TI Molecular mechanism(s) of burn-induced insulin resistance in murine skeletal muscle: Role of IRS phosphorylation SO LIFE SCIENCES LA English DT Article DE burn injury; insulin resistance; insulin receptor substrate-1; SAPK/JNK; Akt kinase ID NECROSIS-FACTOR-ALPHA; RECEPTOR SUBSTRATE-1; SERINE/THREONINE PHOSPHORYLATION; TYROSINE PHOSPHORYLATION; TNF-ALPHA; DEGRADATION; OBESITY; PROTEINS; KINASE; INJURY AB Hyperglycemia, glucose intolerance and elevated insulin levels frequently occur in burned patients; however, the mechanism(s) for this insulin resistance has not been fully elucidated. One possible mechanism could involve alterations in the phosphorylation of serine 307 of the insulin receptor substrate-1 (IRS-1) via activation of stress kinase enzymes, including SAPK/JNK. In the present study we examined the time course of the effect of burn injury to mice on: levels of IRS-1 protein, phosphorylation of serine 307 of IRS-1, SAPK/JNK kinase levels and activity and Akt kinase activity in hind limb skeletal muscle. Burn injury produced a reduction in hind limb muscle mass 24 h after injury, and, which persisted for 168 h. At 24 h after injury, there was a dramatic (-9-fold) increase in phosphorylation of IRS-1 serine 307 followed by a more moderate elevation thereafter. Total IRS-1 protein was slightly elevated at 24 h after injury and decreased to levels below sham treated animals at the later times. Burn injury did not appear to change total SAPK/JNK protein content, however, enzyme activity was increased for 7 days after injury. Akt kinase activity was decreased in skeletal muscle following burn injury; providing a biochemical basis for burn-induced insulin resistance. These findings are consistent with the hypothesis that burn-induced insulin resistance may be related, at least in part, to alterations in the phosphorylation of key proteins in the insulin signaling cascade, including IRS-1, and that changes in stress kinases, such as SAPK/JNK produced by burn injury, may be responsible for these changes in phosphorylation. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Nucl Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Joslin Diabet Fdn, Boston, MA 02114 USA. RP Carter, EA (reprint author), Massachusetts Gen Hosp, Dept Surg, 51 Blossom St, Boston, MA 02114 USA. EM eacarter@partners.org FU NIGMS NIH HHS [2 P50 GM21700-27AI] NR 25 TC 32 Z9 38 U1 0 U2 0 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 OCT 28 PY 2005 VL 77 IS 24 BP 3068 EP 3077 DI 10.1016/j.lfs.2005.02.034 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 975OQ UT WOS:000232672200008 PM 15982669 ER PT J AU Tomlins, SA Rhodes, DR Perner, S Dhanasekaran, SM Mehra, R Sun, XW Varambally, S Cao, XH Tchinda, J Kuefer, R Lee, C Montie, JE Shah, RB Pienta, KJ Rubin, MA Chinnaiyan, AM AF Tomlins, SA Rhodes, DR Perner, S Dhanasekaran, SM Mehra, R Sun, XW Varambally, S Cao, XH Tchinda, J Kuefer, R Lee, C Montie, JE Shah, RB Pienta, KJ Rubin, MA Chinnaiyan, AM TI Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer SO SCIENCE LA English DT Article ID EWINGS-SARCOMA TRANSLOCATION; EXPRESSION PROFILES; MULTIPLE-MYELOMA; EWS GENE; LEUKEMIA; CLASSIFICATION; FAMILY; TUMOR; FUSES AB Recurrent chromosomal rearrangements have not been well characterized in common carcinomas. We used a bioinformatics approach to discover candidate oncogenic chromosomal aberrations on the basis of outlier gene expression. Two ETS transcription factors, ERG and ETV1, were identified as outliers in prostate cancer. We identified recurrent gene fusions of the 5' untranslated region of TMPRSS2 to ERG or ETV1 in prostate cancer tissues with outlier expression. By using fluorescence in situ hybridization, we demonstrated that 23 of 29 prostate cancer samples harbor rearrangements in ERG or ETV1. Cell line experiments suggest that the androgen-responsive promoter elements of TMPRSS2 mediate the overexpression of ETS family members in prostate cancer. These results have implications in the development of carcinomas and the molecular diagnosis and treatment of prostate cancer. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Bioinformat Program, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Michigan Urol Ctr, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ Ulm, Fac Med, Dept Urol, D-89075 Ulm, Germany. RP Chinnaiyan, AM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine St, Ann Arbor, MI 48109 USA. EM arul@umich.edu RI Pienta, Kenneth/E-7679-2015; OI Pienta, Kenneth/0000-0002-4138-2186; Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [5P30 CA46592, P50CA69568, R01 CA97063, UO1 CA111275-01]; NIA NIH HHS [R01AG21404] NR 32 TC 1961 Z9 2029 U1 12 U2 119 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 28 PY 2005 VL 310 IS 5748 BP 644 EP 648 DI 10.1126/science.1117679 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 980ET UT WOS:000232997700032 PM 16254181 ER PT J AU Oliveira, JG Barabasi, AL AF Oliveira, JG Barabasi, AL TI Human dynamics: Darwin and Einstein correspondence patterns SO NATURE LA English DT Editorial Material C1 Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. Univ Notre Dame, Dept Phys, Notre Dame, IN 46556 USA. Univ Aveiro, Dept Fis, P-3810193 Aveiro, Portugal. Harvard Univ, Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. RP Oliveira, JG (reprint author), Univ Notre Dame, Ctr Complex Network Res, Notre Dame, IN 46556 USA. EM alb@nd.edu RI Oliveira, Joao/H-3256-2012; Universidade Aveiro, Departamento Fisica/E-4128-2013 OI Oliveira, Joao/0000-0002-1199-4667; NR 10 TC 196 Z9 222 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 OCT 27 PY 2005 VL 437 IS 7063 BP 1251 EP 1251 DI 10.1038/4371251a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977UQ UT WOS:000232829100032 PM 16251946 ER PT J AU Siegel, JM AF Siegel, JM TI Clues to the functions of mammalian sleep SO NATURE LA English DT Review ID SLOW-WAVE SLEEP; REM-SLEEP; BRAIN-STEM; RAT-BRAIN; DROSOPHILA-MELANOGASTER; PARADOXICAL SLEEP; TACHYGLOSSUS-ACULEATUS; MEMORY CONSOLIDATION; RETICULAR-FORMATION; ENERGY-METABOLISM AB The functions of mammalian sleep remain unclear. Most theories suggest a role for non-rapid eye movement (NREM) sleep in energy conservation and in nervous system recuperation. Theories of REM sleep have suggested a role for this state in periodic brain activation during sleep, in localized recuperative processes and in emotional regulation. Across mammals, the amount and nature of sleep are correlated with age, body size and ecological variables, such as whether the animals live in a terrestrial or an aquatic environment, their diet and the safety of their sleeping site. Sleep may be an efficient time for the completion of a number of functions, but variations in sleep expression indicate that these functions may differ across species. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat, VA GLAHS Sepulveda, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, North Hills, CA 91343 USA. RP Siegel, JM (reprint author), Univ Calif Los Angeles, Sch Med, Dept Psychiat, VA GLAHS Sepulveda, North Hills, CA 91343 USA. EM JSiegel@ucla.edu NR 100 TC 294 Z9 301 U1 11 U2 107 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 27 PY 2005 VL 437 IS 7063 BP 1264 EP 1271 DI 10.1038/nature04285 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977UQ UT WOS:000232829100039 PM 16251951 ER PT J AU Altshuler, D Brooks, LD Chakravarti, A Collins, FS Daly, MJ Donnelly, P Gibbs, RA Belmont, JW Boudreau, A Leal, SM Hardenbol, P Pasternak, S Wheeler, DA Willis, TD Yu, FL Yang, HM Zeng, CQ Gao, Y Hu, HR Hu, WT Li, CH Lin, W Liu, SQ Pan, H Tang, XL Wang, J Wang, W Yu, J Zhang, B Zhang, QR Zhao, HB Zhao, H Zhou, J Gabriel, SB Barry, R Blumenstiel, B Camargo, A Defelice, M Faggart, M Goyette, M Gupta, S Moore, J Nguyen, H Onofrio, RC Parkin, M Roy, J Stahl, E Winchester, E Ziaugra, L Shen, Y Yao, ZJ Huang, W Chu, X He, YG Jin, L Liu, YF Shen, YY Sun, WW Wang, HF Wang, Y Wang, Y Wang, Y Xiong, XY Xu, L Waye, MMY Tsui, SKW Xue, H Wong, JTF Galver, ILM Fan, JB Murray, SS Oliphant, AR Chee, MS Montpetit, A Chagnon, F Ferretti, V Leboeuf, M Olivier, JF Phillips, MS Roumy, S Sallee, C Verner, A Hudson, TJ Frazer, KA Ballinger, DG Cox, DR Hinds, DA Stuve, LL Kwok, PY Cai, DM Koboldt, DC Miller, RD Pawlikowska, L Taillon-Miller, P Xiao, M Tsui, LC Mak, W Sham, PC Song, YQ Tam, PKH Nakamura, Y Kawaguchi, T Kitamoto, T Morizono, T Nagashima, A Ohnishi, Y Sekine, A Tanaka, T Tsunoda, T Deloukas, P Bird, CP Delgado, M Dermitzakis, ET Gwilliam, R Hunt, S Morrison, J Powell, D Stranger, BE Whittaker, P Bentley, DR Daly, MJ de Bakker, PIW Barrett, J Fry, B Maller, J McCarroll, S Patterson, N Pe'er, I Purcell, S Richter, DJ Sabeti, P Saxena, R Schaffner, SF Varilly, P Stein, LD Krishnan, L Smith, AV Thorisson, GA Chen, PE Cutler, DJ Kashuk, CS Lin, S Abecasis, GR Guan, WH Munro, HM Qin, ZHS Thomas, DJ McVean, G Bottolo, L Eyheramendy, S Freeman, C Marchini, J Myers, S Spencer, C Stephens, M Cardon, LR Clarke, G Evans, DM Morris, AP Weir, BS Tsunoda, T Mullikin, JC Sherry, ST Feolo, M Zhang, HC Zeng, CQ Zhao, H Matsuda, I Fukushima, Y Macer, DR Suda, E Rotimi, CN Adebamowo, CA Ajayi, I Aniagwu, T Marshall, PA Nkwodimmah, C Royal, CDM Leppert, MF Dixon, M Peiffer, A Qiu, RZ Kent, A Kato, K Niikawa, N Adewole, IF Knoppers, BM Foster, MW Clayton, EW Muzny, D Nazareth, L Sodergren, E Weinstock, GM Wheeler, DA Yakub, I Gabriel, SB Richter, DJ Ziaugra, L Birren, BW Wilson, RK Fulton, LL Rogers, J Burton, J Carter, NP Clee, CM Griffiths, M Jones, MC McLay, K Plumb, RW Ross, MT Sims, SK Willey, DL Chen, Z Han, H Kang, L Godbout, M Wallenburg, JC Archeveque, PL Bellemare, G Saeki, K Wang, HG An, DC Fu, HB Li, Q Wang, Z Wang, RW Holden, AL Brooks, LD McEwen, JE Bird, CR Guyer, MS Nailer, PJ Wang, VO Peterson, JL Shi, M Spiegel, J Sung, LM Witonsky, J Zacharia, LF Kennedy, K Jamieson, R Stewart, J AF Altshuler, D Brooks, LD Chakravarti, A Collins, FS Daly, MJ Donnelly, P Gibbs, RA Belmont, JW Boudreau, A Leal, SM Hardenbol, P Pasternak, S Wheeler, DA Willis, TD Yu, FL Yang, HM Zeng, CQ Gao, Y Hu, HR Hu, WT Li, CH Lin, W Liu, SQ Pan, H Tang, XL Wang, J Wang, W Yu, J Zhang, B Zhang, QR Zhao, HB Zhao, H Zhou, J Gabriel, SB Barry, R Blumenstiel, B Camargo, A Defelice, M Faggart, M Goyette, M Gupta, S Moore, J Nguyen, H Onofrio, RC Parkin, M Roy, J Stahl, E Winchester, E Ziaugra, L Shen, Y Yao, ZJ Huang, W Chu, X He, YG Jin, L Liu, YF Shen, YY Sun, WW Wang, HF Wang, Y Wang, Y Wang, Y Xiong, XY Xu, L Waye, MMY Tsui, SKW Xue, H Wong, JTF Galver, ILM Fan, JB Murray, SS Oliphant, AR Chee, MS Montpetit, A Chagnon, F Ferretti, V Leboeuf, M Olivier, JF Phillips, MS Roumy, S Sallee, C Verner, A Hudson, TJ Frazer, KA Ballinger, DG Cox, DR Hinds, DA Stuve, LL Kwok, PY Cai, DM Koboldt, DC Miller, RD Pawlikowska, L Taillon-Miller, P Xiao, M Tsui, LC Mak, W Sham, PC Song, YQ Tam, PKH Nakamura, Y Kawaguchi, T Kitamoto, T Morizono, T Nagashima, A Ohnishi, Y Sekine, A Tanaka, T Tsunoda, T Deloukas, P Bird, CP Delgado, M Dermitzakis, ET Gwilliam, R Hunt, S Morrison, J Powell, D Stranger, BE Whittaker, P Bentley, DR Daly, MJ de Bakker, PIW Barrett, J Fry, B Maller, J McCarroll, S Patterson, N Pe'er, I Purcell, S Richter, DJ Sabeti, P Saxena, R Schaffner, SF Varilly, P Stein, LD Krishnan, L Smith, AV Thorisson, GA Chen, PE Cutler, DJ Kashuk, CS Lin, S Abecasis, GR Guan, WH Munro, HM Qin, ZHS Thomas, DJ McVean, G Bottolo, L Eyheramendy, S Freeman, C Marchini, J Myers, S Spencer, C Stephens, M Cardon, LR Clarke, G Evans, DM Morris, AP Weir, BS Tsunoda, T Mullikin, JC Sherry, ST Feolo, M Zhang, HC Zeng, CQ Zhao, H Matsuda, I Fukushima, Y Macer, DR Suda, E Rotimi, CN Adebamowo, CA Ajayi, I Aniagwu, T Marshall, PA Nkwodimmah, C Royal, CDM Leppert, MF Dixon, M Peiffer, A Qiu, RZ Kent, A Kato, K Niikawa, N Adewole, IF Knoppers, BM Foster, MW Clayton, EW Muzny, D Nazareth, L Sodergren, E Weinstock, GM Wheeler, DA Yakub, I Gabriel, SB Richter, DJ Ziaugra, L Birren, BW Wilson, RK Fulton, LL Rogers, J Burton, J Carter, NP Clee, CM Griffiths, M Jones, MC McLay, K Plumb, RW Ross, MT Sims, SK Willey, DL Chen, Z Han, H Kang, L Godbout, M Wallenburg, JC Archeveque, PL Bellemare, G Saeki, K Wang, HG An, DC Fu, HB Li, Q Wang, Z Wang, RW Holden, AL Brooks, LD McEwen, JE Bird, CR Guyer, MS Nailer, PJ Wang, VO Peterson, JL Shi, M Spiegel, J Sung, LM Witonsky, J Zacharia, LF Kennedy, K Jamieson, R Stewart, J CA Int HapMap Consortium TI A haplotype map of the human genome SO NATURE LA English DT Review ID SINGLE-NUCLEOTIDE POLYMORPHISM; RECENT POSITIVE SELECTION; FACTOR-H POLYMORPHISM; LINKAGE-DISEQUILIBRIUM; MACULAR DEGENERATION; RECOMBINATION RATES; HUMAN-POPULATIONS; SEGMENTAL DUPLICATIONS; MEIOTIC RECOMBINATION; TYROSINE-PHOSPHATASE AB Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms ( SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution. C1 Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. ParAllele Biosci Inc, San Francisco, CA 94080 USA. Chinese Acad Sci, Beijing Genom Inst, Beijing 100300, Peoples R China. Chinese Natl Human Genome Ctr, Beijing Econ Technol Dev Area, Beijing 100176, Peoples R China. Chinese Natl Human Genome Ctr Shanghai, Shanghai 201203, Peoples R China. Chinese Univ Hong Kong, Dept Biochem, Croucher Lab Human Genom, Shatin, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. Illumina, San Diego, CA 92121 USA. Prognosys Biosci Inc, San Diego, CA 92121 USA. McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. Univ Montreal, Publ Law Res Ctr CRDP, Montreal, PQ H3C 3J7, Canada. Perlegen Sci Inc, Mountain View, CA 94043 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Univ Hong Kong, Genome Res Ctr, Pokfulam, Hong Kong, Peoples R China. Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. RIKEN, SNP Res Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Solexa Ltd, Saffron Walden CB10 1XL, Essex, England. Cold Spring Harbor Lab, New York, NY 11724 USA. Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Univ Washington, Dept Stat, Washington, DC 98195 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. Natl Human Genome Res Inst, US Natl Inst Hlth, Bethesda, MD 20892 USA. US Natl Inst Hlth, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Beijing Normal Univ, Beijing 100875, Peoples R China. Hlth Sci Univ Hokkaido, Ishikari, Hokkaido, Japan. Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 3908621, Japan. UNESCO, Bangkok 10110, Thailand. Univ Tsukuba, Eubios Eth Inst, Tsukuba 3058691, Japan. Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. Univ Ibadan, Coll Med, Ibadan, Oyo State, Nigeria. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT 84112 USA. Chinese Acad Social Sci, Ctr Appl Eth, Beijing 100054, Peoples R China. Genet Interest Grp, London N1 3QP, England. Kyoto Univ, Inst Res Humanities, Sakyo Ku, Kyoto 6068501, Japan. Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan. Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 8528523, Japan. Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. Vanderbilt Univ, Ctr Genet & Hlth Policy, Nashville, TN 37232 USA. Wellcome Trust Res Labs, London NW1 2BE, England. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Chinese Acad Sci, Beijing 100864, Peoples R China. Genome Canada, Ottawa, ON K2P 1P1, Canada. McGill Univ, Off Technol Transfer, Montreal, PQ H3A 2A7, Canada. Genome Quebec, Montreal, PQ H3B 1S6, Canada. Minist Educ Culture Sports Sci & Technol, Chiyoda Ku, Tokyo 1008959, Japan. Minist Sci & Technol, Beijing 100862, Peoples R China. Human Genet Resource Adm China, Beijing 100081, Peoples R China. SNP Consortium, Deerfield, IL 60015 USA. Novartis Pharmaceut, Biomarker Dev, E Hanover, NJ 07936 USA. US Natl Inst Hlth, Off Technol Transfer, Rockville, MD 20852 USA. Univ Maryland, Sch Law, Baltimore, MD 21201 USA. Frost & Sullivan, Palo Alto, CA 94303 USA. RP Altshuler, D (reprint author), Harvard Univ, Broad Inst, 1 Kendall Sq, Cambridge, MA 02139 USA. EM altshuler@molbio.mgh.harvard.edu; donnelly@stats.ox.ac.uk RI Varilly, Patrick/C-8118-2013; Evans, David/H-6325-2013; de Bakker, Paul/B-8730-2009; Kwok, Pui-Yan/F-7725-2014; Tsunoda, Tatsuhiko/K-2061-2014; Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tsui, Stephen Kwok-Wing/E-4385-2015; Tanaka, Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; Deloukas, Panos/B-2922-2013; Jin, Li/C-1468-2009; Dermitzakis, Emmanouil/B-7687-2013; Tam, Paul/C-4405-2009; Abecasis, Goncalo/B-7840-2010; Thorisson, Gudmundur/E-7359-2010; Altshuler, David/A-4476-2009; Tsui, Lap-chee/A-1081-2010; Schaffner, Stephen/D-1189-2011; Song, You-Qiang/E-5207-2011; Song, You-qiang/C-4401-2009; Qin, Zhaohui/E-8196-2011; 郑, 征/C-8514-2011 OI Adebamowo, Clement/0000-0002-6571-2880; Abecasis, Goncalo/0000-0003-1509-1825; Xue, Hong/0000-0002-8133-9828; Stranger, Barbara/0000-0001-9021-7331; He, Yungang/0000-0002-2931-2871; Evans, David/0000-0003-0663-4621; Varilly, Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858; Kwok, Pui-Yan/0000-0002-5087-3059; Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tsui, Stephen Kwok-Wing/0000-0003-0686-4259; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; Belmont, John/0000-0001-7409-3578; Hudson, Thomas/0000-0002-1376-4849; Deloukas, Panos/0000-0001-9251-070X; Jin, Li/0000-0002-4546-2415; Thorisson, Gudmundur/0000-0001-5635-1860; Altshuler, David/0000-0002-7250-4107; Qin, Zhaohui/0000-0002-1583-146X; NR 103 TC 3469 Z9 3579 U1 29 U2 363 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 27 PY 2005 VL 437 IS 7063 BP 1299 EP 1320 DI 10.1038/nature04226 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977UQ UT WOS:000232829100044 ER PT J AU Chaguturu, S Vallabhaneni, S AF Chaguturu, S Vallabhaneni, S TI Aiding and abetting - Nursing crises at home and abroad SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Brown Med Sch, Providence, RI USA. RP Chaguturu, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 26 Z9 28 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 27 PY 2005 VL 353 IS 17 BP 1761 EP 1763 DI 10.1056/NEJMp058201 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 977OL UT WOS:000232813000001 PM 16251530 ER PT J AU Berry, DA Cronin, KA Plevritis, SK Fryback, DG Clarke, L Zelen, M Mandelblatt, JS Yakovlev, AY Habbema, JDF Feuer, EJ AF Berry, DA Cronin, KA Plevritis, SK Fryback, DG Clarke, L Zelen, M Mandelblatt, JS Yakovlev, AY Habbema, JDF Feuer, EJ CA CISNET Collaborators TI Effect of screening and adjuvant therapy on mortality from breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIALS; UNITED-STATES; SOCIETY GUIDELINES; FOLLOW-UP; MAMMOGRAPHY; TAMOXIFEN; PROGRESS AB BACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. RESULTS: The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. CONCLUSIONS: Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Unit 447, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Wisconsin, Madison, WI USA. Cornerstone Syst, Lynden, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Univ Rochester, Rochester, NY USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RP Berry, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Unit 447, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dberry@mdanderson.org RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU NCI NIH HHS [U01CA69976, CA88177, CA88202, CA88211, CA88248, CA88270, CA88278, CA88283, U01CA63731, U01CA63736, U01CA63740, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 27 TC 1113 Z9 1146 U1 6 U2 79 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 27 PY 2005 VL 353 IS 17 BP 1784 EP 1792 DI 10.1056/NEJMoa050518 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 977OL UT WOS:000232813000006 PM 16251534 ER PT J AU Korzenik, J Chung, DC Digumarthy, S Badizadegan, K Moss, JD Harris, NL Goldfinger, S Tso, L Hung, K AF Korzenik, J Chung, DC Digumarthy, S Badizadegan, K Moss, JD Harris, NL Goldfinger, S Tso, L Hung, K TI A 43-year-old man with lower gastrointestinal bleeding - Hereditary hemorrhagic telangiectasia and atypical juvenile polyposis with dysplasia and intramucosal carcinoma, associated with a germ-line mutation in the MADH4 gene. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PULMONARY ARTERIOVENOUS-MALFORMATIONS; FAMILIAL JUVENILE; BMPR1A MUTATIONS; COLI; SMAD4; ENDOGLIN; CANCER; RISK C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Korzenik, J (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 26 TC 3 Z9 4 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 27 PY 2005 VL 353 IS 17 BP 1836 EP 1844 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 977OL UT WOS:000232813000013 PM 16251540 ER PT J AU Tanzi, RE AF Tanzi, RE TI Tangles and neurodegenerative disease - A surprising twist SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID TAU C1 Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Tanzi, RE (reprint author), Massachusetts Gen Hosp, Genet & Aging Res Unit, Charlestown, MA 02129 USA. NR 5 TC 14 Z9 16 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 27 PY 2005 VL 353 IS 17 BP 1853 EP 1855 DI 10.1056/NEJMcibr055003 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 977OL UT WOS:000232813000017 PM 16251544 ER PT J AU Yu, QY Ciemerych, MA Sicinski, P AF Yu, QY Ciemerych, MA Sicinski, P TI Ras and Myc can drive oncogenic cell proliferation through individual D-cyclins SO ONCOGENE LA English DT Article DE D-cyclins; oncogenic transformation; Ras; Myc ID BREAST-CANCER CELLS; TRANSCRIPTIONAL INDUCTION; EXPRESSION; GENE; TRANSFORMATION; PATHWAY; KINASE; PROTEIN; MOUSE; PHOSPHORYLATION AB D-type cyclins serve as cell cycle recipients of several oncogenic pathways. The specific sequences of the promoters of the cyclin D genes are thought to render particular D-cyclins responsive to specific oncogenic pathways. For instance, the Ras oncogene was postulated to signal through cyclin D1, while Myc can impact the cell cycle machinery by transcriptionally upregulating cyclin D2. In the current study we engineered mouse fibroblasts to express only cyclin D1, only D2, or only D3. These 'single-cyclin' cells allowed us to rigorously test the ability of cyclin D1, D2, or D3, when expressed on their own, to serve as recipients of the Ras- and Myc-driven oncogenic pathways. We found that each of the D-cyclins was sufficient to drive oncogenic proliferation of mouse fibroblasts. This, together with our recent observations that cells lacking all three D-cyclins show greatly reduced susceptibility to the oncogenic action of Ras and Myc, reveals that the Ras and Myc oncogenes can impact the core cell cycle machinery through all three D-cyclins. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Peking Univ, Sch Oncol, Beijing Canc Hosp, Dept Cell Biol, Beijing 100034, Peoples R China. Univ Warsaw, Inst Zool, Dept Embryol, PL-02089 Warsaw, Poland. RP Sicinski, P (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. EM peter_sicinski@dfci.harvard.edu FU NCI NIH HHS [R01 CA83688] NR 43 TC 37 Z9 38 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 27 PY 2005 VL 24 IS 47 BP 7114 EP 7119 DI 10.1038/sj.onc.1208853 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 977WC UT WOS:000232833200013 PM 16103884 ER PT J AU Slee, SJ Higgs, MH Fairhall, AL Spain, WJ AF Slee, SJ Higgs, MH Fairhall, AL Spain, WJ TI Two-dimensional time coding in the auditory brainstem SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sound localization; covariance analysis; phase-locking; potassium channel; spike; nucleus magnocellularis ID RETINAL GANGLION-CELLS; AVIAN NUCLEUS MAGNOCELLULARIS; CONTRAST GAIN-CONTROL; COCHLEAR NUCLEUS; SPIKE TRAINS; RECEPTIVE-FIELDS; SINGLE-NEURON; INFORMATION; ADAPTATION; MODEL AB Avian nucleus magnocellularis (NM) spikes provide a temporal code representing sound arrival times to downstream neurons that compute sound source location. NMcells act as high-pass filters by responding only to discrete synaptic events while ignoring temporally summed EPSPs. This high degree of input selectivity insures that each output spike from NM unambiguously represents inputs that contain precise temporal information. However, we lack a quantitative description of the computation performed by NM cells. A powerful model for predicting output firing rate given an arbitrary current input is given by a linear/nonlinear cascade: the stimulus is compared with a known relevant feature by linear filtering, and based on that comparison, a nonlinear function predicts the firing response. Spike-triggered covariance analysis allows us to determine a generalization of this model in which firing depends on more than one spike-triggering feature or stimulus dimension. We found two current features relevant for NM spike generation; the most important simply smooths the current on short time scales, whereas the second confers sensitivity to rapid changes. A model based on these two features captured more mutual information between current and spikes than a model based on a single feature. We used this analysis to characterize the changes in the computation brought about by pharmacological manipulation of the biophysical properties of the neurons. Blockage of low-threshold voltage-gated potassium channels selectively eliminated the requirement for the second stimulus feature, generalizing our understanding of input selectivity by NM cells. This study demonstrates the power of covariance analysis for investigating single neuron computation. C1 Univ Washington, Dept Neurol 127, Seattle, WA 98108 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98108 USA. Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. RP Spain, WJ (reprint author), Univ Washington, Dept Neurol 127, 1660 S Columbian Way, Seattle, WA 98108 USA. EM spain@u.washington.edu FU BLRD VA [I01 BX000386] NR 54 TC 57 Z9 57 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 26 PY 2005 VL 25 IS 43 BP 9978 EP 9988 DI 10.1523/JNEUROSCI.2666-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 977VU UT WOS:000232832400018 PM 16251446 ER PT J AU Mareninova, O Shin, JM Vagin, O Turdikulova, S Hallen, S Sachs, G AF Mareninova, O Shin, JM Vagin, O Turdikulova, S Hallen, S Sachs, G TI Topography of the membrane domain of the liver Na+-dependent bile acid transporter SO BIOCHEMISTRY LA English DT Article ID IN-VITRO TRANSLATION; TRANSMEMBRANE ORIENTATION; TOPOGENIC SIGNALS; P-GLYCOPROTEIN; TOPOLOGY; PROTEINS; COTRANSPORTER; INSERTION; IDENTIFICATION; CLONING AB The ileal apical and liver basolateral bile acid transporters catalyze the Na+-dependent uptake of these amphipathic molecules in the intestine and liver. They contain nine predicted helical hydrophobic sequences (H1-H9) between the exoplasmic N-glycosylated N terminus and the cytoplasmic C terminus. Previous in vitro translation and in vivo alanine insertion scanning studies gave evidence for either nine or seven transmembrane segments, with H3 and H8 noninserted in the latter model. N-terminal GFP constructs containing either successive predicted segments or only the last two domains of the liver, a membrane anchor signal were expressed in HEK-293 cells, and a C-terminal transporter following glycosylation flag allowed detection of membrane insertion. Western blot analysis with anti-GFP antibody after alkali and PNGase treatment showed that H1, H2, H3 behaved as competent transmembrane (TM) sequences. Results from longer constructs were difficult to interpret. H9, however, but not H8 was membrane-inserted. To analyze the intact transporter, a C-terminal YFP fusion protein was expressed as a functionally active protein in the plasma membrane of HEK-293 cells as seen by confocal microscopy. After limited tryptic digestion to ensure the accessibility of only exoplasmic lysine or arginine residues, molecular weight (MW) analysis of the five cleavage products on SDS-PAGE predicted the presence of seven transmembrane seaments, HI, H2, H3, H4, H5, H6, and H9, with H7 and H8 exoplasmic. This new method provided evidence for seven membrane segments giving a new model of the membrane domain of this protein and probably the homologous ileal transporter, with H7/H8 as the transport region. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Va Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. EM gsachs@ucla.edu OI Turdikulova, Shahlo/0000-0003-0764-2332 FU NIDDK NIH HHS [R01 DK046917, DK46917, DK53462, DK58333, R01 DK053642, R01 DK058333] NR 31 TC 30 Z9 32 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 25 PY 2005 VL 44 IS 42 BP 13702 EP 13712 DI 10.1021/bi051291x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979OK UT WOS:000232954500008 PM 16229460 ER PT J AU Semigran, MJ AF Semigran, MJ TI Type 5 phosphodiesterase inhibition - The focus shifts to the heart SO CIRCULATION LA English DT Editorial Material DE heart failure; natriuretic peptides; pulmonary heart disease; nitric oxide ID NITRIC-OXIDE; CYCLIC-GMP; CARDIAC MYOCYTES; PROTEIN-KINASE; CA2+ CURRENT; SILDENAFIL; CGMP; CONTRACTILE; FAILURE C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Boston, MA 02114 USA. RP Semigran, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiol Div, Fruit St, Boston, MA 02114 USA. EM msemigran@partners.org NR 22 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 BP 2589 EP 2591 DI 10.1161/CIRCULATIONAHA.105.577627 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 977MG UT WOS:000232807300003 PM 16246958 ER PT J AU Deguchi, JO Aikawa, E Libby, P Vachon, JR Inada, M Krane, SM Whittaker, P Aikawa, M AF Deguchi, JO Aikawa, E Libby, P Vachon, JR Inada, M Krane, SM Whittaker, P Aikawa, M TI Matrix metalloproteinase-13/collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques SO CIRCULATION LA English DT Article DE atherosclerosis; collagen; metalloproteinases; pathology; plaque ID TISSUE INHIBITOR; ANEURYSM FORMATION; I COLLAGEN; INTERSTITIAL COLLAGENASE; MYOCARDIAL-INFARCTION; EXTRACELLULAR-MATRIX; MICE; METALLOPROTEINASES; EXPRESSION; GROWTH AB Background-Interstitial collagen plays a crucial structural role in arteries. Matrix metalloproteinases ( MMPs), includingMMP-13/collagenase-3, likely contribute to collagen catabolism in atherosclerotic plaques. Methods and Results-To test the hypothesis that a specific MMP-collagenase influences the development and structure of atherosclerotic plaques, this study used atherosclerosis-susceptible apolipoprotein E-deficient mice that lack MMP-13/collagenase-3 (Mmp-13(-/-)/apoE(-/-)) or express wild- type MMP-13/collagenase-3 (Mmp-13(+/+)/ apoE(-/-)). Both groups consumed an atherogenic diet for 5 ( n = 8) or 10 weeks ( n = 9). Histological analyses of the aortic root of both groups revealed similar plaque size and accumulation of smooth muscle cells ( a collagen-producing cell type) and macrophages ( a major source of plaque collagenases) after 5 and 10 weeks of atherogenic diet. By 10 weeks, the plaques of Mmp-13(-/-)/apoE(-/-) mice contained significantly more interstitial collagen than those of Mmp-13(-/-) apoE(-/-) mice ( P < 0.01). Furthermore, quantitative optical analyses revealed thinner and less aligned periluminal collagen fibers within the plaques of Mmp-13(-/-)/ apoE(-/-) mice versus those from Mmp-13(+/+)/apoE(-/-) mice. Conclusions-These data support the hypothesis that MMP-13/collagenase- 3 plays a vital role in the regulation and organization of collagen in atherosclerotic plaques. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Univ Massachusetts, Sch Med, Dept Emergency Med, Worcester, MA USA. Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA. RP Aikawa, M (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Clin Res Ctr, 77 Ave Louis Pasteur,NRB 741, Boston, MA 02115 USA. EM maikawa@rics.bwh.harvard.edu RI Whittaker, Peter/F-1234-2011; inada, masaki/D-1581-2013 OI Whittaker, Peter/0000-0002-5627-2166; inada, masaki/0000-0002-5066-8506 FU NHLBI NIH HHS [1R01 HL-66086, HL-56985, 1R01 HL-80472]; NIAMS NIH HHS [5R01 AR44815] NR 50 TC 140 Z9 143 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 BP 2708 EP 2715 DI 10.1161/CIRCULATIONAHA.105.562041 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 977MG UT WOS:000232807300018 PM 16230484 ER PT J AU Achenbach, S Ferencik, M Ropers, D Abbara, S Cury, R Hoffmann, U Nieman, K Brady, TJ Moselewski, F AF Achenbach, S Ferencik, M Ropers, D Abbara, S Cury, R Hoffmann, U Nieman, K Brady, TJ Moselewski, F TI Diagnostic accuracy of image postprocessing methods for the detection of coronary artery stenoses by multi-detector computed tomography SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Erlangen Nurnberg, Erlangen, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2650 BP U620 EP U620 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403570 ER PT J AU Aikawa, E Whittaker, P Padera, R Aikawa, M Schoen, FJ AF Aikawa, E Whittaker, P Padera, R Aikawa, M Schoen, FJ TI Human cardiac valve remodeling from fetal to adult: Implications for postnatal adaptation and tissue engineering SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Whittaker, Peter/F-1234-2011 OI Whittaker, Peter/0000-0002-5627-2166 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3338 BP U778 EP U778 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405006 ER PT J AU Boudoulas, KD Burgon, PG Wang, LB Conner, DA Zon, L Pizard, A Shin, JT MacRae, CA Seidman, JG Seidman, CE AF Boudoulas, KD Burgon, PG Wang, LB Conner, DA Zon, L Pizard, A Shin, JT MacRae, CA Seidman, JG Seidman, CE TI C6P: A novel cardiac protein that interacts with lamin A/C SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 974 BP U242 EP U242 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401212 ER PT J AU Carroll, DL Hamilton, GA AF Carroll, DL Hamilton, GA TI Changes in fears and concerns in recipients of an implantable cardioverter defibrillator SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Oslo, Rikshosp, N-0027 Oslo, Norway. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3266 BP U761 EP U761 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404569 ER EF